The association of MMP-2 (matrix metalloproteinase 2, 72-kD collagenase IV) with invasive and metastatic capacity of tumor cells has implicated a potential role in the prognosis for cancer patients. However, no larger study has been done to prove this hypothesis. The present study was therefore designed to investigate the prognostic impact of MMP-2 in a prospective series of 203 gastric cancer patients. MMP-2 expression was measured immunohistochemically and scored semiquantitatively (score 0-3) in carcinoma cells, and results were correlated with clinicopathological tumor parameters and parameters of the urokinase-type plasminogen activator (uPA) system. Survival analyses were done using the Kaplan-Meier method (log-rank statistics) and multivariate Cox analysis. Significant correlations were found for MMP-2 and Laurén's classification, M stage and proteases/inhibitors of the uPA system in the primary tumor. Kaplan-Meier analysis revealed an association of increasing MMP-2 expression with worse prognosis. This was especially seen in patients with a parallel high expression of uPA receptor. However, differences in survival probabilities between low and high MMP-2 levels were not significant. In a separate analysis of diffuse-type cancers, MMP-2 was significantly associated with disease-free (p = 0.0056) and overall survival (p = 0.0426). Multivariately, MMP-2 was not an independent parameter. Our results demonstrate that there is an association of immunohistochemical detection of MMP-2 with prognosis of cancer patients. For diffuse gastric cancers, it is a significant prognostic parameter, however, not of independent impact. The study further suggests that consideration of interrelated tumor-associated proteases like uPA receptor in combination with MMP-2 may improve its prognostic power.

Disease-Free Survival↗

PubMedDate not supplied

Bridging to transplant: allogeneic heart transplantation after xenografting.

Xenografting seems to be a solution to use to bridge time intervals when desperately needed allograft cannot be obtained. A following allograft was never ventured. Nine dogs (weight, 20 to 25 kg; age, 2 years) underwent right cervical heart transplantation. Donors were silver foxes (3 to 4 kg). The animals were treated by triple-drug therapy consisting of cyclosporine, methylprednisolone, and azathioprine in clinical dosages. For control, six recipients received only allogeneic hearts and the identical immunosuppression. After rejection of the xenograft, a second allogeneic heart was anastomosed subsequently to the same right cervical vessels. Routine histologic and immunohistologic examinations were performed. Thromboxane B2 and 6-keto-prostaglandin F1 alpha were determined daily in peripheral blood. After final rejection the sensitization of the recipient was controlled by hemagglutination test. Survival time of the xenografts was 9.6 +/- 1.2 days; the subsequent allogeneic hearts under the same therapy beat for 4.5 +/- 5.0 days. The average survival time of control hearts was 18 +/- 1.9 days. The five hyperacute second allografts showed signs of humoral rejection by absence of inflammation. The release of thromboxane B2 was different in hyperacute, accelerated, or cellular rejection. In contrast to the long-functioning grafts, thromboxane B2 persisted during hyperacute rejection at a high level. However, 6-keto-prostaglandin F1 alpha showed no significant differences between longtime survivors and hyperacute rejecting hearts. After xenogeneic transplantation, all recipients showed hemagglutinating titers between 1:4 and 1:16. Allogeneic grafts have a different kinetics of rejection after xenogeneic heart transplantation compared with control hearts. Thromboxane B2 seems to be an important mediator in hyperacute rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

PubMedDate not supplied

Prognostic influence of blood transfusion on minimal residual disease in resected gastric cancer patients.

BACKGROUND: The effect of blood transfusion on prognosis of resected cancer patients has been debated controversially. Therefore, we raised the hypothesis that transfusion-associated immunomodulation affects minimal residual disease after curative tumour resection, an unknown and uncontrolled phenomenon in all former studies which might significantly influence long-term prognosis. PATIENTS AND METHODS: 104 patients of a prospective study with curatively resected gastric cancer were stratified according to the immunocytochemical detection of disseminated tumour cells in bone marrow and the prognostic impact of allogeneic blood transfusion was tested. Multiple sequential bone marrow aspirations during follow-up were performed in 74 patients to investigate the blood transfusion effect on long-term development of this systemic disease component. RESULTS: Whereas in patients with tumour cell detection in bone marrow a significant association of blood transfusion and survival was seen (P = 0.048; relative risk 2.91; 95% CI 1.51-5.61), this was not found in patients without disseminated tumour cells (P = 0.129). Quantitative development of tumour cells in bone marrow during follow-up demonstrated a significant quantitative increase of tumour cells in transfused patients only (P = 0.028). CONCLUSION: These findings might explain the contradictory results of recent studies and suggest that the prognostic effect of transfusion is mediated through an impact on minimal residual disease in resected cancer patients.

Adult↗