Down-regulation of FA-BRCA Pathway in Cervical Carcinoma Gradually Reversed During the Development of Chemo-tolerance: Clinical Implications.

Cervical cancer is one of the leading causes of cancer death among females, worldwide. The contributory role of different cellular pathways in the process of carcinogenesis is still poorly understood. Our study was focused here to understand the functional evaluation of key regulatory genes of FA-BRCA pathway in the development of CACX and their role in chemo-tolerance of the disease by analyzing the molecular profile of the genes both in normal and tumour tissue of our sample pool, also validated in in silico datasets.

Role of MLH1 and MSH2 deficiency in the development of tumorigenesis and chemo-tolerance of cervical Carcinoma: Clinical implications.

Cervical cancer (CACX) is one of the top causes of cancer death in women globally. The involvement of several cellular pathways in carcinogenesis is still poorly understood. Here, we focused to evaluate the contributory role of Mismatch Repair (MMR) pathway genes-MLH1 and MSH2 in CACX and their association with chemo-tolerance of the disease.

Differential association of hedgehog pathway in development of cervical carcinoma and its chemo-tolerance.

Cervical carcinoma (CACX) is still a dreadful threat to women in developing countries. Available conventional chemo-radiation therapies are not sufficient to restrict the disease recurrence. To unravel the mechanism of the disease recurrence, alteration of hedgehog self-renewal pathway was evaluated during development of CACX and in chemo-tolerance of the tumor.

Promoter methylation and enhanced SKP2 are associated with the downregulation of CDKN1C in cervical squamous cell carcinoma.

Purpose: Cervical Squamous Cell Carcinoma (CSCC) is one of the significant causes of cancer deaths among women. Distinct genetic and epigenetic-altered loci, including chromosomal 11p15.5-15.

Status of universal drug-susceptibility testing among sputum smear-positive tuberculosis patients diagnosed at a tertiary care centre.

Background & Objectives: This study was aimed at estimating the proportion among sputum smear-positive tuberculosis (TB) patients diagnosed at a tertiary care centre in India, who did not undergo universal drug-susceptibility testing (UDST), assessing the sociodemographic and morbidity-related factors associated with it, ascertaining the reasons for not getting tested and estimating the proportion with any drug resistance (DR).

Methods: TB Notification Register and TB Laboratory Register, maintained in Designated Microscopy Centre and Intermediate Research Laboratory, respectively were used to obtain the patient details and information regarding UDST and DR-TB status. Under UDST, the TB patients had undergone rapid molecular tests to check for any DR.

PTPRJ is downregulated in cervical squamous cell carcinoma.

Squamous cell carcinoma of the uterine cervix (CSCC) is one of the leading causes of death in Indian women. Protein tyrosine phosphatase receptor (PTPR) type J (also known as DEP1) is a recently reported tumour suppressor receptor phosphatase. Critical molecular analysis of PTPRJ/DEP1 (11p11.

Hypomethylation of and by downregulation of results in restriction of liver carcinogenesis by amarogentin treatment.

Amarogentin (active component of ) was found to prevent CCl4/NDEA-induced liver carcinogenesis at mild dysplastic stage through modulation of cell cycle, apoptosis, self-renewal pathways. The cell cycle regulatory genes , P16 and RBSP3 were found to be upregulated in restricted liver lesions. To understand the mechanism of upregulation during restriction of cacinogenesis, the effect of amarogentin on epigenetic modification was evaluated in this study.

Pongapin and Karanjin, furanoflavanoids of Pongamia pinnata, induce G2/M arrest and apoptosis in cervical cancer cells by differential reactive oxygen species modulation, DNA damage, and nuclear factor kappa-light-chain-enhancer of activated B cell signaling.

In this study, the antitumor activity of two furanoflavanoid derivatives, Pongapin and Karanjin, was evaluated in comparison with Plumbagin, a plant-derived polyphenol with proven antitumor activity. The compounds differentially inhibit the growth of different cancer cell lines (most effective on HeLa cells), with very low inhibitory effect on the growth of normal mouse embryonic fibroblast cell line. Pongapin like Plumbagin could significantly increase the intracellular reactive oxygen species (ROS) in the HeLa cells by stabilization of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (I-κB) expression and reduction of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression.

Epigallocatechin gallate in combination with eugenol or amarogentin shows synergistic chemotherapeutic potential in cervical cancer cell line.

In this study, antitumor activity of epigallocatechin gallate (EGCG; major component of green tea polyphenol), eugenol (active component of clove), and amarogentin (active component of chirata plant) either alone or in combination were evaluated in Hela cell line. It was evident that EGCG with eugenol-amrogentin could highly inhibit the cellular proliferation and colony formation than individual treatments. Induction of apoptosis was also higher after treatment with EGCG in combination with eugenol-amrogentin than individual compound treatments.

Frequent inactivation of MCC/CTNNBIP1 and overexpression of phospho-beta-catenin(Y654) are associated with breast carcinoma: Clinical and prognostic significance.

Transcriptional activation of β-catenin is a hallmark of Wnt/β-catenin pathway activation. The MCC (Mutated in colorectal cancers) and CTNNBIP1 (catenin, beta interacting protein 1) are two candidate genes which inhibit the transcriptional activity of nuclear β-catenin. The importance of MCC and CTNNBIP1 in breast cancer (BC) development has not yet been studied in detail.

Tea polyphenols EGCG and TF restrict tongue and liver carcinogenesis simultaneously induced by N-nitrosodiethylamine in mice.

The aim of this study is to understand the molecular mechanisms of N-nitrosodiethylamine (NDEA) induced multi-organ carcinogenesis in tongue and liver of the same mouse and restriction of carcinogenesis by Epigallocatechin gallate (EGCG) and Theaflavin (TF), if any. For that purpose, cellular proliferation/apoptosis, prevalence of CD44 positive stem cell population and expressions of some key regulatory genes of self renewal Wnt and Hedgehog (Hh) pathways and some of their associated genes were analyzed in the NDEA induced tongue and liver lesions in absence or presence of EGCG/TF. Chronic NDEA exposure in oral cavity could decrease mice body weights and induce tongue and liver carcinogenesis with similar histological stages (severe dysplasia up to 30thweeks of NDEA administration).

Tea polyphenols epigallocatechin gallete and theaflavin restrict mouse liver carcinogenesis through modulation of self-renewal Wnt and hedgehog pathways.

The aim of this study is to evaluate chemopreventive and therapeutic efficacy of tea polyphenols epigallocatechin gallete (EGCG) and theaflavin (TF) on self-renewal Wnt and Hedgehog (Hh) pathways during CCl4/N-nitosodiethylamine-induced mouse liver carcinogenesis. For this purpose, the effect of EGCG/TF was investigated in liver lesions of different groups at pre-, continuous and post initiation stages of carcinogenesis. Comparatively increased body weights were evident due to EGCG/TF treatment than carcinogen control mice.

Amarogentin regulates self renewal pathways to restrict liver carcinogenesis in experimental mouse model.

Amarogentin, a secoiridoid glycoside isolated from medicinal plant Swertia chirata, was found to restrict CCl4 /N-nitrosodiethyl amine (NDEA) induced mouse liver carcinogenesis by modulating G1/S cell cycle check point and inducing apoptosis. To understand its therapeutic efficacy on stem cell self renewal pathways, prevalence of CD44 positive cancer stem cell (CSC) population, expressions (mRNA/protein) of some key regulatory genes of self renewal Wnt and Hedgehog pathways along with expressions of E-cadherin and EGFR were analyzed during the liver carcinogenesis and in liver cancer cell line HepG2. It was observed that amarogentin could significantly reduce CD44 positive CSCs in both pre and post initiation stages of carcinogenesis than carcinogen control mice.

Prevention of liver carcinogenesis by amarogentin through modulation of G1/S cell cycle check point and induction of apoptosis.

Amarogentin, a secoiridoid glycoside, is an active component of the medicinal plant Swertia chirata. In this study, chemopreventive and chemotherapeutic actions of amarogentin were evaluated in a carbon tetrachloride (CCl(4))/N-nitrosodiethylamine (NDEA)-induced liver carcinogenesis mouse model system during continuous and posttreatment schedule. Better survival, no toxicity and increased body weight were noted in amarogentin-treated mice.

Regular black tea habit could reduce tobacco associated ROS generation and DNA damage in oral mucosa of normal population.

Tobacco and tea habit are very common in world wide. In the present study, an attempt was made to evaluate the effect of regular drinking of black tea on reactive oxygen species (ROS) generation and DNA damage in buccal cells of normal subjects with or without tobacco habit. Expression of ROS associated proteins IκB, NF-κB as well as DNA repair associated proteins p53, MLH1 were also analyzed.

Eugenol restricts DMBA croton oil induced skin carcinogenesis in mice: downregulation of c-Myc and H-ras, and activation of p53 dependent apoptotic pathway.

Background: Eugenol is the active component of essential oil isolated from clove (Syzigium aromaticum). Eugenol has antimutagenic, antigenotoxic, anti-inflammatory properties. The anticarcinogenic effect of eugenol was evident in different types of cell lines.

Sequential loss of cell cycle checkpoint control contributes to malignant transformation of murine embryonic fibroblasts induced by 20-methylcholanthrene.

Definitive information about the number and nature of discrete steps of tumorigenesis is enigmatic. To understand the multistep nature of carcinogenesis, an in vitro model of 20-Methylcholanthrene-treated primary fibroblast cells CNCI-PM-20, from 20-day old Swiss mouse embryo was used. Visible neoplastic changes with distinct morphological variations along with specific chromosomal aberrations like Robertsonian metacentrics, double and single-minute chromosomes and aneuploidy were observed from Passage-20 onwards.

Association of early phase of colorectal carcinogenesis with STAT3 activation and its relevance in apoptosis regulation.

Expression of STAT3/pSTAT3 in colorectal cancer (CRC) patients of Indian origin was studied to assess its significance in early detection and apoptosis regulation. Colorectal tissues with malignant lesions were STAT3/pSTAT3 positive in 66% of the cases and among these positive cases, well differentiated, moderately differentiated and poorly differentiated cancers were 86%, 60% and 0% respectively. All CRC specimens studied were immunoreactive with anti-carcinoembryonic antigen antibody.

Influence of regular black tea consumption on tobacco associated DNA damage and HPV prevalence in human oral mucosa.

Black tea is more widely consumed than green tea worldwide, particularly in India. Therefore, it is necessary to focus attention on black tea with respect to its health promoting and anti-cancer actions. In order to establish the concept that black tea is a potential candidate for cancer prevention, it is important to provide epidemiological evidence derived from investigations of human populations.