May 24, 2024

(2004) Role of promoter hypermethylation in Cisplatin treatment response of male germ cell tumors

(2004) Role of promoter hypermethylation in Cisplatin treatment response of male germ cell tumors. genotoxic chemotherapy. MATERIALS AND METHODS: We conducted a review of literature gathered from PubMed regarding the DNA damage response properties of TGCTs and the germ cells from which they arise, as well as the influence of these mechanisms on therapeutic responses by TGCTs. RESULTS AND DISCUSSION: This review provides a comprehensive evaluation of how the developmental origins of male germ cells and their inherent germ cell-like DNA damage response directly impacts the development and therapeutic sensitivity of TGCTs. CONCLUSIONS: The DNA damage response of germ cells directly impacts the development and therapeutic sensitivity of TGCTs. Recent advances in the study of primordial germ cells, post-natal mitotically-dividing germ cells, and pluripotent stem cells will allow for new investigations into the initiation, progression, and treatment of TGCTs. in the mouse. Reduction of this pro-survival factor in PGCs leads to an increase in apoptotic PGCs in the genital ridge, which could be rescued by deletion of the pro-apoptotic factor (Rucker, et al. RICTOR 2000). This work highlights the importance of maintaining a precise balance of regulatory factors involved in genetic quality control during PGC development, with deviations from normal developmental processes triggering germ cell death. This is further illustrated by studies of the Teratoma (encodes a RNA-binding protein that inhibits microRNA accessibility to target mRNAs (Kedde, et al. 2007). DND1 also destabilizes mRNAs involved in inflammation, cell death, and signaling pathways involved in stem cell pluripotency, thereby suppressing PGC apoptosis (Yamaji, et al. 2017). Loss of PGCs in mutants can be partially rescued by deletion of male mice on a germ cell tumor-resistant strain background were susceptible to teratomas at a significantly higher rate compared to single mutant mice with wild-type (Cook, et al. 2009). These studies elucidate the crucial role of BAX-mediated apoptosis in maintaining a normal populace of PGCs through the elimination of aberrant PGCs with tumor-initiating properties. DNA Damage Responses in Embryonic Germ Cells Once molecular markers specific to PGCs, such as (and (were identified (Elliott, et al. 2007; Payer, et al. 2006; Saitou, et al. 2002), the ability to examine the effects of environmental and genetic perturbations on PGCs became possible. Using ionizing radiation (IR) as a DNA damaging agent, E6-E7.25 mouse PGCs were shown to be hypersensitive to low doses of IR compared to surrounding cells in the embryo (Heyer, et al. 2000). Studies conducted in mice and rats at later stages Clorprenaline HCl of embryonic development also revealed that low doses of IR cause depletion of gonocytes without causing a significant reduction of interstitial cell types or Sertoli cells (Moreno, et al. 2001; Vergouwen, et al. 1995). To interrogate the role of the pro-apoptotic factor TP63 in IR-induced gonocyte apoptosis, another group uncovered wild-type and knock-out embryos at E18. 5 to IR and then assessed germ cell survival in Clorprenaline HCl the testes of newborn animals. Without IR, testes contained significantly more germ cells than unirradiated wild-type controls; however TP63 loss did not diminish the number of apoptotic cells in the testes following IR. This work demonstrates that while the presence of TP63 can trigger gonocyte apoptosis under normal conditions, TP63 is not required for radiation-induced apoptosis, highlighting the presence of multiple, separable pathways for cell death in germ cells (Petre-Lazar, et al. 2006). In addition to the depletion of germ cells brought on by exogenous insults, genetic mutations have been identified that reduce the number of PGCs (Hamer & De Rooij 2018). Several of these mutations are in genes encoding members of the Fanconi Anemia (FA) DNA damage repair pathway (Dong, et al. 2015). So far, mutations in and have each been independently reported to affect PGC development around the time of sex determination in mice (Agoulnik, et al. 2002; Luo, et al. 2014; Nadler & Braun 2000). Unlike what occurs following IR treatment, the reduction in PGC number in these mutants has been linked to a slower proliferation rate as assessed by BrdU Clorprenaline HCl incorporation, without apparent increases in apoptosis (Luo, et al. 2014; Nadler & Braun 2000). Of the FA pathway mutants affecting PGC proliferation, the mechanism behind PGC loss in the loss-of-function mutant has been examined most thoroughly. In order to identify if activation of a specific DDR pathway was responsible for inhibiting PGC proliferation,.