PATIENTS AND METHODS: We retrospectively reviewed data from patients below 18 years of age with iGCTs treated at the University Malaya Medical Center (UMMC) from 1998 to 2017.
RESULTS: Thirty-four patients were identified, with a median follow-up of 3.54 years. Sixteen (47%) patients had pure germinoma tumors (PGs), and the remaining patients had nongerminomatous germ cell tumors (NGGCTs). The median age was 12 years, with a male:female ratio of 4.7:1. Abnormal vision, headache with vomiting, and diabetes insipidus were the commonest presenting symptoms. Twenty-eight patients received initial surgical interventions, 24 were treated with chemotherapy, and 28 received radiotherapy. Eight patients experienced relapses. The 5- and 10-year event-free survival rates were similar at 61.1%±12.6% and 42.9%±12.1% for PG and NGGCT, respectively. The 5- and 10-year overall survival rates were the same at 75.5%±10.8% and 53.3%±12.3% for PG and NGGCT, respectively. Four patients died of treatment-related toxicity. Most of the survivors experienced good quality of life with satisfactory neurologic status.
CONCLUSIONS: The survival rate of childhood iGCTs in UMMC was inferior to that reported in developed countries. Late diagnosis, poor adherence to treatment, and treatment-related complications were the contributing factors. Although these results highlight a single institution experience, they most likely reflect similar treatment patterns, outcomes, and challenges in other centers in Malaysia.
Methodology: Serum samples from six BAVM patients and three control subjects were analyzed using enzyme-linked immunoabsorbent assay (ELISA) for OPN. A total of 10 BAVM patients and five control subjects were analyzed using Multiplex ELISA for MMPs. A total of 16 BAVM tissue samples and two normal brain tissue samples were analyzed using immunohistochemistry.
Result: MMP-2 and -9 were significantly higher in the serum of BAVM patients before and after treatment than in control patients. There were no significant differences of OPN and MMP-9 serum level in BAVM patients before and after treatment. MMP-2 showed a significant elevation after the treatment. Expression of OPN, MMP-2 and -9 proteins were seen in endothelial cells, perivascular cells and brain parenchyma of BAVM tissues.
Conclusion: Findings revealed that the level of MMP-2 and -9 in the serum correlated well with the expression in BAVM tissues in several cases. Knockdown studies will be required to determine the relationships and mechanisms of action of these markers in the near future. In addition, studies will be required to investigate the expression of these markers' potential applications as primary medical therapy targets for BAVM patients.
OBJECTIVES: This study was performed to identify mechanisms of afatinib resistance and to explore potential afatinib-based combination treatments with other targeted inhibitors in oral squamous cell carcinoma.
METHODS: We determined the anti-proliferative effects of afatinib on a panel of oral squamous cell carcinoma cell lines using a crystal violet-growth inhibition assay, click-iT 5-ethynyl-2'-deoxyuridine staining, and cell-cycle analysis. Biochemical assays were performed to study the underlying mechanism of drug treatment as a single agent or in combination with the MEK inhibitor trametinib. We further evaluated and compared the anti-tumor effects of single agent and combined treatment by using oral squamous cell carcinoma xenograft models.
RESULTS: In this study, we showed that afatinib inhibited oral squamous cell carcinoma cell proliferation via cell-cycle arrest at the G0/G1 phase, and inhibited tumor growth in xenograft mouse models. Interestingly, we demonstrated reactivation of the mitogen-activated protein kinase (ERK1/2) pathway in vitro, which possibly reduced the effects of ErbB inhibition. Concomitant treatment of oral squamous cell carcinoma cells with afatinib and trametinib synergized the anti-tumor effects in oral squamous cell carcinoma-bearing mouse models.
CONCLUSIONS: Our findings provide insight into the molecular mechanism of resistance to afatinib and support further clinical evaluation into the combination of afatinib and MEK inhibition in the treatment of oral squamous cell carcinoma.