Expression pattern and clinical significance of beta 2-adrenergic receptor in oral squamous cell carcinoma: an emerging prognostic indicator and future therapeutic target.

PURPOSE: Beta 2-Adrenergic Receptor (ß2-AR) is significantly overexpressed in various types of malignancies, which is associated with the worst prognosis. However, the role of ß2-AR in oral cancer is not well identified. The present study aimed at investigating the ß2-AR gene expression and its significance in relation with the clinicopathological features and overall survival of oral squamous cell carcinoma (OSCC) patients. METHODS: Immunohistochemistry, western blot and quantitative real-time PCR techniques were used to analyze ß2-AR protein and mRNA levels in a total of 65 histopathologically confirmed OSCC tissues (case group) and 65 normal tissues (control group) from the oral cavity. RESULTS: Out of the total of 65 OSCC tissues, 41 tissues (63.1%) exhibited  high expression  for ß2-AR protein. Percent positivity and relative density (mean ± SD) of protein were higher in the case group as compared to the control group (positivity 40.31 ± 3.01 vs. 20.46 ± 1.93, p < 0.001; density 2.77 ± 1.17 vs. 1.28 ± 0.37, p < 0.001). In addition, ß2-AR mRNA level was also upregulated in patients compared to the controls (2.36 ± 1.30 vs. 1.09 ± 0.42, p < 0.001) and showed a positive correlation with immunostaining of protein in OSCC (r = 0.48, p = 0.011). High ß2-AR protein expression was significantly associated with multiple risk habits (p = 0.045), histological differentiation (p = 0.013), clinical TNM stages (p = 0.014), and poor survival (p = 0.006) of patients. In the Cox proportional hazards model, ß2-AR was identified as a prognostic biomarker of OSCC (p = 0.047). CONCLUSION: ß2-AR protein level is identified as an independent significant prognostic factor in patients with oral carcinoma.

Comprehensive study on clinical responses and socioeconomic characteristics of COVID-19 patients during outbreak.

The severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2) causes coronavirus disease 2019 (COVID-19) and emerged as a new public health crisis. This RNA virus, which has an origin in bats, is phenotypically and genotypically diverse. The source of transmission is by direct inhalation or contact with infected droplets or indirect through fomites. The disease shows an average incubation period of 2 to 14 days. The general symptoms include fever, cough, sore throat, breathlessness, fatigue, and malaise, although in a few it is found to be asymptomatic. The immune response shows variation from individual to individual, which varies from pneumonia, chest pain, acute respiratory distress syndrome, and multiorgan failure leading to death. The cytokine and chemokine responses play a major role in the severity of the infection. Laboratory diagnosis is done by molecular investigations. The socioeconomic conditions of individuals also play a role in disease manifestation. Treatment is supportive with symptomatic management. Preventive measures include social distancing, use of face masks, and contact tracing. This review will present a general overview of coronavirus and describe the clinical and socioeconomic features of the COVID-19 patients. It will also introduce comprehensive data of symptomatic and asymptomatic patients among different Asian and Western countries during the current pandemic. Furthermore, it also focuses on the most up-to-date information on effective management and prevention of COVID-19.

Upregulated histone deacetylase 2 gene correlates with the progression of oral squamous cell carcinoma.

BACKGROUND: Histone deacetylases (HDACs) are considered as an essential regulator of cellular proliferation, differentiation, and apoptosis. The HDAC2 enzyme of Class I HDACs plays an important role in tumor progression of human malignancies. OBJECTIVE: The aim of the present study was to analyze the HDAC2 gene expression in pre-oral cancer and oral squamous cell carcinoma (OSCC), and its association with clinico-pathological features. METHODS: The HDAC2 protein expression was analyzed through the immunohistochemistry and western blot techniques in 82 oral pre-malignant, 90 OSCC, and 16 normal control tissues. qRT-PCR was used to quantify the mRNA fold change in all groups. RESULTS: The HDAC2 protein and mRNA levels were significantly higher in OSCC and pre-oral cancer groups compared to the controls. Immunostaining of HDAC2 protein was enhanced in 84.4% of OSCC and 67.1% of pre-cancerous tissue sections (p< 0.01). The mean protein level was analyzed as 1.96 ± 0.44 in oral carcinoma, 1.61 ± 0.39 in pre-cancer and 0.96 ± 0.10 in control tissues. In addition, HDAC2 mean protein level was associated with histological differentiation (OR = 25, p< 0.05) and tumor-node-metastasis (TNM) stages (OR = 6.2, p< 0.05) of OSCC patients. CONCLUSIONS: The upregulated HDAC2 gene in pre-cancer and OSCC tissues indicates its crucial role in the transformation of pre-malignant to malignant carcinoma. It could be a potential cancer biomarker of prognosis and targeted therapy in OSCC.

Increased Gonadotropins and prolactin are linked to infertility in males.

Infertility has become a significant issue among married couples worldwide. The association of variations in reproductive hormones with infertility is evaluated at a tertiary care hospital in North India. A total of 220 infertile males having infertility longer than one year (cases) and 220 age-matched fertile males with confirmed paternity in past two to three years (controls) were enrolled for the study. Serum levels of LH, FSH, testosterone and PRL were measured by Roche e411 autoanalyzer using electrochemiluminescense immunoassay technique. Significant higher levels of serum hormone (mean±SD) were found in cases vs. controls; LH (9.02±7.81 vs. 5.22±1.45 mIU/ml), FSH (11.45±14.02 vs. 4.09±1.62 mIU/ml) and PRL (199.08±80.79 vs. 127.23±81.64 µIU/ml). However, the serum testosterone level was significantly low in cases associated with male infertility (4.62±2.03 vs. 6.82±2.79 ng/ml). LH, FSH and PRL levels were significantly increased in azoospermic, oligozoospermic and asthenozoospermic infertile males while FSH and PRL were significantly elevated in normozoospermic infertile group. Conversely, mean serum testosterone levels were significantly low in all infertile subgroups in comparison to fertile controls. PRL showed a significant prediction of Normozoospermia (AUC=0.836, Z=4.916, p<0.001) in ROC analysis. Data presented here is interesting, requiring further confirmation using larger samples of multiple cohorts.

Does Harvey-Ras gene expression lead to oral squamous cell carcinoma? A clinicopathological aspect.

BACKGROUND: Harvey-Ras (H-Ras) is an important guanosine triphosphatase protein for the regulation of cellular growth and survival. Altered Ras signaling has been observed in different types of cancer either by gene amplification and/or mutation. The H-Ras oncogene mutations are well reported, but expression of the H-Ras gene is still unknown. OBJECTIVE: This study aimed to examine both protein and messenger-RNA (mRNA) expressions of H-Ras in oral squamous cell carcinoma (OSCC) and analyzed the association with risk habits and the clinicopathological profile of cases. METHODOLOGY: A total of 65 tissue specimens of OSCC (case group) and equal number of normal tissues (control group) were included in this study. H-Ras protein and mRNA expressions were analyzed using immunohistochemical and quantitative real time-polymerase chain reaction techniques, respectively. RESULTS: The H-Ras protein was significantly overexpressed in the oral carcinoma group compared to the normal group (P = 0.03). Most of the OSCC cases showed positive staining with moderate expression, while negative and moderate staining was high in the control group. The majority of H-Ras positive cases were found in individuals with multiple risk habits including tobacco chewing. The risk of H-Ras positivity was 1.46 times higher in smokers than non-smokers. H-Ras positivity increased in cases affected with buccal mucosa site and higher grade of carcinoma. Relative mRNA level of H-Ras was significantly elevated in oral carcinoma as compared with the control group (P ≤ 0.001). Protein and mRNA levels of H-Ras in case group was poorly correlated. CONCLUSION: H-Ras oncogene expression was markedly higher in oral carcinoma, and it can be a prognostic marker and target for an effective molecular therapy.

Differential Expression of c-fos Proto-Oncogene in Normal Oral Mucosa versus Squamous Cell Carcinoma

Background: The c-Fos nuclear protein dimerizes with Jun family proteins to form the transcription factor AP-1 complex which participates in signal transduction and regulation of normal cellular processes. In tumorigenesis, c-Fos promotes invasive growth through down-regulation of tumor suppressor genes but its role in oral carcinogenesis is not clear. Objectives: This study concerned c-fos gene expression in normal and malignant tissues of the oral cavity, with attention to associations between expression status and clinico-pathological profiles of OSCC patients. Method: A total of 65 histopathologically confirmed OSCC tissue samples were included in case group along with an equal number of age and sex-matched normal tissue samples of oral cavity for the control group. c-Fos protein and m-RNA expressions were analyzed using immunohistochemistry and qRT-PCR, respectively. Results: A significant low expression of c-Fos protein was observed in OSCC cases than normal control subjects (p= <0.001). The mean percent positivity of c-Fos protein in cases vs. controls was 24.91± 2.7 vs. 49.68± 2.2 (p= <0.001). Most OSCC tissue samples showed weak or moderate c-Fos expression whereas 53.8% of normal tissue sections presented with strong immunostaining. Moreover, the relative m-RNA expression for the c-fos gene was significantly decreased in case group (0.93± 0.48) as compared to the control group (1.22± 0.87). Majority of c-Fos positive cases were diagnosed with well developed tumor. The mean percent positivity of c-Fos protein was significantly lower in higher grade tumor as compared with normal oral mucosa (p= < 0.001). Conclusion: The present study suggested that the c-fos gene is downregulated in oral carcinomas. The disparity of c-Fos protein levels in different pathological grades of tumor and normal oral tissue samples may indicate that loss of c-Fos expression is related with the progression of OSCC.

The rs2070895 (-250G/A) Single Nucleotide Polymorphism in Hepatic Lipase (HL) Gene and the Risk of Coronary Artery Disease in North Indian Population: A Case-Control Study.

INTRODUCTION: Several Single Nucleotide Polymorphisms (SNPs) in lipid transport genes have been shown to be associated with Coronary Artery Disease (CAD). The Hepatic Lipase (HL)glycoprotein is a key component that catalyzes the hydrolysis of triglycerides and phospholipids in all major classes of lipoproteins. AIM: We studied whether the HL gene-250G/A polymorphism affect blood lipid level and the CAD in a North Indian population. MATERIALS AND METHODS: A total number of 477 subjects were enrolled in the study after approval of the Institutional Ethics Committee. Out of 477 subjects, 233 were with coronary artery disease as study group and 244 subjects without coronary artery disease as control group. All subjects recruited with matched ethnicity in age group of 40-70 years. Blood samples were collected in EDTA vials and genomic DNA was extracted from blood using the phenol-chloroform method. Lipid profile was estimated by using a commercially available kit. Polymorphisms in the HL (-250 G/A) gene were analysed by using restriction fragment length polymorphism-polymerase chain reaction (PCR-RFLP) method. The effect of this polymorphism on plasma lipids, lipoproteins and coronary artery disease was determined. RESULTS: In Human Hepatic Lipase (LIPC)-250G/A genotype, the frequencies of GG, GA and AA genotype in CAD group was 80.69%, 15.45% and 3.86%, respectively; in the control group, the corresponding frequencies were 90.16%, 9.02% and 0.82%, respectively. A significant difference was found in the genotype (LIPC-250G/A) distribution between the two groups. Further logistic regression analysis indicated that the GA and AA genotypes in SNP-250G/A were significantly associated with CAD in all genetic models (In codominant model- GA vs. GG, OR=1.91, 95% CI=1. 09-3.37, p=0. 03 and AA vs. GG, OR= 5.26, 95% CI= 1.10-24.60, p=0.04; in dominant model- GA+AA vs. GG, OR=2.19, p=0.004 and in recessive model- AA vs. GG+GA, OR=5.26, p=0.04 whereas, A allele at nucleotide -250G/A in the LIPC gene had an association with increased risk of CAD (OR=2.33, p=<0.008). CONCLUSION: Our findings indicated that the higher frequency of a dominant model (GA+AA) as well as mutant allele A of LIPC-250 G/A polymorphism is significantly associated with risk of CAD and the lipid profile can be used as a predictor of CAD.

Molecular concept in human oral cancer.

The incidence of oral cancer remains high in both Asian and Western countries. Several risk factors associated with development of oral cancer are now well-known, including tobacco chewing, smoking, and alcohol consumption. Cancerous risk factors may cause many genetic events through chromosomal alteration or mutations in genetic material and lead to progression and development of oral cancer through histological progress, carcinogenesis. Oral squamous carcinogenesis is a multistep process in which multiple genetic events occur that alter the normal functions of proto-oncogenes/oncogenes and tumor suppressor genes. Furthermore, these gene alterations can deregulate the normal activity such as increase in the production of growth factors (transforming growth factor-α [TGF-α], TGF-ß, platelet-derived growth factor, etc.) or numbers of cell surface receptors (epidermal growth factor receptor, G-protein-coupled receptor, etc.), enhanced intracellular messenger signaling and mutated production of transcription factors (ras gene family, c-myc gene) which results disturb to tightly regulated signaling pathways of normal cell. Several oncogenes and tumor suppressor genes have been implicated in oral cancer especially cyclin family, ras, PRAD-1, cyclin-dependent kinase inhibitors, p53 and RB1. Viral infections, particularly with oncogenic human papilloma virus subtype (16 and 18) and Epstein-Barr virus have tumorigenic effect on oral epithelia. Worldwide, this is an urgent need to initiate oral cancer research programs at molecular and genetic level which investigates the causes of genetic and molecular defect, responsible for malignancy. This approach may lead to development of target dependent tumor-specific drugs and appropriate gene therapy.

Intentional and non-intentional burn related deaths: a comparative study of socio-demographic profile.

This is a retrospective study of 1689 consecutive admissions of burn deaths to the mortuary over a period of 5 years. The socio-demographic data was collected using special Performa and interviewing the family members, relatives, neighbours and from police reports. Depending on the presence or absence of intentional intent, cases were divided into two groups and compared with regard to their socio-demographic profile. Both groups did not differ significantly with regard to age, sex and educational status. The cases with intentional deaths came from nuclear family, unmarried, student, low socio-economic status, had more stressful life events and suffered larger burns injuries compared with those who experienced non-intentional deaths. The majority of the cases were below the age of 35, unemployed and females outnumbered males in both the groups.

Demographic risk factors, affected anatomical sites and clinicopathological profile for oral squamous cell carcinoma in a north Indian population.

BACKGROUND: Oral cancer is a common form of cancer in India, particularly among men. About 95% are squamous cell carcinomas. Tobacco along with alcohol are regarded as the major risk factors. OBJECTIVES: (i) To determine associations of oral squamous cell carcinoma (OSCC) with respect to gender, age group, socioeconomic status and risk habits; (ii) To observe the distribution of affected oral anatomical sites and clinico-pathological profile in OSCC patients. MATERIALS AND METHODS: This is an unmatched case-control study during period January 2012 to December 2013. Total of 471 confirmed OSCC patients and 556 control subjects were enrolled. Data on socio-demography, risk habits with duration and medical history were recorded. RESULTS: There were significant associations between OSCC with middle age (41-50years; unadjusted OR=1.63, 95%CI=1.05-2.52, p=0.02) (51-60 years; unadjusted OR=1.79, 95%CI=1.15-2.79, p=0.009) and male subjects (unadjusted OR=2.49, 95%CI=1.89-3.27, p=0.0001). Cases with both habits of tobacco chewing and smoking were at a higher risk for OSCC than tobacco chewing alone (unadjusted OR=0.52, 95%CI=0.38-0.72, p=0.0001), duration of risk habits also emerged as a responsible factor for the development of carcinoma. The majority of patients were presented in well-differentiated carcinomas (39.9%). Prevalence of advance stages (TNM stage III, IV) was 23.4% and 18.3% respectively. The buccal mucosa was the most common (35.5%) affected oral site. CONCLUSIONS: In most Asian countries, especially India, there is an important need to initiate the national level public awareness programs to control and prevent oral cancer by screening for early diagnosis and support a tobacco free environment.