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.

Adenocarcinoma↗

PubMedDate not supplied

Prognostic factors in primary gastrointestinal leiomyosarcoma: a retrospective study.

Thirty-six patients who were admitted for surgical resection of leiomyosarcomas of the gastrointestinal tract to the Department of Surgery II, Kanazawa University Hospital, Kanazawa, Japan and its affiliates are included in the study. Follow-up data on survival is available for 32 patients. The clinico-pharmacologic variables, such as tumor site, tumor size, cellularity, mitotic index, and DNA ploidy pattern were analyzed and the results proved to correlate with the prognosis. Thirteen (41%) of the patients presented with distant metastases and/or recurrences, with hematogenous metastasis being the predominant type of recurrence. Local recurrences and/or distant metastases were significantly correlated with survival (p less than 0.001), as was tumor site (p less than 0.03), tumor size (p less than 0.04), surgical treatment (p = 0.05), and DNA ploidy pattern (p = 0.06). Neither the mitotic index nor the cellularity proved to be significantly correlated with survival. Furthermore, some of the patients with local recurrences or distant metastases survived long after resection of recurrent tumors. In view of the results, aggressive surgical resection may be an efficient treatment of recurrences.

Adult↗

PubMedDate not supplied

Hyperthermo-chemotherapy combined with cytoreductive surgery for the treatment of gastric cancer with peritoneal dissemination.

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.

Adult↗

PubMedDate not supplied

Epidermal growth factor stimulates guanine nucleotide binding activity and phosphorylation of ras oncogene proteins.

Several human tumour cell lines contain genes that can transform NIH 3T3 cells into malignant cells. Certain genes have been classified as members of the ras oncogene family, namely, Ha-ras, Ki-ras or N-ras. The proteins encoded by the ras family are generally small (Ha-ras, for example, encodes a protein of molecular weight 21,000 named p21), and are associated with the inner surface of the plasma membrane. The only known biochemical property common to all forms of the ras proteins is the ability to bind guanine nucleotides, a property which may be closely related to the transforming ability of ras proteins. A GTP-dependent, apparent autophosphorylation (on threonine 59) activity has been identified only in the case of the v-Ha-ras protein. Although the role of these biochemical activities in the transformation process remains unclear, we have initiated studies to determine the possible biochemical interactions of ras proteins with other membrane components. We report here the evidence that epidermal growth factor enhances the guanine nucleotide binding activity of activated c-Ha-ras or v-Ha-ras p21, and phosphorylation of v-Ha-ras p21, suggesting that some mitogenic growth factors may regulate those activities.

Animals↗

PubMedDate not supplied

The product of ras is a GTPase and the T24 oncogenic mutant is deficient in this activity.

Ha-ras is a member of a multigene family in man which encode highly related proteins of 189 amino acids (p21). In vitro, ras proteins bind GTP, and p21 mutants with treonine at position 59 autophosphorylate at that residue. Mutation (at amino acids 12 or 61) and elevated expression of ras genes result in cell transformation in culture, and are also observed in many types of human tumours. Normal and mutant transforming ras proteins show no differences in localization, lipidation or GTP binding. However, mutations at position 12 in recombinant (Thr 59) p21 molecules were observed to affect autophosphorylation. We have expressed the full-length normal and T24 transforming (Gly----Val at position 12) Ha-ras proteins in Escherichia coli and have purified them to homogeneity (ref. 19 and M.G. et al., in preparation); these proteins bound GTP with approximately molar stoichiometry and with an affinity comparable to partially purified mammalian proteins. Microinjection of the T24 protein into quiescent rodent fibroblasts resulted in a rapid alteration in cell morphology, stimulation of DNA synthesis and cell division; in contrast, little response was observed with the normal protein. We now report that the normal ras protein has an intrinsic GTPase activity, yielding GDP and Pi. In contrast, the T24 transforming protein is reduced 10-fold in this activity. We suggest that this deficiency in GTPase is the probable cause for the transforming phenotype of the T24 protein.

Amino Acid Sequence↗

PubMedDate not supplied

Morphologic abnormalities in the brain of chronically hemodialyzed patients without cerebrovascular disease.

In this study, the authors evaluated the cerebral atrophy in 56 chronic hemodialyzed patients, who did not have clinical episodes or radiologic findings of cerebrovascular diseases, and 42 controls. Using computed tomography (CT) images, brain atrophy index (BAI), the proportion of subarachnoidal plus ventricular space in the cranial cavity, and ventricular area index (VAI), percent area of ventricle in the brain, were calculated. CT of the brain demonstrated an age-dependent increase in BAI in both hemodialyzed patients and controls. BAI and VAI were greater in hemodialyzed patients than healthy controls and the difference was significant at ages under 60 years in BAI and at ages less than 50 years in VAI. The atrophy of the frontal parts of the brain in patients on hemodialysis for 10 years or more was significantly greater than in patients dialyzed for less than 10 years. There was a significant negative correlation between BAI or VAI and hematocrit. These findings indicate that renal failure or hemodialysis itself might cause cerebral atrophy, and that the cerebral atrophy is more prominent in patients on hemodialysis for a long duration and with low hematocrit.

Adult↗

PubMedDate not supplied

The role of alpha-galactosylceramide-activated Valpha14 natural killer T cells in the regulation of Th2 cell differentiation.

Valpha14 natural killer T (NKT) cells produce large amounts of both IL-4 and IFN-gamma upon stimulation with a ligand, alpha-galactosylceramide (alpha-GalCer), and play a crucial role in various immune responses, including allergic diseases. Interestingly, Valpha14 NKT cells are not essential for the induction of IgE responses but rather induce suppression of specific IgE production upon activation. The suppression in the IgE production is not detected either in Valpha14 NKT cell-deficient mice or in IFN-gamma-deficient mice. Thus, activated Valpha14 NKT cells are likely to exert a potent suppressive activity on Th2 cell differentiation and subsequent IgE production by producing a large amount of IFN-gamma. In marked contrast, little regulatory effect of IL-4 produced by Valpha14 NKT cells on Th2 cell differentiation is suggested.

Animals↗

PubMedDate not supplied

[A case of embolization to a large polycystic kidney with infection].

75 year old female who was hospitalized for abdominal pain and fever up on 12th May 1998. She had been followed as a polycystic kidney patient since few years. The swelling of the right kidney and her general condition became gradually worse. On 18th May, the embolization to the right kidney using pure alcohol and gelatin sponge was performed. Within a month, CT scan showed the reduced volume of the right kidney and her blood examination data as well as her general condition became gradually well. And on 17th June, she left our hospital without any complication.

Aged↗