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hypoxia ovarian cancer

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https://www.readbyqxmd.com/read/27869162/the-histone-demethylase-kdm4b-regulates-peritoneal-seeding-of-ovarian-cancer
#1
C Wilson, L Qiu, Y Hong, T Karnik, G Tadros, B Mau, T Ma, Y Mu, J New, R J Louie, S Gunewardena, A K Godwin, O W Tawfik, J Chien, K F Roby, A J Krieg
Epithelial ovarian cancer (EOC) has poor prognosis and rapid recurrence because of widespread dissemination of peritoneal metastases at diagnosis. Multiple pathways contribute to the aggressiveness of ovarian cancer, including hypoxic signaling mechanisms. In this study, we have determined that the hypoxia-inducible histone demethylase KDM4B is expressed in ∼60% of EOC tumors assayed, including primary and matched metastatic tumors. Expression of KDM4B in tumors is positively correlated with expression of the tumor hypoxia marker CA-IX, and is robustly induced in EOC cell lines exposed to hypoxia...
November 21, 2016: Oncogene
https://www.readbyqxmd.com/read/27690729/endothelin-1-receptor-drives-invadopodia-exploiting-how-%C3%AE-arrestin-1-guides-the-way
#2
Anna Bagnato, Laura Rosanò
Metastatization is a complex multistep process requiring fine-tuned regulated cytoskeleton re-modeling, mediated by the cross-talk of actin with interacting partners, such as the Rho GTPases. Our expanding knowledge of invadopodia, small invasive membrane protrusions composed of a core of F-actin, actin regulators and actin-binding proteins, and hotspots for secretion of extracellular matrix (ECM) proteinases, contributes to clarify critical steps of the metastatic program. Growth factor receptors and their intermediate signaling molecules, along with matrix adhesion and rigidity, pH and hypoxia, act as drivers of cytoskeleton changes and invadopodia formation...
October 3, 2016: Small GTPases
https://www.readbyqxmd.com/read/27689695/epigenetic-regulation-of-glycosylation-and-the-impact-on-chemo-resistance-in-breast-and-ovarian-cancer
#3
Gordon Greville, Amanda McCann, Pauline M Rudd, Radka Saldova
Glycosylation is one of the most fundamental posttranslational modifications in cellular biology and has been shown to be epigenetically regulated. Understanding this process is important as the clinical use of epigenetic therapies such as DNA methyltransferase inhibitors are undergoing clinical trials for the treatment of ovarian and breast cancer. Previous work has demonstrated that altered glycosylation patterns are associated with aggressive disease in women presenting with breast and ovarian cancer. Moreover, the tumor microenvironment of hypoxia results in globally altered DNA methylation and is associated with aggressive cancer phenotypes and chemo-resistance, a feature integral to many cancers...
September 30, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27604906/quantitative-proteomic-profiling-reveals-that-diverse-metabolic-pathways-are-influenced-by-melatonin-in-an-in-vivo-model-of-ovarian-carcinoma
#4
Luiz Gustavo A Chuffa, Luiz Antonio Lupi Júnior, Fábio R F Seiva, Marcelo Martinez, Raquel F Domeniconi, Patricia Fernanda F Pinheiro, Lucilene D Dos Santos, Francisco Eduardo Martinez
To obtain more information into the molecular mechanisms underlying ovarian cancer (OC), we proposed a comparative proteomic analysis in animals receiving long-term melatonin as therapy or only vehicle using multidimensional protein identification combined with mass spectrometry. To induce tumor, a single dose of 100 μg 7,12-dimethylbenz(a)anthracene (DMBA) dissolved in 10 μL of sesame oil was injected under the left ovarian bursa of 20 Fischer 344 rats. The right ovaries were injected with sesame oil only...
October 7, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/27489349/hypoxia-notch1-sox2-signaling-is-important-for-maintaining-cancer-stem-cells-in-ovarian-cancer
#5
Eun Jin Seo, Dae Kyoung Kim, Il Ho Jang, Eun Jung Choi, Sang Hun Shin, Su In Lee, Sang-Mo Kwon, Ki-Hyung Kim, Dong-Soo Suh, Jae Ho Kim
Hypoxia and NOTCH signaling have been reported to be associated with the self-renewal and drug resistance of cancer stem cells (CSCs). However, the molecular mechanisms by which hypoxia and NOTCH signaling stimulate the self-renewal and drug resistance of ovarian CSCs are poorly understood. In the present study, we identified SOX2 as a key transcription factor for CSC-like characteristics in the downstream of hypoxia-induced NOTCH signaling in epithelial ovarian cancer cells. Hypoxic treatment or overexpression of intracellular domain of NOTCH1 (NICD1) in ovarian cancer cells increased sphere formation, drug resistance, and expression of CSC-associated genes such as SOX2, ALDH, and ABC transporters...
July 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27346985/involvement-of-human-chorionic-gonadotropin-in-regulating-vasculogenic-mimicry-and-hypoxia-inducible-factor-1%C3%AE-expression-in-ovarian-cancer-cells
#6
Min Su, Xiangxiang Xu, Weiwei Wei, Sainan Gao, Xiaoying Wang, Caoyi Chen, Yuquan Zhang
BACKGROUND: Human chorionic gonadotropin (hCG) can play a crucial role in angiogenesis. In the present study, we focused on hCG to gain insight into its potential effects on vasculogenic mimicry (VM) in ovarian cancer cells. METHODS: Ovarian cancer OVCAR-3 cells were incubated with different concentrations of recombinant hCG in 3-dimensional cultures. VM was identified by morphological observations and vascular endothelial cell marker detection in OVCAR-3 cells...
2016: Cancer Cell International
https://www.readbyqxmd.com/read/27223082/tunneling-nanotube-formation-is-stimulated-by-hypoxia-in-ovarian-cancer-cells
#7
Snider Desir, Elizabeth L Dickson, Rachel I Vogel, Venugopal Thayanithy, Phillip Wong, Deanna Teoh, Melissa A Geller, Clifford J Steer, Subbaya Subramanian, Emil Lou
In this study, we demonstrated that hypoxic conditions stimulated an increase in tunneling nanotube (TNT) formation in chemoresistant ovarian cancer cells (SKOV3, C200).We found that suppressing the mTOR pathway using either everolimus or metformin led to suppression of TNT formation in vitro, verifying TNTs as a potential target for cancer-directed therapy. Additionally, TNT formation was detected in co-cultures including between platinum-resistant SKOV3 cells, between SKOV3 cells and platinum-chemosensitive A2780 cells, and between SKOV3 cells cultured with benign ovarian epithelial (IOSE) cells; these findings indicate that TNTs are novel conduits for malignant cell interactions and tumor cell interactions with other cells in the microenvironment...
July 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27221674/ursolic-acid-inhibits-proliferation-and-reverses-drug-resistance-of-ovarian-cancer-stem-cells-by-downregulating-abcg2-through-suppressing-the-expression-of-hypoxia-inducible-factor-1%C3%AE-in%C3%A2-vitro
#8
Wen-Jing Wang, Hua Sui, Cong Qi, Qi Li, Jie Zhang, Shao-Fei Wu, Ming-Zhu Mei, Ying-Yu Lu, Yi-Ting Wan, Hannah Chang, Piao-Ting Guo
Hypoxia in tumors is closely related to drug resistance. It has not been verified whether hypoxia-inducible factor-1α (HIF-1α) or ABCG2 is related to hypoxia-induced resistance. Ursolic acid (UA), when used in combination with cisplatin can significantly increase the sensitivity of ovarian cancer stem cells (CSCs) to cisplatin, but the exact mechanism is unknown. The cell growth inhibitory rate of cisplatin under different conditions was evaluated using Cell Counting Kit-8 (CCK-8) in adherence and sphere cells (SKOV3, A2780, and HEY)...
July 2016: Oncology Reports
https://www.readbyqxmd.com/read/27211906/differential-effects-of-rapalogues-dual-kinase-inhibitors-on-human-ovarian-carcinoma-cells-in-vitro
#9
Karly-Rai Rogers-Broadway, Dimple Chudasama, George Pados, Dimitris Tsolakidis, Anastasia Goumenou, Marcia Hall, Emmanouil Karteris
Ovarian cancer is the second most common gynaecological malignancy and was diagnosed in over 7,000 women in 2011 in the UK. There are currently no reliable biomarkers available for use in a regular screening assay for ovarian cancer and due to characteristic late presentation (78% in stages III and IV) ovarian cancer has a low survival rate (35% after 10 years). The mTOR pathway is a central regulator of growth, proliferation, apoptosis and angiogenesis; providing balance between available resources such as amino acids and growth factors, and stresses such as hypoxia, to control cellular behaviour accordingly...
July 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27166196/lysophosphatidic-acid-stimulates-epithelial-to-mesenchymal-transition-marker-slug-snail2-in-ovarian-cancer-cells-via-g%C3%AE-i2-src-and-hif1%C3%AE-signaling-nexus
#10
Ji Hee Ha, Jeremy D Ward, Rangasudhagar Radhakrishnan, Muralidharan Jayaraman, Yong Sang Song, Danny N Dhanasekaran
Recent studies have identified a critical role for lysophosphatidic acid (LPA) in the progression of ovarian cancer. Using a transcription factor activation reporter array, which analyzes 45 distinct transcription factors, it has been observed that LPA observed robustly activates the transcription factor hypoxia-induced factor-1α (HIF1α) in SKOV3.ip ovarian cancer cells. HIF1α showed 150-fold increase in its activation profile compared to the untreated control. Validation of the array analysis indicated that LPA stimulates a rapid increase in the levels of HIF1α in ovarian cancer cells, with an observed maximum level of HIF1α-induction by 4 hours...
June 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27122375/the-role-of-angiogenesis-in-the-persistence-of-chemoresistance-in-epithelial-ovarian-cancer
#11
Osama Nusrat, Jimmy Belotte, Nicole M Fletcher, Ira Memaj, Mohammed G Saed, Michael P Diamond, Ghassan M Saed
OBJECTIVE: Chemoresistance remains a major challenge in the treatment of ovarian cancer. As part of a survival mechanism, tumor cells have been shown to release proangiogenic factors, such as vascular endothelial growth factor (VEGF), through a mechanism that involves the upregulation of hypoxia-induced factor (HIF)-1α. The objective of this study was to compare the expression of VEGF and its receptors (R1 and R2) as well as HIF-1α in chemoresistant epithelial ovarian cancer (EOC) cells to their chemosensitive counterparts and determine their impact on angiogenesis...
April 26, 2016: Reproductive Sciences
https://www.readbyqxmd.com/read/27064283/fak-regulates-platelet-extravasation-and-tumor-growth-after-antiangiogenic-therapy-withdrawal
#12
Monika Haemmerle, Justin Bottsford-Miller, Sunila Pradeep, Morgan L Taylor, Hyun-Jin Choi, Jean M Hansen, Heather J Dalton, Rebecca L Stone, Min Soon Cho, Alpa M Nick, Archana S Nagaraja, Tony Gutschner, Kshipra M Gharpure, Lingegowda S Mangala, Rajesha Rupaimoole, Hee Dong Han, Behrouz Zand, Guillermo N Armaiz-Pena, Sherry Y Wu, Chad V Pecot, Alan R Burns, Gabriel Lopez-Berestein, Vahid Afshar-Kharghan, Anil K Sood
Recent studies in patients with ovarian cancer suggest that tumor growth may be accelerated following cessation of antiangiogenesis therapy; however, the underlying mechanisms are not well understood. In this study, we aimed to compare the effects of therapy withdrawal to those of continuous treatment with various antiangiogenic agents. Cessation of therapy with pazopanib, bevacizumab, and the human and murine anti-VEGF antibody B20 was associated with substantial tumor growth in mouse models of ovarian cancer...
May 2, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27058839/the-biological-significance-and-clinical-applications-of-exosomes-in-ovarian-cancer
#13
REVIEW
Kalpana Deepa Priya Dorayappan, John J Wallbillich, David E Cohn, Karuppaiyah Selvendiran
Exosomes are nano-sized (20-100nm) vesicles released by a variety of cells and are generated within the endosomal system or at the plasma membrane. There is emerging evidence that exosomes play a key role in intercellular communication in ovarian and other cancers. The protein and microRNA content of exosomes has been implicated in various intracellular processes that mediate oncogenesis, tumor spread, and drug resistance. Exosomes may prime distant tissue sites for reception of future metastases and their release can be mediated by the tumor microenvironment (e...
July 2016: Gynecologic Oncology
https://www.readbyqxmd.com/read/27044634/snail-gene-inhibited-by-hypoxia-inducible-factor-1%C3%AE-hif-1%C3%AE-in-epithelial-ovarian-cancer
#14
Pengnan Zhang, Yanmei Liu, Youji Feng, Shujun Gao
The aim of this study was to investigate the relationship between HIF-1α and SNAIL gene expression in the epithelial ovarian cancer (EOC) cell line. EOC cells were treated with hypoxia, hypoxia combined with rapamycin, and control. The expression of HIF-1α and E-cad were assessed by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. The gene expression of SNAIL was studied by RT-PCR and real-time PCR. RNA interference technology was used to determine the relationship between HIF-1α and SNAIL...
September 2016: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/27035330/hypoxia-is-important-in-f%C3%A2-18-fdg-accumulation-in-thecoma%C3%A2-fibroma-tumors-on-f%C3%A2-18-fdg-pet-ct-scans
#15
Hiroko Seino, Shuichi Ono, Hiroyuki Miura, Satoko Morohashi, Yunyan Wu, Fumiyasu Tsushima, Yoshihiro Takai, Hiroshi Kijima
Several studies have noted benign thecoma‑fibroma tumors with positive F‑18 fluorodeoxyglucose (FDG) accumulation mimicking malignant ovarian tumors following F‑18 FDG positron emission tomography (PET). The present study analyzed four cases with false‑positive F‑18 FDG PET/computed tomography (CT) diagnoses of thecoma‑fibroma tumors as malignant tumors due to F‑18 FDG accumulation, compared with eight cases of FDG‑positive ovarian cancers and two cases of FDG‑negative fibromas. Hypoxia inducible factor (HIF)‑1α expression was examined in the six thecoma‑fibroma tumors using reverse transcription‑polymerase chain reaction (RT‑PCR)...
May 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/26967059/hypoxia-inducible-factor-1-alpha-is-required-for-the-tumourigenic-and-aggressive-phenotype-associated-with-rab25-expression-in-ovarian-cancer
#16
Natividad Gomez-Roman, Neha Mohan Sahasrabudhe, Fiona McGregor, Anthony J Chalmers, Jim Cassidy, Jane Plumb
The small GTPase Rab25 has been functionally linked to tumour progression and aggressiveness in ovarian cancer and promotes invasion in three-dimensional environments. This type of migration has been shown to require the expression of the hypoxia-inducible factor 1 alpha (HIF-1α). In this report we demonstrate that Rab25 regulates HIF-1α protein expression in an oxygen independent manner in a panel of cancer cell lines. Regulation of HIF-1α protein expression by Rab25 did not require transcriptional upregulation, but was dependent on de novo protein synthesis through the Erbb2/ERK1/2 and p70S6K/mTOR pathways...
April 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/26909598/nuclear-%C3%AE-arrestin1-is-a-critical-cofactor-of-hypoxia-inducible-factor-1%C3%AE-signaling-in-endothelin-1-induced-ovarian-tumor-progression
#17
Roberta Cianfrocca, Piera Tocci, Laura Rosanò, Valentina Caprara, Rosanna Sestito, Valeriana Di Castro, Anna Bagnato
Hypoxia-inducible factor-1α (HIF-1α) mediates the response to hypoxia or other stimuli, such as growth factors, including endothelin-1 (ET-1), to promote malignant progression in numerous tumors. The importance of cofactors that regulate HIF-1α signalling within tumor is not well understood. Here we elucidate that ET-1/ET(A) receptor (ET(A)R)-induced pathway physically and functionally couples the scaffold protein β-arrestin1 (β-arr1) to HIF-1α signalling. In epithelial ovarian cancer (EOC) cells, ET-1/ET(A)R axis induced vascular-endothelial growth factor (VEGF) expression through HIF-1α nuclear accumulation...
April 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/26868821/hypoxic-conditions-increases-h%C3%A2-s-induced-er-stress-in-a2870-cells
#18
Lubomira Lencesova, Miroslav Vlcek, Olga Krizanova, Sona Hudecova
Hypoxia - a state of lower oxygen demand-is responsible for a higher aggressiveness of tumors and therefore a worse prognosis. During hypoxia, several metabolic pathways are re-organized, e.g., energetic metabolism, modulation of pH, and calcium transport. Calcium is an important second messenger that regulates variety of processes in the cell. Thus, aim of this work was to compare H2S modulation of the intracellular calcium transport systems in hypoxia and in cells grown in standard culture conditions. For all experiments, we used ovarian cancer cell line (A2780)...
March 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/26851019/inhibitory-effects-of-the-four-main-theaflavin-derivatives-found-in-black-tea-on-ovarian-cancer-cells
#19
Ying Gao, Gary O Rankin, Youying Tu, Yi Charlie Chen
BACKGROUND: Some polyphenols induce apoptosis and inhibit angiogenesis. Consumption of black tea, rich in polyphenols, has been found to reduce ovarian cancer risk. Theaflavin (TF1), theaflavin-3-gallate (TF2a), theaflavin-3'-gallate (TF2b) and theaflavin-3, 3'-digallate (TF3) are four main theaflavin derivatives found in black tea. MATERIALS AND METHODS: Cell proliferation assay, Hoechst 33342 staining assay, Caspase-Glo Assay, western blot, human umbilical vein endothelial cell tube formation assay and vascular endothelial growth factor (VEGF) enzyme-linked immunosorbent assay were performed...
February 2016: Anticancer Research
https://www.readbyqxmd.com/read/26801746/overcoming-cisplatin-resistance-of-ovarian-cancer-cells-by-targeting-hif-1-regulated-cancer-metabolism
#20
Zhihong Ai, Yang Lu, Songbo Qiu, Zhen Fan
Cisplatin is currently one of the most effective chemotherapeutic drugs used for treating ovarian cancer; however, resistance to cisplatin is common. In this study, we explored an experimental strategy for overcoming cisplatin resistance of human ovarian cancer from the new perspective of cancer cell metabolism. By using two pairs of genetically matched cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines, we tested the hypothesis that downregulating hypoxia-inducible factor-1 (HIF-1), which regulates metabolic enzymes involved in glycolysis, is a promising strategy for overcoming cisplatin resistance of human ovarian cancer cells...
April 1, 2016: Cancer Letters
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