Plasma Endostatin Levels are Elevated in Patients with Gastric Carcinoma

Angiogenesis is a key process in tumor growth and metastasis. In 27 patients with advanced gastric carcinoma before operation and 9 healthy controls, plasma levels of endostatin (ES), cathepsin L (Cat-L) and soluble VEGF R1/Flt-1 (sVEGF R1), which are known to suppress angiogenesis, tumor growth and metastasis, were measured by ELISA in order to examine the clinical importance of the agents. In addition, expression of CD34, ES and Cat-L in tissues of the gastric carcinoma was investigated immunohistochemically in order to elucidate the correlation with the above plasma levels. Plasma ES levels in gastric carcinoma patients were significantly higher than those in controls (p=0.001). Plasma Cat-L levels in controls were slightly lower, though not significantly (p=0.065), than those in carcinoma patients. There was no significant difference in sVEGF R1 levels between gastric carcinoma patients and controls. Expression of ES and Cat-L in tumor tissues was positively associated with plasma sVEGF R1 levels. Expression of CD34 in tumor tissues was not found to be associated with any plasma markers. Our results suggested that plasma ES levels are elevated in gastric carcinoma and may be useful markers for gastric carcinoma

Selection of Postoperative Systemic Chemotherapy for Advanced Gastric Cancer Patients with Hepatic Metastasis Using the Histoculture Drug Response Assay

The usefulness of histoculture drug response assay (HDRA) before the start of antitumor chemotherapy was explored to predict the antitumor response of chemotherapy for progressive gastric cancer patients with hepatic metastasis. Cancer tissue was collected from 6 advanced gastric cancer patients with hepatic metastasis, to assess whether the tumor is sensitive to chemotherapeutic agents of 5-fluorouracil (5-FU), mitomycin C (MMC), docetaxel hydrate (TXT), and cisplatin (CDDP) by the HDRA method. The size of hepatic tumor was measured by CT scan 3 and 6 months after the start of the chemotherapy and examined the relationship between the selected chemotherapy and antitumor response. Of 6 patients investigated in the present study, 3 patients received monotherapy with TS-1[○!R], which was found to be effective in 2 patients (66.7%). In the patient who received MMC monotherapy, the HDRA showed the cancer tissue to be less sensitive to any of antitumor agents tested, resultantly indicating no antitumor response. In the remaining 2 patients with combination therapy with TS-1[○!R] and MMC, the selected chemotherapeutic agents showed anti-tumor effect. The HDRA is useful to predict the antitumor response of postoperative adjunctive chemotherapy for advanced gastric cancer patients with hepatic metastasis, and plays an important role in selection of antitumor agents

The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut

We used mice deficient in each of the eight types and subtypes of prostanoid receptors and examined the roles of prostanoids in dextran sodium sulfate–induced (DSS-induced) colitis. Among the prostanoid receptor–deficient mice, only EP4-deficient mice and not mice deficient in either DP, EP1, EP2, EP3, FP, IP, or TP developed severe colitis with 3% DSS treatment, which induced only marginal colitis in wild-type mice. This phenotype was mimicked in wild-type mice by administration of an EP4-selective antagonist (AE3-208). The EP4 deficiency impaired mucosal barrier function and induced epithelial loss, crypt damage, and aggregation of neutrophils and lymphocytes in the colon. Conversely, administration of an EP4-selective agonist (AE1-734) to wild-type mice ameliorated severe colitis normally induced with 7% DSS, while that of AE3-208 suppressed recovery from colitis and induced significant proliferation of CD4(+) T cells. In vitro AE3-208 enhanced and AE1-734 suppressed the proliferation and Th1 cytokine production of lamina propria mononuclear cells from the colon. DNA microarray analysis revealed elevated expression of genes associated with immune response and reduced expression of genes with mucosal repair and remodeling in the colon of EP4-deficient mice. We conclude that EP4 maintains intestinal homeostasis by keeping mucosal integrity and downregulating immune response

National trends in the outcomes of subarachnoid haemorrhage and the prognostic influence of stroke centre capability in Japan: retrospective cohort study

Objectives To examine the national, 6-year trends in in-hospital clinical outcomes of patients with subarachnoid haemorrhage (SAH) who underwent clipping or coiling and the prognostic influence of temporal trends in the Comprehensive Stroke Center (CSC) capabilities on patient outcomes in Japan.Design Retrospective study.Setting Six hundred and thirty-one primary care institutions in Japan.Participants Forty-five thousand and eleven patients with SAH who were urgently hospitalised, identified using the J-ASPECT Diagnosis Procedure Combination database.Primary and secondary outcome measures Annual number of patients with SAH who remained untreated, or who received clipping or coiling, in-hospital mortality and poor functional outcomes (modified Rankin Scale: 3–6) at discharge. Each CSC was assessed using a validated scoring system (CSC score: 1–25 points).Results In the overall cohort, in-hospital mortality decreased (year for trend, OR (95% CI): 0.97 (0.96 to 0.99)), while the proportion of poor functional outcomes remained unchanged (1.00 (0.98 to 1.02)). The proportion of patients who underwent clipping gradually decreased from 46.6% to 38.5%, while that of those who received coiling and those left untreated gradually increased from 16.9% to 22.6% and 35.4% to 38%, respectively. In-hospital mortality of coiled (0.94 (0.89 to 0.98)) and untreated (0.93 (0.90 to 0.96)) patients decreased, whereas that of clipped patients remained stable. CSC score improvement was associated with increased use of coiling (per 1-point increase, 1.14 (1.08 to 1.20)) but not with short-term patient outcomes regardless of treatment modality.Conclusions The 6-year trends indicated lower in-hospital mortality for patients with SAH (attributable to better outcomes), increased use of coiling and multidisciplinary care for untreated patients. Further increasing CSC capabilities may improve overall outcomes, mainly by increasing the use of coiling. Additional studies are necessary to determine the effect of confounders such as aneurysm complexity on outcomes of clipped patients in the modern endovascular era