Role of pretreatment neutophil to lymphocyte ratio as an independent prognostic factor in oral squamous cell carcinoma patients: a prospective study in a tertiary care centre

Background: More recently, established systemic inflammation-based prognostic scores have been explored extensively, such as NLR and serum C-reactive protein (CRP). We postulated that NLR might be a readily available and inexpensive objective prognostic index that could be used in daily oncologic clinical practice and could help to stratify patients in clinical trials.Methods: In total, there were 150 patients with OSCC treated at GSVM medical college, Kanpur between October 2012 and January 2015 whose clinical information and laboratory parameters were obtained. The NLR was determined by dividing the absolute neutrophil count by the absolute lymphocyte count, and the NLR data were then dichotomized and divided into two groups as NLR-low and -high.Results: The 3-year OS rate of the NLR-high group tended to be significantly lower than that of the NLR-low group, this relationship was found to be statistically significant (p value <0.05). The 3-year DFS rate in the NLR-high group was lower than that in the NLR-low group; however, there were no significant difference between the two groups.Conclusions: Our findings reported herein demonstrated that pre-treatment NLR is a potential biomarker for predicting the overall survival in oral SCC patients. Combined with other markers, NLR may be used in decision-making and the selection of treatment modality in patients with oral SCC

Outcomes of Hypofractionated Radiation Therapy in Locally Advanced Non-small cell Carcinoma Lung : A Single Institutional Experience

Introduction: Radical treatment in locally advanced non small cell carcinoma lung presents a management dilemma in patients with compromised performance status. Hypofractionated EBRT resolves this by confering high efficacy while avoiding excessive early toxicity. Objectives: To evaluate the efficacy and tolerance of hypofractionated radiotherapy in locally advanced lung cancer patients with compromised performance status. Methods: From January 2019 to January 2020,62 patients were enrolled to receive hypofractionated radiotherapy with 40Gy in 16 fractions with 5 fractions per week (2.5Gy per fraction) because of compromised performance status. Follow-up was conducted at 6 weeks and 3 months for symptomatic and radiological response (RECIST Criteria 1.1) .All results were evaluated statistically. Results: Mean age was 72.7years (+ 6.66) with 66.12% (n=41) above 70 years and 85% in ECOG PS 3. Out of 61 patients, 20% had complete response, 75% had partial response and 3% had stable disease at 6 weeks which progressed to 33% with complete and 62% with partial response at 3 months. 85% achieved symptom palliation. Radiation pneumonitis of grade 2 and above war observed in 60.65% and 62.29% and esophagitis of grade 2 and above was observed in 40.98% and 13.11% at 6 week and 3 months respectively. Conclusions: Hypofractionated RT confers the benefit of avoiding excessive early toxicity while maintaining high efficacy and be a finer alternative in patients with compromised performance status and/or advanced age

A Case Study of the Phenotypic Variations in Barilius Bendelisis (Hamilton) from a Perennial Stream and a Fish Pond of Garhwal Himalayan Region of Uttarakhand, India

A comparative study on the morphometric and meristic variables of Barilius bendelisis (Ham.) from two different water bodies, i.e., Khanda Gad, a perennial spring fed stream and fish pond in the Garhwal Himalayan region of Uttarakhand was made during the present study. A total of 100 specimens were analysed for 26 different morphometric variables and 14 meristic counts. The majority of morphometric variables showed linear relationship when expressed in relation to total length and head length, whereas meristic counts remained constant with increasing body length. Standard length was found to be the highly correlated character in samples from both sites. Principal Component Analysis of 10 significant morphometric variables yielded three components accounting for 73.38% of the total variation. Principal Component Analysis of 3 meristic variables yielded single component accounting for 62.3% of total variation. Discriminant Function Analysis for morphometric and meristic variables showed that 98% and 83% of individuals were allocated into their original populations respectively. The cluster analysis for morphometric characters showed of fish populations from both sites formed two major clades, thus significantly differentiating the two stocks of fish population

Prediction of epigenetically regulated genes in breast cancer cell lines

Methylation of CpG islands within the DNA promoter regions is one mechanism that leads to aberrant gene expression in cancer. In particular, the abnormal methylation of CpG islands may silence associated genes. Therefore, using high-throughput microarrays to measure CpG island methylation will lead to better understanding of tumor pathobiology and progression, while revealing potentially new biomarkers. We have examined a recently developed high-throughput technology for measuring genome-wide methylation patterns called mTACL. Here, we propose a computational pipeline for integrating gene expression and CpG island methylation profles to identify epigenetically regulated genes for a panel of 45 breast cancer cell lines, which is widely used in the Integrative Cancer Biology Program (ICBP). The pipeline (i) reduces the dimensionality of the methylation data, (ii) associates the reduced methylation data with gene expression data, and (iii) ranks methylation-expression associations according to their epigenetic regulation. Dimensionality reduction is performed in two steps: (i) methylation sites are grouped across the genome to identify regions of interest, and (ii) methylation profles are clustered within each region. Associations between the clustered methylation and the gene expression data sets generate candidate matches within a fxed neighborhood around each gene. Finally, the methylation-expression associations are ranked through a logistic regression, and their significance is quantified through permutation analysis. Our two-step dimensionality reduction compressed 90% of the original data, reducing 137,688 methylation sites to 14,505 clusters. Methylation-expression associations produced 18,312 correspondences, which were used to further analyze epigenetic regulation. Logistic regression was used to identify 58 genes from these correspondences that showed a statistically signifcant negative correlation between methylation profles and gene expression in the panel of breast cancer cell lines. Subnetwork enrichment of these genes has identifed 35 common regulators with 6 or more predicted markers. In addition to identifying epigenetically regulated genes, we show evidence of differentially expressed methylation patterns between the basal and luminal subtypes. Our results indicate that the proposed computational protocol is a viable platform for identifying epigenetically regulated genes. Our protocol has generated a list of predictors including COL1A2, TOP2A, TFF1, and VAV3, genes whose key roles in epigenetic regulation is documented in the literature. Subnetwork enrichment of these predicted markers further suggests that epigenetic regulation of individual genes occurs in a coordinated fashion and through common regulators

Role of pretreatment neutophil to lymphocyte ratio as an independent prognostic factor in oral squamous cell carcinoma patients: a prospective study in a tertiary care centre

Background: More recently, established systemic inflammation-based prognostic scores have been explored extensively, such as NLR and serum C-reactive protein (CRP). We postulated that NLR might be a readily available and inexpensive objective prognostic index that could be used in daily oncologic clinical practice and could help to stratify patients in clinical trials.Methods: In total, there were 150 patients with OSCC treated at GSVM medical college, Kanpur between October 2012 and January 2015 whose clinical information and laboratory parameters were obtained. The NLR was determined by dividing the absolute neutrophil count by the absolute lymphocyte count, and the NLR data were then dichotomized and divided into two groups as NLR-low and -high.Results: The 3-year OS rate of the NLR-high group tended to be significantly lower than that of the NLR-low group, this relationship was found to be statistically significant (p value &lt;0.05). The 3-year DFS rate in the NLR-high group was lower than that in the NLR-low group; however, there were no significant difference between the two groups.Conclusions: Our findings reported herein demonstrated that pre-treatment NLR is a potential biomarker for predicting the overall survival in oral SCC patients. Combined with other markers, NLR may be used in decision-making and the selection of treatment modality in patients with oral SCC

Biomed Res-India 2012; 23 (4): 547-550 Age wise distribution of high risk Human Papillomavirus in Northern In- dian women

Abstract Human papillomavirus (HPV) testing was introduced to compensate the poor sensitivity and specificity of the pap smear cytology often used as a diagnostic tool for borderline precancerous lesions. Digene Hybrid Capture Assay 2 (HCA-2) is the only approved test by the U.S. Food and Drug Administration (FDA) for evaluation and confirmation of the cytologically borderline suspected cases. 361 cervical specimens were collected for the high risk HPV analysis. Forty one cervical samples were positive. Age wise distribution showed highest prevalence in the 15-35 age groups which decreased in subsequent years. Present observations are in agreement with similar studies reported from other parts of the world including Southern India

Prediction of epigenetically regulated genes in breast cancer cell lines

Abstract Background Methylation of CpG islands within the DNA promoter regions is one mechanism that leads to aberrant gene expression in cancer. In particular, the abnormal methylation of CpG islands may silence associated genes. Therefore, using high-throughput microarrays to measure CpG island methylation will lead to better understanding of tumor pathobiology and progression, while revealing potentially new biomarkers. We have examined a recently developed high-throughput technology for measuring genome-wide methylation patterns called mTACL. Here, we propose a computational pipeline for integrating gene expression and CpG island methylation profles to identify epigenetically regulated genes for a panel of 45 breast cancer cell lines, which is widely used in the Integrative Cancer Biology Program (ICBP). The pipeline (i) reduces the dimensionality of the methylation data, (ii) associates the reduced methylation data with gene expression data, and (iii) ranks methylation-expression associations according to their epigenetic regulation. Dimensionality reduction is performed in two steps: (i) methylation sites are grouped across the genome to identify regions of interest, and (ii) methylation profles are clustered within each region. Associations between the clustered methylation and the gene expression data sets generate candidate matches within a fxed neighborhood around each gene. Finally, the methylation-expression associations are ranked through a logistic regression, and their significance is quantified through permutation analysis. Results Our two-step dimensionality reduction compressed 90% of the original data, reducing 137,688 methylation sites to 14,505 clusters. Methylation-expression associations produced 18,312 correspondences, which were used to further analyze epigenetic regulation. Logistic regression was used to identify 58 genes from these correspondences that showed a statistically signifcant negative correlation between methylation profles and gene expression in the panel of breast cancer cell lines. Subnetwork enrichment of these genes has identifed 35 common regulators with 6 or more predicted markers. In addition to identifying epigenetically regulated genes, we show evidence of differentially expressed methylation patterns between the basal and luminal subtypes. Conclusions Our results indicate that the proposed computational protocol is a viable platform for identifying epigenetically regulated genes. Our protocol has generated a list of predictors including COL1A2, TOP2A, TFF1, and VAV3, genes whose key roles in epigenetic regulation is documented in the literature. Subnetwork enrichment of these predicted markers further suggests that epigenetic regulation of individual genes occurs in a coordinated fashion and through common regulators.</p

High-throughput method for analyzing methylation of CpGs in targeted genomic regions

A unique microarray-based method for determining the extent of DNA methylation has been developed. It relies on a selective enrichment of the regions to be assayed by target amplification by capture and ligation (mTACL). The assay is quantitatively accurate, relatively precise, and lends itself to high-throughput determination using nanogram amounts of DNA. The measurements using mTACLs are highly reproducible and in excellent agreement with those obtained by sequencing (r = 0.94). In the present work, the methylation status of >145,000 CpGs from 5,472 promoters in 221 samples was measured. The methylation levels of nearby CpGs are correlated, but the correlation falls off dramatically over several hundred base pairs. In some instances, nearby CpGs have very different levels of methylation. Comparison of normal and tumor samples indicates that in tumors, the promoter regions of genes involved in differentiation and signaling are preferentially hypermethylated, whereas those of housekeeping genes remain hypomethylated. mTACL is a platform for profiling the state of methylation of a large number of CpG in many samples in a cost-effective fashion, and is capable of scaling to much larger numbers of CpGs than those collected here