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https://www.readbyqxmd.com/read/28432813/targeting-on-poly-adp-ribose-polymerase-activity-with-dna-damaging-hybrid-lactam-steroid-alkylators-in-wild-type-and-brca1-mutated-ovarian-cancer-cells
#1
Dimitrios T Trafalis, Aikaterini Polonifi, Panayiotis Dalezis, Nikolaos Nikoleousakos, Sotirios Katsamakas, Vassiliki Sarli
Conjugated lactam-steroid alkylators (LSA), have been shown to exhibit superior activity at controlling cancer models and overlap drug resistance to conventional chemotherapy. Hybrid LSAs combine two active compounds in a single molecule and incorporate modified steroids bearing lactam moiety in one or more steroid rings functioning as vectors for cytotoxic agents. We first describe a novel class of LSAs that generate excellent anticancer activity against UWB1.289 and UWB1.289+BRCA1 human ovarian cancer cell lines...
April 22, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28432432/tgf%C3%AE-splicing-and-canonical-pathway-activation-in-high-grade-serous-carcinoma
#2
Neriya Gutgold, Ben Davidson, Liora Jacobs Catane, Arild Holth, Ellen Hellesylt, Claes G Tropé, Anne Dørum, Reuven Reich
The present study analyzed the expression and clinical role of the transforming growth factor-β (TGFβ) pathway in high-grade serous carcinoma (HGSC), with focus on malignant effusions. TGFβ1-3 and TGFβRI-III mRNA expression by qRT-PCR was analyzed in 70 HGSC effusions and 55 solid specimens (28 ovarian, 27 abdominal metastases). Protein expression of Smad2 and Smad3 and their phosphorylated forms by Western blotting was analyzed in 73 specimens (42 effusions, 13 ovarian carcinomas, 18 solid metastases)...
April 21, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28432270/discriminating-between-virilizing-ovary-tumors-and-ovary-hyperthecosis-in-postmenopausal-women-clinical-data-hormonal-profiles-and-image-studies
#3
Viviane Dos Reis Vieira Yance, José Antonio Miguel Marcondes, Michelle Patrocíneo Rocha, Cristiano Roberto Grimaldi Barcellos, Wagner Silva Dantas, Ana Flavia Assis Avila, Ronaldo Hueb Baroni, Filomena Marino Carvalho, Sylvia Asaka Yamashita Hayashida, Berenice Bilharinho Mendonça, Sorahia Domenice
The presence of virilizing signs associated with high serum androgen levels in postmenopausal women is rare. Virilizing ovarian tumors (VOTs) and ovarian stromal hyperthecosis (OH) are the most common etiologies in virilized postmenopausal women. The differential diagnosis between these two conditions is often difficult. OBJECTIVE: To evaluate the contribution of clinical features, hormonal profiles and radiological studies to the differential diagnosis of VOT and OH. DESIGN: A retrospective study...
April 21, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28431566/the-prognostic-value-of-the-preoperative-c-reactive-protein-albumin-ratio-in-ovarian-cancer
#4
Yubo Liu, Shengfu Chen, Chengyu Zheng, Miao Ding, Lan Zhang, Liangan Wang, Meiqing Xie, Jianhua Zhou
BACKGROUND: Inflammation plays an important role in the pathogenesis of ovarian cancer. This study sought to investigate the association between the preoperative c-reactive protein/albumin ratio (CRP/Alb) and oncological outcomes in ovarian cancer patients. METHODS: Two hundred patients with histologically verified ovarian cancer between June 2006 and July 2012 were retrospectively reviewed. Overall survival was evaluated by the Kaplan-Meier method and log-rank test...
April 21, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28431263/epigenetic-therapy-and-chemosensitization-in-solid-malignancy
#5
REVIEW
Sean M Ronnekleiv-Kelly, Anup Sharma, Nita Ahuja
Epigenetic modifications result in dynamic shifts between transcriptionally active and suppressed states. The potentially reversible nature of epigenetic changes underlies the concept of epigenetic therapy, which serves to reprogram cancer cells as opposed to inducing cytotoxicity that occurs with standard chemotherapeutics. There are numerous enzymes involved in epigenetic changes and each can be potentially targetable. Although many investigations have evaluated the clinical potential of the various epigenetic therapies, currently only histone deacetylase inhibitors and DNA methyltransferase inhibitors are approved for use in specific hematologic malignancies...
April 8, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28430641/the-regulation-of-%C3%AE-catenin-activity-and-function-in-cancer-therapeutic-opportunities
#6
REVIEW
Shuang Shang, Fang Hua, Zhuo-Wei Hu
Wnt/β-catenin signaling is an evolutionarily conserved and versatile pathway that is known to be involved in embryonic development, tissue homeostasis and a wide variety of human diseases. Aberrant activation of this pathway gives rise to the accumulation of β-catenin in the nucleus and promotes the transcription of many oncogenes such as c-Myc and CyclinD-1. As a result, it contributes to carcinogenesis and tumor progression of several cancers, including colon cancer, hepatocellular carcinoma, pancreatic cancer, lung cancer and ovarian cancer...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429716/polyembryoma-of-the-testis-a-report-of-two-cases-dominant-within-mixed-germ-cell-tumors-and-review-of-gonadal-polyembryomas
#7
REVIEW
Jennifer N Stall, Robert H Young
Two testicular mixed germ cell tumors, from men of 21 and 41 years, in which polyembryoma predominated are described. A literature review uncovered an additional five testicular and nine ovarian cases. One tumor occurred in a 60-year-old man, but all others occurred within the typical age range of gonadal germ cell tumors. One male presented with gynecomastia and one female with sexual precocity, but all otherwise had standard clinical manifestations. These tumors are typically large with non-specific gross features, but a few have a prominent hemorrhagic appearance...
April 21, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28429358/slpi-promotes-the-gastric-cancer-growth-and-metastasis-by-regulating-the-expression-of-p53-bcl-2-and-caspase-8
#8
X-Y Du, X Liu, Z-J Wang, Y-Y Wang
OBJECTIVE: The incidence of gastric cancer is very high all over the world, but the mechanism of the occurrence and development of gastric cancer is unclear. Secretory leukocyte protease inhibitor (SLPI) is overexpressed in gastric, lung and ovarian cancers, which accelerates the metastasis of cancer cells. In this research, we mainly explored the expression level and possible mechanism of SLPI in gastric cancer. PATIENTS AND METHODS: The expression and clinical significance of SLPI in 68 cases of gastric cancer tissues and adjacent tissues were detected by qRT-PCR...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28428125/ovarian-metastasis-of-a-malignant-melanoma-a-case-report
#9
A Mendel, J J Terzibachian, F Aubin, L Malicenco, R Ramanah, D Riethmuller
Malignant melanoma represents 3% of cancers at the woman. The metastatic gynecological localization are rare and ovary is an exceptional site. Prognosis of metastatic ovary malignant melanoma is pejorative (5% 5 years survival). We report a case observed in a 65-year-old patient, who developed 2 melanomas of the left leg and presented a right ovarian tumor during a supervision tomodensitometric 7 years after diagnostic initial. The immunohistochemical assays after annexectomy confirmed the diagnostic of ovarian metastasis...
April 17, 2017: J Gynecol Obstet Hum Reprod
https://www.readbyqxmd.com/read/28427776/autoantibody-biomarkers-for-the-detection-of-serous-ovarian-cancer
#10
Benjamin A Katchman, Diego Chowell, Garrick Wallstrom, Allison F Vitonis, Joshua LaBaer, Daniel W Cramer, Karen S Anderson
Objective The purpose of this study was to identify a panel of novel serum tumor antigen-associated autoantibody (TAAb) biomarkers for the diagnosis of high-grade serous ovarian cancer. METHODS: To detect TAAb we probed high-density programmable protein microarrays (NAPPA) containing 10,247 antigens with sera from patients with serous ovarian cancer (n=30 cases/30 healthy controls) and measured bound IgG. We identified 735 promising tumor antigens and evaluated these with an independent set of serous ovarian cancer sera (n=30 cases/30 benign disease controls/30 healthy controls)...
April 17, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28427560/stress-adaptive-response-in-ovarian-cancer-drug-resistance-role-of-trap1-in-oxidative-metabolism-driven-inflammation
#11
Maria Rosaria Amoroso, Danilo Swann Matassa, Ilenia Agliarulo, Rosario Avolio, Francesca Maddalena, Valentina Condelli, Matteo Landriscina, Franca Esposito
Metabolic reprogramming is one of the most frequent stress-adaptive response of cancer cells to survive environmental changes and meet increasing nutrient requirements during their growth. These modifications involve cellular bioenergetics and cross talk with surrounding microenvironment, in a dynamic network that connect different molecular processes, such as energy production, inflammatory response, and drug resistance. Even though the Warburg effect has long been considered the main metabolic feature of cancer cells, recent reports identify mitochondrial oxidative metabolism as a driving force for tumor growth in an increasing number of cellular contexts...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28427435/prohibitin-targeting-peptide-coupled-to-ovarian-cancer-luteinization-and-tgf-%C3%AE-pathways
#12
Nour M El-Etreby, Amany A Ghazy, Radwaa Rashad
BACKGROUND: Ovarian epithelial tumor (OET) is a silent disease of late diagnosis and poor prognosis. Currently treatment options are limited and patient response to treatment is difficult to predict so there is a serious need to delineate the real pathogenesis to predict tumour prognosis. Prohibitin (PHB) is an evolutionarily protein that regulates the cell cycle. TGF-β has been shown to be a positive and negative regulator of cellular proliferation and differentiation. The present study provides an overview on the role played by PHB1, TGF-β and LH in ovarian cancer...
April 20, 2017: Journal of Ovarian Research
https://www.readbyqxmd.com/read/28427221/ct-guided-125i-brachytherapy-for-recurrent-ovarian-cancer
#13
Ping Liu, Lina Tong, Bin Huo, Dong Dai, Wenxin Liu, Ke Wang, Ying Wang, Zhi Guo, Hong Ni
This retrospective study was to evaluate the local control and survival of 125I brachytherapy for recurrent ovarian cancer. 52 125I brachytherapy procedures were performed in 47 patients with 51 recurrent ovarian cancer lesions. The follow-up period was 1-55 months (median 12 months). The local control rate (LC) of 3, 6, 12, 24 and 36 months was 93.3%, 77.7%, 58.9%, 38.7% and 19.3%, respectively. Patients with tumor size ≤ 4cm (85.7% vs 40.0%, P = 0.037) and actual D90 between 110 to 130Gy (47.4% vs 66.7% vs 62...
March 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427178/prognostic-value-of-foxm1-in-solid-tumors-a-systematic-review-and-meta-analysis
#14
Lijun Li, Dang Wu, Qun Yu, Lingdi Li, Pin Wu
Accumulated studies have provided controversial evidences of the association between Forkhead Box M1 (FOXM1) expression and survival of human solid tumors. To address this inconsistency, we performed a meta-analysis with 23 studies identified from PubMed and Medline. We found elevated FOXM1-protein expression was significantly associated with worse 3-year overall survival (OS) (OR = 3.30, 95% CI = 2.56 to 4.25, P < 0.00001) 5-year OS (OR =3.35, 95% CI = 2.64 to 4.26, P < 0.00001) and 10-year OS (OR = 5...
February 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427157/the-anti-tumor-efficacy-of-3c23k-a-glyco-engineered-humanized-anti-misrii-antibody-in-an-ovarian-cancer-model-is-mainly-mediated-by-engagement-of-immune-effector-cells
#15
Pauline Estupina, Alexandre Fontayne, Jean-Marc Barret, Nathalie Kersual, Olivier Dubreuil, Marion Le Blay, Alexandre Pichard, Marta Jarlier, Martine Pugnière, Maëva Chauvin, Thierry Chardès, Jean-Pierre Pouget, Emmanuel Deshayes, Alexis Rossignol, Toufik Abache, Christophe de Romeuf, Aurélie Terrier, Lucie Verhaeghe, Christine Gaucher, Jean-François Prost, André Pèlegrin, Isabelle Navarro-Teulon
Ovarian cancer is the leading cause of death in women with gynecological cancers and despite recent advances, new and more efficient therapies are crucially needed. Müllerian Inhibiting Substance type II Receptor (MISRII, also named AMHRII) is expressed in most ovarian cancer subtypes and is a novel potential target for ovarian cancer immunotherapy. We previously developed and tested 12G4, the first murine monoclonal antibody (MAb) against human MISRII. Here, we report the humanization, affinity maturation and glyco-engineering steps of 12G4 to generate the Fc-optimized 3C23K MAb, and the evaluation of its in vivo anti-tumor activity...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426690/phenotypic-characterization-and-anticancer-capacity-of-cd8-cytokine-induced-killer-cells-after-antigen-induced-expansion
#16
Jianhua Liu, Lu Wang, Yaoling Wang, Wenjie Zhang, Yilin Cao
Cytokine-induced killer cells (CIK) have been used in clinic for adoptive immunotherapy in a variety of malignant tumors and have improved the prognosis of cancer patients. However, there are individual differences in the CIK cell preparations including the obvious differences in the ratio of effector CIK cells among different cancer patients. Infusion of such heterogeneous immune cell preparation is an important factor that would affect the therapeutic efficacy. We report here the enrichment and expansion of CD8+ cells from CIK cells cultured for one week using magnetic activated cell sorting (MACS)...
2017: PloS One
https://www.readbyqxmd.com/read/28426098/targeting-chromatin-defects-in-selected-solid-tumors-based-on-oncogene-addiction-synthetic-lethality-and-epigenetic-antagonism
#17
D Morel, G Almouzni, J-C Soria, S Postel-Vinay
Background: Although the role of epigenetic abnormalities has been studied for several years in cancer genesis and development, epigenetic-targeting drugs have historically failed to demonstrate efficacy in solid malignancies. However, successful targeting of chromatin remodeling deficiencies, histone writers and histone reader alterations has been achieved very recently using biomarker-driven and mechanism-based approaches. Epigenetic targeting is now one of the most active areas in drug development and could represent novel therapeutic opportunity for up to 25% of all solid tumors...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28425306/therapeutic-targeting-and-patient-selection-for-cancers-with-homologous-recombination-defects
#18
Francien Talens, Mathilde Jalving, Jourik A Gietema, Marcel A T M van Vugt
DNA double-strand breaks (DSBs) are toxic DNA lesions that can be repaired by non-homologous end-joining (NHEJ) or homologous recombination (HR). Mutations in HR genes elicit a predisposition to cancer; yet, they also result in increased sensitivity to certain DNA damaging agents and poly (ADP-ribose) polymerase (PARP) inhibitors. To optimally implement PARP inhibitor treatment, it is important that patients with HR-deficient tumors are adequately selected. Areas covered: Herein, the authors describe the HR pathway mechanistically and review the treatment of HR-deficient cancers, with a specific focus on PARP inhibition for BRCA1/2-mutated breast and ovarian cancer...
April 20, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28424410/ascites-promotes-cell-migration-through-the-repression-of-mir-125b-in-ovarian-cancer
#19
Lan Yang, Xiaoli Zhang, Yiming Ma, Xinhua Zhao, Bin Li, Hongying Wang
Interactions between ovarian cancer cells and the surrounding tumor microenvironment are not well characterized. Here, we investigated the molecular mechanisms by which malignant ascites promote the metastasis of ovarian cancer. It was found that ovarian cancer ascites promoted ovarian cancer cell migration which was attenuated by either heat inactivation or antibody blockade of TGF-β. High level (at ng/ml level) of TGF-β was detected in the ascites. In addition, ascites repressed the expression of miRNA-125b in a TGF-β-dependent manner...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423708/targeting-the-centriolar-replication-factor-stil-synergizes-with-dna-damaging-agents-for-treatment-of-ovarian-cancer
#20
Noa Rabinowicz, Lingegowda S Mangala, Kevin R Brown, Cintia Checa-Rodriguez, Asher Castiel, Oren Moskovich, Giulia Zarfati, Luba Trakhtenbrot, Adva Levy-Barda, Dahai Jiang, Cristian Rodriguez-Aguayo, Sunila Pradeep, Yael van Praag, Gabriel Lopez-Berestein, Ahuvit David, Ilya Novikov, Pablo Huertas, Robert Rottapel, Anil K Sood, Shai Izraeli
Advanced ovarian cancer is an incurable disease. Thus, novel therapies are required. We wished to identify new therapeutic targets for ovarian cancer. ShRNA screen performed in 42 ovarian cancer cell lines identified the centriolar replication factor STIL as an essential gene for ovarian cancer cells. This was verified in-vivo in orthotopic human ovarian cancer mouse models. STIL depletion by administration of siRNA in neutral liposomes resulted in robust anti-tumor effect that was further enhanced in combination with cisplatin...
March 10, 2017: Oncotarget
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