scholarly journals VAV3 Overexpressed in Cancer Stem Cells Is a Poor Prognostic Indicator in Ovarian Cancer Patients

2015 ◽  
Vol 24 (13) ◽  
pp. 1521-1535 ◽  
Author(s):  
Ah-Young Kwon ◽  
Gwang-Il Kim ◽  
Ju-Yeon Jeong ◽  
Ji-Ye Song ◽  
Kyu-Beom Kwack ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Patients ◽  
Prognostic Indicator ◽  
Poor Prognostic Indicator

scholarly journals Cancer stem cells from epithelial ovarian cancer patients privilege oxidative phosphorylation, and resist glucose deprivation

Oncotarget ◽  
2014 ◽  
Vol 5 (12) ◽  
pp. 4305-4319 ◽  
Author(s):  
Anna Pastò ◽  
Chiara Bellio ◽  
Giorgia Pilotto ◽  
Vincenzo Ciminale ◽  
Micol Silic-Benussi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Oxidative Phosphorylation ◽  
Epithelial Ovarian Cancer ◽  
Cancer Patients ◽  
Glucose Deprivation

Ovarian cancer stem cells (OCSCs): Therapy for advanced chemoresistant ovarian cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16542-e16542
Author(s):  
Prattusha Sengupta ◽  
Sudeshna Gangopadhyay ◽  
Saubhik Sengupta ◽  
Ujjal Kanti Ray ◽  
Ashis Mukhopadhyay
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Drug Sensitivity ◽  
Ex Vivo ◽  
Cancer Site ◽  
Chemotherapeutic Drugs ◽  
Ovarian Cancer Stem Cells

e16542 Background: Invasive and mesenchymal property of Ovarian Cancer Stem Cells (OCSCs)with CD44+/CD133+has made them promising target for targeted treatment. Chemotherapy treatment uses medicine to weaken and destroy cancer cells in body, including cells at original cancer site and any cancer cells that may have spread to another part of body. Chemotherapeutic drugs for advanced chemo-resistant ovarian cancer are yet to be well defined. Combination of drugs is also not fully known. Our objective is to define chemotherapeutic drugs and its action in OCSC which is the major reason for chemo resistance in case of advanced chemo-resistant ovarian cancer patients. Methods: A total of twenty biopsy proven advanced chemo-resistant ovarian cancer patients in the age group of 22-36 years were selected randomly and tested for CD44/CD133 via flow cytometry. Isolated OCSCs were cultured for ex vivo drug sensitivity towards platinum, anthracyclin, docetaxel, rapamycin, sunitinib, sorafenib and gefitinib. Correlation was drawn between cell differentiations, % of stem cells and drug response. Accordingly chemotherapy was designed for a particular patient. Results: We detected OCSCs in 90% of cases. Among positive samples ex vivo drug sensitivity was seen in 4(20%) to rapamycin, 1(5%) to sunitinib, 1(5%) to sorafenib, 1(5%) to gefitinib, 3(15%) to platinum, 1(5%) to anthracyclin, 1(5%) to docetaxel and rest showed no sensitivity to any drug. Conclusions: Thus primary aim to target OCSCs at onset of tumors in ovarian cancer patients to control metastasis and relapse of disease was somewhat obtained. Most interestingly, we found that the chemotherapeutic drugs which were less prescribed for ovarian cancer showed greater sensitivity in comparison to the widely used ones. We like to do animal model study followed by phase I, II and III human clinical trial to establish our hypothesis for better management of chemo-resistant ovarian cancer.

scholarly journals Repositioning Trimebutine Maleate as a Cancer Treatment Targeting Ovarian Cancer Stem Cells

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 918
Author(s):  
Heejin Lee ◽  
Oh-Bin Kwon ◽  
Jae-Eon Lee ◽  
Yong-Hyun Jeon ◽  
Dong-Seok Lee ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Ovarian Cancer Cells ◽  
Therapeutic Drug ◽  
G1 Arrest ◽  
Dead Cell ◽  
Trimebutine Maleate ◽  
Simultaneous Inhibition

The overall five-year survival rate for late-stage patients of ovarian cancer is below 29% due to disease recurrence and drug resistance. Cancer stem cells (CSCs) are known as a major contributor to drug resistance and recurrence. Accordingly, therapies targeting ovarian CSCs are needed to overcome the limitations of present treatments. This study evaluated the effect of trimebutine maleate (TM) targeting ovarian CSCs, using A2780-SP cells acquired by a sphere culture of A2780 epithelial ovarian cancer cells. TM is indicated as a gastrointestinal motility modulator and is known to as a peripheral opioid receptor agonist and a blocker for various channels. The GI50 of TM was approximately 0.4 µM in A2780-SP cells but over 100 µM in A2780 cells, demonstrating CSCs specific growth inhibition. TM induced G0/G1 arrest and increased the AV+/PI+ dead cell population in the A2780-SP samples. Furthermore, TM treatment significantly reduced tumor growth in A2780-SP xenograft mice. Voltage gated calcium channels (VGCC) and calcium-activated potassium channels (BKCa) were overexpressed on ovarian CSCs and targeted by TM; inhibition of both channels reduced A2780-SP cells viability. TM reduced stemness-related protein expression; this tendency was reproduced by the simultaneous inhibition of VGCC and BKCa compared to single channel inhibition. In addition, TM suppressed the Wnt/β-catenin, Notch, and Hedgehog pathways which contribute to many CSCs characteristics. Specifically, further suppression of the Wnt/β-catenin pathway by simultaneous inhibition of BKCa and VGCC is necessary for the effective and selective action of TM. Taken together, TM is a potential therapeutic drug for preventing ovarian cancer recurrence and drug resistance.

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.

scholarly journals Novel Therapeutic Strategies for Ovarian Cancer Stem Cells

2020 ◽  
Vol 10 ◽  
Author(s):  
Nastassja Terraneo ◽  
Francis Jacob ◽  
Anna Dubrovska ◽  
Jürgen Grünberg
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Therapeutic Strategies ◽  
Ovarian Cancer Stem Cells ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

scholarly journals Modeling the Treatment of Glioblastoma Multiforme and Cancer Stem Cells with Ordinary Differential Equations

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Kristen Abernathy ◽  
Jeremy Burke
Keyword(s):  
Stem Cells ◽  
Glioblastoma Multiforme ◽  
Cancer Therapy ◽  
Cancer Stem Cells ◽  
Differential Equations ◽  
Ordinary Differential Equations ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Tumor Recurrence ◽  
Common Event

Despite improvements in cancer therapy and treatments, tumor recurrence is a common event in cancer patients. One explanation of recurrence is that cancer therapy focuses on treatment of tumor cells and does not eradicate cancer stem cells (CSCs). CSCs are postulated to behave similar to normal stem cells in that their role is to maintain homeostasis. That is, when the population of tumor cells is reduced or depleted by treatment, CSCs will repopulate the tumor, causing recurrence. In this paper, we study the application of the CSC Hypothesis to the treatment of glioblastoma multiforme by immunotherapy. We extend the work of Kogan et al. (2008) to incorporate the dynamics of CSCs, prove the existence of a recurrence state, and provide an analysis of possible cancerous states and their dependence on treatment levels.

Abstract AP26: CANCER STEM CELLS: DISTINCT SEEDS FOR RECURRENT OVARIAN CANCER

2019 ◽  
Author(s):  
Nuzhat Ahmed ◽  
Ruth Escalona ◽  
Elif Kadife ◽  
Dilys Leung ◽  
George Kannourakis
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Recurrent Ovarian Cancer

scholarly journals HER2 decreases drug sensitivity of ovarian cancer cells via inducing stem cell-like property in an NFκB-dependent way

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Wenxiang Wang ◽  
Yuxia Gao ◽  
Jing Hai ◽  
Jing Yang ◽  
Shufeng Duan
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Drug Sensitivity ◽  
Ovarian Cancer Cells ◽  
Her2 Overexpression ◽  
Her2 Positive ◽  
Ovarian Cancer Stem Cells

Abstract Increasing evidence shows that cancer stem cells are responsible for drug resistance and relapse of tumors. In breast cancer, human epidermal growth factor receptor 2 (HER2) induces Herceptin resistance by inducing cancer stem cells. In the present study, we explored the effect of HER2 on cancer stem cells induction and drug sensitivity of ovarian cancer cell lines. First, 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. Second, we found that NFκB inhibition by specific inhibitor JSH23 or siRNA targetting subunit p65 dramatically impaired the induction of ovarian cancer stem cells by HER2, indicating that NFκB mediated HER2-induced ovarian cancer stem cells. Third, we found that HER2 KD significantly attenuated the tumorigenicity of ovarian cancer cells. Further, we found that HER2 inhibition increased drastically the sensitivity of ovarian cancer cells to doxorubicin (DOX) or paclitaxel (PTX). Finally, we examined the correlation between HER2 status and stem cell-related genes expression in human ovarian tumor tissues, and found that expressions of OCT4, COX2, and Nanog were higher in HER2 positive tumors than in HER2 negative tumors. Consistently, the 5-year tumor-free survival rate of HER2 positive patients was dramatically lower than HER2 negative patients. Taken together, our data indicate that HER2 decreases drug sensitivity of ovarian cancer cells via inducing stem cell-like property.

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