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Invasive ovarian tumor platinum resistance

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https://www.readbyqxmd.com/read/28486623/platinum-induced-mitochondrial-dna-mutations-confer-lower-sensitivity-to-paclitaxel-by-impairing-tubulin-cytoskeletal-organization
#1
Giulia Girolimetti, Flora Guerra, Luisa Iommarini, Ivana Kurelac, Daniele Vergara, Michele Maffia, Michele Vidone, Laura Benedetta Amato, Giulia Leone, Sabrina Dusi, Valeria Tiranti, Anna Myriam Perrone, Cecilia Bucci, Anna Maria Porcelli, Giuseppe Gasparre
Development of chemoresistance is a cogent clinical issue in oncology, whereby combination of anticancer drugs is usually preferred also to enhance efficacy. Paclitaxel (PTX), combined with carboplatin, represents the standard first-line chemotherapy for different types of cancers. We here depict a double-edge role of mitochondrial DNA (mtDNA) mutations induced in cancer cells after treatment with platinum. MtDNA mutations were positively selected by PTX, and they determined a decrease in the mitochondrial respiratory function, as well as in proliferative and tumorigenic potential, in terms of migratory and invasive capacity...
May 9, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28482906/foxm1-expression-is-significantly-associated-with-chemotherapy-resistance-and-adverse-prognosis-in-non-serous-epithelial-ovarian-cancer-patients
#2
Renata A Tassi, Paola Todeschini, Eric R Siegel, Stefano Calza, Paolo Cappella, Laura Ardighieri, Moris Cadei, Mattia Bugatti, Chiara Romani, Elisabetta Bandiera, Laura Zanotti, Laura Tassone, Donatella Guarino, Concetta Santonocito, Ettore D Capoluongo, Luca Beltrame, Eugenio Erba, Sergio Marchini, Maurizio D'Incalci, Carla Donzelli, Alessandro D Santin, Sergio Pecorelli, Enrico Sartori, Eliana Bignotti, Franco Odicino, Antonella Ravaggi
BACKGROUND: Epithelial ovarian cancer (EOC) is a spectrum of different diseases, which makes their treatment a challenge. Forkhead box M1 (FOXM1) is an oncogene aberrantly expressed in many solid cancers including serous EOC, but its role in non-serous EOCs remains undefined. We examined FOXM1 expression and its correlation to prognosis across the three major EOC subtypes, and its role in tumorigenesis and chemo-resistance in vitro. METHODS: Gene signatures were generated by microarray for 14 clear-cell and 26 endometrioid EOCs, and 15 normal endometrium snap-frozen biopsies...
May 8, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28446239/dasatinib%C3%A2-%C3%A2-gefitinib-a-non-platinum-based-combination-with-enhanced-growth-inhibitory-anti-migratory-and-anti-invasive-potency-against-human-ovarian-cancer-cells
#3
Benoît Thibault, Bertrand Jean-Claude
BACKGROUND: Ovarian cancer is the leading cause of death for gynecological cancers and the 6th cause of women cancer death in developed countries. The late stage detection, the peritoneal dissemination and the acquisition of resistance against carboplatin are the main reasons to explain this poor prognosis and strengthen the need of alternative treatments to improve the management of ovarian cancer and/or to sensitize tumors to platinum salts. Epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (Met) and cellular Src kinase (c-Src) are crucial kinases implied in ovarian tumor growth, survival, invasion and resistance to carboplatin...
April 26, 2017: Journal of Ovarian Research
https://www.readbyqxmd.com/read/28420874/therapeutic-targeting-using-tumor-specific-peptides-inhibits-long-non-coding-rna-hotair-activity-in-ovarian-and-breast-cancer
#4
Ali R Özeş, Yinu Wang, Xingyue Zong, Fang Fang, Jay Pilrose, Kenneth P Nephew
Long non-coding RNAs (lncRNAs) play key roles in human diseases, including cancer. Functional studies of the lncRNA HOTAIR (HOX transcript antisense RNA) provide compelling evidence for therapeutic targeting of HOTAIR in cancer, but targeting lncRNAs in vivo has proven to be difficult. In the current study, we describe a peptide nucleic acids (PNA)-based approach to block the ability of HOTAIR to interact with EZH2 and subsequently inhibit HOTAIR-EZH2 activity and resensitize resistant ovarian tumors to platinum...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28263384/mesothelium-expression-of-vascular-cell-adhesion-molecule-1-vcam-1-is-associated-with-an-unfavorable-prognosis-in-epithelial-ovarian-cancer-eoc
#5
Jennifer M Scalici, Sanja Arapovic, Erin J Saks, Kristen A Atkins, Gina Petroni, Linda R Duska, Jill K Slack-Davis
BACKGROUND: Mesothelium vascular cell adhesion molecule-1 (VCAM-1) expression in the metastatic epithelial ovarian cancer (EOC) microenvironment is induced by tumor and mediates tumor cell invasion. VCAM-1 imaging suggests expression during treatment is an indicator of platinum resistance. Here, we assess the potential prognostic significance of mesothelium VCAM-1 expression and prospectively evaluate whether soluble VCAM-1 (sVCAM-1) is a surrogate for mesothelium expression. METHODS: A retrospective review of EOC patients was performed to evaluate outcomes with mesothelium VCAM-1 expression determined by immunohistochemistry of peritoneum or omentum specimens...
May 15, 2017: Cancer
https://www.readbyqxmd.com/read/27977010/trap1-downregulation-in-human-ovarian-cancer-enhances-invasion-and-epithelial-mesenchymal-transition
#6
Maria R Amoroso, Danilo S Matassa, Ilenia Agliarulo, Rosario Avolio, Haonan Lu, Lorenza Sisinni, Giacomo Lettini, Hani Gabra, Matteo Landriscina, Franca Esposito
Ovarian cancer (OC) is the second leading cause of gynecological cancer death worldwide. Although the list of biomarkers is still growing, molecular mechanisms involved in OC development and progression remain elusive. We recently demonstrated that lower expression of the molecular chaperone TRAP1 in OC patients correlates with higher tumor grade and stage, and platinum resistance. Herein we show that TRAP1 is often deleted in high-grade serous OC patients (N=579), and that TRAP1 expression is correlated with the copy number, suggesting this could be one of the driving mechanisms for the loss of TRAP1 expression in OC...
December 15, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27743201/downregulation-of-foxo3-and-trim31-by-mir-551b-in-side-population-promotes-cell-proliferation-invasion-and-drug-resistance-of-ovarian-cancer
#7
Zhentong Wei, Yan Liu, Yishu Wang, Yandong Zhang, Qinghua Luo, Xiaxia Man, Feng Wei, Xiaowei Yu
Ovarian cancer (OVCa) stem cells are associated with tumor growth, metastasis, and recurrence, which are driving forces behind a majority of the OVCa-related mortality. This subpopulation of cancer cells are characterized by uncontrolled proliferation, high invasiveness, and resistance against the current platinum-based therapy. Thus, targeting OVCa cancer stem cells has been focused in recent therapeutic development. Isolation and purification of cancer stem cells are, however, challenging for the lack of sensitive and specific markers...
November 2016: Medical Oncology
https://www.readbyqxmd.com/read/27648354/paclitaxel-targets-vegf-mediated-angiogenesis-in-ovarian-cancer-treatment
#8
Bin Ai, Zhixin Bie, Shuai Zhang, Ailing Li
Ovarian cancer is one of the gynecologic cancers with the highest mortality, wherein vascular endothelial growth factor (VEGF) is involved in regulating tumor vascularization, growth, migration, and invasion. VEGF-mediated angiogenesis in tumors has been targeted in various cancer treatments, and anti-VEGF therapy has been used clinically for treatment of several types of cancer. Paclitaxel is a natural antitumor agent in the standard front-line treatment that has significant efficiency to treat advanced cancers, including ovarian cancer...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27415751/anticancer-potential-of-diarylidenyl-piperidone-derivatives-ho-4200-and-h-4318-in-cisplatin-resistant-primary-ovarian-cancer
#9
Adam C ElNaggar, Uksha Saini, Shan Naidu, Ross Wanner, Millie Sudhakar, John Fowler, Masaki Nagane, Periannan Kuppusamy, David E Cohn, Karuppaiyah Selvendiran
We have previously developed a novel class of bi-functional compounds based on a diarylidenyl-piperidone (DAP) backbone conjugated to an N-hydroxypyrroline (-NOH; a nitroxide precursor) group capable of selectively inhibiting STAT3 activation, translocation, and DNA binding activity. HO-4200 and H-4318 are 2 such derivatives capable of inducing apoptosis in ovarian cancer cells through this mechanism and demonstrated efficacy in platinum resistant primary ovarian cancer cell populations and tumor tissues. The improved absorption and cellular uptake of HO-4200 by cancer cells was determined using optical and electron paramagnetic resonance spectrometry...
October 2, 2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27292260/elevated-stat3-expression-in-ovarian-cancer-ascites-promotes-invasion-and-metastasis-a-potential-therapeutic-target
#10
U Saini, S Naidu, A C ElNaggar, H K Bid, J J Wallbillich, K Bixel, C Bolyard, A A Suarez, B Kaur, P Kuppusamy, J Hays, P J Goodfellow, D E Cohn, K Selvendiran
Although activation of the STAT3 pathway has been associated with tumor progression in a wide variety of cancer types (including ovarian cancer), the precise mechanism of invasion and metastasis due to STAT3 are not fully delineated in ovarian cancer. We found that pSTAT3 Tyr705 is constitutively activated in patient ascites and ascites-derived ovarian cancer cells (ADOCCs), and the range of STAT3 expression could be very high to low. In vivo transplantation of ADOCCs with high pSTAT3 expression into the ovarian bursa of mice resulted in a large primary tumor and widespread peritoneal metastases...
January 12, 2017: Oncogene
https://www.readbyqxmd.com/read/27223082/tunneling-nanotube-formation-is-stimulated-by-hypoxia-in-ovarian-cancer-cells
#11
Snider Desir, Elizabeth L Dickson, Rachel I Vogel, Venugopal Thayanithy, Phillip Wong, Deanna Teoh, Melissa A Geller, Clifford J Steer, Subbaya Subramanian, Emil Lou
In this study, we demonstrated that hypoxic conditions stimulated an increase in tunneling nanotube (TNT) formation in chemoresistant ovarian cancer cells (SKOV3, C200).We found that suppressing the mTOR pathway using either everolimus or metformin led to suppression of TNT formation in vitro, verifying TNTs as a potential target for cancer-directed therapy. Additionally, TNT formation was detected in co-cultures including between platinum-resistant SKOV3 cells, between SKOV3 cells and platinum-chemosensitive A2780 cells, and between SKOV3 cells cultured with benign ovarian epithelial (IOSE) cells; these findings indicate that TNTs are novel conduits for malignant cell interactions and tumor cell interactions with other cells in the microenvironment...
July 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27170529/mechanistic-nanotherapeutic-approach-based-on-sirna-mediated-dj-1-protein-suppression-for-platinum-resistant-ovarian-cancer
#12
Canan Schumann, Stephanie Chan, Oleh Khalimonchuk, Shannon Khal, Vitaliya Moskal, Vidhi Shah, Adam W G Alani, Olena Taratula, Oleh Taratula
We report an efficient therapeutic modality for platinum resistant ovarian cancer based on siRNA-mediated suppression of a multifunctional DJ-1 protein that is responsible for the proliferation, growth, invasion, oxidative stress, and overall survival of various cancers. The developed therapeutic strategy can work alone or in concert with a low dose of the first line chemotherapeutic agent cisplatin, to elicit a maximal therapeutic response. To achieve an efficient DJ-1 knockdown, we constructed the polypropylenimine dendrimer-based nanoplatform targeted to LHRH receptors overexpressed on ovarian cancer cells...
June 6, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27100483/the-role-of-annexin-a4-in-cancer
#13
Houshan Yao, Chang Sun, Zhiqian Hu, Weijun Wang
Annexin A4 (ANXA4) is a member of the annexin family that binds to both calcium ions and phospholipids. Studies indicate that ANXA4 modulates membrane permeability and membrane trafficking, participates in cellular growth and apoptosis, enhances tumor invasion and promotes anti-tumor drug resistance. The overexpression of ANXA4 has been identified in various clinical epithelial tumors including: lung, gastric, colorectal, pancreatic, gallbladder, breast, renal, ovarian, laryngeal, and prostate cancers. In addition, upregulation and nuclear translocation of ANXA4 have been observed in the progression of colorectal cancer and ovarian serous carcinoma...
2016: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27049921/microrna-520g-promotes-epithelial-ovarian-cancer-progression-and-chemoresistance-via-dapk2-repression
#14
Jing Zhang, Lei Liu, Yunyan Sun, Jiandong Xiang, Dongmei Zhou, Li Wang, Huali Xu, Xiaoming Yang, Na Du, Meng Zhang, Qin Yan, Xiaowei Xi
The lack of efficient tumor progression and chemoresistance indicators leads to high mortality in epithelial ovarian cancer (EOC) patients. Dysregulated miR-520g expression is involved in these processes in hepatic and colorectal cancers. In this study, we found that miR-520g expression gradually increased across normal, benign, borderline and EOC tissues. High miR-520g expression promoted tumor progression and chemoresistance to platinum-based chemotherapy, and reduced survival in EOC patients. miR-520g upregulation increased EOC cell proliferation, induced cell cycle transition and promoted cell invasion, while miR-520g downregulation inhibited tumor-related functions...
May 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/26899534/selective-inhibition-of-tumor-cell-associated-vacuolar-atpase-a2-isoform-overcomes-cisplatin-resistance-in-ovarian-cancer-cells
#15
Arpita Kulshrestha, Gajendra K Katara, Jordyn Ginter, Sahithi Pamarthy, Safaa A Ibrahim, Mukesh K Jaiswal, Corina Sandulescu, Ramayee Periakaruppan, James Dolan, Alice Gilman-Sachs, Kenneth D Beaman
Development of resistance to platinum compounds significantly hinders successful ovarian cancer (OVCA) treatment. In tumor cells, dysregulated pH gradient across cell membranes is a key physiological mechanism of metastasis/chemo-resistance. These pH alterations are mediated by aberrant activation of key multi-subunit proton pumps, Vacuolar-ATPases (V-ATPases). In tumor cells, its 'a2' isoform (V-ATPase-V0a2) is a component of functional plasma-membrane complex and promotes tumor invasion through tumor-acidification and immuno-modulation...
June 2016: Molecular Oncology
https://www.readbyqxmd.com/read/26679603/rad6-upregulation-promotes-stem-cell-like-characteristics-and-platinum-resistance-in-ovarian-cancer
#16
Ranganatha R Somasagara, Kaushlendra Tripathi, Sebastian M Spencer, David W Clark, Reagan Barnett, Lavanya Bachaboina, Jennifer Scalici, Rodney P Rocconi, Gary A Piazza, Komaraiah Palle
Ovarian cancer is the fifth most deadly cancer in women in the United States and despite advances in surgical and chemotherapeutic treatments survival rates have not significantly improved in decades. The poor prognosis for ovarian cancer patients is largely due to the extremely high (80%) recurrence rate of ovarian cancer and because the recurrent tumors are often resistant to the widely utilized platinum-based chemotherapeutic drugs. In this study, expression of Rad6, an E2 ubiquitin-conjugating enzyme, was found to strongly correlate with ovarian cancer progression...
January 15, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/26675258/mir-30a-inhibits-endothelin-a-receptor-and-chemoresistance-in-ovarian-carcinoma
#17
Rosanna Sestito, Roberta Cianfrocca, Laura Rosanò, Piera Tocci, Elisa Semprucci, Valeriana Di Castro, Valentina Caprara, Gabriella Ferrandina, Andrea Sacconi, Giovanni Blandino, Anna Bagnato
Drug resistance remains the major clinical barrier to successful treatment in epithelial ovarian carcinoma (EOC) patients, and the evidence of microRNA involvement in drug resistance has been recently emerging. Endothelin-1 (ET-1)/ETA receptor (ETAR) axis is aberrantly activated in chemoresistant EOC cells and elicits pleiotropic effects promoting epithelial-to-mesenchymal transition (EMT) and the acquisition of chemoresistance. However, the relationship between ETAR and miRNA is still unknown. Hence, in this study we evaluated whether dysregulation of miRNA might enhance ETAR expression in sensitive and resistant EOC cells...
January 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/26458502/loss-of-autophagy-related-protein-beclin-1-may-define-poor-prognosis-in-ovarian-clear-cell-carcinomas
#18
Hiroshi Katagiri, Kentaro Nakayama, Sultana Razia, Kohei Nakamura, Emi Sato, Tomoka Ishibashi, Masako Ishikawa, Kouji Iida, Noriyoshi Ishikawa, Yoshiro Otsuki, Satoru Nakayama, Satoru Kyo
The aim of the present study was to clarify the role of autophagy in cisplatin (CDDP) sensitivity in OCCCs and the role of Beclin 1 in OCCC progression. Autophagy was measured using: i) western blot analysis of LC3 and p62 and ii) microscopic observation of GFP-LC3 puncta. Autophagy was suppressed using chloroquine and Beclin 1 siRNA. Surgical specimens were examined for Beclin 1 protein expression by immunohistochemistry. The correlations between the loss of Beclin 1 expression and clinicopathological characteristics, prognosis and chemosensitivity were investigated...
December 2015: International Journal of Oncology
https://www.readbyqxmd.com/read/26119935/yap-activation-protects-urothelial-cell-carcinoma-from-treatment-induced-dna-damage
#19
E Ciamporcero, H Shen, S Ramakrishnan, S Yu Ku, S Chintala, L Shen, R Adelaiye, K M Miles, C Ullio, S Pizzimenti, M Daga, G Azabdaftari, K Attwood, C Johnson, J Zhang, G Barrera, R Pili
Current standard of care for muscle-invasive urothelial cell carcinoma (UCC) is surgery along with perioperative platinum-based chemotherapy. UCC is sensitive to cisplatin-based regimens, but acquired resistance eventually occurs, and a subset of tumors is intrinsically resistant. Thus, there is an unmet need for new therapeutic approaches to target chemotherapy-resistant UCC. Yes-associated protein (YAP) is a transcriptional co-activator that has been associated with bladder cancer progression and cisplatin resistance in ovarian cancer...
March 24, 2016: Oncogene
https://www.readbyqxmd.com/read/25750333/cyclin-a-correlates-with-yb1-progression-and-resistance-to-chemotherapy-in-human-epithelial-ovarian-cancer
#20
Marek Cybulski, Bożena Jarosz, Andrzej Nowakowski, Witold Jeleniewicz, Elżbieta Kutarska, Wiesława Bednarek, Andrzej Stepulak
BACKGROUND: Cyclin A is a cell-cycle regulatory gene and its overexpression promotes tumor cell growth. Y-Box-binding protein 1 (YB1) is a transcription/translation factor involved in tumor growth, invasion, and drug resistance. We investigated whether an association exists between protein products of these genes in epithelial ovarian cancer (EOC) specimens and clinicopathological parameters, patient response and EOC sensitivity to platinum-based first-line chemotherapy. PATIENTS AND METHODS: Cyclin A and YB1 expression were analyzed by immunohistochemistry in 54 human primary EOC tissues...
March 2015: Anticancer Research
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