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  • 1
    ISSN: 1530-0358
    Keywords: Peritoneal dissemination ; Continuous hyperthermic peritoneal perfusion ; CHPP ; Colorectal cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Continuous hyperthermic peritoneal perfusion (CHPP) combined with administration of anticancer drugs was performed in eight colorectal cancer patients with peritoneal dissemination. An overall response rate of 50 percent was achieved in the eight patients. Two of three complete responders are long, recurrence-free survivors for 15 and 30 months. The two-year survival has been achieved in 18.8 percent of the patients receiving CHPP, and this rate is significantly higher than the rates in P2 and P3 patients who did not receive CHPP. The complications of CHPP with administration of anticancer drugs were mild bone marrow suppression in two (25 percent) of the eight patients and also a mild grade of renal dysfunction in one (12.5 percent), though not lethal. The results suggest that the combination of CHPP with the administration of anticancer drugs is a safe and effective therapy for peritoneal dissemination of colorectal cancers.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1436-3305
    Keywords: Key words MMP-7 ; Gastric cancer ; Peritoneal carcinomatosis ; Peritoneal dissemination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Matrix metalloproteinase-7 (MMP-7) is an important matrix-degrading enzyme that has a large role in the invasion and metastasis of cancer. To discover the mechanism of the formation of peritoneal dissemination in gastric cancer, we studied the mRNA and protein expression of MMP-7 in primary gastric cancers and peritoneal dissemination. Methods. MMP-7 expression in primary gastric cancers (136 patients) was studied by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR), and the results were compared with chinicopathological parameters. Results. MMP-7 mRNA was expressed in 28 (53%) of 53 primary gastric cancers, but not in normal gastric mucosa, fibroblasts, or mesothelial cells. An immunohistochemical method demonstrated that MMP-7 immunoreactivity was found on the cell membrane and cytoplasm of cancer cells. Among 136 primary tumors, 70 (53%) tumors overexpressed MMP-7, and MMP-7 tissue status had significant positive correlation with serosal involvement, lymph node metastasis, poor differentiation of cancer, and peritoneal dissemination. Patients with MMP-7-positive tumor had significantly poorer survival and more frequently died of peritoneal recurrence than did those with MMP-7-negative tumors. All 6 examined peritoneal disseminations expressed MMP-7 mRNA, and 13 of 14 peritoneal disseminations showed immunoreactivity to anti-human MMP-7 monoclonal antibody. Logistic regression analysis showed that MMP-7 immunohistological status was an independent risk factor for peritoneal dissemination, and patients with MMP-7 mRNA-positive tumors had a 9.9-fold higher relative risk for peritoneal metastasis. Conclusion. These results strongly suggest that MMP-7 may have a large role in the formation of peritoneal dissemination in gastric cancer, and that clonal selection of cancer cells with MMP-7 overexpression may occur during the invasion of intraperitoneal free cancer cells from the peritoneal surface into the subperitoneal tissue. MMP-7 tissue status in the primary tumor may be a good indicator of peritoneal dissemination.
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  • 3
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Cinquante-cinq cas de cancer gastrique avancé, à potentiel très malin (stade IV à l'imagerie préopératoire), ont été traités par une chimiothérapie PMUE comprenant une combinaison de CDDP, 75 mg/m2, MMC, 10 mg/Kg poids corporel, d'etopocide, 150 mg/Kg poids corporel et d'UFT, 400 mg/jour. Le CDDP et le MMC ont été donnés par voie intraveineuse à Jl, suivis d'etoposide, 50 mg/jour aux jours 3, 4 et 5. Tous les patients avaient des lésions qui ont pu être évaluées par la tomodensitométrie avant et après le traitement. Ces patients ont été randomisés en deux groupes: 29 ont eu une chimiothérapie néoadjuvante (CNA) par le PMUE en préopératoire, alors que les 26 autres ont d'abord été opérés, et ensuite ont reçu une chimiothérapie PMUE (groupe contrôle). Les caractéristiques des deux groupes ne différaient pas de façon significative. Le taux de réponse était plus haut dans le groupe CNA par rapport au groupe contrôle (62% contre 35%). Le taux de résecabilité était respectivement, de 79 et 88% dans les deux groupes. Le taux de cas potentiellement curables, cependant, était plus élevé dans le groupe CNA par rapport au groupe contrôle (38% contre 15%). Dans les cas de cancer gastrique non réséqués, le pronostic était extrêmement mauvais, quel que soit le groupe. Dans les cancers réséqués, la survie était significativement plus élevée dans le groupe CNA comparé au groupe contrôle. Ces résultats indiquent que chez les patients ayant un cancer gastrique avancé à potentiel très malin, une chimiothérapie néoadjuvante (d'emblée), suivie de chirurgie, peut être le meilleur choix thérapeutique.
    Abstract: Resumen Cincuenta y cinco casos de cáncer gástrico avanzado, en los cuales se había confirmado el Estado IV mediante imágenes diagnósticas preoperatorias, recibieron quimioterapia PMVE con el uso combinado de cisplatino (CDDP) 75 mg/m2, MMC 10 mg/cuerpo, Ectoposide 150 mg/cuerpo y VHF 400 mg/día. El CDDP y el MMC fueron administrados por vía intravenosa en el primer día, seguidos de Ectoposide 50 mg/día en los días 3, 4 y 5. Todos los pacientes exhibían lesiones medibles, las cuales fueron valoradas por escanografía computadorizada antes y después del tratamiento. Los pacientes fueron ubicados al azar en dos grupos; 29 quedaron en el grupo de la quimioterapia neoadyuvante (QNA) en el cual la quimioterapia PMVE fue practicada preoperatoriamente, y los 26 pacientes restantes fueron sometidos primero a operación y luego a quimioterapia PMVE, constituyendose en el grupo de control. Los antecedentes médicos no eran significativamente diferentes en los dos grupos. La respuesta fue mayor en el grupo de QNA en comparación con el grupo control (62% vs 35%). La tasa de resecabilidad fue de 79% y 88% en el grupo QNA y en el grupo de control, respectivamente. Sin embargo, la rata de casos potencialmente curables fue más alta en el grupo de QNA, en comparación con el grupo control (38% vs 15%). En los casos no resecados, sin embargo, la tasa de sobrevida fue significativamente superior en el grupo de QNA en comparación con el grupo control. Tales resulados pueden significar que en pacientes con cáncer gástrico de alto grado y en estado avanzado se debe considerar primero la quimioterapia como paso inicial (quimioterapia neodyuvante), y luego la cirugía.
    Notes: Abstract Fifty-five patients with high-grade advanced gastric cancer in whom the presence of stage IV was confirmed by preoperative diagnostic imaging were treated with PMUE therapy by a combined use of cisplatin (CDDP) 75 mg/m2, mitomycin C (MMC) 10 mg/body, etoposide 150 mg/body, and UFT (a combination of 1-(2-tetrahydrofuryl)-5-fluorouracil and uracil in a molar ratio of 1∶4) 400 mg/day. CDDP and MMC was administered intravenously on the first day, followed by etoposide 50 mg/day on the 3rd, 4th, and 5th days. All the patients had measurable lesions that were evaluated by computed tomography scanning before and after the treatments. These patients were allocated randomly to two groups. Of these cases, 29 belonged to the neoadjuvant chemotherapy (NAC) group to whom PMUE therapy was given preoperatively; the remaining 26 patients underwent operation first and received PMUE thereafter (control group). Background factors did not differ significantly between the two groups. The response rate was higher in the NAC group than in the control group (62% in the former versus 35% in the latter). The resectability rates were 79% and 88% in the NAC and control groups, respectively. However, the rate of potentially curable cases was higher in the NAC group than in the control group (38% in the former versus 15% in the latter). Among the nonresection cases, the prognosis was highly unfavorable in both groups. In the resection cases, however, the survival rate was significantly better in the NAC group than in the control group. These results may indicate that in patients with high-grade, advanced gastric cancer initial chemotherapy (neoadjuvant chemotherapy) and then surgery should be considered.
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  • 4
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé La perfusion péritonéale continue hyperthermique (PPCH) avec des agents anticancéreux comme le mitomycine C et la cis-platine avec sérum physiologique chauffé a été instaurée lorsqu'une carcinose d'origine gastrique a été trouvée. Les effets de la PCH ont été évalués chez 16 patients lors d'un second-look (SL). Cette étude concerne 41 patients avec carcinose péritonéale sans métastase hépatique observés au cours des 6 dernières années. La survie globale médiane était de 437 jours (extrêmes 28 à 1925 jours): le taux de survie a 3 ans était de 28.5%. Les lésions avaient diminué de façon notable chez 7 (50%) de 14 patients. L'ascite a disparu dans 7 des 9 cas. Une survie à long terme (3 ans) a été notée dans 4 cas. Les effets secondaires ont été une insuffisance rénale dans 2 cas (5%), une leucopénie dans 2 cas (5%) et une perforation de l'intestin grêle dans un cas (2%). Les résultats suggèrent que la PPCH est efficace dans le traitement du cancer gastrique avec dissémination péritonéale.
    Abstract: Resumen La perfusión hipertérmica continua (PHTC) con agentes anticancerosos (mitocina G y cisplatino) y solutión salina fue realizada en pacientes con cáncer gástrico con diseminación peritoneal después de resección de la lesión primaria, y el efecto de PHTC fue determinado mediante reexploración (operación de “second look”, OSL). La población de pacientes está constituída por 41 casos de cáncer gástrico con diseminación peritoneal pero sin metástasis hepáticas, tratdos en el curso de los últimos 6 años. La sobrevida media global fue de 437 dias (rango 28 a 1925 días) desde la PHTC hasta la muerte y la tasa de sobrevida a 3 años fue 28.5%. La OSL reveló una notoria disminución de la diseminación peritoneal en 7 (50%) de 14 casos y desaparición de la ascites después de sólo un ciclo de PHTC en 7 de 9 casos con ascitis. Sobrevida de 3 años ocurrió en 4 casos. Los efectos colaterales fueron insuficiencia renal en 2 casos (5%), leucopenia en 2 casos (5%) y perforación del intestino delgado en 1 caso (2%). Los anteriores resultados sugieren que la PHTC es eficaz en el tratamiento del cáncer gástrico con diseminación peritoneal.
    Notes: Abstract Continuous hyperthermic peritoneal perfusion (CHPP) with anticancer agents (mitomycin C and cisplatin) in warm saline was performed in patients with peritoneal dissemination of gastric cancer following resection of the primary lesion. The effect of CHPP was examined by a second-look operation. This study includes 41 cases of gastric cancer with peritoneal dissemination but without liver metastasis treated during the past 6 years. The overall median survival was 14.6 months to 64.2 months from CHPP to death and the 3-year survival rate was 28.5%. Second look surgery revealed a remarkable diminution in the degree of peritoneal dissemination in 7 (50%) of 14 patients with disappearance of ascites after only one course of CHPP in 7 (77.8%) of 9 patients. Long-term 3 year-survival was noted in 4 (9.8%) patients on CHPP. Side effects were renal insufficiency in 2 (5%) patients, leukopenia in 2 (5%) patients, and perforation of the small intestine in 1 (2%) patient. These results suggest the effectiveness of CHPP in the treatment of gastric cancer with peritoneal dissemination.
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  • 5
    ISSN: 1573-7276
    Keywords: gastric cancer ; lymph node metastases ; MT1-MMP ; NMP-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mechanisms of the lymph node metastasis remain unclear. We demonstrate the role of MT1-MMP on the lymph node metastasis using in vivo experimental model of lymph node metastasis by orthotopic implantation of MT1-MMP transfected gastric cancer cell line in the stomach of nude rats. TMK-1 cell line without expression of MT1-MMP was transfected with the pcDNA3 plasmid containing a 3.4-kb MT1-MMP cDNA fragment by calcium phosphate method, and the transfected cell line was designated as TMK-MT. Western blot and RT-PCR analyses showed the specific bands corresponding to MT1-MMP in the TMK-MT cells. By gelatin zymography, the activated form (62-kDa) of MMP-2 was identified in the medium of TMK-MT cell line, but was not detected in TMK-1 cells. Six weeks after orthotopic implantation of TMK-1 and TMK-MT xenografts of nude mouse-subcutaneus tumor into the stomach of nude rats, gastric tumors were found in all the animals. Histologically, the lymphatic invasion was found in the submucosa of the TMK-MT gastric tumors. Lymph node metastasis was not detected in nude rats bearing TMK-1 gastric tumor (0/8). In contrast, lymph node metastasis was detected in five out of 8 rats, bearing TMK-MT gastric tumor. MT1-MMP immunoreactivity was found on the cell membrane and cytoplasm of TMK-MT cells not only in the lymph node metastasis but also in the stomach tumor. These results suggest that MT1-MMP overexpression induced by transfection of its gene may promote lymph node metastasis of transformed cells.
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