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Biomedical subjects

K Tsushima

Publications and source records attributed to K Tsushima.

At least 73 records · Page 4Linked to original sources
PubMed1989

Randomized controlled study of mitomycin C/carboquone/5-fluorouracil/OK-432 (MQ-F-OK) therapy and mitomycin C/5-fluorouracil/doxorubicin (FAM) therapy against advanced liver cancer.

We have previously reported that the combination of mitomycin C, carboquone, 5-fluorouracil and OK-432, including the intra-arterial administration of mitomycin C and carboquone (MQ-F-OK therapy), was effective in the treatment of advanced liver cancer. The Cooperative Study Group conducted a controlled study on MQ-F-OK therapy and the combination of mitomycin C, 5-fluorouracil and doxorubicin, including the intra-arterial administration of mitomycin C and doxorubicin (FAM therapy), against advanced liver cancer. Forty patients with advanced primary or secondary liver cancer were enrolled in this study and randomized into the MQ-F-OK group and the FAM group. Seventeen of the 21 cases in the MQ-F-OK group and 16 of the 19 cases in the FAM group were eligible for response evaluation in accordance with the criteria of the Japan Society for Cancer Therapy. There was no significant difference in the patient characteristics between the two groups. Three cases in the MQ-F-OK group and two in the FAM group showed partial response. There was, however, no significant difference in the response rates and the prolongation of life between the two groups. As for the side-effects, only anemia was observed more frequently in the FAM group than in the MQ-F-OK group. In conclusion, we could not preferentially recommend either MQ-F-OK therapy or FAM therapy for advanced liver cancer. The performance status of the patient was one of the most important factors in the treatment of advanced liver cancer because patients with poor performance status showed poorer results.

Adult↗
PubMed1989

The relationship of flow cytometric DNA analysis and clinicopathology in small-intestinal carcinoids.

Paraffin-embedded archival tissue samples were used for nuclear deoxyribonucleic acid (DNA) content study by flow cytometry on 56 surgically resected, primary, small-intestinal carcinoid tumors. Sample preparation was carried out using the methods of Hedley and Vindelov. To reduce nuclear aggregation, a procedure of sonication was also performed. Nineteen (34%) cases were DNA diploid, 34 (61%) cases showed significantly increased 4C peak (DNA tetraploid), and only three (5%) cases were DNA aneuploid. Cell cycle phase analysis revealed that carcinoid tumors had significantly higher G2% than those of nontumor control tumors. However, there was no significant correlation between clinical parameters and both DNA ploidy pattern and cell cycle phase analysis. Although the difference in survival between patients with DNA nondiploid tumors and DNA diploid tumors was not significant, all of the patients with DNA aneuploid tumor had poor prognosis followed by death from carcinoid tumor.

Adult↗
PubMed1989

[Two cases of gastrointestinal cancers with major responses to sequential methotrexate 5-FU plus 5'-DFUR].

We reported 2 patients treated with Methotrexate (MTX)-Fluorouracil (5-FU) sequential therapy combined with Doxifluridine (5'-DFUR). The method of administration was as follows: MTX 60 mg was given intravenously (iv) followed by 5-FU 600 mg iv 2 hours later in colon cancer and 5 hours later in gastric cancer. Leucovorin 20 mg was administered 3 times every 6 hours beginning 6 hours after 5-FU infusion. This cycle was repeated once a week for 5 weeks. 5'-DFUR 1,200 mg was given orally daily and continued after MTX.5-FU therapy. Patient 1 was a 60-yr-old female with recurrent colon cancer developed four years after sigmoidectomy. She was referred to our hospital for further examinations of elevated serum carcinoembryonic antigen (CEA). The enlarged intraabdominal lymph nodes due to recurrence were demonstrated on computer tomography and the chemotherapy was performed as described above. The swelling of lymph nodes showed marked reduction in size and CEA value was normalized. Patient 2 was a 59-yr-old man with advanced gastric cancer accompanied by giant liver metastasis. Both primary and metastatic lesion responded favorably to this regimen. There was no remarkable side effect in either patient. These results suggest that this method is worth performing in further clinical trials for cancer patients.

Adenocarcinoma↗
PubMed1989

[Phase II study of cisplatin in advanced esophageal cancer and gastric cancer].

Twenty-four patients with advanced gastric cancer and 4 patients with advanced esophageal cancer were treated with cisplatin at a dose of 80-100 mg/m2 for one day or 10-20 mg/m2 for 5 consecutive days every 3-4 weeks. As for gastric cancer, 21 of 24 were evaluable for this study according to the criteria of the Japan Society for Cancer Therapy. Four of 21 patients (19%) showed partial response (PR), 7 displayed no change (NC), and 10 evidenced progressive disease (PD). Among 4 PR cases, only one had effective primary lesion. As for esophageal cancer, all 4 patients were evaluable, while 2 showed no change (NC) and another 2 exhibited progressive disease (PD). Gastrointestinal toxicity occurred in 20 patients despite the use of anti-emetic drugs. Nephrotoxicity and hematological toxicity were observed in 14 patients and 22 patients, respectively. These did not impede the continuous treatment except one case of hematological toxicity. It was concluded that cisplatin is more effective for the metastatic lesion of gastric cancer than primary lesion.

Adenocarcinoma↗
PubMed1988

Transitional cell carcinoma of the renal pelvis: nuclear deoxyribonucleic acid ploidy studied by flow cytometry.

Nuclear deoxyribonucleic acid ploidy analysis by flow cytometry was performed successfully on 109 formalin-fixed paraffin-embedded tissue specimens of transitional cell carcinoma of the renal pelvis. Tumor tissues were from patients who were operated upon between 1960 and 1975, so that long-term clinical followup was available. There were good correlations among deoxyribonucleic acid ploidy pattern and histological grade, pathological stage and clinical outcome. For high grade, high stage tumors deoxyribonucleic acid ploidy pattern provided no additional prognostically important information. However, for the more common low grade, low stage tumors the occasional detection of deoxyribonucleic acid aneuploidy patterns identified an important subgroup of patients who experienced significantly poorer survival.

Actuarial Analysis↗
PubMed1988

Uterine leiomyosarcomas and benign smooth muscle tumors: usefulness of nuclear DNA patterns studied by flow cytometry.

Flow cytometry was used to determine the DNA ploidy pattern of paraffin-embedded archival tissue specimens from 90 surgically resected uterine smooth muscle tumors (49 leiomyosarcomas and 41 leiomyomas). The technique of Hedley was used for preparation of paraffin-embedded tissue into single dissociated nuclei, and the method of Vindeløv was used for staining with propidium iodide. Among the 41 leiomyomas, most tumors (88%) had a DNA diploid pattern; the exceptions were two DNA tetraploid/polyploid and three DNA aneuploid samples. The DNA histograms of the 49 leiomyosarcomas (including 6 epithelioid leiomyosarcomas) were classified as follows: 9 cases (18%) exhibited a DNA diploid pattern, 29 cases (59%) had a DNA tetraploid/polyploid pattern, and 11 cases (23%) had DNA aneuploid peaks. Although DNA ploidy pattern cannot be used diagnostically to distinguish malignant from benign uterine smooth muscle tumors, the nuclear DNA ploidy pattern is an easily measured, objective determination that may have important prognostic significance for patients with uterine leiomyosarcomas.

Adult↗
PubMed1988

Provocation of a paradoxical growth hormone response to corticotropin-releasing hormone by pretreatment with metoclopramide in patients with acromegaly and normal subjects.

Two of 7 patients with acromegaly and one of 7 normal subjects exhibited a paradoxical rise in growth hormone (GH) to human corticotropin-releasing hormone (CRH) when pretreated with metoclopramide, although CRH alone did not induce an increase in GH. In one of these two patients with acromegaly, the GH increase to metoclopramide alone also reached the criteria of a paradoxical response. These two acromegalic patients showed a GH increase to metoclopramide pretreatment before and up to two months after surgery. In another acromegalic patient, whose GH level remained high 5 months after surgery, metoclopramide induced an increase in GH level, while in a patient who had an above-normal GH level 18 months after surgery, the resumption of physiological GH secretion after surgery was evidenced by a postoperative absence of a GH response to metoclopramide. It is suggested from these results that the GH response to metoclopramide and the metoclopramide-provoked GH response to CRH in patients with acromegaly result from the secretion of GH from nonadenomatous cells of the pituitary.

Acromegaly↗
PubMed1988

[MQF-FT and MQF-UFT in gallbladder and bile duct cancer].

Four patients with gallbladder cancer and two with bile duct cancer were treated with mitomycin C, carboquone, 5-fluorouracil and OK-432 (MQF-OK therapy) plus tegafur (FT) or UFT. MQF-OK therapy was administered according to our original method. FT and UFT were orally given in a dose of 600-800 mg/body/day and 300-400 mg/body/day, respectively. Three with gallbladder cancer and one with bile duct cancer showed PR. Myelosuppression was observed in all cases, but recovered in two weeks after MQF therapy. We recommend the further trial of MQF-OK therapy plus FT or UFT for gallbladder and bile duct cancer.

Administration, Oral↗
PubMed1987

In vitro chemotherapy sensitivity testing of human ovarian carcinoma: comparison of optical colony counting and [3H]thymidine incorporation assays.

Optical colony counting was used for assessing drug sensitivity of 87 samples (from 51 primary solid tumors, 19 metastatic solid tumors, and 17 ascites fluids) from 83 common epithelial type ovarian carcinomas. The evaluability rate by the optical counting method was 26.4%. Fifty of these samples were also assessed by a tritiated thymidine ( [3H]dThd) incorporation assay (evaluability rate by incorporation assay, 74%). In the 12 cases fully evaluable by both methods, the correlation coefficients for regression of drug sensitivity data between the methods ranged from 0.503 to 0.976 (mean, 0.745); for the combined data of these cases, the correlation coefficient was 0.707. The new [3H]dThd assay appears useful and efficient for performing in vitro chemotherapy sensitivity testing of human ovarian cancer.

Antineoplastic Agents↗
PubMed1987

Effect of dietary protein on purine nucleoside phosphorylase and xanthine dehydrogenase activities of liver and kidney in chicken and pigeon.

Comparative studies were made on the effects of diets of different protein contents on the activities of purine nucleoside phosphorylase and xanthine dehydrogenase of avian livers and kidneys. In chicken liver and kidney, both enzyme activities were increased with high protein diet, confirming the previous results. In pigeon liver, only purine nucleoside phosphorylase was increased but xanthine dehydrogenase activity was not detected after feeding a high protein diet, while both enzyme activities were increased in the pigeon kidney. The increase in the levels of plasma oxypurines in pigeon serum was consistent with the result that the xanthine dehydrogenase activity of pigeon was not detected in the liver but in the kidney.

Animals↗
PubMed1987

Leiomyosarcomas and benign smooth muscle tumors of the stomach: nuclear DNA patterns studied by flow cytometry.

Paraffin-embedded archival tissue samples were used for determination of DNA ploidy by flow cytometry on 117 surgically resected gastric smooth muscle tumors (44 leiomyosarcomas, 53 leiomyomas, and 20 benign leiomyoblastomas). The technique of Hedley was used for preparation of paraffin-embedded tissue into single dissociated nuclei, and the method of Vindeløv was used for staining with propidium iodide. Among the 53 leiomyomas, the DNA ploidy pattern was diploid in most tumors (87%), except for 2 DNA tetraploid/polyploid and 5 DNA aneuploid samples. In comparison, the 20 benign leiomyoblastomas had more frequent abnormal DNA histograms: DNA tetraploidy/polyploidy in 5 (25%) and DNA aneuploidy in 2 (10%). The DNA histograms of the 44 leiomyosarcomas (including 4 epithelioid leiomyosarcomas) were classified as follows: 20 cases (45%) exhibited a DNA diploid pattern, 14 cases (32%) had a DNA tetraploid/polyploid pattern, and 10 cases (23%) had DNA aneuploid peaks. For the patients with leiomyosarcomas, the DNA ploidy pattern was significantly correlated with survival (P less than 0.001), as were tumor grade (P less than 0.001) and tumor size (P less than 0.05). Furthermore, both benign and malignant gastric smooth muscle tumors with DNA tetraploid/polyploid patterns were significantly larger than those with a DNA diploid histogram (P less than 0.05). DNA ploidy pattern cannot be used for diagnosis--that is, to distinguish malignant from benign gastric smooth muscle tumors. For gastric leiomyosarcomas, however, nuclear DNA ploidy pattern is an easily measured objective determination with important prognostic significance.

Adolescent↗
PubMed1987

[Multiple submucosal cysts of the stomach associated with IIc + III type early gastric cancer--report of a case].

A 59-year-old man was admitted with a complaint of epigastric discomfort, under the diagnosis of gastric cancer, subtotal gastrectomy was performed. In the resected specimen IIc + III type early gastric cancer were observed at the lesser curvature of the corpus and multiple submucosal cysts in almost entire area of the stomach. Histologic examination confirmed early adenocarcinoma and an atypical epithelium, which was present separately. Submucosal cysts consisted of a pseudo-pyloric-gland-type of epithelium, containing some fundic glandular and foveolar epithelium. Frequent erosion and regenerated epithelium and extensive intestinal metaplasia were observed in the gastric mucosa. There was no carcinomatous change in the submucosal cysts.

Adenocarcinoma↗
PubMed1987

Prognostic significance of nuclear deoxyribonucleic acid ploidy patterns in resected hepatic metastases from colorectal carcinoma.

Nuclear deoxyribonucleic acid (DNA) ploidy studies of paraffin-embedded archival tumor specimen blocks were performed by flow cytometry on extracted nuclei from 101 surgically resected hepatic metastases from colorectal cancer. In 28 patients, the corresponding primary carcinoma of the metastases was also studied. Tumor clinicopathology and clinical course of the patients were reviewed. Preparation of paraffin-embedded tissue specimens was performed by the technique of Hedley et al. and stained with propidium iodide according to the method of Vindelov et al. Eighty-eight of 101 metastatic tumors and 26 of 28 primary tumors yielded evaluable DNA histograms. Twenty-six metastases showed a DNA diploid pattern, 25 showed a significantly increased 4C peak (DNA tetraploid/polyploid), and 37 had a DNA aneuploid peak. Ploidy pattern was constant between primary and metastases in 84.6% of tumors. No significant relationship between host and tumor characteristics and ploidy pattern was found except for a correlation between grade 3 metastases and DNA aneuploid. Survival of patients with DNA aneuploid metastases was significantly less than that of patients with DNA diploid metastases (p = 0.03). However, among DNA nondiploid metastases, survival was significantly less for low DNA index metastases (less than or equal to 1.5) than for high DNA index (greater than 1.5) metastases (p less than 0.05). Flow cytometric DNA ploidy measurements may have prognostic value for patients with resected hepatic metastases from colorectal carcinoma.

Colonic Neoplasms↗
PubMed1986

Interaction of milk xanthine oxidase with folic acid. Inhibition of milk xanthine oxidase by folic acid and separation of the enzyme into two fractions on Sepharose 4B/folate gel.

Inhibition of xanthine oxidase by folic acid was reexamined after complete removal of the contaminant which was responsible for time-dependent inactivation (Lewis, A. S., Murphy, L., Mcalla, C., Fleary, M., and Purcell, S. (1984) J. Biol. Chem. 259, 12-15; Spector, T., and Ferone, R. (1984) J. Biol. Chem. 259, 10784-10786). From turnover experiments using stopped flow equipment with a limited amount of xanthine and excess oxygen, and from kinetic analyses with an oxygen electrode, folic acid was found to be an inhibitor of xanthine oxidase. The inhibition was competitive with xanthine with a Ki value of 4.2 X 10(-5) M. From the behavior of the enzyme in affinity chromatography using a Sepharose 4B/folate column, folic acid was also confirmed to be a competitive inhibitor of xanthine oxidase. When enzyme which had been pretreated with oxipurinol was applied to the affinity column, two fractions of xanthine oxidase were separated. The first fraction was found to contain the fully active form (double-active dimers) from the analyses of spectral changes on addition of xanthine, oxipurinol titration, and ESR slow signal, whereas the second fraction was assumed to contain mixed dimers and double-inactive dimers. The ratio of the content of the first fraction to that of the second fraction supports the hypothesis that there are three enzyme species and that there is no interaction either in catalytic activity or in sulfuration or desulfuration reactions between the two subunits.

Animals↗