Cancer is a leading cause of death by disease in children and the second most prevalent of all causes in adults. Testicular germ cell tumors (TGCTs) make up 0.5% of pediatric malignancies, 14% of adolescent malignancies, and are the most common of malignancies in young adult men. Although the biology and clinical presentation of adult TGCTs share a significant overlap with those of the pediatric group, molecular evidence suggests that TGCTs in young children likely represent a distinct group compared to older adolescents and adults. The rarity of this cancer among pediatric ages is consistent with our current understanding, and few studies have analyzed and compared the molecular basis in childhood and adult cancers. Here, we review the major similarities and differences in cancer genetics, cytogenetics, epigenetics, and chemotherapy resistance between pediatric and adult TGCTs. Understanding the biological and molecular processes underlying TGCTs may help improve patient outcomes, and fuel further investigation and clinical research in childhood and adult TGCTs.

Strongyloidiasis is a human parasitic disease caused by the helminth Strongyloides stercoralis whose treatment is particularly difficult in immunosuppressed patients due to their low responsiveness to conventional therapy. Carica papaya and its isolated compounds benzyl isothiocyanate, carpaine and carpasemine are promising compound for the treatment of Strongyloides infections due to their anthelmintic action. This study aims to examine the in vitro ovicidal and larvicidal activity of C. papaya seed hexane extract against Strongyloides venezuelensis, using egg hatching tests and larval motility tests as efficiency markers. The crude extract at the concentrations of 566 – 0.0566 mg/mL or the control with albendazole (0.025 mg/mL) and negative controls (water and PBS) were incubated with an equal volume of egg suspension (± 50 specimens) followed by counting of the specimens after 48 h. The same extract and dilutions were added to L3 larvae suspensions (±50 specimens) followed by analysis of larvae viability after 24, 48, and 72 h. The extract inhibited egg hatching with high efficiency at concentrations of 56.6 mg/mL (95.74%) and 5.66 mg/mL (92.16%). At the concentrations of 566 mg/mL (100%) and 56.66 mg/mL (97.32%), the extract inhibited larval motility as effectively as ivermectin (0.316 mg/mL; 100%), and more effectively than the other dilutions and the negative controls. The larvicidal effect depended on the extract concentration, but not on the treatment period. Therefore, C. papaya seed hexane extract has anthelmintic potential against S. venezuelensis and is a promising compound for the development of phytotherapies to treat strongyloidiasis.

Background: Testicular germ cell tumors (TGCTs), a group of heterogeneous neoplasms, are the most frequent tumors of teenagers and young men, with the incidence rising worldwide. High cure rates can be achieved through cisplatin (CDDP)-based treatment, but approximately 10% of patients present refractory disease and virtually no treatment alternatives. Here, we explored new strategies to treat CDDP-resistant. Methods: In vitro TGCT CDDP-resistance model was established and differential mRNA expression profiles were evaluated using NanoString technology. Then, TGCT cell lines were treated with four potential drugs (PCNA-I1, ML323, T2AA, and MG-132) to overcome CDDP-resistance. Results: We found several differentially expressed genes related to DNA repair and cell cycle regulation on CDDP-resistant cell line (NTERA-2R) compared to parental cell line (NTERA-2P), and the proteasome inhibitor MG-132 demonstrated cytotoxic activity in all cell lines evaluated, even at a nanomolar range. MG-132 also enhanced cell lines' sensitivity to CDDP, increasing apoptosis in both NTERA-2P and NTERA-2R. Conclusions: MG-132 emerges as a potential new drug to treat CDDP-resistant TGCT. Targeted therapy based on molecular mechanism insights may contribute to overcome acquired chemotherapy CDDP-resistance.

BackgroundTesticular Germ Cell Tumors (TGCT) are the most common cancer among young adult men. The TGCT histopathology is diverse, and the frequency of genomic alterations, along with their prognostic role, remains largely unexplored. Herein, we evaluate the mutation profile of a 15-driver gene panel and copy number variation of KRAS in a large series of TGCT from a single reference cancer center.Materials and methodsA cohort of 97 patients with TGCT, diagnosed at the Barretos Cancer Hospital, was evaluated. Real-time PCR was used to assess copy number variation (CNV) of the KRAS gene in 51 cases, and the mutation analysis was performed using the TruSight Tumor 15 (Illumina) panel (TST15) in 65 patients. Univariate analysis was used to compare sample categories in relation to mutational frequencies. Survival analysis was conducted by the Kaplan–Meier method and log-rank test.ResultsKRAS copy number gain was a very frequent event (80.4%) in TGCT and presented a worse prognosis compared with the group with no KRAS copy gain (10y-OS, 90% vs. 81.5%, p = 0.048). Among the 65 TGCT cases, different variants were identified in 11 of 15 genes of the panel, and the TP53 gene was the most recurrently mutated driver gene (27.7%). Variants were also detected in genes such as KIT, KRAS, PDGFRA, EGFR, BRAF, RET, NRAS, PIK3CA, MET, and ERBB2, with some of them potentially targetable.ConclusionAlthough larger studies incorporating collaborative networks may shed the light on the molecular landscape of TGCT, our findings unveal the potential of actionable variants in clinical management for applying targeted therapies.

Tumores de Célula Germinativa (TCGs) são neoplasias benignas ou malignas, classificadas em diferentes histologias: seminomas, não seminomas (teratomas, seio endodérmico, carcinomas embrionários e coriocarcinoma). Dentre os hallmarks of cancer encontra-se a transição epitélio-mesenquimal (EMT), processo no qual as células epiteliais perdem suas características e adquirem fenótipo mesenquimal. A EMT pode ser induzida por diversos fatores, sendo SNAIL e SLUG os protagonistas. A EMT foi associada com diversos canceres, entretanto, há uma escassez de informação da EMT nos TCGs. O objetivo foi avaliar a EMT em diferentes tipos histológicos de TCGs. Foi realizada uma análise in silico, utilizando as plataformas cBioPortal, Oncomine, PAXdb, para avaliar a expressão dos marcadores da EMT em pacientes com TCGs. Os marcadores da EMT também foram avaliados por qPCR e WB em diferentes linhagens de TCGs: carcinoma embrionário (NTERA-2 e 1777N), coriocarcinoma (JEG-3) e teratoma malígno (577MF). As análises in silico revelaram que SNAIL possui maior abundância de proteína no organismo do que SLUG. Contudo, SLUG possui impacto significativo na sobrevida livre de doença. Os tumores não-seminomatosos possuem maior expressão dos marcadores da EMT comparado com os seminomatosos. Dentre os não-seminomatosos, os teratomas apresentaram maior expressão dos marcadores da EMT. As análises in vitro confirmaram os resultados e a linhagem 577MF apresentou menor expressão E-CADERINA e superexpressão de SNAIL, VIMENTINA, FIBRONECTINA, TGF-β, e N-CADERINA. Portanto, a expressão dos marcadores da EMT em TCGs varia de acordo com a histologia, sendo mais expressos em teratomas. Maiores investigações são necessárias para avaliar o papel desses fatores em TCGs.