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Hypoxia AND Ovarian Cancer

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...
August 8, 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
Imran Hussain, Sana Waheed, Kashif A Ahmad, John E Pirog, Viqar Syed
Hypoxia-inducible factor-1alpha (HIF-1α) is aberrantly upregulated in tumors and implicated in angiogenesis, metastasis, and drug resistance. Therefore, developing treatments that target HIF-1α may be a viable therapeutic approach. In Traditional Chinese Medicine (TCM), Scutellaria baicalensis (SB) is used for the treatment of cancer but the anti-cancer mechanisms are not known. We examined the effects of SB on HIF-1α expression in ovarian cancer (OC) cell lines grown under normoxic and hypoxic conditions...
May 24, 2018: Journal of Cellular Biochemistry
Xiaoyu Yu, Yan Wang, Huilei Qiu, Hongtao Song, Di Feng, Yang Jiang, Shuzhe Deng, Hongxue Meng, Jingshu Geng
Objective: Ovarian carcinoma represents one of the deadliest malignancies among female cancer patients. Astrocyte-elevated gene-1 (AEG-1) participates in the ontogenesis of multiple human malignant diseases. Here we evaluated AEG-1, hypoxia-inducible factor- (HIF-) 1 α , nuclear factor kappa-light-chain-enhancer of activated B cells (NF- κ B), and vascular endothelial growth factor (VEGF) amounts in hypoxia induced ovarian carcinoma cells. This study aimed to explore the mechanism by which AEG-1 regulates metastasis in hypoxia induced ovarian carcinoma...
2018: BioMed Research International
Yasumichi Kuwahara, Leslie M Kennedy, Anthony N Karnezis, E Lorena Mora-Blanco, Arlin B Rogers, Christopher D Fletcher, David G Huntsman, Charles W M Roberts, W Kimryn Rathmell, Bernard E Weissman
The new paradigm of mutations in chromatin-modifying genes as driver events in the development of cancers has proved challenging to resolve the complex influences over disease phenotypes. In particular, impaired activities of members of the SWI/SNF chromatin remodeling complex have appeared in an increasing variety of tumors. Mutations in SNF5, a member of this ubiquitously expressed complex, arise in almost all cases of malignant rhabdoid tumor in the absence of additional genetic alterations. Therefore, we studied how activation of additional oncogenic pathways might shift the phenotype of disease driven by SNF5 loss...
July 2018: American Journal of Pathology
Haiyan Tai, Zhiyong Wu, Su'an Sun, Zhigang Zhang, Congjian Xu
Fibroblast growth factor receptor-like-1 (FGFRL1) has been identified as the fifth fibroblast growth factor receptor. So far, little is known about its biological functions, particularly in cancer development. Here, for the first time, we demonstrated the roles of FGFRL1 in ovarian carcinoma (OC). An array and existing databases were used to investigate the expression profile of FGFRL1 and the relationship between FGFRL1 expression and clinicopathological parameters. FGFRL1 was significantly upregulated in OC patients, and high FGFRL1 expression was correlated with poor prognosis...
2018: Journal of Immunology Research
Francesca Vena, Ruochen Jia, Arman Esfandiari, Juan J Garcia-Gomez, Manuel Rodriguez-Justo, Jianguo Ma, Sakeena Syed, Lindsey Crowley, Brian Elenbaas, Samantha Goodstal, John A Hartley, Daniel Hochhauser
Targeting the DNA damage response (DDR) in tumors with defective DNA repair is a clinically successful strategy. The RAS/RAF/MEK/ERK signalling pathway is frequently deregulated in human cancers. In this study, we explored the effects of MEK inhibition on the homologous recombination pathway and explored the potential for combination therapy of MEK inhibitors with DDR inhibitors and a hypoxia-activated prodrug. We studied effects of combining pimasertib, a selective allosteric inhibitor of MEK1/2, with olaparib, a small molecule inhibitor of poly (adenosine diphosphate [ADP]-ribose) polymerases (PARP), and with the hypoxia-activated prodrug evofosfamide in ovarian and pancreatic cancer cell lines...
February 20, 2018: Oncotarget
Maria Giebler, Martin S Staege, Sindy Blauschmidt, Lea I Ohm, Matthias Kraus, Peter Würl, Helge Taubert, Thomas Greither
A wide variety of endogenous retroviral sequences has been demonstrated in the human genome so far, divided into several different families according to the sequence homology to viral strains. While increased expression of human endogenous retrovirus (HERV) elements has already been linked to unfavorable prognosis in hepatocellular carcinoma, breast cancer, and ovarian carcinoma yet less is known about the impact of the expression of different HERV elements on sarcomagenesis in general as well as the outcome of soft tissue sarcoma (STS) patients...
2018: Frontiers in Microbiology
Ke Zhang, Xiangjun Kong, Guangde Feng, Wei Xiang, Long Chen, Fang Yang, Chunyu Cao, Yifei Ding, Hang Chen, Mingxing Chu, Pingqing Wang, Baoyun Zhang
BACKGROUND: Ovarian cancer is a leading cause of the death from gynecologic malignancies. Hypoxia is closely related to the malignant growth of cells. However, the molecular mechanism of hypoxia-regulated ovarian cancer cells remains unclear. Thus, this study was conducted to identify the key genes and pathways implicated in the regulation of hypoxia by bioinformatics analysis. METHODS: Using the datasets of GSE53012 downloaded from the Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) were screened by comparing the RNA expression from cycling hypoxia group, chronic hypoxia group, and control group...
February 26, 2018: Journal of Ovarian Research
Robert B Jones, Kaitlyn A Dorsett, Anita B Hjelmeland, Susan L Bellis
Aberrant cell surface glycosylation is prevalent in tumor cells, and there is ample evidence that glycans have functional roles in carcinogenesis. Nonetheless, many molecular details remain unclear. Tumor cells frequently exhibit increased α2-6 sialylation on N -glycans, a modification that is added by the ST6Gal-I sialyltransferase, and emerging evidence suggests that ST6Gal-I-mediated sialylation promotes the survival of tumor cells exposed to various cell stressors. Here we report that ST6Gal-I protects cancer cells from hypoxic stress...
April 13, 2018: Journal of Biological Chemistry
Ji Hee Ha, Rangasudhagar Radhakrishnan, Muralidharan Jayaraman, Mingda Yan, Jeremy D Ward, Kar-Ming Fung, Katherine Moxley, Anil K Sood, Ciro Isidoro, Priyabrata Mukherjee, Yong Sang Song, Danny N Dhanasekaran
Although hypoxia has been shown to reprogram cancer cells toward glycolytic shift, the identity of extrinsic stimuli that induce metabolic reprogramming independent of hypoxia, especially in ovarian cancer, is largely unknown. In this study, we use patient-derived ovarian cancer cells and high-grade serous ovarian cancer cell lines to demonstrate that lysophosphatidic acid (LPA), a lipid growth factor and GPCR ligand whose levels are substantially increased in ovarian cancer patients, triggers glycolytic shift in ovarian cancer cells...
April 15, 2018: Cancer Research
Shojiro Kitajima, Kian Leong Lee, Hiroki Hikasa, Wendi Sun, Ruby Yun-Ju Huang, Henry Yang, Shinji Matsunaga, Takehiro Yamaguchi, Marito Araki, Hiroyuki Kato, Lorenz Poellinger
Ammonia is a toxic by-product of metabolism that causes cellular stresses. Although a number of proteins are involved in adaptive stress response, specific factors that counteract ammonia-induced cellular stress and regulate cell metabolism to survive against its toxicity have yet to be identified. We demonstrated that the hypoxia-inducible factor-1α (HIF-1α) is stabilized and activated by ammonia stress. HIF-1α activated by ammonium chloride compromises ammonia-induced apoptosis. Furthermore, we identified glutamine synthetase (GS) as a key driver of cancer cell proliferation under ammonia stress and glutamine-dependent metabolism in ovarian cancer stem-like cells expressing CD90...
December 29, 2017: Oncotarget
Lifeng Li, Liping Wang, Jieyao Li, Zhirui Fan, Li Yang, Zhen Zhang, Chaoqi Zhang, Dongli Yue, Guohui Qin, Tengfei Zhang, Feng Li, Xinfeng Chen, Yu Ping, Dan Wang, Qun Gao, Qianyi He, Lan Huang, Hong Li, Jianmin Huang, Xuan Zhao, Wenhua Xue, Zhi Sun, Jingli Lu, Jane J Yu, Jie Zhao, Bin Zhang, Yi Zhang
Metformin is a broadly prescribed drug for type 2 diabetes that exerts antitumor activity, yet the mechanisms underlying this activity remain unclear. We show here that metformin treatment blocks the suppressive function of myeloid-derived suppressor cells (MDSC) in patients with ovarian cancer by downregulating the expression and ectoenzymatic activity of CD39 and CD73 on monocytic and polymononuclear MDSC subsets. Metformin triggered activation of AMP-activated protein kinase α and subsequently suppressed hypoxia-inducible factor α, which was critical for induction of CD39/CD73 expression in MDSC...
April 1, 2018: Cancer Research
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