scholarly journals CCL20 Promotes Ovarian Cancer Chemotherapy Resistance by Regulating ABCB1 Expression

2019 ◽  
Vol 44 (1) ◽  
pp. 21-28 ◽  
Author(s):  
Shan Su ◽  
Xueqin Sun ◽  
Qinghua Zhang ◽  
Zhe Zhang ◽  
Ju Chen
Keyword(s):  
Ovarian Cancer ◽  
Cancer Chemotherapy ◽  
Chemotherapy Resistance

Mitochondrial integration and ovarian cancer chemotherapy resistance

2021 ◽  
pp. 112549
Author(s):  
Luyan Shen ◽  
Meihui Xia ◽  
Yu Zhang ◽  
Haoge Luo ◽  
Delu Dong ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Chemotherapy ◽  
Chemotherapy Resistance

scholarly journals Human carcinoma-associated mesenchymal stem cells promote ovarian cancer chemotherapy resistance via a BMP4/HH signaling loop

Oncotarget ◽  
2016 ◽  
Vol 7 (6) ◽  
pp. 6916-6932 ◽  
Author(s):  
Lan G. Coffman ◽  
Yun-Jung Choi ◽  
Karen McLean ◽  
Benjamin L. Allen ◽  
Marina Pasca di Magliano ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cancer Chemotherapy ◽  
Chemotherapy Resistance ◽  
Human Carcinoma ◽  
Hh Signaling

scholarly journals Characterization of SOX2, OCT4 and NANOG in Ovarian Cancer Tumor-Initiating Cells

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 262
Author(s):  
Mikella Robinson ◽  
Samuel F. Gilbert ◽  
Jennifer A. Waters ◽  
Omar Lujano-Olazaba ◽  
Jacqueline Lara ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Chemotherapy Resistance ◽  
Tumor Initiating Cells ◽  
In Vivo Experiments ◽  
Nanog Expression ◽  
Ovarian Cancer Cell Lines ◽  
Cancer Tumor ◽  
Early Tumor ◽  
Cycle Regulation

The identification of tumor-initiating cells (TICs) has traditionally relied on surface markers including CD133, CD44, CD117, and the aldehyde dehydrogenase (ALDH) enzyme, which have diverse expression across samples. A more reliable indication of TICs may include the expression of embryonic transcription factors that support long-term self-renewal, multipotency, and quiescence. We hypothesize that SOX2, OCT4, and NANOG will be enriched in ovarian TICs and may indicate TICs with high relapse potential. We evaluated a panel of eight ovarian cancer cell lines grown in standard 2-D culture or in spheroid-enriching 3-D culture, and correlated expression with growth characteristics, TIC marker expression, and chemotherapy resistance. RNA-sequencing showed that cell cycle regulation pathways involving SOX2 were elevated in 3-D conditions. HGSOC lines had longer doubling-times, greater chemoresistance, and significantly increased expression of SOX2, OCT4, and NANOG in 3-D conditions. CD117+ or ALDH+/CD133+ cells had increased SOX2, OCT4, and NANOG expression. Limiting dilution in in vivo experiments implicated SOX2, but not OCT4 or NANOG, with early tumor-initiation. An analysis of patient data suggested a stronger role for SOX2, relative to OCT4 or NANOG, for tumor relapse potential. Overall, our findings suggest that SOX2 may be a more consistent indicator of ovarian TICs that contribute to tumor repopulation following chemotherapy. Future studies evaluating SOX2 in TIC biology will increase our understanding of the mechanisms that drive ovarian cancer relapse.

scholarly journals In Ovarian Cancer Multicellular Spheroids, Platelet Releasate Promotes Growth, Expansion of ALDH+ and CD133+ Cancer Stem Cells, and Protection against the Cytotoxic Effects of Cisplatin, Carboplatin and Paclitaxel

2021 ◽  
Vol 22 (6) ◽  
pp. 3019
Author(s):  
Naike Casagrande ◽  
Cinzia Borghese ◽  
Francesco Agostini ◽  
Cristina Durante ◽  
Mario Mazzucato ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Chemotherapy Resistance ◽  
Multicellular Spheroids ◽  
Multicellular Tumor Spheroid ◽  
Activated Platelets ◽  
Clinical Responses ◽  
Bona Fide ◽  
Paclitaxel Treatment

A high platelet count is associated with a poor prognosis in ovarian cancer (OvCa). Despite good clinical responses with platinating agents in combination with taxanes, numerous OvCa patients relapse due to chemotherapy resistance. Here, we report that treatment of OvCa cells A2780, OVCAR5 and MDAH with releasate from activated platelets (PR) promoted multicellular tumor spheroid (MCTS) formation. These OvCa-MCTSs had increased percentages of CD133+ and aldehyde dehydrogenase (ALDH)+ cells, bona fide markers of OvCa cancer stem cells (CSCs). PR increased OVCAR5- and MDAH-MCTS viability and decreased the cytotoxic and pro-apoptotic effects of paclitaxel, cisplatin and carboplatin. PR increased the volume of spontaneously formed OVCAR8-MCTSs and counteracted their size reduction due to cisplatin, carboplatin and paclitaxel treatment. PR promoted the survival of ALDH+ and CD133+ OvCa cells during cisplatin, carboplatin and paclitaxel treatment. In conclusion, molecules and growth factors released by activated platelets (EGF, PDGF, TGF-β, IGF and CCL5) may protect tumor cells from chemotherapy by promoting the expansion of ALDH+ and CD133+ OvCa-CSCs, favoring drug resistance and tumor relapse.

Overexpression of dihydrodiol dehydrogenase is associated with cisplatin-based chemotherapy resistance in ovarian cancer patients

2005 ◽  
Vol 97 (1) ◽  
pp. 110-117 ◽  
Author(s):  
Yi-Jen Chen ◽  
Chiou-Chung Yuan ◽  
Kuan-Chih Chow ◽  
Peng-Hui Wang ◽  
Chiung-Ru Lai ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Chemotherapy Resistance ◽  
Dihydrodiol Dehydrogenase

Selective Inhibitors of Histone Deacetylase 10 (HDAC-10)

2021 ◽  
Vol 28 ◽  
Author(s):  
Eftiola Pojani ◽  
Daniela Barlocco
Keyword(s):  
Histone Deacetylase ◽  
Cancer Chemotherapy ◽  
Chemotherapy Resistance ◽  
Hdac Inhibitors ◽  
Selective Inhibition ◽  
Epigenetic Mechanism ◽  
Inhibitory Potency ◽  
Chemotherapy Drugs ◽  
Hydrogen Bond Interactions ◽  
Class I Hdacs

: Histone acetylation balance is one epigenetic mechanism controlling gene expression associated with disease progression. It has been observed that histone deacetylase 10 (HDAC-10) isozyme contributes to the chemotherapy resistance; in addition, the poor clinical outcome observed in patients with aggressive solid tumors, such as neuroblastoma, has been associated with its overexpression. Moreover, HDAC-10 selective inhibition suppresses the autophagic response, thus providing an improved risk-benefit profile compared to cytotoxic cancer chemotherapy drugs. On these bases, HDAC-10 is becoming an emerging target for drug design. Due to the rapid progress in the development of next-generation HDAC inhibitors, this review article aims to provide an overview on novel selective or dual HDAC-8/10 inhibitors, as new leads for cancer chemotherapy, able to avoid the severe side-effects of several actual approved “pan” HDAC inhibitors. A literature search was conducted in MedLine, PubMed, Caplus, SciFinder Scholar databases from 2015 to the present. Since the disclosure that the HDAC-6 inhibitor Tubastatin A was able to bind HDAC-10 efficiently, several related analogues were synthesized and tested. Both tricyclic (25-30) and bicyclic (31-42) derivatives were considered. The best pharmacological profile was shown by 36 (HDAC-10 pIC50 = 8.4 and pIC50 towards Class I HDACs from 5.2–6.4). In parallel, based on the evidence that high levels of HDAC-8 are a marker of poor prognosis in neuroblastoma treatment, dual HDAC-8/10 inhibitors were designed. The hydroxamic acid TH34 (HDAC-8 and 10 IC50 = 1.9 µM and 7.7 µM, respectively) and the hybrid derivatives 46d, 46e and 46g were the most promising both in terms of potency and selectivity. Literature surveys indicate several structural requirements for inhibitory potency and selectivity towards HDAC-10, e.g., electrostatic and/or hydrogen bond interactions with E274 and complementarity to the P(E,A) CE motif helix.

scholarly journals Newly developed dual topoisomerase inhibitor P8-D6 is highly active in ovarian cancer

2021 ◽  
Vol 13 ◽  
pp. 175883592110598
Author(s):  
Inken Flörkemeier ◽  
Tamara N. Steinhauer ◽  
Nina Hedemann ◽  
Magnus Ölander ◽  
Per Artursson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Topoisomerase I ◽  
Ex Vivo ◽  
Chemotherapy Resistance ◽  
Membrane Integrity ◽  
Three Dimensional ◽  
New Drugs ◽  
Highly Active ◽  
Gynaecologic Neoplasms

Background: Ovarian cancer (OvCa) constitutes a rare and highly aggressive malignancy and is one of the most lethal of all gynaecologic neoplasms. Due to chemotherapy resistance and treatment limitations because of side effects, OvCa is still not sufficiently treatable. Hence, new drugs for OvCa therapy such as P8-D6 with promising antitumour properties have a high clinical need. The benzo[ c]phenanthridine P8-D6 is an effective inductor of apoptosis by acting as a dual topoisomerase I/II inhibitor. Methods: In the present study, the effectiveness of P8-D6 on OvCa was investigated in vitro. In various OvCa cell lines and ex vivo primary cells, the apoptosis induction compared with standard therapeutic agents was determined in two-dimensional monolayers. Expanded by three-dimensional and co-culture, the P8-D6 treated cells were examined for changes in cytotoxicity, apoptosis rate and membrane integrity via scanning electron microscopy (SEM). Likewise, the effects of P8-D6 on non-cancer human ovarian surface epithelial cells and primary human hepatocytes were determined. Results: This study shows a significant P8-D6-induced increase in apoptosis and cytotoxicity in OvCa cells which surpasses the efficacy of well-established drugs like cisplatin or the topoisomerase inhibitors etoposide and topotecan. Non-cancer cells were affected only slightly by P8-D6. Moreover, no hepatotoxic effect in in vitro studies was detected. Conclusion: P8-D6 is a strong and rapid inductor of apoptosis and might be a novel treatment option for OvCa therapy.

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