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https://www.readbyqxmd.com/read/29212208/ruxolitinib-sensitizes-ovarian-cancer-to-reduced-dose-taxol-limits-tumor-growth-and-improves-survival-in-immune-competent-mice
#1
Patrick M Reeves, Mojgan A Abbaslou, Farah R W Kools, Kritchai Vutipongsatorn, Xiaoyun Tong, Christina Gavegano, Raymond F Schinazi, Mark C Poznansky
Background: Chemotherapy initially reduces the tumor burden in patients with ovarian cancer. However, tumors recur in over 70% of patients, creating the need for novel therapeutic approaches. Methods: We evaluated Ruxolitinib, an FDA-approved JAK 1/2 kinase inhibitor, as a potential adjunctive therapy for use with low-dose Taxol (Paclitaxel) by assessing the impact on in vitro proliferation and colony formation of ID8 cells or human TOV-112D ovarian cancer cells, as well as flow cytometric measurement of surface markers associated with cellular stress and stemness by ID8 cells...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29203787/crispr-cas9-derived-models-of-ovarian-high-grade-serous-carcinoma-targeting-brca1-pten-and-nf1-and-correlation-with-platinum-sensitivity
#2
Josephine B Walton, Malcolm Farquharson, Susan Mason, Jennifer Port, Bjorn Kruspig, Suzanne Dowson, David Stevenson, Daniel Murphy, Martin Matzuk, Jaeyeon Kim, Seth Coffelt, Karen Blyth, Iain A McNeish
Transplantable murine models of ovarian high grade serous carcinoma (HGSC) remain an important research tool. We previously showed that ID8, a widely-used syngeneic model of ovarian cancer, lacked any of the frequent mutations in HGSC, and used CRISPR/Cas9 gene editing to generate derivatives with deletions in Trp53 and Brca2. Here we have used one ID8 Trp53 -/- clone to generate further mutants, with additional mutations in Brca1, Pten and Nf1, all of which are frequently mutated or deleted in HGSC. We have also generated clones with triple deletions in Trp53, Brca2 and Pten...
December 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29171115/carboplatin-and-programmed-death-ligand-1-blockade-synergistically-produce-a-similar-antitumor-effect-to-carboplatin-alone-in-murine-id8-ovarian-cancer-model
#3
Xinxin Zhu, Jia Xu, Han Cai, Jinghe Lang
AIM: In advanced, platinum resistant or refractory ovarian cancer (OC), the therapeutic efficacy of carboplatin is controversial. Although anti-programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) pathway blockages show great potential in cancer treatment, the antitumor effect of single anti-PD-L1 pathway monoclonal antibody (mAb) is not obvious in advanced or some poorly immunogenic tumors, including OC. We compared the effects of single or combined carboplatin and anti-PD-L1 mAb treatments and explored the possible antitumor mechanisms in a murine ID8 OC model...
November 24, 2017: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/29150563/nfat5-regulated-macrophage-polarization-supports-the-proinflammatory-function-of-macrophages-and-t-lymphocytes
#4
Mónica Tellechea, Maria Buxadé, Sonia Tejedor, Jose Aramburu, Cristina López-Rodríguez
Macrophages are exquisite sensors of tissue homeostasis that can rapidly switch between pro- and anti-inflammatory or regulatory modes to respond to perturbations in their microenvironment. This functional plasticity involves a precise orchestration of gene expression patterns whose transcriptional regulators have not been fully characterized. We had previously identified the transcription factor NFAT5 as an activator of TLR-induced responses, and in this study we explore its contribution to macrophage functions in different polarization settings...
November 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28927115/wee1-inhibition-by-mk1775-as-a-single-agent-therapy-inhibits-ovarian-cancer-viability
#5
Minghui Zhang, Donye Dominguez, Siqi Chen, Jie Fan, Lei Qin, Alan Long, Xia Li, Yi Zhang, Huirong Shi, Bin Zhang
Wee1-like protein kinase (WEE1) physiologically serves a key function in maintaining the integrity of the cell genome through mediating the activation of cyclin-dependent kinase (CDK)1 and CDK2. Increased expression of WEE1 has been associated with the poor prognosis of patients with ovarian cancer. The present study aimed at examining the in vitro and in vivo antitumor activity of MK1775, a potent pharmacological inhibitor of WEE1, as a single agent against ovarian cancer cells. The cytotoxicity of MK1775 was examined in a panel of tumor cells using MTT in vitro...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28817386/cxcr4-blockade-with-amd3100-enhances-taxol-chemotherapy-to-limit-ovarian-cancer-cell-growth
#6
Patrick M Reeves, Mojgan A Abbaslou, Farah R W Kools, Mark C Poznansky
The standard of care for ovarian cancer includes initial treatment with chemotherapy. Despite initial efficacy, over 70% of patients develop recurrence; thus, there is a need to identify novel approaches that can improve therapeutic outcomes. We evaluated AMD3100 (Plerixafor), an FDA-approved CXCR4 inhibitor, as a potential adjunctive therapy for low-dose Taxol (Paclitaxel) by assessing the impact on in-vitro ovarian cancer cell proliferation. Proliferation was a measure for both human TOV-112D and murine ID8 ovarian cancer cells incubated with AMD3100 and Taxol, either individually or in combination...
August 16, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28667027/synergy-between-paclitaxel-and-anti-cancer-peptide-pnc-27-in-the-treatment-of-ovarian-cancer
#7
Ioannis Alagkiozidis, Constantine Gorelick, Tana Shah, Yi-Ju Amy Chen, Vinita Gupta, Dimitre Stefanov, Abhi Amarnani, Yi-Chun Lee, Ovadia Abulafia, Ehsan Sarafraz-Yazdi, Josef Michl
OBJECTIVES: Paclitaxel is widely used in the treatment of gynecologic malignancies. It targets tumor cells in the M phase of the cell cycle. Cells in other phases survive the insult and repopulate the tumor. PNC-27 is a peptide synthesized of amino acids of the p53-MDM-2 binding domain. It kills various cancer cell lines in a dose-dependent manner. The goal of this study is to assess ovarian cancer cells' sensitivity to PNC-27 after surviving exposure to paclitaxel and to investigate the potential for synergy between PNC-27 and paclitaxel in the treatment of ovarian cancer...
May 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28657225/programmed-death-1-pathway-blockade-produces-a-synergistic-antitumor-effect-combined-application-in-ovarian-cancer
#8
REVIEW
Xinxin Zhu, Jinghe Lang
Programmed death-1 (PD-1) and its ligand are part of the immune checkpoint pathway that down-regulates effector T cells in immune response, thereby causing immune suppression. The PD-1/programmed death-ligand 1 (PD-L1) pathway can be blocked by antibodies to reverse tumor-mediated immunosuppression. However, advanced cancers such as stage III-IV ovarian cancer (OC) and certain types such as ID8 OC (a clone of C57BL/6 mouse OC) may hijack the PD-1/PD-L1 pathway to escape immune attack. When combined with chemotherapy, radiotherapy, targeted therapy, immunotherapy, or other agents, these PD-1/PD-L1 pathway blockages can produce a synergistic antitumor response in OC...
September 2017: Journal of Gynecologic Oncology
https://www.readbyqxmd.com/read/28498806/epigenetic-modifiers-upregulate-mhc-ii-and-impede-ovarian-cancer-tumor-growth
#9
Taylor B Turner, Selene Meza-Perez, Angelina Londoño, Ashwini Katre, Jacelyn E Peabody, Haller J Smith, Andres Forero, Lyse A Norian, J Michael Straughn, Donald J Buchsbaum, Troy D Randall, Rebecca C Arend
Expression of MHC class II pathway proteins in ovarian cancer correlates with prolonged survival. Murine and human ovarian cancer cells were treated with epigenetic modulators - histone deacetylase inhibitors and a DNA methyltransferase inhibitor. mRNA and protein expression of the MHC II pathway were evaluated by qPCR and flow cytometry. Treatment with entinostat and azacytidine of ID8 cells in vitro increased mRNA levels of Cd74, Ciita, and H2-Aa, H2-Eb1. MHC II and CD74 protein expression were increased after treatment with either agent...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28318643/cxcl10-alters-the-tumour-immune-microenvironment-and-disease-progression-in-a-syngeneic-murine-model-of-high-grade-serous-ovarian-cancer
#10
Katrina K Au, Nichole Peterson, Peter Truesdell, Gillian Reid-Schachter, Kasra Khalaj, Runhan Ren, Julie-Ann Francis, Charles H Graham, Andrew W Craig, Madhuri Koti
OBJECTIVE: We recently established that high STAT1 expression and associated T helper type I tumour immune microenvironment (TME) are prognostic and chemotherapy response predictive biomarkers in high-grade serous ovarian cancer (HGSC). STAT1 induced chemokine CXCL10 is key to the recruitment of lymphocytes in the TME and is significantly highly expressed in the tumours from patients with longer survival. In the current study we therefore aimed to elucidate the role CXCL10 in disease progression and tumour immune transcriptomic alterations using the ID8 syngeneic murine model of HGSC...
June 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28150214/exploiting-uptake-of-nanoparticles-by-phagocytes-for-cancer-treatment
#11
Mee Rie Sheen, Steven Fiering
Many cancers including ovarian, pancreatic, colon, liver, and stomach cancers are largely confined to the peritoneal cavity. Peritoneal tumors are directly accessible by intraperitoneal injections. Previously we demonstrated that intraperitoneal injection of nanoparticles and subsequent ingestion by tumor-associated phagocytes can be used to either directly impact tumors or stimulate antitumor immune responses. Here we outline methods to specifically utilize iron oxide nanoparticles with the ID8-Defb29/Vegf-A murine ovarian cancer model and discuss the tendency of phagocytes to ingest nanoparticles and the potential of phagocytes to carry nanoparticles to tumors resulting in direct killing of tumor cells or stimulate antitumor immune responses in peritoneal cancers...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27852034/thrombin-inhibition-and-cisplatin-block-tumor-progression-in-ovarian-cancer-by-alleviating-the-immunosuppressive-microenvironment
#12
Eric T Alexander, Allyson R Minton, Molly C Peters, Joanne van Ryn, Susan K Gilmour
Cancer is often associated with an increased risk of thrombotic complications which can be aggravated by treatment with chemotherapeutics such as cisplatin. Multiple lines of evidence suggest that thrombin activity promotes tumor growth and metastasis. We examined the effect of co-treatment with dabigatran etexilate, a direct thrombin inhibitor, and cisplatin using the murine ID8 ovarian cancer model. Mice receiving co-treatment with both dabigatran etexilate and low dose cisplatin had significantly smaller tumors, developed less ascites and had lower levels of circulating activated platelets and tissue factor (TF) positive microparticles than those treated with dabigatran etexilate or cisplatin alone...
December 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27793901/in-vitro-generation-of-murine-dendritic-cells-for-cancer-immunotherapy-an-optimized-protocol
#13
Thaïs Baert, Abhishek D Garg, Eva Vindevogel, Anaïs VAN Hoylandt, Godelieve Verbist, Patrizia Agostinis, Ignace Vergote, A N Coosemans
BACKGROUND/AIM: Dendritic cell (DC) immunotherapy induces tumor-reactive T-cells. We optimized the maturation of murine DC against ovarian cancer. MATERIALS AND METHODS: Immature DC were generated from bone-marrow progenitor cells and loaded with hypericin-photodynamic-treated (Hyp-PDT) tumor cells (primary maturation). Lipopolysacharide (LPS 1 μg/ml) was used as a secondary maturation stimulus. After 24 h, maturation was assessed using flow cytometry. For in vivo experiments, C57BL/6 mice were vaccinated subcutaneously with matured, loaded mature DC...
November 2016: Anticancer Research
https://www.readbyqxmd.com/read/27793900/the-use-of-toll-like-receptor-4-agonist-to-reshape-the-immune-signature-in-ovarian-cancer
#14
Eva Vindevogel, Thaïs Baert, Anaïs VAN Hoylandt, Godelieve Verbist, Greetje Vande Velde, Abhishek D Garg, Patricia Agostinis, Ignace Vergote, A N Coosemans
BACKGROUND: Dendritic cell (DC) mono-immunotherapy has not been successful so far in ovarian cancer. The addition of a toll-like receptor (TLR) agonist has the potential to boost the innate immune system, in addition to the adoptive immune response initiated by DCs. MATERIALS AND METHODS: ID8-fLuc C57BL/6 mice were injected with DCs loaded with hypericin-based photodynamic therapy-treated tumor lysate. A TLR4 agonist [lipopolysaccharide (LPS)] was administered by different schedules)...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27638860/antitumor-and-antiangiogenic-effects-of-aspirin-pc-in-ovarian-cancer
#15
Yan Huang, Lenard M Lichtenberger, Morgan Taylor, Justin N Bottsford-Miller, Monika Haemmerle, Michael J Wagner, Yasmin Lyons, Sunila Pradeep, Wei Hu, Rebecca A Previs, Jean M Hansen, Dexing Fang, Piotr L Dorniak, Justyna Filant, Elizabeth J Dial, Fangrong Shen, Hiroto Hatakeyama, Anil K Sood
To determine the efficacy of a novel and safer (for gastrointestinal tract) aspirin (aspirin-PC) in preclinical models of ovarian cancer, in vitro dose-response studies were performed to compare the growth-inhibitory effect of aspirin-PC versus aspirin on three human (A2780, SKOV3ip1, and HeyA8) and a mouse (ID8) ovarian cancer cell line over an 8-day culture period. In the in vivo studies, the aspirin test drugs were studied alone and in the presence of a VEGF-A inhibitor (bevacizumab or B20), due to an emerging role for platelets in tumor growth following antiangiogenic therapy, and we examined their underlying mechanisms...
December 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27533079/akt-isoform-specific-effects-in-ovarian-cancer-progression
#16
Nicolle M Linnerth-Petrik, Lisa A Santry, Roger Moorehead, Manfred Jücker, Sarah K Wootton, Jim Petrik
Ovarian cancer remains a significant therapeutic problem and novel, effective therapies are needed. Akt is a serine-threonine kinase that is overexpressed in numerous cancers, including ovarian. Mammalian cells express three Akt isoforms which are encoded by distinct genes. Although there are several Akt inhibitors in clinical trials, most indiscriminately target all isoforms. Current in vitro data and animal knockout experiments suggest that the Akt isoforms may have divergent roles. In this paper, we determined the isoform-specific functions of Akt in ovarian cancer cell proliferation in vitro and in ovarian cancer progression in vivo...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27530326/crispr-cas9-mediated-trp53-and-brca2-knockout-to-generate-improved-murine-models-of-ovarian-high-grade-serous-carcinoma
#17
Josephine Walton, Julianna Blagih, Darren Ennis, Elaine Leung, Suzanne Dowson, Malcolm Farquharson, Laura A Tookman, Clare Orange, Dimitris Athineos, Susan Mason, David Stevenson, Karen Blyth, Douglas Strathdee, Frances R Balkwill, Karen Vousden, Michelle Lockley, Iain A McNeish
There is a need for transplantable murine models of ovarian high-grade serous carcinoma (HGSC) with regard to mutations in the human disease to assist investigations of the relationships between tumor genotype, chemotherapy response, and immune microenvironment. In addressing this need, we performed whole-exome sequencing of ID8, the most widely used transplantable model of ovarian cancer, covering 194,000 exomes at a mean depth of 400× with 90% exons sequenced >50×. We found no functional mutations in genes characteristic of HGSC (Trp53, Brca1, Brca2, Nf1, and Rb1), and p53 remained transcriptionally active...
October 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27447857/il-17a-exacerbates-cisplatin-based-resistance-of-ovca-via-upregulating-the-expression-of-abcg2-and-mdr1-through-gli1-mediated-hh-signaling
#18
Xiulong Niu, Wenxing Liu, Yue Wang, Xiaomei Liu, Hongjian Zhang, Zhijun Li, Hongzhao Li, Yoichiro Iwakura, Weimin Deng
The major obstacle of the tumor chemotherapy, including ovarian cancer (OVCA), is drug resistance. However, the relevance of IL-17A with drug-resistance of OVCA has been poorly elaborated. In this study, we used 2 human OVCA cell lines to investigate the effects of IL-17A on cisplatin (CDDP or DDP)-based resistance in OVCA cells and the underlying mechanisms. Meanwhile, IL-17A-deficient mice and ID8 were used to verify the IL-17A's effects on OVCA chemo-resistance in vivo. Moreover, the relationship between IL-17A level and relevant indices were primarily assessed in ovarian specimens from 55 patients with OVCA...
July 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27329838/ovarian-tumour-growth-is-characterized-by-mevalonate-pathway-gene-signature-in-an-orthotopic-syngeneic-model-of-epithelial-ovarian-cancer
#19
James B Greenaway, Carl Virtanen, Kata Osz, Tamas Revay, Daniel Hardy, Trevor Shepherd, Gabriel DiMattia, Jim Petrik
Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer and often is not detected until late stages when cancer cells transcoelomically metastasize to the abdomen and typically become resistant to therapy resulting in very low survival rates. We utilize an orthotopic, syngeneic mouse model to study late stage disease and have discovered that the tumor cells within the abdominal ascites are irreversibly re-programmed, with an increased tumorigenicity and resistance to apoptosis. The goal of this study was to characterize the reprogramming that occurred in the aggressive ascites-derived cells (28-2 cells) compared to the original cell line used for tumor induction (ID8 cells)...
July 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27238440/evaluation-of-microparticulate-ovarian-cancer-vaccine-via-transdermal-route-of-delivery
#20
Suprita A Tawde, Lipika Chablani, Archana Akalkotkar, Martin J D'Souza
Ovarian cancer is the fifth most commonly occurring malignancy in women, with the highest mortality rate among all the gynecological tumors. Microparticulate vaccine can serve as an immunotherapeutic approach with a promising antigenic delivery system without a need for conventional adjuvants. In this study, a microparticulate vaccine using whole cell lysate of a murine ovarian cancer cell line, ID8 was prepared by spray drying. Further, the effect of interleukins (ILs) such as IL-2 and IL-12 was evaluated in a separate study group by administering them with vaccine particles to enhance the immune response...
August 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
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