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Biomedical subjects

K Kumai

Publications and source records attributed to K Kumai.

At least 73 records · Page 4Linked to original sources
PubMed1993

Experimental and clinical studies on the intraperitoneal administration of cis-diamminedichloroplatinum (II) for peritoneal carcinomatosis caused by gastric cancers.

The effectiveness of the intraperitoneal administration of cis-diamminedichloroplatinum (II) (DDP) on peritoneal carcinomatosis caused by gastric cancers was evaluated. Seventeen patients were treated with one of three protocols, consisting of the intraperitoneal injection (ip) of DDP at doses of 70 and 110 mg/m2, with or without sodium thiosulfate (STS) rescue. The area under the curve (AUC) of DDP for sufficient anticancer activities against cultured human cell lines in vitro was estimated at 240 micrograms h/ml, which was equivalent to the AUC gained by 110 mg/m2 ip DDP in the clinical studies. The cytotoxic activity of DDP was reduced by approximately 50% with 100-fold STS in the AUC in the experimental studies. However, this was achieved only in urine, and not in either the peritoneal cavity or in plasma in the clinical studies. Three cases of a partial response against peritoneal carcinomatosis were seen from a total of four evaluable cases treated with 110 mg/m2 DDP, and no renal toxicities were observed in those treated with the STS rescue. The results of this study led us to conclude that high-dose ip DDP treatment combined with the STS rescue would be useful chemotherapy against peritoneal carcinomatosis caused by gastric cancers.

Adult↗
PubMed1993

Revaluation of endoscopic laser therapy for treatment of early cancer in the stomach.

The efficacy and safety of the endoscopic laser therapy for eradication of early cancer in the stomach was revaluated in fourty-eight patients. In 37 of the 42 patients (88%) treated with the laser therapy alone, the procedure was effective and the complete eradication was confirmed at the end of the follow-up period. In seven of fourteen patients with the incomplete treatment, residual cancer cells were successfully removed by repeated laser therapy. The endoscopic mucosal resection was effective in 21 of the 30 patients (70%) with the early gastric cancer. Interestingly, six of the eleven cases with incomplete treatment with the endoscopic mucosal resection underwent the laser therapy and the complete eradication was achieved in all patients. Although the endoscopic mucosal resection is now the main method for the endoscopic treatment of the early gastric cancer, these data favor offering the endoscopic laser therapy as the combined method with the mucosal resection therapy.

Adult↗
PubMed1993

[Intraperitoneal administration of cis-diamminedichloroplatinum (II) for peritoneal carcinomatosis caused by gastric cancers].

The effectiveness of the intraperitoneal administration of cis-diamminedichloroplatinum (II) for peritoneal carcinomatosis by gastric cancers was evaluated through experimental and clinical studies. In experimental studies, the effect of sodium thiosulfate (STS) on cytotoxic activity of DDP was evaluated by MTT assay using human gastric cancer cell lines. The cytotoxic activity of DDP was reduced by 50% with 100-fold STS in the area under the curve (AUC), whereas 10-fold STS in AUC did not reduce the cytotoxicity of DDP. In clinical studies, patients were treated with one of three protocols: Group A was treated by the intraperitoneal injection (ip) of DDP at a dose of 70 mg/m2, and group B or C was treated by ip DDP at a dose of 110 mg/m2 with or without STS rescue. The pharmacodynamics and the adverse effects of treatments were evaluated between these three protocols. In group C, the means of AUC of STS were 2.43-, 10.8- and 86.8-fold those of total platinum in the peritoneal cavity, plasma, and urine, respectively. There were 1/5, 1/2 and 2/2 partial responses in peritoneal carcinomatosis patients treated with A, B and C. Renal toxicity was not observed in the patients treated with DDP and STS rescue. STS does not seem to reduce the antitumor activity of DDP in peritoneal cavity and plasma, while the renal cytotoxicity was reduced by STS rescue. The result led us to conclude that intraperitoneal DDP treatment combined with STS rescue would be useful chemotherapy against peritoneal carcinomatosis by gastric cancer.

Adult↗
PubMed1992

[Study of DDS to the lymph node-metastases of the gastric cancer by the endoscopic injection of Lip-ADM].

We studied the drug delivery and anti-tumor effect of the endoscopic injection of liposomal adriamycin (Lip-ADM) in the submucosa of stomach by rabbit model. Concerning the drug delivery to regional lymphnode, the lymphnode ADM concentration of Lip-ADM injection group was higher than that of free ADM group (p less than 0.05). We also studied the lymphnodes pathohistologically. The lymphnodes of the rabbits injected with Lip-ADM indicated massive necrosis, whereas those of the rabbits injected with free ADM indicated residual tumor. Among clinical cases, patients injected Lip-ADM had paraaortic lymphnodes in which the adriamycin remained 10 days. The endoscopic injection of Lip-ADM into the submucosa of the stomach appeared to be an effective drug delivery system.

Animals↗
PubMed1992

[Targeting cancer chemotherapy using temperature-sensitive liposomes containing adriamycin conjugated with monoclonal antibodies].

Liposomes have a specific liquid-crystalline phase transition temperature (Tc), at which they release an entrapped drug. Temperature-sensitive liposomes containing adriamycin (TS-Lip-ADM) were made of dipalmitoylphosphatidylcholine (DPPC, Tc: 41 degrees C), distearoylphosphatidylcholine (DSPC, Tc: 54 degrees C), cholesterol and adriamycin. Monoclonal antibodies against human alpha-fetoprotein (AFP) were conjugated to TS-Lip-ADM. When liposomal suspension was immersed in a bath, the release rate of ADM from TS-Lip-ADM = Ab increased, as the temperature increased from 34 degrees C to 42 degrees C. ADM release was dependent on the temperature.

Antibodies, Monoclonal↗
PubMed1992

[Evaluation of the importance of infection as cause of death in patients with malignancy: an analysis of autopsy cases].

The autopsy records of patients who died at Keio University Hospital from January 1, 1970 through December 31, 1974 and from January 1, 1985 through December 31, 1989, were reviewed and their main diseases and the causes of death were determined. The contribution of infections to the death of each patient was classified as follows: Class 1: Infection is the only cause of death. Class 2: Infection is the predominant cause of death. Class 3: Non-infectious disease is the predominant cause of death. Class 4: Infection is independent of patient's death. The total number of autopsy cases and cases with malignancy were 1,140 and 664 in the early 1970's and 1,136 and 826 in the late 1980's, respectively. Patients with hematologic malignancies totalled 90 and 95 in the two periods, respectively. In the early 1970's, 35% of patients with malignancies died of infections [classified as Class 1 (25%) and Class 2 (10%)], and in the late 1980's, 32% of cancer patients died of infections (Class 1 20% and Class 2 12%, respectively). The most important infectious disease was pulmonary infection in the two periods. In patients with other than hematologic cancers (solid cancers), 63% and 58% of patients died of pulmonary infection in the early 1970's and the late 1980's, respectively. The rate of solid cancer patients who died of systemic infection rose from 7% in the early 1970's to 21% in the late 1980's. In hematologic cancer patients, the importance of pulmonary infection and that of systemic infection were comparable in the two periods. Fungus infection in hematologic cancer patients was a serious problem in the two periods, but it became more important in the late 1980's. The most important cause of death of cancer patients in the two periods was the cancers themselves; 39% of patients in the early 1970's and 43% in the late 1980's, respectively, died of marasmus or insufficiency of vital organs due to cancer.

Cause of Death↗
PubMed1991

[Modified operation for an early stage gastric cancer].

The standard operation for gastric cancer is carried out for advanced gastric cancer with serosal invasion accompanying patent disseminative metastasis to the peritoneum of the omental bursa and lymph node metastases. It consists of subtotal or total gastrectomy, omentobursectomy and extended lymph node dissection. An early stage cancer, which in Japan accounts for almost a half of the resectable cases of gastric cancer, shows no serosal invasion, and lymph node metastases are rare if the cancer remains intramucosal. Such cases represent about a half the cases of the early stage cancer. The diagnosis of the early stage cancer, especially if it remains intramucosal, is made by means of preoperative radiological and endoscopic examinations and intraoperative examination. Since 1977 we have been performing a modified operation as well for cases of the early stage cancer. The surgical procedure is as follows: reduction in the size of gastric resection by 2/3, pylorus-preserving gastrectomy and proximal gastric resection; preservation of the distal portion of the greater omentum and transverse incision of the upper abdomen instead of upper midline incision to prevent ileus due to intestinal adhesion to abdominal wound around umbilicus; sparing bursectomy; narrowing the area of lymph node dissection; sparing thoracotomy for cancer in the esophagogastric junction; sparing splenopancreatectomy; preservation of the hepatic branch of the vagal nerve and postoperative temporary oral administration of cholagogue to prevent postgastrectomy cholelithiasis. In addition, the primary lesion is isolated from the blood circulation by means of ligation of the drainage veins to diminish metastasis through the blood vessels (hepatic metastasis, etc.), which is the main cause recurrence after surgery for the early stage cancer. The results of this new surgery are satisfactory; the five-year postoperative survival rate is 100.0% and it reduced the time needed for surgery, anesthesia and blood transfusion.

Humans↗
PubMed1990

The antitumor effects of adriamycin entrapped in liposomes on lymph node metastases.

Adriamycin (ADM) entrapped in liposomes (Lip-ADM) was prepared and its therapeutic effects studied using the mouse leukemia cell line, P388, which metastasized to axillary lymph nodes after inoculation into the foot pads of CDF1 mice. Lip-ADM injections (7.5 mg/kg) were given into the foot pad at two-day intervals. Two series of experiments were performed; one in which Lip-ADM was administered on days 1,3 and 5 following tumor inoculation, and the other in which it was administered on days 5 and 7. Both Lip-ADM injection regimens significantly inhibited metastases to the lymph nodes as compared with mice given injection of saline solution. Furthermore, the therapeutic effects of three Lip-ADM injections were significantly greater than the effects of free ADM. Histological examinations of lymph nodes revealed that three injections of Lip-ADM completely eliminated tumor cells, whereas viable tumor cells were still observed in the lymph nodes after treatment with free ADM. The results of this study suggest that Lip-ADM is useful for the treatment of lymph nodes metastases and that the local injection of Lip-ADM, through such means as endoscopy, would be recommended as a clinical mode of application.

Animals↗
PubMed1990

[Dose intensity in cancer chemotherapy in gastric cancer].

Dose intensity in cancer chemotherapy proposed by Green (1980) and Hryniuk (1984) is a concept of expressing treatments in terms of how much drug is given per unit time (mg/m2/week). It is expected that the dose intensity may clear dose-response relationships which are sometimes obscure in cancer chemotherapy because dose reduction or treatment delay caused by adverse effects. Good correlations between dose intensity and prognosis of cancer patients are observed in breast, lung, ovarian cancer and malignant lymphoma. But only few trials using dose intensity concepts have been performed in chemotherapy for gastric cancer. A randomized controlled trial targeted for dose intensity itself will be necessary to confirm the usefulness of dose intensity concepts.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

[Intraperitoneal administration of anti-cancer drug with cisplatinum (CDDP)].

Six patients were administered cisplatinum (CDDP) i.p. There were four cases with peritoneal dissemination of gastric cancer after gastrectomy and the other two, for whom prophylactic intraperitoneal administration of CDDP had been attempted to prevent peritoneal metastasis. The dose of CDDP was 75-140 mg/body (58-90 mg/m2). The results were 1 PR, 2 NC and 1 PD. The PR case was given intraperitoneal CDDP combined with RF thermotherapy. Liver dysfunctions, renal dysfunctions, bone marrow suppressions, and GI tract disturbances were observed as toxic reactions. The degrees of side effects after i.p. administration were less severe than after i.v. administration. However the indication of CDDP i.p. administration should be decided after case conferences. On pharmacokinetics, non-protein bound platinum was detected at 24 hours after i.p. administration, in ascites and plasma. The concentration of platinum in ascites was about three-fold than in plasma. It was considered that CDDP absorption from ascites into plasma depended on the state of peritoneal dissemination of cancer.

Adult↗
PubMed1989

Temperature-sensitive release of adriamycin, an amphiphilic antitumor agent, from dipalmitoylphosphatidylcholine-cholesterol liposomes.

Drugs for temperature-sensitive liposomes have been limited to the hydrophilic drugs, such as methotrexate and cis-dichlorodiammineplatinum, with a low affinity for the lipid bilayer. It was, however, of importance to investigate whether the concept of temperature-sensitive liposomes can be extended to amphiphilic or lipophilic compounds, because some useful drugs are amphiphilic or lipophilic. In this study we tried to use adriamycin, an amphiphilic antitumor agent, as a drug for temperature-sensitive liposomes. In the absence of serum, the liposomes prepared from dipalmitoylphosphatidylcholine released adriamycin in a temperature-sensitive manner, i.e., they retained the major portion of entrapped adriamycin at a lower temperature 32 degrees C, and released around 70% of the drug at 42 degrees C, a temperature higher than the phase-transition temperature of the phospholipid. However, when serum was present, the liposomes were leaky even at 32 degrees C. To raise the stability of the liposomes, we included various mol% of cholesterol in the liposomal membrane and examined temperature sensitivity and stability of the liposomes in the presence of serum. Our results indicated that the liposomes including 20 mol% cholesterol were considerably stable and exhibited the maximal temperature-sensitive release of adriamycin in the presence of serum.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1989

[Importance of the conjugated antibody for the induction of selective effect of adriamycin conjugated with anti AFP monoclonal antibody and entrapped in liposomes against AFP producing tumors].

We investigated experimentally the effect of adriamycin (ADM) conjugated with anti alpha-fetoprotein (AFP) monoclonal antibodies and entrapped in liposomes (Lip-ADM = AbAFP) in vitro or in vivo. In the present study, we examined the importance of the conjugated antibody for the induction of selective therapeutic effect of Lip-ADM = AbAFP against AFP producing tumors. As the target tumors, AFP producing human hepatoma strain, Li-7, and AFP non-producing human breast cancer strain, MX-1 maintained in BALB/c nu/nu male mice were used. In order to evaluate the importance of the conjugated antibody, we prepared also ADM conjugated with normal mouse IgG, and entrapped in liposomes Lip-ADM = NIgG, of which therapeutic effects were compared with that of Lip-ADM = AbAFP. Judging from the tumor growth curve and the tumor weight, the therapeutic effect of Lip-ADM = AbAFP was greater against Li-7 than that of Lip-ADM = NIgG. On the other hand, both conjugates showed similar effects against MX-1. As the results it is suggested that the antibody which recognizes the antigen expressed on the target tumor cells can solely increase the therapeutic effect of ADM entrapped in liposomes (Lip-ADM) and that the main factors which contribute to the efficient therapeutic effect of the conjugate were the sensitibility to ADM, the affinity of the tumor cells to liposomes and the superiority of the conjugated antibody.

Animals↗
PubMed1989

Immunohistological identification of T and B cells in normal and malignant tissues of the uterine endometrium.

We examined the state of T and B cells in tissues from 61 cases of endometrial cancer by immunohistochemistry with monoclonal antibodies. In cancer tissues, T cells frequently appear in clusters at the tip of the infiltrating cancer. As to age, both T and B cells were rare in 9 out of 11 cases involving endometrial cancer in patients in their 40s. In the normal endometrium, infiltration of numerous T cells was seen in only 2 out of 27 cases (7.4%). However, it was seen in cancer tissues in 28 out of 61 cases (45.9%). Thus the infiltration of numerous T cells into cancer tissues was confirmed. Within the same uterus, T cells seldom infiltrated into the area of the benign endometrium while T cells were seen in large numbers in the cancer foci. This indicates that T cells infiltrate after having recognized cancer cells. Compared to stages I and II, T cell infiltration tended to decrease in stages III and IV. While no fixed relation was found between the degree of histologic differentiation and T cell infiltration, fewer T cells were observed in the cases where cancer penetrated to the depth of cancer invasion and where it occupied a large area. Thus, it was assumed that in the host-immune defence mechanism in particular, T cell infiltration played a key role in tumor immunology of patients with endometrial cancer.

Adult↗
PubMed1989

[Phase II study with cisplatin in advanced stomach and colon carcinoma. Cooperative Study Group of Cisplatin for Stomach and Colon Carcinoma].

A multicenter phase II study was performed to evaluate cisplatin (CDDP) in patients with gastric carcinoma or colon carcinoma. Ninety-nine cases of gastric carcinoma and 25 cases of colon carcinoma were entered into the study. According to the eligibility criteria prepared for the study protocol, 28 and 5 patients were excluded from the stomach and colon group, respectively. CDDP, 70-100 mg/m2, was administered intravenously with sufficient hydration. The efficacy rates evaluated by the UICC tumor reduction criteria were 19.1% (13/68 cases) in gastric carcinoma and 5.0% (1/20 cases) in colon carcinoma. Lymph node metastasis and metastatic abdominal tumor were effective targets for CDDP treatment. As side-effects of CDDP, nausea/vomiting (69.2%) and general malaise (35.2%) were observed. CDDP was thus considered to be one of the effective chemotherapeutic agents for treatment of gastric carcinoma.

Adult↗
PubMed1989

[Gastric remnant cancer--physical and laboratory examination and results of treatment].

A clinical evaluation of re-operation after primary gastric resection for stomach carcinoma as "Second Look Operation" was performed with reference to a surgical treatment for gastric remnant cancer. Ninety-one cases among gastrectomized patients with gastric cancer from 1973 to 1987 underwent re-operation. Gastric remnant cancer in 25 cases (27%), was the second indication for the operation next to ileus. It consisted of 17 cases of recurrent cancer and 8 cases of metachronous cancer. The mean interval between the primary and secondary laparotomy in the former (32 months) was significantly shorter than in the latter (117 months). Resectability of gastric remnant cancer was 100% (8/8) in metachronous cancer and 27% (9/33) in recurrent cancer. A long-term follow-up system for over 10 years with modern physical and laboratory examinations for gastrectomized patients has been a substitute for "Second Look Operation" for find cancer in the gastric remnant.

Biomarkers, Tumor↗
PubMed1988

Pyloric stenosis in a patient with progressive systemic sclerosis.

A 64-year-old Japanese woman with progressive systemic sclerosis (PSS) who developed severe pyloric stenosis is described. The conservative treatments brought only the temporary symptomatic relief, and pyloroplasty became necessary. No ulcerative lesions or tumors were found in the resected stomach or duodenum specimens implicated for stenosis. The histological examinations revealed edema and replacement fibrosis in the pyloric ring. The possible mechanisms of pyloric stenosis are discussed.

Female↗