[A case of "non specific multiple ulcers of the small intestine" with perforation as a presenting sign].
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Humans↗
Biomedical subjects
O Abe
Publications and source records attributed to O Abe.
[Cancer metastasis and recurrence from the standpoint of amplification and expression of oncogenes in human malignant tumors].
We investigated the amplification and expression of oncogenes in human malignant tumors. The survival rates of patients with c-erbB, c-erbB-2, and int-2 oncogene amplification/expression were significantly lower than those of the patients without gene amplification/expression. Many distant organ metastases were observed in esophageal cancer patients with int-2 amplification, in gastric cancer patients with c-erbB-2 over-expression, and in breast cancer patients with int-2 and c-erbB-2 amplification. These results suggest that the amplification/expression of these oncogenes may serve as good markers for determining the biological malignancy of cancers.
Gene Amplification↗
[Modified operation for an early stage gastric cancer].
The standard operation for gastric cancer is carried out for advanced gastric cancer with serosal invasion accompanying patent disseminative metastasis to the peritoneum of the omental bursa and lymph node metastases. It consists of subtotal or total gastrectomy, omentobursectomy and extended lymph node dissection. An early stage cancer, which in Japan accounts for almost a half of the resectable cases of gastric cancer, shows no serosal invasion, and lymph node metastases are rare if the cancer remains intramucosal. Such cases represent about a half the cases of the early stage cancer. The diagnosis of the early stage cancer, especially if it remains intramucosal, is made by means of preoperative radiological and endoscopic examinations and intraoperative examination. Since 1977 we have been performing a modified operation as well for cases of the early stage cancer. The surgical procedure is as follows: reduction in the size of gastric resection by 2/3, pylorus-preserving gastrectomy and proximal gastric resection; preservation of the distal portion of the greater omentum and transverse incision of the upper abdomen instead of upper midline incision to prevent ileus due to intestinal adhesion to abdominal wound around umbilicus; sparing bursectomy; narrowing the area of lymph node dissection; sparing thoracotomy for cancer in the esophagogastric junction; sparing splenopancreatectomy; preservation of the hepatic branch of the vagal nerve and postoperative temporary oral administration of cholagogue to prevent postgastrectomy cholelithiasis. In addition, the primary lesion is isolated from the blood circulation by means of ligation of the drainage veins to diminish metastasis through the blood vessels (hepatic metastasis, etc.), which is the main cause recurrence after surgery for the early stage cancer. The results of this new surgery are satisfactory; the five-year postoperative survival rate is 100.0% and it reduced the time needed for surgery, anesthesia and blood transfusion.
Humans↗
[Antitumor activity and toxicity of KB-5424 R, a newly developed antitumor platinum compound].
KB-5424 (ab-(3-aminopyrrolidine)-cd-[glycolato (2-)-0, 0'] platinum (II) is a newly developed antitumor platinum compound which was synthesized at Kanebo Institute for Cancer Research. When the antitumor activity of KB-5424 was evaluated using several rodent tumors, no significant differences were observed between the antitumor activities of KB-5424, cisplatin (CDDP) and DWA-2114 R (DWA). KB-5424 was divided into two kinds of optical isomers, KB-5424 R and KB-5424 S, of which antitumor activity was compared each other. The maximum increased life span (ILSmax) on L 1210 of KB-5424 R was almost equal to that of CDDP and better than those of KB-5424 S and carboplatin (CBDCA). The antitumor activity of KB-5424 R on a human tumor xenograft MX-1 was almost identical to those of CDDP and CBDCA and better than that of DWA. Since the nephrotoxicity of KB-5424 R was significantly reduced comparing with CDDP, this newly developed antitumor platinum compound was thought to be a promising agent for the clinical application.
Animals↗
[Response to rechallenged tamoxifen of metastatic breast cancer relapsed after surgical adjuvant tamoxifen treatment].
Tamoxifen (TAM), an antiestrogen was administered 20 mg b.i.d. to 20 patients with recurrent breast cancer at the time of first relapse who had been treated with the adjuvant therapy including TAM 10 mg b.i.d.. Patients who had been treated with TAM at least 1 year and in which the relapse had occurred after 3 months or more after the cessation of adjuvant treatment were enrolled in the study. Sixteen patients were evaluated, and a complete response was observed in 3 (19%), partial response in 1 (6%), no change in 5 (31%), and progressive disease in 7 (44%). The response rate was shown to be 25% with 95% confidence interval: 3.8-46.2%. The duration of response ranged from 23+ to 32 weeks. Patients who have received postoperative adjuvant therapy including TAM and have relapsed after the cessation of therapy may retain hormone dependency in responding to a further TAM treatment at the time of relapse of malignancy.
Administration, Oral↗
[Experimental combined chemo- and endocrine therapy with UFT and tamoxifen in human breast carcinoma xenografts serially transplanted into nude mice].
We have investigated the experimental combined chemo- and endocrine therapy of UFT and tamoxifen (TAM) on two human breast carcinoma xenografts, R-27 and Br-10 with estrogen receptors (ER) serially transplanted into nude mice. When sc inoculated tumor started the exponential growth, the treatments were initiated in four groups which were control, UFT 20 mg/kg (as tegafur) po daily for 18 times, TAM 5 mg/kg im twice a week for 6 times and UFT + TAM groups. The antitumor activity of the agents were assessed by the growth curves, the lowest T/C ratios of the relative mean tumor weight and the actual tumor weights at the end of the experiments. TAM alone was effective on both R-27 and ineffective on Br-10, while UFT alone was ineffective on R-27 and Br-10. The combination antitumor activity was observed in R-27 but not in Br-10. When 5 mg of TAM per kg and 20 mg of UFT per kg as tegafur was administered daily po for 2 wk, there were no statistically significant differences between the concentration of 5-FU in UFT alone and UFT + TAM groups for the two strains. By the assay of ER and progesterone receptors using the same specimen, it was observed that ER was stable by the treatment of UFT, while ER was suppressed by the treatment of TAM in both tumor strains. In addition, this suppression of ER by TAM alone was enhanced by the combined treatment with UFT in both the strains.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Response function of accelerated monopole detector in R x T3 space-time.
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Journal Article↗
A phase I study of toremifene.
A Phase I study of the new antiestrogenic drug toremifene was carried out in 27 Japanese women, using oral doses of 10-480 mg per day for one or five days. Serum concentrations reached a dose-dependent maximum 2-6 hours after each oral administration. Side effects were generally mild.
Administration, Oral↗
Changes in the hormone receptors of human breast carcinoma xenografts in nude mice by treatment with cytotoxic agents.
We examined the effect of chemotherapeutic agents on the estrogen receptors (ER) of breast carcinomas in vivo using human breast carcinoma strains (Br-10, T-61) serially transplanted into nude mice. When the tumor size reached approximately 1 X 1 X 1 cm, mitomycin C (MMC) at doses of 1, 2 and 4.5 mg/kg and cyclophosphamide (CPA) at a dose of 120 mg/kg, were administered once intraperitoneally, and the ERs of the tumors were measured sequentially by the dextran-coated charcoal method. Four days after the MMC administration at above doses, the binding sites of ER in Br-10 were not reduced and binding affinity was not affected. When the changes in ER content with time after the treatment with 4.5 mg/kg MMC and 120 mg/kg CPA were investigated, the ER content was found to be stable until 4 days after the treatment with both drugs, although the growth of T-61 had been significantly inhibited by the drugs. From these findings, it seems reasonable to initiate chemotherapy before endocrine therapy, since the chemotherapeutic agents did not reduce the ER content of the breast cancer strains.
Animals↗
Postoperative adjuvant immunochemotherapy with mitomycin C, tegafur, PSK and/or OK-432 for gastric cancer, with special reference to the change in stimulation index after gastrectomy.
In order to evaluate the efficacy of combined immunochemotherapy with mitomycin-C, tegafur, PSK and/or OK-432 as an adjunct for curatively resected gastric cancer, a prospective randomized controlled study using the envelope method was performed, in which 266 institutions from around Japan participated. The 3 year survival rates for all cases, and for ps(+).n(+) cases, were insignificantly higher in the immunochemotherapy groups receiving PSK and/or OK-432 than in the control group. However, because 28.2 per cent of the cases were excluded from the final statistical analyses, the results of this study may have questionable statistical credibility. Changes in the stimulation index (SI) suggest that the administration of PSK may result in an inhibition of the immunosuppressive activity of cancer patients. The high SI group showed a significantly higher 4 year survival rate than the low SI group.
Adjuvants, Immunologic↗
The antitumor effects of adriamycin entrapped in liposomes on lymph node metastases.
Adriamycin (ADM) entrapped in liposomes (Lip-ADM) was prepared and its therapeutic effects studied using the mouse leukemia cell line, P388, which metastasized to axillary lymph nodes after inoculation into the foot pads of CDF1 mice. Lip-ADM injections (7.5 mg/kg) were given into the foot pad at two-day intervals. Two series of experiments were performed; one in which Lip-ADM was administered on days 1,3 and 5 following tumor inoculation, and the other in which it was administered on days 5 and 7. Both Lip-ADM injection regimens significantly inhibited metastases to the lymph nodes as compared with mice given injection of saline solution. Furthermore, the therapeutic effects of three Lip-ADM injections were significantly greater than the effects of free ADM. Histological examinations of lymph nodes revealed that three injections of Lip-ADM completely eliminated tumor cells, whereas viable tumor cells were still observed in the lymph nodes after treatment with free ADM. The results of this study suggest that Lip-ADM is useful for the treatment of lymph nodes metastases and that the local injection of Lip-ADM, through such means as endoscopy, would be recommended as a clinical mode of application.
Animals↗
Nude mouse resists hepatic metastasis of the allogeneic tumor, colon-26.
The ability of the host-immune defense mechanism of nude mice and their immunocompetent littermates to prevent liver metastases from the murine colon carcinoma, colon-26, was assessed. Give thousand tumor cells suspended in 0.05 ml of Hank's balanced salt solution were inoculated into the spleens of BALB/c nu/+ and BALB/c nu/nu mice. On the 21st day after inoculation, all the mice were sacrificed, and the liver metastases counted and the livers weighed. All the BALB/c nu/+ mice were found to have developed hepatic metastases with a mean of 10 nodules, whereas no hepatic metastases were observed in any of the 10 BALB/c nude mice. On the other hand, 4 of 6 nude mice developed hepatic metastases after treatment with anti-asialo GM1 antibody. These results indicate that the BALB/c nude mouse has an excellent host-immune defense mechanism for preventing liver metastasis, with NK cells in the liver and/or blood circulation perhaps playing an important role.
Animals↗
Atrial natriuretic polypeptide after burn injury: blood levels and physiological role in rats.
To define the relationship between atrial natriuretic polypeptide and the physiological changes of water and electrolytes after burns, the changes in plasma hormonal levels, including atrial natriuretic polypeptide, and urinary water and sodium excretions were examined in burned rats. Further, to elucidate the physiological significance of atrial natriuretic polypeptide after burns, the effects of a specific antiserum against atrial natriuretic polypeptide were determined in burned rats. Plasma atrial natriuretic polypeptide levels in rats following 30 per cent BSA full skin thickness burns were elevated for sustained periods (432.3 +/- 156.5 pg/ml, P less than 0.01 on day 1 postburn, 244.5 +/- 73.7 pg/ml, P less than 0.05 on day 3 postburn). Urine volume and sodium excretion decreased significantly during the first 72 h after burns. On day 3 postburn, urine volume and sodium excretion began to increase significantly. Specific rabbit antiserum against atrial natriuretic polypeptide was injected into the burned rats during this diuretic phase. Significant inhibition of diuresis and natriuresis was observed after the injection of antiserum (27.5 +/- 2.4 per cen decrease in urine volume, 57.1 +/- 10.4 per cent decrease in sodium excretion). These results suggest that atrial natriuretic polypeptide plays a physiological role in the regulation of urinary water and sodium excretion after burns.
Aldosterone↗
Clinical study of pirarubicin for breast cancer in Japan. Clinical Study Group of THP for Breast Cancer in Japan.
The efficacy and toxicity of (2''R)-4'-O-tetrahydropyranyl adriamycin (THP) were assessed in the treatment of patients with advanced breast cancer by the Japan THP Study Group. Mean plasma levels of THP after single-dose administration revealed triexponential decay characterized by an initial half-life of 0.89 h. A higher concentration of THP was obtained in the metastatic lymph nodes than in the breast cancer tissue at 4 h after administration (4.01 vs. 1.17 micrograms/g). Whereas 1 complete (CR) and 12 partial response (PR) were observed in 56 evaluable patients after administration of THP alone (23.2%), 1 CR and 12 PR were observed in 37 evaluable patients who had combination therapy including THP (35.1%). Multivariate analysis of prognostic factor revealed that the site of metastases had the most valuable prognostic significance; second was irradiation in the previous treatment, and third was the disease-free interval. Life-table analysis adjusted with the Cox proportional hazard model revealed a similar survival curve of patients receiving THP-cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) to that of those receiving CAF only in spite of the low incidence of toxicity in the THP therapy.
Adult↗
Antitumor activity and pharmacokinetics of a morpholino-anthracycline derivative (KRN8602) against human breast carcinoma xenografts serially transplanted into nude mice.
The antitumor activity and pharmacokinetics of (7R, 8S, 10S)-10-((3-deamino- 3-(4-morpholino)-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy)-8- ethyl- 7,8,9,10-tetrahydro-1,6,7,8,11-pentahydroxy-5,12-naphthacenedione hydrochloride (KRN8602) were evaluated using five human breast carcinoma xenografts in nude mice. The maximum non-toxic dose of KRN8602 was 2 mg/kg by q4d x 3 intraperitoneal and peroral administration. KRN8602 showed significant antitumor activity against MX-1, which is less sensitive to adriamycin, with the chemotherapeutic indices of 13.0 for po administration and 9.5 for ip injection. Although KRN8602 also inhibited the growth of T-61 significantly, the antitumor activity of this agent against the other three breast carcinoma xenografts was limited. To elucidate this discrepancy, pharmacokinetic analysis and MTT assay were conducted using the KRN8602-sensitive MX-1 and KRN8602-insensitive R-27. While no differences were observed in the area under the curve and the peak concentration of KRN8602 for each tumor, a difference in the sensitivity of the tumor strains was obvious in MTT assay. The efficacy of this agent seemed to depend on the sensitivity of each type of tumor cell rather than the concentration of agent in tumor tissues. If it were possible to select patients with sensitive tumor cells to this agent by the MTT assay, the phase II trial might be completed within a short period by reducing the number of studied patients.
Animals↗
Release of ANP and its physiological role in pulmonary injury due to HCl.
The effect of pulmonary injury induced by aspiration of HCl on plasma atrial natriuretic polypeptide (ANP) level was examined in rats given a constant infusion of water and electrolytes. In addition, using specific antiserum against ANP, we investigated the physiological role of ANP in rats after HCl aspiration. Rats were housed individually in metabolic cages and were given a constant infusion of sodium solution via catheters chronically inserted into the jugular vein. Plasma ANP levels were elevated at 3 and 24 h after tracheal injection of 0.2 ml of 0.1 N HCl via the cricothyroid membrane. Urine volume and urinary sodium excretion increased during the first 24 h after acid aspiration. However, this increase was reduced by the injection of anti-ANP serum. Furthermore, the injection of anti-ANP serum resulted in a significant (P less than 0.05) increase in wet lung weight from a value of 0.74 +/- 0.06 (HCl aspiration with normal rabbit serum injection) to 0.83 +/- 0.07% of body weight. These results indicate that ANP plays a physiological role in the regulation of urinary water and sodium excretion after pulmonary acid injury and suggest that ANP elevated in plasma after pulmonary injury may prevent pulmonary edema with its diuretic action and/or some direct action on water movement in the lung.
Animals↗
[Phase I study of FK 435].
We performed phase I study of FK 435, a new antiestrogen, in 30 patients with advanced breast cancer. Slight to moderate adverse reactions were noted as follows. Single-dose study: anorexia, nausea, lassitude in one patient (80 mg), decreased serum calcium in one (160 mg), redness, tenderness in one, facial flushing, hot flushes, headache in one (320 mg). Repeated-dose study: anorexia, nausea in one patient (40 mg/day), anorexia, diarrhea, increased FSH in one, increased PRL in one (80 mg/day). FK 435 was well tolerated. Tmax was 3-5 hours, T1/2 about 25 hours. Most of FK 435 was excreted into urine as glucuronide.
Adult↗
[MTT assay using fresh surgical specimens with reference to the transfer system and reproducibility in "test center" method].
A chemosensitivity test (MTT assay) was conducted using 59 fresh surgical specimens collected from Keio University, Kitasato Institute Hospital and 14 affiliated hospitals, in order to assess the specimen transfer system and the reproducibility of the assay results obtained at Keio University and Kitasato Institute Hospital. Although the optical density yielded by the tumor cells in a number of 5 x 10(4)/well and the number of evaluable cases were significantly reduced through the transfer, the chemosensitivity pattern of the specimen was identical before and after the transfer. Fifty seven of 59 cases were evaluable and the concordant rate of the assay results between the two institutes was 80.6% (108/134) among each case-drug combination. Since the transfer system of the specimen was established and the reproducibility of the assay results in two institutes was confirmed, the "test center" method of the MTT assay appears to be possible by collecting the surgical specimens from the affiliated hospitals.
Adult↗