Validation of biomarkers and immunotherapy in head and neck squamous cell carcinoma using bioinformatics and Mendelian randomization.

BACKGROUND: To promote carcinogenesis through diverse molecular pathways involving dysregulation of gene expression and abnormalities. METHODS: We employed Mendelian randomization (MR) to uncover causal relationships between genetic factors and HNSCC. We used the Inverse Variance Weighted (IVW) method as the primary MR analysis, and validated the results through complementary approaches like MR-Egger regression, weighted median, and mode analyses. RESULTS: Our analysis identified 2210 genes that are differentially expressed in head and neck cancer (HNSCC) compared to normal tissues. Within the protein interaction network, the genes IL1B, CXCL8, CXCL1, and CCL2 stood out as central hubs. Further investigation revealed that these key genes are involved in important biological processes like skin development, wound healing, and fat metabolism. Notably, our Mendelian randomization analysis provided evidence for a causal relationship between the expression of the IL1B gene and the development of HNSCC. CONCLUSIONS: Our analysis identified 5 key genes - IL1B, CXCL8, CXCL1, CCL2, and IL1B - that show significant changes in expression in head and neck cancer. These genes could serve as important new biomarkers to help diagnose this disease and track how it progresses over time. Importantly, these genes are involved in regulating the immune system, suggesting that the body's immune response plays a critical role in head and neck cancer. This provides new avenues for future research to better understand the complex gene expression patterns underlying this type of cancer. Further investigation of these key genes and their regulatory networks could lead to important insights and potential new treatment approaches.

Blocking long noncoding RNA MALAT1 restrained the development of laryngeal and hypopharyngeal carcinoma.

PURPOSE: The long non-coding RNA MALAT1 is a predictive marker in several solid tumors with highly conserved sequences. However, the role of non-coding RNA in development of laryngeal or hypopharyngeal cancer remains unclear. METHODS: Tumor tissues and adjacent non-cancer tissues of 24 patients were collected. We detected the expression of MALAT1 in laryngeal cancer tissues and hypopharyngeal cancer tissues. Moreover, we developed a MALAT1 silencing model in human laryngeal tumor cells by transfecting MALAT1 small interfering RNA into human laryngeal carcinoma cell line Hep-2 and pharyngeal carcinoma cell line FaDu with Lipofectamine 2000 system. Cell cycle analysis, Cell Counting Kit-8 assay, Transwell assay, quantitative reverse transcription PCR, and wound-healing assays were performed to evaluate the impact of MALAT1 depletion on laryngeal or hypopharyngeal cancer cell's growth, proliferation, apoptosis, invasion and migration. RESULTS: MALAT1 was significantly up-regulated in laryngeal and hypopharyngeal carcinoma cells. MALAT1 down-regulation induced the increased apoptosis of both cell lines and suppressed cells' proliferation. Cells were arrested in G1/G2 phase and cells of S phase were significantly decreased. Down-regulation of MALAT1 expression can also inhibit the migration and invasion of laryngeal squamous cell carcinoma cell (Hep-2) and hypopharyngeal cancer cell (FaDu). CONCLUSION: In summary, our deactivation model of MALAT1 disentangled the active function of it as a regulator of gene expression governing the hallmarks of laryngeal and hypopharyngeal cancer. Blocking this long non-coding RNA may restrain the development of laryngeal cancer.

Small-cell lung cancer with recurrent syncope as the initial symptom: A case report and literature review.

Small-cell lung cancer (SCLC) presenting with syncope as the initial symptom is rare in adults. This onset of tumour-induced syncope cannot be screened or differentiated by coronary angiography, magnetic resonance angiography of the neck or 24-hour dynamic electrocardiogram. We herein describe the case of a 61-year-old man who presented with recurrent syncope that resolved after the first course of chemotherapy (carboplatin plus etoposide) for SCLC. A mass measuring 57×53 mm was identified in the left hilum, and a diagnosis of limited-disease SCLC (T4N2M0, IIIB) was made. Considering the rapid and complete remission after the treatment of the primary lesion, we hypothesised that the syncope was neurogenic and associated with cancer. Thus, 8 similar cases retrieved from PubMed were reviewed and, for the first time, the mechanism underlying the syncope was identified, which may involve tumour location, neurobiology and other inducing factors. Thus, for the treatment of such SCLC patients, standard chemotherapy is crucial for preventing syncopal attacks.

Effects of sildenafil on prognosis in patients with pulmonary hypertension after left-sided valvular surgery.

INTRODUCTION: Sildenafil (Viagra, Pfizer) is being used to treat pulmonary hypertension (PH). However, there are limited data on the effects of sildenafil on patients with PH after left-sided valvular surgery. The purpose of this study was to determine the optimal dosage and the effects of sildenafil on prognosis of patients with PH after left-sided valvular surgery. METHODS: This randomised controlled trial, double-blind study enrolled patients with PH undergoing left-sided valvular surgery in our hospital from January to December, 2010. Ninety patients were enrolled. And 0.5 mg/kg sildenafil citrate or placebo was administered through nasogastric tubes, the haemodynamics changes in the 0.5/1/2/4 hours were assessed. The sildenafil citrate/placebo was continued to the discharges and the early prognoses of these patients were compared. RESULTS: Compared with placebo, a 0.5 mg/kg dose of sildenafil significantly reduced the time of mechanical ventilation, stay-in-ICU and hospitalisation duration. CONCLUSIONS: Sildenafil might be beneficial to the early prognosis of patients with PH after left-sided valvular surgery.