Search

PURPOSE: Cervical cancer (CC) is the most common cancer affecting women worldwide. Human papillomavirus (HPV) infection is a major contributing factor for the development of CC. The development of CC occurs progressively from precancer stages to cancerous stages (ie, invasive squamous cell carcinoma [ISCC] and adenocarcinoma [ADC]). ADC is a rare form of CC that develops from the mucinous endocervical epithelium. It is believed that the downstream targets of Notch signaling contribute to the etiology of CC. One such target is HES1, whose role in the modulation of ADC is unknown. The purpose of this study is to determine the role of HES1 protein in HPV-associated ADC subtype of CC and also to compare its expression in histologic subtypes of precancer and ISCC. PATIENTS AND METHODS: A total of 148 patients (30 with precancers, 98 with ISCC, and 20 with ADC) and 40 normal control participants were analyzed for the expression of HES1 via immunohistochemistry, with results validated by immunoblotting. RESULTS: The comparison between HPV-16 and HES1 expression was significant in precancer (cervical intraepithelial neoplasia grades 1 to 3; P = .013), ISCC (International Federation of Gynecology and Obstetrics stages I to IV; P = .001), and ADC (P = .007). An overall significant mean difference was observed between HES1, JAG1, and Notch-3 proteins in precancer (P = .001), ISCC (P = .001), and ADC (P = .001). Pairwise comparisons between HES1 and JAG1 and HES1 and Notch-3 were also found to be significant. CONCLUSION: This study showed that among all HPV-16–positive precancers, the major HES1 positivity signal arises from cervical intraepithelial neoplasia grades 2 and 3 that develops into ISCC. Moreover, HPV-16–positive ADC also showed an association with HES1. The HES1, JAG1, and Notch-3 proteins showed their synergistic role in modulating HPV associated ADC along with histologic subtypes of precancer and ISCC of CC.

Introduction Dohra is a locally produced areca nut preparations used with or without tobacco in Allahabad, Jaunpur and Pratapgarh districts of Uttar Pradesh (UP), India. Different varieties of Dohra exist such as Sukha Dohra, Geela Dohra, etc. Evidence suggests that it causes Oral Potentially Malignant Disorders and Oral Cancer. It contains arecoline which is a well-known carcinogen. In order to understand the potential role of Dohra in causing cancer biochemical profiling of different varieties of Dohra is needed. Aim To describe the biochemical profile of different varieties of Dohra. Methods Different varieties of Dohra were collected from Allahabad, Jaunpur and Pratapgarh districts of UP. All the varieties of Dohra were analyzed for biochemical profiling through Continuous Flow Autoanalyzer (CFA) using Flow View Solution 3700 Analyzer (version 1.2.2) software. Results The biochemical changes at arecoline levels were observed in different varieties of Dohra. The detailed chemical profiling will be furnished in the meeting. Conclusions Different varieties of Dohra preparations are produced and each of them have a different biochemical profile. The Dohra is rich is arecoline and hence its use should be banned/avoided.

Introduction Kiwam (Qiwam) is a partially fermented tobacco product consumed with Betal Quid (Paan). The major constituents of this product are tobacco, saffron (Zaffrani) and some additives. It contains Tobacco-Specific Nitrosamines (TSNA) which is considered as a cancer-causing agent. To elucidate the carcinogenic property of Kiwam, biochemical profiling of its constituents at different stages of processing is needed. The major processing steps involved in the formation of Kiwam and biochemical profiling/changes at each processing step is still unknown. Aim To describe the major processing steps and biochemical changes that occurs at each processing step during the preparation of Kiwam. Method Tobacco leaves and stems were boiled in water followed by filtering of the constituents to remove the leaves and stem residues. The filtrate is again boiled to form a thick paste residue. The resultant paste was partially fermented through sun curing, and lastly saffron along with some additives were added. The samples from each step were analyzed for biochemical profiling through Continuous Flow Autoanalyzer (CFA) using Flow View Solution 3700 Analyzer (version 1.2.2) software. Results The biochemical changes at TSNA levels were observed at each processing steps. The detailed chemical profiling will be presented during the meeting. Conclusions Processing of Kiwam involves four major steps i.e. (i) boiling of tobacco leaves and stem (ii) filtration of product (iii) re-boiling of the filtrate till the paste is formed (iv) partial fermentation through sun curing. Kiwam is rich in TSNA and hence its use should be avoided.

Oral cancer etiology is complex and controlled by multi-factorial events including genetic events. Candidate gene studies, genome-wide association studies, and next-generation sequencing identified various chromosomal loci to be associated with oral cancer. There is no available review that could give us the comprehensive picture of genetic loci identified to be associated with oral cancer by candidate gene studies–based, genome-wide association studies–based, and next-generation sequencing–based approaches. A systematic literature search was performed in the PubMed database to identify the loci associated with oral cancer by exclusive candidate gene studies–based, genome-wide association studies–based, and next-generation sequencing–based study approaches. The information of loci associated with oral cancer is made online through the resource “ORNATE.” Next, screening of the loci validated by candidate gene studies and next-generation sequencing approach or by two independent studies within candidate gene studies or next-generation sequencing approaches were performed. A total of 264 loci were identified to be associated with oral cancer by candidate gene studies, genome-wide association studies, and next-generation sequencing approaches. In total, 28 loci, that is, 14q32.33 (AKT1) , 5q22.2 (APC) , 11q22.3 (ATM) , 2q33.1 (CASP8) , 11q13.3 (CCND1) , 16q22.1 (CDH1) , 9p21.3 (CDKN2A) , 1q31.1 (COX-2) , 7p11.2 (EGFR) , 22q13.2 (EP300) , 4q35.2 (FAT1) , 4q31.3 (FBXW7) , 4p16.3 (FGFR3) , 1p13.3 (GSTM1-GSTT1) , 11q13.2 (GSTP1) , 11p15.5 (H-RAS) , 3p25.3 (hOGG1) , 1q32.1 (IL-10) , 4q13.3 (IL-8) , 12p12.1 (KRAS) , 12q15 (MDM2) , 12q13.12 (MLL2) , 9q34.3 (NOTCH1) , 17p13.1 (p53) , 3q26.32 (PIK3CA) , 10q23.31 (PTEN) , 13q14.2 (RB1) , and 5q14.2 (XRCC4) , were validated to be associated with oral cancer. “ORNATE” gives a snapshot of genetic loci associated with oral cancer. All 28 loci were validated to be linked to oral cancer for which further fine-mapping followed by gene-by-gene and gene–environment interaction studies is needed to confirm their involvement in modifying oral cancer.