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Biomedical subjects

H Sekine

Publications and source records attributed to H Sekine.

At least 145 records · Page 8Linked to original sources

[Double channel chemotherapy with intra-arterial infusion of DDP and concurrent intra-venous infusion of sodium thiosulfate (STS) in bladder cancer].

Ten patients with bladder cancer were treated with double channel chemotherapy which included intra-arterial infusion of DDP and concurrent intra-venous infusion of STS, a neutralizing agent against DDP. The method allows the administration of a relatively high dose of DDP to localized malignant tumors by protection from systemic cytotoxicity of DDP by STS. DDP in a dose of 100-150 mg/m2 of body surface was infused either to the internal iliac artery at a portion close to the superior vesical artery or to the aortic bifurcation by the Seldinger technique over 30 minutes, and infusion of 20 g STS to the peripheral vein was simultaneously started and continued for 2-3 hours. One patient achieved a complete response and 2 patients achieved a partial response. The response rate was 30%. Histopathologically, 4 out of 8 patients showed an effect of 2 grades or more by Oboshi-Shimosato's criteria. Invasive or hypervascular tumors seem to be more responsive to the present treatment than superficial or hypovascular ones. Side effects were relatively mild inspite of a large dose of DDP. It should be noted that concurrent STS infusion efficiently counteracts the renal toxicity of DDP.

Adult↗

Use of a murine monoclonal antibody for detection of circulating plasma DF3 antigen levels in breast cancer patients.

The murine monoclonal antibody (MAb), designated DF3, reacts with a 300,000-mol wt mammary epithelial antigen. A sequential double-determinant radioimmunoassay (RIA) has been developed to monitor circulating DF3 antigen. Using this assay, we have demonstrated that 33 of 36 normal women had plasma RIA antigen levels less than 150 U/ml. In contrast, 33 of 43 patients (76%) with metastatic breast cancer had RIA DF3 antigen levels greater than or equal to 150 U/ml. The difference between these two groups was statistically significant (P less than 0.001). Similar results have been obtained with a double-determinant enzyme-linked immunoassay (EIA). Only 6 of 111 age-matched normal subjects had EIA DF3 antigens levels greater than or equal to 30 U/ml, while 42 of 58 patients (72%) with breast cancer had levels equal to or above this value. Thus, similar patterns of specificity are obtained with the EIA or RIA. The elevation of circulating DF3 antigen levels in breast cancer patients has been confirmed by transfer blot assays. MAb DF3 reactivity occurred predominantly with circulating antigens of three different molecular weights ranging from 300,000 to approximately 400,000 mol wt. We also demonstrate that patients with both primary and metastatic breast cancer who were free of detectable disease at the time of sampling have DF3 antigen levels that are similar to those obtained from normal subjects. While patients with hepatoma (27%) and ovarian carcinoma (47%) also had elevated circulating DF3 antigen levels, the results suggest that DF3 antigen levels may be useful in distinguishing breast cancer patients from those with esophageal, gastric, colorectal, pancreatic, and lung carcinomas. Furthermore, the results of the RIA, EIA, and transblot analyses demonstrate that the measurement of circulating DF3 antigen levels provides a new and potentially useful marker to follow the clinical course of patients with metastatic breast cancer.

Adult↗

Circulating DF3 and CA125 antigen levels in serum from patients with epithelial ovarian carcinoma.

The murine monoclonal antibody (MAb), designated DF3, reacts with a 300-kilodalton (kd) mammary epithelial antigen. A sequential double-determinant enzyme-linked immunoassay (EIA) has been developed to monitor circulating DF3 antigen. Previous studies have demonstrated that the use of the DF3 EIA provides a new and potentially useful marker to follow the clinical course of patients with metastatic breast cancer. In the present study, we have monitored circulating DF3 antigen in the serum of patients with epithelial ovarian carcinomas and non-ovarian gynecologic malignancies. Twenty-one of 45 patients (47%) with ovarian carcinoma had elevated DF3 antigen levels (greater than or equal to 30 U/mL). In contrast, three of 20 patients (15%) with non-ovarian gynecologic malignancies, and only four of 59 control women (7%) had elevation of circulating DF3 antigen. The difference between DF3 antigen values from patients with ovarian cancer and from controls was significant (P less than .001). The elevation of circulating DF3 antigen in ovarian cancer patients has also been confirmed by transblot assays. MAb DF3 reactivity occurred predominately with circulating antigens of molecular weights (mol wt) ranging from 300 to 450 kd. Furthermore, DF3 antigen levels have been shown to correlate with progression of disease in six patients with ovarian cancer and after resection of disease in two others. The half-life of circulating DF3 antigen was approximately 45 to 60 days. The results also demonstrate that DF3 antigen is distinct from CA125, a glycoprotein associated with coelomic epithelium and developmental amnion. The use of both the DF3 EIA and the immunoradiometric assay previously described to detect circulating CA125 suggests that determining levels of both markers may enhance the sensitivity of monitoring the course of ovarian cancer. Furthermore, the use of both assays may be useful in distinguishing ovarian cancer from other malignancies.

Adult↗

[A case of Werner's syndrome with neurogenic bladder].

The present report is Werner's-syndrome associated with a neurogenic bladder. The patient visited our clinic with the chief complaint of retention of urine and urinary tract infections. The diagnosis of Werner's syndrome was made because the patient had such clinical features as bird-like or "masked" face, short stature, graying of the hair in youth, cataracts in youth, skin changes like scleroderma principally on limbs, early menopause. After trans-urethral-resection of bladder neck and administration of distigmine bromide, her bladder function was improved, she could urinate by herself and she was free from urinary tract infections.

Adult↗

[Sequential intravesical chemotherapy with mitomycin C and adriamycin for superficial bladder tumor (preliminary report)].

Intravesical chemotherapy with sequential instillation of mitomycin C and adriamycin was carried out on 19 patients with superficial bladder cancer (Ta, T1 and Tis). Twenty milligram of mitomycin C on day 1 and 40 mg of adriamycin on day 2 were instilled into the bladder, this treatment being repeated weekly for 5 consecutive weeks if there were no serious side effects. The following results were obtained. Of 16 evaluable patients, 10 patients (63%) achieved complete response and 2 patients achieved partial response, 4 patients showing no response. In patients with high grade tumor, especially with carcinoma in situ, a high CR rate (6/7 or 86%) was achieved. Chemical cystitis occurred in 10 out of 19 (53%) patients. In 5 of the 6 patients who suffered from severe cystitis symptoms, treatment was discontinued. However, the symptoms resolved within 4 weeks in all patients.

Adult↗

Purification and characterization of a high molecular weight glycoprotein detectable in human milk and breast carcinomas.

The murine monoclonal antibody (MAb) designated DF3 has defined a high m.w. antigen detectable in human breast carcinomas and in human milk. DF3 antigen is detectable on apical borders of secretory mammary epithelial cells and in the cytosol of less differentiated malignant cells. DF3 antigen expression has been shown to correlate with the degree of human breast tumor differentiation, and the detection of a cross-reactive species in human milk has suggested that DF3 antigen might be useful as a biochemical marker of differentiated mammary epithelial cells. To further characterize DF3 antigen, we have developed an approach to purify the cross-reactive species by using gel filtration and antibody affinity chromatography. The affinity column-purified DF3 antigen was absorbed by wheat germ agglutinin and peanut agglutinin, but not by concanavalin A or lentil lectin. In contrast, wheat germ agglutinin inhibited MAb DF3 reactivity with the purified antigen, whereas there was little, if any, inhibition when using peanut agglutinin. These findings are thus consistent with the involvement of terminal N-acetyl-D-neuraminic acid and/or N-acetylglucosamine residues in the antigenic site. DF3 antigenicity was also sensitive to neuraminidase, but not chondroitinase ABC, chondroitinase AC, chondroitin-4-sulfatase, or hyaluronidase. Furthermore, DF3 antigen was sensitive to Pronase, subtilisin BPN', and alpha-chymotrypsin. The presence of O-glycosidic linkages between carbohydrate and protein in the DF3 antigenic site was further supported by the presence of NaBH4-sensitive sites. Together, these results suggest that sialyl oligosaccharides present on a peptide backbone are required for maintaining DF3 antigenicity. Similar findings have been demonstrated for DF3 antigen purified from both human milk and breast cancer effusions. However, the DF3 antigen in human milk consisted of a single high m.w. species, whereas the tumor-associated antigen consisted of two distinct glycoproteins with m.w. of 330,000 and 450,000. These findings may be relevant to the recent demonstration that distinct high m.w. DF3 antigens are elevated in the circulation of patients with breast carcinoma.

Antibodies, Monoclonal↗

A high selective screening test for methamphetamine in human urine.

A high selective screening test (Ad-Tip method) for methamphetamine in human urine has been devised. The method involves a brief extraction from a urine sample with an Ad-Tip (ODS-silica minicolumn), washing, eluting with modified Simon's reagent, and coloration with carbonate buffer. Detection limit of methamphetamine in urine is 1 microgram/ml and the test takes within 3 min/sample. The results of the Ad-Tip method were almost identical to those of laboratory analyses.

Acetates↗

Inhibition of growth of HeLa cells by new synthetic protease inhibitors.

Tryptic hydrolysis of benzoyl-DL-arginine p-nitroanilide was competitively inhibited by phenyl and substituted phenyl esters of trans-4-guanidinomethylcyclohexanecarboxylic acid (GMCHA), amidinopiperidine-4-carboxylic acid (APCA), amidinopiperidine-3-carboxylic acid (AP3CA), amidinopiperidine-4-acetic acid (APAA), amidinopiperidine-4-propionic acid (APPA), amidinopiperidine-3-propionic acid (AP3PA), amidinopiperidine-4-butyric acid (APBA), and amidinopiperidine-3-butyric acid (AP3BA). The 4-tert-butylphenyl (tBP) ester of APPA was the most effective inhibitor, its K1 value being 5.0 X 10(-7) M. The free acids and phenols had no inhibitory effect at 10(-3) M. The tBP esters of GMCHA, APPA, and APBA caused 50-60% inhibition of growth of HeLa cells, their effects being dose-dependent, while same esters of APCA, AP3PA, APPA, AP3PA, and AP3BA inhibited the growth by 30-40%. The phenyl esters of these were less inhibitory than the tBP esters. A protease preparation obtained from HeLa cells by sonication and ultrafiltration through a molecular sieve membrane strongly hydrolyzed the fluorescent peptides Boc-Val-Pro-Arg-MCA and Bz-Arg-MCA. This proteolytic activity was not affected by soybean trypsin inhibitor but was strongly inhibited by the tBP esters of GMCHA, APAA, and APBA, their effects roughly paralleling their inhibitions of the growth of HeLa cells.

Cell Division↗

[Combination chemotherapy with bleomycin, vinca alkaloid and cisplatin (BVP) for advanced urothelial cancer].

Since October 1979, 18 patients with metastatic urothelial cancer have been treated with combination chemotherapy of bleomycin (5-10 mg/day administered on days 1 to 7), vinca alkaloid (vinblastine 5-10 mg/day or vincristine 1 mg/sqm on days 8 and 9) and CDDP (60 mg/sqm on day 10). CR was achieved in 3 of the 18 patients and PR in 6 patients. Over-all, the response rate was 50%. Among 3 patients who achieved CR, 2 patients are still free of disease for 31 months and for 28 months, and the other is alive with cancer for 26 months. The 2-year survival rate was 58% in responders (CR + PR) and 0% in nonresponders. (p less than 0.005). In many cases, the response was observed after the first or second course of BVP therapy, and there was a relatively good response in patients with lymphnode metastasis alone. The treatment was tolerated well and common toxic effects were nausea, vomiting of moderate to severe degree (100%), myelosuppression (50%) and mild nephrotoxicity (22%). As to the choice of vinca alkaloids, vincristine seemed to be the treatment of choice because it was less toxic than vinblastine and was almost equally effective.

Aged↗

[Adjuvant chemotherapy following total cystectomy for invasive bladder cancer with bleomycin, vincristine and methotrexate].

Eleven patients with invasive bladder cancer were treated with combination chemotherapy consisting of bleomycin (5 mg, i.m., day 1-7), vincristine (1 mg/sq.m.i.v., day 8) and methotrexate (200-300 mg/sq.m.i.v. day 8). Chemotherapy was started about 4 weeks following total cystectomy and repeated every 2 or 3 weeks at least for one year. Five of the patients were free of disease at the mean follow-up time of 35.6 months, ranging from 21 to 50 month. The 3-year survival rate was 54.5%. Bone marrow suppression (36%), nausea and vomiting (55%) were observed, but they were not serious and well tolerated. These results suggest that this regimen could be used safely as an adjuvant chemotherapy following total cystectomy for patients with invasive bladder cancer. Further evaluation will be necessary.

Adult↗

[Bleomycin, vinca alkaloid and cis-diamminedichloroplatinum combination chemotherapy for advanced testicular tumors].

Thirteen patients with advanced testicular tumors (seminoma 2, non-seminoma 11) were treated with combination chemotherapy involving BLM, vinca alkaloid and CDDP (BVP) as induction therapy and followed with CPM, VCR and CDDP as maintenance therapy. BVP and COP administration was repeated every 3 and 4 to 8 weeks for 1 year, if there were no serious side effects. The overall response rate (CR + PR) was 92% with a 69% CR rate. At a mean follow-up of 30 months (7-52 month range), 54% of the patients were alive with no evidence of disease. Bulky metastases, failure to respond to prior chemotherapy and teratomatous metastases were considered to be poor prognostic factors. The toxicity of BVP was similar to that reported for CDDP, except that allergic reaction occurred in 3 patients after several courses of treatment. Two of the 3 went into anaphylactic shock.

Adult↗