A teratoma is a benign tumor containing a mixture of differentiated tissues and organotypic derivatives of the three germ layers, while a teratocarcinoma also contains embryonal carcinoma cells (EC cells). Experimental teratomas and teratocarcinomas have been derived from early mammalian embryos transplanted into the adult animal (ectopic sites). In the rat, the pluripotency of the transplanted epiblast was demonstrated and a quantifiable restriction of developmental potential persisted after subsequent transplantation of chemically defined cultivated postimplantation embryos. The rat is nonpermissive for teratocarcinoma development and rat pluripotent cell lines have been established only recently. Transplantation of mouse embryos, epiblast, or embryonic stem cells (mESCs) gave rise to teratocarcinomas. The pluripotency of reprogrammed human cells has been tested by a 'gold standard' trilaminar teratoma assay in immunocompromised mice in vivo. Human pluripotent stem cells proposed for use in regenerative medicine such as human embryonic stem cell (hESC), human nuclear-transfer/therapeutic cloning embryonic stem cell (NT-ESC), or human induced pluripotent stem cell (hiPSC) lines, once differentiated in vitro to the desired cell type, should be again tested in a long-term animal teratoma assay to exclude their malignancy. Such an approach led to a recently implemented human therapy with retinal pigmented epithelium. For greater biosafety, the teratoma assay should be standardized and complemented by assessments of mutations/epimutations, RNA/protein expression, and possible immunogenicity of autologous pluripotent cells. Furthermore, the standardized teratoma assay should be directed more to the assessment of EC/malignant cell features than of differentiated tissues, especially after a unique case of human therapy with neural stem cells was found to lead to malignancy. For further resources related to this article, please visit the WIREs website.
Prostate cancer (PCa) represents the most commonly diagnosed neoplasm among men. miRNAs, as biomarkers, could further improve reliability in distinguishing malignant versus nonmalignant, and aggressive versus nonaggressive PCa. However, conflicting data was reported for certain miRNAs, and there was a lack of consistency and reproducibility, which has been attributed to diverse (pre)analytical factors. In order to address current challenges in miRNA clinical research on PCa, a PubMed-based literature search was conducted with the last update in May 2019. After identifying critical variations in designs and protocols that undermined clear-cut evidence acquisition, and reliable translation into clinical practice, we propose guidelines for most critical steps that should be considered in future research of miRNA as biomarkers, especially in PCa.
Objective: To investigate the role of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in the development of cervical metastases in papillary thyroid cancer. Our hypothesis is that level of expression of MMPs and TIMPs is associated with the development of cervical metastases and the pattern of metastatic process in papillary thyroid cancer.Design: This research retrospectively investigates the expression of MMP-1, -2 and -9 as well as TIMP-1 and -2 in papillary thyroid carcinoma tissue. Tissue specimens were immunohistochemically treated with primary monoclonal antibodies against MMP-1, MMP-2, MMP-9, TIMP-1 and TIMP-2.Setting: Single-centre study.Participants: In total, samples of 159 patients were analysed. In all patients, total thyroidectomy was performed, whereas 102 patients underwent selective neck dissection of either central (level VI) or lateral neck (level II-V). Subjects were divided into four groups. Main outcome measures: Matrix metalloproteinases and TIMPs expression valueswere analysed in each group, and groups were compared to each other.Results: Total number of patients was 159, of which 125 were women and 34 men.Comparing expression levels of MMPs and TIMPs in metastatic (study groups) and non-metastatic (control group), papillary thyroid carcinomas yielded significant differences in MMP-1 and TIMP-1 expression levels, where the highest expression values were found in the group with metastasis in lateral neck. Expression levels of MMP-2, MMP-9 and TIMP-2 did not differ statistically significant among the groups. Conclusion:Elevated expression of MMP-1 and TIMP-1 in tumour tissue can be considered a predictive factor for the development of metastases.
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