Dharamshila Cancer Hospital and Research Centre

About: Dharamshila Cancer Hospital and Research Centre is a based out in . It is known for research contribution in the topics: Cancer & DNA damage. The organization has 10 authors who have published 9 publications receiving 195 citations.

Concomitant presence of mutations in mitochondrial genome and p53 in cancer development—A study in north Indian sporadic breast and esophageal cancer patients

Abstract: Mitochondrial DNA alterations in recent years have been suggested as modifier events, providing a possible proliferative advantage to the tumor cells In order to provide further insight into the process of tumorigenesis, a study of whole mitochondria genome was conducted in 134 tissue samples obtained from 2 unrelated cancers (tumor and adjacent normal tissues from 36 breast cancer and 31 esophageal squamous cell carcinoma (ESCC) patients) with known p53 somatic mutation background Fifteen of 36 (4166%) breast and 12 of 31 (3871%) ESCC tumors were found to contain at least 1 mtDNA somatic mutation, which correlated significantly with the concomitant presence of somatic mutation in DNA binding domain of the p53 gene (Breast cancer, p = 0006; ESCC, p = 0002) Interestingly, mutations in the non D-loop region of the mtDNA contributed significantly (Breast cancer, p = 0004; ESCC, p = 0032) in comparison to the hotspot-D-Loop-region The concomitant presence of mutations in p53 and mtDNA were also predominant in breast cancer tumors with poor prognosis, that is, with the advanced stage, grade and the ER/PR negativity Also, the observation made was apparently well explained in 10398A bearing N haplogroup genetic background with increased presence of novel and pathogenic germline mutation in mtDNA Our study suggests that the concomitant presence of somatic alteration in mtDNA and the DNA binding domain of the p53 gene facilitates cell survival and tumorigenesis, requiring specialized therapeutic intervention because of a possible resistance to conventional chemotherapy

Analysis of ovarian tumor pathology by Fourier Transform Infrared Spectroscopy.

Abstract: Ovarian cancer is the second most common cancer among women and the leading cause of death among gynecologic malignancies. In recent years, infrared (IR) spectroscopy has gained attention as a simple and inexpensive method for the biomedical study of several diseases. In the present study infrared spectra of normal and malignant ovarian tissues were recorded in the 650 cm-1 to 4000 cm-1 region. Post surgical tissue samples were taken from the normal and tumor sections of the tissue. Fourier Transform Infrared (FTIR) data on twelve cases of ovarian cancer with different grades of malignancy from patients of different age groups were analyzed. Significant spectral differences between the normal and the ovarian cancerous tissues were observed. In particular changes in frequency and intensity in the spectral region of protein, nucleic acid and lipid vibrational modes were observed. It was evident that the sample-to-sample or patient-to-patient variations were small and the spectral differences between normal and diseased tissues were reproducible. The measured spectroscopic features, which are the spectroscopic fingerprints of the tissues, provided the important differentiating information about the malignant and normal tissues. The findings of this study demonstrate the possible use of infrared spectroscopy in differentiating normal and malignant ovarian tissues.

Investigation of DNA damage response and apoptotic gene methylation pattern in sporadic breast tumors using high throughput quantitative DNA methylation analysis technology

Abstract: Background- Sporadic breast cancer like many other cancers is proposed to be a manifestation of abnormal genetic and epigenetic changes. For the past decade our laboratory has identified genes involved in DNA damage response (DDR), apoptosis and immunesurvelliance pathways to influence sporadic breast cancer risk in north Indian population. Further to enhance our knowledge at the epigenetic level, we performed DNA methylation study involving 17 gene promoter regions belonging to DNA damage response (DDR) and death receptor apoptotic pathway in 162 paired normal and cancerous breast tissues from 81 sporadic breast cancer patients, using a high throughput quantitative DNA methylation analysis technology.

Gynaecological malignancies from palliative care perspective.

Abstract: Of the approximately 80,000 new cases of all cancers detected every year in India, 10-15% are gynecological malignancies. As per population-based registries under the National Cancer Registry Program, the leading sites of cancer among women are the cervix uteri, breast, and oral cavity. About 50-60% of all cancers among women in India are mainly of the following four organs: cervix uteri, breast, corpus uteri, and ovaries. Over 70% of these women report for diagnostic and treatment services at an advanced stage of disease, resulting in poor survival and high mortality rates. Among all gynecological cancers, ovarian cancer is the deadliest one and, in 2/3(rd) of the cases, is detected in an advanced stage. But, in India and in other developing countries, due to inadequate screening facilities for the preventable cancer cervix, this kills more women than any other cancer in females. Gynecology Oncologist as a sub-specialist has an immensely important role in curtailing the menace of gynecological malignancies by providing comprehensive preventive, curative, palliative and follow-up services, with the aim of assuring a good quality of life to women as a cornerstone of cancer management.

Functional implication of TRAIL −716 C/T promoter polymorphism on its in vitro and in vivo expression and the susceptibility to sporadic breast tumor

Abstract: Recently, TRAIL function has been elucidated beyond its known classical role of mediating cellular homeostasis and immune surveillance against transformed cells. Here, we show how CC genotype of −716 TRAIL promoter SNP rendered risk for sporadic breast cancer as compared to the CT and TT genotypes (Precessive model = 0.018, OR = 1.4, 95% CI = 1.1–1.9; Pallele model = 0.010, OR = 1.3, 95% CI = 1.1–1.7). The in silico prediction of the introduction of core Sp1/Sp3-binding motif suggested the functional significance of the SNP variation. This functional implication was validated by luciferase assay in HeLa (P = 0.026), MCF-7 (P = 0.022), HepG2 (P = 0.024), and HT1080 (P = 0.030) cells and also by real-time expression studies on tumor tissues (P = 0.01), revealing the transcriptionally repressed status of −716 T when compared to −716 C allele. The SNP–SNP interactions reflected an enhanced protective effect of CT and TT genotypes with the protective genetic backgrounds of TP53-BRCA2 (P = 0.002, OR = 0.2, 95% CI = 0.1–0.6), IFNG (P = 0.0000002, OR = 0.3, 95% CI = 0.2–0.4), and common variant Casp8 (P = 0.0003, OR = 0.5, 95% CI = 0.3–0.7). Interestingly, a comparison with clinical parameters showed overrepresented CT and TT genotypes in progressing (P = 0.041) and ER/PR negative tumors (P = 0.024/0.006). This was explained by increased apoptotic index, calculated as a ratio of selected pro-apoptotic and anti-apoptotic gene expression profiles, in CC genotyped tumors, favoring either intrinsic (P = 0.008,0.018) or extrinsic (P = 0.025,0.217) pathway depending upon the ER/PR status. Our study reveals for the first time that a promoter SNP of TRAIL functionally modulates the gene and consequently its role in breast cancer pathogenesis, cautioning to consider the −716 TRAIL SNP status in patients undergoing TRAIL therapy.