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Germ cell cancer

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https://www.readbyqxmd.com/read/28634159/a-role-for-the-nonsense-mediated-mrna-decay-pathway-in-maintaining-genome-stability-in-caenorhabditis-elegans
#1
Víctor González-Huici, Bin Wang, Anton Gartner
Ionizing radiation (IR) is commonly used in cancer therapy and is a main source of DNA double-strand-breaks (DSBs), one of the most toxic forms of DNA damage. We have used Caenorhabditis elegans as an invertebrate model to identify novel factors required for repair of DNA damage inflicted by IR. We have performed an unbiased genetic screen, finding that smg-1 mutations confer strong hypersensitivity to IR. SMG-1 is a phosphoinositide-3 kinase (PI3K) kinase involved in mediating nonsense-mediated mRNA decay (NMD) of transcripts containing premature stop codons and related to the ATM and ATR kinases which are at the apex of DNA damage signalling pathways...
June 20, 2017: Genetics
https://www.readbyqxmd.com/read/28631119/-expression-of-cancer-testis-ct-antigens-in-pediatric-and-adolescent-melanomas
#2
REVIEW
N Behrendt, T Schultewolter, K Busam, D Frosina, G Spagnoli, A Jungbluth
BACKGROUND: One of the main problems in the diagnostics of pediatric melanomas is the differentiation from benign dermal lesions typical for this age group, such as Spitz nevus. The biological behavior of pediatric melanomas differs considerably from that of melanomas in adults. MATERIAL AND METHODS: Cancer testis (CT) antigens are named after their typical expression pattern since they are present in various types of malignant tumors but in normal adult tissues are solely expressed in testicular germ cells...
June 19, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28630245/internal-carotid-artery-occlusion-and-stroke-as-a-complication-of-cisplatin-based-chemotherapy-for-metastatic-testicular-germ-cell-tumour
#3
Roberto Christian Cerrud-Rodriguez, Maria Gabriela Quinteros, Mohammed Azam
Testicular tumours are the most common tumours in young men. Germ cell tumours (GCTs) account for 95% of all testicular cancers, and the non-seminomatous type (NSGCT) accounts for 50% of all GCTs. Cisplatin-based chemotherapy is curative in up to 90% of patients, but it is not without its inherent risks. Ischaemic stroke is a very uncommon, but severe complication of cisplatin-based chemotherapy. Strokes in young patients cause a disproportionately large economic impact by leaving victims disabled during their most productive years and strains the healthcare system with expensive hospital stays...
June 18, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28615984/papillary-thyroid-microcarcinoma-arising-within-a-mature-ovarian-teratoma-case-report-and-review-of-the-literature
#4
Maria M Pineyro, Jimena Pereda, Pamela Schou, Karina de Los Santos, Soledad de la Peña, Benedicta Caserta, Raul Pisabarro
Mature cystic teratoma is the most common kind of ovarian germ cell tumor. Malignant transformation is uncommon, with thyroid cancer rarely found. Papillary thyroid microcarcinoma has rarely been described as associated with ovarian teratomas. We report a case of a 34-year-old woman who presented with abdominal pain and an ovarian mass. After surgery, the patient was diagnosed with a follicular variant papillary thyroid microcarcinoma that arose within a mature cystic ovarian teratoma. Based on the small size of the primary lesion and patient preferences, no further treatment was performed...
2017: Clinical Medicine Insights. Endocrinology and Diabetes
https://www.readbyqxmd.com/read/28612512/the-germline-factor-ddx4-functions-in-blood-derived-cancer-cell-phenotypes
#5
Natalie Schudrowitz, Satoshi Takagi, Gary M Wessel, Mamiko Yajima
DDX4 (the human ortholog of Drosophila Vasa) is an RNA helicase and is present in the germ lines of all metazoans tested. It was historically thought to be expressed specifically in germline cells, but with additional organisms studied, it is now clear that in some animals DDX4/Vasa functions outside of the germline, in a variety of somatic cells in the embryo and adult. In this report, we document that DDX4 is widely expressed in soma-derived cancer cell lines, including myeloma (IM-9) and leukemia (THP-1) cells...
June 14, 2017: Cancer Science
https://www.readbyqxmd.com/read/28612337/microrna-371a-3p-as-informative-biomarker-for-the-follow-up-of-testicular-germ-cell-cancer-patients
#6
Ton van Agthoven, Wil M H Eijkenboom, Leendert H J Looijenga
PURPOSE: α-fetoprotein (AFP) and human chorionic gonadotropin subunit beta (B-HCG) are informative serum biomarkers for the primary diagnosis and follow-up of testicular germ cell cancer (TGCC) patients. About 20% of TGCC patients with a non-seminoma (NS) and about 80% with a seminoma (SE) are, however, negative for these biomarkers. Embryonic stem cell microRNAs (miRs) may serve as promising alternative serum biomarkers. Here we investigated a retrospective series of serum samples from selected TGCC patients who developed a relapse in time to test the possible additional value of the serum-based ampTSmiR test compared to the conventional serum-based protein biomarkers for follow-up...
June 13, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28607084/systems-guided-forward-genetic-screen-reveals-a-critical-role-of-the-replication-stress-response-protein-etaa1-in-t-cell-clonal-expansion
#7
Lisa A Miosge, Yovina Sontani, Aaron Chuah, Keisuke Horikawa, Tiffany A Russell, Yan Mei, Mayura V Wagle, Debbie R Howard, Anselm Enders, David C Tscharke, Christopher C Goodnow, Ian A Parish
T-cell immunity requires extremely rapid clonal proliferation of rare, antigen-specific T lymphocytes to form effector cells. Here we identify a critical role for ETAA1 in this process by surveying random germ line mutations in mice using exome sequencing and bioinformatic annotation to prioritize mutations in genes of unknown function with potential effects on the immune system, followed by breeding to homozygosity and testing for immune system phenotypes. Effector CD8(+) and CD4(+) T-cell formation following immunization, lymphocytic choriomeningitis virus (LCMV) infection, or herpes simplex virus 1 (HSV1) infection was profoundly decreased despite normal immune cell development in adult mice homozygous for two different Etaa1 mutations: an exon 2 skipping allele that deletes Gly78-Leu119, and a Cys166Stop truncating allele that eliminates most of the 877-aa protein...
June 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28604732/meta-analysis-of-five-genome-wide-association-studies-identifies-multiple-new-loci-associated-with-testicular-germ-cell-tumor
#8
Zhaoming Wang, Katherine A McGlynn, Ewa Rajpert-De Meyts, D Timothy Bishop, Charles C Chung, Marlene D Dalgaard, Mark H Greene, Ramneek Gupta, Tom Grotmol, Trine B Haugen, Robert Karlsson, Kevin Litchfield, Nandita Mitra, Kasper Nielsen, Louise C Pyle, Stephen M Schwartz, Vésteinn Thorsson, Saran Vardhanabhuti, Fredrik Wiklund, Clare Turnbull, Stephen J Chanock, Peter A Kanetsky, Katherine L Nathanson
The international Testicular Cancer Consortium (TECAC) combined five published genome-wide association studies of testicular germ cell tumor (TGCT; 3,558 cases and 13,970 controls) to identify new susceptibility loci. We conducted a fixed-effects meta-analysis, including, to our knowledge, the first analysis of the X chromosome. Eight new loci mapping to 2q14.2, 3q26.2, 4q35.2, 7q36.3, 10q26.13, 15q21.3, 15q22.31, and Xq28 achieved genome-wide significance (P < 5 × 10(-8)). Most loci harbor biologically plausible candidate genes...
June 12, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28604728/identification-of-19-new-risk-loci-and-potential-regulatory-mechanisms-influencing-susceptibility-to-testicular-germ-cell-tumor
#9
Kevin Litchfield, Max Levy, Giulia Orlando, Chey Loveday, Philip J Law, Gabriele Migliorini, Amy Holroyd, Peter Broderick, Robert Karlsson, Trine B Haugen, Wenche Kristiansen, Jérémie Nsengimana, Kerry Fenwick, Ioannis Assiotis, ZSofia Kote-Jarai, Alison M Dunning, Kenneth Muir, Julian Peto, Rosalind Eeles, Douglas F Easton, Darshna Dudakia, Nick Orr, Nora Pashayan, D Timothy Bishop, Alison Reid, Robert A Huddart, Janet Shipley, Tom Grotmol, Fredrik Wiklund, Richard S Houlston, Clare Turnbull
Genome-wide association studies (GWAS) have transformed understanding of susceptibility to testicular germ cell tumors (TGCTs), but much of the heritability remains unexplained. Here we report a new GWAS, a meta-analysis with previous GWAS and a replication series, totaling 7,319 TGCT cases and 23,082 controls. We identify 19 new TGCT risk loci, roughly doubling the number of known TGCT risk loci to 44. By performing in situ Hi-C in TGCT cells, we provide evidence for a network of physical interactions among all 44 TGCT risk SNPs and candidate causal genes...
June 12, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28604461/chemosensitivity-of-brca1-mutated-ovarian-cancer-cells-and-established-cytotoxic-agents
#10
Caroline van Haaften, Jaap van Eendenburg, Arnoud Boot, Willem E Corver, Lucien Haans, Tom van Wezel, J Baptist Trimbos
OBJECTIVE: Serous adenocarcinomas that arise in patients with inherited mutations in the tumor suppressor genes BRCA1 and BRCA2 are initially well treatable with platinum/paclitaxel. For recurrent disease in patients with BRCA1 or BRCA2 mutations, olaparib treatment is available. To study additional therapeutic regimens, a better understanding of the cellular and molecular mechanisms of the tumors in in vitro models is important. METHODS/MATERIALS: From a high-grade serous ovarian tumor of a BRCA1 mutation carrier, we established 3 distinct cell line subclones, OVCA-TR3...
June 10, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28594943/childhood-cancer-risk-in-those-with-chromosomal-and-non-chromosomal-congenital-anomalies-in-washington-state-1984-2013
#11
Marlena S Norwood, Philip J Lupo, Eric J Chow, Michael E Scheurer, Sharon E Plon, Heather E Danysh, Logan G Spector, Susan E Carozza, David R Doody, Beth A Mueller
BACKGROUND: The presence of a congenital anomaly is associated with increased childhood cancer risk, likely due to large effects of Down syndrome and chromosomal anomalies for leukemia. Less is known about associations with presence of non-chromosomal anomalies. METHODS: Records of children diagnosed with cancer at <20 years of age during 1984-2013 in Washington State cancer registries were linked to their birth certificates (N = 4,105). A comparison group of children born in the same years was identified...
2017: PloS One
https://www.readbyqxmd.com/read/28591464/risk-of-low-bone-mineral-density-in-testicular-germ-cell-cancer-survivors-association-with-hypogonadism-and-treatment-modality
#12
S Isaksson, K Bogefors, K Åkesson, L Egund, J Bobjer, I Leijonhufvud, A Giwercman
The cure rate of testicular cancer exceeds 95%, but testicular cancer survivors (TCS) are at increased risk of hypogonadism (HG). It has been suggested that TCS have reduced bone mineral density (BMD), but it is unclear whether this is related to HG or a direct effect of cancer therapy. The aim of this study was to evaluate whether TCS have decreased BMD, and if BMD is related to HG and/or the cancer treatment given. We investigated 91 TCS (mean age at diagnosis: 31 years; mean 9.3 years follow-up) and equal number of age matched controls (mean age at inclusion 40...
June 7, 2017: Andrology
https://www.readbyqxmd.com/read/28591197/efficacy-of-targeted-drugs-in-germ-cell-cancer-cell-lines-with-differential-cisplatin-sensitivity
#13
Judith Schaffrath, Hans-Joachim Schmoll, Wieland Voigt, Lutz P Müller, Carsten Müller-Tidow, Thomas Mueller
METHODS: The in vitro activity of kinase inhibitors targeting mTOR (RAD001), EGFR, HER2/neu, VEGFR (AEE788) and IGF-1R (AEW541) alone or in combination with cisplatin was tested in the cisplatin sensitive TGCT cell lines H12.1 and GCT72 as well as in the resistant cell lines H12.1RA, H12.1D, 1411HP and 1777NRpmet using the sulforhodamin-B-(SRB)-cytotoxicity-assay. To evaluate the activity of the kinase inhibitors, western blot analysis of the targeted receptors and their phosphorylated state was performed before and after exposure to each substance...
2017: PloS One
https://www.readbyqxmd.com/read/28580709/early-ovariectomy-reveals-the-germline-encoding-of-natural-anti-a-and-tn-cross-reactive-immunoglobulin-m-igm-arising-from-developmental-o-galnac-glycosylations-germline-encoded-natural-anti-a-tn-cross-reactive-igm
#14
Peter Arend
While native blood group A-like glycans have not been demonstrated in prokaryotic microorganisms as a source of human "natural" anti-A isoagglutinin production, and metazoan eukaryotic N-acetylgalactosamine O-glycosylation of serine or threonine residues (O-GalNAc-Ser/Thr-R) does not occur in bacteria, the O-GalNAc glycan-bearing ovarian glycolipids, discovered in C57BL/10 mice, are complementary to the syngeneic anti-A-reactive immunoglobulin M (IgM), which is not present in animals that have undergone ovariectomy prior to the onset of puberty...
June 5, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28580303/the-role-of-bromodomain-testis-specific-factor-brdt-in-cancer-a-biomarker-and-a-possible-therapeutic-target
#15
REVIEW
Ekaterina Bourova-Flin, Florent Chuffart, Sophie Rousseaux, Saadi Khochbin
Cancer cells have recently been shown to activate hundreds of normally silent tissue-restricted genes, including a specific subset associated with cancer progression and poor prognosis. Within these genes, a class of testis-specific genes designed as cancer/testis, attracted special attention because of their oncogenic roles as well as their potential use in immunotherapy. Here we focus on one of these genes encoding the testis-specific member of the bromodomain and extra-terminal (BET) family, known as BRDT...
2017: Cell Journal
https://www.readbyqxmd.com/read/28574707/new-ustilaginoidins-from-rice-false-smut-balls-caused-by-villosiclava-virens-and-their-phytotoxic-and-cytotoxic-activities
#16
Weibo Sun, Ali Wang, Dan Xu, Weixuan Wang, Jiajia Meng, Jungui Dai, Yang Liu, Daowan Lai, Ligang Zhou
Ustilaginoidins are a class of bis-naphtho-γ-pyrones, typically produced by Villosiclava virens, the pathogen of the rice false smut (RFS) which has been one of the most destructive rice fungal diseases. Previously, we found that the ustilaginoidins identified from the culture of V. virens on rice medium were less polar than those reported from the RFS balls in general. In this study, we re-investigated the HPLC-DAD-HRMS profile of the EtOAc extract of the RFS balls, and found several interesting peaks that corresponding to new ustilaginoidins...
June 2, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28573637/clinical-significance-of-androgen-secretion-disorders-in-men-with-a-malignancy
#17
REVIEW
Pawel J Wiechno, Grazyna M Poniatowska, Wojciech Michalski, Jakub Kucharz, Malgorzata Sadowska, Joanna Jonska-Gmyrek, Karol Nietupski, Joanna Rzymowska, Tomasz Demkow
Cancer and its treatment can lead in men to testosterone deficiency, accompanied by somatic and mental symptoms. Germ cell tumours and their treatment may disturb the pituitary-gonadal axis, hence leading to significant clinical abnormalities. In some prostate cancer patients, castration, temporary or permanent, is a desired therapeutic condition. Yet, it is burdened with various side effects of complex intensity and significance. Last but not least, patients in the terminal stage of a malignancy present with low testosterone concentrations as a part of anorexia-cachexia syndrome...
July 2017: Medical Oncology
https://www.readbyqxmd.com/read/28555838/spontaneous-cd4-and-cd8-t-cell-responses-directed-against-cancer-testis-antigens-are-present-in-the-peripheral-blood-of-testicular-cancer-patients
#18
Hayden Pearce, Paul Hutton, Shalini Chaudhri, Emilio Porfiri, Prashant Patel, Richard Viney, Paul Ah Moss
Cancer/Testis Antigen (CTAg) expression is restricted to spermatogenic cells in an immune-privileged site within the testis. However, these proteins are expressed aberrantly by malignant cells and T cell responses against CTAgs develop in many cancer patients. We investigated the prevalence, magnitude and phenotype of CTAg-specific T cells in the blood of patients with testicular germ cell tumors (TGCTs). CD8(+) and CD4(+) T cell responses against MAGE-A family antigens were present in 44% (20/45) of patients' samples assayed by ex vivo IFN-γ ELISPOT...
May 28, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28550453/exchange-of-genetic-sequences-between-viruses-and-hosts
#19
Robin A Weiss
Although genetic transfer between viruses and vertebrate hosts occurs less frequently than gene flow between bacteriophages and prokaryotes, it is extensive and has affected the evolution of both parties. With retroviruses, the integration of proviral DNA into chromosomal DNA can result in the activation of adjacent host gene expression and in the transduction of host transcripts into retroviral genomes as oncogenes. Yet in contrast to lysogenic phage, there is little evidence that viral oncogenes persist in a chain of natural transmission or that retroviral transduction is a significant driver of the horizontal spread of host genes...
May 28, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28546713/current-concepts-of-epigenetics-in-testicular-cancer
#20
REVIEW
Alfredo Harb-De la Rosa, Meenakkshy Manoharan, Ahmed Saeed Goolam
Testicular germ cell tumors (GCTs) are characterized into seminomas (SGCTs) and non-seminomatous testicular germ cell tumors (NSGCTs). Serum tumor markers (STMs) play an important role in testicular cancer as they provide useful information for diagnosis, staging, and detection of recurrence. Nonetheless, additional tumor markers for early diagnosis and therapeutic options are required to enhance specificity of serological diagnosis of testes cancers. Epigenetics is defined as inherited changes in gene expression that are not encoded in the DNA structure...
June 2017: Indian Journal of Surgical Oncology
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