Cancers, Vol. 11, Pages 1224: Disulfiram Overcomes Cisplatin Resistance in Human Embryonal Carcinoma Cells

Cancers, Vol. 11, Pages 1224: Disulfiram Overcomes Cisplatin Resistance in Human Embryonal Carcinoma Cells Cancers doi: 10.3390/cancers11091224 Authors: Silvia Schmidtova Katarina Kalavska Katarina Gercakova Zuzana Cierna Svetlana Miklikova Bozena Smolkova Verona Buocikova Viera Miskovska Erika Durinikova Monika Burikova Michal Chovanec Miroslava Matuskova Michal Mego Lucia Kucerova Cisplatin resistance in testicular germ cell tumors (TGCTs) is a clinical challenge. We investigated the underlying mechanisms associated with cancer stem cell (CSC) markers and modalities circumventing the chemoresistance. Chemoresistant models (designated as CisR) of human embryonal carcinoma cell lines NTERA-2 and NCCIT were derived and characterized using flow cytometry, gene expression, functional and protein arrays. Tumorigenicity was determined on immunodeficient mouse model. Disulfiram was used to examine chemosensitization of resistant cells. ALDH1A3 isoform expression was evaluated by immunohistochemistry in 216 patients’ tissue samples. Chemoresistant cells were significantly more resistant to cisplatin, carboplatin and oxaliplatin compared to parental cells. NTERA-2 CisR cells exhibited altered morphology and increased tumorigenicity. High ALDH1A3 expression and increased ALDH activity were detected in both refractory cell lines. Disulfiram in combination with cisplatin showed synergy for NTERA-2 CisR and NCCIT CisR cells and inhibited growth...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research

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chael J. Spinella A greater understanding of the hypersensitivity and curability of testicular germ cell tumors (TGCTs) has the potential to inform strategies to sensitize other solid tumors to conventional chemotherapies. The mechanisms of cisplatin hypersensitivity and resistance in embryonal carcinoma (EC), the stem cells of TGCTs, remain largely undefined. To study the mechanisms of cisplatin resistance we generated a large panel of independently derived, acquired resistant clones from three distinct parental EC models employing a protocol designed to match standard of care regimens of TGCT patients. Transcriptomic...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
In this study, we generated TCam-2 cells double-deficient for SOX2 and FOXA2 using the CRISPR/Cas9 technique and xenografted those cells into the flank of nude mice. Upon loss of SOX2 and FOXA2, TCam-2 maintained a seminoma cell fate for at least twelve weeks, demonstrating that both factors are key players in the reprogramming to an EC-like cell fate. Therefore, our study adds an important piece to the puzzle of GCT development and plasticity, providing interesting insights in what can be expected in a patient, when GCT cells are confronted with different microenvironments.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Katarina Rejlekova1, Maria C. Cursano2, Ugo De Giorgi3 and Michal Mego1* 12nd Department of Oncology, Faculty of Medicine, National Cancer Institute, Comenius University, Bratislava, Slovakia 2Oncology Unit, Università Campus Bio-Medico, Rome, Italy 3Medical Oncology Department, Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRCCS, Meldola, Italy Testicular germ cell tumors (TGCTs) represent the most common solid tumor in young men and is a model of curable cancer. The effectiveness of cisplatin-based chemotherapy secures more than 95% of patients' 5-years survival rate. Howeve...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
CONCLUSION: Finally, the pathogenesis of testicular germ cell tumor needs to be deeply understood so that it will improve data on stem cells, tumorigenesis and disease tumor management by more selective treatment. PMID: 30636617 [PubMed - as supplied by publisher]
Source: Recent Patents on Anti-Cancer Drug Discovery - Category: Cancer & Oncology Tags: Recent Pat Anticancer Drug Discov Source Type: research
UCLA researchers have made new inroads into understanding germ cell tumors, a diverse and rare group of cancers that begin in germ cells — the cells that develop into sperm and eggs. The researchers developed a protocol to recreate germ cell tumor cells from stem cells and used the new model to study the genetics of the cancer.Their findings could point the way toward new drugs to treat germ cell tumors, which account for around 3 percent of all cases of childhood and adolescent cancer.The study, published in Stem Cell Research, was led by Amander Clark, a UCLA professor of molecular cell and developmental biology an...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news
Contributors : Amy M Lyndaker ; Claire Anderson ; Robert S WeissSeries Type : Genome variation profiling by genome tiling arrayOrganism : Mus musculusTesticular germ cell tumors are among the most responsive solid cancers to conventional chemotherapy. To elucidate the underlying mechanisms, we developed a mouse testicular germ cell tumor model in which germ cell-specific oncogenic Kras activation and tumor suppressor Pten inactivation was driven by CRE-mediated recombination. The resulting mice rapidly developed malignant, metastatic testicular cancers composed of both teratoma and embryonal carcinoma, the latter of which ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome variation profiling by genome tiling array Mus musculus Source Type: research
Publication date: 14 November 2017 Source:Cell Reports, Volume 21, Issue 7 Author(s): Timothy M. Pierpont, Amy M. Lyndaker, Claire M. Anderson, Qiming Jin, Elizabeth S. Moore, Jamie L. Roden, Alicia Braxton, Lina Bagepalli, Nandita Kataria, Hilary Zhaoxu Hu, Jason Garness, Matthew S. Cook, Blanche Capel, Donald H. Schlafer, Teresa Southard, Robert S. Weiss Testicular germ cell tumors (TGCTs) are among the most responsive solid cancers to conventional chemotherapy. To elucidate the underlying mechanisms, we developed a mouse TGCT model featuring germ cell-specific Kras activation and Pten inactivation. The resulting m...
Source: Cell Reports - Category: Cytology Source Type: research
ConclusionsThere is considerable immunophenotypic overlap between the two components in these mixed neoplasms and a panel of markers should be used to facilitate the distinction. We propose that OCT4‐expressing somatic cancer cells differentiate into GCT and represent spontaneously induced pluripotent stem cells, possibly conditioned by aging‐related epigenetic factors. These neoplasms have features of pre pubertal type GCT showing lack of 12p gain, preponderance of YST and coexistence with immature neuroectoderm. However, there may also be undifferentiated stem cell areas with embryoid bodies, of the type seen in post...
Source: Histopathology - Category: Pathology Authors: Tags: Original Article Source Type: research
Authors: Albany C, Hever-Jardine MP, von Herrmann KM, Yim CY, Tam J, Warzecha JM, Shin L, Bock SE, Curran BS, Chaudhry AS, Kim F, Sandusky GE, Taverna P, Freemantle SJ, Christensen BC, Einhorn LH, Spinella MJ Abstract Testicular germ cell tumors (TGCTs) are the most common cancers of young males. A substantial portion of TGCT patients are refractory to cisplatin. There are no effective therapies for these patients, many of whom die from progressive disease. Embryonal carcinoma (EC) are the stem cells of TGCTs. In prior in vitro studies we found that EC cells were highly sensitive to the DNA methyltransferase inhibi...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Testicular germ cell tumors (TGCTs) share germline ancestry but diverge phenotypically and clinically as seminoma (SE) and nonseminoma (NSE), the latter including the pluripotent embryonal carcinoma (EC) and its differentiated derivatives, teratoma (TE), yolk sac tumor (YST), and choriocarcinoma. Epigenomes from TGCTs may illuminate reprogramming in both normal development and testicular tumorigenesis. Herein we investigate pure-histological forms of 130 TGCTs for conserved and subtype-specific DNA methylation, including analysis of relatedness to pluripotent stem cell (ESC, iPSC), primordial germ cell (PGC), and different...
Source: Genome Research - Category: Genetics & Stem Cells Authors: Tags: RESEARCH Source Type: research
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