IL-6 in the Ecosystem of Head and Neck Cancer: Possible Therapeutic Perspectives

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(20), P. 11027 - 11027

Published: Oct. 13, 2021

Interleukin-6 (IL-6) is a highly potent cytokine involved in multiple biological processes. It was previously reported to play distinct role inflammation, autoimmune and psychiatric disorders, ageing various types of cancer. Furthermore, it understood that IL-6 its signaling pathways are substantial players orchestrating the cancer microenvironment. Thus, they appear be potential targets anti-tumor therapy. The aim this article elucidate tumor ecosystem review possible therapeutic approaches head neck

Language: Английский

---

Protection by hydroxychloroquine prevents placental injury in obstetric antiphospholipid syndrome

Journal of Cellular and Molecular Medicine, Journal Year: 2022, Volume and Issue: 26(15), P. 4357 - 4370

Published: June 29, 2022

Abstract Obstetric antiphospholipid syndrome (OAPS) is mediated by antibodies (aPLs, and anti‐β2 glycoprotein I antibody the main pathogenic antibody), recurrent abortion, preeclampsia, foetal growth restriction other placental diseases are clinical characteristics of pathological pregnancy. It a disease that seriously threatens health pregnant women. Hydroxychloroquine (HCQ) was originally used as an anti‐malaria drug has now shown benefit in refractory OAPS where conventional treatment failed, with expectation providing protective benefits for both mother foetus. However, its efficacy mechanism action still unclear. After data were collected to determine therapeutic effect, human trophoblast cells early pregnancy prepared treated aPL. addition HCQ, proliferation, invasion, migration tubule formation observed so HCQ on could be determined. By establishing obstetric APS mouse model similar situation, we able detect effect The normal function affected Antibodies reduce ability invade migrate can impair formation, which closely related insufficiency. partially reverse these side effects. In model, found prevented death reduced incidence Therefore, improve outcomes aPL inhibition disease. OAPS, use needs considered.

Language: Английский

---

Tafenoquine and its derivatives as inhibitors for the severe acute respiratory syndrome coronavirus 2

Journal of Biological Chemistry, Journal Year: 2022, Volume and Issue: 298(3), P. 101658 - 101658

Published: Jan. 30, 2022

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has severely affected human lives around the world as well global economy. Therefore, effective treatments against COVID-19 are urgently needed. Here, we screened a library containing Food and Drug Administration (FDA)-approved compounds to identify drugs that could target SARS-CoV-2 main protease (Mpro), which is indispensable for viral protein maturation regard an important therapeutic target. We identified antimalarial drug tafenoquine (TFQ), approved radical cure of Plasmodium vivax malaria prophylaxis, top candidate inhibit Mpro activity. crystal structure in complex with TFQ revealed noncovalently bound reshaped substrate-binding pocket altering loop region (residues 139-144) near catalytic Cys145, block catalysis its peptide substrates. also found inhibited transmembrane serine (TMPRSS2). Furthermore, one derivative, compound 7, showed better index than on TMPRSS2 may therefore infectibility SARS-CoV-2, including several mutant variants. These results suggest new potential strategies infection rising

Language: Английский

---

Dexamethasone Modulates the Cytokine Response but Not COVID-19-Induced Coagulopathy in Critically Ill

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(8), P. 7278 - 7278

Published: April 14, 2023

Severe forms of coronavirus 2019 (COVID-19) disease are caused by an exaggerated systemic inflammatory response and subsequent inflammation-related coagulopathy. Anti-inflammatory treatment with low dose dexamethasone has been shown to reduce mortality in COVID-19 patients requiring oxygen therapy. However, the mechanisms action corticosteroids have not extensively studied critically ill context COVID-19. Plasma biomarkers immune responses, endothelial platelet activation, neutrophil extracellular trap formation, coagulopathy were compared between treated or for severe Dexamethasone significantly reduced lymphoid critical but had little effect on myeloid no The benefits outcome can be partially explained a modulation reduction Future studies should explore impact combining other immunomodulatory anticoagulant drugs

Language: Английский

---

Phase I trial of hydroxychloroquine to enhance palbociclib and letrozole efficacy in ER+/HER2− breast cancer

npj Breast Cancer, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 26, 2025

Abstract Endocrine therapy with CDK4/6 inhibitors is standard for estrogen receptor-positive, HER2−negative metastatic breast cancer (ER+/HER2− MBC), yet clinical resistance develops. Previously, we demonstrated that low doses of palbociclib activate autophagy, reversing initial G1 cell cycle arrest, while high concentrations induce off-target senescence. The autophagy inhibitor hydroxychloroquine (HCQ) induced on-target senescence at lower doses. We conducted a phase I trial (NCT03774472 registered in ClinicalTrials.gov on 8/20/2018) HCQ (400, 600, 800 mg/day) (75 mg/day continuous) and letrozole, using 3 + design. Primary objectives included safety, tolerability, determining the recommended 2 dose (RP2D) HCQ. Secondary tumor response biomarker analysis. Fourteen ER+/HER2− MBC patients were evaluable [400 mg ( n = 4), 600 6)]. Grade adverse events (AEs) hematological (3 mg), skin rash (2 anorexia (1 400 no serious AEs. best responses partial (2), stable (11), progression (1). Tumor reductions ranged from 11% to 30%, one 55% increase. two responders sustained size 30% over an extended treatment period, lasting nearly 300 days. Biomarker analysis significant decreases Ki67, Rb, nuclear cyclin E levels increases markers p62 LAMP1, suggesting correlation between these biomarkers response. This study safe well-tolerated RP2D was established continuous low-dose letrozole (2.5 mg/day). These findings suggest adding could potentially enhance efficacy therapy, pending verification larger randomized studies.

Language: Английский

---

Safety of Hydroxychloroquine: What a Dermatologist Should Know

American Journal of Clinical Dermatology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

The unique immunomodulatory properties of hydroxychloroquine (HCQ) have attracted considerable interest beyond its use for malaria and rheumatological diseases, including a variety dermatological conditions. Over recent years, especially after the coronavirus disease 2019 (COVID-19) pandemic, prescription HCQ has also significantly expanded, sometimes inappropriately, thus posing additional challenges on optimal use, due to emerging safety issues. In this review, we provide dermatologists with latest advancements selected clinically relevant toxicities, namely retinopathy, pro-arrhythmia, cutaneous reactions, neuropsychiatric effects. It is hoped update can assist identify high-risk patients tailored monitoring, screening, risk minimization strategies, supporting safer prescribing.

Language: Английский

---

High-dose hydroxychloroquine induces changes in low-frequency brain oscillations in electrocorticographic records not concurrent with alterations in cardiac, hepatic, and renal function in wistar rats

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 186, P. 117980 - 117980

Published: April 13, 2025

Language: Английский

---

The controversial therapeutic journey of chloroquine and hydroxychloroquine in the battle against SARS-CoV-2: A comprehensive review

Medicine in Drug Discovery, Journal Year: 2021, Volume and Issue: 10, P. 100085 - 100085

Published: March 11, 2021

Recently, the pandemic outbreak of a novel coronavirus, officially termed as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), indicated by pulmonary infection in humans, has become one most significant challenges for public health. In current fight against coronavirus disease-2019, medical and health authorities across world focused on quick diagnosis isolation patients; meanwhile, researchers worldwide are exploring possibility developing vaccines therapeutic options to combat this deadly disease. based various small clinical observations, uncontrolled case studies previously reported antiviral activity SARS-CoV-1 chloroquine (CQ) hydroxychloroquine (HCQ) have attracted exceptional consideration possible agents SARS-CoV-2. However, there reports little no effect CQ or HCQ SARS-CoV-2, many raised concerns about their cardiac toxicity. Here, review, we examine chemistry, molecular mechanism, pharmacology, including scenario future prospects treatment

Language: Английский

---

Science's Response to CoVID‐19

ChemMedChem, Journal Year: 2021, Volume and Issue: 16(15), P. 2288 - 2314

Published: April 3, 2021

Abstract CoVID‐19 is a multi‐symptomatic disease which has made global impact due to its ability spread rapidly, and relatively high mortality rate. Beyond the heroic efforts develop vaccines, we do not discuss herein, response of scientists clinicians this complex problem reflected need detect diagnose patients likely show adverse symptoms, treat severe critical CoVID‐19. Here aim encapsulate these varied sometimes conflicting approaches resulting data in terms chemistry biology. In process highlight emerging concepts, potential future applications that may arise out immense effort.

Language: Английский

---

Bridging animal and clinical research during SARS-CoV-2 pandemic: A new-old challenge

EBioMedicine, Journal Year: 2021, Volume and Issue: 66, P. 103291 - 103291

Published: April 1, 2021

Many milestones in medical history rest on animal modeling of human diseases. The SARS-CoV-2 pandemic has evoked a tremendous investigative effort primarily centered clinical studies. However, several SARS-CoV-2/COVID-19 models have been developed and pre-clinical findings aimed at supporting evidence rapidly emerge. In this review, we characterize the existing exposing their relevance limitations as well outline utility COVID-19 drug vaccine development. Concurrently, summarize status trial research discuss novel tactics utilized largest multi-center trials aiming to accelerate generation reliable results that may subsequently shape treatment practices. We also highlight areas improvement for studies order elevate translational utility. pandemics, optimize use strained resources short time-frame, optimizing strengthening synergy between preclinical domains is pivotal.

Language: Английский

---