JAK/STAT

Frailty and risk of serious infections in patients with rheumatoid arthritis treated with biologic or targeted-synthetic DMARDs

309 | Feb 04 2024

Frailty significantly amplifies the risk of serious infections and hospitalizations in rheumatoid arthritis patients starting biologic or targeted synthetic disease-modifying drugs, emphasizing the crucial need for tailored interventions in higher-risk populations. [Read the Full Post]

Binding Thermodynamics of Fourth-Generation EGFR Inhibitors Revealed by Absolute Binding Free Energy Calculations

266 | Jan 26 2024

Your detailed study on BLU-945 and its analogues' enhanced binding affinities to EGFR mutants sheds critical light on potential mechanisms for combating drug resistance in NSCLC, potentially steering future drug development toward more effective treatments. [Read the Full Post]

Isolinderalactone Induces Apoptosis, Autophagy, Cell Cycle Arrest and MAPK Activation through ROS-Mediated Signaling in Colorectal Cancer Cell Lines

447 | Jan 23 2024

Isolinderalactone demonstrates significant potential as a therapeutic agent for colorectal cancer by inducing G2/M phase arrest, apoptosis, autophagy, and MAPK pathway activation via ROS-mediated signaling in human CRC cells. [Read the Full Post]

Astragalus polysaccharide ameliorates insulin resistance in HepG2 cells through activating the STAT5/IGF-1 pathway

458 | Jan 21 2024

Astragalus polysaccharide alleviates insulin resistance in HepG2 cells by activating the STAT5/IGF-1 pathway, as evidenced by its restoration of impaired glucose uptake and modulation of IGF-1, IGF-1 receptor, AKT, and STAT5 signaling, findings reinforced by the counteraction of its effects by the STAT5 inhibitor AG490. [Read the Full Post]

Exosomes from PYCR1 knockdown bone marrow mesenchymal stem inhibits aerobic glycolysis and the growth of bladder cancer cells via regulation of the EGFR/PI3K/AKT pathway

186 | Jan 20 2024

The study demonstrates that bone marrow mesenchymal stem cell-derived exosomes loaded with si-PYCR1 suppress aerobic glycolysis and bladder cancer growth via the PI3K/AKT pathway by targeting EGFR, showcasing a promising therapeutic avenue for the disease. [Read the Full Post]

JAK2 Inhibitor, Fedratinib, Inhibits P-gp Activity and Co-Treatment Induces Cytotoxicity in Antimitotic Drug-Treated P-gp Overexpressing Resistant KBV20C Cancer Cells

263 | Jan 17 2024

Fedratinib's combination with vincristine demonstrates promising cytotoxicity specifically in P-glycoprotein-overexpressing drug-resistant cancer cells, suggesting its potential as an effective co-treatment strategy for multidrug-resistant cancers. [Read the Full Post]

Targeting exon 20 insertion mutations in lung cancer

223 | Jan 14 2024

Recent clinical evidence suggests that targeted therapies like mobocertinib and amivantamab offer promising antitumor activity for patients with EGFR exon 20 insertions in non-small cell lung cancer, while ongoing trials with novel treatments such as DZD9008 and CLN-081 hold potential for further improving survival outcomes in this challenging subset of patients. [Read the Full Post]

Novel Janus-kinase (JAK) Inhibitors in Myelofibrosis

262 | Jan 11 2024

This comprehensive review highlights the evolving landscape of JAK inhibitors in myelofibrosis treatment, emphasizing their varying efficacy in addressing symptoms and the need for further studies to ascertain their precise impact and facilitate more personalized therapeutic approaches. [Read the Full Post]

MTX-211 Inhibits GSH Synthesis through Keap1/NRF2/GCLM Axis and Exerts Antitumor Effects in Bladder Cancer

310 | Jan 10 2024

MTX-211 demonstrates promising potential as a therapeutic agent for bladder cancer by inhibiting cell proliferation through the Keap1/NRF2/GCLM signaling pathway and depleting intracellular GSH levels. [Read the Full Post]

Evolution of Ritlecitinib Population Pharmacokinetic Models During Clinical Drug Development

320 | Dec 31 2023

The iterative development of a population pharmacokinetic model for ritlecitinib, integrating data from diverse clinical trials, culminated in a refined two-compartment model with direct-response non-stationary clearance, informing critical clinical decisions and shaping the drug's label across varied conditions. [Read the Full Post]

Synergistic Antibiofilm Action of Cinnamomum verum and Brazilian Green Propolis Hydroethanolic Extracts against Multidrug-Resistant Strains of Acinetobacter baumannii and Pseudomonas aeruginosa and Their Biocompatibility on Human Keratinocytes

242 | Dec 24 2023

A study evaluating Cinnamomum verum and Brazilian green propolis extracts revealed their potent antibacterial and antibiofilm properties against multidrug-resistant strains of Acinetobacter baumannii and Pseudomonas aeruginosa, showcasing biocompatibility with human cells and suggesting a promising alternative approach to combat these pathogens. [Read the Full Post]

Pseudolycorine chloride ameliorates Th17 cell-mediated central nervous system autoimmunity by restraining myeloid-derived suppressor cell expansion

297 | Dec 18 2023

Pseudolycorine chloride (PLY), a constituent of Narcissus tazetta L. var. Chinensis Roem, demonstrates immunomodulatory effects by inhibiting myeloid-derived suppressor cells (MDSCs) and Th17 cell-mediated inflammation, making it a promising candidate for the treatment of multiple sclerosis and other autoimmune diseases. [Read the Full Post]

Supervised screening of Tecovirimat-like compounds as potential inhibitors for the monkeypox virus E8L protein

302 | Dec 10 2023

The study utilized computational methods and machine learning-guided screening to identify five promising drugs, ABX-1431, Alflutinib, Avacopan, Caspitant, and Darapalib, which effectively engage the MPXV E8L surface binding protein with higher affinity than Tecovirimat, potentially offering new avenues for the development of personalized treatments for Monkeypox virus infections. [Read the Full Post]

Dnmt3a is downregulated by Stat5a and mediates G0/G1 arrest by suppressing the miR-17-5p/Cdkn1a axis in Jak2V617F cells

296 | Dec 06 2023

**In Jak2V617F positive classical myeloproliferative neoplasms, aberrant activation of Stat5a downregulates Dnmt3a through binding to its promoter, leading to dysregulation of the miR-17-5p/Cdkn1a axis and G0/G1 cell cycle arrest, providing a potential therapeutic target.** [Read the Full Post]

Antifibrotic mechanism of avitinib in bleomycin-induced pulmonary fibrosis in mice

236 | Dec 01 2023

A new study demonstrates that avitinib attenuates bleomycin-induced pulmonary fibrosis in mice by inhibiting alveolar epithelial cell injury and myofibroblast activation, indicating its potential as a therapeutic option for this condition. [Read the Full Post]

Overfit deep neural network for predicting drug-target interactions

642 | Nov 27 2023

The OverfitDTI framework utilizes intentionally overfitted deep neural networks to accurately capture the intricate relationships between drugs and targets, enabling precise drug-target interaction predictions, as demonstrated by the successful identification and experimental validation of TEK inhibitors. [Read the Full Post]

Direct Differentiation of Bone Marrow Mononucleated Cells Into Insulin-Producing Cells Using 4 Specific Soluble Factors

249 | Nov 23 2023

The study developed a differentiation method using a unique combination of four differentiation-inducing factors to transform bone marrow-derived stem cells into mature insulin-producing cells, offering a potential novel approach for cell-based therapy in diabetes mellitus. [Read the Full Post]

Hydrogen Sulfide Improves Outcomes in a Murine Model of Necrotizing Enterocolitis via the Cys440 Residue on Endothelial Nitric Oxide Synthase

394 | Nov 17 2023

GYY4137 administration improves clinical outcomes, attenuates intestinal and lung injury, and enhances perfusion in a murine model of necrotizing enterocolitis, with these protective effects being contingent upon the presence of the Cys440 residue in endothelial nitric oxide synthase (eNOS). [Read the Full Post]

Non-oncology drug (meticrane) shows anti-cancer ability in synergy with epigenetic inhibitors and appears to be involved passively in targeting cancer cells

621 | Nov 17 2023

Meticrane, a non-oncology drug originally used to treat hypertension, exhibits promising anti-cancer effects on leukemia and liver cancer cells, including synergistic interactions with epigenetic inhibitors, alterations in gene expression associated with non-cancer pathways, and considerable binding affinity to key cancer-related proteins, although it does not enhance the cytotoxicity of cytokine-induced killer cells, suggesting its potential as a novel cancer therapy warrants further investigation. [Read the Full Post]

Scutellarin suppresses the metastasis of triple-negative breast cancer via targeting TNFα/TNFR2-RUNX1-triggered G-CSF expression in endothelial cells

618 | Nov 13 2023

Scutellarin (SC) inhibits metastasis in triple-negative breast cancer (TNBC) by disrupting the TNFα/TNFR2-initiated RUNX1 activation and subsequent G-CSF production in TNBC-associated endothelial cells (ECs). [Read the Full Post]

Tumor-associated astrocytes promote tumor progression of Sonic Hedgehog medulloblastoma by secreting lipocalin-2

474 | Nov 12 2023

The research reveals that tumor-associated astrocytes (TAAs) secrete lipocalin-2 (LCN2) through the STAT3 signaling pathway, promoting the progression of Sonic Hedgehog (SHH) subgroup medulloblastoma (MB) and indicating LCN2's potential as a prognostic marker and therapeutic target. [Read the Full Post]

Inhibiting STAT5 significantly attenuated Ang II-induced cardiac dysfunction and inflammation

214 | Oct 28 2023

Inhibition of STAT5 using STAT5-IN-1 effectively reduces cardiac hypertrophy in Ang II-induced mice by decreasing inflammation, suggesting a potential therapeutic strategy for mitigating hypertrophy. [Read the Full Post]

[Efficacy of Tyrosine Kinase Inhibitor Combined with Decitabine, Homoharringtonine, Interferon in the Maintenance Therapy of Blast Phase Chronic Myeloid Leukemia]

230 | Oct 21 2023

The combination of tyrosine kinase inhibitor (TKI) with decitabine, homoharringtonine, and interferon as maintenance therapy significantly prolongs event-free survival, duration of remission, and overall survival in blast phase chronic myeloid leukemia (CML-BP) patients who have achieved a major hematological response compared to TKI combined with conventional chemotherapy. [Read the Full Post]

Inhibition of ErbB3 and Associated Regulatory Pathways Potently Impairs Malignant Peripheral Nerve Sheath Tumor Proliferation and Survival

211 | Oct 16 2023

The study identified erbB3, calmodulin, PIM kinases, and Src family members as potential therapeutic targets in MPNSTs and demonstrated that combinatorial therapies targeting these pathways are more effective in reducing proliferation and survival. [Read the Full Post]

Bioactive components and molecular mechanisms of Salvia miltiorrhiza Bunge in promoting blood circulation to remove blood stasis

408 | Oct 16 2023

Salvia miltiorrhiza Bunge (SM) contains phenolic acids and tanshinones that synergistically target multiple signaling pathways to enhance blood circulation and alleviate blood stasis, making it an effective herbal medicine for the treatment of blood stasis syndrome. [Read the Full Post]

RNF112-mediated FOXM1 ubiquitination suppresses the proliferation and invasion of gastric cancer

443 | Sep 27 2023

RNF112 suppresses gastric cancer progression by directly ubiquitinating FOXM1, making the RNF112/FOXM1 axis a potential prognostic biomarker and therapeutic target in gastric cancer. [Read the Full Post]

Discovery of the allosteric inhibitor from actinomyces metabolites to target EGFRCSTMLR mutant protein: molecular modeling and free energy approach

96 | Sep 20 2023

The study identified compound C_42 as a potential drug candidate with strong binding affinity, favorable structural characteristics, and promising potential as an EGFR inhibitor for cancer treatment. [Read the Full Post]

Development and Therapeutic Implications of Tyrosine Kinase 2 Inhibitors

246 | Sep 19 2023

Selective TYK2 inhibitors, such as deucravacitinib and ropsacitinib, offer a promising approach for treating inflammatory and autoimmune diseases with improved efficacy and safety profiles compared to broad JAK inhibitors. [Read the Full Post]

Novel Therapies in Plaque Psoriasis: A Review of Tyrosine Kinase 2 Inhibitors

261 | Sep 18 2023

Deucravacitinib, an allosteric tyrosine kinase 2 inhibitor, has been approved as a first-in-class treatment for moderate-to-severe plaque psoriasis and shows improved safety compared to orthosteric Janus kinase inhibitors. [Read the Full Post]

Start Selective and Rigidify: The Discovery Path toward a Next Generation of EGFR Tyrosine Kinase Inhibitors

156 | Sep 09 2023

BI-4020, a noncovalent, wild-type EGFR sparing, macrocyclic TKI, demonstrates potent inhibition of EGFR variants including T790M and C797S, and induces tumor regressions in a cross-resistant EGFRdel19 T790M C797S xenograft model. [Read the Full Post]

Deuterium in drug discovery: progress, opportunities and challenges

405 | Sep 05 2023

Deuteration, the substitution of a hydrogen atom with its heavy isotope deuterium, has emerged as a promising strategy in drug discovery and development, offering the potential to enhance drug efficacy and safety through improved pharmacokinetic and toxicity profiles. [Read the Full Post]

Clinical Utility of Deucravacitinib for the Management of Moderate to Severe Plaque Psoriasis

135 | Sep 05 2023

Deucravacitinib, a first-in-class TYK2 small molecule inhibitor, shows significant clinical efficacy and a favorable safety profile in the treatment of moderate-to-severe psoriasis based on a systematic review and meta-analysis of randomized controlled trials. [Read the Full Post]

Efficacy and Safety of Tyrosine Kinase 2/Janus Kinase 1 Inhibitor Brepocitinib for Active Psoriatic Arthritis: A Phase IIb Randomized Controlled Trial

274 | Aug 28 2023

The phase IIb study showed that brepocitinib at doses of 30 mg and 60 mg once daily (QD) was more effective than placebo in reducing symptoms of psoriatic arthritis (PsA) and demonstrated a favorable safety profile throughout the 52-week study. [Read the Full Post]

Comparing how well abrocitinib and dupilumab treat atopic dermatitis signs and symptoms: a plain language summary

156 | Aug 25 2023

The summary discusses a clinical study that found abrocitinib to be more effective than dupilumab in quickly improving the signs and symptoms of moderate to severe atopic dermatitis (AD) in individuals who did not respond to prescribed topical medications. [Read the Full Post]

Efficacy and safety of abrocitinib for moderate-to-severe atopic dermatitis in adolescents and adults: Meta-analysis

283 | Aug 25 2023

This meta-analysis suggests that abrocitinib is both safe and effective in treating moderate-to-severe atopic dermatitis in adolescents and adults, with the 200 mg dose showing a greater efficacy compared to the 100 mg dose. [Read the Full Post]

Pulsatilla Saponins Inhibit Experimental Lung Metastasis of Melanoma via Targeting STAT6-Mediated M2 Macrophages Polarization

209 | Aug 21 2023

Pulsatilla saponins derived from Pulsatilla chinensis effectively suppress tumor progression by inhibiting the polarization of M2 macrophages through the STAT6 signaling pathway, revealing a novel mechanism for their anti-tumor activity. [Read the Full Post]

Interaction between Radiation Therapy and Targeted Therapies in HER2-Positive Breast Cancer: Literature Review, Levels of Evidence for Safety and Recommendations for Optimal Treatment Sequence

165 | Jul 31 2023

This literature review examines the risks and safety of combining radiotherapy with anti-HER2 therapies in breast cancer, suggesting that monoclonal antibodies and checkpoint inhibitors can be safely combined with radiation, while caution is warranted for tyrosine kinase inhibitors and antibody-drug conjugates due to limited evidence. [Read the Full Post]

A narrative review from gut to lungs: non-small cell lung cancer and the gastrointestinal microbiome

411 | Jul 24 2023

The gut microbiome plays a crucial role in modulating the immune response and therapeutic outcomes in lung cancer, highlighting the potential for microbiome-based interventions to improve treatment efficacy. [Read the Full Post]

A case of nocardiosis in a patient with ulcerative colitis on chronic corticosteroids, infliximab, and upadacitinib

265 | Jul 21 2023

Immunosuppressed patients, particularly those with ulcerative colitis, are at an increased risk of unmasking obscure infections, necessitating early detection and treatment to mitigate the associated morbidity and mortality. [Read the Full Post]

The differential effects of upadacitinib treatment on skin rashes of four anatomical sites in patients with atopic dermatitis

168 | Jul 21 2023

Upadacitinib demonstrated higher therapeutic efficacy in reducing skin rashes in the lower limbs compared to the trunk and head and neck in patients with moderate-to-severe atopic dermatitis. [Read the Full Post]

Pharmacotherapeutic advances for splenomegaly in myelofibrosis

0 | Jul 15 2023

Myelofibrosis, a hematologic malignancy characterized by splenomegaly, is primarily treated with JAK inhibitors, although spleen size reduction is not consistent, and new pharmacotherapies and combination treatments are being explored to improve outcomes. [Read the Full Post]

Comprehensive profiling of clinical JAK inhibitors in myeloproliferative neoplasms

290 | Jul 15 2023

The comprehensive profiling of four JAK2 inhibitors revealed their distinct clinical profiles, including differential effects on JAK-STAT signaling, inflammatory response, erythroid colony formation, leukemic engraftment, and iron regulation, providing valuable insights for personalized therapy in myeloproliferative neoplasm patients. [Read the Full Post]

PIM2 Promotes the Development of Ovarian Endometriosis by Enhancing Glycolysis and Fibrosis

161 | Jul 11 2023

PIM2 promotes the development of endometriosis through its role in enhancing glycolysis and fibrosis, suggesting it as a potential therapeutic target for the disease. [Read the Full Post]

A Phase I Study to Investigate the Safety, Tolerability and Pharmacokinetics of Napabucasin Combined with Sorafenib in Japanese Patients with Unresectable Hepatocellular Carcinoma

235 | Jul 10 2023

This phase I study in Japanese patients with unresectable hepatocellular carcinoma (HCC) demonstrated that the combination of napabucasin and sorafenib showed promising preliminary antitumor activity with manageable side effects. [Read the Full Post]

PIM Kinases in Multiple Myeloma

224 | Jul 10 2023

PIM kinase inhibitors show promise as a potential treatment for multiple myeloma, and their combination with other targeted agents, including immunomodulatory drugs, holds great potential for improving patient outcomes. [Read the Full Post]

PIM Kinase as an Executional Target in Cancer

356 | Jul 10 2023

PIM kinases, including PIM1, PIM2, and PIM3, are oncogenes that promote cell survival and cell cycle progression in various cancers, and the development of PIM kinase inhibitors shows promise in targeting these pathways for the treatment of human cancer. [Read the Full Post]

Blockade of mutant RAS oncogenic signaling with a special emphasis on KRAS

210 | Jul 06 2023

RAS proteins, including KRAS, HRAS, and NRAS, function as GTPases and play crucial roles in cell signaling pathways involved in growth, division, and survival, with RAS mutations being common in various cancers, particularly KRAS mutations in lung, colorectal, and pancreatic cancers. [Read the Full Post]

Itacitinib Population Pharmacokinetics and Exposure-Response in Patients With Acute Graft-Versus-Host Disease

182 | Jul 01 2023

This article presents a population pharmacokinetic analysis and exposure-response assessment of itacitinib for the treatment of acute graft-versus-host disease, revealing significant predictors of treatment response and recommending dose reductions when co-administered with strong CYP3A inhibitors. [Read the Full Post]

Erlotinib-Loaded Dendrimer Nanocomposites as a Targeted Lung Cancer Chemotherapy

173 | Jun 28 2023

The study found that the cationic G4 PAMAM dendrimer formulation of erlotinib showed superior antiproliferative activity against A549 lung cells compared to neutral G5 dendrimers and erlotinib alone, suggesting its potential as a targeted and sustained-release carrier for lung cancer treatment. [Read the Full Post]

Extraordinary clinical response to ibrutinib in low-grade ovarian cancer guided by organoid drug testing

263 | Jun 28 2023

This case study showcases the efficacy of ex vivo drug testing using patient-derived tumor organoids as a precision medicine approach, leading to significant clinical improvement and prolonged stable disease in a patient with platinum-resistant, advanced low-grade serous ovarian cancer. [Read the Full Post]

FOXK1 regulates epithelial-mesenchymal transition and radiation sensitivity in nasopharyngeal carcinoma via the JAK/STAT3 signaling pathway

214 | Jun 20 2023

Interference with FOXK1 in nasopharyngeal carcinoma cells through the JAK/STAT3 pathway regulates EMT, enhances radiosensitivity, and inhibits tumor progression [Read the Full Post]

JAK inhibitors for rheumatoid arthritis

0 | Jun 20 2023

JAK inhibitors have shown promise in treating rheumatoid arthritis by selectively modulating immune and inflammatory pathways, although their in vivo selectivity and long-term safety profile still require further investigation. [Read the Full Post]

Constitutive JAK/STAT signaling is the primary mechanism of resistance to JAKi in TYK2-rearranged acute lymphoblastic leukemia

393 | Jun 19 2023

The study demonstrates that sustained treatment with the JAK/TYK2 inhibitor cerdulatinib leads to JAK1 overexpression and enhanced JAK/STAT signaling in TYK2-rearranged ALL cells, but withdrawal of the drug reverses these effects, while histone deacetylase inhibitor (HDACi) therapies show efficacy against cerdulatinib-resistant cells, offering a potential alternative treatment approach for TYK2-rearranged B-ALL patients who have developed resistance to JAKi. [Read the Full Post]

Health Status, Quality of Life, Psychosocial Well-being, and Wearables Data of Patients With Active Ulcerative Colitis Receiving Filgotinib Therapy (FilgoColitis Study): Protocol for a Real-world Observational Study

188 | Jun 18 2023

The FilgoColitis study is a prospective observational study evaluating the long-term effectiveness of filgotinib in patients with active ulcerative colitis, focusing on patient-reported outcomes and incorporating the use of innovative wearables to collect physical activity data. [Read the Full Post]

Efficacy and safety of selective JAK 1 inhibitor filgotinib in active rheumatoid arthritis patients with inadequate response to methotrexate: comparative study with filgotinib and tocilizumab examined by clinical index as well as musculoskeletal ultrasound assessment (TRANSFORM study): study protocol for a randomized, open-label, parallel-group, multicenter, and non-inferiority clinical trial

183 | Jun 18 2023

This interventional clinical trial aims to compare the effectiveness of filgotinib monotherapy to tocilizumab monotherapy in rheumatoid arthritis patients with an inadequate response to methotrexate, utilizing clinical disease activity indices, musculoskeletal ultrasound, and serum biomarkers as evaluation parameters. [Read the Full Post]

A Non-Canonical Role for the Glycosyltransferase Enzyme UGT2B17 as a Novel Constituent of the B Cell Receptor Signalosome

236 | Jun 18 2023

Elevated expression of glycosyltransferase UGT2B17 in chronic lymphocytic leukemia (CLL) is associated with poor survival, enhanced BCR pathway signaling, and increased phosphorylation of Bruton tyrosine kinase (BTK), highlighting its potential as an oncogenic factor and therapeutic target. [Read the Full Post]

Blockade of STAT3/IL-4 overcomes EGFR T790M-cis-L792F-induced resistance to osimertinib via suppressing M2 macrophages polarization

116 | Jun 04 2023

The study suggests that targeting the EGFR T790M-cis-L792F/STAT3 Tyr705/IL-4 pathway could be a potential strategy to suppress osimertinib resistance in NSCLC. [Read the Full Post]

Discovery of Potent and Wild-Type-Sparing Fourth-Generation EGFR Inhibitors for Treatment of Osimertinib-Resistance NSCLC

227 | Jun 02 2023

The development of Osimertinib derivatives as fourth-generation inhibitors for the treatment of Osimertinib-resistant NSCLC, particularly the top candidate D51, shows promising selectivity and antitumor activity with favorable in vivo druggability. [Read the Full Post]

Commiphora myrrha stimulates insulin secretion from β-cells through activation of atypical protein kinase C and mitogen-activated protein kinase

328 | May 22 2023

The study investigated the molecular mechanism of action of Commiphora myrrha (CM)-induced insulin secretion and found that CM directly stimulates insulin secretion through activating known downstream effectors of insulin-stimulus secretion coupling, which is completely dependent on protein kinase activation, particularly the phosphorylation and activation of PKCζ and ERK1/2. [Read the Full Post]

PYCR1 promotes the malignant progression of lung cancer through the JAK-STAT3 signaling pathway via PRODH-dependent glutamine synthesize

229 | May 18 2023

PYCR1 has clinical significance in the diagnosis and prognosis of lung cancer, and its pro-tumorigenic role in lung cancer may be attributed to its regulation of the JAK-STAT3 signaling pathway and the metabolism link between proline and glutamine. [Read the Full Post]

A phase I/II study of epertinib plus trastuzumab with or without chemotherapy in patients with HER2-positive metastatic breast cancer

284 | May 15 2023

This study evaluated the safety, tolerability, pharmacokinetics, and antitumor activity of daily oral epertinib combined with trastuzumab, vinorelbine, or capecitabine in patients with pre-treated HER2-positive metastatic breast cancer, with promising results. [Read the Full Post]

Comparative effectiveness of mobocertinib and standard of care in patients with NSCLC with EGFR exon 20 insertion mutations: An indirect comparison

200 | May 14 2023

This study compared the effectiveness of mobocertinib, a novel EGFR tyrosine kinase inhibitor, with real-world treatments in platinum-pretreated patients with advanced EGFR ex20ins-mutant NSCLC, and found that mobocertinib provided substantially improved outcomes. [Read the Full Post]

JAK inhibitors for rheumatoid arthritis

321 | Apr 29 2023

JAK inhibitors represent a promising class of drugs for the treatment of rheumatoid arthritis, with varying degrees of selectivity for different JAK isoforms, and precision medicine approaches may enhance their effectiveness in the future. [Read the Full Post]

Muscle-Specific Ablation of Glucose Transporter 1 (GLUT1) Does Not Impair Basal or Overload-Stimulated Skeletal Muscle Glucose Uptake

416 | Apr 15 2023

The study found that GLUT1 is not necessary for basal muscle glucose uptake and suggests a novel glucose transport mechanism mediates overload-stimulated glucose uptake. [Read the Full Post]

Omicron-induced interferon signalling prevents influenza A H1N1 and H5N1 virus infection

282 | Apr 09 2023

Recent research shows that Omicron but not Delta induces a strong interferon response in primary human cells, protects cells from super-infection with influenza A viruses, and the response is mediated via MDA5 recognition of double-stranded RNA and involves the production of biologically active type I (α/β) and III (λ) interferons. [Read the Full Post]

Excellent Repigmentation of Generalized Vitiligo with Oral Baricitinib Combined with NB-UVB Phototherapy

240 | Apr 09 2023

Oral baricitinib combined with NB-UVB phototherapy has shown to be a successful treatment option for refractory vitiligo by blocking the JAK-STAT pathway and stimulating melanocyte production. [Read the Full Post]

The Current Role of Disease-modifying Osteoarthritis Drugs

297 | Apr 07 2023

The review explores the potential of disease-modifying osteoarthritis drugs (DMOADs) to induce repair and regeneration of articular tissues, but their clinical effectiveness has not yet been demonstrated for managing OA. [Read the Full Post]

A Novel Quantum Dots-Based Fluorescent Sensor for Determination of the Anticancer Dacomitinib: Application to Dosage Forms

235 | Apr 01 2023

The study proposes a novel spectrofluorimetric method for determining the concentration of dacomitinib using newly synthesized nitrogen-doped carbon quantum dots as fluorescent probes, which exhibit native fluorescence and are selectively quenched by increasing concentrations of dacomitinib, offering a simple, efficient, and eco-friendly means of determining the concentration of dacomitinib. [Read the Full Post]

An evaluation of fedratinib for adult patients with newly diagnosed and previously treated myelofibrosis

362 | Apr 01 2023

Fedratinib is a selective JAK2 inhibitor that has been approved by the FDA for the treatment of intermediate-2 or high-risk primary or secondary MF, providing a second-line treatment option for patients who failed or discontinued ruxolitinib, but new combinations with other targeted therapies are needed to improve management of the disease. [Read the Full Post]

Pharmacotherapeutic advances for splenomegaly in myelofibrosis

402 | Apr 01 2023

Myelofibrosis is a hematologic malignancy characterized by splenomegaly in most patients, with JAK inhibitors being the primary pharmacologic treatment option, but alternative therapies and non-pharmacologic approaches may also be considered, and novel combination therapies are being explored. [Read the Full Post]

New therapies in non-small cell lung cancer with EGFR exon 20 insertion mutations

255 | Mar 31 2023

The review identified promising therapies for NSCLC with EGFR exon 20 insertion mutations, but further comparative studies with larger sample sizes and better design are needed to confirm their efficacy. [Read the Full Post]

Development and Optimisation of Inhalable EGCG Nano-Liposomes as a Potential Treatment for Pulmonary Arterial Hypertension by Implementation of the Design of Experiments Approach

411 | Mar 21 2023

The research developed an inhalable EGCG nano-liposome formulation with desirable properties and demonstrated its potential effectiveness in treating PAH by inhibiting the TGFβ pathway. [Read the Full Post]

Targeting Echinococcus multilocularis PIM kinase for improving anti-parasitic chemotherapy

417 | Mar 18 2023

The study identified PIM kinase as a potential target for the development of novel treatments for alveolar echinococcosis, and demonstrated the utility of high-throughput in silico approaches to design small molecule compounds of higher specificity for parasite cells. [Read the Full Post]

Dishevelled 2 regulates cancer cell proliferation and T cell mediated immunity in HER2-positive breast cancer

137 | Mar 15 2023

The study demonstrated the potential immune regulatory role of DVL2 proteins in HER2+ breast cancer, and suggested further investigation of DVL paralogs as potential therapeutic targets. [Read the Full Post]

Fludarabine or cyclophosphamide in combination with total body irradiation as myeloablative conditioning prior to allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia: an analysis by the Acute Leukemia Working Party of the EBMT

242 | Feb 22 2023

In this study, results showed that TBI/Cy conditioning was associated with reduced risk of relapse and increased risk of grade 2-4 acute GVHD, while a matched-pair analysis revealed a reduced rate of relapse and no significant effect on other transplantation outcomes when compared to TBI/Flu, leading to the conclusion that TBI/Cy should be considered a preferable regimen for allo-HCT in adult patients with ALL in complete remission. [Read the Full Post]

Current therapeutic modalities and chemopreventive role of natural products in liver cancer: Progress and promise

832 | Feb 19 2023

Liver cancer treatment options depend on the progression stage of the disease and may include surgery, ablation and radiotherapy, first-line drugs and immunotherapy, and second-line chemotherapeutic drugs, while natural compounds like resveratrol, curcumin and diallyl sulfide are emerging as promising anticancer agents to manage liver cancer. [Read the Full Post]

Transferrin receptor 2 deficiency promotes macrophage polarization and inflammatory arthritis

337 | Feb 18 2023

Tfr2 deletion results in increased joint swelling and bone erosion in a K/BxN serum-transfer arthritis model, which may be due to Tfr2's role in suppressing pro-inflammatory M1-like polarization in macrophages. [Read the Full Post]

STAT3 promotes differentiation of monocytes to MDSCs via CD39/CD73-adenosine signal pathway in oral squamous cell carcinoma

126 | Feb 01 2023

The study found that STAT3 blockade reduced the expression of CD39/CD73 and the synthesis of adenosine, inhibiting monocytes to MDSCs differentiation, leading to prominent anti-tumor efficacy in OSCC mouse model and suggesting STAT3 blockade as a promising therapeutic strategy for oral squamous cell carcinoma. [Read the Full Post]

Ferroptosis-related differentially expressed genes serve as new biomarkers in ischemic stroke and identification of therapeutic drugs

344 | Jan 05 2023

Yinjiang Zhang et al. found that ferroptosis played a critical role in the diversity and complexity of the IS immune microenvironment. [Read the Full Post]

ZD6474 Attenuates Fibrosis and Inhibits Neovascularization in Human Pterygium by Suppressing AKT-mTOR Signaling Pathway

364 | Jan 05 2023

Wenting Liu et al. found that ZD6474 was more effective than MMC in reducing fibrosis and EMT in HPFs. [Read the Full Post]

Comprehensive Analysis of Circular RNA Expression Profiles in Gefitinib-Resistant Lung Adenocarcinoma Patients

261 | Dec 28 2022

Junyong Zou et al. validated that upregulations of hsa_circ_0030591 and hsa_circ_0040348 might play key roles in EGFR-TKI resistance and thus serving as candidates for biomarker. [Read the Full Post]

A mitophagy-related gene signature associated with prognosis and immune microenvironment in colorectal cancer

511 | Dec 24 2022

Cong Zhang et al. developed a novel mitophagy-related gene signature that could be utilized not only as an independent predictive biomarker but also as a tool for tailoring personalizing treatment for CRC patients. [Read the Full Post]

Safety and tolerability of bosutinib in patients with amyotrophic lateral sclerosis (iDReAM study): A multicentre, open-label, dose-escalation phase 1 trial

364 | Dec 23 2022

Keiko Imamura et al. found that the treatment-responsive patients could be distinguished by lower levels of plasma NFL. [Read the Full Post]

KMT2D deficiency drives lung squamous cell carcinoma and hypersensitivity to RTK-RAS inhibition

197 | Dec 22 2022

Yuanwang Pan et al identified KMT2D as a pivotal epigenetic modulator for LUSC oncogenesis and suggested that KMT2D loss renders LUSC therapeutically vulnerable to RTK-RAS inhibition. [Read the Full Post]

Fifty Shades of Scandium: Comparative Study of PET Capabilities Using Sc-43 and Sc-44 with Respect to Conventional Clinical Radionuclides

184 | Dec 11 2022

Thiago V M Lima et al. thought that accurate quantitative scandium-43/44 PET/CT was achievable in commercial devices. [Read the Full Post]

Development of resistance to FGFR inhibition in urothelial carcinoma via multiple pathways in vitro

297 | Nov 29 2022

Geoffrey A Pettitt et al. indicated a benefit from treatment interruptions or re-treatment following disease relapse in some patients. [Read the Full Post]

Predictors of anemia response to momelotinib therapy in myelofibrosis and impact on survival

362 | Nov 27 2022

Naseema Gangat et al. suggested a short-term survival benefit associated with anemia response in momelotinib-treated patients with MF. [Read the Full Post]

MPN-379 Matching-Adjusted Indirect Comparison (MAIC) of Pelabresib (CPI-0610) in Combination With Ruxolitinib vs. JAK Inhibitor Monotherapy in Patients With Intermediate or High-Risk Myelofibrosis

381 | Nov 27 2022

Vikas Gupta et al. suggested that MAIC-adjusted improvements observed in SVR35 and TSS50 at Week 24 with pelabresib and ruxolitinib vs. ruxolitinib, fedratinib, or momelotinib monotherapy were consistent with unadjusted comparisons. [Read the Full Post]

Amivantamab in the Treatment of Metastatic NSCLC: Patient Selection and Special Considerations

125 | Nov 12 2022

Iacopo Petrini et al. found that in combination with chemotherapy and lazertinib in NSCLCs who progressed on osimertinib (MARIPOSA-2). [Read the Full Post]

YH25448, an Irreversible EGFR-TKI with Potent Intracranial Activity in EGFR Mutant Non-Small Cell Lung Cancer

0 | Nov 12 2022

Jiyeon Yun et al. suggested that YH25448 is a promising third-generation EGFR inhibitor, which may be more effective and better tolerated than the currently approved osimertinib. [Read the Full Post]

Poziotinib for EGFR exon 20-mutant NSCLC: Clinical efficacy, resistance mechanisms, and impact of insertion location on drug sensitivity

120 | Oct 27 2022

Yasir Y Elamin et al. found that poziotinib was active in EGFR exon 20-mutant NSCLC, although this activity was influenced by insertion location. [Read the Full Post]

HER2 in Non-Small Cell Lung Cancer: A Review of Emerging Therapies

170 | Oct 26 2022

Natalie F Uy et al. summarized recent progress in novel HER2-targeted agents, and projected next steps in advancing treatment for the thousands of patients with HER2 altered NSCLC. [Read the Full Post]

Preclinical Test of Dacomitinib, an Irreversible EGFR Inhibitor, Confirms Its Effectiveness for Glioblastoma

0 | Oct 20 2022

Cristina Zahonero et al. found that dacomitinib clearly affected receptor signaling in vivo and that its strong antitumoral effect was independent of the presence of mutant receptor isoforms although it could be affected by the PTEN status [Read the Full Post]

Int J Oncol . 2022 Oct;61(4):114. doi: 10.3892/ijo.2022.5404. Epub 2022 Aug 3. Targeting PIM2 by JP11646 results in significant antitumor effects in solid tumors

413 | Oct 04 2022

Eriko Katsuta et al. found that JP11646 may thus be a possible treatment strategy for multiple types of solid cancers. [Read the Full Post]

Imatinib induces diastolic dysfunction and ventricular early-repolarization delay in the halothane-anesthetized dogs: Class effects of tyrosine kinase inhibitors

108 | Oct 03 2022

Koki Chiba et al. found that imatinib suppressed ventricular active relaxation and early repolarization, which might suggest the association of mitochondrial dysfunction-associated inhibition of ATP production. [Read the Full Post]

Hepatocellular carcinoma-derived exosomal miRNA-761 regulates the tumor microenvironment by targeting the SOCS2/JAK2/STAT3 pathway

138 | Sep 30 2022

Xiao-Hu Zhou et al. found that exosomal miR-761 modulated the tumor microenvironment via SOCS2/JAK2/STAT3 pathway-dependent activation of CAFs. [Read the Full Post]

Randomized, Double-Blind, Placebo-Controlled Phase III Study of Paclitaxel ± Napabucasin in Pretreated Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

124 | Sep 14 2022

Manish A Shah et al. showed that adding napabucasin to paclitaxel did not improve survival in patients with pretreated advanced gastric or GEJ adenocarcinoma. [Read the Full Post]

Combining Organoid Models with Next-Generation Sequencing to Reveal Tumor Heterogeneity and Predict Therapeutic Response in Breast Cancer

291 | Sep 06 2022

Yuhong Liu et al. thought that the combined use of tumor organoids and NGS was a potential way to test tumor heterogeneity and predict drug response in ER + BC, which contributed to the development of personalized therapy. [Read the Full Post]

Drug Repurposing Based on Protozoan Proteome: In Vitro Evaluation of In Silico Screened Compounds against Toxoplasma gondii

112 | Aug 27 2022

Débora Chaves Cajazeiro et al. found that interactions with the Na+/K+ ATPase transporter for Homo sapiens and Mus musculus, indicating a possible mechanism of action of this compound. [Read the Full Post]

MiR-630 suppresses non-small cell lung cancer by targeting vimentin

155 | Aug 26 2022

Bin Wang et al. thought that MiR-630 constrained the progression of NSCLC by inhibiting JAK2/STAT3 pathway and downregulating VIM expression. [Read the Full Post]

Evaluation of the Efficacy of Saracatinib-Loaded Nanoparticles in Lymphatic Metastases of HNSCC with the Aid of Bioluminescence Imaging

178 | Aug 13 2022

Liwei Lang et al. showed great potential to evaluate treatments on metastatic diseases with the aid of bioluminescent technology. [Read the Full Post]

Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline

233 | Aug 01 2022

Navneet Singh et al. thought that for patients with an anaplastic lymphoma kinase rearrangement, a performance status (PS) of 0-2, and previously untreated NSCLC, clinicians should offer alectinib or brigatinib or lorlatinib. [Read the Full Post]

Comparative Efficacy and Safety of Janus Kinase Inhibitors and Secukinumab in Patients with Active Ankylosing Spondylitis: A Systematic Review and Meta-Analysis

416 | Jul 13 2022

Young Ho Lee suggested that tofacitinib 5 mg had the highest likelihood of being the best treatment for achieving the ASAS40 response rate, followed by upadacitinib 15 mg, secukinumab 150 mg, filgotinib 200 mg, and placebo. [Read the Full Post]

Screening of epidermal growth factor receptor inhibitors in natural products by capillary electrophoresis combined with high performance liquid chromatography-tandem mass spectrometry

0 | Jul 13 2022

Feng Li et al. demonstrated a significant merit of the method in the identification of the bioactive compounds in natural products. [Read the Full Post]

Predictive role of CD36 expression in HER2-positive breast cancer patients receiving neoadjuvant trastuzumab

286 | Jul 08 2022

Francesca Ligorio et al. thought that high CD36 expression predicted worse clinical outcomes in early-stage HER2+ BC treated with trastuzumab-based neoadjuvant therapy. [Read the Full Post]

Survival benefit of using pemetrexed for EGFR mutation-positive advanced non-small-cell lung cancer in a randomized phase III study comparing gefitinib to cisplatin plus docetaxel (WJTOG3405)

264 | Jun 23 2022

Naoki Haratake et al. thought that pemetrexed should be administered without fail as a sequential treatment to improve the prognosis of EGFR-mutated NSCLC as well as like EGFR-tyrosine kinase inhibitors. [Read the Full Post]

Clinical efficacy of osimertinib in EGFR-mutant non-small cell lung cancer with distant metastasis

356 | Jun 15 2022

Soei Gen et al. thought that osimertinib provided better clinical benefits than 1st- and 2nd-generation EGFR-TKIs for patients with EGFR-mutant NSCLC, particularly those with brain or bone metastases and exon 19 deletion. [Read the Full Post]

Systemic Treatment Patterns and Outcomes in Patients With EGFR Mutated Non-small Cell Lung Cancer and Leptomeningeal Disease

326 | May 26 2022

Cristina M Merkhofer et.al found that prior exposure to osimertinib appeared to favorably influence the natural history of LM disease. [Read the Full Post]

Abrocitinib: A New FDA-Approved Drug for Moderate-to-Severe Atopic Dermatitis

626 | May 20 2022

Patrick O Perche et al. thought that abrocitinib was an efficacious oral JAK 1 inhibitor recently FDA-approved for patients ≥ 18 years old with moderate-to-severe AD who had not responded to systemic medications or when contraindicated otherwise. [Read the Full Post]

Lorlatinib Versus Pemetrexed-Based Chemotherapy in Patients With ALK-rearranged NSCLC Previously Treated With Alectinib

439 | May 08 2022

Yuki Takeyasu et al. showed that clinical outcomes of PEM and LOR after failure of alectinib were similar in patients with ALK-positive NSCLC. [Read the Full Post]

Alternating therapy with osimertinib and afatinib for treatment-naive patients with EGFR-mutated advanced non-small cell lung cancer: A single-group, open-label phase 2 trial (WJOG10818L)

480 | May 02 2022

Hidetoshi Hayashi et al. found that Alternating therapy with osimertinib and afatinib for treatment-naive patients with EGFR- mutated advanced NSCLC did not meet its primary end point, despite the encouraging efficacy and safety profile of this treatment strategy. [Read the Full Post]

FLT3 mutations in acute myeloid leukemia: a review focusing on clinically applicable drugs

389 | May 02 2022

Jae-Sook Ahn et al. summarized information on clinically available FLT3 inhibitors for the management of AML with FLT3 mutations. [Read the Full Post]

Unique Presentation of Bortezomib-Associated Thrombotic Microangiopathy Responsive to Therapeutic Plasma Exchange and Eculizumab Therapy

392 | Apr 27 2022

Robert C Sterner et al. demonstrated the possible utility of TPE with plasma replacement. [Read the Full Post]

Changes in Blood Cell Deformability in Chorea-Acanthocytosis and Effects of Treatment With Dasatinib or Lithium

267 | Apr 23 2022

Felix Reichel et al. found that the need for a systematic assessment of the contribution of impaired blood cell mechanics to the clinical manifestation of ChAc. [Read the Full Post]

Nuclear translocation of p85β promotes tumorigenesis of PIK3CA helical domain mutant cancer

775 | Apr 19 2022

Yujun Hao et al. found that the drug combination could be an effective therapeutic approach for PIK3CA helical domain mutant tumors. [Read the Full Post]

What's new in myeloproliferative neoplasia

843 | Mar 19 2022

Stefan Schmidt et al. revealed components of the alarmin complex (S100A8 und S100A9) drove this local sterile inflammation process, which also represented a potential therapeutic target, as the S100A8 and A9 inhibitor Tasquinimod reduced fibrosis in a pre-clinical animal model. [Read the Full Post]

The role of the atypical chemokine receptor CCRL2 in myelodysplastic syndrome and secondary acute myeloid leukemia

741 | Mar 18 2022

Theodoros Karantanos et al. implicated CCRL2 as an MDS/sAML cell growth mediator, partially through JAK2/STAT signaling. [Read the Full Post]

Construction of an Immune-Autophagy Prognostic Model Based on ssGSEA Immune Scoring Algorithm Analysis and Prognostic Value Exploration of the Immune-Autophagy Gene in Endometrial Carcinoma (EC) Based on Bioinformatics

459 | Mar 13 2022

Xiaomin Xu et al. constructed the immuno-autophagy prognosis model of endometrial cancer and identified three high-risk immunoautophagy genes, including VEGFA, CCL2, and Ifng. [Read the Full Post]

Baricitinib for relapsing giant cell arteritis: a prospective open-label 52-week pilot study

744 | Feb 23 2022

Matthew J Koster et al. showed that in this proof-of-concept study, baricitinib at 4 mg/day was well tolerated and discontinuation of GC was allowed in most patients with relapsing GCA. [Read the Full Post]

Drug survival of biologics and novel immunomodulators for rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, and psoriasis - A nationwide cohort study from the DANBIO and DERMBIO registries

527 | Feb 22 2022

Alexander Egeberg et al. emphasized that although these diseases had many overlaps in their pathogenesis, there was a need for an individualized treatment approach that considered the underlying disease, patient profile, and treatment history. [Read the Full Post]

Bidirectional Responses of Eight Neuroinflammation-Related Transcriptional Factors to 64 Flavonoids in Astrocytes with Transposable Insulated Signaling Pathway Reporters

414 | Feb 12 2022

Valeri V Mossine et al. conclude that transposable insulated reporters of transcriptional activation represent a convenient neurochemistry tool in screening for activators/inhibitors of signaling pathways. [Read the Full Post]

Role of epidermal growth factor receptor inhibitor-induced interferon pathway signaling in the head and neck squamous cell carcinoma therapeutic response

560 | Jan 31 2022

Sean P Korpela et al. found that heterogeneous, tumor cell-intrinsic, EGFR/ERBB inhibitor-induced IFN pathway activation in HNSCC and suggest that individual tumor responses to oncogene-targeted agents are a sum of direct growth inhibitory effects and variably-induced participation of host immune cells. [Read the Full Post]

HER2 Tyrosine Kinase Inhibitors in the Sensitization to Cancers Resistant to HER2 Antibodies

471 | Jan 30 2022

Heena Singla et al. thought that act synergistically with the HER2-antibody resulting in an additive clinical response in patients. [Read the Full Post]

Experiences of running a stratified medicine adaptive platform trial: Challenges and lessons learned from 10 years of the FOCUS4 trial in metastatic colorectal cancer

379 | Jan 30 2022

Louise C Brown et al. found that adaptive stratified medicine platform studies were feasible in common cancers but present challenges. [Read the Full Post]

The Effect of STAT3 Signal Pathway Activation on Retinopathy of Prematurity

338 | Jan 29 2022

Jianbing Ren et al. provided potential novel therapeutic approach to the prevention and treatment of ROP. [Read the Full Post]

CYT387 Inhibits the Hyperproliferative Potential of Fibroblast-like Synoviocytes via Modulation of IL-6/JAK1/STAT3 Signaling in Rheumatoid Arthritis

624 | Jan 04 2022

Susmita Srivastava et al. found that CYT387 inhibits proliferation, migration, and pathogenic diseased potential of FLS isolated from adjuvant-induced arthritic (AA) rats via targeting IL-6/JAK1/STAT3 signaling cascade. [Read the Full Post]

A phase 1b study of erlotinib and momelotinib for the treatment of EGFR-mutated, tyrosine kinase inhibitor-naive metastatic non-small cell lung cancer

665 | Jan 03 2022

Sukhmani K Padda et al. showed that the JAK1/2 and TBK1 inhibitor momelotinib in combination with erlotinib did not appear to enhance benefit over the historical data of erlotinib monotherapy in patients with EGFR-mutated NSCLC. [Read the Full Post]

YH25448, an Irreversible EGFR-TKI with Potent Intracranial Activity in EGFR Mutant Non-Small Cell Lung Cancer

0 | Dec 20 2021

Jiyeon Yun et al. suggested that YH25448 was a promising third-generation EGFR inhibitor, which might be more effective and better tolerated than the currently approved osimertinib. [Read the Full Post]

Cardiac Safety Assessment of Lazertinib: Findings From Patients With EGFR Mutation-Positive Advanced NSCLC and Preclinical Studies

606 | Dec 19 2021

Seong Bok Jang et al. indicated that lazertinib was not associated with increased cardiac risk. [Read the Full Post]

Poziotinib in Non-Small-Cell Lung Cancer Harboring HER2 Exon 20 Insertion Mutations After Prior Therapies: ZENITH20-2 Trial

689 | Dec 02 2021

Xiuning Le et al. found that Poziotinib demonstrated antitumor activity in previously treated patients with HER2 exon 20 insertion NSCLC. [Read the Full Post]

Lapatinib and poziotinib overcome ABCB1-mediated paclitaxel resistance in ovarian cancer

653 | Dec 02 2021

J Robert McCorkle et al. thought that lapatinib and poziotinib combined with paclitaxel synergizes to inhibit the proliferation of ABCB1-overexpressing ovarian cancer cells in vitro. [Read the Full Post]

Preclinical Test of Dacomitinib, an Irreversible EGFR Inhibitor, Confirms Its Effectiveness for Glioblastoma

0 | Nov 26 2021

Cristina Zahonero et al. found that dacomitinib clearly affected receptor signaling in vivo and that its strong antitumoral effect was independent of the presence of mutant receptor isoforms although it could be affected by the PTEN status. [Read the Full Post]

Construction of a ceRNA Network and Analysis of Tumor Immune Infiltration in Pancreatic Adenocarcinoma

583 | Nov 12 2021

Jingjing Xiao et sl. suggested that the IC50 values of gemcitabine in PAAD were not significantly different between the high and low risk groups. [Read the Full Post]

Pim kinase inhibitor co-treatment decreases alternative non-homologous end-joining DNA repair and genomic instability induced by topoisomerase 2 inhibitors in cells with FLT3 internal tandem duplication

737 | Nov 12 2021

Mario Scarpa et al. found that Pim kinase inhibitor co-treatment both enhanced TOP2 inhibitor cytotoxicity and decreased TOP2 inhibitor-induced genomic instability in cells with FLT3-ITD. [Read the Full Post]

The Circadian Rhythms of STAT3 in the Rat Pineal Gland and Its Involvement in Arylalkylamine-N-Acetyltransferase Regulation

652 | Nov 09 2021

Simona Moravcová et al. suggested that the higher nocturnal endogenous level of STAT3 in the pineal gland decelerated or hampered the process of NA-induced AANAT activation or affected the AANAT enzyme stability. [Read the Full Post]

A Novel Small Molecule, LCG-N25, Inhibits Oral Streptococcal Biofilm

461 | Oct 23 2021

Xiaoying Lyu et al. suggested that LCG-N25 may represent a promising antimicrobial agent that can be used as an adjuvant to the management of dental caries. [Read the Full Post]

Modelling hypersensitivity to trastuzumab defines biomarkers of response in HER2 positive breast cancer

814 | Oct 15 2021

Laura Díaz-Gil et al. thought that the identification of trastuzumab response biomarkers might be used to select patients particularly sensitive to facilitate the use of trastuzumab-based therapies and refine follow-up guidelines in patients with HER2+ tumors. [Read the Full Post]

Successful treatment of hepatosplenic T-cell lymphoma with fludarabine, high-dose cytarabine and subsequent unrelated umbilical cord blood transplantation

816 | Oct 04 2021

Takaya Honda et al. found a heterozygous nonsense c.2961C>G (p.Tyr987Ter) variant of the KMT2C gene. [Read the Full Post]

The imbalance of Th17/Treg via STAT3 activation modulates cognitive impairment in P. gingivalis LPS-induced periodontitis mice

505 | Oct 03 2021

Xu Zhang et al. thought that the STAT3 signaling pathway might have immunoregulatory effects on the mouth-to-brain axis. [Read the Full Post]

An organ-on-a-chip model for pre-clinical drug evaluation in progressive non-genetic cardiomyopathy

827 | Sep 19 2021

Erika Yan Wang et al. found multifaceted cardioprotective effects of relaxin in restoring contractile function and reducing fibrotic remodeling. [Read the Full Post]

Effects of the Fyn kinase inhibitor saracatinib on ventral striatal activity during performance of an fMRI monetary incentive delay task in individuals family history positive or negative for alcohol use disorder. A pilot randomised trial

746 | Sep 17 2021

Krishna T Patel et al. suggested a possible therapeutic role for Src/Fyn kinase inhibitors in AUD risk. [Read the Full Post]

Brigatinib causes tumor shrinkage in both NF2-deficient meningioma and schwannoma through inhibition of multiple tyrosine kinases but not ALK

794 | Sep 07 2021

Long-Sheng Chang et al. demonstrated the power of the de novo unbiased approach for drug discovery and represented a major step forward in the advancement of therapeutics for the treatment of NF2 related malignancies. [Read the Full Post]

Tofacitinib Ameliorates Lupus Through Suppression of T Cell Activation Mediated by TGF-Beta Type I Receptor

1203 | Aug 20 2021

Qing Yan et al. thought that tofacitinib could suppress T cell activation by upregulating TGFβRI expression, which provided a possible molecular mechanism underlying clinical efficacy of tofacitinib in treating SLE patients. [Read the Full Post]

MiR-221 confers lapatinib resistance by negatively regulating p27 kip1 in HER2-positive breast cancer

1039 | Aug 16 2021

Thanh Kieu Huynh et al. suggested Src inhibition as a potential strategy to overcome lapatinib resistance. [Read the Full Post]

Bruton's tyrosine kinase (BTK) mediates resistance to EGFR inhibition in non-small-cell lung carcinoma

777 | Aug 01 2021

Chi-Tai Yeh et al. suggested that BTK mediated stemness and EMT properties, and inhibition of BTK potentiated the effect of Gefitinib and Osimertinib in NSCLC cells resistant to TKI. [Read the Full Post]

XHL11, a novel selective EGFR inhibitor, overcomes EGFR T790M-mediated resistance in non-small cell lung cancer

563 | Jul 07 2021

Yi Li et al. thought that XHL11 might be developed as a promising EGFR TKI for the therapeutic use of NSCLC patients. [Read the Full Post]

Using JAK inhibitor to treat cytokine release syndrome developed after chimeric antigen receptor T cell therapy for patients with refractory acute lymphoblastic leukemia: A case report

972 | Jun 30 2021

Fu Ming Zi et al. found that Ruxolitinib could be used as an alternative therapeutic approach for severe and refractory CRS without impairing CAR-T amplification and anti-tumor effect. [Read the Full Post]

Enteral lorlatinib after alectinib as a treatment option in anaplastic lymphoma kinase-positive non-small cell lung cancer with triple problems: carcinomatous meningitis, poor performance status, and dysphagia-a case report

651 | Jun 16 2021

Kota Sasaki et al. thought that lorlatinib could be a treatment option for patients with ALK-positive NSCLC showing carcinomatous meningitis, poor PS, and dysphagia upon failure of other ALK inhibitor-based treatments. [Read the Full Post]

Efficacy of tyrosine kinase inhibitors against lung cancer with EGFR exon 18 deletion: Case report and pooled analysis

1151 | Jun 08 2021

Rafael Rubiera-Pebe et al. showed that afatinib was associated with a greater tumor response rate and a longer PFS than the first generation TKIs. [Read the Full Post]

Triazole antifungal use for prophylaxis and treatment of invasive fungal diseases for patients receiving gilteritinib

817 | Jun 08 2021

Muneerah M Aleissa et al. found that concomitant gilteritinib and triazole therapy was feasible and was not associated with clinically meaningful increase in gilteritinib-related AEs. [Read the Full Post]

Analysis of chemotherapy-induced peripheral neuropathy using the Japanese Adverse Drug Event Report database

957 | Jun 02 2021

Misaki Inoue et al. revealed several drugs associated with a high risk for CIPN development. [Read the Full Post]

IGF1R and Src inhibition induce synergistic cytotoxicity in HNSCC through inhibition of FAK

555 | May 26 2021

Christine E Lehman et al. found that treatment with BMS754807 and dasatinib, or a FAK inhibitor alone, significantly increased cleaved-PARP in human ex-vivo HNSCC patient tissues demonstrating a potential clinical utility for targeting FAK or the combined targeting of the IGF1R with Src. [Read the Full Post]

Inhibition of the Histone Methyltransferase EZH2 Enhances Protumor Monocyte Recruitment in Human Mesothelioma Spheroids

1014 | May 17 2021

Silvia Mola et al. found that TAMs were a driving force for MPM growth, progression, and resistance to tazemetostat. [Read the Full Post]

In vivo Pharmacokinetic Drug-Drug Interaction Studies Between Fedratinib and Antifungal Agents Based on a Newly Developed and Validated UPLC/MS-MS Method

1070 | Apr 04 2021

Congrong Tang et al. thought that the toxicity of fedratinib should be avoided when the concurrent use of fedratinib with CYP3A4 inhibitors might occur. [Read the Full Post]

Current Clinical Investigations in Myelofibrosis

1190 | Apr 04 2021

Sangeetha Venugopal et al. provided insight into the novel therapies under clinical evaluation. [Read the Full Post]

Pharmacological inhibition of IKKβ dampens NLRP3 inflammasome activation after priming in the human myeloid cell line THP-1

952 | Mar 25 2021

Adeline Unterreiner et al. suggested that IκKβ might fulfill a dual role in coupling priming and activation of the NLRP3 inflammasome. [Read the Full Post]

Immediate Effect of Baricitinib on Arthritis and Biological Disease-Modifying Antirheumatic Drug-Induced Psoriasis-Like Skin Lesions in Two Patients with Rheumatoid Arthritis

1037 | Mar 05 2021

Yoshifumi Tada et al. found that baricitinib was initiated because of RA flare and resulted in immediate beneficial effects on arthritis as well as skin lesions. [Read the Full Post]

In-vitro evaluation of the immunomodulatory effects of baricitinib: implication for COVID-19 therapy

1092 | Mar 04 2021

Linda Petrone et al. found that exogenous addition of baricitinib decreased the in-vitro SARS-CoV-2-specific response in COVID-19 patients using a whole-blood platform. [Read the Full Post]

EGR1 knockdown alleviates the cerebral injury in rats with intracerebral hemorrhage (ICH) via STAT3/NF-κB pathway by reducing RXRα acetylation level

689 | Feb 23 2021

Lijuan Xie et al. found that EGR1 increased RXRα acetylation level by regulating p300, thereby aggravating brain damage in ICH rat model and dysfunction in BMECs, which might through the STAT3/NF-κB pathway. [Read the Full Post]

Stomatin-like Protein 2 Promotes Tumor Cell Survival by Activating the JAK2-STAT3-PIM1 Pathway, Suggesting a Novel Therapy in CRC

756 | Feb 07 2021

Qiang Liu et al. suggested that SLP-2 controlled the JAK2-STAT3-PIM1 oncogenic pathway, offering a rationale for a novel therapeutic strategy with combined SGI-1776 and TG-101348 in CRC. [Read the Full Post]

Role of epidermal growth factor receptor inhibitor-induced interferon pathway signaling in the head and neck squamous cell carcinoma therapeutic response

644 | Feb 06 2021

Sean P Korpela 1 et al. found eterogeneous, tumor cell-intrinsic, EGFR/ERBB inhibitor-induced IFN pathway activation in HNSCC and suggest that individual tumor responses to oncogene-targeted agents are a sum of direct growth inhibitory effects and variably-induced participation of host immune cells. [Read the Full Post]

STAT3 Is an Upstream Regulator of Granzyme G in the Maternal-To-Zygotic Transition of Mouse Embryos

503 | Feb 05 2021

Huan Ou-Yang et al. suggested that STAT3, a maternal protein, was a critical transcription factor and regulated Gzmg transcription activity in preimplantation mouse embryos. [Read the Full Post]

Dual inhibition of FOXM1 and its compensatory signaling pathway decreased the survival of ovarian cancer cells

564 | Feb 05 2021

Dae Woo Lee et al. found that the addition of tipifarnib or rottlerin to inhibit N‑Ras or p‑PKCδ (S664), respectively, inhibited the compensatory signaling pathway response induced by FDI‑6 in HeyA8 cells. [Read the Full Post]

PIM1 inhibitor synergizes the anti-tumor effect of osimertinib via STAT3 dephosphorylation in EGFR-mutant non-small cell lung cancer

536 | Jan 31 2021

Ziyi Sun et al. found that PIM1 was a poor prognostic factor for NSCLC. [Read the Full Post]

MOMENTUM: momelotinib vs danazol in patients with myelofibrosis previously treated with JAKi who are symptomatic and anemic

918 | Jan 13 2021

Srdan Verstovsek et al.showed that the MOMENTUM Phase III study was designed to confirm and extend observations of safety and clinical activity of MMB. [Read the Full Post]

CYT387, a Novel JAK2 Inhibitor, Suppresses IL-13-Induced Epidermal Barrier Dysfunction Via miR-143 Targeting IL-13Rα1 and STAT3

1008 | Jan 13 2021

Yan Zu et al. revealed that the protective effects and the underlying mechanisms of CYT387 in AD, which provided evidence that miR-143 might be a novel therapeutic target for AD. [Read the Full Post]

EGFR C797S as a Resistance Mechanism of Lazertinib in Non-small Cell Lung Cancer with EGFR T790M Mutation

536 | Dec 30 2020

Sehhoon Park et al. reported the first case of resistance mechanism to the novel third-generation EGFR TKI, lazertinib, which showed promising clinical efficacy in phase 1-2 study. [Read the Full Post]

Poziotinib suppresses ovarian cancer stem cell growth via inhibition of HER4-mediated STAT5 pathway

733 | Dec 15 2020

Heejin Lee et al. suggested that HER4 might be a promising therapeutic target for ovarian CSCs, and that poziotinib might be an effective therapeutic option for the prevention of ovarian cancer recurrence. [Read the Full Post]

Poziotinib Inhibits the Efflux Activity of the ABCB1 and ABCG2 Transporters and the Expression of the ABCG2 Transporter Protein in Multidrug Resistant Colon Cancer Cells

642 | Dec 14 2020

Yongchao Zhang et al. showed that poziotinib interacted with the ABCB1 and ABCG2 transporter, suggesting that poziotinib might increase the efficacy of certain chemotherapeutic drugs used in treating MDR CRC. [Read the Full Post]

Preclinical Test of Dacomitinib, an Irreversible EGFR Inhibitor, Confirms Its Effectiveness for Glioblastoma

969 | Dec 08 2020

Cristina Zahonero et al. confirmd that dacomitinib clearly affected receptor signaling in vivo and that its strong antitumoral effect was independent of the presence of mutant receptor isoforms although it could be affected by the PTEN status (as it was less effective in a PTEN-deleted GBM line). [Read the Full Post]

Co-targeting PIM and PI3K/mTOR using multikinase inhibitor AUM302 and a combination of AZD-1208 and BEZ235 in prostate cancer

867 | Nov 22 2020

Sabina Luszczak et al. believed that a co-targeting approach was a viable therapeutic strategy that should be developed further in pre-clinical studies. [Read the Full Post]

Cost-effectiveness of treatments for HER2-positive metastatic breast cancer and associated metastases: an overview of systematic reviews

542 | Nov 21 2020

Vakaramoko Diaby et al. examined evidence on the cost-effectiveness of treatments for HER2-positive metastatic breast cancer and associated metastases through a review of systematic reviews on the topic. [Read the Full Post]

Cucurbitacin E and I target the JAK/STAT pathway and induce apoptosis in Sézary cells

1572 | Nov 18 2020

Isabella J Brouwer et al. suggested that STAT3 played a preferential role in the mechanism of action of these cucurbitacins. [Read the Full Post]

To inhibit TrxR1 is to inactivate STAT3-Inhibition of TrxR1 enzymatic function by STAT3 small molecule inhibitors

560 | Oct 29 2020

Sander Busker et al. suggested that targeting of TrxR1 might be a common feature for many small molecules that inhibited cellular STAT3 function. [Read the Full Post]

SHP2 is a multifunctional therapeutic target in drug resistant metastatic breast cancer

709 | Oct 19 2020

Hao Chen et al.found that SHP2 constituted a shared signaling node allowing MBC cells to simultaneously engage a diversity of growth and survival pathways, including those derived from the ECM. [Read the Full Post]

A study of human leukocyte antigen-haploidentical hematopoietic stem cells transplantation combined with allogenic mesenchymal stem cell infusion for treatment of severe aplastic anemia in pediatric and adolescent patients

834 | Sep 29 2020

Li Ding et al. suggested that cotransplantation of HLA-haploidentical HSC and allogenic mesenchymal stem cell might provide an effective and safe treatment for children and adolescents with SAA who lacked matched donors. [Read the Full Post]

Xanthatin alleviates airway inflammation in asthmatic mice by regulating the STAT3/NF-κB signaling pathway

614 | Sep 28 2020

Jingxia Chang et al. concluded that Xanthatin attenuated airway inflammation in asthmatic mice through blocking the STAT3/NFκB signaling pathway, indicating the potential of Xanthatin as a useful therapeutic agent for asthma. [Read the Full Post]

Gefitinib Versus Gefitinib Plus Pemetrexed and Carboplatin Chemotherapy in EGFR-Mutated Lung Cancer

0 | Sep 11 2020

Vanita Noronha et al. found that adding pemetrexed and carboplatin chemotherapy to gefitinib significantly prolonged PFS and OS but increased toxicity in patients with NSCLC. [Read the Full Post]

Dual inhibition of Src and PLK1 regulate stemness and induce apoptosis through Notch1-SOX2 signaling in EGFRvIII positive glioma stem cells (GSCs)

726 | Sep 09 2020

Xuetao Li et al. indicated that p-Src and PLK1 contributed to cancer stemness in EGFRvIII-positive GSCs by driving Notch1-SOX2 signaling, a finding that had important clinical implications. [Read the Full Post]

IGF2BP1 is a targetable SRC/MAPK-dependent driver of invasive growth in ovarian cancer

725 | Sep 09 2020

Nadine Bley et al. provided a rationale for the therapeutic benefit of combinatorial SRC/MEK inhibition in mesenchymal-like HGSOC. [Read the Full Post]

Optimal Care for Patients with Anaplastic Lymphoma Kinase (ALK)-Positive Non-Small Cell Lung Cancer: A Review on the Role and Utility of ALK Inhibitors

583 | Aug 23 2020

Abhay Singh et al. provided a summary of the clinical development of crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib and highlighted current management paradigms, current and evolving clinical information, emerging clinical decision-making and sequencing of therapy in advanced, metastatic, or recurrent ALK-positive NSCLC. [Read the Full Post]

Screening of epidermal growth factor receptor inhibitors in natural products by capillary electrophoresis combined with high performance liquid chromatography-tandem mass spectrometry

0 | Jul 29 2020

Feng Li et al. demonstrated a significant merit of our method in the identification of the bioactive compounds in natural products. [Read the Full Post]

Effectiveness and Costs Among Rheumatoid Arthritis Patients Treated with Targeted Immunomodulators Using Real-World U.S. Data

992 | Jul 28 2020

Mahdi Gharaibeh et al. showed that the range of patients who were effectively treated with first-line therapy was higher for certain tumor necrosis factor inhibitors and tocilizumab. [Read the Full Post]

Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial

1081 | Jul 22 2020

Cristina Saura et al.showed that N+C significantly improved PFS and time to intervention for CNS disease versus L+C. No new N+C safety signals were observed. [Read the Full Post]

In vitro and in vivo efficacies of inhibitors of the EGFR/MEK/ERK signaling in the treatment of alveolar echinococcosis

755 | Jul 17 2020

Zhe Cheng et al. demonstrated the potential of EGFR-mediated signaling as a target for the development of novel anti-AE agents. [Read the Full Post]

Efficacy of Gefitinib Combined With 125 I Radioactive Particles in the Treatment of Transplanted Lung Cancer Tumors in Nude Mice

849 | Jul 02 2020

Chaojie Li et al. found that Gefitinib combined with 125I radioactive particles brachytherapy could significantly inhibit tumor growth. [Read the Full Post]

Afatinib for the Treatment of NSCLC Harboring Uncommon EGFR Mutations: A Database of 693 Cases

999 | Jun 19 2020

James Chih-Hsin Yang et al. found that Afatinib has clinical activity in NSCLC against major uncommon and compound EGFR mutatios. It also has broad activity against other uncommon EGFR mutations and some exon 20 insertions. The data support the use of afatinib in these settings. [Read the Full Post]

Exploring the Relevance of Senotherapeutics for the Current SARS-CoV-2 Emergency and Similar Future Global Health Threats

1035 | Jun 05 2020

Marco Malavolta et al. explored the idea that an exacerbated inflammatory response, in particular that mediated by IL-6, migtht drive the deleterious consequences of the infection. [Read the Full Post]

A Natural Anthraquinone Derivative Shikonin Synergizes With AZD9291 Against wtEGFR NSCLC Cells Through Reactive Oxygen Species-Mediated Endoplasmic Reticulum Stress

578 | Jun 01 2020

Xiu Hu et al. suggested that combining shikonin with AZD9291was a promising therapeutic strategy for treating wtEGFR NSCLC patients. [Read the Full Post]

Essential Thrombocythemia Treatment Algorithm 2018

925 | May 24 2020

Ayalew Tefferi et al. provided a point-of-care treatment algorithm that was risk-adapted and based on evidence and decades of experience. [Read the Full Post]

YH25448, an Irreversible EGFR-TKI With Potent Intracranial Activity in EGFR Mutant Non-Small Cell Lung Cancer

1328 | Apr 23 2020

Jiyeon Yun et al. suggested that YH25448 is a promising third-generation EGFR inhibitor, which may be more effective and better tolerated than the currently approved osimertinib. [Read the Full Post]

Design, Synthesis and Biological Evaluation of 2-amino-4-(1,2,4-triazol)pyridine Derivatives as Potent EGFR Inhibitors to Overcome TKI-resistance

600 | Apr 22 2020

Haikui Yang et al. provided 2-amino-4-(1,2,4-triazol)pyridines as a new scaffold for EGFRT790M and/or EGFRvⅢ inhibitor. [Read the Full Post]

Drug resistance occurred in a newly characterized preclinical model of lung cancer brain metastasis

635 | Apr 10 2020

Shah N et al. demonstrated that brain metastases of lung cancer cells may independently prompt drug resistance without drug treatment. [Read the Full Post]

Sphingosine Kinase 1 in Breast Cancer-A New Molecular Marker and a Therapy Target

702 | Apr 09 2020

Alshaker H et al. concluded that SK1 may have a potential as a target for precision medicine, its high expression being a negative prognostic marker in ER-negative breast cancer, as well as a target for chemosensitization therapy. [Read the Full Post]

AZD1208, a Pan-Pim Kinase Inhibitor, Has Anti-Growth Effect on 93T449 Human Liposarcoma Cells via Control of the Expression and Phosphorylation of Pim-3, mTOR, 4EBP-1, S6, STAT-3 and AMPK

698 | Mar 30 2020

Yadav AK et al. demonstrated that AZD1208 inhibits growth of liposarcoma cells and that this activity is mediated through Pim-3 kinase, STAT-3, mTOR, S6 and AMPK expression and phosphorylation pathways. [Read the Full Post]

Real-World Data of Triplet Combination of Trastuzumab, Lapatinib, and Chemotherapy in HER2-Positive Metastatic Breast Cancer: A Multicenter Retrospective Study

572 | Mar 29 2020

Li Y et al. indicated that TLC demonstrated promising effects and tolerable safety in HER2+MBC, even in patients with BM, providing a theoretical basis for clinical practice. [Read the Full Post]

Molecular alterations and poziotinib efficacy, a pan-HER inhibitor, in human epidermal growth factor receptor 2 (HER2)-positive breast cancers: Combined exploratory biomarker analysis from a phase II clinical trial of poziotinib for refractory HER2-positive breast cancer patients

614 | Mar 11 2020

Koga T et al. identified HER2 CN amplification, PIK3CA pathway alteration, and ERBB3 cytoplasmic mutation showed predictive roles on clinical outcomes of HER2-positive MBC treated with poziotinib. [Read the Full Post]

Activity of a novel HER2 inhibitor, poziotinib, for HER2 exon 20 mutations in lung cancer and mechanism of acquired resistance: An in vitro study

704 | Mar 10 2020

Koga T et al. identified the secondary C805S at the covalent binding site of HER2 to poziotinib as a potential mechanism of acquired resistance. HSP90 inhibitors might be a therapeutic strategy for the C805S secondary mutation. [Read the Full Post]

Phase I Dose-Escalation Study of the pan-HER Inhibitor, PF299804, in Patients With Advanced Malignant Solid Tumors

632 | Mar 02 2020

Pasi A Jänne et al. showed the MTD of PF299804 is 45 mg/d. Both continuous and intermittent treatment schedules were well tolerated, and encouraging signs of antitumor activity were observed in gefitinib/erlotinib treated NSCLC patients. [Read the Full Post]

AZD1208, a Pan-Pim Kinase Inhibitor, Has Anti-Growth Effect on 93T449 Human Liposarcoma Cells via Control of the Expression and Phosphorylation of Pim-3, mTOR, 4EBP-1, S6, STAT-3 and AMPK

570 | Feb 17 2020

Yadav AK et al. demonstrated that AZD1208 inhibits growth of liposarcoma cells and that this activity is mediated through Pim-3 kinase, STAT-3, mTOR, S6 and AMPK expression and phosphorylation pathways. [Read the Full Post]

Administration of Lapatinib with Food Increases Its Plasma Concentration in Chinese Patients with Metastatic Breast Cancer: A Prospective Phase II Study

735 | Feb 16 2020

Xu F et al. showed that receiving lapatinib with food can increase its plasma concentration with no significantly increased drug-related toxicity. We suggest that a larger-sample-size clinical trial is needed to fully understand the effect of administration of lapatinib with food. [Read the Full Post]

The JAK2 inhibitor AZD1480 inhibits hepatitis A virus replication in Huh7 cells

913 | Feb 12 2020

Jiang X et al. proposed that AZD1480 can inhibit HAV IRES activity and HAV replication through the inhibition of the La protein. [Read the Full Post]

Treatment outcome and clinical characteristics of HER2 mutated advanced non-small cell lung cancer patients in China

695 | Feb 01 2020

Fei Xu et al. found that HER2 mutated lung cancer patients were younger, mostly females, never or light smokers, with histologically diagnosed adenocarcinomas. Compared with afatinib, chemotherapy might bring more benefit to HER2 mutated advanced lung cancer patients, especially the most common type of HER2 exon 20 insertions, A775_G776insYVMA subtype. [Read the Full Post]

Determination of Somatic Mutations and Tumor Mutation Burden in Plasma by CAPP-Seq during Afatinib Treatment in NSCLC Patients Resistance to Osimertinib

880 | Feb 01 2020

Ishii H et al. demonstrated that detection of mutant allele frequency and TMB of ctDNA by CAPP-Seq could help determine the effectiveness of and resistance to afatinib. [Read the Full Post]

Napabucasin: An Update on the First-in-Class Cancer Stemness Inhibitor

0 | Jan 05 2020

Hubbard JM and Grothey A indicated that napabucasin may prove useful in targeting cancer stem cells, with the potential to suppress metastasis and prevent relapse in patients with varying cancer types. [Read the Full Post]

Identification of RNPC3 as a novel JAK2 fusion partner gene in B-acute lymphoblastic leukemia refractory to combination therapy including ruxolitinib

879 | Dec 31 2019

Chen X et al. suggested the potential need for a diagnostic FISH analysis as well as RNA-Seq in the appropriate clinical setting. [Read the Full Post]

The development of HKI-272 and related compounds for the treatment of cancer

794 | Dec 22 2019

Wissner A et al. highlight the findings that these irreversible inhibitors retain activity against tumors that have acquired a resistance to the reversible binding inhibitors gefitinib and erlotinib. The promising interim clinical trial results for HKI-272 and EKB-569 in treating colon, lung, and breast cancers are summarized. [Read the Full Post]

Fludarabine-PET in a murine model of multiple myeloma

1113 | Dec 08 2019

Hovhannisyan N et al. suggested that [18F]fludarabine-PET might represent an alternative and perhaps more specific modality for MM imaging when compared to [18F]FDG. Nevertheless, more investigations are required to extend this conclusion to humans. [Read the Full Post]

Pre-metastatic niche triggers SDF-1/CXCR4 axis and promotes organ colonisation by hepatocellular circulating tumour cells via downregulation of Prrx1

636 | Dec 04 2019

Tang Y et al. demonstrated that decreased expression of Prrx1 stimulates SDF-1/CXCR4 signalling and contributes to organ colonisation with blood CTCs in HCC. STAT3 inhibition and specific blockade of CXCR4 have clinical potential as therapeutics for eliminating organ metastasis in advanced HCC. [Read the Full Post]

The Potent ALK Inhibitor Brigatinib (AP26113) Overcomes Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in Preclinical Models

864 | Nov 02 2019

Zhang S et al. provided the molecular basis for the promising activity being observed in ALK+, crizotinib-resistant patients with NSCLC being treated with brigatinib in clinical trials. [Read the Full Post]

Lapatinib Resistance in Breast Cancer Cells Is Accompanied by Phosphorylation-Mediated Reprogramming of Glycolysis

834 | Oct 15 2019

Ruprecht B et al. offered deeper perspectives on cancer drug resistance and suggests new biomarkers and treatment options for lapatinib-resistant cancers. [Read the Full Post]

Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis

965 | Oct 09 2019

Sandborn WJ et al. showed that in patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo. [Read the Full Post]

Screening of epidermal growth factor receptor inhibitors in natural products by capillary electrophoresis combined with high performance liquid chromatography-tandem mass spectrometry

839 | Oct 09 2019

Li F et al. demonstrated a significant merit of our method in the identification of the bioactive compounds in natural products. [Read the Full Post]

BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models

889 | Oct 05 2019

Li D et al. showed that BIBW2992, an anilino-quinazoline designed to irreversibly bind EGFR and HER2, potently suppresses the kinase activity of wild-type and activated EGFR and HER2 mutants, including erlotinib-resistant isoforms. Consistent with this activity, BIBW2992 suppresses transformation in isogenic cell-based assays, inhibits survival of cancer cell lines and induces tumor regression in xenograft and transgenic lung cancer models, with superior activity over erlotinib. These findings encourage further testing of BIBW2992 in lung cancer patients harboring EGFR or HER2 oncogenes. [Read the Full Post]

ZD1839 (Iressa): an orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy

757 | Sep 03 2019

Wakeling AE et al. indicated the potential utility of ZD1839 in the treatment of many human tumors and indicate that continuous once-a-day p.o. dosing might be a suitable therapeutic regimen. [Read the Full Post]

Gefitinib Versus Gefitinib Plus Pemetrexed and Carboplatin Chemotherapy in EGFR-Mutated Lung Cancer

913 | Aug 15 2019

Noronha V et al. found that adding pemetrexed and carboplatin chemotherapy to gefitinib significantly prolonged PFS and OS but increased toxicity in patients with NSCLC. [Read the Full Post]

Yiqi Chutan Tang Reduces Gefitinib-Induced Drug Resistance in Non-Small-Cell Lung Cancer by Targeting Apoptosis and Autophagy

759 | Aug 15 2019

Zhang J et al. provided a new treatment strategy for patients with EGFR-TKI resistance in NSCLC. [Read the Full Post]

Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis

1091 | Aug 07 2019

Verstovsek S et al. indicated that INCB018424 was associated with marked and durable clinical benefits in patients with myelofibrosis for whom no approved therapies existed. [Read the Full Post]

Overcoming Acquired Resistance to AZD9291, A Third-Generation EGFR Inhibitor, through Modulation of MEK/ERK-Dependent Bim and Mcl-1 Degradation

727 | Jul 25 2019

Shi P et al. showed that modulation of MEK/ERK-dependent Bim and Mcl-1 degradation critically mediates sensitivity and resistance of EGFR-mutant NSCLC cells to AZD9291 and hence is an effective strategy to overcome acquired resistance to AZD9291. [Read the Full Post]

JAK1/2 Inhibitors AZD1480 and CYT387 Inhibit Canine B-Cell Lymphoma Growth by Increasing Apoptosis and Disrupting Cell Proliferation

1035 | Jul 08 2019

Lu Z et al. justified further phase I/II clinical investigations of the safety and efficacy of JAK1/2 inhibitors in canine DLBCL and suggest new opportunities for novel anticancer therapies. [Read the Full Post]

A high-performance liquid chromatography-tandem mass spectrometry method for the determination of lifrafenib, a novel RAF kinase and EGFR inhibitor, in human plasma and urine and its application in clinical pharmacokinetic study

811 | Jul 01 2019

Yao X et al. showed robust and sensitive, it successfully fulfilled the requirement of clinical pharmacokinetic study of lifirafenib in Chinese patients with locally advanced or metastatic solid tumors. [Read the Full Post]

Simultaneous Inhibition of EGFR and HER2 via Afatinib Augments the Radiosensitivity of Nasopharyngeal Carcinoma Cells

966 | Jun 18 2019

Huang F et al. indicated the potential of repositioning afatinib or other ERBB-family-targeted agents for improving radiation response in NPC cells. [Read the Full Post]

Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing, Potent, Orally Active Inhibitor of Anaplastic Lymphoma Kinase

1004 | Jun 12 2019

Huang WS et al. showed that brigatinib represents the most clinically advanced phosphine oxide-containing drug candidate to date and is currently being evaluated in a global phase 2 registration trial. [Read the Full Post]

Regulation of Skeletal Muscle DRP-1 and FIS-1 Protein Expression by IL-6 Signaling

880 | Jun 03 2019

Fix DK et al. elevated IL-6 can directly induce DRP-1 and FIS-1 expression through gp130 signaling in cultured myotubes and skeletal muscle. Furthermore, ERK 1/2 signaling is necessary for the IL-6 induction of DRP-1 and FIS-1 expression in myotubes. [Read the Full Post]

Bendamustine plus rituximab versus fludarabine plus rituximab for patients with relapsed indolent and mantle-cell lymphomas: a multicentre, randomised, open-label, non-inferiority phase 3 trial

1238 | May 21 2019

Rummel M et al. indicated that in combination with rituximab, bendamustine was more effective than fludarabine, suggesting that bendamustine plus rituximab may be the preferred treatment option for patients with relapsed indolent and mantle-cell lymphomas. [Read the Full Post]

Thromboembolic events in polycythemia vera

1199 | Apr 27 2019

Griesshammer M et al. discussed factors associated with thrombosis and recent data on current treatments, including anticoagulation, highlighting the need for more controlled studies to determine the most effective cytoreductive therapies for reducing the risk of thrombosis in patients with PV. [Read the Full Post]

Mechanisms of Action of Ruxolitinib in Murine Models of Hemophagocytic Lymphohistiocytosis

1441 | Apr 26 2019

Ruxolitinib operates through IFNγ-dependent and independent mechanisms to dampen HLH by targeting the deleterious effects of T cells and neutrophils, the latter representing an unappreciated and understudied cell type that contributes to HLH pathogenesis. [Read the Full Post]

PIM kinase inhibitor AZD1208 for treatment of MYC-driven prostate cancer

1084 | Apr 14 2019

Kirschner AN et al. showed that PIM inhibition is a potential treatment for MYC-driven prostate cancers including CRPC, and its effectiveness may be enhanced by activators of the p53 pathway, such as radiation. [Read the Full Post]

Napabucasin: An Update on the First-in-Class Cancer Stemness Inhibitor

974 | Apr 11 2019

Hubbard JM et al. showed that napabucasin may prove useful in targeting cancer stem cells, with the potential to suppress metastasis and prevent relapse in patients with varying cancer types. [Read the Full Post]

lncRNA MIR100HG-derived miR-100 and miR-125b mediate cetuximab resistance via Wnt/β-catenin signaling

0 | Apr 10 2019

Lu Y et al. described a double-negative feedback loop between MIR100HG and the transcription factor GATA6, whereby GATA6 represses MIR100HG, but this repression is relieved by miR-125b targeting of GATA6. These findings identify a clinically actionable, epigenetic cause of cetuximab resistance. [Read the Full Post]

Safety and Efficacy Profile of Neratinib: A Systematic Review and Meta-Analysis of 23 Prospective Clinical Trials

947 | Mar 20 2019

Tao Z et al. demonstrated that neratinib provides a benefit in survival outcome. When combined with other anticancer agents, neratinib may hold promise for treating breast cancer with central nervous system metastases. [Read the Full Post]

Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial

1233 | Mar 19 2019

Martin M et al. showed that at the 5-year follow-up, 1 year of extended adjuvant therapy with neratinib, administered after chemotherapy and trastuzumab, significantly reduced the proportion of clinically relevant breast cancer relapses-ie, those that might lead to death, such as distant and locoregional relapses outside the preserved breast-without increasing the risk of long-term toxicity. An analysis of overall survival is planned after 248 events. [Read the Full Post]

Design and molecular modeling of novel P38α MAPK inhibitors targeting breast cancer, synthesized from oxygen heterocyclic natural compounds

2928 | Feb 24 2019

Abdelhafez OM et al. indicated these promising results of cytotoxic activity and significant inhibition of p38α MAP kinase, were confirmed by exploring the effect of benzofuran derivative (18) on the apoptotic induction and cell cycle progression of MCF-7 cell line. Compound 18 induced preG1 apoptosis and cell growth arrest at G2/M phase preventing the mitotic cycle. Moreover it activated the caspase-7 which executes apoptosis. Molecular docking study was carried out using GOLD program to predict the mode of binding interaction of the synthesized compounds into the target p38α MAPK. Additionally, the physicochemical properties and ADME parameters of compound 18 were examined in silico to investigate its drug-likeness. [Read the Full Post]

The thrombopoietin/MPL axis is activated in the Gata1low mouse model of myelofibrosis and is associated with a defective RPS14 signature

1434 | Dec 30 2018

Zingariello M et al. showed that Gata1low mice are a bona fide model of MF, which recapitulates the hyperactivation of the TPO/MPL/JAK2 axis observed in megakaryocytes from myelofibrotic patients. [Read the Full Post]

Adipocyte-specific CD1d-deficiency mitigates diet-induced obesity and insulin resistance in mice

0 | Dec 30 2018

Satoh M et al. indicated that interactions between NKT cells and CD1d-expressing adipocytes producing endogenous NKT cell ligands play a critical role in the induction of inflammation and functional modulation of adipose tissue that leads to obesity. [Read the Full Post]

SOCS3 overexpression enhances ADM resistance in bladder cancer T24 cells

1479 | Nov 28 2018

Li MZ et al. indicated that SOCS3 reduction was associated with bladder cancer sensitivity to ADM. SOCS3 overexpression decreased JAK-STAT3 signaling pathway activity, declined Bcl-2 expression, inhibited cell proliferation, elevated cell apoptosis, and enhanced ADM sensitivity in T24 cells. [Read the Full Post]

Host Serine/Threonine Kinases mTOR and Protein Kinase C-α Promote InlB-Mediated Entry of Listeria monocytogenes

6083 | Nov 21 2018

Bhalla M et al. identified mTOR and PKC-α to be host factors exploited by Listeria to promote infection. PKC-α controls Listeria entry, at least in part, by regulating the actin cytoskeleton downstream of the Met receptor. [Read the Full Post]

JAK2 inhibitor CEP-33779 prevents mouse oocyte maturation in vitro

1277 | Nov 15 2018

Wu C et al. suggested that JAK2 regulated the microfilaments aggregation during the mouse oocyte maturation. [Read the Full Post]

Stress-induced dynamic regulation of mitochondrial STAT3 and its association with cyclophilin D reduce mitochondrial ROS production

1038 | Nov 03 2018

Meier JA et al. outlined a role for mitochondrially localized STAT3 in sensing and responding to external stimuli. [Read the Full Post]

Construction of a novel cell-based assay for the evaluation of anti-EGFR drug efficacy against EGFR mutation

0 | Oct 25 2018

Hoshi H et al. successfully developed a novel cell-based assay for evaluating the efficacy of anti-EGFR drugs against EGFR mutation. [Read the Full Post]

Diverse drug-resistance mechanisms can emerge from drug-tolerant cancer persister cells

1034 | Oct 25 2018

Ramirez M et al. found that the drug-tolerant persister state does not limit--and may even provide a latent reservoir of cells for--the emergence of heterogeneous drug-resistance mechanisms. [Read the Full Post]

Construction of a novel cell-based assay for the evaluation of anti-EGFR drug efficacy against EGFR mutation

1747 | Oct 20 2018

Hoshi H et al. successfully developed a novel cell-based assay for evaluating the efficacy of anti-EGFR drugs against EGFR mutation. [Read the Full Post]

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells

0 | Oct 14 2018

Grygielewicz P et al. provided experimental evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these patients. [Read the Full Post]

JAK/STAT signaling pathway-mediated immune response in silkworm (Bombyx mori) challenged by Beauveria bassiana

1120 | Sep 09 2018

Geng T et al. suggested that BmCTL5 might be one pattern recognition receptors for JAK/STAT signaling pathway in silkworm. These findings yield insights for better understand the molecular mechanisms of JAK/STAT signaling pathway in antifungal immune response in silkworm. [Read the Full Post]

microRNA-200a silencing protects neural stem cells against cerebral ischemia/reperfusion injury

1105 | Sep 09 2018

Ma J et al. indicated miR-200a silencing protects NSCs from OGD/R-induced injury, possibly via regulating the STATs/c-Myc and MAPK/c-Myc signalings. [Read the Full Post]

Differences in gene expression and alterations in cell cycle of acute myeloid leukemia cell lines after treatment with JAK inhibitors

1460 | Sep 07 2018

Gunerka P et al. suggested that observed effect of JAK2 inhibitors on transcription and cell cycle level in different cell lines are associated not with activity within JAK family, but presumably with other off-target activities. [Read the Full Post]

Niclosamide inhibition of STAT3 synergizes with erlotinib in human colon cancer

0 | Sep 05 2018

Shi L et al. suggested that erlotinib and niclosamide combination provides an effective therapeutic approach to improving the prognosis of colon cancer. [Read the Full Post]

MicroRNA-17 regulates autophagy to promote hepatic ischemia/reperfusion injury via suppression of signal transductions and activation of transcription-3 expression

985 | Sep 02 2018

Li S et al. showed that high levels of miR-17 expression can function to up-regulate autophagy to aggravate hepatic IRI by suppressing Stat3 expression. Liver Transplantation 22 1697-1709 2016 AASLD. [Read the Full Post]

Downregulation of the Syk Signaling Pathway in Intestinal Dendritic Cells Is Sufficient To Induce Dendritic Cells That Inhibit Colitis

1708 | Aug 22 2018

Hang L et al. indicated that downmodulation of Syk expression and phosphorylation in intestinal DCs could be important mechanisms through which helminths induce regulatory DCs that limit colitis. [Read the Full Post]

JAK2 inhibition sensitizes resistant EGFR-mutant lung adenocarcinoma to tyrosine kinase inhibitors

1219 | Aug 02 2018

Gao SP et al. revealed a mechanism whereby JAK2 inhibition overcomes acquired resistance to EGFR inhibitors and support the use of combination therapy with JAK and EGFR inhibitors for the treatment of EGFR-dependent NSCLC. [Read the Full Post]

Activation of the IGF1R pathway potentially mediates acquired resistance to mutant-selective 3rd-generation EGF receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer

1428 | Aug 01 2018

Park JH et al. suggested that activation of the IGF1R pathway associated with IGFBP3 loss can induce an acquired resistance to the mutant-selective EGFR-TKI, WZ4002. Therefore, a combined therapy of IGF1R inhibitors and mutant-selective EGFR-TKIs might be a viable treatment strategy for overcoming acquired resistance. [Read the Full Post]

B7-H4 facilitates proliferation of esophageal squamous cell carcinoma cells through promoting interleukin-6/signal transducer and activator of transcription 3 pathway activation

1740 | Jul 13 2018

Chen X et al. provided the first evidence that B7-H4 facilitated ESCC cell proliferation through promoting IL-6/STAT3 positive loopback pathway activation. [Read the Full Post]

EGF-mediated EGFR/ERK signaling pathway promotes germinative cell proliferation in Echinococcus multilocularis that contributes to larval growth and development

1717 | Jun 08 2018

Cheng Z et al. demonstrated the contribution of EGF-mediated EGFR/ERK signaling to the regulation of germinative cells in E. multilocularis, and suggest the EGFR/ERK signaling as a potential therapeutic target for AE and perhaps other human cestodiasis. [Read the Full Post]

Cancer Cell-derived Exosomes Induce Mitogen-activated Protein Kinase-dependent Monocyte Survival by Transport of Functional Receptor Tyrosine Kinases

1717 | May 28 2018

Song X et al. provided insights into the long sought question on monocyte survival prior to formation of plentiful TAMs in the tumor microenvironment. [Read the Full Post]

Niclosamide inhibition of STAT3 synergizes with erlotinib in human colon cancer

1696 | May 28 2018

Shi L et al. suggested that erlotinib and niclosamide combination provides an effective therapeutic approach to improving the prognosis of colon cancer. [Read the Full Post]

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells

0 | May 21 2018

Grygielewicz P et al. provided experimental evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these patients. [Read the Full Post]

Therapeutic implication of HER2 in advanced biliary tract cancer

1587 | May 10 2018

Nam AR et al. suggested that HER2 could be a therapeutic target, and that a HER2-targeting strategy should be developed further in patients with HER2-positive advanced BTC. [Read the Full Post]

Pharmacologic Inhibition of JAK1/JAK2 Signaling Reduces Experimental Murine Acute GVHD While Preserving GVT Effects

1922 | Apr 24 2018

Carniti C et al. provided further evidence that JAK inhibition represents a new and potentially clinically relevant approach to GVHD prevention. [Read the Full Post]

Cancer-associated fibroblasts attenuate Cisplatin-induced apoptosis in ovarian cancer cells by promoting STAT3 signaling

1234 | Apr 06 2018

Yan H et al. suggested that CAFs could activate the anti-apoptotic STAT3 signaling, thereby decrease the Cisplatin-induced apoptosis and promote chemoresistance in ovarian cancer. [Read the Full Post]

FYN promotes breast cancer progression through epithelial-mesenchymal transition

2285 | Mar 29 2018

Xie YG et al. found that FYN was overexpressed in breast cancer and overexpression of FYN promoted cell proliferation, migration and invasion in the MCF10A cells, whereas depletion of FYN suppressed cell proliferation, migration and invasion in the MDA-MB-231 cells. Moreover, FYN upregulated the expression of mesenchymal markers and epithelial-mesenchymal transition (EMT)-related transcription factors, and downregulated the expression of epithelial markers, suggesting that FYN induces EMT in breast cancer cells. Furthermore, FYN was transcriptionally regulated by FOXO1 and mediated FGF2-induced EMT through both the PI3K/AKT and ERK/MAPK pathways. [Read the Full Post]

Anti-leukaemic activity of the TYK2 selective inhibitor NDI-031301 in T-cell acute lymphoblastic leukaemia

2377 | Mar 23 2018

Akahane K et al. supported selective inhibition of TYK2 as a promising potential therapeutic strategy for T-ALL. [Read the Full Post]

NF-YA promotes invasion and angiogenesis by upregulating EZH2-STAT3 signaling in human melanoma cells

1920 | Mar 15 2018

Xu Z et al. indicated that overexpression of NF-YA contributes to tumor angiogenesis through EZH2-STAT3 signaling in human melanoma cells, highlighting NF-YA as a potential therapeutic target in human melanoma. [Read the Full Post]

Endothelial STAT3 Activation Increases Vascular Leakage Through Downregulating Tight Junction Proteins: Implications for Diabetic Retinopathy

1754 | Mar 15 2018

Yun JH et al. suggested the potential importance of IL-6/STAT3 signaling in regulating endothelial permeability and provide a therapeutic target to prevent the pathology of diabetic retinopathy. [Read the Full Post]

Ginsenoside Rg3 inhibits epithelial-mesenchymal transition (EMT) and invasion of lung cancer by down-regulating FUT4

1591 | Feb 17 2018

Tian L et al. indicated Rg3 inhibits EMT and invasion of lung cancer by down-regulating FUT4 mediated EGFR inactivation and blocking MAPK and NF-κB signal pathways. Rg3 may be a potentially effective agent for the treatment of lung cancer. [Read the Full Post]

Dihydroartemisin inhibits glioma invasiveness via a ROS to P53 to β-catenin signaling

4539 | Feb 16 2018

Que Z et al. indicated that DHA inhibited the migration and invasion of human glioma cells with different types of p53 via different pathways. [Read the Full Post]

Epigallocatechin gallate reverses cTnI-low expression-induced age-related heart diastolic dysfunction through histone acetylation modification

2482 | Jan 11 2018

Pan B et al. provided new insights into histone acetylation mechanisms of EGCG treatment that may contribute to the prevention of CDD in ageing populations. [Read the Full Post]

Tyrosine receptor kinase B is a drug target in astrocytomas

3443 | Dec 31 2017

Ni J et al. proposed NTRK2 as a potential therapeutic target in the subset of astrocytoma patients defined by QKI-NTRK2 fusion. [Read the Full Post]

PD-L1 Is Upregulated by Simultaneous Amplification of the PD-L1 and JAK2 Genes in Non-Small Cell Lung Cancer

2154 | Dec 25 2017

Ikeda S et al. suggested that expression of PD-L1 protein is upregulated by the simultaneous amplification of the PD-L1 and JAK2 genes through JAK-STAT signaling in NCSLC. [Read the Full Post]

Ethacrynic acid improves the antitumor effects of irreversible epidermal growth factor receptor tyrosine kinase inhibitors in breast cancer

0 | Dec 24 2017

Liu B et al. concluded that EA synergistically enhances the antitumor effects of irreversible EGFR TKIs in breast cancer. [Read the Full Post]

Neratinib induces ErbB2 ubiquitylation and endocytic degradation via HSP90 dissociation in breast cancer cells

2054 | Dec 24 2017

Zhang Y et al. provided novel insights into the mechanism of ErbB2 inhibition by neratinib. [Read the Full Post]

The AXL receptor tyrosine kinase is associated with adverse prognosis and distant metastasis in esophageal squamous cell carcinoma

2022 | Dec 15 2017

Hsieh MS et al. concluded that AXL is a strong adverse prognostic factor for ESCC. Therapeutic agents targeting AXL have great potential to improve prognosis of ESCC patients. [Read the Full Post]

THZ1 targeting CDK7 suppresses STAT transcriptional activity and sensitizes T-cell lymphomas to BCL2 inhibitors

1494 | Dec 14 2017

Cayrol F et al. showed that the combination of THZ1 and the BH3 mimetic obatoclax improves lymphoma growth control in a primary PTCL ex vivo culture and in two STAT3-mutant PTCL xenografts, delineating a potential targeted agent-based therapeutic option for these patients. [Read the Full Post]

Interleukin-6 suppression reduces tumour self-seeding by circulating tumour cells in a human osteosarcoma nude mouse model

1465 | Dec 12 2017

Zhang Y et al. provided a novel strategy for future therapeutic interventions to prevent osteosarcoma progression and recurrence. [Read the Full Post]

MET Copy Number Gain Is Associated with Gefitinib Resistance in Leptomeningeal Carcinomatosis of EGFR-mutant Lung Cancer

2220 | Dec 10 2017

Nanjo S et al. suggested that combination therapy with MET inhibitors may be promising for controlling leptomeningeal carcinomatosis that acquires resistance to EGFR-TKIs [Read the Full Post]

Control of translational activation by PIM kinase in activated B-cell diffuse large B-cell lymphoma confers sensitivity to inhibition by PIM447

1521 | Dec 02 2017

Peters TL et al. characterized recurrent PIM1 protein-coding mutations found in DLBCL clinical samples and find most preserve the wild-type protein's ability to protect cells from apoptosis but do not bypass activity of PIM447. Pan-PIM inhibition therefore may have an important role to play in the therapy of selected ABC-DLBCL cases. [Read the Full Post]

Photodynamic therapy activated STAT3 associated pathways: Targeting intrinsic apoptotic pathways to increase PDT efficacy in human squamous carcinoma cells

2197 | Nov 23 2017

Qiao L et al. confirmed that 5-ALA-PDT might be an effective treatment for human squamous carcinoma by inhibiting the tumor cell A431growth and for the first time demonstrated that the expression of STAT3 was significantly reduced at 24h after 5-ALA-PDT treatment. [Read the Full Post]

Amplification of EGFR Wild-Type Alleles in Non-Small Cell Lung Cancer Cells Confers Acquired Resistance to Mutation-Selective EGFR Tyrosine Kinase Inhibitors

0 | Nov 21 2017

Nukaga S et al. provided evidence of wild-type allele-mediated resistance, a novel concept of acquired resistance in response to mutation-selective inhibitor therapy in cancer treatment. [Read the Full Post]

Quantitative proteomics of breast tumors: Tissue quality assessment to clinical biomarkers

2105 | Nov 06 2017

Chen Y, et al. showed that combined with biomarkers for tissue quality and histological content are implemented in a three-tier multiplexed assay platform, which is translated from cell line models into frozen tumor tissues banked from breast cancer patients. [Read the Full Post]

JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma

2369 | Nov 05 2017

Nairismägi ML et al. showed that inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available. [Read the Full Post]

Platelet-derived growth factor BB enhances osteoclast formation and osteoclast precursor cell chemotaxis

1999 | Nov 05 2017

Li DQ et al. showed that PDGF-BB enhanced RAW264.7 cell migration and gene expression of osteoclastogenic signaling molecules (i.e., nuclear factor of activated T cells 1, dendrocyte-expressed seven transmembrane protein, and B-cell lymphoma 2), and treatment with AG-1295, AG-490, or S3I-201 (a STAT3 inhibitor) reduced this effect. PDGF-BB enhanced osteoclast formation, osteoclast precursor cell chemotaxis, and phosphorylation of STAT3, Akt, and ERK1/2. but AG-1295 and AG-490 reduced this effect. These findings reflect the complexity of PDGF-BB in bone biology. [Read the Full Post]

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells

4554 | Oct 09 2017

Grygielewicz P et al. provide experimental evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these patients. [Read the Full Post]

STAT1 as a downstream mediator of ERK signaling contributes to bone cancer pain by regulating MHC II expression in spinal microglia

2025 | Oct 04 2017

Song Z et al. suggested that STAT1 contributes to bone cancer pain as a downstream mediator of ERK signaling by regulating MHC II expression in spinal microglia. [Read the Full Post]

Regulation of TRPM7 Function by IL-6 through the JAK2-STAT3 Signaling Pathway

1440 | Sep 05 2017

Liu A et al. indicated IL-6 inhibits the inward TRPM7 current via the JAK2-STAT3 signaling pathway. [Read the Full Post]

Oncogene swap as a novel mechanism of acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitor in lung cancer

1982 | Aug 31 2017

Mizuuchi H et al. analyzed multiple lesions from a patient who died of acquired resistance to gefitinib, then found a clinical example of an oncogene swap in which the EGFR mutation was lost and a MET gene copy was gained. In conclusion, an "oncogene swap" from EGFR to MET is a novel resistant mechanism to the EGFR-TKI. This novel mechanism should be considered in order to avoid futile inhibition of the original oncogene. [Read the Full Post]

Interleukin 6 induces cell proliferation of clear cell renal cell carcinoma by suppressing hepaCAM via the STAT3-dependent up-regulation of DNMT1 or DNMT3b

1841 | Aug 17 2017

Quan Z et al. provided a novel signal pathway regulating cell proliferation, potentially representing a therapeutic target for RCC. [Read the Full Post]

Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma

2156 | Aug 17 2017

Dai M et al. demonstrated for the first time the crucial role of the insulin/STAT3/DHCR24/PGR axis in the progression of EC by modulating the metastasis and progesterone response, which could serve as potential therapeutic targets for the treatment of EC with progesterone receptor loss. [Read the Full Post]

Lipopolysaccharide increases IL-6 secretion via activation of the ERK1/2 signaling pathway to up-regulate RANKL gene expression in MLO-Y4 cells

1748 | Aug 16 2017

Yu K et al. indicated that LPS up-regulates osteocyte expression of RANKL and IL-6, and the increased RANKL is associated with the up-regulation of IL-6, which involves the ERK1/2 pathway. [Read the Full Post]

BRG1 targeting STAT3/VEGFC signaling regulates lymphangiogenesis in colorectal cancer

1711 | Aug 09 2017

Zhu X et al. demonstration of the important roles of the BRG1/STAT3/VEGFC in tumor-associated lymphangiogenesis might lead to the discovery of novel therapeutic targets in the treatment of cancers with BRG1 loss of function. [Read the Full Post]

Long-term treatment with EGFR inhibitor erlotinib attenuates renal inflammatory cytokines but not nephropathy in Alport syndrome mouse model

2427 | Jul 28 2017

Omachi K et al. suggested that EGFR signaling is upregulated in kidney, but although inhibiting this signaling pathway suppressed renal inflammatory cytokines, it did not ameliorate renal dysfunction in AS mouse model. [Read the Full Post]

miR-17-5p down-regulation contributes to erlotinib resistance in non-small cell lung cancer cells

2463 | Jul 28 2017

Zhang W et al. indicated that miR-17-5p down-regulation contributes to erlotinib resistance of NSCLC by modulating its target genes such as EZH1 and plasma miR-17-5p might be a potential biomarker of erlotinib response in NSCLC patients. [Read the Full Post]

17β-estradiol-induced growth of triple-negative breast cancer cells is prevented by the reduction of GPER expression after treatment with gefitinib

5712 | Jul 26 2017

Girgert R et al. showed that reduction of GPER expression is a promising therapeutic approach for TNBC. [Read the Full Post]

Effect of alpha lipoic acid on retinal ganglion cell survival in an optic nerve crush model

2711 | Jul 17 2017

Liu R et al. conclude that the endogenous EPO/EPOR signaling pathway may contribute to the protective effects of ALA in the retina after ONC injury. [Read the Full Post]

miR-17-5p down-regulation contributes to erlotinib resistance in non-small cell lung cancer cells

2880 | Jun 29 2017

Zhang W et al. indicated that miR-17-5p down-regulation contributes to erlotinib resistance of NSCLC by modulating its target genes such as EZH1 and plasma miR-17-5p might be a potential biomarker of erlotinib response in NSCLC patients [Read the Full Post]

Amplification of EGFR Wild-Type Alleles in Non-Small Cell Lung Cancer Cells Confers Acquired Resistance to Mutation-Selective EGFR Tyrosine Kinase Inhibitors

3781 | Jun 27 2017

Nukaga S et al. provided evidence of wild-type allele-mediated resistance, a novel concept of acquired resistance in response to mutation-selective inhibitor therapy in cancer treatment. [Read the Full Post]

Ethacrynic acid improves the antitumor effects of irreversible epidermal growth factor receptor tyrosine kinase inhibitors in breast cancer

2969 | Jun 16 2017

Liu B et al. concluded that EA synergistically enhances the antitumor effects of irreversible EGFR TKIs in breast cancer. [Read the Full Post]

Functionalized gold nanoparticles improve afatinib delivery into cancer cells

2886 | Jun 16 2017

Coelho SC et al. found that PEGAuNPs with afatinib is a promising antitumor delivery system for cancer therapy as it improves drug efficacy, allowing a reduction in drug dose used and minimizing possible toxicity-related side effects. [Read the Full Post]

Platelet-derived growth factor (PDGF)-induced activation of Erk5 MAP-kinase is dependent on Mekk2, Mek1/2, PKC and PI3-kinase, and affects BMP signaling

6078 | Jun 14 2017

Tsioumpekou M et al. found that PDGF-BB-induced Erk5 activation involves parallel stimulatory and inhibitory pathways and promotes Smad1/5/8 signaling. [Read the Full Post]

Metformin and gefitinib cooperate to inhibit bladder cancer growth via both AMPK and EGFR pathways joining at Akt and Erk

2294 | Jun 11 2017

Peng M, et al. found these two drugs may be an excellent combination for the treatment of bladder cancer through intravesical instillation. [Read the Full Post]

Adipocyte-specific CD1d-deficiency mitigates diet-induced obesity and insulin resistance in mice

3746 | Jun 11 2017

Satoh M et al. indicated that interactions between NKT cells and CD1d-expressing adipocytes producing endogenous NKT cell ligands play a critical role in the induction of inflammation and functional modulation of adipose tissue that leads to obesity. [Read the Full Post]

Synergistic effect of pacritinib with erlotinib on JAK2-mediated resistance in epidermal gowth factor receptor mutation-positive non-small cell lung Cancer

0 | May 28 2017

Ochi N et al. found that pacritinib combined with EGFR-TKI might be a potent strategy against JAK2-mediated EGFR-TKI resistance. [Read the Full Post]

Epidermal growth factor receptor inhibitor cancer drug gefitinib modulates cell growth and differentiation of acute myeloid leukemia cells via histamine receptors

1960 | May 28 2017

Yadav M et al. found that HRs play critical roles in anti-cancer effects of gefitinib in both EGFR-deficient and EGFR-rich environments. [Read the Full Post]

The Expression and Regulation of Interleukin-33 in Human Epidermal Keratinocytes: A New Mediator of Atopic Dermatitis and Its Possible Signaling Pathway

3133 | May 26 2017

Du HY et al. found that IL-33 plays an important role in the pathogenesis of immune inflammatory responses in AD, which might be a possible therapeutic target in the treatment of AD. [Read the Full Post]

ErbB2-dependent downregulation of a pro-apoptotic protein Perp is required for oncogenic transformation of breast epithelial cells.

0 | May 18 2017

Khan IA et al. have identified a novel mechanism of ErbB2-mediated mechanism of anoikis resistance of ErbB2-overproducing breast epithelial cells. [Read the Full Post]

Identification of Novel Inhibitors of the Type I Interferon Induction Pathway Using Cell-Based High-Throughput Screening

2863 | May 17 2017

Gage ZO et al. demonstrate that one of these compounds acts at or upstream of IRF3 phosphorylation. [Read the Full Post]

EGFR Activation Leads to Cell Death Independent of PI3K/AKT/mTOR in an AD293 Cell Line

0 | May 14 2017

Treda C et al. showed another EGFR function, dependent on environmental factors, which could be employed in therapy and drug design. [Read the Full Post]

A Platform for Rapid, Quantitative Assessment of Multiple Drug Combinations Simultaneously in Solid Tumors In Vivo

2478 | May 12 2017

Dey J et al. found a platform for rapid, quantitative assessment of multiple drug combinations simultaneously in solid tumors In vivo. [Read the Full Post]

Utilising the EGFR interactome to identify mechanisms of drug resistance in non-small cell lung cancer - Proof of concept towards a systems pharmacology approach.

0 | May 09 2017

Saafan H et al.found that knowledge of these mechanisms is a pivotal step to build an integrative model of drug resistance in a systems pharmacology manner and to be able to investigate the interplay of these mechanisms and ultimately recommend combinatorial treatment strategies to overcome drug resistance. [Read the Full Post]

Utilising the EGFR interactome to identify mechanisms of drug resistance in non-small cell lung cancer - Proof of concept towards a systems pharmacology approach.

0 | May 08 2017

Saafan H et al. found that knowledge of these mechanisms is a pivotal step to build an integrative model of drug resistance in a systems pharmacology manner and to be able to investigate the interplay of these mechanisms and ultimately recommend combinatorial treatment strategies to overcome drug resistance. [Read the Full Post]

EGFR inhibitors identified as a potential treatment for chordoma in a focused compound screen

0 | May 07 2017

Scheipl S et al provided evidence for exploring the efficacy of EGFR inhibitors in the treatment of patients with chordoma and studying possible resistance mechanisms to these compounds in vitro and in vivo. [Read the Full Post]

Severe Early-Onset Combined Immunodeficiency due to Heterozygous Gain-of-Function Mutations in STAT1

2889 | Apr 19 2017

Baris S et al. found thatJAK kinase inhibitors may potentially be useful in some patients as adjunct therapy pending definitive treatment with bone marrow transplantation. [Read the Full Post]

Developmental expression of STATs, nuclear factor-κB and inflammatory genes in the jejunum of piglets during weaning

2954 | Apr 18 2017

Yi H et al found weaning caused severe inflammation associated with activation of the NF-κB and STAT-3 pathways and suppression of STAT-1 and STAT-6 in the jejunum of piglets. [Read the Full Post]

EGFR Exon 18 Mutations in Lung Cancer: Molecular Predictors of Augmented Sensitivity to Afatinib or Neratinib as Compared with First- or Third-Generation TKIs

2680 | Feb 05 2017

Kobayashi Y, et al.’‘s result shows that’Lung cancers harboring exon 18 mutations should not be overlooked in clinical practice. These cases can be best treated with afatinib or neratinib, although the currently available in vitro diagnostic kits cannot detect all exon 18 mutations [Read the Full Post]

Signaling through the Phosphatidylinositol 3-Kinase (PI3K)/ Mammalian Target of Rapamycin (mTOR) Axis is Responsible for Aerobic Glycolysis mediated by Glucose Transporter in Epidermal Growth Factor Receptor (EGFR)-mutated Lung Adenocarcinoma

1958 | Feb 04 2017

Makinoshima H, et al.‘s results suggest that PI3K/AKT/mTOR signaling is indispensable for the regulation of aerobic glycolysis in EGFR-mutated LAD cells. [Read the Full Post]

Delayed Administration of WP1066, an STAT3 Inhibitor, Ameliorates Radiation-Induced Lung Injury in Mice

3416 | Jan 28 2017

The activation of STAT3 pathway might play an important part in the pathogenesis of radiation-induced lung injury. The protective effects of delayed treatment of WP1066 suggested STAT3 signaling could be a therapeutic target for radiation pneumonitis. [Read the Full Post]

Signaling through the Phosphatidylinositol 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Axis Is Responsible for Aerobic Glycolysis mediated by Glucose Transporter in Epidermal Growth Factor Receptor (EGFR)-mutated Lung Adenocarcinoma

2142 | Jan 02 2017

Makinoshima H et al. suggested that PI3K/AKT/mTOR signaling is indispensable for the regulation of aerobic glycolysis in EGFR-mutated LAD cells. [Read the Full Post]

EGFR Exon 18 Mutations in Lung Cancer: Molecular Predictors of Augmented Sensitivity to Afatinib or Neratinib as Compared with First- or Third-Generation TKIs

2601 | Jan 02 2017

Lung cancers harboring exon 18 mutations should not be overlooked in clinical practice. These cases can be best treated with afatinib or neratinib, although the currently available in vitro diagnostic kits cannot detect all exon 18 mutations. [Read the Full Post]

Synergistic effect of pacritinib with erlotinib on JAK2-mediated resistance in epidermal gowth factor receptor mutation-positive non-small cell lung Cancer

2861 | Oct 25 2016

Ochi N et al. found that pacritinib combined with EGFR-TKI might be a potent strategy against JAK2-mediated EGFR-TKI resistance. [Read the Full Post]

ErbB2-dependent downregulation of a pro-apoptotic protein Perp is required for oncogenic transformation of breast epithelial cells

3397 | Oct 14 2016

Khan IA et al. identified a novel mechanism of ErbB2-mediated mechanism of anoikis resistance of ErbB2-overproducing breast epithelial cells. [Read the Full Post]

EGFR Activation Leads to Cell Death Independent of PI3K/AKT/mTOR in an AD293 Cell Line

3487 | Oct 14 2016

Treda C et al. showed another EGFR function, dependent on environmental factors, which could be employed in therapy and drug design. [Read the Full Post]

Utilising the EGFR interactome to identify mechanisms of drug resistance in non-small cell lung cancer - Proof of concept towards a systems pharmacology approach

3000 | Oct 08 2016

Saafan H et al. identified that differential proteins in the EGFR interactome of HCC4006rERLO0.5 cells could be related to multiple resistance mechanisms including alterations in growth factor receptor expression, cellular remodelling processes suggesting epithelial-to-mesenchymal transition as well as alterations in downstream signalling. [Read the Full Post]

EGFR inhibitors identified as a potential treatment for chordoma in a focused compound screen

3246 | Sep 30 2016

Scheipl S et al. provided evidence for exploring the efficacy of EGFR inhibitors in the treatment of patients with chordoma and studying possible resistance mechanisms to these compounds in vitro and in vivo. [Read the Full Post]

Developmental expression of STATs, nuclear factor-κB and inflammatory genes in the jejunum of piglets during weaning

7088 | Sep 20 2016

Yi H et al. found that weaning caused severe inflammation associated with activation of the NF-κB and STAT-3 pathways and suppression of STAT-1 and STAT-6 in the jejunum of piglets. [Read the Full Post]

Tcfap2c acts as a key factor in mammary tumorigenesis

5104 | Mar 27 2015

Park et al. conducted a serious experiments to gain greater insight into functions of TFAP2C on mammary tumorigeneisis in MMTV-Neu transgenic female mice. [Read the Full Post]

GPRC5A directly inhibits EGFR signaling to suppress lung tumorigenesis

6389 | Mar 20 2015

Zhong et al. revealed that GPRC5A negatively regulates EGFR signaling and its downstream signaling STAT3. [Read the Full Post]

CY190602, a novel DNA/HDAC dual-targeting drug with enhanced anti-cancer potency

9892 | Mar 19 2015

Liu et al. demonstrated a novel bendamustine-derived drug, CY190602, enhanced anticancer potency. [Read the Full Post]

Molecular changes of the transformation of NSCLC to SCLC TKI-resistant EGFR mutant cancers

4988 | Mar 16 2015

Niederst et al. demonstrated the molecular changes occur in NSCLC to small-cell lung cancer (SCLC) transformed TKI-resistant EGFR mutant cancers. [Read the Full Post]

AXL regulates cetuximab resistance in HNSCC and NSCLC

6590 | Mar 13 2015

Brand et al. demonstrated that AXL-EGFR signaling positive feedback loop is one of the mechanism of developing cetuximab resistance. [Read the Full Post]

Inactivating mutations of SMARCE1 promotes EGFR expression and suppress the responses to MET and ALK inhibitors in lung cancer

6788 | Feb 26 2015

The study conducted by Papadakis et al. showed inactivating mutations in SMARCE1 gene, which encodes SWI/SNF subunit, upregulate EGFR expression and induce resistance to MET and ALK inhibitors in non-small cell lung cancers (NSCLCs). [Read the Full Post]

Tofacitinib promotes myeloid-derived suppressor cells expansion and reduces disease severity of arthritis SKG mice

7096 | Jan 14 2015

Nishimura et al. revealed that tofacitinib has effect on promoting MDSCs expansion and ameliorating arthritis in SKG mice. [Read the Full Post]

The mechanism of resistance to JAK2 inhibitor in myeloproliferative neoplasms patients

12901 | Jan 07 2015

Winter et al. identified the underlying mechanism of the emerging JAK2 inhibitor therapy resistance in MPNs patients, and found the RAS and pathways mediated by AKT and ERK contribute to the resistance. [Read the Full Post]

An unusual mechanism of ERBB4 in regulating tumor related gene expression

9833 | Jan 06 2015

Haskins et al. found ERBB4 activated the transcriptional coactivator YAP by binding to its ligand neuregulin 1 (NRG1), to regulate gene expression of cancer cells. [Read the Full Post]

The inhibition of JAK signaling promotes the conversion from white to brown adipocytes

8715 | Dec 17 2014

By using a screening platform of small molecules identification, Moisan et al. found two inhibitors of JAK signaling were able to convert white adipocytes to brown adipocytes. [Read the Full Post]

The Notch signaling controls maintenance of memory CD4+ T cells

10469 | Dec 16 2014

Recently, Maekawa et al. demonstrated Notch signaling is important for the survival of memory CD4+ T cells by regulating glucose uptake. [Read the Full Post]

KIAA1199 provides a connection between oncogenic signaling of NF-κB and EGFR

6620 | Dec 01 2014

Shostak et al. showed the connection between the two oncogenic cascades by identifying a key factor, KIAA1199, that associated with human papillomavirus (HPV) infection. [Read the Full Post]

GP130/JAK/STAT3 signaling pathway induces multiple myeloma

11650 | Nov 24 2014

Dechow et al. determined GP130/JAK/STAT3 signaling pathway is sufficient to induce MM generation in mice retroviral murine BM transduction-transplantation model. [Read the Full Post]

The mechanism of drug resistance in BRAF (V600E) mutant melanoma

9913 | Nov 19 2014

Sun et al. demonstrated the resistance of BRAF (V600E) is reversible and adaptive. The process involves several transduction factors, such as EGFR, PDGFRB, TGF-β, and SOX10. [Read the Full Post]

Combination of PI3K/mTOR and EGFR inhibitors suppresses KRAS-mutant colorectal cancer

7409 | Nov 14 2014

Belmont et al. demonstrated combination of PI3K/mTOR and EGFR inhibitors may become a novel therapy in patients with KRAS-mutant CRC. [Read the Full Post]

Interactions between Slit-Robo and JAK-STAT signaling in regulation of stem cell-niche adhesion

9113 | Nov 10 2014

Rachel R. Stine et al. found Slit-Robo and JAK-STAT signaling pathways play key roles in stem cells competition within their niches. [Read the Full Post]

FGF21 is not required for CR-mediated IGF-1 reduction or cell proliferation inhibition

8326 | Nov 06 2014

Thompson et al. found that, in response to moderate CR, phosphorylated STAT5 may act as a key molecule, and FGF21 was not required for the down-regulation of IGF-1 expression level or cell proliferation rates. [Read the Full Post]

JAK2 and MPL are two main regulators of TPO-induced megakaryopoiesis

7506 | Nov 03 2014

Megakaryopoiesis is regulated by TPO, which activates multiple signaling molecules. Besancenot et al. demonstrated that the protein levels of JAK2 and MPL determine TPO-induced megakaryopoiesis. [Read the Full Post]

Neural stem cells "heal" target cells via extracellular vesicles

4507 | Oct 29 2014

Cossetti et al. found NPCs communicate to the host via extracellular vesicles (EVs) and also investigated the cytokine-regulated pathways involved in the communication. It comes to a novel view in the understanding the mechanisms of stem cell therapy. [Read the Full Post]

Endocrine therapy has become the most important systemic treatment

4899 | Mar 10 2014

Imatinib is a multi-target inhibitor of v-Abl, c-Kit and PDGFR with IC50 of 0.6 μM, 0.1 μM and 0.1 μM, respectively. [Read the Full Post]

Afatinib is a drug approved in much of the world

4732 | Mar 07 2014

BIBW2992 shows potent activity against both wild-type and mutant forms of EGFR and HER2. [Read the Full Post]

WP1066 is a cell permeable AG 490 tyrphostin analog

6675 | Jan 15 2014

WP1066 is a novel inhibitor of JAK2 and STAT3 with IC50 of 2.30 μM and 2.43 μM in HEL cells; shows activity to JAK2, STAT3, STAT5, and ERK1/2 not JAK1 and JAK3. [Read the Full Post]

Gefitinib is used to treat non small cell lung cancer in people

4620 | Dec 04 2013

Gefitinib (ZD-1839) is an EGFR inhibitor for Tyr1173, Tyr992, Tyr1173 and Tyr992 in the NR6wtEGFR and NR6W cells with IC50 of 37 nM, 37nM, 26 nM and 57 nM, respectively. [Read the Full Post]

R428 inhibits angiogenesis in corneal micropocket and tumor models

4690 | Nov 13 2013

R428 is an inhibitor of Axl with IC50 of 14 nM, >100-fold selective for Axl versus Abl. Selectivty for Axl is also greater than Mer and Tyro3 and InsR, EGFR, HER2, and PDGFRβ. [Read the Full Post]

This study is designed to evaluate the efficacy and safety of tofacitinib

7279 | Oct 30 2013

Tofacitinib citrate inhibits IL-2-mediated human T cell blast proliferation and IL-15-induced CD69 expression with IC50 of 11 nM and 48 nM, respectively. [Read the Full Post]

Gefitinib were not considered clinically relevant

5400 | Nov 15 2012

There were no statistically significant differences in the mean percent baseline slopes over the 6 h of testing, and any Gefitinib differences were not considered clinically relevant [Read the Full Post]

EGFR INHIBITORS AGAINST THE CANCERS

4923 | Sep 12 2012

INHIBITION OF EGFR: Among those few cascades which play an important role in the functioning of cells, epidermal growth factor receptor or EGFR pathway is one that has a vital role in growth, survival and proliferation of cells. The importance of this cascade can only be observed and understood in case of development of tumors and fatal diseases related to the uncontrolled cell growth caused by the improper regulation of EGFR signaling pathway. Over or mutated expression of the EGFR is associated with different types of cancers like colon, lung and breast cancers and with multiform glioblastoma, anal and epithelial cancers. Therefore the treatment of these cancers by using the phenomenon of EGFR inhibition is found to be an attractive approach that led to magnify the importance of Erbb1 inhibitor. These inhibitors along with their use in clinical processes, are also concerned with the survival of patients and different EGFR antagonists and agonists are also in use for the revelation of various other cascades and the effects of EGFR pathway on them. EGFR inhibitors can be obtained from any relevant supplier at a very normal cost. [Read the Full Post]

ERLOTINIB– INHIBITOR OF EGFR

517 | Sep 03 2012

CHARACTERISTICS OF ERLOTINIB Erlotinib is one of the tyrosine kinase inhibitors which is also referred OSI-420 EGFR inhibitor which is typically named as HCl salt. Epidermal growth factor tyrosine kinase receptor is sometimes seen abnormal in numerous kinds of cancers so that they are being utilized for the anti-cancer therapy. Plenty of new medicines are being created by using a similar approach [1]. Erlotinib structure revealed that it contained 2 quinazoline rings in its structures and it showed to inhibit the EGFR auto phosphorylation which eventually stops the pathway that is involved in the overexpression of genes. Around 18mg/ml in dimethyl sulfoxide (DMSO) is the Erlotinib solubility however it is scarcely soluble in water and ethanol. For inhibition of EGFR 20nM is Erlotinib IC50 [2]. It is readily oxidized therefore care should be taken to extend its shelf life. Approximately $65 per 1000mg is Erlotinib price and any one can get OSI-420 for any kind of purpose under this trade name. [Read the Full Post]

EGFR INHIBITORS IN CANCER THERAPY

5465 | Aug 17 2012

EGFR AND DEVELOPMENT OF CANCER: Among a variety of signal transduction pathways vital for cell survival, growth, and proliferation etc. EGFR pathway is considered to be quite important. Its importance has been judged by analyzing the processes like tumor development and some other diseases occurring due to uncontrolled growth of cells. Mostly EGFR signaling pathway malfunctioning has been linked with the development of such types of diseases in the body for example; colon cancer, breast and lung cancer and with anal cancer, multiform Glioblastoma and epithelial cancer. Therefore targeting EGFR for cancer therapy is a feasible approach. This EGFR inhibiting strategy magnifies the HER-1inhibitor and its importance. These inhibitors have a very significant role in the patients’ survival from the disease. Different EGFR agonists and antagonists are used for the purpose of unveiling the role of this molecule in the cell as well as looking for a most efficient EGFR inhibitor. These inhibitors are available at a very reasonable price and can be bought for any purpose. [Read the Full Post]

EGFR INHIBITORS AGAINST TUMORS

4840 | Jul 29 2012

EGFR INHIBITION: There are few pathways which play important roles in the cellular functioning and among these EGFR (epidermal growth factor receptor) pathway is one which is vital for the cell growth, proliferation and survival. The significance of this pathway can only be understood by the formation of cancers and fatal diseases associated with uncontrolled growth of cells due to dysregulation of EGFR signaling pathway. Mutated or over expression of EGFR is linked with many types of cancers for example breast, colon and lung cancers and also with glioblastoma multiform, epithelial and anal cancers. Therefore an attractive strategy to treat cancers was EGFR inhibition by using EGFR inhibitors. In addition to this use in clinics these are also involved in patient survival and various EGFR agonists and antagonists are also being used for the elucidation of different other pathways and effects of EGFR signaling pathway on them. These inhibitors are available at normal prices from any of the relevant supplier. [Read the Full Post]

ERLOTINIB– THE HCL SALT

5847 | Jun 19 2012

ERLOTINIB AND ITS PROPERTIES Erlotinib comes under the category of tyrosine kinase inhibitorswhich is also called OSI-420 EGFR inhibitor and usually named as HCl salt. Epidermal growth factor tyrosine kinase receptor is usually seen abnormal in various types of cancers so they are being employed for the anti-cancer therapy. A lot of new medicines are being produced by using the same approach [1]. Erlotinib structure revealed that it contained two quinazoline rings in its structures and it showed to inhibit the EGFR auto phosphorylationwhich eventually stops the pathway which is involved in the overexpression of genes. Around 18mg/ml in dimethyl sulfoxide (DMSO) is the Erlotinib solubility however it is scarcely soluble in water and ethanol. For inhibition of EGFR 20nM is Erlotinib IC50 [2]. It is easily oxidize able so care must be taken to increase its shelf life. Approximately $65 per 1000mg is Erlotinib price and buy OSI-420 for any kind of purpose under this trade name. [Read the Full Post]

GEFITINIB; AN EGFR INHIBITOR

5010 | May 28 2012

PROPERTIES AND MODE OF ACTION Gefitinib is one of several tyrosine kinase inhibitors that are quite efficient in their activity. Gefitinib is actually an EGFR inhibitor. It is marketed by the two companies i.e., Teva and AstraZeneca. Gefitinib EGFR inhibitor is a strong inhibitory compound and Gefitinib structure shows the presence of a ring in it i.e., anilinoquinazoline. One can buy Gefitinib in the form of a 1 gm vial in approximately $80. Scientists can purchase Gefitinib for research or treatment purposes. Gefitinib solubility can be achieved in organic solvents like ethanol, DMSO and DMF and Gefitinib stability for approximately 2 years can be achieved if it is stored at -20 oC. Gefitinib IC50 for EGFR inhibition against Tyr 992 and Tyr 1173 is 37 nM and 57 nM respectively. Different types of assays have been designed to clinically analyze the pharmacokinetics and sensitivity of the drug. These assays are based upon some predicting markers e.g., EGFR mutated genes, copy number or K-Ras mutations. [Read the Full Post]

GEFITINIB – EGFR REGULATING DRUG FOR LUNG CANCER

4570 | May 02 2012

GEFITINIB: PROPERTIES AND MECHANISM OF ACTION There are two companies that are marketing Gefitinib named AstraZeneca and Teva. Gefitinib drug is actually Gefitinib EGFR inhibitor molecule that is an efficient and strong compound and has undergone clinical trials. Gefitinib structure reveals that a ring of anilinoquinazoline is present in it. Gefitinib price for a 1 gram vial is around $80 and due to its reasonable price one can purchase Gefitinib EGFR inhibitor very easily for laboratory or research purposes from any supplier Gefitinib. Gefitinib stability is for almost 2 years if stored at -20 degrees. To inhibit Tyr 1173 and Tyr 992 properly, the Gefitinib IC50 is found to be 57 nM and 37 nM respectively for inhibition of EGFR. Various Gefitinib assays were carried out to check the sensitivity and pharmacokinetic properties of this drug and those clinical assays were found to base upon some certain predictive markers like EGFR mutated genes, mutations in K-Ras and copy number. [Read the Full Post]

ERLOTINIB (OSI-420) –A SALT OF HCL

4081 | May 01 2012

INTRODUCTION: Erlotinib drug is commonly known as HCl salt. It is also called as OSI-420 EGFR inhibitor. It is a small molecule of tyrosine kinase inhibitor that works against the receptor for epidermal growth factor. This epidermal growth factor results usually very high levels of expression and mostly gets mutated in case of various types of tumors, hence a valuable and attractive target for anti-tumor therapy. One can order OSI-420 to any of the supplier OSI-420. So one can purchase OSI-420 by paying Erlotinib price to its supplier that is around $65 for 1000 mg vial. Erlotinib structure describes that it has 2 rings of quinazoline. OSI-420 has found to be inhibiting the autophosphorylation of epidermal growth factor to render downstreaming of already stopped signaling cascade by binding to ATP binding site of EGFR in the reversible manner leading to a permanat change in its conformation or structure. Erlotinib solubility is 18 mg/ml in DMSO while it is very poorly soluble in water and ethanol. To inhibit EGFR tyrosine kinase enzyme in human, Erlotinib IC50 was found to be almost 20 nM. OSI-420 EGFR inhibitor must be kept far away from different oxidizing agents so that it will remain stable and safe. [Read the Full Post]

GEFITINIB – EGFR REGULATOR IN LUNG CANCER

3634 | Apr 12 2012

PROPERTIES OF GEFITINIB AND MECHANISM OF ACTION: Teva and AstraZeneca are the manufacturing and marketing companies of Gefitinib. Gefitinib EGFR (HER) inhibitor is a strong and efficient compound that has undergone clinical evaluations. An anilinoquinazoline ring is present in the structure of Gefitinib. For a 1 gram package the price for Gefitinib is about $80 due to this reasonable cost its easier to buy Gefitinib. If someone wants to order Gefitinib for research or laboratory uses one can contact any of Gefitinib suppliers. It can be stable for 2 years if properly stored at -20 oC. For proper inhibition of Tyr992and Tyr1173 Gefitinib IC50 is 57nM and 37nM respectively for EGFR inhibition. Different Gefitinib assays are done to analyze the pharmacokinetics, sensitivity and effect of this agent and those assays were based on certain predictive markers such as EGFR mutated gene, K-Ras mutations and copy number. In routine researchers use HDRA (histoculture drug response assay) or ELISA (enzyme linked immunosorbent assay) of human serum in order to analyze its pharmacokinetics studies. The mechanism behind the actions of Gefitinib is the binding of this compound competitively with EGFR ATP-binding site in cancer cells surface hence resulting in the inhibition of EGFR tyrosine phosphorylation induced by ligand to check downstream pathways. [Read the Full Post]

ERLOTINIB (OSI-420) – AN HCL SALT

3735 | Apr 02 2012

INTRODUCTION: Erlotinib is commonly known as Erlotinib salt of HCl. It is a very small tyrosine kinase inhibitor molecule, works against the epidermal growth factor receptor. This EGFR usually gives high level of expression and most often gets mutated in different types of cancers, hence an attractive target for the anti-cancer therapy. Researchers can purchase Erlotinib from supplier Erlotinib which sale it under the trading name of Tarceva. By paying Erlotinib prices around $65 for a 1000 mg vial one can buy OSI-420. Structure of Erlotinib reveals that it is having 2 rings of quinazoline. Erlotinib has found to inhibit the autophosphorylation of EGFR to render the downstreaming of stopped signaling pathway by binding to the ATP binding region of EGFR in a reversible manner causing a permanent conformational change in its structure. Erlotinib is poorly soluble in ethanol and water but gives a solution of 18 mg/ml upon heating in DMSO. For the inhibition of EGFR tyrosine kinase in human, Erlotinib IC50 is found to be near 20 nM. Erlotinib must be stored far away from oxidizing agents to keep it safe and stable. [Read the Full Post]

GEFITINIB – REFGULATING EGFR in CANCER

3583 | Mar 19 2012

Introduction: The HER (EGFR) pathway and Gefitinib Protein kinases have been established in recent years as prime targets for selective inhibition in many disorders involving cell proliferation or cell migration. The extent of the protein kinase system is very large with hundreds of different proteins interacting together to send multitude of signals to nuclei determining growth, death, transcription or response to any form damage or stress. To enable understanding of the mechanism of action for all these proteins they have been classified under pathways which are directly related. One of these pathways that is significant in its effects is the HER pathway, originally known as the EGFR pathway in relation to the epithelial growth factor. However, more proteins related to EGFR were recognized (ErRB 2-4) and the HER family was born. The location of this series of proteins is too span across the cell membrane from the extracellular region (head) into the cytosole (tail). Attachment of ligands to the extracellular sites cause structural changes to the protein which expose tyrosine kinase binding domains in the section of the protein located in the cytosole. [Read the Full Post]

ERLOTINIB – A ONE STOP SHOP

3378 | Mar 19 2012

Introduction: The HER (EGFR) pathway and Erlotinib Extracellular and intercellular signaling is a major process in the regulation of the life and death of cells within in any tissue matrix. One of the most well known and significant of these signaling steams is the HER protein family pathway consisting of four distinct receptors. Originally this was solely recognized as HER1 receptor called, due to its ligand association and since it was primarily found in epithelial cells, the “epithelial growth factor receptor”. Abbreviated to the acronym EGFR this receptor has since been found to have a family of 3 other closely related protein receptors, HER 2-4. Unfortunately these were known as ErB2-4 before the relationship with EGFR was determined, since then the entire family has been renamed to the HER family. These receptors consist of an extracellular section (head) with a Trans-membrane section and a cytosolic section (tail). Ligands binding to the extracellular domains initiate a dimerization between receptors which in turn induce conformational changes. [Read the Full Post]

EGFR INHIBITORS VERSUS CANCER

3477 | Mar 20 2012

Introduction: The HER family of proteins Recently collated and renamed as a single family of homologous series of proteins the HER family represents a major group of cellular membrane signal transmitters. Confusingly in literature the new naming system is inconsistently followed and the four HER receptors are often referred to as EGFR (HER1; ErRB1), ErRB2 (HER2), ErRB3 (HER3) and ErRB4 (HER4). These receptors have a very specific mode of action in that extracellular ligands can bind to the surface receptor domains on the cell membrane. Binding to any one of four different versions the ligand can stimulate a number of possible responses. Upon binding, the complex formed will alter conformationally and dimerize with another HER receptor increasing the number of permutations possible in the signaling process. The Dimerization initiates changes in the conformational state of the protein that induces the intercellular segment of the protein to reveal binding domains previously hidden. The protein will auto-phosphorylate activating it to receiving intercellular protein binding which starts the signaling process with the cell. The number of pathways that can be activated in different ways is large leading to contradictory responses. [Read the Full Post]

CP-690550: THE CURE FOR ARTHRITIS

7044 | Mar 20 2012

Introduction: JAK and its role in signaling pathways The protein kinase family plays an essential role in the government of the growth or death properties of mammalian tissues. These proteins form an interrelated, redundant system that is capable of selectively initiating the growth of certain cell types in response to the needs of the host system. To do this the protein kinase super family is subdivided into a series of related protein kinases which make up a signaling pathway, traveling from the extracellular matrix into the cell nucleus. The Janus kinase pathway is one which is activated in response to the action of cytokines on the cytokine transmembrane receptors. Since these receptors have no kinase ability themselves they are total dependant on the Janus kinases (JAK) for activity. [Read the Full Post]

INCB18424 – JACKING THE JAK2

7554 | Mar 20 2012

Introduction: JAK2 in relation to metabolic blood disorders The transmission of signals from extracellular factors through the cell membrane to effect actions within the cell cytosole and nucleus is conducted along pathways of protein to protein interactions. Many metabolic disorders have been associated with aberrations in these pathways causing a variety of destructive cellular actions. Many of these diseases possess no known cure and in response research has focused on the mechanisms behind the progression of these diseases. One area that has received a lot of attention is the possibility that the natural immune function can be detrimental to healthy growth patterns if over stimulated by mutations in the genetic information of individuals. A key series of proteins in the immune response is the Janus kinases (JAK), a series of four distinct but domain related kinases located in the cellular cytosole. These kinases form a distinct link between extracellular immune function ligands and a direct regulation of transcription of genetic information. However, a mutation of the JAK2 isoform has been associated with degenerative effects such as myeloproliferative neoplasms, thrombocythemia, polycythemia vera and psoriasis. [Read the Full Post]

TASOCITINIB: THE REVOLUTION IN ARTHRITIS MANAGEMENT

7436 | Mar 18 2012

Introduction: Inhibition of the JAK pathway The protein kinases are a super family of protein that govern the control of cellular growth, creation of vascular structure and many other processes the control the way in which cells and tissue regenerate. In is estimated that 30% of all cellular regulation is governed by protein kinases. Protein kinases are subdivided into 7 different classifications of which one is the tyrosine kinases. These kinases operate by phosphorylation of a tyrosine amino acid residue transferring a signal down a cascade of protein to regulate cellular processes. A further subdivision of the tyrosine kinases can be made into receptor based kinases and non receptor based kinases. The Janus kinases (JAK) are a sub family of the receptor based tyrosine kinases. Signals from the JAK regulate the cytokines, the GM-CSF family and the GP130 receptor family. JAK kinases exist in the 4 distinct isoforms with twinned phosphorylation domains. Inhibitors of the JAK kinases have been demonstrated to have a positive effect on cancerous cells both in vivo and in vitro. [Read the Full Post]

RUXOLITINIB: THE JACK FOR JAK INHIBITION

7645 | Mar 13 2012

Ruxolitinib: Inhibition of the Janus Kinases The janus kinases are a sub family of the protein kinases and are refer to as non receptor tyrosine kinases. Signals from the Janus kinases regulate several different types of proteins such as the cytokine receptor family (interferon), the GM-CSF family and the GP130 receptor family. The JAK kinases occur in four isoforms, with two matching phosphorylation domains, one for activity one for regulation. JAK2 in been shown to be mutated in several conditions including thrombocthemia and myeloprliferation disorders. In relation to haematological maliganacies the JAK2 mutation have been shown to essential for tumor growth and proliferation. Inhibiting the JAK2 kinase offers a potential mechanism for chemotherapeutic action. Ruxolitinib is a small, molecule inhibitor that has been established to inhibit the Janus kinases; early clinic work established that Ruxolitinib has sufficient anti-tumor activity to warrant further investigation. [Read the Full Post]

EGFR INHIBITORS CONTROLLING TUMORIGENESIS

4439 | Mar 13 2012

Introduction: The EGFR’s role in the HER pathway A major pathway in the regulation of cell growth / death is the HER pathway, this pathway consists of four structurally related proteins primarily located in the cell membrane. The family members consist of HER1 (also known as EGFR), HER2 (also known as ErbB2), HER3 (also known as ErbB3) and HER4 (also known as ErbB4). These receptors consist of an extracellular head and an intracellular tail lying across the cell membrane. Ligands binding to the extracellular receptor induce conformational changes which reveal binding domains within the intracellular tail. Auto-phosphorylation of the tyrosine kinase domain is a result of the HER receptor forming dimers and depending on which of several different ligands induced the change the tail section attracts proteins to initiate signaling cascades to the nucleus. Ligands that trigger this signaling pathway consist of endothelial growth factor (EGF), transforming growth factor alpha (TGFα), beracellulin (BTC), epiregulin (EPR) and amphiregulin (AREG). [Read the Full Post]

Roles of PIM serine/threonine kinases in cancers

7468 | Oct 27 2011

The Pim family of Ser/Thr kinases has been first identified in murine Moloney leukemia virus induced lymphomas, and is composed of three isoforms, Pim-1, Pim-2 and Pim-3. The following studies show that Pims are constitutively activated in many cancers. Of which, Pim-1 and Pim-2 were found to show the elevated levels mostly in hematologic malignancies and prostate cancer, while increased Pim-3 expression was mainly observed in different solid tumors. [Read the Full Post]

Mumenthaler, S. M., P. Y. Ng, et al. (2009). "Pharmacologic inhibition of Pim kinases alters prostate cancer cell growth and resensitizes chemoresistant cells to taxanes." Mol Cancer Ther 8(10): 2882-2893.

5244 | Jul 17 2011

These findings support the idea that inhibiting Pim kinases, in combination with a chemotherapeutic agent, could play an important role in prostate cancer treatment by targeting the clinical problem of chemoresistance. [Read the Full Post]

Chen, L. S., S. Redkar, et al. (2009). "Pim kinase inhibitor, SGI-1776, induces apoptosis in chronic lymphocytic leukemia cells." Blood 114(19): 4150-4157.

4831 | Jun 6 2011

Consistent with a decline in new RNA synthesis, MCL-1 transcript levels were decreased after treatment with SGI-1776. These data suggest that SGI-1776 induces apoptosis in CLL and that the mechanism involves Mcl-1 reduction. [Read the Full Post]

Bianco, R., T. Gelardi, et al. (2007). "Rational bases for the development of EGFR inhibitors for cancer treatment." Int J Biochem Cell Biol 39(7-8): 1416-1431.

3780 | May 11 2011

This article reviews the EGFR role in carcinogenesis and tumor progression as rational bases for the development of specific therapeutic inhibitors. [Read the Full Post]

Bachmann, M. and T. Moroy (2005). "The serine/threonine kinase Pim-1." Int J Biochem Cell Biol 37(4): 726-730.

5006 | Apr 16 2011

Pim-1 is able to phosphorylate different targets, most of which are involved in cell cycle progression or apoptosis. Pim-1 expression can be induced by several external stimuli in particular by a number of cytokines relevant in the immune system, which led to the labeling of Pim-1 as a "booster" for the immune response. [Read the Full Post]

Fischer, O. M., S. Hart, et al. (2003). "EGFR signal transactivation in cancer cells." Biochem Soc Trans 31(Pt 6): 1203-1208.

3704 | Mar 11 2011

Together with investigations revealing the importance of this GPCR-EGFR cross-talk mechanism in cardiac hypertrophy, Helicobacter pylori -induced pathophysiological processes and cystic fibrosis, these findings support an important role for GPCR ligand-dependent EGFR signal transactivation in diverse pathophysiological disorders. [Read the Full Post]