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Biomedical subjects

Y Takatsuka

Publications and source records attributed to Y Takatsuka.

At least 19 recordsLinked to original sources
PubMed2002

Phase II study of weekly docetaxel in patients with metastatic breast cancer.

BACKGROUND: This study was conducted to investigate the efficacy and toxicity of weekly docetaxel administration in patients with metastatic breast cancer. PATIENTS AND METHODS: Thirty-seven women were treated with 1 h infusions of docetaxel at 40 mg/m2/week after pre-medication with 8 mg dexamethazone. Each cycle consisted of three consecutive weekly treatments followed by a 1 week rest. All patients were assessed for toxicity; five patients were not assessable for clinical response, time to progression (TTP) and overall survival (OS) because of early treatment failure, but they were included in intention-to-treat analysis. RESULTS: Patients received a median of four cycles (range, 1-9), with a median dose intensity of 28 mg/m2/week (range 22-30) and a median relative dose intensity of 0.95 (range 0.73-1.0). No patients showed complete response, whereas 14 had partial response, which accounted for 38% of objective response rate [95% confidence interval (CI) 22% to 53%]. In addition, three patients (8%, 95% CI 0% to 17%) had stable disease over 6 months. Clinical responses were achieved at a median of three cycles (range 1-4 cycles). The median TTP and OS were 5 and 12 months, respectively. The weekly docetaxel regimen was generally well tolerated. About half of the patients experienced grade > or = 1 neutropenia; only 19% had grade 3/4 neutropenia, including one case of grade 4. No febrile neutropenia was observed and fluid retention syndrome was uncommon. Non-hematologic toxicity, however, such as asthenia/fatigue, nail damage, tearing or hearing disorders, was seen with successive treatment cycles. CONCLUSIONS: Weekly docetaxel at 40 mg/m2/week is an active and feasible regimen for patients with metastatic breast cancer.

Adult↗
PubMed2002

Successful treatment for leg ulcers due to hydroxyurea in a patient with chronic myelogenous leukaemia.

A 51-year-old male who had intractable leg ulcers during treatment for chronic myelogenous leukaemia with hydroxyurea (HU) is reported. His leg ulcers were treated by application of tretinoin tocoferil (TT) ointment after surgical debridement; good results were obtained. Although stopping HU administration is vitally important, surgical debridement and TT application are effective for treating leg ulcers due to HU.

Antineoplastic Agents↗
PubMed2001

Improved outcome of adult T cell leukemia/lymphoma with allogeneic hematopoietic stem cell transplantation.

Adult T cell leukemia/lymphoma (ATL) is a poor prognosis T cell malignancy. In order to improve the outcome, we employed allogeneic stem cell transplantation (allo-SCT) for ATL in 10 patients, nine of whom were from HLA-identical siblings and one from an unrelated donor. Conditioning regimens varied among the patients except that all received total body irradiation. The patients tolerated the regimens well with mild, if any toxicity, and engraftment occurred in all cases. Median leukemia-free survival after allo-SCT was 17.5+ months (range 3.7-34.4+). Six of the 10 patients developed acute GVHD (one case each with grade I, III or IV, and three cases with grade II) and three patients developed extensive chronic GVHD. Four patients died after allo-SCT during the study period from either acute GVHD (grade IV), pneumonitis, gastrointestinal bleeding or renal insufficiency. Two of the 10 cases with no symptoms of GVHD relapsed with clinical ATL. These results strongly suggest that allo-SCT may improve the survival in ATL if a controlled degree of GVHD develops.

Adult↗
PubMed2000

Limited but definite efficacy of prophylactic hepatic arterial infusion chemotherapy after curative resection of colorectal liver metastases: A randomized study.

BACKGROUND: Greater than 50% of patients who undergo curative resection of liver metastases from colorectal carcinoma develop recurrent disease in the residual liver. Although several studies have attempted to use hepatic arterial infusion (HAI) chemotherapy to prevent recurrence, to the authors' knowledge the efficacy of the treatment has not yet been determined. METHODS: Nineteen patients who underwent curative hepatectomy for metastatic colorectal carcinoma randomly were assigned into the HAI group (nine patients) or the control group (ten patients). Patients in the HAI group received continuous intraarterial infusion of 5-fluorouracil (5-FU) (500 mg/day) for 4 days followed by a 3-day rest. The treatment was continued for 6 weeks. RESULTS: The median follow-up period was 62.2 months. The recurrence was confirmed in three patients in the HAI group and in eight patients in the control group. Of these, recurrence in the remnant liver was observed in one patient and in six patients, respectively. The median disease free interval after hepatectomy was 62.6 months in the HAI group and 13.8 months in the control group. The 1-year, 2-year, and 3-year disease free survival rates were 77.8%, 77.8%, and 66.7%, respectively, in the HAI group and 50.0%, 30.0%, and 20.0%, respectively, in the control group. Significant prolongation of disease free survival was observed in the HAI group (P = 0.045). No patients in the HAI group reported any adverse effect of >/= Grade 2 (according to the National Cancer Institute Common Toxicity Criteria). Two patients in the HAI group and five patients in the control group were dead of disease at the time of last follow-up. The 1-year, 3-year, and 5-year cumulative survival rates for the HAI group were 88.9%, 77.8%, and 77.8%, respectively, whereas those of the control group were 100.0%, 50.0%, and 50.0%, respectively (P = 0.2686). CONCLUSIONS: This randomized study revealed that short term HAI of 5-FU after curative resection of colorectal hepatic metastases is effective in preventing the recurrence of disease without any serious complications.

Administration, Oral↗
PubMed2000

Optimal management of the axilla in patients with breast cancer.

BACKGROUND: Although most surgeons perform some form of axillary lymph node dissection (ALND) as part of locoregional management of operable breast cancer, the extent of dissection remains controversial. PATIENTS AND METHODS: Observation of the axilla trial (protocol I) and partial dissection trial (protocol I) began in January 1996. Between January 1996 and May 2000, 45 post-menopausal and 207 women with clinically node-negative breast cancer were enrolled into protocol I and protocol II respectively. RESULTS: The 4-year cumulative incidence rate of axillary recurrence was 7% in patients with untreated the axilla. The 4-year overall survival rate was 98% in patients with untreated the axilla. The 4-year disease-free and overall survival rates were 96% and 98% respectively in patients treated with partial dissection. CONCLUSION: Total axillary dissection seems to be unnecessary in Japanese breast cancer patients with relatively small tumors.

Adult↗
PubMed2000

Gene cloning and molecular characterization of lysine decarboxylase from Selenomonas ruminantium delineate its evolutionary relationship to ornithine decarboxylases from eukaryotes.

Lysine decarboxylase (LDC; EC 4.1.1.18) from Selenomonas ruminantium comprises two identical monomeric subunits of 43 kDa and has decarboxylating activities toward both L-lysine and L-ornithine with similar K(m) and V(max) values (Y. Takatsuka, M. Onoda, T. Sugiyama, K. Muramoto, T. Tomita, and Y. Kamio, Biosci. Biotechnol. Biochem. 62:1063-1069, 1999). Here, the LDC-encoding gene (ldc) of this bacterium was cloned and characterized. DNA sequencing analysis revealed that the amino acid sequence of S. ruminantium LDC is 35% identical to those of eukaryotic ornithine decarboxylases (ODCs; EC 4.1.1.17), including the mouse, Saccharomyces cerevisiae, Neurospora crassa, Trypanosoma brucei, and Caenorhabditis elegans enzymes. In addition, 26 amino acid residues, K69, D88, E94, D134, R154, K169, H197, D233, G235, G236, G237, F238, E274, G276, R277, Y278, K294, Y323, Y331, D332, C360, D361, D364, G387, Y389, and F397 (mouse ODC numbering), all of which are implicated in the formation of the pyridoxal phosphate-binding domain and the substrate-binding domain and in dimer stabilization with the eukaryotic ODCs, were also conserved in S. ruminantium LDC. Computer analysis of the putative secondary structure of S. ruminantium LDC showed that it is approximately 70% identical to that of mouse ODC. We identified five amino acid residues, A44, G45, V46, P54, and S322, within the LDC catalytic domain that confer decarboxylase activities toward both L-lysine and L-ornithine with a substrate specificity ratio of 0.83 (defined as the k(cat)/K(m) ratio obtained with L-ornithine relative to that obtained with L-lysine). We have succeeded in converting S. ruminantium LDC to form with a substrate specificity ratio of 58 (70 times that of wild-type LDC) by constructing a mutant protein, A44V/G45T/V46P/P54D/S322A. In this study, we also showed that G350 is a crucial residue for stabilization of the dimer in S. ruminantium LDC.

Amino Acid Sequence↗
PubMed1999

Surgical Margin Status as a Cause of Local Failure after Breast Conserving Therapy.

BACKGROUND: To elucidate the cause of in-breast recurrence after breast conserving surgery, we analyzed the characteristics of resected specimens histopathologically, especially the surgical margin status. MATERIALS AND METHODS: 1) Pathological surgical margin positivity was reevaluated in terms of the distance from the resected surgical margin by pathologists from seven institutions in 486 cases with complete stepwise pathological examination. 2) We reviewed pathological specimens including surgical margins from 30 patients with in-breast recurrence for whom serial sections of resected primary breast cancer specimens were available and made comparisons of the time to in-breast recurrence. RESULTS: Cancer cells at the surgical margin were present at a rate of 4.1% on the surface and 15.2% within 5 mm on the areolar side of the surgical margin. Histopathologically, the reasons for local recurrence after breast conserving therapy included a positive surgical margin (21/30), lymphatic permeation (4/30), and others (5/30). The last category included cases with an inadequate margin diagnosis because of a biopsy scar. Disease-free intervals for the patients without postoperative radiotherapy decreased as the volume of cancer cell nests in thesurgical margin increased (P=0.06). On the other hand, this trend was not observed in the group with postoperative radiotherapy. CONCLUSION: Adequate materials are essential for accurate evaluation of surgical margin status. Quantitative evaluation of surgical margin status, apart fromwhether or not radiotherapy was performed, is important for estimating the riskand disease-free period to in-breast recurrence.

Journal Article↗
PubMed1999

A Retrospective Study of Breast Cancer Patients Treated with Quadrantectomy without Radiation Therapy.

BACKGROUND: Radiation therapy after breast-conserving surgery (BCS) reduces the risk of local recurrence. However, whether radiation therapy is necessary forall patients undergoing BCS remains unclear. METHODS: In order to determine the selection criteria for patients who can safely omit radiation therapy and to confirm the survival benefit of quadrantectomy without radiation therapy, we reviewed 107 patients who underwent quadrantectomy without radiation therapy between February 1988 and July 1995. RESULTS: The 5-year overall survival, disease-free survival and cumulative local recurrence rates were 93.7%, 80.7% and 12.1% respectively. There were no significant differences of 5-year overall survival (94.0% vs 94.1%) and disease-free survival rates (83.1% vs 70.0%) between patients with or without tamoxifen. The 5-year cumulative local recurrence rate of patients with tamoxifen, however, tended to be lower (p = 0.0810) than that of patients without tamoxifen. The 5-year cumulative local recurrence rate of the patients aged 45 or less was significantly higher than that of patients aged from 45 to 55 years and those over 55 (p= 0.0090 and 0.0089, respectively). In ER positive patients, the 5-year cumulative local recurrence rate of patients with tamoxifen tended to be lower (p= 0.0791) than that of patients without tamoxifen. CONCLUSION: The survival rate of quadrantectomy without radiation therapy wasacceptable. While the risk of local recurrence following quadrantectomy withoutradiation therapy is substantial, radiation therapy following quadrantectomy might not be necessary in elderly ER positive women receiving adjuvant tamoxifen therapy.

Journal Article↗
PubMed1999

A Case of Advanced Breast Cancer Successfully Treated with Primary Endocrine Therapy.

We present a case of a premenopausal woman with advanced hormone-sensitive breast cancer who was successfully treated with primary endocrine therapy consisting of ovarian ablation followed by a combined endocrine regimen of the aromataseinhibitor fadrozole 2 mg daily and tamoxifen 20 mg daily. During the 5 months treatment period, PR evaluation of the loco-regional lesions was performed. The patient then underwent mastectomy with axillary lymph node dissection followed byfadrozole and tamoxifen therapy. Throughout the treatment course, no adverse events were encountered and the patient has been enjoying a favorable quality of life. As shown by this case, primary endocrine therapy is a promising treatment option for hormonesensitive breast cancer. However, this modality should be continued to be regarded as experimental.

Journal Article↗
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↗