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61.
Tetsuro Kubota Shin Fujita Susumu Kodaira Takaaki Yamamoto Kazuya Josui Yoshito Arisawa Akihiko Suto Kyuya Ishibiki Osahiko Abe Kazunori Mabuchi Makoto Fuse 《Cancer science》1991,82(4):476-482
Experimental chemotherapy with 5-fluorouracil (5-FU; 60 mg/kg), l-hexylcarbamoyl-5-fluorouracil (HCFU; 70 mg/kg), 3-(3-(6-benzoyloxy-3-cyano-2-pyridyloxycarbonyI)benzoyl)-l-ethoxymethyl-5-fluorouracil (BOF-A2; 30 mg/kg) and UFT (20 mg/kg as tegafur with uracil at a molar ratio of 1:4) was performed using human gastric (H-111) and colon (Co-4) carcinoma strains in nude mice. 5-FU was administered ip with a q4d × 3 schedule and the other agents were given po daily for three weeks. Concentrations of 5-FU in the serum and the tumor were assessed by gas chromatography-ntass fragmentography, two hours or 12 days (5-FU) after the last treatment, and thymidy late synthetase (TS) was assayed according to the method of Spears et al. using the same schedule. The antitumor activity of the agents was assessed in terms of the actual tumor weight at the end of the experiment. HCFU was effective against both strains and 5-FU was effective against Co-4, although the other agents were ineffective against either strain. Statistically significant correlations were found between the serum and tumor concentrations of 5-FU and antitumor activity. Statistically significant correlations were also observed between the antitumor activity and TS inhibition rate (TSIR) and the activity of free thymidylate synthetase (TSfree), with higher TSIR and lower TSfree resulting in higher antitumor activity. Therefore, TSIR and TSfree were thought to be promising indicators for predicting the antitumor activity of fluoropyrimidines. 相似文献
62.
Tetsuro Kubota Akihiko Suto Kazuya Josui Kyuya Ishibiki Osahiko Abe Yoshinori Yamada Fumiki Asanuma Eiji Kawamura Jun-ichi Koh Eiichi Shiina Takao Inada Yoshiro Ogata 《Cancer science》1990,81(8):827-833
The antitumor activity and pharmacokinetics of (7 R , 8 S , 10 S )-10-((3-deamino-3-(4-morpholino)-2,3,6-trideoxy-α- 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×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. 相似文献
63.
Osahiko Abe Kazuaki Asaishi Masaru Izuo Kohji Enomoto Hiroki Koyama Takeshi Tominaga Yasuo Nomura Akira Ohshima Nobuo Aoki Toshiyasu Tsukada 《Surgery today》1995,25(8):701-710
The effects of medroxyprogesterone acetate (MPA) therapy on advanced or recurrent breast cancer and its influence on blood coagulation and the fibrinolytic system were compared among three different therapy regimens consisting of cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) + MPA and CAF or MPA alone. A clinical response was observed in 42.9% (9/21) of the patients for CAF + MPA, 36.4% (8/22) for CAF and 23.8% (5/21) for MPA alone. No marked thrombosis or its prodromal condition was observed in any group. The effects on the test values for blood coagulation and the fibrinolytic system did not significantly change in the CAF group. However, both AT-III and protein C significantly increased above the normal ranges in the CAF + MPA and MPA groups. Increases in factor X, plasminogen, and 2-plasmin inhibitor/plasmin complex (PIC) and decreases in fibrinogen, tissue plasminogen activator, and D-dimer, were all observed in the MPA and CAF + MPA groups, especially in the MPA group, although these changes remained within the normal ranges. The data indicated that MPA has various influences on blood coagulation and the fibrinolytic system, but these changes did not suggest activation of the blood coagulation system.Study Group for the Chemo-endocrine Therapy of MPA for Breast Cancer 相似文献
64.
Watanabe Toru; Narabayashi Masaru; Haga Shunsuke; Yamada Yoshinori; Kawamura Eiji; Enomoto Koji; Kusama Mikihiro; Kimura Kousaburo; Adachi Isamu; Abe Osahiko 《Japanese journal of clinical oncology》1993,23(4):246-249
We performed a preliminary phase II clinical trial of MX2; 3'-deamino-3'-morpholino-13-deoxy-10-hydroxycarminomycin (KRN8602) in patients with metastaticbreast cancer who had failed to respond to previous chemotherapeuticregimens after clinical evidence of systemic disease. Twelvepatients at a single institute received KRN8602 at a dose of35 mg/m2 intravenously once every three weeks. All the patientswere folio wed-up until their disease progressed. There wasone complete response lasting 17 weeks and one partial responselasting eight weeks. Among the 12 patients, World Health Organization(WHO) grades 3 and 4 neutropenia were observed in five and twopatients, respectively. Grade 3 anemia was observed in threepatients but severe thrombocytopenia was not observed. Grade3 nausea/vomiting was observed in eight patients. Alopecia wasnot observed. The results of this preliminary phase II trialsuggest a need for further testing of the anti-tumor activityof KRN8602 in patients with metastatic breast cancer. 相似文献
65.
Hiroyuki Konno MD Takushi Tadakuma Koichiro Kumai Takayuki Takahashi Kyuya Ishibiki Osahiko Abe Shukichi Sakaguchi 《Surgery today》1990,20(4):424-428
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 injections
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. 相似文献
66.
Tominaga T Toi M Abe O Ohashi Y Uchino J Hayasaka H Abe R Izuo M Enomoto K Watanabe H Yoshida M Taguchi T Koyama H Senoo T Toge T Monden Y Hattori T Nomura Y Sugimachi K Hirata K Nakazato H Miura S Morimoto T Asaishi K Kimijima I Ota J Sonoo H Yamaguchi S;'-BC Study Group 《International journal of oncology》2002,20(3):517-525
To assess the efficacy of 5'-DFUR, an intermediate of capecitabine, for adjuvant treatment of early breast cancer, we conducted an open-labeled multi-center randomized controlled trial to compare postoperative 5'-DFUR treatment with surgery alone. We enrolled 1217 primary breast cancer patients and randomly assigned them into two treatment groups; one received six-month postoperative 5'-DFUR treatment by consecutive or intermittent administration, and the other surgery alone. Follow-up surveys were conducted once a year for all subjects simultaneously and examined their outcome/presence or absence of the cancer recurrence. The central study committee reviewed all follow-up data and judged the recurrence data to be used for the analysis. Eight-year follow-up data showed no significant differences in relapse-free and overall survival between the two groups, and 5'-DFUR treatment regimen showed an extremely high tolerance. Possible explanations are discussed for the finding of no significant survival difference between adjuvant 6-month 5'-DFUR monotherapy and surgery alone in early breast cancer. 相似文献
67.
The antitumor effects of 5-fluorouracil (5-FU) and its derivatives depend upon the activity of nucleoside metabolic enzymes in tumor tissues. Thymidine phosphorylase (TP) converts 5'-deoxy-5-fluorouridine (5'-DFUR), an intermediate metabolite of capecitabine, to 5-FU. The relationship between TP expression in tumor tissues and patient survival was retrospectively examined in early-stage breast cancer patients treated with either oral 5'-DFUR administered for 6 months or surgery alone in a prospective randomized controlled trial. Thymidine phosphorylase expression in tumor cells and tumor-associated stromal (TAS) cells was examined by immunohistochemistry in 650 tissue samples from patients in this trial (n = 1217). Eight-year follow-up data showed that high TP expression in tumor cells was a significant prognostic indicator of a favorable outcome only for the patients in the 5'-DFUR group. Thus, TP expression was shown to be a predictive factor of 5'-DFUR efficacy. Conversely, a low TP expression in TAS cells was also a potent favorable prognostic indicator. These results on TP status in 2 tumor cell types could provide novel information for predicting prognosis for a patient subgroup, which would receive a probable therapeutic effect from 5'-DFUR, and presumably, from adjuvant therapy of capecitabine in early-stage breast cancer. Determination of TP status might also identify a patient subgroup whose prognosis is quite favorable even without adjuvant therapy. Further investigations on prognostic and predictive implications of TP activity in a clinical setting are warranted. 相似文献
68.
Soji Ozawa MD Nobutoshi Ando Yohtaro Shinozawa Tai Ohmori Kenichi Kase Toshimi Sato Osahiko Abe 《Surgery today》1989,19(1):86-92
Two cases of resected esophageal mucoepidermoid carcinoma are described herein. Case 1, a 56-year-old man, had an ulcerous
lesion of 6.5 cm in length, in the lower esophagus and a small skin tumor of 0.5 cm in diameter, in the forehead. Pathologic
studies of both tumors revealed mucoepidermoid carcinoma. This case was therefore considered to be a primary tumor of the
esophagus with skin metastasis. The patient was alive and well when last seen, 15 months after his operation. Case 2, a 66-year-old
man, had a long ulcerous lesion of 9.0 cm in length, in the mid-thoracic and lower esophagus. The tumor had invaded the aorta
and the membranous portion of the left main bronchus, and therefore complete resection was impossible. The patient died of
mediastinal recurrence only 3 months after his operation in spite of postoperative irradiation. A review of the literature
showed that this tumor has a much greater incidence of rapid recurrence and distant metastasis, regardless of treatment, than
usual squamous cell carcinoma of the esophagus. In order to establish and accurate diagnosis of mucoepidermoid carcinoma,
alcian blue and/or mucicarmin staining of the endoscopic biopsy specimen should be performed if the tumor contains both glandular
and squamous cell carcinoma. 相似文献
69.
Dr. Akio Hara Masahiko Watanabe Susumu Kodaira Tatsuo Teramoto Osahiko Abe En-Cong Gong Setsuo Hirohashi Yukio Simosato 《Diseases of the colon and rectum》1987,30(6):440-443
The epithelial expression of carbohydrate antigen, stage-specific embryonic antigen 1 (SSEA-1) was examined immunohistochemically
in noncancerous specimens from patients with familial polyposis coli, and compared with the colorectal epithelia from patients
with sporadic colorectal cancer. In mucosa remote from carcinoma of sporadic cases, SSEA-1 was expressed only faintly in the
lower crypts. In mucosa adjacent to carcinoma of sporadic cases, SSEA-1 was expressed not only in the lower crypts but also
in the upper crypts. These results corresponded to those observed in the authors' previous study. In the flat mucosa of familial
polyposis coli cases, SSEA-1 was detected not only in the lower crypts, but also in both upper crypts and the surface epithelium
in contrast with the flat mucosa of sporadic cases. The staining pattern in the upper crypts of the flat mucosa of familial
polyposis coli cases was very similar to that of the mucosa adjacent to carcinoma of sporadic cases, but was stronger and
more diffuse in the surface epithelium. In microscopic adenomas, SSEA-1 was expressed diffusely. These results demonstrate
that the flat mucosa of patients with familial polyposis coli shows preneoplastic changes similar to those in the mucosa adjacent
to carcinoma of sporadic cases, and that SSEA-1 is related to adenoma formation in the early stage of carcinogenesis in the
colorectum. In addition, the results suggest that immunohistochemical studies of flat mucosa may be useful for the early detection
of high-risk individuals in a familial polyposis coli family.
Some of the data in this study were presented at the meeting of the XIth Biennial Congress of the International Society of
University Colon and Rectal Surgeons, Dallas, Texas. May 1986.
Supported in part by a grant from Ministry of Education, Science and Culture, Japan. 相似文献
70.
Tetsuro Kubota Koichi Kubouchi Jun-ichi Koh Fumiki Asanuma Koji Enomoto Kyuya Ishibiki Osahiko Abe 《Surgery today》1984,14(1):78-84
Cytotoxic and endocrine therapy on a human breast carcinoma (Br-10) serially transplanted into nude mice was given with reference
to the sequence of drug administration. Mitomycin C (MMC) was combined with 2.5 mg/kg of tamoxifen (TAM). MMC was dissolved
in 0.2 ml of physiological saline and administered intraperitoneally once weekly. TAM was dissolved in 0.1 ml of sesame oil
and administered intramuscularly twice weekly. Both drugs were administered in the reverse sequence for 2 or 3 weeks. Cytosol
estrogen receptor (ERc), nuclear estrogen receptor (ERn) and progesterone receptor (PgR), and3H-thymidine uptake labeling index (L.I.) were assayed after the treatment. When 1.5 mg/kg of MMC was combined with TAM, statistically
significant differences were nil between the different sequential administrations. When the MMC administration was reduced
to 0.75 mg/kg and 2 weeks, respectively, the MMC→TAM sequence was more effective than the reversed sequential administration.
MMC preserved ERc and depressed L.I. to almost half of that of the control tumor. TAM generated the ER systems and slightly
depressed L.I. These different modes of action between MMC and TAM on ER systems and L.I. may explain the antitumor effects
of different sequential administrations. 相似文献