Oral squamous cell carcinoma (SCC) is a prevalent malignant disease worldwide, especially so in Taiwan. Early- or even preclinical-stage detection is critical for reducing morbidity and mortality from oral SCC. Epidemiological and genome association studies are useful for identifying clinicopathological risk factors for preventive, diagnostic, and therapeutic approaches of oral SCC. For advanced oral SCC, effective treatments are critical to prolonging survival and enhancing quality of life. As oral SCC is characteristic of regional invasion with lymph node metastases, understanding the aggressive features of oral SCC, particularly in lymphangiogenesis, is essential for determining effective treatments. Emerging evidence has demonstrated that the tumor microenvironment (TME) plays a pivotal role in tumor growth, invasion, and metastases. Recent clinical successes in immune checkpoint inhibitors either alone or combined with chemotherapy have also supported the therapeutic value of immunotherapy in oral SCC. This review summarizes critical advances in basic knowledge of oral SCC from the perspective of clinicopathological risk factors, molecular tumorigenesis, and the TME. We also highlight our recent investigations on the microbiome, genome association studies, lymphangiogenesis, and immunomodulation in oral SCC. This review may provide new insights for oral SCC treatment by systematically interpreting emerging evidence from various preclinical and clinical studies.

High collagen type XI alpha 1 (COL11A1) levels are associated with tumor progression, chemoresistance, and poor patient survival in several cancer types. MicroRNAs (miRNAs) are dysregulated in multiple cancers, including epithelial ovarian carcinoma (EOC); however, the regulation of COL11A1 by miRNAs in EOC remains unclear. We examined the role of miRNAs in regulating COL11A1 expression. We identified miR-509 and miR-335 as the candidate miRNAs through an online database search. EOC cell treatment with miR-335 mimics abrogated COL11A1 expression and suppressed cell proliferation and invasion, besides increasing the sensitivity of EOC cells to cisplatin. Conversely, treatment with miR-335 inhibitors prompted cell growth/invasiveness and chemoresistance of EOC cells. miR-335 inhibited COL11A1 transcription, thus reducing the invasiveness and chemoresistance of EOC cells via the Ets-1/MMP3 and Akt/c/EBPβ/PDK1 axes, respectively. Furthermore, it did not directly regulate PDK1 but increased PDK1 ubiquitination and degradation through COL11A1 inhibition. In vivo findings highlighted significantly decreased miR-335 mRNA expressions in EOC samples. Furthermore, patients with low miR335 levels were susceptible to advanced-stage cancer, poor response to chemotherapy, and early relapse. This study highlighted the importance of miR-335 in downregulating COL11A1-mediated ovarian tumor progression, chemoresistance, and poor survival and suggested its potential application as a therapeutic target.

Melatonin, a naturally biosynthesized molecule secreted by the pineal gland, exhibits antitumor activities against several different types of cancer. The mechanisms of action of melatonin against tumor progression involve cellular apoptosis, antimetastatic activity, antioxidant and mutagenic effects, antiangiogenic activity, and the restoration of cancer immune surveillance. Melatonin has anticancer activity when administered alone or in combination with standard chemotherapeutic agents, with measurable improvements seen in the clinical endpoints of tumor regression and patient survival. However, scant clinical evidence supports the use of melatonin in bladder cancer treatment. Our study has found that melatonin treatment suppresses the bladder cancer cell migratory ability by inhibiting the epithelial-mesenchymal transition (EMT) process, which appears to be linked to melatonin-induced decreases in bladder cancer cell autophagy. Finally, an evaluation of in vivo melatonin-induced antitumor effects in an orthotopic animal model of bladder cancer indicated that melatonin treatment slightly prolonged the survival of tumor-bearing mice. Our study offers novel insights into the use of melatonin in bladder cancer treatment.

Background and objectives: High-flow nasal cannula (HFNC) can be used as a respiratory support strategy for patients with acute respiratory failure (ARF). However, no clear evidence exists to support or oppose HFNC use in immunocompromised patients. Thus, this meta-analysis aims to assess the effects of HFNC, compared to conventional oxygen therapy (COT) and noninvasive ventilation (NIV), on the outcomes in immunocompromised patients with ARF. The Pubmed, Embase and Cochrane databases were searched up to November 2018. Materials and Methods: Only clinical studies comparing the effect of HFNC with COT or NIV for immunocompromised patients with ARF were included. The outcome included the rate of intubation, mortality and length of stay (LOS). Results: A total of eight studies involving 1433 immunocompromised patients with ARF were enrolled. The pooled analysis showed that HFNC was significantly associated with a reduced intubation rate (risk ratio (RR), 0.83; 95% confidence interval (CI), 0.74–0.94, I² = 0%). Among subgroup analysis, HFNC was associated with a lower intubation rate than COT (RR, 0.86; 95% CI, 0.75–0.95, I² = 0%) and NIV (RR, 0.59; 95% CI, 0.40–0.86, I² = 0%), respectively. However, there was no significant difference between HFNC and control groups in terms of 28-day mortality (RR, 0.78; 95% CI, 0.58–1.04, I² = 48%), and intensive care unit (ICU) mortality (RR, 0.87; 95% CI, 0.73–1.05, I² = 57%). The ICU and hospital LOS were similar between HFNC and control groups (ICU LOS: mean difference, 0.49 days; 95% CI, −0.25–1.23, I² = 69%; hospital LOS: mean difference, −0.12 days; 95% CI, −1.86–1.61, I² = 64%). Conclusions: Use of HFNC may decrease the intubation rate in immunocompromised patients with ARF compared with the control group, including COT and NIV. However, HFNC could not provide additional survival benefit or shorten the LOS. Further large, randomized controlled trials are needed to confirm these findings.

Acute myeloid leukemia (AML) is one of the most frequent forms of acute leukemia and the second most common leukemia subtype in adults. In 2020, the incidence of AML in the United States was estimated to be ~4 cases per 100,000 adults. The FMS‑like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) and tyrosine kinase domain (TKD) mutation are major prognostic indicators of AML. They are more frequently observed in younger AML patients (aged <60 years), likely due to their association with de novo. Additionally, these mutations have a stronger negative impact on survival in younger patients. Therefore, quizartinib and gilteritinib are second‑generation FLT3 inhibitors that are frequently applied for treating patients with AML. However, to the best of our knowledge, few studies have compared the efficacy of second‑generation FLT3 inhibitors for AML treatment. Therefore, the present study conducted a comprehensive search for studies on the efficacy and safety of FLT3 inhibitors across PubMed, Embase, the Cochrane Library and ClinicalTrials.gov. The search criteria were limited to randomized controlled trials (RCTs). Subsequently, a meta‑analysis was performed on a total of five randomized controlled trials, involving 1,543 participants in total, using a random‑effects model. In each RCT, compared to the salvage chemotherapy used in the control group, the groups that received second‑generation FLT3 inhibitors experienced significant improvements in overall survival (hazard ratio, 0.717; 95% CI, 0.604‑0.850; P<0.001). In addition, overall survival was found to be consistent across the different types of second‑generation FLT3 inhibitors used and different types of AML. The risks associated with a prolonged heart‑rate corrected QT interval (QTc) interval were next evaluated. Compared with the salvage chemotherapy used in the control group, the second‑generation FLT3 inhibitor group exhibited a significantly higher risk of having a prolonged QTc interval (odds ratio, 6.311; 95% CI, 3.061‑13.013; P<0.001). In conclusion, these findings suggest that second‑generation FLT3 inhibitors can improve the overall survival of patients with AML. However, QTc prolongation is a potential adverse effect that should be monitored.