Clinical significance of heparanase activity in primary resected non-small cell lung cancer

Clinicopathological significances of heparanase activity in non-small cell lung cancer (NSCLC) were investigated by analyzing 76 resected specimens of NSCLC. Heparanase activities in NSCLC were significantly higher than non-cancerous lung tissues (P < 0.0001). The heparanase activities of NSCLC were significantly higher in larger diameter tumors (P = 0.0141) or with metastasis to ipsilateral mediastinal lymph nodes (P = 0.0004). The activities of heparanase in primary tumors were increased significantly according to the pathological stage of the progression of the disease (P =0.0009). Among the clinicopathological parameters, histological cell type and evidence of ipsilateral lymph node metastasis showed a significant association with elevated heparanase activities, whereas age, degree of differentiation and tumor diameter did not. Kaplan-Meier curves for overall and disease-free survival demonstrated a significant difference between patients with elevated and non-elevated heparanase activity by log-rank test (P = 0.0145 and 0.0002, respectively). Multivariate analysis showed heparanase activity was an independent factor to influence disease-free survival in our study. These results suggest that heparanase activity could be used as a prognostic indicator for postoperative patients with NSCLC and heparanase might be a promising molecular target for treatment of NSCLC.     

Csk defines the ability of integrin-mediated cell adhesion and migration in human colon cancer cells: implication for a potential role in cancer metastasis

Progression of human colon cancer is often associated with elevated expression and activity of the Src family tyrosine kinase (SFK). SFK is ordinarily in equilibrium between inactive and primed states by a balance of negative regulatory kinase Csk and its counteracting tyrosine phosphatase(s), both of which act on the regulatory C-terminal tyrosine of SFK. To evaluate the contribution of the regulatory system of SFK in cancer progression, we here modulated the equilibrium status of SFK by introducing wild-type or dominant-negative Csk in human epithelial colon cancer cells, HCT15 and HT29. Overexpression of wild-type Csk induced decreased SFK activation, increased cell-cell contacts mediated by E-cadherin, decreased the number of focal contacts and decreased cell adhesion/migration and in vitro invasiveness. Conversely, expression of a dominant-negative Csk resulted in elevated SFK activation, enhanced phosphorylation of FAK and paxilllin, enhanced cell scattering, an increased number of focal contacts, dramatic rearrangement of actin cytoskeleton and increased cell adhesion/migration and in vitro invasiveness. In these scattered cells, however, localization, expression and phosphorylation of either E-cadherin or beta-catenin were not significantly affected, suggesting that the E-cadherin-mediated cell-cell contact is indirectly regulated by SFK. Furthermore, all these events occurred absolutely dependent on integrin-mediated cell adhesion. These findings demonstrate that Csk defines the ability of integrin-SFK-mediated cell adhesion signaling that influences the metastatic potential of cancer cells.     

Enhanced regional washout of technetium-99m-sestamibi in patients with coronary spastic angina

BACKGROUND: Reverse redistribution and rapid washout of 99mTc-sestamibi are observed in patients with acute myocardial infarction and may indicate viable myocardium. However, the clinical significance of this phenomenon has not been rigorously examined in other cardiac diseases. Thus, we investigated whether reverse redistribution and washout of 99mTc-sestamibi could be used in the diagnosis and follow-up of patients with coronary spastic angina. METHODS: Thirty patients diagnosed as coronary spastic angina were examined. During coronary arteriography, spasm was induced by provocation test with ergonovine, and only total or subtotal occlusion was considered positive. Myocardial perfusion tomography was obtained 45 min (early) and 3 hr (delayed) after 99mTc-sestamibi injection. Segmental defect score was visually graded from 0 (normal) to 4 (defect), and a total defect score was determined as the sum of defect scores for all segments. Washout rate of 99mTc-sestamibi from the myocardium was calculated for each segment. After medical treatment with calcium antagonists and nitrates for 3 months, 99mTc-sestamibi imaging was repeated. RESULTS: Out of 30 patients, on the early images 17 (57%) patients demonstrated decreased 99mTc-sestamibi uptake in spastic segments; on the other hand, 24 (80%) patients did decreased 99mTc-sestamibi uptake in spastic segments on delayed images. Total defect scores in delayed images were higher than those in early images (6.9 +/- 0.3 vs. 3.6 +/- 0.4, p < 0.01). Reverse redistribution of 99mTc-sestamibi was observed in 17 out of 30 patients (57%) with coronary spastic angina. Washout rate of 99mTc-sestamibi from spastic segments was higher than that from non-spastic segments (16 +/- 2% vs. 11 +/- 5%, p < 0.01). After medical treatment, washout rate from spastic segments was decreased to 10 +/- 4 (p < 0.01), and left ventricular ejection fraction was increased from 63 +/- 8% to 73 +/- 4% (p < 0.01). CONCLUSION: Rapid washout of 99mTc-sestamibi was observed in patients with coronary spastic angina and might indicate that the ability of myocyte to retain the tracer was impaired due to repetitive brief ischemia by coronary spasm. The early and delayed 99mTc-sestamibi imaging provides useful information for the diagnosis and responses to the treatment in patients with coronary spastic angina.     

Stromal cell-derived factor-1α improves infarcted heart function through angiogenesis in mice

BACKGROUND: Local delivery of stromal cell-derived factor-1alpha (SDF-1) has been demonstrated to improve hind limb ischemia through enhanced neovascularization in animals. It was hypothesized that local administration of SDF-1 also contributes to neovascularization of ischemic heart. METHOD: Acute myocardial infarction was created by left coronary artery ligation in C57BL/6J mice. Immediately after infarction induction, mice were treated by injection directly into the center of ischemic myocardium either with saline (control group) or SDF-1 (SDF-1 group). Cardiac function was measured on echocardiogram 2 and 4 weeks after infarction. On week 4 mice were killed to evaluate infarction size and capillary vessel density. To determine the contribution of bone marrow cells to angiogenesis, the same procedures were performed on C57BL/6J chimeric mice reconstituted with green fluorescent protein-positive bone marrow cells. RESULTS: Fractional shortening was greater in the SDF-1 group at 4 weeks (0.31 +/- 0.06% vs 0.23 +/- 0.03%, P = 0.037). The infarct area was smaller in the SDF-1 group compared to the control group (9.31 +/- 2.76% vs 18.07 +/- 5.69%, P = 0.028). Green fluorescent protein-positive cells accumulated predominantly at the peri-infarction site, and were located with the capillary vessels. Capillary vessel density was significantly increased in the SDF-1 group (13.08 +/- 4.11 vessels/mm(2) vs 34.50 +/- 7.59 vessels/mm(2), P = 0.014). CONCLUSIONS: SDF-1 protects against deterioration of cardiac function after acute myocardial infarction by promoting angiogenesis. The safety and long-term prognosis of this treatment remains to be determined.     

ABC transporter AtABCG25 is involved in abscisic acid transport and responses

Abscisic acid (ABA) is one of the most important phytohormones involved in abiotic stress responses, seed maturation, germination, and senescence. ABA is predominantly produced in vascular tissues and exerts hormonal responses in various cells, including guard cells. Although ABA responses require extrusion of ABA from ABA-producing cells in an intercellular ABA signaling pathway, the transport mechanisms of ABA through the plasma membrane remain unknown. Here we isolated an ATP-binding cassette (ABC) transporter gene, AtABCG25, from Arabidopsis by genetically screening for ABA sensitivity. AtABCG25 was expressed mainly in vascular tissues. The fluorescent protein-fused AtABCG25 was localized at the plasma membrane in plant cells. In membrane vesicles derived from AtABCG25-expressing insect cells, AtABCG25 exhibited ATP-dependent ABA transport. The AtABCG25-overexpressing plants showed higher leaf temperatures, implying an influence on stomatal regulation. These results strongly suggest that AtABCG25 is an exporter of ABA and is involved in the intercellular ABA signaling pathway. The presence of the ABA transport mechanism sheds light on the active control of multicellular ABA responses to environmental stresses among plant cells.     

Surveillance interval of endoscopic examinations for colorectal cancer screening

Background: There have been a few evidence‐based studies concerning the relationship between the length of the surveillance interval of colonoscopic examinations and the risk of colorectal cancer (CRC). The aim of the present study was to assess the appropriate interval between endoscopic examinations for CRC screening in a retrospective cohort study. Methods: The cohort included subjects in whom cancer was not detected at the initial endoscopic examination and in whom endoscopic examination(s) was subsequently performed one or more times. The results of the endoscopic examinations performed in the mass screening for CRC between November 1983 and March 1999 were analyzed. The study end point was the detection of CRC and the detection rates of cancer were assessed among those who underwent examinations at various intervals between successive endoscopic examinations. Results: Among the 117 636 cohort subjects, 63 invasive cancer cases and 112 mucosal cancer cases were found. The odds ratio (OR) for invasive cancer was not significantly elevated even when the interval between successive examinations was over 5 years. The OR for mucosal or invasive cancer was significantly elevated among the subjects in whom the interval between successive examinations was over 5 years (OR, 1.71; 95% confidence interval (CI), 1.07–2.73), than among those in whom the interval was 1 year. Conclusions: Since prolongation of the interval between endoscopic examinations of up to 5 years did not result in any change in the cancer risk among persons who are at average risk for CRC, 5 years may be an adequate interval between endoscopic examinations in the mass screening for CRC.     

Effects of 12-O-Tetradecanoyl Phorbol-13-Acetate (TPA) on Rat Thymocytes

The short-term incubation of rat thymocytes with 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in a significant increase in sialyltransferase (S-T) activity and a decrease in terminal deoxyribonucleotidyl transferase (TdT) activity. The ratio of peanut agglutinin (PNA)-positive cells and of TdT-positive cells in TPA-treated cells also decreased. However, TPA had no significant effects on the viability, morphology, DNA synthesis, and DNA polymerase alpha activity of the cells. More marked changes were observed by incubating a non-T, non-B human lymphoid leukaemia cell line with TPA. Similar findings were also noted in TPA-treated mouse thymocytes. These changes may represent an aspect of TPA-induced differentiation of murine thymocytes.