Dual blockade of MET and VEGFR2 signaling pathways as a potential therapeutic maneuver for peritoneal carcinomatosis in scirrhous gastric cancer.

Scirrhous gastric cancer frequently develops into peritoneal carcinomatosis with malignant ascites, leading to an extremely poor prognosis. We had demonstrated that paracrine hepatocyte growth factor (HGF)-induced MET activation promotes peritoneal carcinomatosis with ascites formation. The vascular endothelial growth factor (VEGF) receptor (VEGFR)/VEGF axis facilitates tumor progression and formation of malignant ascites. This study investigated the role of MET and VEGFR2 in the development of peritoneal carcinomatosis with malignant ascites. Cabozantinib is a dual inhibitor of MET and VEGFR2. We examined the effects of cabozantinib on MET- and VEGFR2-mediated progression of peritoneal carcinomatosis in human scirrhous gastric cancer in vitro and in vivo. Cabozantinib inhibited HGF-stimulated proliferation of scirrhous cancer cell lines NUGC4 and GCIY, with a high potential to generate peritoneal carcinomatosis with ascites fluid, as well as the constitutive proliferation of MKN45 cells with MET amplification. Cabozantinib also inhibited the phosphorylation of both MET and VEGFR2 in scirrhous cancer cells and HGF- or VEGF-stimulated HUVECs. It effectively reduced ascitic fluid and prolonged the survival of NUGC4-inoculated nude mice. In clinical specimens, malignant ascites fluid from patients with peritoneal carcinomatosis contained high levels of HGF and VEGF. Our results strongly suggest that MET- and VEGFR2-mediated signaling pathways play pivotal roles in the pathogenesis of peritoneal carcinomatosis in scirrhous gastric cancer. Thus, the dual blockade of MET and VEGFR2 signaling may be a potential therapeutic maneuver for peritoneal carcinomatosis in scirrhous gastric cancer.

[A Super-Aged Patient with Advanced ALK-Positive NSCLC and Malignant Pericardial Effusion Causing Cardiac Tamponade].

Here we report the case of an 88-year-old female with serious respiratory discomfort who exhibited significant heart enlargement and left pleural effusion in her chest X-ray. She developed cardiac tamponade with massive pericardial effusion, and the cytological analysis and diagnostic imaging revealed adenocarcinoma of an unknown primary site. Although supportive care was offered, due to her super-age and malignant pericardial effusion presenting cardiac tamponade, she and her family requested a detailed examination and active treatment. She was enrolled into our medical oncology department, and we immediately performed a cell block cytological examination procedure and drained the pleural effusion. The immunohistochemical and FISH analyses revealed anaplastic lymphoma kinase(ALK)-rearranged non-small cell lung cancer. An ALK tyrosine kinase inhibitor, alectinib, was administered and resulted in a prompt and effective improvement in clinical outcome. This case indicates that we should attempt to achieve an accurate diagnosis, even when patients are super-aged and exhibit serious progress disease conditions. The pleural effusion cell block analysis may be highly useful for the prompt and precise diagnosis of malignancies.