Addition of epidermal growth factor receptor inhibitors to standard chemotherapy increases survival of advanced head and neck squamous cell carcinoma patients: A systematic review and meta-analysis.

Head and neck squamous cell carcinoma (HNSCC) is among the common tumors associated with high mortality. The aim of our meta-analysis was to determine how additional anti-epidermal growth factor receptor (EGFR) therapy to standard chemotherapy affects the progression-free (PFS) and overall survival (OS) of the patients, besides the most common side effects. We used CENTRAL, MEDLINE, and Embase databases until October 26, 2020, and included 13 eligible randomized controlled trials in our systematic research. The pooled hazard ratios (HR) for the main outcomes from the original data were estimated and for the other dichotomous outcomes, odds ratios (ORs) with their 95% confidence intervals (CI) were calculated. Addition of EGFR inhibitors to conventional chemotherapy significantly decreased the death and disease progression (for PFS HR: 0.68, 95% CI: 0.55-0.81, I2  = 65.5%, p = 0.005) and mortality (for OS HR: 0.83, 95% CI: 0.72-0.94, I2  = 42.3%, p = 0.076). In the EGFR inhibitor group, we revealed an increased chance of the over Grade 3 skin rashes (OR: 4.86; 95% CI: 1.52-15.49, I2  = 2.3%, p = 0.407), and all Grade skin rashes (OR: 18.32, 95% CI: 8.07-41.60, I2  = 56.6%, p = 0.032). Despite their unwanted dermatological side effects, the addition of EGFR inhibitors is recommended to be included in advanced HNSCC therapy.

Janus Kinase Inhibitors Improve Disease Activity and Patient-Reported Outcomes in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of 24,135 Patients.

Pain, fatigue, and physical activity are major determinants of life quality in rheumatoid arthritis (RA). Janus kinase (JAK) inhibitors have emerged as effective medications in RA and have been reported to exert direct analgesic effect in addition to reducing joint inflammation. This analysis aims to give an extensive summary of JAK inhibitors especially focusing on pain and patient reported outcomes (PRO). MEDLINE, CENTRAL, Embase, Scopus, and Web of Science databases were searched on the 26 October 2020, and 50 randomized controlled trials including 24,135 adult patients with active RA met the inclusion criteria. JAK inhibitors yielded significantly better results in all 36 outcomes compared to placebo. JAK monotherapy proved to be more effective than methotrexate in 9 out of 11 efficacy outcomes. In comparison to biological disease-modifying antirheumatic drugs, JAK inhibitors show statistical superiority in 13 of the 19 efficacy outcomes. Analgesic effect determined using the visual analogue scale and American College of Rheumatology (ACR) 20/50/70 response rates was significantly greater in the JAK group in all comparisons, and no significant difference regarding safety could be explored. This meta-analysis gives a comprehensive overview of JAK inhibitors and provides evidence for their superiority in improving PROs and disease activity indices in RA.

Functional Transient Receptor Potential Ankyrin 1 and Vanilloid 1 Ion Channels Are Overexpressed in Human Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is a common cancer with poor prognosis. Transient Receptor Potential Ankyrin 1 (TRPA1) and Vanilloid 1 (TRPV1) receptors are non-selective cation channels expressed on primary sensory neurons and epithelial and immune cells. TRPV1 mRNA and immunopositivity, as well as TRPA1-like immunoreactivity upregulation, were demonstrated in OSCC, but selectivity problems with the antibodies still raise questions and their functional relevance is unclear. Therefore, here, we investigated TRPA1 and TRPV1 expressions in OSCC and analyzed their functions. TRPA1 and TRPV1 mRNA were determined by RNAscope in situ hybridization and qPCR. Radioactive 45Ca2+ uptake and ATP-based luminescence indicating cell viability were measured in PE/CA-PJ41 cells in response to the TRPA1 agonist allyl-isothiocyanate (AITC) and TRPV1 agonist capsaicin to determine receptor function. Both TRPA1 and TRPV1 mRNA are expressed in the squamous epithelium of the human oral mucosa and in PE/CA-PJ41 cells, and their expressions are significantly upregulated in OSCC compared to healthy mucosa. TRPA1 and TRPV1 activation (100 µM AITC, 100 nM capsaicin) induced 45Ca2+-influx into PE/CA-PJ41 cells. Both AITC (10 nM-5 µM) and capsaicin (100 nM-45 µM) reduced cell viability, reaching significant decrease at 100 nM AITC and 45 µM capsaicin. We provide the first evidence for the presence of non-neuronal TRPA1 receptor in the OSCC and confirm the expression of TRPV1 channel. These channels are functionally active and might regulate cancer cell viability.

Transient Receptor Potential (TRP) Channels in Head-and-Neck Squamous Cell Carcinomas: Diagnostic, Prognostic, and Therapeutic Potentials.

Head-and-neck squamous cell carcinomas (HNSCC) remain a leading cause of cancer morbidity and mortality worldwide. This is a largely preventable disease with smoking, alcohol abuse, and human papilloma virus (HPV) being the main risk factors. Yet, many patients are diagnosed with advanced disease, and no survival improvement has been seen for oral SCC in the past decade. Clearly, new diagnostic and prognostic markers are needed for early diagnosis and to guide therapy. Gene expression studies implied the involvement of transient receptor potential (TRP) channels in the pathogenesis of HNSCC. TRPs are expressed in normal epithelium where they play a key role in proliferation and differentiation. There is increasing evidence that the expression of TRP channels may change in HNSCC with important implications for diagnosis, prognosis, and therapy. In this review, we propose that TRP channel expression may afford a novel opportunity for early diagnosis of HNSCC and targeted molecular treatment.

Head and neck mucosal melanoma: clinicopathological analysis of 5 cases and review of the literature.

Mucosal melanoma in the region of head and neck is a rare and aggressive tumor. Diagnosis is usually late due to the quick, vertical spread of the disease, the a lack of early or specific signs and because of the location of lesions. The mainstay of treatment is radical surgical resection. The value of sentinel lymph node biopsy, lymphadenectomy and radiotherapy is still unclear. The objective of this study is to report five patients with primer malignant mucosal melanoma and briefly summarize the current literature of the etiology, staging and treatment of the disease.