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Biomedical subjects

K Ota

Publications and source records attributed to K Ota.

At least 559 records · Page 31Linked to original sources

[Phase I study of a recombinant gamma interferon (S-6810)].

A phase I study of a recombinant gamma interferon (S-6810) was conducted in a cooperative study involving 11 institutions. S-6810 was administered at doses of 2, 4, 8, 12, 32 and 64 X 10(6) U/m2 by one-hour infusion for 5 consecutive days. A total of 40 courses were administered to 31 patients. High fever exceeding 38 degrees C with chills occurred in about 80% of patients. The incidences of other toxicities were fatigue in 50%, gastrointestinal toxicities in 30-40%, and changes in hepatic enzymes and hematologic toxicities in 20-30%. Dose-limiting factors were judged to be hypotension, leukopenia and central nervous toxicity. Maximum tolerated dose was 64 X 10(6) U/m2 and an optimal dose for phase II study was considered to be 6 X 10(6) U/m2 by daily chronic schedule. Blood concentration was highest at the end of infusion, and then decreased rapidly with a biphasic curve. The peak concentrations were elevated by escalation of doses. A partial response was observed in a patient with mycosis fungoides.

Adult↗

Functional deterioration of the peritoneum: does it occur in the absence of peritonitis?

Peritoneal function in relation to the occurrence of peritonitis and the osmolarity of the dialysate was studied in 72 CAPD patients with a mean duration of treatment of 16.5 +/- 9.0 months (group 1). Data from 24 of these patients, who were on CAPD for longer than 2 years (average 28.6 +/- 4.9), were subjected to further detailed analysis (group 2). Each group consisted of two subgroups, one of patients who had experienced peritonitis and one of patients who had had no episodes of peritonitis. Results from group 1 revealed that the use of hyperosmolar bags increased in parallel with the duration of CAPD treatment even in the non-peritonitis subgroup, and that peritonitis enhanced the tendency to use hyperosmolar dialysate solutions. This phenomenon was also observed in the peritonitis subgroup of group 2, but was not apparent in the non-peritonitis subgroup of group 2 when examined as a whole: however, individual analysis revealed that some of them had a similar tendency to use hyperosmolar dialysate, as was seen in the peritonitis subgroup. These results confirm that the peritonitis impairs the ultrafiltration capability of the peritoneum. The results also suggest that the long-term use of hyperosmolar dialysate may be associated with decreased ultrafiltration, hence emphasis should be placed upon the use of hyperosmolar dialysate solutions for long-term CAPD.

Adult↗

Clonal T cell population in angioimmunoblastic lymphadenopathy and related lesions.

The arrangements of the T cell receptor (TCR) beta genes were studied in lymph node specimens with the histological characteristics of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD), AILD-like T cell lymphoma (AILD-T), T-zone lymphoma, or Lennert's lymphoma. Eight of 11 cases with AILD or AILD-T showed clonal rearrangements of TCR beta genes: all three AILD cases showed clonal rearrangements of TCR beta genes, while five of 8 AILD-T cases exhibited clonal rearrangement patterns. Malignant lymphoma evolved in one AILD case showed the same rearrangement band of TCR beta genes as its primary AILD lesion. The rearrangement of TCR beta genes was also observed in 2 out of 3 cases with T-zone lymphoma and 2 out of 2 cases with Lennert's lymphoma. None of the cases studied, except one AILD-T case, exhibited clonal rearrangements of immunoglobulin heavy chain genes. The results suggested that a significant proportion of AILD, AILD-T, T-zone lymphoma and Lennert's lymphoma cases are malignancies of peripheral T cell origin.

Adult↗

[Report on nationwide pooled data and cohort investigation in UFT phase II study].

Based on the overall results of a UFT phase II study made in 104 institutions in Japan from April of 1979 to September of 1980, there was a response rate of 27.7% with 3 CR cases and 49 PR cases out of 188 stomach cancer cases considered as evaluable according to solid cancer chemotherapy direct efficacy criteria. Other response rates were spleen cancer 25%, gallbladder cancer 25%, liver cancer 19.2%, colorectal cancer 25%, breast cancer 32% and lung cancer 7%. Side effects out of 551 cases were, loss of appetite 24.3%, nausea/vomiting 12.5%, diarrhea 11.1% and other digestive system symptoms mainly. The hematologic side effects were mild, being 6.9%. According to the UFT phase II study, in 438 evaluable cases followed for 5 years after testing, the results were analyzed in terms of therapeutic efficacy and survival time. In 185 stomach cancer cases, 50% survival time was 185 days, with CR + PR cases 336 days, MR + NC cases 183 days, and PD cases 97 days. Colorectal cancer showed a 50% survival time of 227 days in 54 cases, while that for 49 breast cancer cases was 505 days. Total Ftorafur (FT) results using the same criteria from the UFT phase II study revealed, from a comparison of dosage and disease type, that UFT did not enhance FT side effects; rather, it markedly increases effectiveness. Therefore, on the basis of its response rate and the survival time for the cases of digestive system cancer, UFT is considered an effective anticancer agent.

Anorexia↗

[Cytarabine].

Cytarabine (ara-C) is the first line agent with its excellent activity for acute myelogenous leukemia. Combination therapy of MFC (mitomycin C, 5-FU, ara-C) has been used for GI tract cancer with a synergistic effect on L-1210 mouse leukemia. In the results of research on the administration, a high dose ara-C is an effective agent in the refractory cases to the standard dose ara-C and the combination with daunorubicin is applied to a remission consolidation therapy. A small dose ara-C is used against an atypical leukemia with its mechanism of induction of differenciation. On the other hand, in the development of its derivertive compounds ancitabine or enocitabine (BH-AC) were induced to a treatment of acute myelogenous leukemia. Especially BH-AC is the first choice agent for acute myelogenous leukemia combined with other agents.

Animals↗

[Biochemical modulation with sequential methotrexate (MTX)-5-fluorouracil (5-FU) treatment].

The results of a cooperative study on sequential MTX-5-FU treatment of gastrointestinal cancer were presented. The treatment consisted of three methods, A, B, C. At zero time, MTX 30 mg/m2 (A), 100 mg/m2 (B) and 300 mg/m2 (C) i.v. infusion were given, and 5-FU 600 mg/m2 (A, B, C) was infused 1-3 hours after MTX in gastric cancer patients and 7 hours afterwards in colorectal cancer patients. Twenty-four hours after MTX, leucovorin rescue of 10 mg/m2 p.o. was given either 0 times or once in A, 6 times in B and 8 times in C every 6 hours. In gastric cancer patients, the response rate was 23.2% of 56 cases in A, 40.5% of 37 cases in B and 0% of 3 cases in C. In colorectal cancer patients, the response rate was 28.6% of 21 cases in A, 20.0% of 15 cases in B and 0% of 3 cases in C. Median survival was 7.4 months (M) in total, 5.5 M in A and 7.6 M in B for gastric cancer, and 8.1 M in total, 10.9 M in A and 7.8 Min B for colorectal cancer. Side effects were mild and tolerable. In summary, in this phase II study on gastric cancer, although the response was limited with A, the relatively high response rate of 40.5% with B was promising. The subsequent phase III study will need to evaluate the biochemical modulation with sequential MTX-5-FU treatment in gastric cancer patients.

Aged↗

Effect of corticosteroid on passively transferred experimental allergic neuritis.

Effect of prednisolone on experimental allergic neuritis (EAN) in Lewis rats was studied. In order to exclude the influence of residual antigens, we evaluated the effect in EAN passively transferred with living lymphoid cells. Prednisolone, when administered after the passive transfer, prevented EAN both clinically and histologically, but when administered after the clinical onset, it had little influence on the course of the disease. Prednisolone was suspected to have suppressed the sensitized cells, but to have had no remarkable effect after the clinical onset.

Animals↗

[Second-generation cisplatin analogs].

Since the introduction into clinical practice in 1972, cisplatin (CDDP) has assumed an important role in the treatment of various tumors such as testicular, ovarian or pulmonary cancer. Its toxicities include emesis, renal impairment, neuropathy, hearing loss and anemia. In clinical trials renal toxicity has been proved to be dose limiting factor. Thus the total number of courses which may be given is limited. For this reason second-generation CDDP analogues with reduced toxicity have been tried to develop and are reaching clinical testing. A number of studies have now been published relating the results of these trials. The best studied of these analogues is carboplatin (CBDCA, JM-8) which was noted to be less nephrotoxic, but more myelosuppressive than CDDP in preclinical study. Phase I trials have shown that CBDCA is relatively free of renal toxicity and that its dose limiting factor is myelosuppression, especially thrombocytopenia. In phase II trials CBDCA has been shown to be an active agent in advanced carcinomas of the ovary, head and neck, lung and urogenital organs. Similar results have been obtained in clinical trials of iproplatin (CHIP, JM-9) which is synthesized as an analogue of CDDP. Two other analogues developed in Japan have been evaluated to be active for various mouse tumors in preclinical studies. Phase I trials of these agents is now ongoing.

Bone Marrow↗

Phenotyping of proliferating lymphocytes in angioimmunoblastic lymphadenopathy and related lesions by the double immunoenzymatic staining technique.

Biopsy specimens of lymph nodes with the histologic characteristics of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) were obtained from 9 cases (4 cases of AILD and 5 cases of AILD-like T lymphoma [AILD-T]) and histologically analyzed by the use of a double immunoenzymatic staining technique with the combination of a monoclonal antibody against lymphocyte membrane antigen and that against human DNA polymerase alpha (pol alpha), which is detectable in the nucleus of the cells in G1, S, and G2 phases. In all 9 cases, the pol alpha + proliferating cells had a peripheral T-cell phenotype with T11 and Leu-4 antigens, whereas proliferating B cells with B1 antigen were rarely observed. As for T-cell subset antigens, the proliferating T cells had T4+ helper/inducer phenotype in 7 cases, while T8+ suppressor/killer T cells proliferated in 2 cases, although a significant number of T4+ proliferating cells were also recognized. The study on malignant lymphomas that evolved in the 2 cases showed that the T-subset antigens on major proliferating tumor cells were the same as those found in the preceding AILD lesions, suggesting that lymphoma T cells originate from the AILD lesion. The results suggested that AILD without histologic manifestations of malignancy and AILD-T may be a neoplastic disease derived from either subset of peripheral T cells.

Adult↗

[Implantation of a vascular access device in cancer treatment: operation or angiographic technic?].

Thirty cancer patients, who were diagnosed to be beyond the operable stage, were treated by intra-arterial anticancer agent infusion via an implantable vascular access device (VAD) combined with local hyperthermia and/or charcoal hemoperfusion. The VAD was implanted by a surgical procedure in 14 patients, or by a technique similar to super-selective angiography mainly via the femoral artery in the remaining 16 patients who could not be operated on because of their seriously severe clinical condition and/or the difficulty involved in approaching the tumor feeding artery due to the presence of huge tumors or multiple lymph node metastasis. No serious complications were seen in these treatments. However, the catheter became occluded after an average post-implantation period of 9 months in 6 patients in the operative group. Since an operative procedure is very often too invasive for end-stage cancer patients and may enhance tumor growth, VAD implantation utilizing an angiographic technique is recommendable for the treatment of advanced cancer.

Adult↗

[Sequential methotrexate-5-fluorouracil (MTX-5-FU) treatment of patients with advanced gastric and colorectal cancer. Sequential Methotrexate-5-FU Study Group].

A multicenter cooperative study was conducted from July 1984 to March 1986 to evaluate the clinical efficacy of sequential MTX-5-FU treatment in 96 cases of advanced gastric cancer and 39 cases of colorectal cancer. 5-FU 600 mg/m2 i.v. was given and MTX 30 mg/m2 (A), 100 mg/m2 (B) and 300 mg/m2 (C) i.v. were given, and the administration interval between MTX and 5-FU was 1 to 3 h for the gastric cancer group, and 7 h for the colorectal cancer group. Leucovorin rescue of 10 mg/m2 p.o. was given 24 h after MTX administration. In the gastric cancer group, the response rate for Regimen A was 23.2% (CR 1 and PR 12) out of 56 evaluable cases, and for Regimen B, 40.5% (CR 1 and PR 14) out of 37 evaluable cases. In the colorectal cancer group, the response rate for Regimen A was 28.6% (PR 6) out of 21 evaluable cases and for Regimen B, 20.0% (PR 3) out of 15 cases. Median survival time for the gastric cancer group was 5.5 months with Regimen A and 7.6 months with Regimen B, and for the colorectal cancer group 10.9 months with Regimen A and 7.9 months with Regimen B. Main adverse effects were marrow impairment and gastrointestinal symptoms such as nausea, diarrhea, and stomatitis. In this study Regimen B showed relatively good results. In order to evaluate the biochemical modulation occurring with sequential MTX-5-FU treatment, a further phase III study in gastric cancer patients should be conducted.

Adult↗