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Biomedical subjects

Y Takatsuka

Publications and source records attributed to Y Takatsuka.

At least 37 records · Page 2Linked to original sources
PubMed1999

Prospective Randomized Study of Cyclophosphamide, Epirubicin, and 5-Fluorouracil versus Cyclophosphamide, Adriamycin, and 5-Fluorouracil in Advanced or Recurrent Breast Cancer.

BACKGROUND: Treatment with cyclophosphamide, adriamycin, and 5-fluorouracil (CAF), a widely used, potent regimen is sometimes restricted by the myelotoxicityand myocardiotoxicity of adriamycin (ADR). In a prospective randomized controlled study of patients with advanced or recurrent breast cancer, the efficacy and toxicity of a CEF regimen, in which epirubicin (EPI) was substituted for ADR, was compared with CAF. METHODS: 138 female patients under 75 years of age who had unresectable or recurrent breast cancer during the period from October, 1989 to September, 1991, were randomized to one of two treatment regimens. The first regimen consisted of cyclophosphamide 100 mg p.o. d1-14, adriamycin 30 mg/m(2) i.v. d1, 8 and 5-fluorouracil 500 mg/m(2) i.v. d1, 8 (CAF). In the second regimen, EPI 30 mg/m(2) i.v. d1, 8was substituted for ADR (CEF). Both regimens were delivered q4 weeks. RESULTS: Of 138 patients, 105 (CEF 56, CAF 49) were evaluable for response and survival, and all were evaluable for toxicity (CEF 68, CAF 70). The median course of lots CEF and CAF was 3 cycles. Response rates (complete response plus partial response) with CEF and CAF were 35.7% (20/56) and 36.7% (18/49), respectively. Adverse effects were similar in the two groups, but severe leukopenia (CEF 36.8%, CAF 64.3%) and hepatic toxicity (CEF 1.5%, CAF 12.9%) were encountered more frequently with CAF than with CEF. The duration of 50% survival was 135.9 weeks for CEF and 172.1 weeks for CAF (not significant). CONCLUSION: At an equal dose of EPI and ADR response rates and survival of the CEF group were similar to those of the CAF group, but adverse effects were fewer in the CEF group.

Journal Article↗
PubMed1999

Myelodysplastic syndrome in a patient with adult T-cell leukaemia.

A 53-year-old female who developed myelodysplastic syndrome (MDS) after chemotherapy for adult T-cell leukaemia (ATL) is described. The latent period of therapy-related MDS (t-MDS) from the time of diagnosis of ATL was approximately 35 months. Cytogenetic analysis of the bone marrow cells at the time of diagnosis of t-MDS revealed a clonal abnormality; 46,XX,add(7)(p13), der(17)t(3;17)(p11;p13). Although monoclonal integration of human T lymphotropic virus type I (HTLV-I) proviral DNA was detected in the peripheral blood lymphocytes at ATL diagnosis, bone marrow cells at t-MDS diagnosis did not show monoclonal integration of HTLV-I. To our knowledge, this is the first report of t-MDS associated with ATL.

Adolescent↗
PubMed1999

Novel characteristics of Selenomonas ruminantium lysine decarboxylase capable of decarboxylating both L-lysine and L-ornithine.

Lysine decarboxylase (LDC; EC 4.1.1.18) of Selenomonas ruminantium is a constitutive enzyme and is involved in the synthesis of cadaverine, which is an essential constituent of the peptidoglycan for normal cell growth. We purified the S. ruminantium LDC by an improved method including hydrophobic chromatography and studied the fine characteristics of the enzyme. Kinetic study of LDC showed that S. ruminantium LDC decarboxylated both L-lysine and L-ornithine with similar Km and the decarboxylase activities towards both substrates were competitively and irreversibly inhibited by DL-alpha-difluoromethylornithine, which is a specific inhibitor of ornithine decarboxylase (EC 4.1.1.17). We also showed a drastic descent of LDC activity owing to the degradation of LDC at entry into the stationary phase of cell growth.

Amino Acid Sequence↗
PubMed1999

Identification of the amino acid residues conferring substrate specificity upon Selenomonas ruminantium lysine decarboxylase.

Lysine decarboxylase (LDC, EC 4.1.1.18) from Selenomonas ruminantium has decarboxylating activities towards both L-lysine and L-ornithine with similar K(m) and Vmax. Here, we identified four amino acid residues that confer substrate specificity upon S. ruminantium LDC and that are located in its catalytic domain. We have succeeded in converting S. ruminantium LDC to an enzyme with a preference in decarboxylating activity for L-ornithine when the four-residue of LDC were replaced by the corresponding residues of mouse ornithine decarboxylase (EC 4.1.1.17).

Amino Acid Sequence↗
PubMed1999

[Pharmacological study of weekly docetaxel in patients with metastatic breast cancer].

A pharmacological comparison of weekly administrations of docetaxel (TXT) and standard/conventional TXT was carried out among patients with metastatic breast cancer. Fifteen patients were enrolled in this study of weekly TXT (TXT: 40 mg/body/week x 3 with 1 week interruptions in 10 patients) and standard TXT (TXT: 60 mg/m2/3 weeks in 5 patients). The median dose intensity (DI) of weekly TXT (20.63 mg/m2/week) was similar to that of standard TXT, and the median relative dose intensity (RDI) of weekly TXT was 0.98. The median area under the plasma concentration-time curve (AUC) of weekly TXT (1.20 micrograms.h/ml) was smaller than that of standard TXT (1.87 micrograms.h/ml). Therefore, there were remarkable decreases in both median percent of decrease in neutrophil counts and grade 3, 4 neutropenia with weekly TXT. These pharmacological data show that weekly TXT is a well-tolerated and feasible schedule for the treatment of metastatic breast cancer.

Adult↗
PubMed1999

[The efficacy and limitation of hepatic arterial infusion chemotherapy for colorectal liver metastases].

We investigated the efficacy and limitation of hepatic arterial infusion (HAI) chemotherapy for colorectal liver metastases. In terms of prophylactic HAI following curative resection of liver, the 5-year disease-free survival of HAI group (12 g of 5-FU administered in 6 weeks) was 66.7%, whereas that of randomly selected control group was 20.0%. The difference was statistically significant (p = 0.045). Recurrent disease was confirmed in three cases of HAI group (one in liver) and in 8 patients of the control group (6 in liver). However, the overall survival was not significantly different between the groups. Thus, the short-term HAI of 5-FU is effective in decreasing the recurrence of disease. As for the treatment of unresectable liver metastases, some patients received HAI of 5-FU (1,000-1,500 mg/w) showed prolonged survival with partial remission of the disease. However, the 1-, 2-, and 3-year cumulative survival of HAI group (n = 27) was 69.3, 34.1 and 11.4%, respectively, against 61.3, 22.6 and 9.4%, respectively, in the transarterial embolization (TAE) group (n = 31). Therefore it is important to estimate the effect in the early phase of HAI, and aggressively continue the treatment in selected patients for whom it is suitable.

Administration, Oral↗
PubMed1998

Mucocele-like Tumor of the Breast: A Case Report and Assessment of Aspirated Cytological Specimens.

BACKGROUND: Mucocele-like tumor(MLT)is a rare benign condition, and ofter misdiagnosed as mucinous carcinoma. METHODS: We encountered a 31-year-old woman with MLT of the breast. The patient presented with an elastic hard mass, 0.5cm in diameter, located in the upper outer quadrant of the right breast. RESULTS: Physical examination as well as ultrasonography and mammography indicated a benign lesion. However, mucinous carcinoma was suspected based on aspiration biopsy cytology. MLT was finally diagnosed on excisional biopsy. CONCLUSION: Awareness of this breast disease helps to prevent misdiagnosis and unnecessary surgery.

Journal Article↗
PubMed1998

The Current Status of the Treatment of Ductal Carcinoma In Situ of Japanese Women, Especially Breast Conserving Operation in Relation to the Surgical Margin and Short Term Outcome.

The indications for a breast conserving operation in the treatment of ductal carcinoma in situ (DCIS) of the breast with clinical manifestations other than mammographically detected calcifications are controversial. A positive surgical margin has been suggested to be an improtant risk factor for local recurrence after a breast conserving operation. We attempted to clarify the frequency of positive surgical margins when performing breast conserving operations for DCIS, identify the risk factors for positive margins, and also to evaluate the short-term outcome. Between 1988 and 1992, 5571 breast cancer cases were surgically treated at the 7 institutions of the authors, of which 375 cases (6.7%) were histologically diagnosed as DCIS. The most frequent clinical manifestation was a tumor in 64% of the cases, followed by nipple discharge in 23% and calcification on mammography in 12%. Of these 375 cases, 242 cases were analyzed. Sixty-six cases had undergone a breast conserving operation. Axillary dissection was not performed in 29 cases. The median follow up period was 61.4 months. The initial surgical margin was positive in 29% of the cases. The most significant factor for a positive surgical margin was young age fllowed by large tumor size. There were four cases with local recurrence. Three recurrences developed in the same quadrant. All four cases remain alive after total mastectomy. There were no cases with distant metastasis or axillary recurrence. Breast cancerving operation for DCIS have shown satisfactory results to date, and when clear surgical margins can be obtained, this procedure, without axillary dissection, should be considered even for patients with clinical manifestations other than mammographically detected calcifications.

Journal Article↗
PubMed1998

Granulocyte colony-stimulating factor in the combination chemotherapy for adult T-cell leukemia (ATL).

We evaluated the effect of granulocyte colony-stimulating factor (G-CSF) on the median survival of 17 patients with Adult T-cell leukemia (ATL). Standard-dose combination chemotherapy using the response-oriented cyclic multidrug (RCM) protocol with G-CSF (lenograstim 2 microg/kg/day or filgrastim 50 microg/m2/day) was administered between October 1990 and December 1994. Complete responses (CR) were achieved in 11 (64.7%) patients, and partial responses (PR) in 4 (23.5%) patients. The median duration of survival was 7.4 months, compared with 6.0 months in ATL patients treated with the RCM protocol alone (historical controls) (n.s.). Infectious complications were the cause of death in 4 (26.7%) of the 15 patients who died. The median duration of neutropenia (absolute neutrophil count < 1.0 x 10(9)/L) was 6 days. G-CSF, in the doses and schedules used here, may have shortened the duration of neutropenia and reduced the incidence of fatal infectious complications. However, concomitant use of G-CSF did not prolong the median duration of survival in patients with ATL treated according to the RCM protocol.

Adjuvants, Immunologic↗
PubMed1998

[Treatment strategy for recurrent breast cancer].

In recent years, many kinds of efficacious modalities have been available for the treatment of recurrent breast cancer. Endocrine therapy is essentially the treatment of choice for both premenopausal and postmenopausal patients. The recommended sequence of endocrine therapies is described as follows: In premenopausal women, ovarian ablation (LH-RH agonists) is considered the first-line therapy, with tamoxifen (TAM) and aromatase inhibitors (AI) as the second-line alternatives. In postmenopausal women, the recommended first and second-line therapy is TAM and AI, respectively. Medroxyprogesterone acetate (MPA) should be used as the third-line agent, irrespective of menopausal status. However, efficacy of combinations such as LH-RH agonist plus TAM for premenopausal women and TAM plus AI for the postmenopausals is still uncertain. Patients with rapidly progressing and/or endocrine-resistant tumor should be treated with anthracycline containing regimen such as CAF (cyclophosphamide, adriamycin, 5-fluorouracil). As for the palliative modality, chemotherapy (CAF, doxifluidine) combined with MPA has resulted in improved QOL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Prognostic impact of urokinase-type plasminogen activator (PA), PA inhibitor type-1, and tissue-type PA antigen levels in node-negative breast cancer: a prospective study on multicenter basis.

Urokinase-type plasminogen activator (u-PA) is a key protease in cancer invasion and metastasis. Recent studies demonstrated that u-PA, plasminogen activator inhibitor type-1 (PAI-1), and tissue-type plasminogen activator (t-PA) are prognostic factors in breast cancer. However, there have been no prospective studies of node-negative breast cancer on a multicenter basis. On the other hand, some patients, even those with node-negative breast cancer, developed recurrence, and only tumor size is available as a predicting factor in this group. Therefore, it is necessary to find other prognostic factors in node-negative breast cancer to determine suitable adjuvant therapies. Tissue samples in this prospective study were obtained from 130 patients with node-negative invasive breast cancer who underwent radical operation at four hospitals. The median follow-up was 52.6 months. u-PA, PAI-1, and t-PA antigen levels were assayed by ELISA kits using the cytosolic fractions of tumors. Patients with high u-PA, high PAI-1, or low t-PA had significantly higher relapse rates than did those with low u-PA, low PAI-1, or high t-PA, respectively, by the Kaplan-Meier method (P = 0.006, 0.032, and 0.028, respectively). Analyses of the combinations of both u-PA and PAI-1 or both u-PA and t-PA showed that the differences in relapse rate between the high- and low-risk groups were statistically very significant. In the univariate analysis, u-PA, PAI-1, t-PA, progesterone receptor, and tumor size (T3 versus T1) were significantly correlated with relapse. However, the multivariate analysis revealed that only u-PA (P = 0.023) was an independent prognostic factor. This study showed that u-PA was a new significant independent prognostic factor in node-negative breast cancer.

Adult↗
PubMed1998

[Intra-arterial chemotherapy to improve quality of life in cases of unresectable advanced or recurrent breast cancer].

We performed repetitive intra-arterial infusion chemotherapy (I.A.) with epirubicin in order to improve the quality of life (QOL) in 3 cases with locally advanced or recurrent breast cancer which were diagnosed as surgically unresectable and seemed uncontrollable by outpatient systemic chemotherapy. The patients were admitted to our hospital for chest wall invasion, lymph node metastasis, bleeding, pain, or edema in upper extremity. Therapeutic effects included 1 case of CR and 2 cases of PR in the primary site, and similar effects were obtained in metastasized lymph nodes. We could perform mastectomy in both of the 2 cases with locally advanced cancer after I.A., Although leukocytopenia, which was the dose limiting factor in this regimen, was observed in all 3 cases, it was Grade 2 or 3 and recovered by G-CSF. With regard to their QOL, symptoms which had driven them to inpatient treatment remarkably improved in all of the cases. Thus, after 2 series of I.A. they could receive maintenance systemic chemotherapy as outpatients. Our findings showed that the I.A. as a local control treatment in patients with unresectable advanced or recurrent breast cancer is useful for the improvement of their QOL.

Antibiotics, Antineoplastic↗
PubMed1998

[Long-term survival in a case of multiple liver metastasis from postoperative gastric cancer effectively treated by hepatic intraarterial infusion chemotherapy using MMC and pirarubicin].

We experienced a case of multiple liver metastasis from postoperative gastric cancer who showed long-term survival with hepatic arterial infusion chemotherapy (HAI) of MMC and pirarubicin. A catheter was inserted into the hepatic artery, and 4 mg of MMC and 20 mg of pirarubicin were administered through an implantable port catheter every two to four weeks. The total dose of MMC and pirarubicin by the time of this report was 164 mg and 820 mg, respectively. The follow-up CT scan 2 months after the beginning of HAI showed a decrement of the liver tumors. The decrease rate at 12 and 17 months was 50% and 70%, respectively, which was diagnosed as partial response (PR). The therapeutic effect at 49 months is still PR without any sign of tumor enlargement of extra hepatic lesion.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

[Effects of intravenous infusion of 5-FU and intraperitoneal injection of low-dose CDDP on 3 cases with ascites owing to peritonitis carcinomatosa of postoperative gastric carcinoma and debility].

We examined the effects of intravenous infusion of 5-FU and intraperitoneal injection of low-dose CDDP on 3 cases with ascites owing to peritonitis carcinomatosa of postoperative gastric carcinoma and debility. Intravenous infusion of 5-FU (250-1,000 mg/body) and intraperitoneal injection of CDDP (20-25 mg/body) carried out for 2-5 days. As a result, QOL of 3 cases was fairly improved. The PS (Performance Status) of 2 cases improved from Grade 4 to 2, and another one improved from Grade 4 to 3. Adverse effects of Grade 1 according to the WHO criteria were observed in 1 case (leukocytopenia and diarrhea). This palliative chemotherapy method appeared to be safe and effective for ascites due to peritonitis carcinomatosa of postoperative gastric carcinoma and debility.

Aged↗
PubMed1998

[A case of locally advanced breast cancer successfully treated with intra-arterial infusion chemotherapy of high-dose epirubicin].

A case of locally advanced breast cancer was treated with intra-arterial infusion chemotherapy using high-dose epirubicin. The 1st and 2nd cycle consisted of 210 mg (day 1, 4, 7) and 150 mg (day 1, 4, 7), respectively. After completion of 2 cycles of the regimen, remarkable loco-regional control and improved QOL were obtained. Leucopenia (nadir; 1,000/mm3) was the dose limiting factor, but well-tolerated with supportive therapy. The patient underwent salvage surgery and maintenance intra-venous chemotherapy (epirubicin; 30 mg/3 weeks). At this writing, the patient is enjoying favorable QOL. These findings suggested that this modality was effective for cases with exctensive loco-regional involvement.

Antibiotics, Antineoplastic↗
PubMed1997

A prospective study on the prognostic significance of urokinase-type plasminogen activator levels in breast cancer tissue.

Urokinase-type plasminogen activator (u-PA), which cleaves plasminogen to yield plasmin, is a serine protease of fibrinolysis and is presumed to play a key role in extracellular proteolysis and facilitate the migration of cancer cells. This study was conducted prospectively to evaluate the prognostic significance of u-PA antigen level in breast cancer tissues. u-PA concentrations in the cytosol of 226 breast cancer tissues were determined prospectively by enzyme-linked immunosorbent assay using cytosol fractions prepared for steroid hormone assay. The median follow-up period of the patients was 60 months. Various prognostic factors were evaluated by univariate analysis or multivariate analysis using the Cox proportional-hazards method. Patients with primary breast cancer containing high levels of u-PA had a significantly shorter disease-free survival than patients with low levels of u-PA antigens. In multivariate analysis, a high level of u-PA was an independent risk factor for disease-free survival, being independent of age, axillary node status, and estrogen receptor status. Among the major prognostic factors, a high u-PA antigen level, lymph node involvement, and a positive estrogen receptor status were the most important for predicting relapse-free survival (P = 0.044, P < 0.0001, P = 0.0039). This first prospective study confirmed the prognostic significance of the u-PA antigen level in association with other major prognostic factors. The results of our present study suggest that u-PA in breast cancer tissue might be involved in breast cancer invasion and metastasis.

Age Factors↗
PubMed1997

Midkine expression in human breast cancers: expression of truncated form.

The expression of midkine (MK), a growth/differentiation factor, was assessed in 34 surgically resected specimens of primary breast cancer or mastopathy. Using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, all of the non-cancerous and cancerous tissues were found to express MK except for one breast cancer specimen. Northern blot analysis revealed that MK mRNA was also expressed in the normal breast tissues examined. Immunohistochemical analysis of the MK protein was performed on a limited number of the specimens, showing that some cancerous tissues were immunoreactive with anti-MK antibodies. Furthermore, using RT-PCR analysis, expression of not only the wild-type but also a truncated form of MK, which was recently found in various human tumor cell lines, was detected in 6 of 26 cancerous tissues but not in non-cancerous tissues.

Blotting, Northern↗