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https://www.readbyqxmd.com/read/29133618/therapeutic-impact-of-nanoparticle-therapy-targeting-tumor-associate-macrophages
#1
Courtney Penn, Kun Yang, Hong Zong, Jae-Young Lim, Alex Cole, Dongli Yang, James Baker, Sascha N Goonewardena, Ronald J Buckanovich
Antiangiogenic therapies, despite initial encouragement, have demonstrated a limited benefit in ovarian cancer. Laboratory studies suggest anti-angiogenic therapy induced hypoxia can induce tumor "stemness' as resistance to antiangiogenic therapy develops and limits the therapeutic benefit. Resistance to antiangiogenic therapy and an induction of tumor stemness may be mediated by proangiogenic tumor associated macrophages (TAMs). As such TAMs have been proposed as a therapeutic target. We demonstrate here that ovarian TAMs express high levels of the folate receptor-2 (FOLR2) and can be selectively targeted using G5-dendrimer nanoparticles using methotrexate as both a ligand and a toxin...
November 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29059175/induction-of-anti-vegf-therapy-resistance-by-upregulated-expression-of-microseminoprotein-msmp
#2
T Mitamura, S Pradeep, M McGuire, S Y Wu, S Ma, H Hatakeyama, Y A Lyons, T Hisamatsu, K Noh, A Villar-Prados, X Chen, C Ivan, C Rodriguez-Aguayo, W Hu, G Lopez-Berestein, R L Coleman, A K Sood
Anti-vascular endothelial growth factor (VEGF) therapy has demonstrated efficacy in treating human metastatic cancers, but therapeutic resistance is a practical limitation and most tumors eventually become unresponsive. To identify microenvironmental factors underlying the resistance of cancer to antiangiogenesis therapy, we conducted genomic analyses of intraperitoneal ovarian tumors in which adaptive resistance to anti-VEGF therapy (B20 antibody) developed. We found that expression of the microseminoprotein, prostate-associated (MSMP) gene was substantially upregulated in resistant compared with control tumors...
October 23, 2017: Oncogene
https://www.readbyqxmd.com/read/29050245/von-hippel-lindau-regulates-interleukin-32%C3%AE-stability-in-ovarian-cancer-cells
#3
Hyo Jeong Yong, Jeong Su Park, Ae Lee Jeong, Sora Han, Sunyi Lee, Hye In Ka, Buyanravjkh Sumiyasuren, Hyun Jeong Joo, Su Jeong So, Ji Young Park, Do-Young Yoon, Jong-Seok Lim, Myeong-Seok Lee, Hee Gu Lee, Young Yang
Hypoxia-induced interleukin-32β (IL-32β) shifts the metabolic program to the enhanced glycolytic pathway. In the present study, the underlying mechanism by which hypoxia-induced IL-32β stability is regulated was investigated in ovarian cancer cells. IL-32β expression increased under hypoxic conditions in ovarian cancer cells as it did in breast cancer cells. The amount of IL-32β was regulated by post-translational control rather than by transcriptional activation. Under normoxic conditions, IL-32β was continuously eliminated through ubiquitin-dependent degradation by the von-Hippel Lindau (VHL) E3 ligase complex...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29033850/designing-dietary-recommendations-using-system-level-interactomics-analysis-and-network-based-inference
#4
Tingting Zheng, Yueqiong Ni, Jun Li, Billy K C Chow, Gianni Panagiotou
Background: A range of computational methods that rely on the analysis of genome-wide expression datasets have been developed and successfully used for drug repositioning. The success of these methods is based on the hypothesis that introducing a factor (in this case, a drug molecule) that could reverse the disease gene expression signature will lead to a therapeutic effect. However, it has also been shown that globally reversing the disease expression signature is not a prerequisite for drug activity. On the other hand, the basic idea of significant anti-correlation in expression profiles could have great value for establishing diet-disease associations and could provide new insights into the role of dietary interventions in disease...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28959512/hypoxia-activated-alkylating-agents-in-brca1-mutant-ovarian-serous-carcinoma
#5
Michael Conroy, Mitesh J Borad, Alan H Bryce
Breast cancer 1 antigen (BRCA 1) and breast cancer 2 antigen (BRCA2) genes play a significant role in deoxyribonucleic acid (DNA) repair by means of interstrand crosslink repair, and deleterious germline mutations of these are responsible for most hereditary breast and ovarian cancers. Therapeutic strategies which specifically target interstrand crosslink repair can therefore be helpful in patients with harmful mutations. We describe two patients with advanced ovarian cancer and deleterious BRCA1 mutations who were treated with TH-302, a hypoxia-activated alkylating agent...
July 26, 2017: Curēus
https://www.readbyqxmd.com/read/28928801/ginsenoside-rb1-inhibits-hypoxia-induced-epithelial-mesenchymal-transition-in-ovarian-cancer-cells-by-regulating-microrna-25
#6
Dan Liu, Ting Liu, Yue Teng, Wei Chen, Le Zhao, Xu Li
Metastasis frequently occurs in advanced ovarian cancer, which not only leads to substantial mortality but also becomes a major challenge to effective treatment. Epithelial-mesenchymal transition (EMT) is a key mechanism facilitating cancer metastasis. Targeting the EMT process with more efficacious and less toxic agents to prevent metastasis is of significant therapeutic value for ovarian cancer treatment. The anti-EMT function and mechanism of ginsenoside Rb1, a monomer composition extracted from the traditional Chinese herb Panax ginseng or P...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28912871/paeonol-enhances-the-sensitivity-of-human-ovarian-cancer-cells-to-radiotherapy-induced-apoptosis-due-to-downregulation-of-the-phosphatidylinositol-3-kinase-akt-phosphatase-and-tensin-homolog-pathway-and-inhibition-of-vascular-endothelial-growth-factor
#7
Hai-Mei Zhou, Qin-Xiang Sun, Yan Cheng
Radiotherapy is a vital and effective method to treat solid tumors. However, in many tumor types, development of resistance of cancer cells and cytotoxicity in normal tissues presents a major therapeutic problem. It is therefore crucial to identify and develop novel sensitizing agents that may improve the response to radiation therapy without causing any adverse effects. The present study aimed to investigate whether paeonol, a bioactive flavonoid, was able to confer sensitivity to radiation in human ovarian cancer cells...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28878214/hypoxia-inducible-factor-1-alpha-promotes-cancer-stem-cells-like-properties-in-human-ovarian-cancer-cells-by-upregulating-sirt1-expression
#8
Jie Qin, Yan Liu, Yongkui Lu, Meiling Liu, Manli Li, Juan Li, Lijuan Wu
Ovarian cancer have a poor overall survival rate in patients, and late disease presentation and chemoresistance are the main factors that lead to the mortality of ovarian cancer. Cancer stem cells (CSCs), a small subpopulation of cancer cells, have been associated with resistance to chemo- and radio-therapy in cancer treatment. Hypoxia is a common characteristic of many malignant tumors, and increased HIF-1α expression predicts the poor prognosis of ovarian cancer. In this study, we reported the relationship between hypoxia and cancer stem cells-like properties in human ovarian cancer cell lines SKOV3 and HO8910, we found that hypoxia induced cancer stem cells-like properties in ovarian cancer cells...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28791360/classical-vegf-notch-and-ang-signalling-in-cancer-angiogenesis-alternative-approaches-and-future-directions-review
#9
Nunzia Caporarello, Gabriella Lupo, Melania Olivieri, Martina Cristaldi, Maria Teresa Cambria, Mario Salmeri, Carmelina Daniela Anfuso
Angiogenesis is the formation of new vessels starting from pre-existing vasculature. Tumour environment is characterized by 'aberrant angiogenesis', whose main features are tortuous and permeable blood vessels, heterogeneous both in their structure and in efficiency of perfusion and very different from normal vessels. Therapeutic strategies targeting the three pathways chiefly involved in tumour angiogenesis, VEGF, Notch and Ang signalling, have been identified to block the vascular supply to the tumour. However, phenomena of toxicity, development of primary and secondary resistance and hypoxia significantly blunted the effects of anti-angiogenic drugs in several tumour types...
October 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28754884/von-hippel-lindau-regulates-interleukin-32%C3%AE-stability-in-ovarian-cancer-cells
#10
Hyo Jeong Yong, Jeong Su Park, Ae Lee Jeong, Sora Han, Sunyi Lee, Hye In Ka, Buyanravjkh Sumiyasuren, Hyun Jeong Joo, Su Jeong So, Ji Young Park, Do-Young Yoon, Jong Seok Lim, Myeong-Seok Lee, Hee Gu Lee, Young Yang
Hypoxia-induced interleukin-32β (IL-32β) shifts the metabolic program to the enhanced glycolytic pathway. In the present study, the underlying mechanism by which hypoxia-induced IL-32β stability is regulated was investigated in ovarian cancer cells. IL-32β expression increased under hypoxic conditions in ovarian cancer cells as it did in breast cancer cells. The amount of IL-32β was regulated by post-translational control rather than by transcriptional activation. Under normoxic conditions, IL-32β was continuously eliminated through ubiquitin-dependent degradation by the von-Hippel Lindau (VHL) E3 ligase complex...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28726915/oleuropein-represses-the-radiation-resistance-of-ovarian-cancer-by-inhibiting-hypoxia-and-microrna-299-targetted-heparanase-expression
#11
Yubai Xing, Dawei Cui, Shun Wang, Pingping Wang, Xiaojing Xing, Hui Li
Radiotherapy in ovarian cancer frequently invokes resistance; this severely compromises its therapeutic effect and results in poor clinical prognosis. How to overcome the acquired resistance and re-sensitize tumors to radiation is the central question in this clinical setting. Cancer cell survival was evaluated using a clonogenic assay. The microRNA expression profile was analyzed using a microarray. Transcript expression was determined using real time PCR. The expression of protein was determined by immunoblotting...
August 1, 2017: Food & Function
https://www.readbyqxmd.com/read/28678326/expression-levels-of-pten-hif-1%C3%AE-and-vegf-as-prognostic-factors-in-ovarian-cancer
#12
W Shen, H-L Li, L Liu, J-X Cheng
OBJECTIVE: Epithelial ovarian cancer is associated with high mortality, mostly because of delayed diagnosis, necessitating the search for novel diagnostic and prognostic markers. Here we evaluated the association between expression levels of phosphatase and tensin homolog (PTEN), hypoxia-inducible factor (HIF)-1α, and vascular endothelial growth factor (VEGF), and ovarian cancer. PATIENTS AND METHODS: Expressions of these proteins were assessed by immunohistochemistry in 21 specimens of normal ovary tissues and 76 specimens of ovarian cancer tissues...
June 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28603724/pulmonary-embolism-in-transit
#13
Anna Koulova, Ramin Malekan, Wilbert S Aronow, Howard A Cooper
A 65-year-old woman with recently diagnosed ovarian cancer presented with near syncope, tachypnea, and hypoxia. Transthoracic echocardiography revealed a dilated and hypokinetic right ventricle and a large, mobile mass in the right atrium prolapsing across the tricuspid valve. She was diagnosed with pulmonary embolism in transit and emergent embolectomy was recommended.
May 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28586039/exosomes-derived-from-hypoxic-epithelial-ovarian-cancer-deliver-microrna-940-to-induce-macrophage-m2-polarization
#14
Xin Chen, Xiang Ying, Xinjing Wang, Xiaoli Wu, Qinyi Zhu, Xipeng Wang
Hypoxia is a common feature of solid tumors. It is closely related to tumor progression. Exosomal microRNAs derived from cancers are considered to be mediators between cancer cells and the tumor microenvironment. In addition, the number of tumor-associated macrophages (TAMs) in the tumor microenvironment has also been demonstrated to correlate with tumor development. However, the relationship between tumor-secreted exosomes and TAM polarization under hypoxic conditions during tumor progression is not clear...
June 6, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28506752/thio-functionalized-carbohydrate-thiosemicarbazones-and-evaluation-of-their-anticancer-activity
#15
Anna Czubatka-Bieńkowska, Joanna Sarnik, Anna Macieja, Grzegorz Galita, Zbigniew J Witczak, Tomasz Poplawski
Thiosemicarbazides and their analogs have shown potential medical applications as antiviral, antibacterial and anticancer drugs. We designed, synthesized and evaluated in vitro anticancer activity against ovarian (A2780), cervix (HeLa), colon (LoVo), breast (MCF-7) and brain (MO59J) human cancer cell lines of seven novel compounds -S-glycosylated thiosemicarbazones. We assessed the cyto- and genotoxic properties of all novel compounds using a variety of methods including comet assay, XTT assay, various fluorescent assays and toxicology PathwayFinder expression array...
June 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28459376/ginsenoside-20-s-rg3-suppresses-ovarian-cancer-migration-via-hypoxia-inducible-factor-1-alpha-and-nuclear-factor-kappa-b-signals
#16
Ting Liu, Le Zhao, Huilian Hou, Lu Ding, Wei Chen, Xu Li
Hypoxia-inducible factor 1 is believed to play a prominent role in the survival and developing progress of cancers. As a result, inhibiting α subunit of hypoxia-inducible factor 1 represents an attractive strategy against tumor. Although hypoxia-inducible factor 1α is a hypoxia-regulated subunit, increasing evidence indicates that hypoxia-inducible factor 1α could stable expression under normoxic conditions, regulated by non-hypoxia-mediated mechanisms. However, there are few strategies to target hypoxia-inducible factor 1α under normoxic conditions...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28450115/iron-regulatory-protein-2-in-ovarian-endometrial-cysts
#17
Motoki Takenaka, Noriko Suzuki, Minako Mori, Tasuku Hirayama, Hideko Nagasawa, Ken-Ichiro Morishige
Ovarian endometrial cysts cause some kinds of ovarian cancer, and iron is considered as one factor of carcinogenesis. In contrast, hypoxia is associated with progression, angiogenesis, metastasis, and resistance to therapy in cancer. We investigated hypoxia-induced perturbation of iron homeostasis in terms of labile iron, iron deposition, and iron regulatory protein (IRP) in ovarian endometrial cysts. Iron deposition, expression of IRPs, and a protein marker of hypoxia in human ovarian endometrial cysts were analyzed histologically...
June 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28417928/potential-coagulation-factor-driven-pro-inflammatory-responses-in-ovarian-cancer-tissues-associated-with-insufficient-o%C3%A2-and-plasma-supply
#18
REVIEW
Shiro Koizume, Yohei Miyagi
Tissue factor (TF) is a cell surface receptor for coagulation factor VII (fVII). The TF-activated fVII (fVIIa) complex is an essential initiator of the extrinsic blood coagulation process. Interactions between cancer cells and immune cells via coagulation factors and adhesion molecules can promote progression of cancer, including epithelial ovarian cancer (EOC). This process is not necessarily advantageous, as tumor tissues generally undergo hypoxia due to aberrant vasculature, followed by reduced access to plasma components such as coagulation factors...
April 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28401704/hif-1%C3%AE-binding-to-aeg-1-promoter-induced-upregulated-aeg-1-expression-associated-with-metastasis-in-ovarian-cancer
#19
Ting Zhao, Chenyan Zhao, Yanting Zhou, Jing Zheng, Shujun Gao, Yuan Lu
Ovarian cancer with the highest mortality rate among gynecological malignancies is one of common cancers among female cancer patients. As reported in recent years, AEG-1 was associated with the occurrence, development, and metastasis of ovarian cancer, but the mechanisms remain unclear. In the current study, invasion capabilities of ovarian cancer OVCAR3 cells were measured by viral infection and transwell assay. Western blot analysis was used to evaluate the expression levels of β-catenin, E-cadherin, MMP2, and MMP9...
May 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28398226/melatonin-reduces-angiogenesis-in-serous-papillary-ovarian-carcinoma-of-ethanol-preferring-rats
#20
Yohan Ricci Zonta, Marcelo Martinez, Isabel Cristina C Camargo, Raquel F Domeniconi, Luiz Antonio Lupi Júnior, Patricia Fernanda F Pinheiro, Russel J Reiter, Francisco Eduardo Martinez, Luiz Gustavo A Chuffa
Angiogenesis is a hallmark of ovarian cancer (OC); the ingrowth of blood vessels promotes rapid cell growth and the associated metastasis. Melatonin is a well-characterized indoleamine that possesses important anti-angiogenic properties in a set of aggressive solid tumors. Herein, we evaluated the role of melatonin therapy on the angiogenic signaling pathway in OC of an ethanol-preferring rat model that mimics the same pathophysiological conditions occurring in women. OC was chemically induced with a single injection of 7,12-dimethylbenz(a)anthracene (DMBA) under the ovarian bursa...
April 11, 2017: International Journal of Molecular Sciences
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