Department Of Human Genetics And Molecular Medicine
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Item Brain metastasis in breast cancer: focus on genes and signaling pathways involved, blood�brain barrier and treatment strategies(Springer Science and Business Media Deutschland GmbH, 2023-03-10T00:00:00) Chhichholiya, Yogita; Ruthuparna, Malayil; Velagaleti, Harini; Munshi, AnjanaBreast cancer�(BC) is one of the most prevalent types of cancer in women. Despite advancement in early detection and efficient treatment, recurrence and metastasis continue to pose a significant risk to the life of BC patients. Brain metastasis�(BM) reported in 17�20 percent of BC patients is considered as a major cause of mortality and morbidity in these patients. BM includes various steps from primary breast tumor to secondary tumor formation. Various steps involved are primary tumor formation, angiogenesis, invasion, extravasation, and brain colonization. Genes involved in different pathways have been reported to be associated with BC cells metastasizing to the brain. ADAM8 gene, EN1 transcription factor, WNT, and VEGF signaling pathway have been associated with primary breast tumor; MMP1, COX2, XCR4, PI3k/Akt, ERK and MAPK pathways in angiogenesis; Noth, CD44, Zo-1, CEMIP, S0X2 and OLIG2 are involved in invasion, extravasation and colonization, respectively. In addition, the blood�brain barrier is also a key factor in BM. Dysregulation of cell junctions, tumor microenvironment and loss of function of microglia leads to BBB disruption ultimately resulting in BM. Various therapeutic strategies are currently used to control the BM in BC. Oncolytic virus therapy, immune checkpoint inhibitors, mTOR-PI3k inhibitors and immunotherapy have been developed to target various genes involved in BM in BC. In addition, RNA interference (RNAi) and CRISPR/Cas9 are novel interventions in the field of BCBM where research to validate these and clinical trials are being carried out. Gaining a better knowledge of metastasis biology is critical for establishing better treatment methods and attaining long-term therapeutic efficacies against BC. The current review has been compiled with an aim to evaluate the role of various genes and signaling pathways involved in multiple steps of BM in BC. The therapeutic strategies being used currently and the novel ones being explored to control BM in BC have also been discussed at length. � 2023, The Author(s), under exclusive licence to Federaci�n de Sociedades Espa�olas de Oncolog�a (FESEO).Item Prognostic significance of CHAC1 expression in breast cancer(Springer Science and Business Media B.V., 2022-06-21T00:00:00) Mehta, Vikrant; Meena, Jaipal; Kasana, Harit; Munshi, Anjana; Chander, HarishBackground: An emerging component of Unfolded Protein Response (UPR) pathway, cation transport regulator homolog 1 (CHAC1) has been conferred with the ability to degrade intracellular glutathione and induce apoptosis, however, many reports have suggested a role of CHAC1 in cancer progression. Our study aimed to investigate CHAC1 mRNA levels in large breast cancer datasets using online tools and both mRNA and protein levels in different breast cancer cell lines. Methods and results: Analysis of clinical information from various online tools (UALCAN, GEPIA2, TIMER2, GENT2, UCSCXena, bcGenExMiner 4.8, Km Plotter, and Enrichr) was done to elucidate the CHAC1 mRNA expression in large breast cancer patient dataset and its correlation with disease progression. Later, in vitro techniques were employed to explore the mRNA and protein expression of CHAC1 in breast cancer cell lines. Evidence from bioinformatics analysis as well as in vitro studies indicated a high overall expression of CHAC1 in breast tumor samples and had a significant impact on the prognosis and survival of patients. Enhanced CHAC1 levels in the aggressive breast tumor subtypes such as Human Epidermal growth factor receptor 2 (HER2) and Triple Negative Breast Cancer (TNBC) were evident. Our findings hint toward the possible role of CHAC1 in facilitating the aggressiveness of breast cancer and the disease outcome. Conclusion: In summary, CHAC1 is constantly up-regulated in breast cancer leading to a poor prognosis. CHAC1, therefore, could be a promising candidate in the analysis of breast cancer diagnosis and prognosis. � 2022, The Author(s), under exclusive licence to Springer Nature B.V.Item Role of p53 gene in breast cancer: Focus on mutation spectrum and therapeutic strategies(Bentham Science Publishers B.V., 2018) Kaur, Raman Preet; Vasudeva, Kanika; Kumar, Roshan; Munshi, AnjanaTP53 is a tumor suppressor gene which is commonly mutated in various cancers including breast cancer. Alterations in the gene lead to an altered expression of various genes that are directly or indirectly under the transcriptional control of p53. This results in malfunctioning of DNA damage repair pathways, cell-cycle arrest, chromatin remodeling and apoptosis. Different mutations in TP53 gene have been reported in different ethnic groups and exon 4 and intron 3 are reported to be frequently mutated in breast cancer patients especially triple-negative breast cancer. Increased global burden of TP53 mutated breast tumors has paved the path for various therapies targeting p53/TP53. Numerous molecules including nutilins, MI series, RO5693, PRIMA-1, RITA, etc. have been developed. Majority of these restore p53/TP53 function by targeting negative regulators of p53/TP53, wtp53/TP53 (wild-type) and mtp53/TP53 (mutant). Most of these molecules are in the preclinical phase except for two APR-246 and COTI-2 that have progressed to clinical trials. The current review has been compiled with an aim to give an overview of mutations in p53 across various ethnic groups, the effect of these alterations on TP53 function and the therapeutic strategies developed till date targeting p53/TP53 especially in breast cancer.Item Serum Albumin Levels in Breast Cancer: Correlation with Overall Survival(SciTechnol, 2017) Kaur, Raman Preet; Rubal; Dhiman, Monisha; Vashitstha, Rajesh; Munshi, AnjanaIntroduction: Albumin in an important biomarker that indicates malnutrition as well as inflammation. The aim of the study was to evaluate the albumin levels in breast cancer patients and its association with overall survival among breast cancer patients of Malwa region of Punjab. Material and methods: The study was planned in Malwa region of Punjab. Sampling was done from Guru Gobind Singh Medical College and Hospital and Max Hospital. The estimation of albumin levels was done at Central University of Punjab. 250 patients with breast cancer and 250 age and sex matched controls were involved in the study. Albumin levels were estimated using fully automated bio analyzer Erba 200. Follow-up interviews were conducted at an interval of 3, 6, 12 and 15 months to determine the outcome among breast cancer patients. Results: Low levels of albumin was found among the diseased in comparison with controls (p<0.000). Higher albumin levels associated significantly with overall survival in breast cancer patients [χ2: 11.95, p<0.000; odds ratio: 7.636 (95% CI, 2.047- 28.49)]. Conclusion: Elevated levels of albumin (>3.5 g/dl) are associated significantly with increased overall survival among breast cancer patients. Albumin estimation may be a simple and inexpensive tool for the risk assessment and outcome of the disease in Malwa region of Punjab where the incidence of breast cancer is reported to be very high.