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Hypoxia AND Ovarian Cancer

Xiaolan Zhu, Huiling Shen, Xinming Yin, Meiling Yang, Hong Wei, Qi Chen, Fan Feng, Yueqin Liu, Wenlin Xu, Yuefeng Li
BACKGROUND: How exosomal microRNAs (miRNAs) derived from macrophages contribute to the development of drug resistance in the context of the hypoxic tumor microenvironment in epithelial ovarian cancer (EOC) remains poorly understood. METHODS: The miRNA levels were detected by qRT-PCR. Protein levels of HIF-1α, CD163 and PTEN-PI3K/AKT pathway were assessed by Western blot (WB) and Immunohistochemistry (IHC). Exosomes were isolated, and then confirmed by Transmission electron microscopy (TEM), Nanoparticle Tracking Analysis (NTA) and WB...
February 15, 2019: Journal of Experimental & Clinical Cancer Research: CR
Zaira Rehman, Ammad Fahim, Attya Bhatti, Hajra Sadia, Peter John
The hypoxic tumor microenvironment is the major contributor of chemotherapy resistance in solid tumors. One of the key regulators of hypoxic responses within the cell is the hypoxia inducible factor-1α (HIF-1α) that is involved in transcription of genes promoting cell survival and chemotherapy resistance. Multidrug resistance gene-1 (MDR1) and Lysosome-associated protein transmembrane 4B-35 (LAPTM4B-35) are among those notable players which augment their responses to cellular hypoxia. MDR1 is the hypoxia responsive gene involved in multidrug resistance phenotype while LAPTM4B-35 is involved in chemotherapy resistance by stabilizing HIF-1α and overexpressing MDR1...
2019: PeerJ
Chunyan Chen, Jiangchuan Sun, Shuning Chen, Yujiao Liu, Shenyin Zhu, Zhigang Wang, Shufang Chang
Purpose: Nanomedicine has emerged as a novel therapeutic modality for cancer treatment and diagnosis. Lipid-polymer hybrid nanoparticles (LPHNPs) are core-shell nanoparticle (NP) structures comprising polymer cores and lipid shells, which exhibit complementary characteristics of both polymeric NPs and liposomes. However, it is difficult to wrap perfluoropentane (PFP) into core-shell NPs in the existing preparation process, which limits its application in the integration of diagnosis and treatment...
2019: International Journal of Nanomedicine
Hiroyuki Suzuki, Mitsutake Yano, Mariko Miyazawa, Masaki Miyazawa, Naoki Ogane, Kosei Hasegawa, Hitoshi Tsuda, Masayuki Yoshida, Ryugo Okagaki, Osamu Ishihara, Masanori Yasuda
BACKGROUND: Ovarian clear cell carcinoma (OCCC) is the second most common ovarian cancer after serous carcinoma in Japan. OCCC has a more unfavorable clinical outcome due to a poor response to platinum-based chemotherapy, compared with serous carcinoma. Hypoxia inducible factor-1α (HIF-1α) is a key regulator of cellular response to hypoxia and plays an important role in tumor growth, and HIF-1α gene single-nucleotide polymorphisms (SNPs) adversely affect the outcome in some cancers...
January 24, 2019: Journal of Ovarian Research
Peter C Hart, Tatsuyuki Chiyoda, Xiaojing Liu, Melanie Weigert, Marion Curtis, Chun-Yi Chiang, Rachel Loth, Ricardo Lastra, Stephanie M McGregor, Jason W Locasale, Ernst Lengyel, Iris L Romero
The role of phospholipid signaling in ovarian cancer (OvCa) is poorly understood. Sphingosine-1-phosphate (S1P) is a bioactive metabolite of sphingosine that has been associated with tumor progression through enhanced cell proliferation and motility. Similarly, sphingosine kinases (SPHK), which catalyze the formation of S1P and thus regulate the sphingolipid rheostat, have been reported to promote tumor growth in a variety of cancers. The findings reported here show that exogenous S1P or overexpression of SPHK1 increased proliferation, migration, invasion and stem-like phenotypes in OvCa cell lines...
January 17, 2019: Molecular Cancer Research: MCR
Yongqing Cai, Jian Huang, Haiyan Xing, Bin Li, Ling Li, Xianfeng Wang, Dan Peng, Jianhong Chen
Background/purpose: The aim of this study was to investigate the role and mechanisms of the formyl peptide receptor (FPR) and the toll-like receptor 9 (TLR9) in hypoxia-induced chemoresistance of human ovarian cancer cells. Materials and methods: SKOV3 cells were exposed to hypoxia for 24 hours, the supernatant was collected to stimulate normoxia-cultured SKOV3, and the inhibition rate of cell growth was detected with CCK8 test. The agonist of TLR9 CpG ODN and the agonist of FPR fMLF were applied to investigate the chemosensitivity of SKOV3 cells to cisplatin...
2019: OncoTargets and Therapy
Dawei Wang, Dong You, Lei Li
Galectin-3 (Gal-3) is a multifunctional carbohydrate-binding protein associated with cell migration, cell proliferation, cell adhesion, and cell-cell interaction in tumor cells. It has been implied to be involved in the tumor progression and chemoresistance of epithelial ovarian cancer (EOC). However, it is unclear whether the Gal-3-mediated regulation on the EOC chemosensitivity is associated with hypoxia or mitochondrial dysfunction. In the present study, we examined the regulation by Gal-3 overexpression on cisplatin-sensitivity or cisplatin-resistance in EOC cells in vitro...
2019: Journal of Toxicological Sciences
Edith Emmings, Sally Mullany, Zenas Chang, Charles N Landen, Stig Linder, Martina Bazzaro
Ovarian cancer is the leading cause of death from gynecologic malignancy in the Western world. This is due, in part, to the fact that despite standard treatment of surgery and platinum/paclitaxel most patients recur with ultimately chemoresistant disease. Ovarian cancer is a unique form of solid tumor that develops, metastasizes and recurs in the same space, the abdominal cavity, which becomes a unique microenvironment characterized by ascites, hypoxia and low glucose levels. It is under these conditions that cancer cells adapt and switch to mitochondrial respiration, which becomes crucial to their survival, and therefore an ideal metabolic target for chemoresistant ovarian cancer...
January 8, 2019: International Journal of Molecular Sciences
Jun-Jun Qiu, Xiao-Jing Lin, Ting-Ting Zheng, Xiao-Yan Tang, Ke-Qin Hua
Purpose: Hypoxia is a key stress that triggers apoptosis in various tumors, including epithelial ovarian cancer (EOC). Previous researches identified a hypoxia-upregulated lncRNA named "a natural antisense transcript of hypoxia-inducible factor 1 (aHIF)" in some tumors. However, the contribution of aHIF to EOC remains unclear. Here, we aimed to investigate the expression, function, and underlying mechanisms of aHIF in EOC progression under hypoxia. Materials and methods: Expression levels of aHIF in EOC tissues were tested...
2018: OncoTargets and Therapy
Miao He, Huizhe Wu, Qian Jiang, Yinuo Liu, Li Han, Yuanyuan Yan, Binbin Wei, Fangxiao Liu, Xiaolan Deng, Huiying Chen, Lin Zhao, Min Wang, Xin Wu, Weifan Yao, Haishan Zhao, Jianjun Chen, Minjie Wei
Ovarian cancer stem cells (OCSCs) are sources of tumor chemoresistance and recurrence. A hypoxic microenvironment contributes to the chemoresistance of cancer stem cells (CSCs), but the underlying mechanism is not fully understood yet. Here, we show that increased HIF-2α expression is associated with enhanced stemness of OCSCs and poor outcomes in ovarian cancer patients. OVCAR-3 and CAOV-3 sphere-forming (OVCAR-3 S and CAOV-3 S) cells with OCSC-like properties showed strong resistance to adriamycin (ADR)...
February 2019: Molecular Oncology
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
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