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Biomedical subjects

S Komiyama

Publications and source records attributed to S Komiyama.

At least 145 records · Page 8Linked to original sources

Pimaricin potentiation of bleomycin activity against murine tumors.

Antitumor activity of bleomycin against Ehrlich ascites carcinoma in mice was examined in the presence and absence of a polyene antibiotic, pimaricin. A single intraperitoneal (ip) injection of bleomycin and pimaricin in combination into tumor-bearing mice on day 1 produced a synergistic life-prolongation effect as compared with that of each agent alone. Accumulation of abdominal ascites was almost completely blocked by bleomycin in combination with the tetraene antibiotic. Frequent ip injection of small doses of bleomycin and pimaricin on day 1 produced a much greater increase in life span than the single ip injection. To obtain effective synergism under these treatment schedules, it appeared that the dose of bleomycin should be reciprocally proportional to the dose of pimaricin.

Animals↗

Potentiation of mitomycin C, 6-mercaptopurine, bleomycin, cis-diamminedichloroplatinum and 5-fluorouracil by mycotrienins and mycotrienols.

Mycotrienins I and II and mycotrienols I and II are ansamycin antibiotics containing a triene structure, isolated from Streptomyces rishiriensis. An amphotericin B-resistant clone (AMBR-1) derived from cultured Chinese hamster V79 cells was cross-resistant to mycotrienins I and II, but not to mycotrienol I or II. These four ansamycin antibiotics were found to potentiate significantly the action of some anti-cancer agents including 5-fluorouracil, cis-diamminedichloroplatinum, bleomycin, mitomycin C and 6-mercaptopurine against cultured V79 cells. The action of adriamycin was not potentiated. These four ansamycin antibiotics showed a synergism spectrum similar to that of smaller polyene antibiotics.

Animals↗

[Retinoids and cancer].

In this article, we survey recent advances in basic as well as clinical studies on retinoids including structure-function correlation of retinoids, effects of retinoids on cell growth, anticancer activities, immunological potentiation, initiation and promotion of cancer, differentiation, and chemoprevention.

Animals↗

[Partial laryngectomy following combined FAR therapy--evaluation of survival rate and region of recurrence studied by an antomical map].

The clinical records of 75 consecutive patients undergoing partial laryngectomy at Kyushu University Hospital were reviewed. Almost all the patients were treated by combined preoperative FAR therapy (5 FU, vitamin A and irradiation). Among 57 patients, the (estimated) five year survival rate was 76%. The cure rate among 18 patients in whom horizontal laryngectomy was done was high (75%) compared with results presented in other reports. This may be ascribable to the preoperative FAR therapy. Anatomically, critical regions of recurrence were the subglottic region and anterior commissure in vertical partial laryngectomy.

Combined Modality Therapy↗

[Experimental and clinical studies on application of vitamin A to cancer treatment].

Retinol-type vitamin A enhances cytocidal effect of several anticancer agents or radiation in in vitro as well as in vivo. We describe therapeutic effect fo a combination therapy of vitamin A and other agents which has been applied to cancer patients since 1972. We also discuss a possible role of vitamin A in the efficient synergistic effect.

Antineoplastic Agents↗

Biofeedback therapy for spastic dysphonia.

Spastic dysphonia is a disorder of phonation which is characterized by a strained, creaking, and choked vocal attack, a tense and squeezed voice sound. Spastic dysphonia in a functional voice disorder can be classified into two types from the viewpoint of activities of the extrinsic and intrinsic laryngeal muscle groups. A functional voice disorder pertaining to abnormal activities of the intrinsic and extrinsic laryngeal muscles results in spastic dysphonia. The adductor spastic dysphonia may be due to abnormal actions of the intrinsic laryngeal muscles as such is relieved by sectioning of the recurrent nerve, while spastic dysphonia mainly dealing with the extrinsic laryngeal muscles is relieved by relaxation on monitoring an electromyographic feedback system. Within 3 months we encountered two patients whose extrinsic laryngeal muscles were hyperactive on phonation. A trial on injection of lidocaine into extrinsic laryngeal muscles made their muscles relax. So, biofeedback therapy of relaxation was began using a monitoring system of EMG burst regarding to hypertonicity of the extrinsic laryngeal muscles. Normal vocal abilities were recovered using a biotrainer as a monitoring device of electromyographic feedback.

Adult↗

[Moderate dose methotrexate with citrovorum factor rescue therapy in the treatment of head and neck cancer].

A clinical trial of moderate dose methotrexate (MTX)-CF rescue was conducted in 12 institutions. Thirty-seven patients with head and neck carcinoma entered this trial, of which 32 were evaluable. MTX was administered 350 mg/m2 (500 mg/body) by i.v. drip over 6 hours. Three hours after completion of MTX infusion, CF rescue was started. There was no complete response in 32 patients. Nine patients showed partial response with the response rate of 28%. The response rates were 21% for the group of patients treated previously, and 75% for the group untreated previously. MTX concentration in plasma was determined at 6, 24, 48 and 72 hours after the initiation of MTX infusion, and the assay results revealed a safe range. GI disturbances were seen at the rates of 11 to 38%. Bone marrow suppression was mild and no renal toxicity was observed. We concluded that the moderate dose MTX-CF rescue therapy was useful for head and neck carcinoma. As a next step, we are planning to conduct a clinical trial of high-dose MTX.

Adult↗

[Antitumor effect of UFT against malignant tumors of maxillary sinus--clinical and biochemical study].

Antitumor effect of UFT against malignant tumors of the maxillary sinus (male 8, female 5) was examined clinically and biochemically. According to the Karnofsky's criteria, the clinical effectiveness was demonstrated as follows; I-B: 1, I-A: 2, 0-C: 1, 0-B: 2, 0-A: 2, 0-0: 4, unknown: 1. While according to a Japanese Criteria for Evaluation of Clinical Effects of Cancer Chemotherapy on Solid Tumors the results were assessed as follows: CR: 1, PR: 3, NC: 3, PD: 5, unknown: 1. Generally side effect was mild and found in four patients. 5-FU levels in tissue specimens of the two patients were determined. 5-FU levels in the tumor tissues were 1.3 and 2.4 times higher than those of the normal tissues, respectively.

Adenocarcinoma↗

Local immune system in the developing fetal larynx.

Using histopathological and immunofluorescent techniques, we investigated the development of the glandular system of the larynx from 12 human fetuses. Glandular buds were first observed at the fourth month of gestation and glandular distribution became evident from the fifth month in the larynx. Ciliated or nonciliated epithelium covered the cavity of the larynx, with the exception of the true vocal cord. Immunofluorescent examination revealed the presence of IgG in the fetal larynx, but there was little fluorescence for IgA, IgM and IgE. Secretory component (SC) synthesis, on the other hand, was found in each serous-type glandular epithelium or acinus from the fourth month on. Our observations suggest that the local immune system by SC, which binds to IgA as SIgA in human laryngeal mucosa, is inherently acquired in the fetal larynx.

Epithelium↗

Enhancement of the antitumor effect of 6-mercaptopurine by vitamin A.

The inhibition of the growth of HeLa cells in culture by 6-mercaptopurine was greatly enhanced in combination with retinol, retinal or retinol acetate, but not in combination with retinoic acid or retinol palmitate. The antitumor effect of retinol palmitate combined with 6-mercaptopurine was examined in BDF1 mice with L1210 leukemia. The blood level of retinol, a strong potentiator of 6-mercaptopurine among vitamin A compounds, was increased in BDF1 mice after retinol palmitate injection. Retinol palmitate was found to enhance the antitumor effect of 6-mercaptopurine against murine L1210 leukemia to a significant extent (69% increase in life span).

Animals↗

Antitumor effect of a combination of 6-methylthioinosine and amphotericin B on mouse leukemia L1210.

Antileukemic activity of 5 kinds of sulfur-containing purine ribonucleosides were examined in the presence and absence of amphotericin B against L1210 in mice. Among these compounds, 6-methylthioninosine was potentiated by amphotericin B. 6-Methylthioinosine in combination with amphotericin B produced a 75% increase in the lifespans, which was greater than the increase in lifespans by 6-methylthioinosine (38%) or amphotericin B alone (2%). Antitumor effects of other sulfur-containing ribonucleosides, such as 6-thiocyanatoguanine, 6-thiocyanatopurine, 6-thiocyanatoinosine, and 6-methylthiopurine, were not augmented by amphotericin B.

Adjuvants, Immunologic↗

Classification of polyene antibiotics according to their synergistic effect in combination with bleomycin A2 or fusidic acid.

Five polyene antibiotics were compared for their effects on colony formation of either Chinese hamster V79 or Saccharomyces cerevisiae cells. A 10 to 40 times higher concentration of amphotericin B (heptaene) or nystatin (degenerated heptaene) was necessary to inhibit colony formation of hamster cells than that needed to inhibit colony formation of yeast cells. In contrast, colony formation of both hamster and yeast cells was inhibited to the same extent by similar concentrations of filipin (pentaene), pentamycin (pentaene), or pimaricin (tetraene). The five polyene antibiotics were also compared for their effects on colony formation of either V79 or S. cerevisiae cells when combined with a nonpolyene antibiotic, fusidic acid or bleomycin A2. Amphotericin B or nystatin could augment the cytocidal effect of fusidic acid but not that of bleomycin A2, whereas pentamycin or pimaricin could augment the cytocidal effect of both fusidic acid and bleomycin A2 against hamster and yeast cells. Filipin was found to enhance the action of fusidic acid and bleomycin upon growth of mammalian cells, whereas the pentaene polyene significantly potentiated the action of fusidic acid, but not that of bleomycin A2, against S. cerevisiae. It was therefore suggested that these polyene antibiotics be classified into two groups: group 1 (pimaricin, pentamycin, and filipin) and group 2 (amphotericin B and nystatin).

Amphotericin B↗

Synergistic effect of vitamin A and fusidic acid on Hela cells in vitro.

Examinations were made to see if various vitamin A compounds, including retinol, retinal, retinol palmitate, retinol acetate, and retinoic acid, enhance the action of fusidic acid, an antibiotic and inhibitor of protein synthesis, on human carcinoma HeLa cells in vitro. Among these vitamins, retinal and retinol were found to potentiate strongly the effect of fusidic acid on HeLa cells. In this system, however, retinol palmitate, retinoic acid, and retinol acetate in 10 approximately 20 microgram/ml concentration were not found to enhance the effect of fusidic acid significantly.

Cell Survival↗

Control of permeation of bleomycin A2 by polyene antibiotics in cultured Chinese hamster cells.

Control of permeation of bleomycin A2, a well-known antitumor antibiotic, in combination with various polyene macrolide antibiotics was analyzed in cultured Chinese hamster cells in vitro. Three polyene antibiotics, filipin, pentamycin, and pimaricin, were found to enhance the action of bleomycin A2 remarkably, while amphotericin B or nystatin could not. Although DNA synthesis and colony-forming activity of polyene-sensitive Chinese hamster V79 cells were synergistically inhibited by the combination of filipin and bleomycin A2, in a polyene-resistant subline (AMBR-1) derived from V79, they were only slightly affected in the presence of both drugs. The cellular uptake of [14C]bleomycin A2 by V79 was enhanced 2- to 4-fold in the presence of increasing doses of filipin or pentamycin, but not in the presence of amphotericin B. The treatment of V79 cells with filipin for 20 to 30 min was enought to block DNA synthesis almost completely when combined with 20 microgram belomycin A2 per ml. The pretreatment of the hamster cells with 6 microgram filipin per ml for 60 min continued to enhance the inhibitory action by bleomycin A2 of DNA synthesis up to 5 hr after the removal of filipin from the cultured medium.

Amphotericin B↗

Synergistic combination therapy of 5-fluorouracil, vitamin A and cobalt-60 radiation upon head and neck tumors.

We have applied a triple combination of 5-fluorouracil (5FU), vitamin A and cobalt-60 radiation (FAR therapy) to clinical treatment of head and neck tumors since 1972. The treatment of 33 patients with cancer of larynx and 15 patients with hypopharyngeal or cervical esophageal cancer with FAR therapy during three years from 1972 to 1974 resulted in highly effective synergism in vivo, and the improved points of this therapy were presented.

Cobalt Radioisotopes↗

Potentiation of cytostatic effect of sulfur- or chlorine-containing purines and related ribonucleosides by amphotericin-B on cultured mouse leukemia cells.

Synergistic effects of sulfur-containing purines and related ribonucleosides (6-thioinosine, 6-thioguanine, 6-thiocyanatopurine, 6-methylthioinosine, 6-thiocyanatoguanine, 6-thiocyanatoguanosine, 6-phenacylthioinosine, 6-nitrobenzlythioinosine, 6-(p-chlorobenzyl)thioinosine, 6-(p-nitrobenzyl)thioguanosine, 6-benzylthioinosine, 6-ethylthioinosine, 6-benzylthioguanine, 6-benzylthiopurine, 6-methylthiopurine, and 6-thiocyanatoinosine) and chlorine-containing purine and its ribonucleoside, (6-chloropuine and 6-chloropurine riboside), in combination with the polyene antibiotic, Amphotericin-B, on cell survival and synthesis of DNA were examined in mouse leukemia L5178Y cells. 6-Methylthioinosine, 6-thiocyanatopurine, 6-thiocyanatoinsoine, 6-methylthiopurine, and 6-thiocyanatoguanine (or -guanosine) among sulfur-containing compounds were strongly potentiated by Amphotericin-B, and 6-chloropurine riboside, which is electronically analogous to methylthioinosine, was also enhanced by the polyene. Thiocyanoto or methylthio group at position 6 of the purine ring seems to be important for the polyene-mediated potentiation. 6-Methylthioinosine alone had much greater effect on DNA synthesis of HeLa cells than on L5178Y cells, and Amphotericin-B failed to potentiate the action of 6-methylthioinosine in HeLa cells.

Amphotericin B↗