Abstract 5457: MAD2γ, a new MAD2 isoform, is ubiquitously expressed in distinct cell lines, reduces mitotic arrest, and associates with resistance to cisplatin-based chemotherapy in testicular germ cell tumors

2015 ◽  
Author(s):  
Alejandro Lopez-Saavedra ◽  
Rodrigo Caceres ◽  
Fernando Luna ◽  
Irwin Hernandez ◽  
Luis Alonso Herrera
Keyword(s):  
Germ Cell ◽  
Cell Lines ◽  
Germ Cell Tumors ◽  
Mitotic Arrest ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Distinct Cell

Association between ERCC1 and XPA expression and polymorphisms and the response to cisplatin in patients with non-seminomatous testicular germ cell tumors.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4555-4555
Author(s):  
Julia Mendoza ◽  
Jorge Martinez-Cedillo ◽  
Carlos Alberto Hernández ◽  
Delia Pérez-Montiel ◽  
Clementina Castro ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Lines ◽  
Cancer Cell ◽  
Excision Repair ◽  
Cox Model ◽  
Germ Cell Tumors ◽  
Cancer Cell Lines ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Ercc1 Expression

4555 Background: Cisplatin-based chemotherapy cures over 80% of testicular germ cell tumors (TGCTs); nucleotide-excision repair (NER) modifies the sensitivity to cisplatin. In this work we explored the association between NER-proteins and their polymorphisms (SNPs) with cisplatin-sensitivity (CPS) and overall survival (OS) of patients with advanced non-seminomatous (ns)-TGCTs treated with bleomycin-etoposide-cisplatin (BEP). Methods: ERCC1, XPA-expression and gammaH2AX-presence, were tested in cisplatin-treated cancer cell lines. ERCC1 and XPA-expression were also analyzed in ns-TGCTs by qPCR. Immunohistochemistry was performed to detect ERCC1 protein in ns-TGCTs specimens. The SNPs were genotyped by PCR-RFLPs technique. Results: High basal ERCC1-expression was observed in non-CPS cancer cell lines; ERCC1-expression augmented further, as well as gammaH2AX, after cisplatin-treatment. Basal ERCC1 expression increases in the non-CPS patients in Mexican and Peruvian populations compared to CPS patients (p<0.001; p=0.002). XPAexpression levels weren’t different. These polymorphisms weren’t associated with CPS or OS. ERCC1-positive immunostaining was observed in 30/108 patients (27.8%). From 76 patients that were CPS, 59 (77.6%) were ERCC1-negative, compared with 17 (22.4%) that were ERCC1-positive (p=0.05). 5-year OS probability was smaller for those patients ERCC1-positive and non-CPS (15.38%) than tumor ERCC1-negative and CPS (89.3%) (p<0.001). Using the Cox Model, adjusted on the prognosis groups, the hazard ratio (HR) of death in patients with ERCC1-negative and non-CPS was >14.43 and in patients ERCC1-positive and non-CPS the HR was >11.86 (p<0.001). Conclusions: High-levels of ERCC1-expression and ERCC1-protein are associated with non-CPS, suggesting the use of ERCC1 as a potential indicator of response to cisplatin-based chemotherapy and the prognosis in patients with ns-TGCTs. Moreover, it’s important to identify patients potentially non-CPS in order to diminish the toxicity of cisplatin and improved quality of life avoiding adverse effects due to this agent. Work supported by CONACYT 83959 and PAPIIT IN213311-3.

scholarly journals XIST-Promoter Demethylation as Tissue Biomarker for Testicular Germ Cell Tumors and Spermatogenesis Quality

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1385 ◽  
Author(s):  
Lobo ◽  
Nunes ◽  
Gillis ◽  
Barros-Silva ◽  
Miranda-Gonçalves ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Lines ◽  
X Chromosome ◽  
Germ Cell Tumors ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Lower Amount ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Xist Promoter

Background: The event of X chromosome inactivation induced by XIST, which is physiologically observed in females, is retained in testicular germ cell tumors (TGCTs), as a result of a supernumerary X chromosome constitution. X chromosome inactivation also occurs in male germline, specifically during spermatogenesis. We aimed to analyze the promoter methylation status of XIST in a series of TGCT tissues, representative cell lines, and testicular parenchyma. Methods: Two independent cohorts were included, comprising a total of 413 TGCT samples, four (T)GCT cell lines, and 86 testicular parenchyma samples. The relative amount of methylated and demethylated XIST promoter fragments was assessed by quantitative methylation-specific PCR (qMSP) and more sensitive high-resolution melting (HRM) methylation analyses. Results: Seminomas showed a lower amount of methylated XIST fragments as compared to non-seminomas or normal testis (p < 0.0001), allowing for a good discrimination among these groups (area under the curve 0.83 and 0.81, respectively). Seminomas showed a significantly higher content of demethylated XIST as compared to non-seminomas. The percentage of demethylated XIST fragment in cell lines reflected their chromosomal constitution (number of extra X chromosomes). A novel and strong positive correlation between the Johnsen’s score and XIST demethylation was identified (r = 0.75, p < 0.0001). Conclusions: The X chromosome inactivation event and demethylated XIST promoter are promising biomarkers for TGCTs and for assessing spermatogenesis quality.

scholarly journals Phytoestrogens regulate the proliferation and expression of stem cell factors in cell lines of malignant testicular germ cell tumors

2013 ◽  
Vol 43 (5) ◽  
pp. 1385-1394 ◽  
Author(s):  
ASTRID HASIBEDER ◽  
VIVEK VENKATARAMANI ◽  
PAUL THELEN ◽  
HEINZ-JOACHIM RADZUN ◽  
STEFAN SCHWEYER
Keyword(s):  
Stem Cell ◽  
Germ Cell ◽  
Cell Lines ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Stem Cell Factors

scholarly journals MAD2γ, a novel MAD2 isoform, reduces mitotic arrest and is associated with resistance in testicular germ cell tumors

Cell Cycle ◽  
2016 ◽  
Vol 15 (15) ◽  
pp. 2066-2076 ◽  
Author(s):  
Alejandro López-Saavedra ◽  
Miguel Ramírez-Otero ◽  
José Díaz-Chávez ◽  
Rodrigo Cáceres-Gutiérrez ◽  
Monserrat Justo-Garrido ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
Mitotic Arrest ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell

Serum Lactate Dehydrogenase Isoenzyme 1 and Relapse in Patients with Nonseminomatous Testicular Germ Cell Tumors Clinical Stage I

2001 ◽  
Vol 40 (4) ◽  
pp. 536-540 ◽  
Author(s):  
Finn Edler von Eyben ◽  
Ebbe Lindegaard Madsen ◽  
Ole Blaabjerg ◽  
Per Hyltoft Petersen ◽  
Hans von der Maase ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Germ Cell ◽  
Clinical Stage ◽  
Germ Cell Tumors ◽  
Serum Lactate ◽  
Stage I ◽  
Serum Lactate Dehydrogenase ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Dehydrogenase Isoenzyme

Molecular Mechanisms of Resistance in Testicular Germ Cell Tumors - clinical Implications

2018 ◽  
Vol 18 (10) ◽  
pp. 967-978 ◽  
Author(s):  
Katarina Kalavska ◽  
Vincenza Conteduca ◽  
Ugo De Giorgi ◽  
Michal Mego
Keyword(s):  
Germ Cell ◽  
Molecular Mechanisms ◽  
Cisplatin Resistance ◽  
Apoptotic Cell ◽  
Germ Cell Tumors ◽  
Treatment Resistance ◽  
Experimental Models ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Repair Capacity

Testicular germ cell tumors (TGCTs) represent the most common malignancy in men aged 15-35. Due to these tumors’ biological and clinical characteristics, they can serve as an appropriate system for studying molecular mechanisms associated with cisplatin-based treatment resistance. This review describes treatment resistance from clinical and molecular viewpoints. Cisplatin resistance is determined by various biological mechanisms, including the modulation of the DNA repair capacity of cancer cells, alterations to apoptotic cell death pathways, deregulation of gene expression pathways, epigenetic alterations and insufficient DNA binding. Moreover, this review describes TGCTs as a model system that enables the study of the cellular features of cancer stem cells in metastatic process and describes experimental models that can be used to study treatment resistance in TGCTs. All of the abovementioned aspects may help to elucidate the molecular mechanisms underlying cisplatin resistance and may help to identify promising new therapeutic targets.

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