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https://www.readbyqxmd.com/read/28448663/prame-as-a-potential-target-for-immunotherapy-in-metastatic-uveal-melanoma
#1
Gülçin Gezgin, Sietse J Luk, Jinfeng Cao, Mehmet Dogrusöz, Dirk M van der Steen, Renate S Hagedoorn, Daniëlle Krijgsman, Pieter A van der Velden, Matthew G Field, Gregorius P M Luyten, Karoly Szuhai, J William Harbour, Ekaterina S Jordanova, Mirjam H M Heemskerk, Martine J Jager
Importance: Uveal melanoma (UM) is an intraocular primary malignant neoplasm that often gives rise to metastatic disease for which there are no effective therapies. A substantial proportion of UMs express the cancer-testis antigen PRAME (preferentially expressed antigen in melanoma), which can potentially be targeted by adoptive T-cell therapy. Objective: To determine whether there may be a rationale for PRAME-directed T-cell therapy for metastatic UM. Design, Setting, and Participants: An experimental study using a retrospective cohort of 64 patients with UM (median follow-up, 62 months) was conducted from January 8, 2015, to November 20, 2016, at the Leiden University Medical Center...
April 27, 2017: JAMA Ophthalmology
https://www.readbyqxmd.com/read/28446800/oxidative-stress-evoked-damages-on-rat-sperm-and-attenuated-antioxidant-status-on-consumption-of-aspartame
#2
I Ashok, P S Poornima, D Wankhar, R Ravindran, R Sheeladevi
Although several studies on toxic effect of aspartame metabolite have been studied, controversial reports over the use of aspartame owing to the fact that it releases methanol as one of its metabolite during metabolism exist. This present study is proposed to investigate whether aspartame (40 mg kg(-1) b.wt) administration for 90 days could induce oxidative stress and alter antioxidant status of epididymal sperm in Wistar strain male albino rats. To mimic the human methanol metabolism, methotrexate (MTX)-treated rats were included to study the effects of aspartame...
April 27, 2017: International Journal of Impotence Research
https://www.readbyqxmd.com/read/28446726/low-concentration-of-bpa-induces-mice-spermatocytes-apoptosis-via-gpr30
#3
Chaoliang Wang, Jianxiang Zhang, Qi Li, Tianbiao Zhang, Zishi Deng, Jing Lian, Donghui Jia, Rui Li, Tao Zheng, Xiaoju Ding, Fan Yang, Chao Ma, Rui Wang, Weixing Zhang, Jian Guo Wen
Bisphenol A (BPA) acts as xenoestrogen and has a great impact on disorders of human reproductive system. However, the mechanism through which BPA can affect human testicular function remains to be indentified. GPR30 is a novel membrane estrogen receptor with high-affinity and low-capacity binding to estrogens. We demonstrated that estrogen receptor α (ERα), estrogen receptor β (ERβ) as well as GPR30 are expressed in mouse spermatocyte-derived GC-2 cells using Real-time PCR. We treated the cells with different doses of BPA and found that even low doses of BPA can inhibit GC-2 cell growth using MTT assay...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28446721/senp3-grants-tight-junction-integrity-and-cytoskeleton-architecture-in-mouse-sertoli-cells
#4
Di Wu, Chun-Jie Huang, Faheem Ahmed Khan, Xiao-Fei Jiao, Xiao-Ming Liu, Nuruliarizki Shinta Pandupuspitasari, Rahim Dad Brohi, Li-Jun Huo
Germ cells develop in a sophisticated immune privileged microenvironment provided by specialized junctions contiguous the basement membrane of the adjacent Sertoli cells that constituted the blood-testis barrier (BTB) in seminiferous epithelium of testis in mammals. Deciphering the molecular regulatory machinery of BTB activity is central to improve male fertility and the role of post-translational modification including SUMOylation pathway is one of the key factors. Herein, we unveiled the mystery of the SUMO-2/3 specific protease SENP3 (Sentrin-specific protease 3) in BTB dynamics regulation...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28446509/inhibition-of-the-all-trans-retinoic-acid-hydroxylases-cyp26a1-and-cyp26b1-results-in-dynamic-tissue-specific-changes-in-endogenous-atra-signaling
#5
Faith Stevison, Cathryn Hogarth, Sasmita Tripathy, Travis Kent, Nina Isoherranen
all-trans-retinoic acid (atRA), the active metabolite of vitamin A, is a ligand for several nuclear receptors and acts as a critical regulator of many physiological processes. The cytochrome P450 family 26 (CYP26) enzymes are responsible for atRA clearance, and are potential drug targets to increase concentrations of endogenous atRA in a tissue-specific manner. Talarozole is a potent inhibitor of CYP26A1 and CYP26B1, and has shown some success in clinical trials. Yet, it is not known what magnitude of change is needed in tissue atRA concentrations to promote atRA signaling changes...
April 26, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28446200/human-germ-stem-cell-specific-gene-tex19-influences-cancer-cell-proliferation-and-cancer-prognosis
#6
Vicente Planells-Palop, Ali Hazazi, Julia Feichtinger, Jana Jezkova, Gerhard Thallinger, Naif O Alsiwiehri, Mikhlid Almutairi, Lee Parry, Jane A Wakeman, Ramsay J McFarlane
BACKGROUND: Cancer/testis (CT) genes have expression normally restricted to the testis, but become activated during oncogenesis, so they have excellent potential as cancer-specific biomarkers. Evidence is starting to emerge to indicate that they also provide function(s) in the oncogenic programme. Human TEX19 is a recently identified CT gene, but a functional role for TEX19 in cancer has not yet been defined. METHODS: siRNA was used to deplete TEX19 levels in various cancer cell lines...
April 26, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28445692/perspectives-on-testicular-sex-cord-stromal-tumors-and-those-composed-of-both-germ-cells-and-sex-cord-stromal-derivatives-with-a-comparison-to-corresponding-ovarian-neoplasms
#7
Lawrence M Roth, Bingjian Lyu, Liang Cheng
Sex cord-stromal tumors (SCSTs) are the second most frequent category of testicular neoplasms, accounting for approximately 2-5% of cases. Both genetic and epigenetic factors account for the differences in frequency and histologic composition between testicular and ovarian SCSTs. For example, large cell calcifying Sertoli cell tumor and intratubular large cell hyalinizing Sertoli cell neoplasia occur in the testis but have not been described in the ovary. In this article, we discuss recently described diagnostic entities as well as inconsistencies in nomenclature used in the recent World Health Organization classifications of SCSTs in the testis and ovary...
April 23, 2017: Human Pathology
https://www.readbyqxmd.com/read/28444387/meiotic-genes-are-enriched-in-regions-of-reduced-archaic-ancestry
#8
B Jégou, S Sankararaman, A D Rolland, D Reich, F Chalmel
About 1-6% of the genetic ancestry of modern humans today originates from admixture with archaic humans. It has recently been shown that autosomal genomic regions with a reduced proportion of Neanderthal and Denisovan ancestries are significantly enriched in genes that are more expressed in testis than in other tissues. To determine whether a cellular segregation pattern would exist, we combined maps of archaic introgression with a cross-analysis of three transcriptomic datasets deciphering the transcriptional landscape of human gonadal cell types...
April 21, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28444146/nonsense-in-the-testis-multiple-roles-for-nonsense-mediated-decay-revealed-in-male-reproduction
#9
Clinton C MacDonald, Petar N Grozdanov
Nonsense-mediated mRNA decay, or NMD, is a quality control mechanism that identifies cytoplasmic mRNAs containing translational termination (stop) codons in specific contexts - either premature termination codons or unusually long 3΄ untranslated regions - and targets them for degradation. In recent studies, researchers in different labs have knocked out important genes involved in NMD, Upf2 and Upf3a, and one component of chromatoid bodies, Tdrd6, and examined the consequences for spermatogenesis. Disruption of Upf2 during early stages of spermatogenesis resulted in disappearance of nearly all spermatogenic cells through loss of NMD...
April 22, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28442050/lonidamine-ethyl-ester-mediated-remodelling-of-the-sertoli-cell-cytoskeleton-induces-phosphorylation-of-plakoglobin-and-promotes-its-interaction-with-%C3%AE-catenin-at-the-blood-testis-barrier
#10
Dolores D Mruk, Michele Bonanomi, Bruno Silvestrini
Several compounds affect male fertility by disrupting the adhesion of germ cells to Sertoli cells, which results in the release of undeveloped germ cells into the seminiferous tubule lumen that are incapable of fertilising the ovum. Indazole carboxylic acids are one class of compounds exhibiting such effects and they have been investigated as non-hormonal contraceptives for potential human use. The aims of this study were to investigate the effects of lonidamine-ethyl ester, an indazole carboxylic acid, on spermatogenesis and cell junctions, in particular, desmosomes...
April 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28441376/nut-midline-carcinoma-a-rare-malignancy
#11
Sameer Al Diffalha, Nidal Al Aukla, Saleh Hasan, Shohreh Dickinson, Farah Khalil
Nuclear protein of the testis (NUT) midline carcinoma can present in the head, neck, and mediastinum. In general, it presents in young adult men and has a poor prognosis. We report on a case of NUT midline carcinoma of the mediastinum in a man 27 years of age without any prior malignancy. Due to the location of the tumor, mediastinal lymphoma and germ cell tumor were initially considered; however, immunohistochemistry was performed using NUT antibody that revealed it to be NUT midline carcinoma. Although guidelines exist for squamous cell carcinoma of the head, neck, and mediastinum, no such specific guidelines are available for NUT midline carcinoma, which looks morphologically similar to squamous cell carcinoma but behaves more aggressively and carries a poor prognosis...
April 2017: Cancer Control: Journal of the Moffitt Cancer Center
https://www.readbyqxmd.com/read/28440264/use-of-testicular-sperm-for-intracytoplasmic-sperm-injection-in-men-with-high-sperm-dna-fragmentation-a-swot-analysis
#12
Sandro C Esteves, Matheus Roque, Nicolás Garrido
Spermatozoa retrieved from the testis of men with high levels of sperm DNA fragmentation (SDF) in the neat semen tend to have better DNA quality. Given the negative impact of SDF on the outcomes of Assisted Reproductive Technology (ART), an increased interest has emerged about the use of testicular sperm for intracytoplasmic sperm injection (Testi-ICSI). In this article, we used a SWOT (strengths, weaknesses, opportunities, and threats) analysis to summarize the advantages and drawbacks of this intervention...
April 18, 2017: Asian Journal of Andrology
https://www.readbyqxmd.com/read/28439887/clinical-significance-of-recurrent-copy-number-aberrations-in-b-lineage-acute-lymphoblastic-leukaemia-without-recurrent-fusion-genes-across-age-cohorts
#13
Monica Messina, Sabina Chiaretti, Anna Lucia Fedullo, Alfonso Piciocchi, Maria Cristina Puzzolo, Alessia Lauretti, Valentina Gianfelici, Valerio Apicella, Paola Fazi, Geertruy Te Kronnie, Anna Maria Testi, Antonella Vitale, Anna Guarini, Robin Foà
Copy number aberrations (CNAs) represent cooperating events in B-lineage acute lymphoblastic leukaemia (B-ALL); however, their clinical relevance across different age cohorts is unclear. We analysed the recurrent CNAs in 157 age-stratified B-ALL negative cases for recurrent rearrangements (B-NEG ALL), and their association with patients' clinico-biological features. We found that: (i) CDKN2A/RB1-deleted and EBF1-deleted adults had a shorter disease-free survival than those with wild-type, (ii) among the unfavourable markers, CDKN2A/RB1 deletions and K/NRAS mutations retained their impact in multivariate analysis, encouraging the evaluation of CDKN2A/RB1 deletions and RAS mutations in the diagnostic/prognostic workflow to refine ALL risk assessment...
April 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28439067/perfluorooctanesulfonate-pfos-induced-sertoli-cell-injury-through-a-disruption-of-f-actin-and-microtubule-organization-is-mediated-by-akt1-2
#14
Ying Gao, Haiqi Chen, Xiang Xiao, Wing-Yee Lui, Will M Lee, Dolores D Mruk, C Yan Cheng
PFOS (perfluorooctanesulfonate, or perfluorooctane sulfonic acid) is an anthropogenic fluorosurfactant widely used in consumer products. While its use in Europe, Canada and the U.S. has been banned due to its human toxicity, it continues to be used in China and other developing countries as a global pollutant. Herein, using an in vitro model of Sertoli cell blood-testis barrier (BTB), PFOS was found to induce Sertoli cell injury by perturbing actin cytoskeleton through changes in the spatial expression of actin regulatory proteins...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28439006/murine-model-indicates-22q11-2-signaling-adaptor-crkl-is-a-dosage-sensitive-regulator-of-genitourinary-development
#15
Meade Haller, Qianxing Mo, Akira Imamoto, Dolores J Lamb
The spectrum of congenital anomalies affecting either the upper tract (kidneys and ureters) or lower tract (reproductive organs) of the genitourinary (GU) system are fundamentally linked by the developmental origin of multiple GU tissues, including the kidneys, gonads, and reproductive ductal systems: the intermediate mesoderm. Although ∼31% of DiGeorge/del22q11.2 syndrome patients exhibit GU defects, little focus has been placed on the molecular etiology of GU defects in this syndrome. Among del22q11.2 patients exhibiting GU anomalies, we have mapped the smallest relevant region to only five genes, including CRKLCRKL encodes a src-homology adaptor protein implicated in mediating tyrosine kinase signaling, and is expressed in the developing GU-tract in mice and humans...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438869/correlation-between-expression-of-the-cancer-testis-antigen-kk-lc-1-and-helicobacter-pylori-infection-in-gastric-cancer
#16
Takashi Fukuyama, Nobue Futawatari, Yoshinobu Ichiki, Akiko Shida, Taiga Yamazaki, Yatsushi Nishi, Hiroshi Nonoguchi, Yoshihito Takahashi, Hitoshi Yamazaki, Noritada Kobayashi
BACKGROUND/AIM: Our previous study indicated that Kita-kyushu lung cancer antigen-1 (KK-LC-1) is a cancer/testis antigen (CTA) expressed in 82% of gastric cancer cases. Here, we investigated the relationship between KK-LC-1 expression and Helicobacter pylori infection in Japanese patients with gastric cancer. PATIENTS AND METHODS: We examined CTA expression in 25 surgical gastric cancer specimens and anti-H. pylori IgGs in the serum of each patient. RESULTS: KK-LC-1 was expressed in 80% of tumor samples, markedly higher than melanoma antigen gene (MAGE)-A1, MAGE-A3, MAGE-A4, synovial sarcoma, X breakpoint 4 (SSX4) and New York esophageal squamous cell carcinoma-1 (NY-ESO-1)...
May 2017: In Vivo
https://www.readbyqxmd.com/read/28438683/identification-and-expression-of-piwil2-in-turbot-scophthalmus-maximus-with-implications-of-the-involvement-in-embryonic-and-gonadal-development
#17
Huizhen Wang, Bo Wang, Xiaobing Liu, Yuezhong Liu, Xinxin Du, Quanqi Zhang, XuBo Wang
Piwil2, a member of the Argonaute family, is involved in the biogenesis of PIWI-interacting RNAs (piRNAs) and plays an important role in regulating gametogenesis. In the present study, we identified turbot Scophthalmus maximus piwil2 gene, named Smpiwil2, which contained a PAZ domain and a PIWI domain. Sequence comparison, genomic structure and phylogenetic analyses showed that Smpiwil2 is homologous to that of teleosts and tetrapods. The Smpiwil2 transcript showed higher expression in ovary than in testis, demonstrating a sexually dimorphic gene expression pattern...
April 21, 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/28438518/testicular-spermatogenesis-and-sperm-morphology-in-martarega-bentoi-heteroptera-notonectidae
#18
Ademária M Novais, Glenda Dias, José Lino-Neto
The testicular, spermatogenesis and sperm morphology of the backswimmer Martarega bentoi was described using light and transmission electron microscopy. In this species, a pair of testes, two deferent ducts, two different pairs of accessory glands, and an ejaculatory duct form the male reproductive system. Each testis consists of two testicular follicles, which are arranged side by side in snail shape. The follicles are filled with cysts at different stages of spermatogenesis, but in the same cyst the germ cells (up to 64) are in the same stage...
April 21, 2017: Arthropod Structure & Development
https://www.readbyqxmd.com/read/28438170/immunolocalization-of-steroidogenic-enzymes-in-the-vaginal-mucous-of-galea-spixii-during-the-estrous-cycle
#19
Amilton Cesar Dos Santos, Alan James Conley, Moacir Franco de Oliveira, Gleidson Benevides Oliveira, Diego Carvalho Viana, Antônio Chaves de Assis Neto
BACKGROUND: The synthesis of sex steroids is controlled by several enzymes such as17α-hydroxylase cytochrome P450 (P450c17) catalyzing androgen synthesis and aromatase cytochrome P450 (P450arom) catalyzing estrogen synthesis, both of which must complex with the redox partner NADPH-cytochrome P450 oxidoreductase (CPR) for activity. Previous studies have identified expression of steroidogenic enzymes in vaginal tissue, suggesting local sex steroid synthesis. The current studies investigate P450c17, P450aromatase and CPR expression in vaginal mucosa of Galea spixii (Spix cavy) by immuno-histochemical and western immunoblot analyses...
April 24, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28435402/synchronous-bilateral-testis-cancer-clinical-and-oncological-management
#20
Davide Campobasso, Stefania Ferretti, Antonio Frattini
Synchronous bilateral testis cancer (SBTC) is a rare event. It represents only 0.5-1% of all new cases of testicular cancer. Patients with this disease require careful management for psychological, oncological, and medical problems. We performed a PubMed search for all series that reported SBTC. We considered only articles in English, reporting on more than three cases. We also performed an analysis of the reported evidence regarding testosterone replacement and surgical treatment. We found 10 studies satisfying inclusion criteria for a total of 73 patients...
2017: Contemporary Oncology Współczesna Onkologia
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