Press Release on ovarian cancer Research: April – 2019

MicroRNA‐mediated drug resistance in ovarian cancer

The development of intrinsic or noninheritable  resistance to therapy agents utilized in the treatment of varied human cancers may be a major obstacle for the no-hit abolition of cancer. The accumulated efforts within the understanding the precise mechanisms of development of multidrug resistance (MDR) have crystal rectifier to the introduction of many distinctive and customary mechanisms. Recent studies demonstrate the restrictive role of little noncoding RNA or miRNA within the many elements of cancer biology. much all aspects of cell physiology underneath traditional and illness conditions are rumored to be controlled by miRNAs. during this review, we tend to discuss however the miRNA profile is modified upon MDR development and therefore the important restrictive role compete by miRNAs in overcoming resistance to therapy agents. it’s hoped that additional studies can support the employment of those differentially expressed miRNAs as prognostic and prognostic markers, further as novel therapeutic targets to beat resistance in sex gland cancer. [1]

Association of Breast and Ovarian Cancers With Predisposition Genes Identified by Large-Scale Sequencing

Importance  Since the invention of BRCA1 and BRCA2, multiple high- and moderate-penetrance genes are reported  as risk factors for hereditary carcinoma, female internal reproductive organ cancer, or both; but, it’s unclear whether or not these findings represent the whole genetic landscape of those cancers. Systematic investigation of the genetic contributions to breast and female internal reproductive organ cancers is required to verify these findings and explore doubtless new associations.

Objective to verify reported  and establish extra predisposition genes for breast or female internal reproductive organ cancer.

Design, Setting, and Participants during this sample of 11 416 patients with clinical options of carcinoma, female internal reproductive organ cancer, or each UN agency were referred for genetic testing from 1200 hospitals and clinics across the us and of 3988 controls who were referred for genetic testing for noncancer conditions between 2014 and 2015, whole-exome sequencing was conducted and gene-phenotype associations were examined. Case-control analyses victimization the ordination Aggregation info as a group of reference controls were additionally conducted.

Main Outcomes and Measures carcinoma risk related to unhealthful variants among 625 cancer predisposition genes; association of known predisposition breast or female internal reproductive organ cancer genes with the breast cancer subtypes invasive ductal, invasive lobe, internal secretion receptor–positive, internal secretion receptor–negative, and male, and with early-onset illness.

Results  Of 9639 patients with carcinoma, 3960 (41.1%) were early-onset cases (≤45 years at diagnosis) and 123 (1.3%) were male, with men having AN older age at designation than girls (mean [SD] age, 61.8 [12.8] vs 48.6 [11.4] years). Of 2051 girls with female internal reproductive organ cancer, 445 (21.7%) received a designation at forty five years or younger. Enrichment of unhealthful variants were known in four non-BRCA

genes related to carcinoma risk: ATM (odds quantitative relation [OR], 2.97; 95% CI, 1.67-5.68), CHEK2 (OR, 2.19; 95% CI, 1.40-3.56), PALB2 (OR, 5.53; 95% CI, 2.24-17.65), and MSH6 (OR, 2.59; 95% CI, 1.35-5.44). exaggerated risk for female internal reproductive organ cancer was related to four genes: MSH6 (OR, 4.16; 95% CI, 1.95-9.47), RAD51C (OR, not estimable; false-discovery rate–corrected P = .004), TP53 (OR, 18.50; 95% CI, 2.56-808.10), and ATM (OR, 2.85; 95% CI, 1.30-6.32). Neither the MRN complicated genes nor CDKN2A was related to exaggerated breast or female internal reproductive organ cancer risk. The findings additionally don’t support antecedently reported  carcinoma associations with the female internal reproductive organ cancer susceptibleness genes BRIP1, RAD51C, and RAD51D, or match repair genes MSH2 and PMS2.

Conclusions and connectedness  The results of this large-scale exome sequencing of patients and controls shed lightweight on each well-established and debatable non-BRCA predisposition cistron associations with breast or female internal reproductive organ cancer reported  up to now and will implicate extra breast or ovarian cancer susceptibleness gene candidates concerned in deoxyribonucleic acid repair and genomic maintenance. [2]

Mainstreamed genetic testing for women with ovarian cancer: first-year experience

Background sex gland cancer is that the fifth most typical reason behind cancer death for ladies within the GB. Up to eighteenth of cases are often attributed to germline mutations in BRCA1 and BRCA2genes. distinctive patients United Nations agency carry a BRCA mutation provides necessary info regarding potential response to treatment and eligibility for therapies like poly ADP sugar enzyme (PARP) inhibitors. Implementation of systematic genetic testing of patients with sex gland cancer via medicine clinics (mainstreamed genetic testing, MGT) is increasing.

Methods and results This service analysis reports on the primary year of MGT at a tertiary medicine centre in London, UK. In total, 122 patients with best non-mucinous sex gland cancer underwent BRCA germline testing via MGT. Eighteen patients (14.8%) were found to hold a hurtful BRCA1/BRCA2 mutation. Four BRCA carriers failed to meet previous criteria for genetic testing and would are incomprehensible . Six BRCA carriers accessed PARP inhibitors post-MGT. solely twenty two of patients with a variant of unknown significance (VUS) were said clinical biology services.

Conclusions MGT seems to be a possible approach of providing BRCA testing to patients with sex gland cancer. larger clarity of however oncologists use VUS results is required, yet as further analysis on psychosocial implications of MGT for patients with sex gland cancer, which can embody corporeal testing within the future. [3]

An evolving story of the metastatic voyage of ovarian cancer cells: cellular and molecular orchestration of the adipose-rich metastatic microenvironment

Metastasis may be a complicated multistep method that involves essential interactions between cancer cells and a spread of stromal elements within the growth microenvironment, that deeply influence the various aspects of the pathological process cascade and organ response of dispersive cancer cells. sex gland cancer is that the most deadly gynaecological malignancy and is characterised by serous membrane disseminated metastasis. proof has incontestible that sex gland cancer possesses specific pathological process response for the adipose-rich peritoneum, that incorporates a important role within the creation of the malignancy microenvironment in the intraperitoneal cavity. Considering the distinct biology of sex gland cancer metastasis, the elucidation of the cellular and molecular mechanisms underlying the reciprocal interaction between sex gland cancer cells and close stromal cell varieties within the adipose-rich pathological process microenvironment can give additional insights into the event of novel therapeutic approaches for patients with advanced ovarian cancer. Herein, we have a tendency to review the biological mechanisms that regulate the extremely musical group disturbance between sex gland cancer cells and varied cancer-associated stromal cells within the malignancy microenvironment with relevancy the peritoneum by illustrating however totally different stromal cells concertedly contribute to the event of ovarian cancer metastasis and pathological process response for the omentum. [4]

Cytotoxic and Apoptotic Effects of the Bark of Two Common Mango (Mangifera indica) Varieties from Sri Lanka on Breast and Ovarian Cancer Cells

Aims: this study was planned to judge cytotoxic and apoptotic properties of the bark of 2 common mango varieties (Mangifera indica L.) adult in Sri Lanka [Rata Amba (RA) and Karthakolomban (KA)] in MCF-7 (ER positive breast cancer), MDA-MB-231 (triple negative breast cancer), SKOV-3 (ovarian animal tissue cancer) neoplastic cell lines and traditional exocrine gland epithelial cells (MCF-10A).

Place and length of the Study: At the Institute of organic chemistry, biological science and Biotechnology, University of national capital between first of Feb 2015 to Apr 2015.

Methodology: Cancer cells and traditional cells were treated with organic extracts (hexane, chloroform, ester and methanol) of RA and Ka bark and cytotoxic effects were evaluated by SRB assay. atom scavenging ability on one,1-diphenyl-2-picrylhydrazyl (DPPH) was additionally tested for active extracts. what is more, apoptotic effects of cytotoxic extracts were analysed by peptidase three and seven activation, deoxyribonucleic acid fragmentation, acridine orange/ethidium bromide (AO/EB) and Hoechst staining.

Results: Of the four solvent extracts used, solely the wood alcohol extract showed anti-proliferative effects against all 3 neoplastic cell lines in an exceedingly dose-dependent manner. toxicity of the wood alcohol extract of RA was higher (MCF-7 IC50- eighty one.1 µg/mL, MDA-MB-231 IC50- ninety one. five µg/mL and SKOV-3 IC50- seventy one.5 µg/mL) compared to it of the wood alcohol extract of Ka (MCF-7 IC50- 123.9 µg/mL, MDA-MB-231 IC50- 111.2 µg/mL and SKOV-3 IC50- 137.2 µg/mL). each the wood alcohol extracts showed less toxicity to traditional exocrine gland animal tissue cells [IC50- 255.6 µg/mL (RA) and IC50- vi15.6 µg/mL (KA)]. wood alcohol extracts additionally exhibited robust atom scavenging ability on one,1-diphenyl-2-picrylhydrazyl (DPPH). what is more, wood alcohol extract showed apoptotic impact against all tested neoplastic cell lines.

Conclusion: Overall findings of this study recommend that wood alcohol extracts of the bark of 2 common mango varieties tested exhibit toxicity through induction of programmed cell death through peptidase dependent mechanisms. [5]

Reference

[1] Mihanfar, A., Fattahi, A. and Nejabati, H.R., 2019. MicroRNA‐mediated drug resistance in ovarian cancer. Journal of cellular physiology, 234(4), pp.3180-3191. (Web Link)

[2] Lu, H.M., Li, S., Black, M.H., Lee, S., Hoiness, R., Wu, S., Mu, W., Huether, R., Chen, J., Sridhar, S. and Tian, Y., 2019. Association of breast and ovarian cancers with predisposition genes identified by large-scale sequencing. JAMA oncology, 5(1), pp.51-57. (Web Link)

[3] Rahman, B., Lanceley, A., Kristeleit, R.S., Ledermann, J.A., Lockley, M., McCormack, M., Mould, T. and Side, L., 2019. Mainstreamed genetic testing for women with ovarian cancer: first-year experience. Journal of medical genetics, 56(3), pp.195-198. (Web Link)

[4] An evolving story of the metastatic voyage of ovarian cancer cells: cellular and molecular orchestration of the adipose-rich metastatic microenvironment

Takeshi Motohara, Kenta Masuda, Matteo Morotti, Yiyan Zheng, Salma El-Sahhar, Kay Yi Chong, Nina Wietek, Abdulkhaliq Alsaadi, Mohammad Karaminejadranjbar, Zhiyuan Hu, Mara Artibani, Laura Santana Gonzalez, Hidetaka Katabuchi, Hideyuki Saya & Ahmed Ashour Ahmed

Oncogene (2018) (Web Link)

[5] Ediriweera, M., Tennekoon, K., Samarakoon, S., Thabrew, I. and de Silva, E. D. (2016) “Cytotoxic and Apoptotic Effects of the Bark of Two Common Mango (Mangifera indica) Varieties from Sri Lanka on Breast and Ovarian Cancer Cells”, Journal of Pharmaceutical Research International, 10(2), pp. 1-7. doi: 10.9734/BJPR/2016/24004. (Web Link)

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