Cancer is one of the leading cause of death in the world with the prevalence of >10 million mortalities annually. Current cancer treatments include surgical intervention, radiation, and taking chemotherapeutic drugs, which often kill the healthy cells and result in toxicity in patients. Therefore, researchers are looking for ways to be able to eliminate just cancerous cells. Intra-tumor heterogeneity of cancerous cells is the main obstacle on the way of an effective cancer treatment. However, better comprehension of molecular basis of tumor and the advent of new diagnostic technologies can help to improve the treatment of various cancers. Therefore, study of epigenetic changes, gene expression of cancerous cells and employing methods that enable us to correct or minimize these changes is critically important. In this paper, we will review the recent advanced strategies being used in the field of cancer research.
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To perform a quantitative olfactory test in positive COVID19 RT-PCR admitted patients and asymptomatic ones, to evaluate the association between hyposmia and disease severity. This is a Cross sectional study. Ninety-one patients including 68 inpatients and 23 asymptomatic healthcare workers with positive COVID-19 RT-PCRs. Methods: Demographics and clinical characteristics were collected. Iran Smell Identification Test (IR-SIT), a highly accurate 6-odorant test was used to evaluate the reliability of self-reported hyposmia and determine the correlation of the measured olfactory dysfunction with disease severity. Twenty-two of 91 patients (24%) reported hyposmia, while 41/91 (45%) patients had measurable olfactory dysfunction (IR-SIT score 1–4, p < 0.05). Mean age of the 68 inpatients and 23 asymptomatic patients were 43.97 ± 16.13 years; M:F 43:25, and 43.87 ± 12.76 years; M:F 8:15 respectively. Of 68 patients, 20 were graded as severe, and 48/68 had mild course of disease. IR-SIT detected hyposmia in 80% of patients with severe disease, and 50% with mild disease, respectively. The risk of disease severity was significantly increased for patients with olfactory dysfunction and was detected 4 times higher when compared to patients with mild disease (OR 4, 95% CI: 1.166–13.728, p = 0.028). Olfactory Dysfunction was present in 80% of patients with severe course. The risk of disease severity is significantly increased with olfactory dysfunction in admitted patients.
Novel coronavirus disease (COVID-19) pandemic has become a global health emergency. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interacts with angiotensin-converting enzyme 2 (ACE2) to enter the cells and infects diverse human tissues. It has been reported that a few conditions, including cancer, predispose individuals to SARS-CoV-2 infection and severe form of COVID-19. These findings led us to evaluate the susceptibility of colon adenocarcinoma (COAD) patients to SARS-CoV-2 infection by investigation of ACE2 expression in their tumor tissues. The expression analysis revealed that both mRNA and protein levels of ACE2 had increased in colon cancer samples than normal group. Next, the prognosis analysis has indicated that the upregulation of ACE2 was not correlated with patient survival outcomes. Further assessment displayed the hypomethylation of the ACE2 gene promoter in COAD patients. Surprisingly, this methylation status has a strong negative correlation with ACE2 gene expression. The functional enrichment analysis of the genes that had similar expression patterns with ACE2 in colon cancer tissues demonstrated that they mainly enriched in Vitamin digestion and absorption, Sulfur relay system, and Fat digestion and absorption pathways. Finally, we found that ACE2 gene expression had a significant association with the immune cell infiltration levels in COAD patients. In conclusion, it has plausible that COAD patients are more likely to be infected with SARS-CoV-2 and experience severe injuries. Moreover, COVID-19 would bring unfavorable survival outcomes of patients with colon cancer by the way of immune cell infiltration linked process. The present study highlights the importance of preventive actions for COAD patients during the COVID-19 pandemic.
Background: Head and neck squamous cell carcinoma (HNSCC) includes a group of heterogeneous tumors with generally invasive behavior. The PI3K/AKT pathway plays an important role in the pathogenesis of HNSCC. Methods: In the current study, we investigated the expression of two negative feedback regulators of the PI3K pathway, namely PHLDA3 and GRHL3, in 45 paired samples of HNSCC and adjacent non-cancerous tissues (ANCTs). Results: While expression of GRHL3 was down-regulated in tumoral tissues compared with ANCTs by the factor 4.21, PHLDA3 expression levels were up-regulated by 5.99-times. Gender-based analysis revealed a significant down-regulation of GRHL3 gene expression level in male patients compared with the control samples and significant up-regulation of PHLDA3 gene expression level in both sexes compared with the control samples. Differences in the expressions of both genes were significant in patients aged more than 60 years, but not in the younger patients. Expression of GRHL3 was only down-regulated in patients with positive smoking history. Expression of GRHL3 was decreased in grades 2 and 3 samples compared with controls. There was a significant increase in transcript levels of PHLDA3 in stages II and III HNSCC samples compared with the controls group. ROC curve analysis indicated that the expression level of PHLDA3 could be a promising marker for the diagnosis of HNSCC patients with a sensitivity and specificity of 0.666 and 0.688, respectively. In addition, sensitivity and specificity of GRHL3 were 0.755 and 0.577, respectively. Discussion: The current study indicates dysregulation of regulators of PI3K pathway in HNSCC and their potential application as putative biomarkers for this cancer.
Hypoxanthine phosphoribosyl transferase (HPRT1), as a salvage pathway enzyme, plays a crucial role in modulating the cell cycle and has been reported to be overexpressed in multiple cancers. Nevertheless, the relationship between the HPRT1 and Head and Neck Squamous Cell Carcinomas (HNSCC) has not been investigated so far. We first evaluated the expression of HPRT1 at transcriptomic and proteomic levels in tumor and healthy control tissues and its clinical value using The Cancer Genome Atlas (TCGA), Human Protein Atlas, Kaplan-Meier Plotter databases, GSE107591, and quantitative real-time PCR analysis. Then, we employed the COSMIC and cBioPortal databases to assess the mutations of the HPRT1 gene and their association with survival outcomes of patients with HNSCC. Finally, we performed the functional enrichment analysis for HPRT1 co-expressed genes in HNSCC utilizing the Enrichr database. The mRNA and protein expressions of HPRT1 were significantly elevated in HNSCC compared with normal tissues. Besides, the upregulation of HPRT1 expression was correlated with age, sex, pathological stage, and histological grades of HNSCC patients. Moreover, the increased expression of HPRT1 in cancer tissues exhibited a strong capacity for being a promising biomarker for the diagnosis and prognosis of patients with HNSCC. The co-expressed genes of HPRT1 were mainly enriched in several cancer-related processes such as DNA replication and cell cycle. The present study demonstrated that the overexpression of HPRT1 is significantly correlated with the progression of HNSCC and may serve as a useful biomarker for the early detection and risk stratification of patients with HNSCC.
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