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ovarian cancer drug resistance

Agnieszka Owczarczyk-Saczonek, Lesław Bernard Lahuta, Magdalena Ligor, Waldemar Placek, Ryszard Józef Górecki, Bogusław Buszewski
INTRODUCTION: Myo -inositol and its derivatives cyclitols play an important role in the processes of cell regulation, signal transduction, osmoregulation, and ion channel physiology, and are a component of the cell membrane. Free cyclitols present in food or released during the degradation of galactosyl cyclitols by bacteria (in digestive tract) show some physiological benefits. AIM: The aim of this paper is to present and analyze the documented data about curative and healing properties of cyclitols...
December 3, 2018: Nutrients
Evgeny N Imyanitov, Grigoriy A Yanus
Neoadjuvant therapy (NAT) is widely utilized in the routine management of cancer patients and various clinical trials for the treatment of breast, ovarian, rectal, esophageal, head and neck, lung, prostate and many other cancer types. There is a number of potential benefits of applying systemic treatment before the operation. NAT may significantly reduce the tumor burden thus allowing less traumatic surgery. NAT is often considered as personalized in vivo drug sensitivity test, as it allows rapid evaluation of tumor response to a given therapy and consequent adjustment of further treatment planning...
December 2018: Chinese Clinical Oncology
Zalitha Pieterse, Monica Angelica Amaya-Padilla, Terence Singomat, Mudra Binju, Bau Dilam Madjid, Yu Yu, Pritinder Kaur
Ovarian cancer is typically diagnosed at advanced stages (III or IV), with metastasis ensuing at stage III. Complete remission is infrequent and is not achieved in almost half of the women diagnosed with ovarian cancer. Consequently, management and treatment of this disease is challenging as many patients are faced with tumour recurrence disseminating to surrounding organs further complicated with acquired chemo-resistance. The cancer stem cell theory proposes the idea that a drug resistant subset of tumour cells drive tumour progression, metastasis and ultimately, recurrent disease...
November 30, 2018: International Journal of Biochemistry & Cell Biology
Faye R Harris, Piyan Zhang, Lin Yang, Xiaonan Hou, Konstantinos Leventakos, Saravut J Weroha, George Vasmatzis, Irina V Kovtun
Ovarian cancer is most lethal gynecologic malignancy. About 75% of ovarian cancer patients relapse and/or develop chemo-resistant disease after initial response to standard-of-care treatment with platinum-based therapies. HER2 amplifications and overexpression in ovarian cancer are reported to vary, and responses to HER2 inhibitors have been poor. Next generation sequencing technologies in conjunction with testing using patient-derived xenografts (PDX) allow validation of personalized treatments. Using a whole-genome mate-pair next generation sequencing (MPseq) protocol, we identified several high grade serous ovarian cancers (HGS-OC) with DNA alterations in genes encoding members of the ERBB2 pathway...
November 30, 2018: Molecular Oncology
Pinar Kanlikilicer, Recep Bayraktar, Merve Denizli, Mohammed H Rashed, Cristina Ivan, Burcu Aslan, Rahul Mitra, Kubra Karagoz, Emine Bayraktar, Xinna Zhang, Cristian Rodriguez-Aguayo, Amr Ahmed El-Arabey, Nermin Kahraman, Seyda Baydogan, Ozgur Ozkayar, Michael L Gatza, Bulent Ozpolat, George A Calin, Anil K Sood, Gabriel Lopez-Berestein
BACKGROUND: Circulating miRNAs are known to play important roles in intercellular communication. However, the effects of exosomal miRNAs on cells are not fully understood. METHODS: To investigate the role of exosomal miR-1246 in ovarian cancer (OC) microenvironment, we performed RPPA as well as many other in vitro functional assays in ovarian cancer cells (sensitive; HeyA8, Skov3ip1, A2780 and chemoresistant; HeyA8-MDR, Skov3-TR, A2780-CP20). Therapeutic effect of miR-1246 inhibitor treatment was tested in OC animal model...
November 25, 2018: EBioMedicine
Navid Neyshaburinezhad, Maryam Hashemi, Mohammad Ramezani, Sepideh Arabzadeh, Javad Behravan, Fatemeh Kalalinia
Objectives: Crocetin, one of the main substances of saffron extract, has anti-cancer effects. Drug resistance proteins (e.g. MRP1 and MRP2) are important reasons for the failure of cancer therapy. We intended to investigate the efficacy of crocetin on MRP1 and MRP2 activity in human ovarian cisplatin-resistant carcinoma cell line (A2780-RCIS). Materials and Methods: The cytotoxic effect of crocetin was evaluated by the MTT assay. The efficacy of crocetin on MRP1 and MRP2 expression at mRNA level was studied by real-time RT-PCR...
November 2018: Iranian Journal of Basic Medical Sciences
Elahe Seyed Hosseini, Marziyeh Alizadeh Zarei, Sadegh Babashah, Roohollah Nakhaei Sistani, Majid Sadeghizadeh, Hamad Haddad Kashani, Javad Amini Mahabadi, Fatemeh Izadpanah, Mohhamad Ali Atlasi, Hossein Nikzad
Drug resistance remains a major challenge in the treatment of patients with ovarian cancer. Therefore, the development of new anticancer drugs is a clinical priority to develop more effective therapies. New approaches to improve clinical outcomes and limit the toxicity of anticancer drugs focus on chemoprevention. The aim of this study was to determine the effects of dendrosomal nanocurcumin (DNC) and oxaliplatin (Oxa) and their combination on cell death and apoptosis induction in human ovarian carcinoma cell lines analyzed by MTT assay and flow cytometry, respectively...
November 26, 2018: Cell Biology and Toxicology
Jeanne M Quinn, Molly M Greenwade, Marguerite L Palisoul, Gregory Opara, Katina Massad, Lei Guo, Peinan Zhao, Hollie Beck-Noia, Ian S Hagemann, Andrea R Hagemann, Carolyn K McCourt, Premal H Thaker, Matthew A Powell, David G Mutch, Katherine C Fuh
Ovarian cancer (OvCa), one of the deadliest malignancies in female cancer patients, is characterized by recurrence and poor response to cytotoxic chemotherapies. Fewer than 30% of patients with resistant disease will respond to additional chemotherapy treatments. This study aims to determine whether and how inhibition of the receptor tyrosine kinase AXL can restore sensitivity to front-line platinum and taxane therapy in OvCa. AXL staining was quantified in a patient tissue microarray and correlated with chemoresponse of patients...
November 26, 2018: Molecular Cancer Therapeutics
Yizhou Joseph He, Khyati Meghani, Marie-Christine Caron, Chunyu Yang, Daryl A Ronato, Jie Bian, Anchal Sharma, Jessica Moore, Joshi Niraj, Alexandre Detappe, John G Doench, Gaelle Legube, David E Root, Alan D D'Andrea, Pascal Drané, Subhajyoti De, Panagiotis A Konstantinopoulos, Jean-Yves Masson, Dipanjan Chowdhury
Limited DNA end resection is the key to impaired homologous recombination in BRCA1-mutant cancer cells. Here, using a loss-of-function CRISPR screen, we identify DYNLL1 as an inhibitor of DNA end resection. The loss of DYNLL1 enables DNA end resection and restores homologous recombination in BRCA1-mutant cells, thereby inducing resistance to platinum drugs and inhibitors of poly(ADP-ribose) polymerase. Low BRCA1 expression correlates with increased chromosomal aberrations in primary ovarian carcinomas, and the junction sequences of somatic structural variants indicate diminished homologous recombination...
November 2018: Nature
Brian Kawahara, Sivakumar Ramadoss, Gautam Chaudhuri, Carla Janzen, Suvajit Sen, Pradip K Mascharak
Cisplatin resistance remains a major impediment to effective treatment of ovarian cancer. Despite initial platinum responsiveness, thiol-containing peptides and proteins, glutathione (GSH) and metallothionein (MT), bind and inactivate cisplatin in cancer cells. Indeed, high levels of GSH and MT in ovarian cancers impart cisplatin resistance and are predictive of poor prognosis. Cystathionine β-synthase (CBS), an enzyme involved in sulfur metabolism, is overexpressed in ovarian cancer tissues and is itself associated with cisplatin resistance...
November 10, 2018: Journal of Inorganic Biochemistry
Khansa Al-Jorani, Anja Rüther, Rukshani Haputhanthri, Glen B Deacon, Hsiu Lin Li, Carleen Cullinane, Bayden R Wood
Attenuated Total Reflection Fourier Transform Infrared (ATR-FT-IR) spectroscopy has been applied to compare the effect of the new organoamidoplatinum(ii) complexes [Pt{NH(p-HC6F4)CH2CH2N(p-HC6F4)}(py)(O2CR)] (R = C6F4 or 2,4,6-Me3C6H2) with cisplatin on cells from one cisplatin-sensitive ovarian cancer cell line (A2780) and one cisplatin-resistant ovarian cancer cell line (A2780R). After incubation of the cells with cisplatin, 1 and 2 for 48 hours, distinct changes were found in the ATR-FT-IR spectra. Comparison of the second derivative spectra suggests that 1 and 2 induce similar chemical changes in both cell lines, A2780 and A2780R, while cisplatin had a slight effect on A2780 and A2780R cells...
November 20, 2018: Analyst
Yalan Guo, Ke Wang, Xiaoyu Chen, Haihong Li, Qi Wan, Susan Morris-Natschke, Kuo-Hsiung Lee, Ying Chen
Twenty-five seco-4-methyl-DCK derivatives were designed, synthesized and evaluated for chemoreversal activity when combined with paclitaxel or vincristine in two drug-resistant cancer cell lines (A2780/T and KB-V) respectively. Most of the new compounds displayed moderate to significant MDR reversal activities in the P-gp overexpressing A2780/T and KB-V cells. Especially, compounds 7o and 7y showed the most potent chemosensitization activities with more than 496 and 735 reversal ratios at a concentration of 10 μM...
November 12, 2018: Bioorganic & Medicinal Chemistry Letters
Haixia Wang, Youjun Luo, Tiankui Qiao, Zhaoxia Wu, Zhonghua Huang
Luteolin, a polyphenolic flavone, has been demonstrated to exert anti-tumor activity in various cancer types. Cisplatin drug resistance is a major obstacle in the management of ovarian cancer. In the present study, we investigated the chemo-sensitizing effect of luteolin in both cisplatin-resistant ovarian cancer cell line and a mice xenotransplant model. In vitro, CCK-8 assay showed that luteolin inhibited cell proliferation in a dose-dependent manner, and luteolin enhanced anti-proliferation effect of cisplatin on cisplatin-resistant ovarian cancer CAOV3/DDP cells...
November 19, 2018: Journal of Ovarian Research
Z Ping Lin, Yong-Lian Zhu, Ying-Chun Lo, Jake Moscarelli, Amy Xiong, Yasmin Korayem, Pamela H Huang, Smith Giri, Patricia LoRusso, Elena S Ratner
PARP inhibitors target BRCA mutations and defective homologous recombination repair (HRR) for the treatment of epithelial ovarian cancer (EOC). However, the treatment of HRR-proficient EOC with PARP inhibitors remains challenging. The objective of this study was to determine whether the combination of triapine (ribonucleotide reductase inhibitor), cediranib (vascular endothelial growth factor receptor tyrosine kinase inhibitor), and the PARP inhibitor olaparib synergized against BRCA wild-type and HRR-proficient EOC in xenograft mouse models...
2018: PloS One
Siwei Liu, Bingyu Zou, Tian Tian, Xiaohui Luo, Banyun Mao, Xun Zhang, Huajiang Lei
To determine how the lncRNA FER1L4 in ovarian cancer cells influences paclitaxel (PTX) resistance, we examined the expression level of FER1L4 in human ovarian epithelial cell lines IOSE80 and HOSEpiC and human ovarian cancer cell lines OVCAR-3, Caov-3, and SKOV3 through RNA isolation and quantitative polymerase chain reaction (qRT-PCR). SKOV3 cell lines were treated with PTX. The cell survival rate and apoptosis rate of SKOV3 and SKOV3-PR at different PTX dose levels were evaluated. Next, qRT-PCR was performed to detect the expression of FER1L4 in SKOV3 and SKOV3-PR cell lines...
November 15, 2018: Journal of Cellular Biochemistry
Ying Jiang, Jing Jiang, Haiqing Jia, Zhiwei Qiao, Jingru Zhang
BACKGROUND/AIMS: In platinum-based chemotherapy for ovarian cancer, acquired drug resistance is a frequent occurrence. Because recent studies have demonstrated that dysregulation of microRNAs (miRNAs) is partly responsible for the induction of acquired drug resistance in cancers, we hypothesized that correcting the dysregulation of key miRNAs would reverse the acquired resistance to platinum-based drugs in ovarian cancer. METHODS: Cisplatin-resistant SKOV3 and A2780 ovarian cancer cell lines (SKOV3-R and A2780-R, respectively) were established by long-term exposure to cisplatin...
2018: Cellular Physiology and Biochemistry
Shou Li, Xiaoyun Zhao, Shijie Chang, Yanqiu Li, Min Guo, Yifu Guan
ERp57 has been identified to be associated with the chemoresistance of human ovarian cancer. However, its biological roles in the chemoresistance phenotype remain unclear. In the present study, the association of ERp57 with paclitaxel‑resistant cellular behavior was investigated and the sensitivity enhancement of chemoresistant human ovarian cancer cells to paclitaxel was examined using ERp57‑small interfering (si)RNA silencing. Cell viability, cell proliferation, cell apoptosis and cell migration were detected using an MTT assay, clonogenic assay, flow cytometry analysis and transwell assay...
January 2019: International Journal of Oncology
Zhi Huang, Wei Zhou, Yongtao Li, Mei Cao, Tianqi Wang, Yakun Ma, Qingxiang Guo, Xin Wang, Chao Zhang, Chenglan Zhang, Wenzhi Shen, Yanhua Liu, Yanan Chen, Jianyu Zheng, Shengyong Yang, Yan Fan, Rong Xiang
Despite initial progress in preclinical models, most known histone deacetylase inhibitors (HDACis) used as a single agent have failed to show clinical benefits in nearly all types of solid tumours. Hence, the efficacy of HDACis in solid tumours remains uncertain. Herein, we developed a hybrid HDAC inhibitor that sensitized solid tumours to HDAC-targeted treatment. Methods: A hybrid molecule, Roxyl-zhc-84 was designed and synthesized with novel architecture. The pharmacokinetics and toxicity of Roxyl-zhc-84 were analysed...
2018: Theranostics
Parvin Ataie-Kachoie, Krishna Pillai, Samina Badar, Javed Akhter, David Lawson Morris
Ovarian cancer is a lethal disease since treated patients often die from relapse. Resistance to current treatment regime involving doxorubicin and gemcitabine is well known. Hence, we set forth to develop a more effective therapy by combining current treatment drugs with monepantel, an antihelminth drug with proven anticancer effect. In vitro cytotoxicity were first investigated with pegylated liposomal doxorubicin (PLD), gemcitabine, monepantel as single agents and then in combination with monepantel on ovarian tumor cells...
2018: American Journal of Cancer Research
Leilei Niu, Hua Ni, Yingzi Hou, Quan Du, Hua Li
Drug-resistance of platinum remains a big challenge for effective treatment of patients with ovarian cancer. MicroRNAs (miRNAs) act as post-transcriptional regulators of gene expression and are associated with multi-drug resistance. Our study aims on identifying role of miRNAs in drug-resistance of platinum in ovarian cancer. In present study, we compared the expression profiles of miRNAs between three pairs of platinum-resistant and platinum-sensitive ovarian tissues and found that miR-509-3p was significantly down-regulated in cisplatin-resistant ovarian cancer tissues...
November 5, 2018: Gene
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