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https://www.readbyqxmd.com/read/28543997/the-mutational-frequency-of-braf-and-kras-in-low-grade-serous-testicular-neoplasms-a-case-series
#1
Paidamwoyo Gwiti, Ildikó Vereczkey, David Cundell, Shazia Aslam, Tim Clench, Jeremy Braybrooke, Muhammed Sohail, Zsombor Melegh
AIMS: Low grade serous neoplasms of the testis are rare neoplasms that demonstrate striking morphological similarities with the better-understood ovarian neoplasms. The cell of origin, relation to serous ovarian tumour and the pathogenesis of these neoplasms are not fully established. METHODS AND RESULTS: As low grade serous ovarian neoplasms are known to harbour mutations in the MAP-kinase pathway, we investigated the involvement of BRAF and KRAS mutations in low grade testicular serous tumour by way of mutational analysis of 7 cases...
May 19, 2017: Histopathology
https://www.readbyqxmd.com/read/28543772/parp-inhibitor-rucaparib-induces-changes-in-nad-levels-in-cells-and-liver-tissues-as-assessed-by-mrs
#2
Gilberto S Almeida, Carlo M Bawn, Martin Galler, Ian Wilson, Huw D Thomas, Suzanne Kyle, Nicola J Curtin, David R Newell, Ross J Maxwell
Poly(adenosine diphosphate ribose) polymerases (PARPs) are multifunctional proteins which play a role in many cellular processes. Namely, PARP1 and PARP2 have been shown to be involved in DNA repair, and therefore are valid targets in cancer treatment with PARP inhibitors, such as rucaparib, currently in clinical trials. Proton magnetic resonance spectroscopy ((1) H-MRS) was used to study the impact of rucaparib in vitro and ex vivo in liver tissue from mice, via quantitative analysis of nicotinamide adenosine diphosphate (NAD(+) ) spectra, to assess the potential of MRS as a biomarker of the PARP inhibitor response...
May 22, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/28537896/5t4-oncofoetal-glycoprotein-an-old-target-for-a-novel-prostate-cancer-immunotherapy
#3
Federica Cappuccini, Emily Pollock, Stephen Stribbling, Adrian V S Hill, Irina Redchenko
The tumour-associated antigen 5T4 is an attractive target for cancer immunotherapy. However to date, reported 5T4-specific cellular immune responses induced by various immunisation platforms have been largely weak or non-existent. In the present study, we have evaluated a heterologous prime boost regime based on the simian adenovirus ChAdOx1 and modified vaccinia virus Ankara (MVA) expressing 5T4 for immunogenicity and tumour protective efficacy in a mouse cancer model. Vaccination-induced immune responses were strong, durable and attributable primarily to CD8+ T cells...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28530221/micu1-drives-glycolysis-and-chemoresistance-in-ovarian-cancer
#4
Prabir K Chakraborty, Soumyajit Banerjee Mustafi, Xunhao Xiong, Shailendra Kumar Dhar Dwivedi, Vasyl Nesin, Sounik Saha, Min Zhang, Danny Dhanasekaran, Muralidharan Jayaraman, Robert Mannel, Kathleen Moore, Scott McMeekin, Da Yang, Rosemary Zuna, Kai Ding, Leonidas Tsiokas, Resham Bhattacharya, Priyabrata Mukherjee
Cancer cells actively promote aerobic glycolysis to sustain their metabolic requirements through mechanisms not always clear. Here, we demonstrate that the gatekeeper of mitochondrial Ca(2+) uptake, Mitochondrial Calcium Uptake 1 (MICU1/CBARA1) drives aerobic glycolysis in ovarian cancer. We show that MICU1 is overexpressed in a panel of ovarian cancer cell lines and that MICU1 overexpression correlates with poor overall survival (OS). Silencing MICU1 in vitro increases oxygen consumption, decreases lactate production, inhibits clonal growth, migration and invasion of ovarian cancer cells, whereas silencing in vivo inhibits tumour growth, increases cisplatin efficacy and OS...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28529602/super-aqueous-solubility-of-albendazole-in-%C3%AE-cyclodextrin-for-parenteral-application-in-cancer-therapy
#5
Krishna Pillai, Javed Akhter, David Lawson Morris
Poor aqueous solubility of anticancer drug, albendazole (ABZ), prevents parenteral application. Here, we demonstrate how to increase the aqueous solubility of ABZ to 6- 8 mg/ml using sulfobutylether - β-cyclodextrin (SBE-β-CD) or Hydroxypropyl- β-cyclodextrin (HP- β-CD) by manipulation of complexation parameters such as the physical state of ABZ (ionized in acetic acid), the concentration of ionised ABZ, agitation time and temperature. Solubility was first examined with suspension of excess ABZ powder in cyclodextrin (CD) solutions at pH (2...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28511463/unusually-high-serum-levels-of-ca-19-9-in-an-ovarian-tumour-malignant-or-benign
#6
Divya Pandey, Ritu Sharma, Shakti Sharma, Sudha Salhan
Carbohydrate antigen 19-9 (CA 19-9) is a tumour marker found to be elevated in some ovarian tumours. We share our experience with a 55-year-old postmenopausal lady with unusually high CA19-9 levels arising from a benign mucinous cystadenoma of the ovary. The levels returned to normal eight weeks following staging laparotomy and a total abdominal hysterectomy with bilateral salpingo-oopherectomy. This report shows rare and significant elevation of CA 19-9 levels with benign mucinous cystadenomas of the ovary thus showing that women with unusually elevated tumour markers may actually harbour benign disease...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28511399/primary-ovarian-endometrioid-stromal-sarcoma-presenting-with-infertility
#7
Sandhya Ilanthodi, Vishwanath Meghashree, Muktha Ramesh Pai
Endometrioid Stromal Sarcoma (ESS) is an uncommon tumour that occurs in women over wide age range of 11 years to 76 years accounting for only 0.2% of all uterine malignancies and for 15%-26% of primary uterine sarcomas. These tumours arising from ovary are extremely rare. Most of them are associated with nulliparous or perimenopausal women. It is commonly associated with endometriosis of the ovary. Here we present this rare case to emphasize on the uniqueness and histomorphology of ovarian ESS in patients with endometriosis...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28511230/-papillary-cystadenoma-a-rare-differential-diagnosis-of-a-paratesticular-tumour
#8
Désirée Louise Dräger, Sarah Zonnur, Andreas Erbersdobler, Chris Protzel, Oliver W Hakenberg
Testicular and paratesticular cystadenomas arise from an oviduct-like structure, which, morphologically, is almost identical with the ovarian surface epithelium. These are very rare benign tumours of adults. They present as asymptomatic cystic lesions. Bilateral paratesticular cystadenomas are associated with the Von-Hippel-Lindau syndrome and may be associated with infertility. Most cystadenomas are benign, but a few cases of malignant transformation of embryonic remnants have been reported in the appendix testis, including cases of adenocarcinoma, cystadenocarcinoma, and a Müllerian-type epithelial tumour with a low malignant potential...
May 16, 2017: Aktuelle Urologie
https://www.readbyqxmd.com/read/28510616/salvage-high-dose-chemotherapy-in-female-patients-with-relapsed-refractory-germ-cell-tumors-a-retrospective-analysis-of-the-european-group-for-blood-and-marrow-transplantation-ebmt
#9
U De Giorgi, S Richard, M Badoglio, E Kanfer, J H Bourrhis, E Nicolas-Virelizier, K Vettenranta, B Lioure, S Martin, P Dreger, M K Schuler, K Thomson, E Scarpi, G Rosti, F Selle, G Mangili, F Lanza, M Bregni
Background: High-dose chemotherapy (HDC) with hematopoietic progenitor cell transplantation is a standard option for relapsed/refractory testicular germ cell tumor (GCT), but only few data have been reported in female patients with GCT. We conducted a retrospective analysis of female patients with GCT treated with HDC and registered with the European Society for Blood and Marrow Transplantation (EBMT). Patients and methods: Between 1985 and 2013, 60 registered female patients with GCT, median age 27 years (range 15-48), were treated with salvage HDC...
May 16, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28494767/intestinal-differentiated-mucinous-adenocarcinoma-of-the-endometrium-with-sporadic-msi-high-status-a-case-report
#10
Mafalda Trippel, Sara Imboden, Andrea Papadia, Michael D Mueller, Nando Mertineit, Kirsi Härmä, Alina Nicolae, Erik Vassella, Tilman T Rau
BACKGROUND: Intestinal differentiation of primary mucinous adenocarcinoma of the uterine corpus is exceedingly rare in comparison to the approximately 25% rate in endocervical and ovarian mucinous carcinoma. Additionally, little is known about the related genetic and epigenetic alterations, even though large-scale molecular characterisation of the different types of endometrial cancer took place in the TCGA project along the entities defined by the recent WHO classification. CASE PRESENTATION: We present a 62-year-old patient harbouring a primary mucinous carcinoma of the uterine corpus with a morphological resemblance to mucinous colorectal adenocarcinoma...
May 12, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28490659/runx-transcription-factors-at-the-interface-of-stem-cells-and-cancer
#11
REVIEW
Elitza Deltcheva, Rachael Nimmo
The RUNX1 transcription factor is a critical regulator of normal haematopoiesis and its functional disruption by point mutations, deletions or translocations is a major causative factor leading to leukaemia. In the majority of cases, genetic changes in RUNX1 are linked to loss of function classifying it broadly as a tumour suppressor. Despite this, several recent studies have reported the need for a certain level of active RUNX1 for the maintenance and propagation of acute myeloid leukaemia and acute lymphoblastic leukaemia cells, suggesting an oncosupportive role of RUNX1...
May 10, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28490612/pathology-update-to-the-manchester-scoring-system-based-on-testing-in-over-4000-families
#12
D Gareth Evans, Elaine F Harkness, Inga Plaskocinska, Andrew J Wallace, Tara Clancy, Emma R Woodward, Tony A Howell, Marc Tischkowitz, Fiona Lalloo
BACKGROUND: While the requirement for thresholds for testing for mutations in BRCA1/2 is being questioned, they are likely to remain for individuals unaffected by a relevant cancer. It is still useful to provide pretesting likelihoods, but models need to take into account tumour pathology. METHODS: The Manchester Scoring System (MSS) is a well-used, simple, paper-based model for assessing carrier probability that already incorporates pathology data. We have used mutation testing data from 4115 unrelated samples from affected non-Jewish individuals alongside tumour pathology to further refine the scoring system...
May 10, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28485183/ovarian-sertoli-leydig-cell-tumours-how-typical-is-their-typical-presentation
#13
Lidia María Melero Cortés, M Ángeles Martínez Maestre, M Begoña Vieites Pérez-Quintela, Pietro Gambadauro
Ovarian Sertoli-Leydig cell tumours (OSLCT) are rare and typically present with androgenic manifestations in women of the 2nd-3rd decade. Out of 228 diagnoses of ovarian sex cord-stromal tumours recorded at an academic institution during a 14-year period, eight women were surgically treated for OSLCT. Patient mean age was 54.8 years (range 19-81), five women being in the postmenopausal stage (62.5%). Only one woman presented with androgenic manifestations (12.5%), four with abnormal/postmenopausal uterine bleeding (50%), and three with abdominal pain (37...
May 9, 2017: Journal of Obstetrics and Gynaecology: the Journal of the Institute of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28477318/molecular-characterization-and-clinical-interpretation-of-brca1-brca2-variants-in-families-from-murcia-south-eastern-spain-with-hereditary-breast-and-ovarian-cancer-clinical-pathological-features-in-brca-carriers-and-non-carriers
#14
Xavier Gabaldó Barrios, Mª Desamparados Sarabia Meseguer, Miguel Marín Vera, Ana Isabel Sánchez Bermúdez, José Antonio Macías Cerrolaza, Pilar Sánchez Henarejos, Marta Zafra Poves, Mª Rosario García Hernández, Encarna Cuevas Tortosa, Ángeles Aliaga Baño, Verónica Castillo Guardiola, Pedro Martínez Hernández, Isabel Tovar Zapata, Enrique Martínez Barba, Francisco Ayala de la Peña, José Luis Alonso Romero, José Antonio Noguera Velasco, Francisco Ruiz Espejo
This is the first study performed in Murcia (south-eastern Spain) in which 592 families with hereditary breast and ovarian cancer were identified thanks to Genetic Counselling Units from this area over 6 years. Diagnostic performance was 18.1% and 194 different genetic variants were obtained. Variants with uncertain significance accounted for only 5.6% of the total number of reports, so our population has been well characterised. In BRCA1 gene, two novel variants were found (c.1859delT and c.3205C > T) and the most frequently detected mutations were c...
May 5, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28474297/niraparib-first-global-approval
#15
Lesley J Scott
Oral niraparib, a highly-selective, potent poly(ADP-ribose) polymerase (PARP)-1 and PARP-2 inhibitor, is approved in the USA for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. It is also under regulatory review in the EU for use in maintenance treatment in patients with platinum-sensitive, recurrent epithelial ovarian cancer who are in response to platinum-based chemotherapy...
June 2017: Drugs
https://www.readbyqxmd.com/read/28473713/structure-aided-design-of-a-neu5gc-specific-lectin
#16
Christopher J Day, Adrienne W Paton, Melanie A Higgins, Lucy K Shewell, Freda E-C Jen, Benjamin L Schulz, Brock P Herdman, James C Paton, Michael P Jennings
Subtilase cytotoxin (SubAB) of Escherichia coli is an AB5 class bacterial toxin. The pentameric B subunit (SubB) binds the cellular carbohydrate receptor, α2-3-linked N-glycolylneuraminic acid (Neu5Gc). Neu5Gc is not expressed on normal human cells, but is expressed by cancer cells. Elevated Neu5Gc has been observed in breast, ovarian, prostate, colon and lung cancer. The presence of Neu5Gc is prognostically important, and correlates with invasiveness, metastasis and tumour grade. Neu5Gc binding by SubB suggests that it may have utility as a diagnostic tool for the detection Neu5Gc tumor antigens...
May 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28471128/sclerosing-stromal-tumour-of-the-ovary-in-a-postmenopausal-woman-presenting-with-virilization
#17
Özhan Özdemir, CemalReşat Atalay, Ertuğrul Şen, Esra Özhamam
Sclerosing stromal tumours are rare benign ovarian neoplasms of the sex cord stromal that occur predominantly in the second and third decades of life. To date, fewer than 200 cases have been described in the literature and most patients have menstrual irregularities and pelvic pain. Sclerosing stromal tumours were reported in which the inactive tumours did not represent endocrine clinical symptoms; however, currently according to several reports, it is the active tumour that produce hormones. Only a few cases of virilizing sclerosing stromal tumours of the ovary have been described in the literature and in this report first describes sclerosing stromal tumour of the ovary in a postmenopausal woman presenting with virilization...
July 2016: Journal of Experimental Therapeutics & Oncology
https://www.readbyqxmd.com/read/28466842/comprehensive-population-wide-analysis-of-lynch-syndrome-in-iceland-reveals-founder-mutations-in-msh6-and-pms2
#18
Sigurdis Haraldsdottir, Thorunn Rafnar, Wendy L Frankel, Sylvia Einarsdottir, Asgeir Sigurdsson, Heather Hampel, Petur Snaebjornsson, Gisli Masson, Daniel Weng, Reynir Arngrimsson, Birte Kehr, Ahmet Yilmaz, Stefan Haraldsson, Patrick Sulem, Tryggvi Stefansson, Peter G Shields, Fridbjorn Sigurdsson, Tanios Bekaii-Saab, Pall H Moller, Margret Steinarsdottir, Kristin Alexiusdottir, Megan Hitchins, Colin C Pritchard, Albert de la Chapelle, Jon G Jonasson, Richard M Goldberg, Kari Stefansson
Lynch syndrome, caused by germline mutations in the mismatch repair genes, is associated with increased cancer risk. Here using a large whole-genome sequencing data bank, cancer registry and colorectal tumour bank we determine the prevalence of Lynch syndrome, associated cancer risks and pathogenicity of several variants in the Icelandic population. We use colorectal cancer samples from 1,182 patients diagnosed between 2000-2009. One-hundred and thirty-two (11.2%) tumours are mismatch repair deficient per immunohistochemistry...
May 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28463960/phase-i-dose-escalation-studies-of-roniciclib-a-pan-cyclin-dependent-kinase-inhibitor-in-advanced-malignancies
#19
Rastislav Bahleda, Juneko E Grilley-Olson, Ramaswamy Govindan, Fabrice Barlesi, Laurent Greillier, Maurice Perol, Isabelle Ray-Coquard, Dirk Strumberg, Beate Schultheis, Grace K Dy, Gérard Zalcman, Glen J Weiss, Annette O Walter, Martin Kornacker, Prabhu Rajagopalan, David Henderson, Hendrik Nogai, Matthias Ocker, Jean-Charles Soria
BACKGROUND: To evaluate safety, pharmacokinetics, and maximum tolerated dose of roniciclib in patients with advanced malignancies, with dose expansion to evaluate clinical benefit at the recommended phase II dose (RP2D). METHODS: Two phase I dose-escalation studies evaluated two roniciclib dosing schedules: 3 days on/4 days off or 4 weeks on/2 weeks off. The expansion phase included patients with small-cell lung cancer (SCLC), ovarian cancer, or tumour mutations involving the CDK signalling pathway...
May 2, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28463959/pre-diagnosis-diet-and-survival-after-a-diagnosis-of-ovarian-cancer
#20
Mary C Playdon, Christina M Nagle, Torukiri I Ibiebele, Leah M Ferrucci, Melinda M Protani, Jonathan Carter, Simon E Hyde, Deborah Neesham, James L Nicklin, Susan T Mayne, Penelope M Webb
BACKGROUND: The relationship between diet and survival after ovarian cancer diagnosis is unclear as a result of a limited number of studies and inconsistent findings. METHODS: We examined the association between pre-diagnostic diet and overall survival in a population-based cohort (n=811) of Australian women diagnosed with invasive epithelial ovarian cancer between 2002 and 2005. Diet was measured by validated food frequency questionnaire. Deaths were ascertained up to 31 August 2014 via medical record review and Australian National Death Index linkage...
May 2, 2017: British Journal of Cancer
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