Cisplatin­resistant germ cell tumor models: An exploration of the epithelial­mesenchymal transition regulator SLUG.

Germ cell tumors (GCTs) constitute diverse neoplasms arising in the gonads or extragonadal locations. Testicular GCTs (TGCTs) are the predominant solid tumors in adolescents and young men. Despite cisplatin serving as the primary therapeutic intervention for TGCTs, 10­20% of patients with advanced disease demonstrate resistance to cisplatin­based chemotherapy, and epithelial­mesenchymal transition (EMT) is a potential contributor to this resistance. EMT is regulated by various factors, including the snail family transcriptional repressor 2 (SLUG) transcriptional factor, and, to the best of our knowledge, remains unexplored within TGCTs. Therefore, the present study investigated the EMT transcription factor SLUG in TGCTs. In silico analyses were performed to investigate the expression of EMT markers in TGCTs. In addition, a cisplatin­resistant model for TGCTs was developed using the NTERA­2 cell line, and a mouse model was also established. Subsequently, EMT was assessed both in vitro and in vivo within the cisplatin­resistant models using quantitative PCR and western blot analyses. The results of the in silico analysis showed that the different histologies exhibited distinct expression profiles for EMT markers. Seminomas exhibited a lower expression of EMT markers, whereas embryonal carcinomas and mixed GCT demonstrated high expression. Notably, patients with lower SLUG expression had longer median progression­free survival (46.4 months vs. 28.0 months, P=0.022). In the in vitro analysis, EMT­associated genes [fibronectin; vimentin (VIM); actin, α2, smooth muscle; collagen type I α1; transforming growth factor­ß1; and SLUG] were upregulated in the cisplatin­resistant NTERA­2 (NTERA­2R) cell line after 72 h of cisplatin treatment. Consistent with this finding, the NTERA­2R mouse model demonstrated a significant upregulation in the expression levels of VIM and SLUG. In conclusion, the present findings suggested that SLUG may serve a crucial role in connecting EMT with the development of cisplatin resistance, and targeting SLUG may be a putative therapeutic strategy to mitigate cisplatin resistance.

Decoding the Roles of Astrocytes and Hedgehog Signaling in Medulloblastoma.

The molecular evolution of medulloblastoma is more complex than previously imagined, as emerging evidence suggests that multiple interactions between the tumor cells and components of the tumor microenvironment (TME) are important for tumor promotion and progression. The identification of several molecular networks within the TME, which interact with tumoral cells, has provided new clues to understand the tumorigenic roles of many TME components as well as potential therapeutic targets. In this review, we discuss the most recent studies regarding the roles of astrocytes in supporting sonic hedgehog (SHH) subgroup medulloblastoma (MB) and provide an overview of MB progression through SHH expression and signal transduction mechanisms into the complex tumor microenvironment. In addition, we highlight the associations between tumor and stromal cells as possible prognostic markers that could be targeted with new therapeutic strategies.

ICAM-1 (Lys469Glu) and PECAM-1 (Leu125Val) polymorphisms in diffuse astrocytomas.

Cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1) play an important role in glioma invasion and angiogenesis. The aim of this study was to investigate whether specific genetic polymorphisms of ICAM-1 and PECAM-1 could be associated with glioma development and progression. Single-nucleotide polymorphism in codon 469 of ICAM-1 and codon 125 of PECAM-1 were examined in 158 patients with astrocytomas and 162 controls using polymerase chain reaction and restriction enzyme analysis. The distribution of PECAM-1 polymorphic genotypes in astrocytomas did not show any significant difference. However, a specific ICAM-1 genotype (G/G, corresponding to Lys469Glu) exhibited higher frequency in grade II astrocytomas compared to controls, grade III, and grade IV astrocytomas; suggesting that this polymorphism could be involved in the development of grade II astrocytomas.

Factors associated with location of death of children with cancer in palliative care.

OBJECTIVE: The aim of this study was to identify factors associated with location of death of patients receiving palliative care in a pediatric oncology unit. METHODS: A palliative care program was developed in the pediatric department in order to provide specialized attention to the patient and family in end-of-life. The program is coordinated by a nurse, delivering a simultaneous interdisciplinary team approach with focus on identification and training of a family care provider as well as local resources supplemented by support of a social worker and the community. All 87 patients in palliative care were followed by the team. The factors associated with the location of death (home or hospital) were evaluated for the 71 patients who died prior to analysis. RESULTS: Forty-two (59%) patients died at home. Factors significantly associated with dying at home were: male with an Odds Ratio (OR) = 3.80, 95% Confidence Interval (CI) = 1.26-11.76; public health insurance (OR) = 4.95, 95%[CI] = 1.03-26.75, low educational level of the caregiver (OR) = 11.11 95%[CI] = 1.65-94.66 and low educational level of the mother (OR) = 7.07 95%[CI] = 1.37-40.14. Gender was the only independent factor associated with location of death: a boy had a higher risk of dying at home, (OR) = 4.25, 95%[CI] = 1.37-13.21 when compared to a girl. SIGNIFICANCE OF RESULTS: In our society we are still not able to provide hospice care or home care for all children, although increasing emphasis has been placed on utilizing local resources. Even though we had increased the number of desired home deaths, it is still a challenge to meet patients and families' requests. A team approach, the recognition of the factors involved, and adequate health and community support have helped us to meet the child and family's needs.