Understanding the Role of the Transcription Factor Sp1 in Ovarian Cancer: from Theory to Practice.

Ovarian cancer (OC) is one of the deadliest cancers among women contributing to high risk of mortality, mainly owing to delayed detection. There is no specific biomarker for its detection in early stages. However, recent findings show that over-expression of specificity protein 1 (Sp1) is involved in many OC cases. The ubiquitous transcription of Sp1 apparently mediates the maintenance of normal and cancerous biological processes such as cell growth, differentiation, angiogenesis, apoptosis, cellular reprogramming and tumorigenesis. Sp1 exerts its effects on cellular genes containing putative GC-rich Sp1-binding site in their promoters. A better understanding of the mechanisms underlying Sp1 transcription factor (TF) regulation and functions in OC tumorigenesis could help identify novel prognostic markers, to target cancer stem cells (CSCs) by following cellular reprogramming and enable the development of novel therapies for future generations. In this review, we address the structure, function, and biology of Sp1 in normal and cancer cells, underpinning the involvement of Sp1 in OC tumorigenesis. In addition, we have highlighted the influence of Sp1 TF in cellular reprogramming of iPSCs and how it plays a role in controlling CSCs. This review highlights the drugs targeting Sp1 and their action on cancer cells. In conclusion, we predict that research in this direction will be highly beneficial for OC treatment, and chemotherapeutic drugs targeting Sp1 will emerge as a promising therapy for OC.

New insight into NANOG: A novel therapeutic target for ovarian cancer (OC).

Cancer incidence, metastasis, drug resistance and recurrence are still the critical issues of oncological diseases especially Ovarian cancer (OC). It has been suggested that drug resistance and disease relapse are the main causes for the aggressive nature of OC. There is an immediate need to develop novel strategies to understand the mechanism to overcome chemoresistance. Nanog has been found to regulate stemness like cells inside the cancer cells that are termed as Cancer Stem Cells (CSCs). These cells show high self-renewal capacity with a peculiar potential in tumour initiation, heterogeneity, progression, metastasis, recurrence, radiotherapy and multi drug resistance. Recent studies have demonstrated that Nanog, a key transcription factor for pluripotency, has been playing a major role in chemoresistance. In this review, we address the functions of Nanog in both normal and cancer cells, how Nanog is involved in OC tumorigenesis and chemoresistance. This review also highlights the methods that are used for targeting Nanog as a remedy for treating OC. Thus, through this review, we predict that these concepts will open new avenues of research in ovarian cancer stem cells, and would propose Nanog as a target to improve the outcome of chemotherapy.

Targeting phosphoinositide-3-kinase pathway in biliary tract cancers: A remedial route?

Biliary tract cancers (BTC) are aggressive tumours with a low survival rate. At the advent of the genomic era, various genetic mutations in cell signalling pathways have been incriminated in carcinogenesis. Genomic analysis studies have connected main components of the phosphoinositide-3-kinase (PI3K) signalling pathway to BTC. PI3K pathway playing a central role in cell signalling and being deregulated in various tumours has been studied as a target for chemotherapy. Novel compounds have also been identified in preclinical trials that specifically target the PI3K pathway in BTCs, but these studies have not accelerated to clinical use. These novel compounds can be examined in upcoming studies to validate them as potential therapeutic agents, as further research is required to combat the growing need for adjuvant chemotherapy to successfully battle this tumour type. Furthermore, these molecules could also be used along with gemcitabine, cisplatin and 5-fluorouracil to improve sensitivity of the tumour tissue to chemotherapy. This review focuses on the basics of PI3K signalling, genetic alterations of this pathway in BTCs and current advancement in targeting this pathway in BTCs. It emphasizes the need for gene-based drug screening in BTC. It may reveal various novel targets and drugs for amelioration of survival in patients with BTC and serve as a stepping stone for further research.

Longer Telomere Length of T lymphocytes in Patients with Early and Chronic Psychosis.

OBJECTIVE: To investigate pathological conditions that act as sources of pro-inflammatory cytokines and cytotoxic substances to examine telomere length (TL) in patients with either early (duration of illness [DI] ≤5 years) or chronic (DI >5 years) psychosis using T lymphocytes. METHODS: Based on these factors and the important role that T lymphocytes play in inflammation, the present study measured the TL of T lymphocytes in patients with either early or chronic psychosis. Additionally, smoking, metabolic syndrome, depression, and cognitive functioning were assessed to control for confounding effects. RESULTS: TL was significantly longer in patients with early and chronic psychosis than in healthy control subjects and, moreover, the significance of these findings remained after controlling for age, smoking, metabolic syndrome, DI, chlorpromazine-equivalent dose, and cognitive functioning (F=9.57, degree of freedom=2, p<0.001). Additionally, the DI, chlorpromazine-equivalent doses, and the five-factor scores of the Positive and Negative Syndrome Scale were not significantly correlated with the TL of T lymphocytes in either all patients or each psychosis group. CONCLUSION: Possible mechanisms underlying the effects of antipsychotic medications on telomerase are discussed in the present study, but further studies measuring both telomerase activity and TL using a prospective design will be required.

An Outline of Meat Consumption in the Indian Population - A Pilot Review.

The consumption of meat is increasing in India and agriculture is considered as the backbone of a majority of people. Livestock plays a significant role, and poultry and dairy are the major sectors contributing to economic development. The majority of meats consumed in India are fish, bovine, mutton, goat, pig, and poultry. In Indian context, culture, traditions, customs, and taboos influence meat consumption to a great extent. However, studies show that urbanization has been causing a rise in demand for meat products. India is the world's second largest exporter of beef. In India, 95% of goat meat produced is consumed locally. Meat consumption, in particular, is determined by the religions where pork is forbidden to Muslims and beef is prohibited to Hindus. The preference and consumption of chicken meat can be considered as a universal phenomenon and chicken meat is greatly accepted by consumers in India as compared to the other meat consumption. The increase of chicken meat consumption is due to the versatility of the meat, relatively low cost in comparison to other meat, and the acceptance of the chicken meat to all religions. There has been a great rise in the production of livestock products and this is expected to continue in the future. The pattern of meat consumption depends considerably on culture, tradition and urbanization. This review was formulated with the objective of identifying the meat consumption patterns in a typical Indian society.

Estimation of cytogenetic risk among coke oven workers exposed to polycyclic aromatic hydrocarbons.

Polycyclic aromatic hydrocarbons (PAHs) result from the incomplete combustion of natural or synthetic organic materials. The working environment at a coke plant can negatively affect the employed workers who were exposed to coke oven emissions containing PAHs, which formed and released into the environment by the process of pyrolysis of coke. This study aims to analyze the relationship between the exposure of PAHs and the risk of genetic damages such as chromosomal alteration (CA), micronucleus (MN), and DNA damage (PCR-RFLP) in peripheral blood lymphocytes of 27 coke oven workers and equal number of control subjects. The exposed subjects and controls were divided into two groups based on their age (group I<35 years and group II ≥35 years). The exposed subjects were further classified into two groups based on the exposure period (<12 years and ≥12 years). The frequencies of CA and MN in exposed subjects are relatively high with respect to controls. The XRCC1 399 Arg/gln polymorphism showed a substantial smaller difference in allele frequencies between exposed and control subjects. Based on present data, it was concluded that coke oven workers under risk should be monitored for adverse effects of the any long-term exposure.

Evaluation of chromosomal alteration in electrical workers occupationally exposed to low frequency of electro magnetic field (EMFs) in Coimbatore population, India.

Extremely low frequency electro magnetic fields (EMFs) have been classified as possibly carcinogenic to humans by the International Agency for Research on Cancer. An increased number of chromosomal alterations in peripheral lymphocytes are correlated with elevated incidence of cancer. The aim of the present study was to assess occupationally induced chromosomal damage in EMF workers exposed to low levels of radiation. We used conventional metaphase chromosome aberration (CA) analysis and the micronucleus (MN) assay as biological indicators of non ionizing radiation exposure. In the present study totally 70 subjects were selected including 50 exposed and 20 controls. Informed written consent was obtained from all participants and the study was performed in accordance with the Declaration of Helsinki and the approval of the local ethical committee. A higher degree of CA and MN was observed in exposed subjects compared to controls, the frequency of CA being significantly enhanced with long years of exposure (P<0.05). Moreover increase in CA and MN with age was noted in both exposed subjects and controls, but was significantly greater in the former. The results of this study demonstrated that a significant induction of cytogenetic damage in peripheral lymphocytes of workers occupationally exposed to EMFs in electric transformer and distribution stations. In conclusion, our findings suggest that EMFs possess genotoxic capability, as measured by CA and MN assays; CA analysis appeared more sensitive than other cytogenetic end-points. It can be concluded that chronic occupational exposure to EMFs may lead to an increased risk of genetic damage among electrical workers.

Evaluation of genetic alterations in inhabitants of a naturally high level background radiation and Kudankulam nuclear power project site in India.

Evaluation of genetic alterations in inhabitants of an area of Tamil Nadu, India, chronically exposed to high background radiation (HBRA), was the major purpose of the present study. A total of 216 samples (exposed inhabitants, 108; control subjects, 108) were selected based on the confirmation of radiation dose level using thermoluminescence dosimetry (TLD). After signing a consent form, volunteers provided blood samples (5 ml each) to establish cell cultures at 52 h. One hundred complete metaphase cells from each subject were evaluated for karyotyping. The frequencies of chromosomal alterations (CA) were found to be higher in the exposed groups and the aberrations predominately observed were of chromatid-type. Smoking was found to have considerable effect on the frequency of CA in exposed subjects. With the comet assay for DNA damage, a significant increase in comet tail frequency was also observed in exposed subjects compared to controls. At present there are no radioepidemiological data regarding the cytogenetic studies in these areas. Furthermore, the Kudankulam nuclear power plant nuclear power plant is being constructed in the same area. The study gives potentially important information on the general health effects due to radiation exposure and increases people's understanding of the hazardous nature of chronic low level natural radiation exposure. However, we may conclude that the HBRA by itself does not pose any significant risk of genetic damage as measured by conventional cytogenetic analysis.