Testicular germ cell tumor (TGCT) is the most common solid malignancy occurring in young men between 20 and 34 years of age, and its incidence has increased significantly over the last decades. TGCTs ...can be subdivided into seminoma and nonseminoma germ cell tumors (NSGCTs), which includes yolk sac tumor, choriocarcinoma, embryonal cell carcinoma, and teratoma. Seminomas and NSGCTs present significant differences in therapy, prognosis, and both show characteristics of the Primordial Germ Cells (PGCs).
I undertook a search of bibliographic data from peer-reviewed research literature.
Seventy papers were included in the mini-review showing that a large number of new biomarkers have given further advantages to discriminate the different histotypes and could represent useful novel molecular targets for anticancer strategies.
A deeper understanding of the pathogenesis of TGCTs is likely to significantly improve not only our knowledge on stem cells and oncogenesis but also the disease management with more selective tumor treatment.
Testicular germ cell tumors (TGCTs) are the leading form of solid cancer and death affecting males between the ages of 20 and 40. Today, their surgical resection and chemotherapy are the treatments ...of first choice, even if sometimes this is not enough to save the lives of patients with TGCT. As seen for several tumors, the deregulation of microRNAs (miRNAs) is also a key feature in TGCTs. miRNAs are small molecules of RNA with biological activity that are released into biological fluids by testicular cancer cells. Their presence, therefore, can be detected and monitored by considering miRNAs as diagnostic and prognostic markers for TGCTs. The purpose of this review is to collect all the studies executed on miRNAs that have a potential role as biomarkers for testicular tumors.
In the last decade novel therapeutic approaches for the treatment of cancer have been proposed: inhibitors of serine/threonine and tyrosine kinases, angiogenesis inhibitors, gene therapy approaches ...and others. In some cases the clinical trials have confirmed the efficacy of these approaches. Here, we will review the discovered molecular targets for the treatment of testicular germ cell tumors.
The most common solid malignancy of young men aged 20 to 34 years is testicular germ cell tumor. In addition, the incidence of these tumors has significantly increased throughout the last years. ...Testicular germ cell tumors are classified into seminoma and nonseminoma germ cell tumors, which take in yolk sac tumor, embryonal cell carcinoma, choriocarcinoma, and teratoma. There are noteworthy differences about therapy and prognosis of seminomas and nonseminoma germ cell tumors, even though both share characteristics of the primordial germ cells.
The study is focused on different molecular mechanisms strongly involved in testicular germ cell line tumors underlying new strategies to treat this human neoplasia.
Bibliographic data from peer-reviewed research, patent and clinical trial literature, and around eighty papers and patents have been included in this review.
Our study reveals that several biomarkers are usefully utilized to discriminate among different histotypes. Moreover, we found new patents regarding testicular germ cell tumor treatments such as the expression of claudin 6, monoclonal antibody (Brentuximab Vedotin), immune checkpoint blockade (ICB) with the FDA-approved drugs pembrolizumab and nivolumab or the oncolytic virus Pelareorep, the combination of selective inhibitors of Aurora kinase.
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.
NEK2 is a serine/threonine kinase that promotes centrosome splitting and ensures correct chromosome segregation during the G2/M phase of the cell cycle, through phosphorylation of specific ...substrates. Aberrant expression and activity of NEK2 in cancer cells lead to dysregulation of the centrosome cycle and aneuploidy. Thus, a tight regulation of NEK2 function is needed during cell cycle progression. In this study, we found that NEK2 localizes in the nucleus of cancer cells derived from several tissues. In particular, NEK2 co-localizes in splicing speckles with SRSF1 and SRSF2. Moreover, NEK2 interacts with several splicing factors and phosphorylates some of them, including the oncogenic SRSF1 protein. Overexpression of NEK2 induces phosphorylation of endogenous SR proteins and affects the splicing activity of SRSF1 toward reporter minigenes and endogenous targets, independently of SRPK1. Conversely, knockdown of NEK2, like that of SRSF1, induces expression of pro-apoptotic variants from SRSF1-target genes and sensitizes cells to apoptosis. Our results identify NEK2 as a novel splicing factor kinase and suggest that part of its oncogenic activity may be ascribed to its ability to modulate alternative splicing, a key step in gene expression regulation that is frequently altered in cancer cells.
Previous studies have demonstrated that d-aspartic acid (d-Asp) has a role in regulating the release and synthesis of testosterone in rats. In this study, we investigated the molecular pathway by ...which this amino acid triggers its action in the rat testis. We found expression of N-Methyl-D-Aspartic Acid (NMDA) receptor messenger RNAs for NR1, NR2A, and NR2D receptor subunits. After d-Asp administration, NR1 and NR2A messenger RNA levels were significantly higher than those of controls, whereas NR2D levels remained unchanged. Expression of extracellular signal–regulated kinase (ERK) 1 protein was higher than that of ERK2 protein in the testis of both d-Asp–treated rats and controls. d-Asp administration increased testis levels of both phosphorylated ERK (P-ERK) 1 and 2. Using immunohistochemical technique, NR1 and P-ERK 1 or 2 proteins were preferentially localized within the spermatogonia. Moreover, d-Asp administration increased both serum and testis testosterone levels but not estradiol levels. Finally, in d-Asp–treated rats, testicular androgen receptor protein levels were significantly increased, whereas both estrogen receptor α and P-450 aromatase levels were significantly decreased. Conclusively, our results, besides strengthening the evidence that d-Asp administration in rats induces testosterone synthesis, demonstrate for the first time that d-Asp (1) induces testicular NMDA receptor–ERK pathway, (2) upregulates androgen receptor expression, and (3) downregulates estrogen receptor expression.
Extragonadal germ cell tumors (EGGCTs) are uncommon neoplasms, which arise in anatomical locations other than gonads. The pathogenesis of these neoplasms is still poorly understood and it is a matter ...of debate if they really represent extragondal primary neoplasms or rather extragondal metastasis from occult gonadal neoplasms. The actual observations suggest that EGGCTs represent a unique entity, so their biology and behavior are substantially different from gonadal counterparts. The diagnosis of EGGCTs is often challenging, and differential diagnosis is particularly wide. Nevertheless, a correct diagnosis is essential for the correct management of the patient. We summarize the state of art about EGGCTs, with particular emphasis on diagnosis and prognosis.
Extragonadal germ cell tumors (EGGCTs) are uncommon neoplasms with peculiar molecular and pathological features; the diagnosis of these neoplasms may be challenging, due to wide differential diagnosis depending to the variable anatomical location. The authors summarize the state of art about EGGCTs, with particular emphasis on diagnosis and prognosis.
Testicular germ cell tumors (TGCTs) are the most frequent solid malignant tumors in men 20–40 years of age and the most frequent cause of death from solid tumors in this age group. TGCTs can be ...subdivided into seminoma and non-seminoma germ cell tumors (NSGCTs), including embryonal cell carcinoma, choriocarcinoma, yolk sac tumor, and teratoma. Seminomas and NSGCTs do not only present distinctive clinical features, but they also show significant differences as far as therapy and prognosis are concerned. The different therapeutic outcome might be explained by inherent properties of the cells from which testicular neoplasia originates. The unique treatment sensitivity of TGCTs is unexplained so far, but it is likely to be related to intrinsic molecular characteristics of the primordial germ cells/gonocytes, from which these tumors originate. Many discovered biomarkers including OCT3/4, SOX2, SOX17, HMGA1, Nek2, GPR30, Aurora-B, estrogen receptor β, and others have given further advantages to discriminate between histological subgroups and could represent useful novel molecular targets for antineoplastic strategies.
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