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Biomedical subjects

K Kumai

Publications and source records attributed to K Kumai.

At least 55 records · Page 3Linked to original sources
PubMed1996

Improvement of pharmacokinetics and antitumor activity against human hepatoma cell line by using adriamycin-entrapped stealth liposomes.

Preferential accumulation in the reticuloendothelial system is one of the major obstacles to the use of liposomes as a drug carrier for targeting therapy. To reduce their uptake, ganglioside GM1 was introduced into the components of conventional liposomes that had been used in our targeting experiments. Two types of such liposomes were prepared. Tissue distribution studies on Adriamycin entrapped in both types of liposomes clearly indicated that the uptake of Adriamycin by liver and spleen decreased to the level comparable to that of free Adriamycin administration. By contrast, the level of Adriamycin in the serum remains high, and some increase was observed in the accumulation to the tumor. Furthermore, Adriamycin in these liposomes, which were conjugated with anti-alpha-fetoprotein (AFP) antibody, inhibited the growth of AFP-positive human hepatoma Li-7 more efficiently than free Adriamycin or Adriamycin in antibody-conjugated conventional liposomes.

Animals↗
PubMed1996

Serial growth of human malignant fibrous histiocytoma xenografts in immunodeficient mice.

Malignant fibrous histiocytoma (MFH) is on of the most common soft tissue sarcomas of adulthood, the only treatment for which involves surgical resection of the extremities and retroperitoneum, while no standard postoperative adjuvant chemotherapy has been established. We report herein on the establishment of a serially transplantable MFH strain in immunodeficient mice. An intraperitoneal tumor was resected from a patient with multiple recurrent MFH, inoculated into the subcutaneous tissue of mice with severe combined immunodeficiency (SCID), and established as a serially transplantable MFH strain, MH-1. The chemosensitivity of MH-1 was similar to that of the original fresh surgical specimen, as confirmed by the 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) test. We believe that this serially transplantable strain will be useful for further studies on chemotherapy effective against MFH.

Abdominal Neoplasms↗
PubMed1996

Gastric plasmacytoma: report of a case.

A 54-year-old man with primary gastric plasma-cytoma is herein reported. After the patient had been diagnosed as having malignant lymphoma by gastrofiberscopy and a radiologic upper GI examination, a total gastrectomy was performed. Both histological and immunohistochemical studies showed plasmacytoma cells infiltrating the entire stomach wall, producing IgM-lambda, and indicating a final diagnosis of primary gastric plasmacytoma. Monoclonal immunoglobulin was not detected in the serum throughout the course. The case is discussed with reference to other reported cases of primary gastric plasmacytoma.

Gastrectomy↗
PubMed1996

The modulating effect of interferon alpha-2a on the antitumor activity of UFT against a human gastric carcinoma xenograft, SC-1-NU, in nude mice.

The modulating effect of recombinant human interferon alpha-2a (IFN) on the antitumor activity of UFT, a mixed compound of tegafur and uracil at a molar ratio of 1:4, was investigated against SC-1-NU, a human gastric cancer xenograft serially transplanted in nude mice. IFN was administered subcutaneously at a dose of 60,000 IU/mouse daily for 14 days, and UFT was given at a dose of 15 mg/kg as tegafur daily, except on Sundays, for 3 weeks. The agents were administered either alone or simultaneously. Synergistic antitumor activity on SC-1-NU was produced by the combination of IFN and UFT without any increment of side effects, and the combination therapy also increased intratumoral thymidylate synthetase (TS) inhibition and the amount of 5-fluorouracil (5-FU) in the intratumoral RNA. Thus, IFN seems to modulate the antitumor activity of UFT against SC-1-NU through an inhibition of DNA synthesis and RNA distortion, and therefore this combination could be useful for clinical application.

Adenocarcinoma↗
PubMed1996

[Modified surgery for early gastric cancer].

Based on the sufficiently accumulated results of early gastric cancer (EGC), particularly the diagnostic accuracy regarding the depth of cancerous involvement in the gastric wall, lymph node metastasis, pattern of recurrence etc., the modified surgery has been induced for the treatment of EGC since late 1970's. The modification is as follows depending on the depth and location of EGC: constriction of size of gastric resection; narrowing of the extent of lymphadenectomy; preserving omentum, pancreas, spleen, pylorus, vagal nerve, lower esophageal sphincter etc; sparing thoracotomy. This kind of surgery has resulted in remarkable reduction of blood loss during surgery, reduced operation time and hospital stay, which have brought improved QOL to the patients as well as satisfactory survival rate after surgery.

Aged↗
PubMed1996

[Laparoscopic surgery for early gastric cancer].

We have successfully treated 40 patients with early gastric cancer by using two different laparoscopic procedures since March 1992, which are laparoscopic wedge resection of the stomach using a lesion-lifting method (n = 25) and laparoscopic intragastric mucosal resection (n = 15). The indication is as follows; 1) mucosal cancer, 2) < 25 mm, if the lesion is protruded type, 3) < 15 mm and U1 (-), if the lesion is depressive type. All patients were discharged within 4-8 days uneventfully. The resected specimens were 66 +/- 16 mm and 48 +/- 8 mm in diameter respectively, and had a sufficient surgical margin horizontally (16 +/- 5 mm, 8 +/- 4 mm) and vertically. Histology revealed they were all curative surgeries except one case in whom an additional gastrectomy with lymph node dissection by laparotomy was required one month after surgery because lymphatic invasion had been revealed by pathology. In conclusion, these laparoscopic procedures are curative and minimally invasive treatment for early gastric cancer.

Adult↗
PubMed1996

[Laparoscopic curative surgery for early gastric cancer].

We have successfully treated 40 patients with early gastric cancer by using two different laparoscopic procedures since March 1992, which are laparoscopic wedge resection of the stomach using a lesion-lifting method (n = 25) and laparoscopic intragastric mucosal resection (n = 15). The indication is as follows; 1) mucosal cancer, 2) < 25 mm, if the lesion is protruded type, 3) < 15 mm and Ul(-), if the lesion is depressive type. All patients were discharged within 4-8 days uneventfully. The resected specimens were 66 +/- 16 mm and 48 +/- 8 mm in diameter respectively, and had a sufficient surgical margin horizontally (16 +/- 5 mm, 8 +/- 4 mm) and vertically. Histology revealed they were all curative surgeries except one case in whom an additional gastrectomy with lymph node dissection by lapalotomy was required one month after surgery because lymphatic invasion had been revealed by pathology. In conclusion, these laparoscopic procedures are curative and minimally invasive treatment for early gastric cancer.

Gastrectomy↗
PubMed1995

Antitumor activity of cis-diamminedichloroplatinum (II) depends on its time x concentration product against human gastric cancer cell lines in vitro.

A pharmacodynamic study of cisplatin (DDP) was conducted using the gastric cancer cell lines MKN-45 and MKN-74 in vitro. Ten thousand tumor cells were incubated with 0.4-500 micrograms/ml DDP for 1-25 h, followed by recovery culture for a further 48 h. At the end of incubation, cell viability was detected by the MTT end-point, and the inhibition rate was compared in relation to the incubation time, DDP concentration, and the time X concentration product (area under the curve in vitro: AUC vitro). In both of the cell lines, the IC50 and IC90 values decreased as the exposure time increased, going a linear curve with a slope of almost -1, and showing a typical log-log AUC vitro-dependent curve. These results indicate that the antitumor activity of DDP is dependent on its AUC vitro, suggesting the clinical usefulness of this drug when administered daily in small divided doses.

Antineoplastic Agents↗
PubMed1995

Active oxygen species in formation of acute gastric mucosal lesions induced by thermal injury in rats.

Active oxygen species generated by circulating leukocytes and released from the gastric mucosa were measured in the process of acute gastric mucosal lesion formation after thermal injury in rats. Alterations of luminol-dependent chemiluminescence activities generated by leukocytes obtained from the gastric vein and the inferior vena cava were approximately same. A decrease in chemiluminescence activity 15 min after thermal injury and a significant increase in chemiluminescence activity 5 hr after thermal injury were observed in leukocytes from both veins. From 15 min to 12 hr after thermal injury, luciferin-dependent chemiluminescence activities were significantly higher than that of the control group. Oral administration of rebamipide resulted in decreased mucosal lesion formation. Rebamipide, an antiulcer agent that protects the mucosa from damage in various animal models decreased chemiluminescence activities only released from the gastric mucosa but not from circulating leukocytes. These results suggest that two different pathways of active oxygen species formation may exist in the pathogenesis of acute gastric mucosal lesions after thermal injury.

Acute Disease↗
PubMed1995

[Late phase II trial of high-dose l-leucovorin and 5-fluorouracil in advanced colorectal carcinoma. l-Leucovorin and 5-FU Study Group (Japan Eastern Group)].

A multicenter cooperative study was conducted from Dec. 1992 to April 1994 to evaluate the clinical efficacy of high-dose l-leucovorin (l-LV) and 5-fluorouracil (5-FU) treatment in 76 patients with advanced colorectal carcinoma. Treatment consisted of intravenous bolus injection of 5-FU (600 mg/m2) 1-hour after the initiation of a 2-hour infusion l-LV (250 mg/m2), 6 weekly treatments were administered followed by a two-week rest. These treatment were repeated until progressive disease or intolerable toxicity. Seventy patients were evaluated for response. Responses were the following: PR 21, NC 29, PD 20 and the overall response rate was 30%. Grade 4 hematological side-effect was observed in three cases, and severe diarrhea in one case. These data suggested that high-dose l-LV and 5-FU was effective for advanced colorectal carcinoma but showed some hematological toxicity, and a further investigation should be carried out.

Aged↗
PubMed1995

[A randomized early phase II study of l-leucovorin and 5-fluorouracil in gastric cancer. l-Leucovorin and 5-FU Study Group].

A randomized early phase II study using l-leucovorin (l-LV) and 5-fluorouracil (5-FU) in gastric cancer was conducted. The administration schedules: Arm A was 250 mg/m2 of l-LV and 600 mg/m2 of 5-FU weekly, arm B was 100 mg/m2 of l-LV and 370 mg/m2 of 5-FU for 5 consecutive days, and arm C was 10 mg/m2 of l-LV and 370 mg/m2 of 5-FU for 5 consecutive days. PR was obtained in 10/28 (35.7%) of arm A, 7/28 (25.0%) of arm B and 0/17 (0%) of arm C, in complete cases. In eligible cases, 30.3%, 21.9% and 0%, respectively. Because there was no responder in arm C, the entry to arm C was stopped by controller at the point where 17 patients were treated with arm C. Median survival time was 9.6 months in arm A, 8.0 months in arm B and 5.9 months in arm C. Major toxicities were stomatitis, diarrhea and neutropenia. Stomatitis was seen more in arm B and C than in arm A. These data suggest that the high dose of l-LV and 5-FU seems to be a very promising combination, but there was no responder using low-dose l-LV schedule against gastric cancer. We thus selected arm A for the next late phase II study against gastric cancer.

Adenocarcinoma↗
PubMed1995

Active oxygen species generation by circulating leukocytes and gastric submucosal microcirculatory disturbances in the early period after thermal injury.

The purpose of the present study was to determine the pattern of microcirculatory disturbance to investigate the causes of gastric mucosal blood flow depression in the early period after thermal injury. Male Wistar rats were anesthetized and a 30% full skin-thickness dorsal burn was inflicted. Active oxygen species (AOS) generated by circulating leukocytes were measured by chemiluminescence. Contraction of arterioles and venules was observed by intravital microscopy, and rolling or sticking of leukocytes in venules was counted using fluorescence microscopy. AOS generation by circulating leukocytes was diminished and arteriolar contraction and increases in rolling or sticking leukocytes in venules were observed 15 min after thermal injury. Decreased AOS generation by circulating leukocytes, contractions of arterioles, and increased rolling or sticking of leukocytes in venules was observed in the early period after thermal injury. Arteriolar contraction may explain decreases in mucosal blood flow. Moreover, decreased AOS generation by circulating leukocytes does not obviate the potential participation of leukocytes in microcirculatory disturbances, because rolling or sticking leukocytes were increased significantly 15 min after thermal injury.

Animals↗
PubMed1994

Dose intensity of mitomycin C in adjuvant cancer chemotherapy for patients with gastric cancer.

Using a cohort of macroscopic curative resections of gastric cancer at stages II, III, and IV, a randomized controlled trial was performed to elucidate the dose efficacy of intensive adjuvant cancer chemotherapy with mitomycin C. Between June 1983 and December 1986, 336 patients with gastric cancer from 31 institutes were enrolled in the study. The cohort was stratified randomly by the telephone method into two arms. Group A received 20 mg and 10 mg of mitomycin C per body intravenously (IV) on postoperative days 0 and 1, respectively, and then tegafur at 600 mg/body daily perorally (PO) from postoperative week 2 for 1 year. Group B also received 0.2 mg of mitomycin C per kg IV at 3, 6, 9, and 12 months after surgery. The background factors in groups A and B were essentially identical, and the adverse effects were tolerable in both groups. The total administered doses of mitomycin C were significantly higher in group B than in group A, according to the protocol. Although no significant differences were observed in the actuarial overall survival rates between groups A and B at stages II, III, and IV, favorable survival was observed in group B, which received histologically absolute curative resection. This dose-intensive adjuvant cancer chemotherapy would be useful for gastric cancer patients treated by histologically curative surgery.

Chemotherapy, Adjuvant↗
PubMed1994

Combination chemotherapy with mitomycin C and cisplatin for advanced gastric cancer with multiple liver metastases.

A patient with advanced gastric cancer with multiple liver metastases was treated by reduction surgery at the primary site as well as by the intraarterial administration of mitomycin C (MMC) and cisplatin (CDDP) through a reservoir catheter inserted into the proper hepatic artery. After a palliative subtotal gastrectomy, MMC 8 mg/m2 was administered intraarterially (i.a.) followed by the administration of CDDP 80 or 40 mg/m2 i.a. with an interval of less than 1 week. After the completion of five courses of this regimen, a complete reduction of the hepatic tumors was achieved, while the level of serum carcinoembryonic antigen decreased to the normal range. The patient is currently alive with signs of disease recurrence at 17 months after initial diagnosis, while additional therapy with MMC + CDDP was continuously undergone until 17 months' after initial diagnosis with various interval. Although thrombocytopenia occurred during the treatment, it resolved within a few weeks after completing the combination chemotherapy without any specific treatment. The present case showed a better prognosis than we had expected, which suggested that combination chemotherapy with MMC and CDDP might thus be clinically useful because of its excellent antitumor activity and low toxicity.

Adenocarcinoma↗
PubMed1994

Improvement of therapeutic effect by using Fab' fragment in the treatment of carcinoembryonic antigen-positive human solid tumors with adriamycin-entrapped immunoliposomes.

To improve the therapeutic efficiency adriamycin entrapped in antibody-conjugated liposomes, Fab' fragment was used instead of the whole antibody molecule. The murine monoclonal antibody, 21B2, against human carcinoembryonic antigen (CEA) was digested with pepsin, and the thiol residue of intra-heavy chain produced by reduction of F(ab')2 with dithiothreitol was conjugated to liposomes containing adriamycin. The tissue distribution of adriamycin delivered with these liposomes was studied in BALB/c nu/nu female mice bearing CEA-positive human gastric cancer strain MKN-45. An increase in delivery of adriamycin to the tumor was observed in the mice given liposomes with Fab' fragment as compared to those given liposomes with whole antibody. However, the preferential distribution of adriamycin in liposomes to the reticuloendothelial cells remained the same regardless of the use of Fab' fragment. For investigation of in vivo therapeutic effect, three i.v. injections of free adriamycin or adriamycin in liposomes equivalent to 5 mg/kg were given, and adriamycin in Fab' fragment-conjugated liposomes was found most effective in the inhibition of tumor growth. This was confirmed in terms of actual tumor weights excised and CEA concentration in the blood, as well as by pathological observations. The advantages of using Fab' fragment instead of whole antibody are discussed.

Animals↗
PubMed1994

Single-cell suspension assay with an MTT end point is useful for evaluating the optimal adjuvant chemotherapy for advanced gastric cancer.

One hundred and forty-eight patients with gastric cancer admitted to Keio University Hospital between July 1988 and October 1992 underwent resection of the primary lesion, as well as single-cell suspension assay of fresh surgical materials with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT assay) for chemosensitivity evaluation. Fifty patients with histologically stage III or IV gastric cancer were enrolled in this study, among whom 10 received no chemotherapy after surgery while 40 received chemotherapy at equivalent dose levels after surgery. The patients given chemotherapy were divided into two groups consisting of an "Adapted" group treated with at least one agent identified as effective by the assay, and a "Non-adapted" group treated with agents to which the cells were not sensitive in the assay, in order to identify the optimal cut-off inhibition rate (IR) in MTT assay for evaluation of the appropriate adjuvant cancer chemotherapy after surgery. A cut-off IR of 30% was optimal for differentiating the survival rates between the "Adapted" and "Non-adapted" groups. Patients treated with drugs which showed more than 30% IR on their surgical specimens showed a better survival rate than patients treated with drugs which were ineffective in the assay.

Adult↗