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Hypoxia AND Ovarian Cancer

Ilona Szabłowska-Gadomska, Magdalena Ducher, Magdalena Orzechowska, Joanna Bogusławska-Duch, Magdalena Kowalska, Helena Poławska, Maciej Małecki
Gynecological cancers constitute a serious problem in the world. Their advanced stages are often characterized by the accumulation of ascites, which leads to spreading of cancer cells outside their primary focus. Despite progress in the treatment, prognoses are still not satisfactory. The main causes of these failures are chemoresistance, metastases and recurrences of the disease, which is influenced by, among others, the microenvironment of cancer cells. This study investigated the effect of the microenvironment, which create ascites derived from patients with ovarian and endometrial cancer to non-gynecological HEK 293 cells...
2018: Polish Journal of Pathology: Official Journal of the Polish Society of Pathologists
Bin Chang, Jiao Meng, Huimin Zhu, Xiang Du, Lili Sun, Lei Wang, Shugang Li, Gong Yang
BACKGROUND: Regulated in development and DNA damage response (REDD1), a gene responding to hypoxia or multiple DNA damage events, was recently implicated in cancer development and progression. Previously, in vivo and in vitro experiments indicated that REDD1 functions as an oncogene in ovarian cancer cells. However, the role of REDD1 in cancer cell migration and invasion and in clinical significance of prognostic values is not examined in detail. METHODS: We detected the REDD1 protein expression by immunohistochemistry in 18 normal ovarian surface epithelium or fallopian tube epithelium specimens, 24 ovarian borderline tumors, and 229 ovarian cancers...
November 14, 2018: Diagnostic Pathology
Dan Wang, Yan Xu, Lu Feng, Pin Yin, Shuang Shuang Song, Feng Wu, Ping Yan, Zhiqing Liang
Regulator of G‑protein signaling 5 (RGS5), a tissue‑specific signal‑regulating molecule, plays a key role in the development of the vasculature. It was recently found that RGS5 is abundantly expressed in epithelial ovarian cancer (EOC) compared with the normal ovaries. However, the distribution of RGS5 in EOC and its significance require further investigation. The aim of the present study was to investigate the expression of RGS5 in EOC, as well as its association with cancer differentiation, metastasis and clinicopathological parameters...
October 22, 2018: Oncology Reports
Lan G Coffman, Alexander T Pearson, Leonard G Frisbie, Zachary Freeman, Elizabeth Christie, David D Bowtell, Ronald J Buckanovich
Carcinoma-associated mesenchymal stem cells (CA-MSCs) are critical stromal progenitor cells within the tumor microenvironment (TME). We previously demonstrated that CA-MSCs differentially express bone morphogenetic protein family members, promote tumor cell growth, increase cancer "stemness," and chemotherapy resistance. Here, we use RNA sequencing of normal omental MSCs and ovarian CA-MSCs to demonstrate global changes in CA-MSC gene expression. Using these expression profiles, we create a unique predictive algorithm to classify CA-MSCs...
October 23, 2018: Stem Cells
Shuning Chen, Yujiao Liu, Shenyin Zhu, Chunyan Chen, Wan Xie, Linlin Xiao, Yi Zhu, Lan Hao, Zhigang Wang, Jiangchuan Sun, Shufang Chang
Chemotherapy and photo-sonodynamic therapy (PSDT) can be combined through drug delivery nano-platforms to enhance the anti-tumor efficacy, however, which is limited by hypoxia in tumor, thereby causing chemotherapy resistance. Perfluoropentane (PFP) has the ability to carry oxygen and to enhance ultrasound or photoacoustic imaging after vaporization. Herein, we constructed a kind of nanoparticles (PTX/ICG and oxygen loaded PLGA nanoparticles (PIO_NPs)), which had PFP core carrying oxygen and PLGA shell loaded indocyanine green (ICG) and paclitaxel (PTX)...
November 2018: Drug Delivery
Vidhi M Shah, Duc X Nguyen, Adel Al Fatease, Pragnesh Patel, Brianna Cote, Yeonhee Woo, Rohi Gheewala, Yvonne Pham, Man Gia Huynh, Christen Gannett, Deepa A Rao, Adam W G Alani
In this work, a new sphingomyelin-cholesterol liposomal formulation (CPD100Li) for the delivery of a hypoxia activated prodrug of vinblastine, mon-N-oxide (CPD100), is developed. The optimized liposomal formulation uses an ionophore (A23187) mediated pH-gradient method. Optimized CPD100Li is characterized for size, drug loading, and stability. The in vitro toxicity of CPD100Li is assessed on different aspects of cell proliferation and apoptosis of ES2 ovarian cancer under normoxic and hypoxic conditions. The pharmacokinetics of CPD100Li in mice as well as the influence of A23187 on the retention of CPD100 are assessed...
December 10, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Sun Hee Kang, Jihyoung Cho, Hasong Jeong, Sun Young Kwon
Purpose: Expression of RNA-binding motif protein 3 (RBM3) is induced by hypoxia and hypothermia. Recently, high expression of RBM3 was reported to be associated with a good prognosis in colon cancer, prostate cancer, ovarian cancer, and malignant melanoma. Studies on RBM3 in invasive breast carcinoma (IBC), however, are limited. Methods: RBM3 expression was examined using a tissue microarray from 361 patients with IBC. Immunohistochemistry was performed for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 to compare the expression of these markers...
September 2018: Journal of Breast Cancer
Michael M Song, Monish R Makena, Ashly Hindle, Balakrishna Koneru, Thinh H Nguyen, Dattesh U Verlekar, Hwangeui Cho, Barry J Maurer, Min H Kang, C Patrick Reynolds
OBJECTIVE: All-trans-N-(4-hydroxyphenyl)retinamide or fenretinide (4-HPR) acts by reactive oxygen species (ROS) and dihydroceramides (DHCers). In early-phase clinical trials 4-HPR has achieved complete responses in T-cell lymphomas (TCL) and neuroblastoma (NB) and signals of activity in ovarian cancer (OV). We defined the activity of 4-HPR metabolites in N-(4-methoxyphenyl)retinamide (MPR), 4-oxo-N-(4-hydroxyphenyl)retinamide (oxoHPR), and the 4-HPR isomer 13-cis-fenretinide (cis-HPR) in NB, OV, and TCL cell lines cultured in physiological hypoxia...
September 27, 2018: Anti-cancer Drugs
Fangyi Long, Weixin Liu, Ping Jia, Huafei Wang, Gang Jiang, Ting Wang
In this study, the viability and apoptosis of ovarian cancer cell line OVCAR-3 were assessed using MTT and flow cytometry analysis. GFP-tagged LC3 plasmid transfection was utilized to demonstrate the occurrence of autophagy. The expression of HIF-1α, Beclin1, LC3 and β-actin were determined with Western blot analysis. We found that hypoxia could inhibit cisplatin induced apoptosis in OVCAR-3 cells and enhance the chemoresistance to cisplatin. Furthermore, GFP-tagged LC3 plasmid transfection and western blot were used to demonstrate that hypoxia induced chemoresistance of OVCAR-3 cells to cisplatin is related to HIF-1α-induced autophagy...
September 1, 2018: Die Pharmazie
Aneta Rogalska, Ewa Forma, Magdalena Bryś, Agnieszka Śliwińska, Agnieszka Marczak
Although cancer cells need more glucose than normal cells to maintain energy demand, chronic hyperglycemia induces metabolic alteration that may dysregulate signaling pathways, including the O-GlcNAcylation and HIF1A (Hypoxia-inducible factor 1-alpha) pathways. Metformin was demonstrated to evoke metabolic stress and induce cancer cell death. The aim of this study was to determine the cytotoxic efficiency of metformin on SKOV-3 cells cultured in hyperglycemia and normoglycemia. To identify the potential mechanism, we assessed the expression of O-linked β- N -acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3)...
September 13, 2018: International Journal of Molecular Sciences
Hak Rae Lee, Faith Leslie, Samira M Azarin
Background: While hypoxia has been well-studied in various tumor microenvironments, its role in cancer cell dormancy is poorly understood, in part due to a lack of well-established in vitro and in vivo models. Hypoxic conditions under conventional hypoxia chambers are relatively unstable and cannot be maintained during characterization outside the chamber since normoxic response is quickly established. To address this challenge, we report a robust in vitro cancer dormancy model under a hypoxia-mimicking microenvironment using cobalt chloride (CoCl2 ), a hypoxia-mimetic agent, which stabilizes hypoxia inducible factor 1-alpha (HIF1α), a major regulator of hypoxia signaling...
2018: Journal of Biological Engineering
Xin Chen, Jieru Zhou, Xiaoduan Li, Xinjing Wang, Yingying Lin, Xipeng Wang
Recently, cancer has been considered to be a complex system that includes the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are the most common immune-related stromal cells in the TME, and communication between cancer cells and TAMs is crucial for the progression of epithelial ovarian cancer (EOC). In this study, we revealed that exosomes derived from EOC cells remodel macrophages to a tumor-promoted phenotype, namely TAMs. In addition, hypoxic microenvironments have been postulated to facilitate this process in the TME, and hypoxia-inducible factors (HIFs) play an important role in this process...
October 28, 2018: Cancer Letters
Masahide Tanaka, Koichiro Takahashi, Yuki Kurihara, Mihoko Yamamoto-Rikitake, Shinsuke Ogusu, Haruki Hirakawa, Hironori Sadamatsu, Kazutoshi Komiya, Tomomi Nakamura, Naoko Sueoka-Aragane
Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare disease that shows hypoxia with severe pulmonary hypertension related to malignant tumor. Diagnosis is difficult due to rapid clinical progression and the need to demonstrate pathological findings from lung biopsy. A 64-year-old woman visited our hospital with hypoxia and pulmonary hypertension. Diffuse granular shadows in the centrilobular area and ground-glass shadows in both lungs and left ovarian tumor were found on radiological imaging. PTTM was suspected, but pulmonary artery blood aspiration by right cardiac catheter failed to detect cancer cells...
May 2018: Case Reports in Oncology
Kshipra M Gharpure, Sunila Pradeep, Marta Sans, Rajesha Rupaimoole, Cristina Ivan, Sherry Y Wu, Emine Bayraktar, Archana S Nagaraja, Lingegowda S Mangala, Xinna Zhang, Monika Haemmerle, Wei Hu, Cristian Rodriguez-Aguayo, Michael McGuire, Celia Sze Ling Mak, Xiuhui Chen, Michelle A Tran, Alejandro Villar-Prados, Guillermo Armaiz Pena, Ragini Kondetimmanahalli, Ryan Nini, Pranavi Koppula, Prahlad Ram, Jinsong Liu, Gabriel Lopez-Berestein, Keith Baggerly, Livia S Eberlin, Anil K Sood
The standard treatment for high-grade serous ovarian cancer is primary debulking surgery followed by chemotherapy. The extent of metastasis and invasive potential of lesions can influence the outcome of these primary surgeries. Here, we explored the underlying mechanisms that could increase metastatic potential in ovarian cancer. We discovered that FABP4 (fatty acid binding protein) can substantially increase the metastatic potential of cancer cells. We also found that miR-409-3p regulates FABP4 in ovarian cancer cells and that hypoxia decreases miR-409-3p levels...
July 26, 2018: Nature Communications
Yunjie Xu, Weinan Gao, Yong Zhang, Shanshan Wu, Yanan Liu, Xinyue Deng, Lili Xie, Jiayan Yang, Huimei Yu, Jing Su, Liankun Sun
The poor prognosis and high mortality of patients with ovarian cancer result in part from their poor response to platinum-based chemotherapy. However, the precise mechanism behind cisplatin resistance is still not fully understood. In the present study, the authors explored the mechanism of resistance to cisplatin from the perspective of glucose metabolism in human ovarian cancer. The experiments using genetically matched ovarian cancer cell lines SKOV3 (cisplatin-sensitive) and SKOV3/DDP (cisplatin-resistant) in the present study provided some important findings...
September 2018: International Journal of Oncology
Ksenia S Anufrieva, Victoria О Shender, Georgij P Arapidi, Marat S Pavlyukov, Michail I Shakhparonov, Polina V Shnaider, Ivan O Butenko, Maria A Lagarkova, Vadim M Govorun
BACKGROUND: Abnormal pre-mRNA splicing regulation is common in cancer, but the effects of chemotherapy on this process remain unclear. METHODS: To evaluate the effect of chemotherapy on slicing regulation, we performed meta-analyses of previously published transcriptomic, proteomic, phosphoproteomic, and secretome datasets. Our findings were verified by LC-MS/MS, western blotting, immunofluorescence, and FACS analyses of multiple cancer cell lines treated with cisplatin and pladienolide B...
June 27, 2018: Genome Medicine
Sofia C Nunes, Cristiano Ramos, Filipa Lopes-Coelho, Catarina O Sequeira, Fernanda Silva, Sofia Gouveia-Fernandes, Armanda Rodrigues, António Guimarães, Margarida Silveira, Sofia Abreu, Vítor E Santo, Catarina Brito, Ana Félix, Sofia A Pereira, Jacinta Serpa
Ovarian cancer is the second most common gynaecologic malignancy and the main cause of death from gynaecologic cancer, due to late diagnosis and chemoresistance. Studies have reported the role of cysteine in cancer, by contributing for hydrogen sulphide (H2 S) generation and as a precursor of glutathione (GSH). However, the role of cysteine in the adaptation to hypoxia and therapy response remains unclear. We used several ovarian cancer cell lines, ES2, OVCAR3, OVCAR8, A2780 and A2780cisR, to clarify cysteine relevance in ovarian cancer cells survival upon hypoxia and carboplatin...
June 22, 2018: Scientific Reports
Sofia C Nunes, Filipa Lopes-Coelho, Sofia Gouveia-Fernandes, Cristiano Ramos, Sofia A Pereira, Jacinta Serpa
BACKGROUND: Ovarian cancer is the second most common gynaecologic malignancy and the most common cause of death from gynaecologic cancer, especially due to diagnosis at an advanced stage, when a cure is rare. As ovarian tumour grows, cancer cells are exposed to regions of hypoxia. Hypoxia is known to be partially responsible for tumour progression, metastasis and resistance to therapies. These suggest that hypoxia entails a selective pressure in which the adapted cells not only have a fitness increase under the selective environment, but also in non-selective adverse environments...
June 19, 2018: BMC Evolutionary Biology
Jeff Hirst, Harsh B Pathak, Stephen Hyter, Ziyan Y Pessetto, Thuc Ly, Stefan Graw, Devin C Koestler, Adam J Krieg, Katherine F Roby, Andrew K Godwin
Drug development for first-line treatment of epithelial ovarian cancer (EOC) has been stagnant for almost three decades. Traditional cell culture methods for primary drug screening do not always accurately reflect clinical disease. To overcome this barrier, we grew a panel of EOC cell lines in three-dimensional (3D) cell cultures to form multicellular tumor spheroids (MCTS). We characterized these MCTS for molecular and cellular features of EOC and performed a comparative screen with cells grown using two-dimensional (2D) cell culture to identify previously unappreciated anticancer drugs...
August 1, 2018: Cancer Research
Kshipra M Gharpure, Olivia D Lara, Yunfei Wen, Sunila Pradeep, Chris LaFargue, Cristina Ivan, Rajesha Rupaimoole, Wei Hu, Lingegowda S Mangala, Sherry Y Wu, Archana S Nagaraja, Keith Baggerly, Anil K Sood
Primary debulking surgery followed by adjuvant chemotherapy is the standard treatment for ovarian cancer. Residual disease after primary surgery is associated with poor patient outcome. Previously, we discovered ADH1B to be a molecular biomarker of residual disease. In the current study, we investigated the functional role of ADH1B in promoting ovarian cancer cell invasiveness and contributing to residual disease. We discovered that ADH1B overexpression leads to a more infiltrative cancer cell phenotype, promotes metastasis, increases the adhesion of cancer cells to mesothelial cells, and increases extracellular matrix degradation...
May 18, 2018: Oncotarget
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