Angiogenesis and Lymphangiogenesis of Gastric Cancer

Tumor angiogenesis is the result of an imbalance between positive and negative angiogenic factors released by tumor and host cells into the microenvironment of the neoplastic tissue. The stroma constitutes a large part of most solid tumors, and cancer-stromal cell interactions contribute functionally to tumor growth and metastasis. Activated fibroblasts and macrophages in tumor stroma play important roles in angiogenesis and tumor progression. In gastric cancer, tumor cells and stromal cells produce various angiogenic factors, including vascular endothelial growth factor, interleukin-8, platelet-derived endothelial cell growth factor, and angiopoietin. In addition, Helicobacter pylori infection increases tumor cell expression of metastasis-related genes including those encoding several angiogenic factors. We review the current understanding of molecular mechanisms involved in angiogenesis and lymphangiogenesis of human gastric cancer

Analysis of DOC and Ram for NSCLC

Background: Current clinical trials demonstrated that combination regimens comprising chemotherapy and immunotherapy lead to better patient outcomes compared to chemotherapy alone as the first line of treatment for non-small cell lung cancer (NSCLC). In addition, the combination therapy of docetaxel (Doc) and ramucirumab (Ram) was considered one of the standard treatments for advanced or relapsed NSCLC patients. However, little is known about the therapeutic responders of this combination therapy among previously treated NSCLC patients. In the present study, we aimed to identify predictive factors for therapeutic response, including programmed death-ligand 1 (PD-L1) expression in tumors, for Doc treatment in combination with Ram. Methods: We retrospectively analyzed a total of 135 advanced or relapsed NSCLC patients who were refractory to platinum-based chemotherapy at eleven institutions in Japan between July 2016 and November 2018. Results: Our observations showed that PD-L1 expression in tumors is not associated with the efficacy of combined therapy of Doc and Ram in previously treated NSCLC patients. Analysis of the patient clinical profiles indicated that prior treatment with immune checkpoint inhibitors (ICIs) is a reliable predictor for the good progression-free survival (PFS) to this combination therapy (P=0.041). Conclusions: Our retrospective study indicated that combination regimens comprising chemotherapy and ICIs followed by Doc and Ram could be an optimal therapeutic option for NSCLC patients regardless of the PD-L1 status of tumors. Further investigations are required to strengthen clinical evidence demonstrating the effectiveness of the combination therapy of Doc plus Ram in previously treated NSCLC patients

Computed tomographic arteriography in the diagnosis of hepatocellular carcinoma.

Computed tomographic arteriography (CTA) was performed in 30 patients with hepatocellular carcinoma (HCC). Detection of HCC by CTA was compared with that of conventional celiac or hepatic arteriography. CT scanning was performed immediately, 30 seconds and 1 min after an injection of 5 to 10 ml of contrast medium into the common or proper hepatic artery. Repeated infusions allowed whole liver sections to be visualized. HCC was localized in 28 of the 30 patients by conventional arteriography, with CTA detecting the masses in 27 of the 28 patients. CTA imaging presented the tumor mass in 1 of the 2 patients missed by arteriography. Conventional arteriography delineated the boundaries of HCC in 15 (50%) of the 30 patients. CTA clearly delineated the masses in 26 (87%) of the 30 patients including 11 patients in which the tumor borders were obscure by conventional arteriography. HCC lesions smaller than 1 cm in diameter were detected only by CTA in 6 (20%) of the patients. It was concluded that CTA is both useful and necessary in the demarcation of small HCC masses.</p

Cancer-Stromal Cell Interaction and Tumor Angiogenesis in Gastric Cancer

Recent studies in molecular and cellular biology have shown that tumor growth and metastasis are not determined by cancer cells alone but also by a variety of stromal cells. The stroma constitutes a large part of most solid tumors, and cancer-stromal cell interaction contributes functionally to tumor growth and metastasis. Angiogenesis is the result of an imbalance between positive and negative angiogenic factors released by tumor and host cells into the microenvironment of the neoplastic tissue. In gastric cancer, tumor cells and stromal cells produce various angiogenic factors, including vascular endothelial growth factor, interleukin-8, and platelet-derived endothelial cell growth factor. The microenvironment in the gastric mucosa may also influence the angiogenic phenotype of gastric cancer. Helicobacter pylori infection increases expression of several angiogenic factors by tumor cells. Activated fibroblasts and macrophages in tumor stroma also play an important role in angiogenesis and tumor progression. We review the current understanding of cancer-stromal cell interaction as it pertains to tumor angiogenesis in gastric cancer

Stroma-Directed Molecular Targeted Therapy in Gastric Cancer

Recent studies in molecular and cellular biology have shown that tumor growth and metastasis are not determined by cancer cells alone, but also by a variety of stromal cells. Tumor stroma contains abundant extracellular matrix and several types of cells, including carcinoma-associated fibroblasts (CAFs), endothelial cells, pericytes and inflammatory cells including macrophages. In gastric cancer tissues, tumor cells express platelet-derived growth factor (PDGF)-B. Stromal cells, including CAFs, pericytes and lymphatic endothelial cells, express PDGF receptor (PDGFR)-β. Administration of PDGFR tyrosine kinase inhibitor significantly decreases stromal reaction, lymphatic vessel area and pericyte coverage of tumor microvessels. Administration of PDGFR tyrosine kinase inhibitor in combination with cytotoxic chemotherapeutic drug(s) impairs the progressive growth and metastasis of gastric cancer. Activated stroma might serve as a novel therapeutic target in cases of gastric cancer

Association between Helicobacter suis infection and the pathogenesis of gastric mucosa-associated lymphoid tissue lymphoma

Objective: In patients with Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma, eradication therapy is only effective in some cases, suggesting that infections with non-H. pylori Helicobacter (NHPH) species may also be involved. Therefore, we examined the prevalence of infection with Helicobacter suis, an NHPH, in gastric MALT lymphoma patients. Methods: We examined the H. suis infection status of 15 patients with H. pylori-negative gastric MALT lymphoma. To examine the infection prevalence through species-specific PCR analysis, DNA was extracted from the lymphoma lesion and the background gastric mucosa. We compared the PCR products amplified from DNA extracted from different lesions. Results: H. suis was detected in 3 of the 15 cases (20.0%), but only in the background gastric mucosa and not in the lymphoma lesion. H. suis was completely eradicated in all three cases and two of the three cases exhibited complete remission of the lymphoma. Conclusion: These results indicated that H. suis infection may be involved in the pathogenesis of gastric MALT lymphoma. We conclude that it is desirable to use multiple biopsies, including the background mucosa, to evaluate NHPH infection in gastric MALT lymphoma patients.This research was partially supported by the PUH Research Grant Program (Advanced Research A)