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https://www.readbyqxmd.com/read/29352572/phase-i-combination-study-of-the-parp-inhibitor-veliparib-plus-carboplatin-and-gemcitabine-in-patients-with-advanced-ovarian-cancer-and-other-solid-malignancies
#1
Heidi J Gray, Katherine Bell-McGuinn, Gini F Fleming, Mihaela Cristea, Hao Xiong, Danielle Sullivan, Yan Luo, Mark D McKee, Wijith Munasinghe, Lainie P Martin
OBJECTIVE: Determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of veliparib combined with carboplatin and gemcitabine in patients with advanced ovarian cancer and other nonhematologic malignancies. METHODS: In this phase I study, patients with metastatic or unresectable solid tumors and ≤2 prior chemotherapy regimens received veliparib combined with carboplatin area under the curve (AUC) 4 on day 1 and gemcitabine 800mg/m2 on days 1 and 8 of a 21-day cycle for maximum 10cycles, followed by optional veliparib maintenance therapy...
January 15, 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29351920/exceptional-response-to-pembrolizumab-in-a-metastatic-chemotherapy-radiation-resistant-ovarian-cancer-patient-harboring-a-cd274-pd-l1-genetic-rearrangement
#2
Stefania Bellone, Natalia Buza, Jungmin Choi, Luca Zammataro, Laurie Gay, Julia A Elvin, David L Rimm, Yuting Liu, Elena Ratner, Peter E Schwartz, Alessandro D Santin
PURPOSE: Ovarian carcinoma no longer responsive to surgery and chemotherapy remains an incurable disease. Alternative therapeutic options remain desperately needed. EXPERIMENTAL DESIGN: We describe a heavily pretreated ovarian cancer patient with recurrent disease experiencing a remarkable clinical response to treatment with the anti-PD1 immune check-point inhibitor pembrolizumab. The clinical, pathological, and genomic characteristics of this exceptional ovarian cancer responder were carefully investigated using immunohistochemistry (IHC), quantitative multiplex fluorescence methods (ie, automated quantitative analysis, AQUA) and whole exome sequencing (WES) techniques...
January 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29351847/phosphorylation-of-ezh2-by-ampk-suppresses-prc2-methyltransferase-activity-and-oncogenic-function
#3
Lixin Wan, Kexin Xu, Yongkun Wei, Jinfang Zhang, Tao Han, Christopher Fry, Zhao Zhang, Yao Vickie Wang, Liyu Huang, Min Yuan, Weiya Xia, Wei-Chao Chang, Wen-Chien Huang, Chien-Liang Liu, Yuan-Ching Chang, Jinsong Liu, Yun Wu, Victor X Jin, Xiangpeng Dai, Jianfeng Guo, Jia Liu, Shulong Jiang, Jin Li, John M Asara, Myles Brown, Mien-Chie Hung, Wenyi Wei
Sustained energy starvation leads to activation of AMP-activated protein kinase (AMPK), which coordinates energy status with numerous cellular processes including metabolism, protein synthesis, and autophagy. Here, we report that AMPK phosphorylates the histone methyltransferase EZH2 at T311 to disrupt the interaction between EZH2 and SUZ12, another core component of the polycomb repressive complex 2 (PRC2), leading to attenuated PRC2-dependent methylation of histone H3 at Lys27. As such, PRC2 target genes, many of which are known tumor suppressors, were upregulated upon T311-EZH2 phosphorylation, which suppressed tumor cell growth both in cell culture and mouse xenografts...
January 18, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29351780/fancm-and-recql-genetic-variants-and-breast-cancer-susceptibility-relevance-to-south-poland-and-west-ukraine
#4
Tú Nguyen-Dumont, Aleksander Myszka, Pawel Karpinski, Maria M Sasiadek, Hayane Akopyan, Fleur Hammet, Helen Tsimiklis, Daniel J Park, Bernard J Pope, Ryszard Slezak, Nataliya Kitsera, Aleksandra Siekierzynska, Melissa C Southey
BACKGROUND: FANCM and RECQL have recently been reported as breast cancer susceptibility genes and it has been suggested that they should be included on gene panel tests for breast cancer predisposition. However, the clinical value of testing for mutations in RECQL and FANCM remains to be determined. In this study, we have characterised the spectrum of FANCM and RECQL mutations in women affected with breast or ovarian cancer from South-West Poland and West Ukraine. METHODS: We applied Hi-Plex, an amplicon-based enrichment method for targeted massively parallel sequencing, to screen the coding exons and proximal intron-exon junctions of FANCM and RECQL in germline DNA from unrelated women affected with breast cancer (n = 338) and ovarian cancer (n = 89) from Poland (n = 304) and Ukraine (n = 123)...
January 19, 2018: BMC Medical Genetics
https://www.readbyqxmd.com/read/29351580/maternal-nutrient-restriction-impairs-young-adult-offspring-ovarian-signaling-resulting-in-reproductive-dysfunction-and-follicle-loss
#5
K A Chan, P A Jazwiec, W Gohir, J J Petrik, D M Sloboda
Reproductive abnormalities are included as health complications in offspring exposed to poor prenatal nutrition. We have previously shown in a rodent model, that offspring born to nutrient restriction during pregnancy are born small, enter puberty early, and display characteristics of early ovarian aging as adults. The present study investigated whether key proteins involved in follicle recruitment and growth mediate ovarian follicle loss. Pregnant rats were randomized to: a standard diet throughout pregnancy and lactation (CON), or a calorie-restricted (50% of control) diet (UN) during pregnancy...
January 17, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29351485/insulin-signaling-displayed-a-differential-tissue-specific-response-to-low-dose-dht-in-female-mice
#6
Stanley Andrisse, Katelyn Billings, Ping Xue, Sheng Wu
Hyperandrogenemia and hyperinsulinemia are believed to play prominent roles in polycystic ovarian syndrome (PCOS). We explored the effects of low dose dihydrotestosterone (DHT), a PCOS model, on insulin signaling in metabolic and re-productive tissues in a female mouse model. Insulin resistance in the energy storage tissues is associated with type 2 diabetes. Insulin signaling in the ovaries and pituitary either directly or indirectly stimulates androgen production. Energy storage and reproductive tissues were isolated and molecular assays were performed...
December 19, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29351241/molecular-characterization-and-expression-profiles-of-sp-uchl3-and-sp-uchl5-during-gonad-development-of-scylla-paramamosain
#7
Kunhuang Han, Yanbin Dai, Ziping Zhang, Zhihua Zou, Yilei Wang
Ubiquitin C-terminal hydrolases (UCHLs) are a subset of deubiquitinating enzymes, and are involved in numerous physiological processes. However, the role of UCHLs during gonad development has not been studied in crustaceans. In this study, we have first cloned and analyzed expression profiling of Sp-uchl3 and Sp-uchl5 genes from mud crab Scylla paramamosain. The full-length cDNA of Sp-uchl3 is of 1804 bp. Its expression level in the ovary was significantly higher than in other tissues (p < 0.01), and during gonadal development, its expression in both O1 and O5 stages was significantly higher than in the other three stages of ovaries (p < 0...
January 19, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29351018/the-behavior-and-reproductive-physiology-of-a-solitary-progressive-provisioning-vespid-wasp-evidence-for-a-solitary-cycle-origin-of-reproductive-castes
#8
Hans C Kelstrup, Klaus Hartfelder, Tiago Falcon Lopes, Theresa C Wossler
The emergence of queens and workers from solitary antecedents mark a major evolutionary transition in the history of life. The solitary progressive provisioning wasp Synagris cornuta, a member of the subfamily Eumeninae (basal to eusocial vespid wasps), alternates between behavioral states characterized as queenlike and worker-like. Akin to a queen in eusocial wasps, a S. cornuta female initiates construction of a cell into which she oviposits and then, similar to a worker, cares for the brood as it develops...
February 2018: American Naturalist
https://www.readbyqxmd.com/read/29350350/biochemical-changes-and-clinical-outcomes-in-34-patients-with-classic-galactosemia
#9
Tatiana Yuzyuk, Krista Viau, Ashley Andrews, Marzia Pasquali, Nicola Longo
Impaired activity of galactose-1-phosphate uridyltransferase (GALT) causes galactosemia, an autosomal recessive disorder of galactose metabolism. Early initiation of a galactose-restricted diet can prevent or resolve neonatal complications. Despite therapy, patients often experience long-term complications including speech impairment, learning disabilities, and premature ovarian insufficiency in females. This study evaluates clinical outcomes in 34 galactosemia patients with markedly reduced GALT activity and compares outcomes between patients with different levels of mean galactose-1-phosphate in red blood cells (GAL1P) using logistic regression: group 1 (n = 13) GAL1P ≤1...
January 19, 2018: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29349823/tibolone-and-risk-of-gynecological-hormone-sensitive-cancer
#10
Ellen Christine Leth Løkkegaard, Lina Steinrud Mørch
Risk of ovarian cancer with hormone therapy is associated with use of both unopposed estrogen therapy and combined estrogen-progestin therapy, whereas for endometrial cancer addition of continuous progestin decreases the estrogen induced increased risk. Less is known about risk with use of tibolone; a synthetic steroid with estrogenic, progestagenic, and androgenic properties. We assessed these associations in a prospective cohort study, including all Danish women 50-79 years of age and followed 1995-2009. National Danish Registers captured individually updated exposure information, cancer cases including histology and confounding factors...
January 19, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29349754/strategies-to-maintain-fertility-in-young-breast-cancer-patients
#11
Elizabeth S Constance, Molly B Moravek, Jacqueline S Jeruss
Breast cancer is the most frequently occurring cancer in women of reproductive age. Treatments for breast cancer may eliminate or diminish fertility, making discussions about fertility preservation essential prior to initiation of gonadotoxic therapies. Additionally, even in patients who do not require chemotherapy, the use of adjuvant endocrine therapy will often push patients out of the reproductive window before treatment is completed. The only established methods for fertility preservation are oocyte or embryo cryopreservation, but experimental methods, such as ovarian suppression with GnRH agonists and ovarian tissue cryopreservation, show great promise...
2018: Cancer Treatment and Research
https://www.readbyqxmd.com/read/29349725/ki67-proliferative-index-in-carcinoid-tumors-involving-ovary
#12
Xiaotun Zhang, Andrea Jones, Sarah M Jenkins, Yajue Huang
Primary ovarian carcinoid tumors are rare neoplasms that constitute less than 0.1% of all ovarian carcinomas. However, carcinoid tumors metastatic to ovaries are more common. Cell proliferative rate is an important factor in the determination of neuroendocrine tumor prognosis. Limited data are available as regards Ki67 proliferation index in predicting the physiological features of carcinoid tumors involving the ovary. Pathology files of Mayo Clinic Rochester (1995-2014) were searched, and clinical information was collected from medical records...
January 18, 2018: Endocrine Pathology
https://www.readbyqxmd.com/read/29349677/mercuric-chloride-induced-ovarian-oxidative-stress-by-suppressing-nrf2-keap1-signal-pathway-and-its-downstream-genes-in-laying-hens
#13
Yan Ma, Mingkun Zhu, Liping Miao, Xiaoyun Zhang, Xinyang Dong, Xiaoting Zou
The present study evaluated the effects of mercury chloride (HgCl2) on follicular atresia rate, sex hormone secretion, and ovarian oxidative stress in laying hens. Antioxidant enzyme genes and the nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) signal pathway were further studied to uncover the molecular mechanism. A total of 768 40-week-old Hy-Line Brown laying hens were randomly allocated to four treatments with eight pens per treatment and 24 hens of each pen...
January 18, 2018: Biological Trace Element Research
https://www.readbyqxmd.com/read/29349392/ovarian-hyperstimulation-syndrome-as-a-rare-cause-of-acute-bilateral-limb-and-renal-ischemia
#14
Anita Quintas, Maria Emilia Ferreira, Frederico Bastos Gonçalves, José Aragão de Morais, Joao Albuquerque E Castro, Luís Mota Capitao
Ovarian hyperstimulation syndrome (OHS) is a rare and potentially fatal condition, particularly when it is associated with arterial thromboembolic events. We present a case of acute ischemia of both lower limbs and left kidney due to OHS. The clinical presentation included voluminous ascites, pleural effusion, and significant ovarian enlargement. Subsequently, bilateral severe acute limb ischemia and left kidney segmental infarction were established. Surgical thromboembolectomy and muscle débridement of the lower limbs were necessary, and the patient recovered with partial limitations...
June 2017: Journal of Vascular Surgery Cases and Innovative Techniques
https://www.readbyqxmd.com/read/29348902/feasibility-and-outcome-of-primary-laparoscopic-cytoreductive-surgery-for-advanced-epithelial-ovarian-cancer-a-comparison-to-laparotomic-surgery-in-retrospective-cohorts
#15
Huamao Liang, Hongyan Guo, Chunyu Zhang, FuLi Zhu, Yu Wu, Kun Zhang, Hua Li, Jinsong Han
Objectives: To assess the feasibility and outcome of primary laparoscopic cytoreductive surgery on advanced epithelial ovarian cancer in comparison with conventional open surgery. Materials and Methods: Patients undergoing primary laparoscopic cytoreductive surgery (LCS) from March 2007 to December 2016 were matched to controls treated with laparotomic cytoreduction during the same period. Procedural data and outcomes were analyzed. Results: The LCS group (n = 64) and laparotomic group (n = 68) had similar age, BMI, stages, histologic type and grading...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348863/no-association-between-tp53-arg72pro-polymorphism-and-ovarian-cancer-risk-evidence-from-10113-subjects
#16
Anqi Zhang, Ting-Yan Shi, Yuan Zhao, Junmiao Xiang, Danyang Yu, Zongwen Liang, Chaoyi Xu, Qiong Zhang, Yue Hu, Danhan Wang, Jing He, Ping Duan
The TP53 gene product is an important regulator of cell growth and a tumor suppressor. The association between TP53 Arg72Pro polymorphism and ovarian cancer risk has been widely investigated, but the results are contradictory. We therefore searched the PubMed, EMBASE and Chinese Biomedical databases for studies on the relation between TP53 Arg72Pro polymorphism and ovarian cancer risk. Our final meta-analysis included 24 published studies with 3271 cases and 6842 controls. Pooled results indicated that there was no significant association between TP53 Arg72Pro polymorphism and ovarian cancer risk [Pro/Pro vs...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348860/silencing-ror1-and-ror2-inhibits-invasion-and-adhesion-in-an-organotypic-model-of-ovarian-cancer-metastasis
#17
Claire Henry, Neville Hacker, Caroline Ford
OBJECTIVE: Elevated expression of the ROR1 and ROR2 Wnt receptors has been noted in both the tumour and stromal compartments of ovarian cancer patient tissue samples. In vitro studies have suggested these receptors play a role in ovarian cancer metastasis. However, these previous studies have utilised simple 2D in vitro models to investigate cancer cell growth and migration, which does not allow investigation of stromal involvement in Wnt driven metastasis. AIM: To investigate targeting ROR1 and ROR2 using a primary co-culture 3D model of epithelial ovarian cancer dissemination to the omentum...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348829/roflumilast-restores-camp-pka-creb-signaling-axis-for-ftmt-mediated-tumor-inhibition-of-ovarian-cancer
#18
Shipeng Gong, Yongning Chen, Fanliang Meng, Yadi Zhang, Huan Wu, Fei Wu
The abrogation of cAMP generation by overexpression of PDE isoforms promotes the inflammatory pathology, and the PDE inhibitors have showed the potential anti-inflammation effects in clinical. However, the function of PDE inhibitors in cancer treatment remains unclear. We here investigated the role of PDE4 inhibitor Roflumilast in the treatment of ovarian cancer. We found that Roflumilast could effectively inhibit the proliferation, and induce apoptosis and cell cycle arrest in two ovarian cancer cell lines OVCAR3 and SKOV3...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348823/prevalence-of-pathogenic-germline-variants-detected-by-multigene-sequencing-in-unselected-japanese-patients-with-ovarian-cancer
#19
Akira Hirasawa, Issei Imoto, Takuya Naruto, Tomoko Akahane, Wataru Yamagami, Hiroyuki Nomura, Kiyoshi Masuda, Nobuyuki Susumu, Hitoshi Tsuda, Daisuke Aoki
Pathogenic germline BRCA1, BRCA2 (BRCA1/2), and several other gene variants predispose women to primary ovarian, fallopian tube, and peritoneal carcinoma (OC), although variant frequency and relevance information is scarce in Japanese women with OC. Using targeted panel sequencing, we screened 230 unselected Japanese women with OC from our hospital-based cohort for pathogenic germline variants in 75 or 79 OC-associated genes. Pathogenic variants of 11 genes were identified in 41 (17.8%) women: 19 (8.3%; BRCA1), 8 (3...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348552/tpglda-novel-prediction-of-associations-between-lncrnas-and-diseases-via-lncrna-disease-gene-tripartite-graph
#20
Liang Ding, Minghui Wang, Dongdong Sun, Ao Li
Accumulating evidences have indicated that lncRNAs play an important role in various human complex diseases. However, known disease-related lncRNAs are still comparatively small in number, and experimental identification is time-consuming and labor-intensive. Therefore, developing a useful computational method for inferring potential associations between lncRNAs and diseases has become a hot topic, which can significantly help people to explore complex human diseases at the molecular level and effectively advance the quality of disease diagnostics, therapy, prognosis and prevention...
January 18, 2018: Scientific Reports
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