scholarly journals In Preclinical Model of Ovarian Cancer, the SGK1 Inhibitor SI113 Counteracts the Development of Paclitaxel Resistance and Restores Drug Sensitivity

2019 ◽  
Vol 12 (8) ◽  
pp. 1045-1055 ◽  
Author(s):  
Lucia D'Antona ◽  
Vincenzo Dattilo ◽  
Giada Catalogna ◽  
Domenica Scumaci ◽  
Claudia Vincenza Fiumara ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Drug Sensitivity ◽  
Preclinical Model ◽  
Paclitaxel Resistance

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.

scholarly journals Ex vivo activity of cytotoxic drugs and targeted agents in small intestinal neuroendocrine tumors

2018 ◽  
Vol 25 (4) ◽  
pp. 471-480
Author(s):  
Kosmas Daskalakis ◽  
Olov Norlén ◽  
Andreas Karakatsanis ◽  
Per Hellman ◽  
Rolf Larsson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Drug Sensitivity ◽  
Kinase Inhibitors ◽  
Ex Vivo ◽  
Great Variability ◽  
Protein Kinase Inhibitors ◽  
Cytotoxic Drugs ◽  
Targeted Agents ◽  
Small Intestinal ◽  
Tumor Types

Small intestinal neuroendocrine tumors (SI-NETs) are generally considered resistant to systemic treatment. To date, predictive markers for drug activity are lacking. Tumor samples from 27 patients with SI-NETs were analyzed ex vivo for sensitivity to a panel of cytotoxic drugs and targeted agents using a short-term total cell kill assay. Samples of renal cancer, colorectal cancer (CRC), ovarian cancer and chronic lymphocytic leukemia (CLL) were included for comparison. For the SI-NET subset, drug sensitivity was analyzed in relation to clinicopathological variables and pre-treatment biomarkers. For cytotoxic drugs, SI-NETs demonstrated similar or higher sensitivity to 5-FU, platinum, gemcitabine and doxorubicin compared with CRC. For several of the targeted kinase inhibitors, SI-NET was among the most sensitive solid tumor types. CLL and ovarian cancer were generally the most sensitive tumor types to both cytotoxic drugs and protein kinase inhibitors. SI-NET was more sensitive to the mTOR inhibitor sirolimus than the other solid tumor types tested. Individual SI-NET samples demonstrated great variability in ex vivo sensitivity for most drugs. Cross-resistance between different drugs also varied considerably, being higher among protein kinase inhibitors. Age, stage, grade, peritoneal carcinomatosis and extra-abdominal metastases as well as serum chromogranin A and urine 5-HIAA concentrations at diagnosis did not correlate to drug sensitivity ex vivo. SI-NETs exhibit intermediate sensitivity ex vivo to cytotoxic and targeted drugs. Clinicopathological factors and currently used biomarkers are not clearly associated to ex vivo sensitivity, challenging these criteria for treatment decisions in SI-NET. The great variability in drug sensitivity calls for individualized selection of therapy.

scholarly journals The inhibition of UBC13 expression and blockage of the DNMT1-CHFR-Aurora A pathway contribute to paclitaxel resistance in ovarian cancer

2018 ◽  
Vol 9 (2) ◽  
Author(s):  
Xu Zhang ◽  
Yan Feng ◽  
Xin-Yu Wang ◽  
Ya-Nan Zhang ◽  
Chun-Nv Yuan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Aurora A ◽  
Paclitaxel Resistance

scholarly journals Mitochondria P-glycoprotein confers paclitaxel resistance on ovarian cancer cells

2019 ◽  
Vol Volume 12 ◽  
pp. 3881-3891 ◽  
Author(s):  
Weina Guo ◽  
Weihong Dong ◽  
Min Li ◽  
Yi Shen
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Paclitaxel Resistance ◽  
P Glycoprotein

scholarly journals Abdominal FLASH irradiation reduces radiation-induced gastrointestinal toxicity for the treatment of ovarian cancer in mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Karen Levy ◽  
Suchitra Natarajan ◽  
Jinghui Wang ◽  
Stephanie Chow ◽  
Joshua T. Eggold ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Radiation Therapy ◽  
Dose Rate ◽  
Cancer Metastasis ◽  
Therapeutic Index ◽  
Similar Efficacy ◽  
High Dose Rate ◽  
Tumor Burden ◽  
Preclinical Model ◽  
High Dose

AbstractRadiation therapy is the most effective cytotoxic therapy for localized tumors. However, normal tissue toxicity limits the radiation dose and the curative potential of radiation therapy when treating larger target volumes. In particular, the highly radiosensitive intestine limits the use of radiation for patients with intra-abdominal tumors. In metastatic ovarian cancer, total abdominal irradiation (TAI) was used as an effective postsurgical adjuvant therapy in the management of abdominal metastases. However, TAI fell out of favor due to high toxicity of the intestine. Here we utilized an innovative preclinical irradiation platform to compare the safety and efficacy of TAI ultra-high dose rate FLASH irradiation to conventional dose rate (CONV) irradiation in mice. We demonstrate that single high dose TAI-FLASH produced less mortality from gastrointestinal syndrome, spared gut function and epithelial integrity, and spared cell death in crypt base columnar cells compared to TAI-CONV irradiation. Importantly, TAI-FLASH and TAI-CONV irradiation had similar efficacy in reducing tumor burden while improving intestinal function in a preclinical model of ovarian cancer metastasis. These findings suggest that FLASH irradiation may be an effective strategy to enhance the therapeutic index of abdominal radiotherapy, with potential application to metastatic ovarian cancer.

Therapeutic Efficacy of 213Bi-labeled sdAbs in a Preclinical Model of Ovarian Cancer

2020 ◽  
Vol 17 (9) ◽  
pp. 3553-3566
Author(s):  
Yana Dekempeneer ◽  
Vicky Caveliers ◽  
Maarten Ooms ◽  
Dominic Maertens ◽  
Mireille Gysemans ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Therapeutic Efficacy ◽  
Preclinical Model
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