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Hepatocyte growth factor ( HGF ) is involved in malignant behavior of cancers as a mediator of tumor-stromal interactions, facilitating tumor invasion and metastasis. We have investigated whether a blockade of HGF using recombinant NK4, an HGF antagonist, would lead to growth inhibition of the human gastric carcinoma cell line, TMK1. To evaluate the function of endogenous NK4 and investigate its potential inhibitory effect, TMK1 cells were transfected with NK4 plasmid. After selection, NK4-expressing cells ( T11 ) were obtained, and cell growth was evaluated. Significant growth inhibition was observed in the T11-group compared to the control both in vitro and in vivo. Moreover, we investigated the effect of exogenous NK4 transferred by an adenovirus vector ( AdCMV.NK4 ). Cell proliferation of AdCMV.NK4 infected TMK1 cells was significantly inhibited compared with the control group. We also assessed the in vivo tumor suppression effect of AdCMV.NK4. The tumor volume following treatment with AdCMV.NK4 was significantly inhibited compared to that of the control group. These findings indicate that NK4 gene expression has a potential role in controlling proliferation of cancer cells. In conclusion, NK4 is a promising therapeutic agent and its gene delivery may be a new approach to treating patients with advanced gastric cancer.

Background The prognosis for patients with stage Ib (second English edition of the Japanese classification of gastric carcinoma) gastric cancer is promising, with an expected 5-year survival of 90%. Despite this relatively high survival rate, the outcome for patients who experience recurrence is poor. To date, however, prognostic and recurrence factors for stage Ib gastric cancer are poorly understood, and appropriate adjuvant chemotherapy protocols have not been developed. Methods We retrospectively analyzed data from 86 stage Ib gastric cancer patients who underwent curative gastrectomy to determine the rates and predictive factors of recurrence. Results Eleven patients showed recurrence, with a 12.8% 5-year cumulative recurrence rate. Nearly all of these patients were initially histologically diagnosed with poorly differentiated adenocarcinoma. Based on univariate analyses, recurrence was associated with gender and histological type. Multivariate analyses revealed that the only independent risk factor for recurrence was histologically undifferentiated-type adenocarcinoma. The 5-year survival rate of patients with undifferentiated-type adenocarcinoma was 84%. The predominant recurrence pattern was peritoneal dissemination, and was typically observed 1-3 years post-resection. ConclusionThis retrospective study identified undifferentiated-type adenocarcinoma as the only risk factor for recurrence in stage Ib gastric cancer patients. Although randomized controlled studies are necessary, stage Ib gastric cancer patients with this identified recurrence risk factor would be candidates for adjuvant chemotherapy.

A 68-year

Background-Invasive colorectal adenocarcinomas have bundles of eosinophilic spindle cells, which are regarded as myofibroblasts, in their desmoplastic stroma, some of which are continuous with the muscularis mucosa. Aim-To investigate the relation between the eosinophilic spindle cells and the muscularis mucosa based on their cytoskeletal phenotypes in early invasive colorectal adenocarcinoma. Methods-Formalin fixed, paraYn wax embedded tissues of 17 early invasive colorectal adenocarcinomas were immunostained for -smooth muscle actin ( -SMA), desmin, and vimentin. Results-The phenotype of the muscularis mucosa was -SMA positive, desmin positive, and vimentin weakly positive, whereas the eosinophilic spindle cells showed a decreased degree of immunoreactivity for -SMA and desmin in particular, and an increased degree of immunoreactivity for vimentin. The degree of phenotypic diVerence between the muscularis mucosa and the eosinophilic spindle cells was greater in the eosinophilic spindle cells in the centre of the invasive area that were not continuous with the muscularis mucosa than in the eosinophilic spindle cells continuous with the muscularis mucosa. Conclusions-These findings suggest that the smooth muscle cells of the muscularis mucosa change their phenotype to become eosinophilic spindle cells, namely myofibroblasts, in the early invasive area of colorectal adenocarcinoma. (J Clin Pathol 2000;53:878-881)

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The purpose of this study was to evaluate the effect of prostaglandin E I (PGEj) on CO 2 reactivity during cerebral aneurysm surgery in 37patients under neuroleptoanaesthesia (NLA ) (avant l'hypotension : 2,74 ._+ 0, pendant l'hypotension : 2,54 +__ O, apr~s l'hypotension : 2, que dans le groupe B ( avant I 'hypotension 1, 54 ._+ O, pendant l'hypotension 1, apr~s l'hypotension 1,49 ._+ 0, (P < O, 01