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ovarian cancer drug resistance

Fuqiang Yin, Shang Yi, Luwei Wei, Bingbing Zhao, Jinqian Li, Xiangxue Cai, Caihua Dong, Xia Liu
The outcome for patients with ovarian cancer (OC) is poor because of drug resistance. Therefore, identification of factors that affect drug resistance and prognosis in OC is needed. In the present study, we identified 131 genes significantly dysregulated in 90 platinum-resistant OC tissues compared with 197 sensitive tissues, of which 30 were significantly associated with disease-free survival (DFS; n = 16), overall survival (OS; n = 6), or both (n = 8) in 489 OC patients of the The Cancer Genome Atlas cohort...
October 18, 2018: Journal of Cellular Biochemistry
Vahideh Tarhriz, Mojgan Bandehpour, Siavoush Dastmalchi, Elaheh Ouladsahebmadarek, Habib Zarredar, Shirin Eyvazi
Ovarian cancer (OC) is the fifth leading cause of cancer-related death among women. The high mortality rate is due to lack of early symptoms, late diagnosis, limited treatment options, and also emerging of drug resistance. Todays, molecular markers have become promising in tumor-targeted therapy. Several molecular markers have been known in OC immunotherapy. Identification of the specific molecular markers with prognostic significance is interested. CD24 is a small sialoglycoprotein which is localized in lipid rafts through its glycosylphosphatidylinositol (GPI) anchor...
October 14, 2018: Journal of Cellular Physiology
Claudia Matteucci, Emanuela Balestrieri, Ayele Argaw-Denboba, Paola Sinibaldi-Vallebona
Cancer incidence and mortality, metastasis, drug resistance and recurrence are still the critical issues of oncological diseases. In this scenario, increasing scientific evidences demonstrate that the activation of human endogenous retroviruses (HERVs) is involved in the aggressiveness of tumors such as melanoma, breast, germ cell, renal, ovarian, liver and haematological cancers. In their dynamic regulation, HERVs have also proved to be important determinants of pluripotency in human embryonic stem cells (ESC) and of the reprogramming process of induced pluripotent stem cells (iPSCs)...
October 11, 2018: Seminars in Cancer Biology
Wenxiang Wang, Yuxia Gao, Jing Hai, Jing Yang, Shufeng Duan
Increasing evidence shows that cancer stem cells are responsible for drug resistance and relapse of tumors. In breast cancer, HER2 induces Herceptin resistance by inducing cancer stem cells. In this study, we explored the effect of HER2 on cancer stem cells induction and drug sensitivity of ovarian cancer cell lines. Firstly, we found that HER2 overexpression (HER2 OE) induced, while HER2 knockdown (HER2 KD) decreased CD44+/CD24- population. Consistently, HER2 expression was closely correlated with the sphere formation efficiency (SFE) of ovarian cancer cells...
October 12, 2018: Bioscience Reports
Fengmei Yang, Bo Gao, Wei Chen, Enfu Du, Yong Liang, Xiuxue Hu, Xiaofeng Yang
The sensitivity of tumor cells to chemotherapy drugs may become attenuated accounts for various reasons. Reduced drug sensitivity may cause the failure of chemotherapy and affect the prognosis of patients with cancer. This study investigates the relationship between the expression levels of lung resistance protein (LRP) and placental glutathione S-transferase-P1 (GSTP1), the resistance of primary epithelial ovarian cancer (PEOC) to chemotherapy, and the prognosis of patients with platinum drug-resistant PEOC...
October 2018: Medicine (Baltimore)
Partha Basu, Asima Mukhopadhyay, Ikuo Konishi
Recent advances in molecular biology of cancer have led to the development of targeted agents, mainly of monoclonal antibodies and small-molecule compounds. Unlike traditional drugs that inhibit DNA synthesis and mitosis, these agents target the signaling pathways of cancer cells, stroma, and vasculature in tumor tissues. For gynecologic cancers, drugs targeting angiogenesis such as anti-VEGF antibody have been used in the treatment of advanced or recurrent ovarian and cervical cancers, and the drugs targeting homologous recombination deficiency such as PARP inhibitors have been approved for maintenance after chemotherapy in platinum-sensitive ovarian cancer...
October 2018: International Journal of Gynaecology and Obstetrics
Anil Belur Nagaraj, Peronne Joseph, Olga Kovalenko, QuanQiu Wang, Rong Xu, Analisa DiFeo
OBJECTIVE: To evaluate the utility of amiodarone and its derivative dronedarone as novel drug repositioning candidates in EOC and to determine the potential pathways targeted by these drugs. METHODS: Drug-predict bioinformatics platform was used to assess the utility of amiodarone as a novel drug-repurposing candidate in EOC. EOC cells were treated with amiodarone and dronedarone. Cell death was assessed by Annexin V staining. Cell viability and cell survival were assessed by MTT and clonogenics assays respectively...
October 6, 2018: Gynecologic Oncology
Jinglu Wang, Dylan C Dean, Francis J Hornicek, Huirong Shi, Zhenfeng Duan
Despite the surgical and chemotherapeutic advances over the past few decades, ovarian cancer remains the leading cause of gynecological cancer-related mortality. The absence of biomarkers in early detection and the development of drug resistance are principal causes of treatment failure in ovarian cancer. Recent progress in RNA sequencing (RNA-Seq) with Next Generation Sequencing technology has expanded the understanding of the molecular pathogenesis of ovarian cancer. As compared to previous hybridization-based microarray and Sanger sequence-based methods, RNA-Seq provides multiple layers of resolutions and transcriptome complexity, with less background noise and a broader dynamic range of RNA expression...
October 5, 2018: Gynecologic Oncology
Jonathan M Pantshwa, Khadija Rhoda, Sarah J Clift, Priyamvada Pradeep, Yahya E Choonara, Pradeep Kumar, Lisa C du Toit, Clement Penny, Viness Pillay
The present study aimed to design and develop a nanocomposite drug delivery system employing an antineoplastic-loaded antibody functionalized nanomicelle encapsulated within a Chitosan⁻Poly(vinylpyrrolidone)⁻Poly(N-isopropylacrylamide) (C⁻P⁻N) hydrogel to form an in situ forming implant (ISFI), responsive to temperature and pH for cancer cell-targeting following intraperitoneal implantation. The optimum nanomicelle formulation was surface-functionalized with anti-MUC 16 (antibody) for the targeted delivery of methotrexate to human ovarian carcinoma (NIH:OVCAR-5) cells in Athymic nude mice that expressed MUC16, as a preferential form of intraperitoneal ovarian cancer (OC) chemotherapy...
October 4, 2018: International Journal of Molecular Sciences
Sanrong Li, Jing Ma, Caiying Hu, Xing Zhang, Deyong Xiao, Lili Hao, Wenjun Xia, Jichun Yang, Ling Hu, Xiaowei Liu, Minghui Dong, Duan Ma, Rensheng Liu
In this study, we used next-generation sequencing methods to screen 300 individuals for BRCA1 and BRCA2 . A novel mutation (c.849dupT) in BRCA2 was identified in a female patient and her unaffected brothers. This mutation leads to the truncation of BRCA2 functional domains. Moreover, BRCA2 mRNA expression levels in mutation carriers are significantly reduced compared to noncarriers. Immunofluorescence and western blot assays showed that this mutation resulted in reduced BRCA2 protein expression. Thus, we identified a novel mutation that damaged the function and expression of BRCA2 in a family with breast cancer history...
September 2018: Journal of Breast Cancer
Maxim Sorokin, Roman Kholodenko, Maria Suntsova, Galina Malakhova, Andrew Garazha, Irina Kholodenko, Elena Poddubskaya, Dmitriy Lantsov, Ivan Stilidi, Petr Arhiri, Andreyan Osipov, Anton Buzdin
Sequential courses of anticancer target therapy lead to selection of drug-resistant cells, which results in continuous decrease of clinical response. Here we present a new approach for predicting effective combinations of target drugs, which act in a synergistic manner. Synergistic combinations of drugs may prevent or postpone acquired resistance, thus increasing treatment efficiency. We cultured human ovarian carcinoma SKOV-3 and neuroblastoma NGP-127 cancer cell lines in the presence of Tyrosine Kinase Inhibitors (Pazopanib, Sorafenib, and Sunitinib) and Rapalogues (Temsirolimus and Everolimus) for four months and obtained cell lines demonstrating increased drug resistance...
September 29, 2018: Cancers
Faguang Mu, Ting Liu, Hanrui Zheng, Xiaofang Xie, Tiantian Lei, Xia He, Suya Du, Rongsheng Tong, Yi Wang
Although surgery and high‑dose radiotherapy have been the standard treatments for glioblastoma multiforme (GBM), these therapies are palliative, due to the high risk of local relapse. Emerging evidence has demonstrated that DNA double‑strand break (DSB) repair serves a critical role in resistance to radiotherapy. Previous studies have revealed that mangiferin possesses anti‑neoplastic effects on human lung adenocarcinoma and ovarian cancer. The present study aimed to investigate the role of mangiferin in radio‑sensitivity inhuman GBM...
October 1, 2018: Oncology Reports
Agata Swiatly, Szymon Plewa, Jan Matysiak, Zenon J Kokot
Ovarian cancer has emerged as one of the leading cause of gynecological malignancies. So far, the measurement of CA125 and HE4 concentrations in blood and transvaginal ultrasound examination are essential ovarian cancer diagnostic methods. However, their sensitivity and specificity are still not sufficient to detect disease at the early stage. Moreover, applied treatment may appear to be ineffective due to drug-resistance. Because of a high mortality rate of ovarian cancer, there is a pressing need to develop innovative strategies leading to a full understanding of complicated molecular pathways related to cancerogenesis...
October 1, 2018: Journal of Ovarian Research
Brittany Haynes, Junko Murai, Jung-Min Lee
Poly(ADP-ribose) polymerase (PARP) inhibition serves as a potent therapeutic option eliciting synthetic lethality in cancers harboring homologous recombination (HR) repair defects, such as BRCA mutations. However, the development of resistance to PARP inhibitors (PARPis) poses a clinical challenge. Restoration of HR competency is one of the many molecular factors contributing to PARPi resistance. Combination therapy with cell cycle checkpoint (ATR, CHK1, and WEE1) inhibitors is being investigated clinically in many cancers, particularly in ovarian cancer, to enhance the efficacy and circumvent resistance to PARPis...
September 11, 2018: Cancer Treatment Reviews
Karolina Sterzyńska, Andrzej Klejewski, Karolina Wojtowicz, Monika Świerczewska, Małgorzata Andrzejewska, Damian Rusek, Maciej Sobkowski, Witold Kędzia, Jacek Brązert, Michał Nowicki, Radosław Januchowski
The major cause of ovarian cancer treatment failure in cancer patients is inherent or acquired during treatment drug resistance of cancer. Matrix Gla protein (MGP) is a secreted, non-collagenous extracellular matrix protein involved in inhibition of tissue calcification. Recently, MGP expression was related to cellular differentiation and tumor progression. A detailed MGP expression analysis in sensitive (A2780) and resistant to paclitaxel (PAC) (A2780PR) and topotecan (TOP) (A2780TR) ovarian cancer cell lines and their corresponding media was performed...
September 25, 2018: International Journal of Molecular Sciences
Han Li, Weijing Zhang, Xiaoying Sun, Jueming Chen, Yue Li, Chunhao Niu, Benke Xu, Yanna Zhang
Background: KIF20A plays an indispensable role in cytokinesis regulation, which is important for tumor proliferation and growth. Recently, the oncogenic role of KIF20A has been well documented in several cancers. However, its clinical role in epithelial ovarian cancer (EOC) remains not reported yet. We investigated its expression and its role in promoting invasion and chemoresistance in EOC cells. Patients and methods: KIF20A transcription and translation levels were investigated in normal ovarian epithelial cell, ovarian cancer cells, and 10 pairs of fresh EOC tissues and adjacent normal ovarian tissues by real-time quantitative polymerase chain reaction and Western blots...
2018: Cancer Management and Research
Hui Hua, Hongying Zhang, Qingbin Kong, Yangfu Jiang
Estrogen is a steroid hormone that has critical roles in reproductive development, bone homeostasis, cardiovascular remodeling and brain functions. However, estrogen also promotes mammary, ovarian and endometrial tumorigenesis. Estrogen antagonists and drugs that reduce estrogen biosynthesis have become highly successful therapeutic agents for breast cancer patients. The effects of estrogen are largely mediated by estrogen receptor (ER) α and ERβ, which are members of the nuclear receptor superfamily of transcription factors...
2018: Experimental Hematology & Oncology
Weiping Zheng, Minhua Li, Yunxia Lin, Xin Zhan
PURPOSE: Ovarian cancer is usually treated with transurethral resection or systemic chemotherapy in clinic. However, the development of drug resistance in ovarian cancer is frequently observed in ovarian cancer patients, leading to failure of tumor inhibition and recurrence. In this study, we aimed to efficiently reverse the drug resistance and enhance the anticancer effects by co-delivery of chemotherapeutic agents and multi-drugs resistant proteins inhibitor in ovarian cancer treatment...
September 19, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Sarah Spreckelmeyer, Margot van der Zee, Benoît Bertrand, Ewen Bodio, Stefan Stürup, Angela Casini
The molecular mechanisms of toxicity and cellular transport of anticancer metallodrugs, including platinum-based agents, have not yet been fully elucidated. The aim of our study was to investigate the relevance of copper transporters (CTR1 and ATP7A/B), organic cation transporters (OCT2) and the multidrug and toxin extrusion proteins (MATE) in the intracellular accumulation of a novel organometallic cytotoxic Au(III) compound in cancer cells in comparison to cisplatin. Specifically, the synthesis and characterization of the gold complex [Au(pyb -H)(PPh2 Ar)Cl]PF6 (PPh2 Ar = 3-[4-(diphenylphosphino)phenyl]-7-methoxy-2H-chromen-2-one] ( 1 ), featuring a coumarin ligand endowed with "smart" fluorescence properties, have been achieved...
2018: Frontiers in Chemistry
Meng Zhang, Qing Cong, Xiao-Yan Zhang, Ming-Xing Zhang, Ying-Ying Lu, Cong-Jian Xu
Patients with ovarian cancer frequently develop acquired drug resistance after the long-term chemotherapy, leading to disease progression. Enhanced epithelial-mesenchymal transition (EMT) has been implicated in chemoresistance of ovarian cancer cells; however, the molecular mechanisms involved are largely undefined. Pyruvate dehydrogenase kinase 1 (PDK1), a key regulatory enzyme in glucose metabolism, has been recognized as a gatekeeper of the Warburg effect, a hallmark of cancer. In this study, the function of PDK1 in cisplatin resistance of ovarian cancer in terms of growth and EMT was investigated...
September 19, 2018: Journal of Cellular Physiology
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