ABSTRACT
BACKGROUND: In Japan, the standard treatment policy for all potentially curable patients with gastric cancer is radical resection including extensive lymphadenectomy. This treatment strategy has been used for both early and advanced gastric cancers, and substantial increases in survival time have been reported. In advanced gastric cancer, lymphatic spread is reported to be one of the most relevant prognostic factors for gastric cancer resected for cure. The purpose of this study was to determine the factors affecting lymph node involvement and to establish guidelines for the extent of lymph node dissection most appropriate for the treatment of gastric cancer. METHODS: The clinicopathological features of 926 patients with gastric cancer were reviewed. Information on the clinicopathological features was obtained from the database of gastric cancer at the Department of Gastroenterological Surgery, Sendai National Hospital. Univariate and multivariate analyses of data for patients with gastric cancer tumors were performed to evaluate the prognostic significance of clinicopathological features. The independent risk factors influencing lymph node metastasis were determined by multiple logistic regression analysis. RESULTS: The following clinicopathologic factors were found to be correlated with prognosis of gastric cancer: (1) macroscopic type, (2) depth of invasion, (3) cancer-stromal relationship, (4) histological growth pattern, (5) lymph node involvement, (6) lymphatic invasion, (7) vascular invasion and (8) tumor site. However, a multivariate analysis revealed that macroscopic type, depth of invasion, lymph node involvement and tumor site are independent risk factors for the prognosis of gastric cancer patients. Among these factors, the prognosis of patients with gastric cancer was most strongly influenced by lymph node involvement (odds ratio, 4.632). According to a multiple logistic regression model, depth of cancer invasion and lymphatic invasion was significantly correlated with lymph node metastases. CONCLUSIONS: Lymph node involvement has the strongest influence on the prognosis of gastric cancer. Among the clinicopathological factors, depth of invasion and microscopically lymphatic invasion are important factors in predicting lymph node metastases. Thus, the ability to perform gastrectomy with dissection of lymph nodes is a basic requirement for gastric cancer surgeons.
Subject(s)
Adenocarcinoma/secondary , Lymph Node Excision , Stomach Neoplasms/pathology , Adenocarcinoma/surgery , Adult , Female , Humans , Logistic Models , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Practice Guidelines as Topic , Prognosis , Risk Factors , Stomach Neoplasms/surgeryABSTRACT
Vascular endothelial growth factor (VEGF) activates ERK and p38 MAPK in endothelial cells (ECs). The present study was aimed to compare its intracellular signal transduction pathways between three primary cultures of human ECs including human aortic ECs (HAECs), human umbilical vein ECs (HUVECs), and human microvascular ECs (HMVECs). VEGF activated ERK and p38 MAPK in all of three ECs. Isoforms of p38 MAPK that were activated by VEGF in HUVECs were p38-alpha and p38-delta. GF109203X, a specific inhibitor of PKC, markedly inhibited VEGF-induced activation of ERK and p38 MAPK in HAECs and HUVECs, whereas it exhibited little effect in HMVECs. In contrast, dominant negative mutant of Ha-Ras almost completely abrogated VEGF-induced activation of ERK and p38 MAPK in HMVECs. Although dominant negative mutant of Ha-Ras substantially inhibited the basal activities of ERK and p38 MAPK, it exhibited marginal effect on VEGF-induced activation of ERK and p38 MAPK in HUVECs and HAECs. The activation of Ras by VEGF appeared to be most prominent in HMVECs. These results indicate that intracellular signal transduction pathways for VEGF-induced activation of MAPKs are heterogeneous and vary depending on the origin of ECs.
Subject(s)
Endothelial Growth Factors/pharmacology , Endothelium, Vascular/enzymology , Lymphokines/pharmacology , MAP Kinase Signaling System/physiology , Signal Transduction/physiology , Aorta/cytology , Cells, Cultured , Endothelium, Vascular/cytology , Humans , MAP Kinase Signaling System/drug effects , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3 , Mitogen-Activated Protein Kinases/metabolism , Neovascularization, Physiologic/physiology , Oncogene Protein p21(ras)/metabolism , Protein Kinase C/metabolism , Signal Transduction/drug effects , Umbilical Veins/cytology , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors , p38 Mitogen-Activated Protein KinasesABSTRACT
A cDNA clone encoding angiopoietin-3 protein (Ang3), a novel member of the angiopoietin family, was identified. Ang3 cDNA was cloned from a human aorta cDNA library. Ang3 is a 503 amino acid protein having 45.1% and 44.7% identity with human angiopoietin-1 and human angiopoietin-2, respectively. Ang3 mRNA is expressed in lung and cultured human umbilical vein endothelial cells (HUVECs). Ang3 mRNA expression in HUVECs was slightly decreased by vascular endothelial cell growth factor treatment, suggesting that the regulation of Ang3 mRNA expression is different from that of Ang2.
Subject(s)
Intercellular Signaling Peptides and Proteins , Proteins/metabolism , Amino Acid Sequence , Angiopoietin-Like Protein 1 , Angiopoietin-like Proteins , Angiopoietins , Blotting, Northern , Chromosome Mapping , Chromosomes, Human, Pair 20 , Cloning, Molecular , Databases, Factual , Dose-Response Relationship, Drug , Gene Expression Regulation , Humans , Molecular Sequence Data , Multigene Family , Physical Chromosome Mapping , Sequence Homology, Amino Acid , Sequence Tagged Sites , Tissue DistributionABSTRACT
We report herein the case of a 32-year-old woman who underwent distal gastrectomy with D2 lymph node dissection for gastric cancer. Microscopic examination of the resected specimen revealed signet-ring cell carcinoma of the stomach with lymph node metastases, and endosalpingiosis in the normal lymph nodes. There was no evidence of malignancy in the peritoneal cavity. To our knowledge, no other case of endosalpingiosis in the lymph nodes along the stomach has ever been reported. The possible significance of endosalpingiosis is discussed following this case report.
Subject(s)
Carcinoma, Signet Ring Cell/pathology , Lymph Nodes/pathology , Stomach Neoplasms/pathology , Adult , Female , HumansABSTRACT
Poland fs syndrome is characterized by a congenital defect of the pectoralis major associated with various types of anomalies of the ipsilateral upper extremity. Furthermore, there have been reports of Poland fs syndrome associated with malignancies such as leukemia, malignant lymphoma, and leiomyosarcoma. We describe two cases of Poland fs syndrome associated with breast cancer. The first patient developed right breast cancer associated with ipsilateral breast hypoplasia, defects of the pectoralis major and minor, and syndactyly. She underwent mastectomy and dissection of the axillary nodes. The second patient had left breast cancer associated with ipsilateral breast hypoplasia, defects of the pectoralis major and minor, and syndactyly. She underwent breast-conserving surgery and dissection of the axillary nodes without irradiation of the breast. Both patients are currently alive and free of disease. Although previously there has been no evidence that links Poland fs syndrome and breast cancer, elucidating the molecularmechanism that causes Poland fs syndrome may further clarify the relationship between Poland fs syndrome and malignancies.
