المؤلفون: Sandeep Kumar, Shalmoli Bhattacharyya, Ashim Das, Gurpreet Singh, Amanjit Bal

المصدر: Breast disease. 41(1)

مصطلحات موضوعية: Cancer Research, Class I Phosphatidylinositol 3-Kinases, TOR Serine-Threonine Kinases, Breast Neoplasms, Triple Negative Breast Neoplasms, General Medicine, MTOR Inhibitors, Cell Line, Phosphatidylinositol 3-Kinases, Oncology, Receptors, Androgen, Cell Line, Tumor, Humans, Female, skin and connective tissue diseases, Signal Transduction

الوصف: BACKGROUND: Agents targeting the PI3K pathway in triple negative breast cancer did not show any significant efficacy so far mostly because of the complex nature of these targeted inhibitors. Targeting the cancer cells with the combination of inhibitors may help in decelerating the regulatory pathways further achieving optimum clinical benefit. In this study, we investigated the effect of PIK3CA and mTOR inhibition in-vitro in triple-negative breast cancer (TNBC) cell lines. OBJECTIVE AND METHODS: Three TNBC cell lines; MDA MB231, MDA MB468, and MDA MB453 were subtyped using immunohistochemistry and were screened for hotspot mutations in PIK3CA and AKT1. All cell lines were treated with different concentrations of inhibitors; PI3K inhibitor (BKM 120), mTOR inhibitor (AZD 8055), and dual PI3K/mTOR inhibitor (BEZ 235), and cell viability was assessed by MTT (3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide), Trypan blue and Annexin-V/PI Assays. RESULTS: Using immunohistochemistry, TNBC cell lines were subtyped as; mesenchymal subtype-specific cell line (MDA MB231), basal subtype-specific cell line (MDA MD468), and Luminal androgen receptor (LAR) subtype-specific cell line (MDA MB453). PIK3CA hot spot mutation (p.H1047R) in exon 20 was identified in the Luminal androgen receptor subtype (MDA MB453 cells) cell line. Cell viability assays showed that the Mesenchymal subtype-specific cell line (MDA MB231) was the most resistant to all inhibitors and the Luminal Androgen subtype (MDA MB453 cells) cell line was more sensitive to BKM120 (PI3K inhibitor) inhibition compared to other subtypes. CONCLUSIONS: This study identified that the Luminal androgen receptor subtype of triple-negative breast cancer with PIK3CA mutation may be targeted with PIK3CA inhibitors with a favorable outcome.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::56b18720d9547f3d4f20290caa1976caTest
https://pubmed.ncbi.nlm.nih.gov/35431224Test

المؤلفون: Rashmi Bagga, Radhika Srinivasan, Shalmoli Bhattacharyya, Shifa Javed

المصدر: Molecular and Cellular Biochemistry. 473:51-62

مصطلحات موضوعية: 0301 basic medicine, Epithelial-Mesenchymal Transition, medicine.medical_treatment, Clinical Biochemistry, Cell, Uterine Cervical Neoplasms, Biology, 03 medical and health sciences, 0302 clinical medicine, Cancer stem cell, Cell Line, Tumor, Gene expression, medicine, Humans, Insulin-Like Growth Factor I, Molecular Biology, Cisplatin, Cervical cancer, Growth factor, Cell Biology, General Medicine, medicine.disease, Neoplasm Proteins, 030104 developmental biology, medicine.anatomical_structure, Apoptosis, Cell culture, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, Cancer research, Female, Signal Transduction, medicine.drug

الوصف: Cancer stem cells (CSC) drive tumour progression and are implicated in relapse and resistance to conventional cancer therapies. Identification of differentially expressed genes by gene expression (GEP) profiling may help identify the differentially activated signalling pathways in cancer stem cells as opposed to bulk tumour cells which will provide new insights into cancer stem cell biology and aid in identification of novel therapeutic targets. Our study focused on the inhibition of CSC from cervical cancer cell lines by targeting insulin-like growth factor (IGF), which was identified by differential GEP. Targeted inhibition of IGF-1 by JB-1 trifluoroacetate (inhibitor of IGF) was carried out in SiHa, RSBS-14 and RSBS-43 cervical cancer derived cell lines. Effect of cisplatin was also evaluated. Inhibition of IGF-1 signalling was confirmed by demonstration of reduction in p-Akt levels. The cell biological effects of IGF-1 inhibition included an increase in G2M/S fraction, increased apoptosis and decreased invasive ability. JB-1 and cisplatin showed synergism. However, transcript levels of stemness and EMT markers showed variable levels following IGF inhibition. Overall, this proof-of-concept study has shown that IGF-1 is an attractive target for inhibition of CSC in invasive cervical cancer.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::619fe4a597bb20186cf48bf314ac728cTest
https://doi.org/10.1007/s11010-020-03807-6Test

المؤلفون: Arup K. Mandal, Shrawan Kumar Singh, Rani Ojha, Ashutosh Chauhan, Shalmoli Bhattacharyya

المصدر: Journal of Cancer Research and Therapeutics, Vol 14, Iss 5, Pp 977-982 (2018)

مصطلحات موضوعية: 0301 basic medicine, Adult, Male, Pathology, medicine.medical_specialty, renal cell carcinoma, medicine.medical_treatment, SPOP, urologic and male genital diseases, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, Renal cell carcinoma, Biomarkers, Tumor, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Carcinoma, Renal Cell, Tumor marker, mammalian target of rapamycin, Aged, Kidney, business.industry, Cancer, Nuclear Proteins, Kidney Neoplasm, General Medicine, Biomarker, Middle Aged, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Nephrectomy, female genital diseases and pregnancy complications, speckle-type POZ protein, Gene Expression Regulation, Neoplastic, Repressor Proteins, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Biomarker (medicine), Female, business

الوصف: Background: Renal cell carcinoma (RCC) is the most common kidney neoplasm and requires an early diagnosis because of poor response to conventional cancer treatments. However, till date, there is no reliable tumor marker available for the diagnosis of RCC. Objective: The aim of the study was to evaluate the expression of speckle-type POZ protein (SPOP) as a biomarker in patients with RCC. Materials and Methods: Blood samples were collected from fifty patients with RCC and ten healthy controls. Tumor tissue samples were obtained from nephrectomy specimen. Adjoining normal renal parenchyma of these fifty patients and eight normal renal tissue samples from normal kidney served as controls. Reverse transcriptase-polymerase chain reaction assay was performed for SPOP and mammalian target of rapamycin expression. Results: SPOP was significantly increased in blood of patients with RCC as compared to controls (0.754 ± 0.32 vs. 0.224 ± 0.14; P < 0.001). Twenty-two patients (44%) had SPOP value more than mean + 2 standard deviation (SD) of controls. In RCC tissue, 42 (84%) patients had increased expression of SPOP more than 0.523 (mean + 2 SD value of SPOP expression in controls). SPOP expression was high in blood of 60% patients and in tumor tissue of 90% patients with clear cell RCC. SPOP was higher in high grade and high stage of RCC. Conclusions: Our result suggests that SPOP expression in blood might have a sensitivity that is low for routine diagnostic use and for screening for RCC. However, SPOP could be a potential tissue diagnostic biomarker in RCC.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fe30990fca4413570cdc5e39d6f65d0aTest
https://pubmed.ncbi.nlm.nih.gov/30197334Test

المؤلفون: Pooja Mehta, Shalmoli Bhattacharyya

المصدر: Food Funct.. 3:164-169

مصطلحات موضوعية: Antioxidant, medicine.medical_treatment, Ascorbic Acid, Pharmacology, Lipid peroxidation, Mice, chemistry.chemical_compound, Spirulina, medicine, Animals, Aspartate Aminotransferases, Spirulina (genus), Liver injury, chemistry.chemical_classification, Cisplatin, Mice, Inbred BALB C, L-Lactate Dehydrogenase, biology, Vitamin C, Vitamins, General Medicine, Alkaline Phosphatase, biology.organism_classification, medicine.disease, Diet, Enzyme, Liver, chemistry, Biochemistry, Dietary Supplements, Toxicity, Female, Lipid Peroxidation, Food Science, medicine.drug

الوصف: Spirulina platensis is a microalgae with potent dietary phyto-antioxidant, anti-inflammatory and anti-carcinogenic properties. We investigated the mechanism of cisplatin induced hepatotoxicity and whether this natural antioxidant provided protection against cisplatin hepatotoxicity. The study was carried out in a mice model where the animals were segregated into different groups according to their treatments, e.g. control group with no treatment, cisplatin treated, cisplatin + Spirulina treated, cisplatin + vitamin C treated and cisplatin + Spirulina + vitamin C treated. The liver marker enzymes were found to be elevated following cisplatin treatment, signifying hepatotoxicity. The supplementation of Spirulina and vitamin C could effectively bring down the levels of these enzymes. Light microscopy also showed that cisplatin treatment induced liver injury and that histopathological abnormalities were prevented by Spirulina and vitamin C supplementation. This protective effect was further substantiated by the estimation of antioxidant levels and extent of lipid peroxidation in the Spirulina, vitamin C and Spirulina + vitamin C supplemented groups as compared to cisplatin alone.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c4f4858d762470b66248ebded32c7b9aTest
https://doi.org/10.1039/c1fo10172bTest