Biomedical subjects

Shinzaburo Noguchi

Publications and source records attributed to Shinzaburo Noguchi.

At least 55 records · Page 3Linked to original sources

PubMed2004

Preoperative evaluation of prognosis in breast cancer patients by [(18)F]2-Deoxy-2-fluoro-D-glucose-positron emission tomography.

PURPOSE: [18F]2-Deoxy-2-fluoro-D-glucose (FDG)-positron emission tomography (PET) was applied to breast cancer patients for the purpose of preoperative evaluation of patient prognosis with more accuracy than conventional TNM staging. METHODS: FDG-PET was performed preoperatively in 81 patients with breast cancer, and the maximum standardized uptake value (SUVmax) of tumors as well as the focal accumulation of FDG in the axillary region (PET-N status) were investigated in their association with patient prognosis. RESULTS: The SUVmax high group (n=40) showed a significantly (P=0.011) poorer prognosis than the SUVmax low group (n=41) (5-year disease-free survival (DFS) rates; 75.0% vs 95.1%). FDG-PET was more accurate in the diagnosis of axillary lymph node status than physical examination, i.e., diagnostic accuracy was 80% and 70% for FDG-PET and physical examination, respectively. The combination of high SUVmax and positive PET-N (+) was shown to be a highly significant risk factor being independent of the clinical T and N factors, i.e., patients with high SUVmax and positive PET-N (+) showed a significantly (P<0.001) poorer prognosis than the other patients (5-year DFS rates; 44.4% vs 96.8%). CONCLUSIONS: These results suggest that FDG-PET is useful in the preoperative evaluation of prognosis in breast cancer patients with more accuracy than conventional TNM staging. It is expected that the indication of neoadjuvant chemotherapy can be decided more precisely by the preoperative evaluation of patient prognosis with FDG-PET due to a possible elimination of overtreatment for those who have good prognosis and, thus, need not to be treated with chemotherapy.

Adult↗

PubMed2004

A phase II study of S-1 in patients with metastatic breast cancer--a Japanese trial by the S-1 Cooperative Study Group, Breast Cancer Working Group.

BACKGROUND: S-1 is a newly developed novel oral dihydrouracil dehydrogenase inhibiting fluoropyrimidine drug consisting of 1 M tegafur (FT), 0.4 M 5-chloro-2, 4-dihydroxypyrimidine (gimeracil), and 1 M potassium oxonate (oteracil), with efficient antitumor activity and low gastrointestinal toxicity which is widely used in Japan against advanced gastric, head and neck cancers. We investigated its clinical efficacy against metastatic breast cancer. METHODS: A non-blind phase II study was carried out to evaluate the efficacy and toxicity in metastatic breast cancer patients. Patients with measurable metastasis foci (n=111) were enrolled, and 108 patients were regarded as eligible. S-1 was administered orally at a standard dose of 80 mg/m2/day b.i.d. One course consisted of 28 consecutive days of administration followed by a 14-day rest, and courses were repeated up to six times. RESULTS: Among the eligible patients, 10 had a complete response and 35 had a partial response, with an overall response rate (CR+PR) of 41.7% (95% confidence interval: CI, 32.3-51.5%). The incidences of toxicity (> or =grade 3) were neutropenia 9.1%, anemia 0.9%, anorexia 3.6%, stomatitis 1.8%, nausea/vomiting 1.8%, diarrhea 0.9%, and fatigue 2.7%, however no treatment-related deaths were observed. The median survival time was 872 days (95% CI, 572-1,110 days). There was no difference in response rate or toxicity between the under 65-year-old group and the older group. CONCLUSION: S-1 was demonstrated to have high efficacy with low gastrointestinal toxicity even in older patients and will be a promising new chemotherapy drug for metastatic breast cancer.

Administration, Oral↗

PubMed2004

Absence of mutations in the Wilms' tumor gene WT1 in primary breast cancer.

BACKGROUND: It was recently demonstrated that the WT1 gene was overexpressed in primary breast cancer and that the high expression levels of WT1 mRNA significantly correlated with poor prognosis. However, it remained undetermined whether or not the WT1 gene expressed in breast cancer had mutations. METHODS: Breast cancer tissues were obtained from 36 patients with breast cancer. WT1 genomic DNA was PCR-amplified and examined for mutations by direct sequencing. RESULTS: The sequencing analysis showed the absence of mutations through the whole 10 exons of the WT1 gene in the 36 cases of primary breast cancer. Two different single nucleotide polymorphisms (SNP) without an amino acid change (Pro42, C to T in exon 1, and/or Arg300, A to G in exon 7) were detected in the WT1 gene in 31 (86%) of the 36 cases examined. CONCLUSION: The results indicate that the wild-type WT1 gene plays an important role in the tumorigenesis of primary breast cancer.

Adult↗

PubMed2004

mRNA expression level of estrogen-inducible gene, alpha 1-antichymotrypsin, is a predictor of early tumor recurrence in patients with invasive breast cancers.

We previously identified 18 genes that correlated with ER positivity by adapter-tagged competitive-PCR analysis of 2412 genes in human breast cancer tissues. The aim of the present study was to determine the prognostic significance of these genes. mRNA expression levels of 12 of the above 18 genes were quantified in breast cancer tissues by real-time PCR assay, and their association with patients' prognosis (n = 110) was studied according to hormone receptor (HR) status. In addition, the genes found to influence prognosis were further investigated to examine whether their mRNA expression could be induced by estrogen in MCF-7 cells in vitro. Of the 12 genes, mRNA expression levels of two [alpha 1-antichymotrypsin (ACT) and stanniocalcin 2 (STC2)] were significantly (P = 0.002 and P = 0.007, respectively) associated with good prognosis in HR-positive (ER and/or PR positive) breast cancer patients treated with adjuvant hormone therapy. Multivariate analysis showed that ACT mRNA level, but not STC2 mRNA level, in HR-positive patients, was a significant prognostic factor (P = 0.042), which was independent of tumor size and lymph node metastases. On the other hand, mRNA expressions of ACT and STC2 were not significantly associated with prognosis in HR-negative patients. Estradiol treatment resulted in a significant increase in the mRNA levels of both ACT and STC2 in MCF-7 cells. The mRNA level of ACT, which is an estrogen-inducible gene, is a significant predictor of good prognosis in HR-positive, but not HR-negative, patients with breast cancers. Since HR-positive patients were treated with adjuvant hormone therapy, we suggest that ACT mRNA level could potentially be used as a predictor of response to hormone therapy, rather than a prognostic factor (predictor of metastatic potential).

Breast Neoplasms↗

PubMed2004

[Molecule based diagnosis].

Based on reviews of the concept of diagnostics and in general and in specific tumour areas it was clear that development of diagnostic procedures involving genomics will allow for much better targeted and tailored treatments in the future. This will result in better efficacy and better tolerability of cancer treatments, but will also allow for progress in prediction, diagnosis and dose selection. Large collaborative projects studying the efficacy and safety of drugs on the genome level is promising to bring important benefits to both patients and the national economy by reducing useless drug therapy. In colorectal cancer there are several genetic defects identified that can act as the target for directed therapy in the future. Expressions of tumour specific antigens open the way for immunological targeted therapies. Developments in the understanding of the genomic basis for resistance to anti-tumour therapy is promising to help targeting patients likely to respond and not develop resistance. A Japanese model is being developed to determine the relative risk of breast cancer of Japanese women. Based on this prevention therapies can be instigated. The last four years have seen the introduction of four novel targeted therapies. If this model should become a standard in the future, much stronger collaboration between academic research and pharmaceutical industry need to develop.

Antineoplastic Agents↗

PubMed2004

High expression of two genes selected by iAFLP: a new prognostic factor of estrogen receptor-positive breast cancer.

To detect patients with poor prognosis among those with estrogen receptor (ER)-positive breast cancer, who generally show good prognosis, we analyzed gene expression profiles of 35 ER-positive tumors by using a high through-put RT-PCR technique, iAFLP. High expression of six genes out of 7,508 was related to poor prognosis in this group. From these six genes, NFE2L2 and TIAL1 were selected as genes associated with poor prognosis by means of a validation study with another set of 56 ER-positive breast cancers. High expression of these two genes was determined to be significantly predictive for poor prognosis of patients with ER-positive breast cancer, and may help to achieve optimal selection of adjuvant treatment for such patients.

Adult↗

PubMed2004

[Evaluation of ten intravenous catheters for operability and safety in the infusion room].

We have a randomized trial to compare the operability and safety of ten 24-gauge intravenous catheters in the infusion room. In the present study, we used 3 intravenous catheters without safety covers (Jelco plus, Surflo flash, Intima) and 7 intravenous catheters with safety covers (Supercath, Introcan safety, Surshield surflo II, Insyte autoguard, Safetouch cath, Protective plus, Acuvance plus). All catheters were used 40 times. The detainment rate of the first time puncture and the incidence of needle accidents with Jelco plus and Insyte autoguard were 98% and 0%, respectively, against 100% and 0%, respectively, for all other catheters. There was no difference in the incidence of these two events in all groups (ANOVA; p > 0.05). On the other hand, all intravenous catheters with safety covers revealed that 1) an in situ needle has a resistance to the catheter (i.e., a resistance during catheter release), and/or 2) blood exposure can not be sufficiently avoided.

Catheterization, Peripheral↗

PubMed2003

Association of serum adiponectin levels with breast cancer risk.

PURPOSE: Adiponectin is a peptide hormone secreted from the adipose tissue, affecting the proliferation and insulin sensitivity of various types of cells. Because association of obesity with breast cancer risk is well established, it is possible that adiponectin plays some role in the development of breast cancer. Thus, in the present study, the association of the serum adiponectin levels with breast cancer risk was investigated. EXPERIMENTAL DESIGN: A case-control study was conducted on 102 breast cancer patients (cases) and 100 healthy women (controls). The serum adiponectin levels of cases and controls were examined in their association with breast cancer risk after adjustment for the various classical risk factors (family history, age at menarche, parity, body mass index, and so forth). In addition, the relationship between the serum adiponectin levels and the various clinicopathological characteristics of breast cancers was studied. RESULTS: Women in the low tertile of serum adiponectin levels were associated with a significantly (P < 0.005) increased risk for breast cancer compared with women in the high tertile [odds ratio (OR), 3.63; 95% confidence interval (CI), 1.61-8.19]. Such an association was observed both in the premenopausal women (OR, 3.46; 95% CI, 0.89-13.50) and in the postmenopausal women (OR, 3.90; 95% CI, 1.23-12.44). The frequency of large (>2 cm) tumors and that of high histological grade (2+3) tumors were significantly (P < 0.005 and P < 0.05, respectively) higher in breast cancer patients in the low tertile of the serum adiponectin levels than those in the high and intermediate tertiles. CONCLUSIONS: These results suggest that the low serum adiponectin levels are significantly associated with an increased risk for breast cancer and that tumors arising in women with the low serum adiponectin levels are more likely to show a biologically aggressive phenotype. The association between obesity and breast cancer risk might be partly explained by adiponectin.

Adiponectin↗

PubMed2003

Mutational analysis of BARD1 in familial breast cancer patients in Japan.

Since BRCA1,which is a breast cancer susceptibility gene, form heterodimers with BARD1, it is speculated that BARD1 mutations might affect the function of BRCA1, contributing to breast carcinogenesis. Thus, in the present study, we have conducted mutational analysis of BARD1 in familial breast cancer patients (n=60) who were tested negative for both BRCA1 and BRCA2 germline mutations. We have been unable to show any clearly deleterious mutations but identified four missence mutations (Ser/Cys 241, Arg/Ser 378, Asn/Ser 470, Val/Met 507), one silent mutation (His/His 506), and one frameshift (in-frame) mutation (1139del21bp). Of these six mutations, one (Asn/Ser 470) was considered as a putative germline mutation since such a mutation was not observed in any of the healthy controls (n=152) but the other five mutations were considered as common genetic polymorphisms since they were frequently observed in the healthy controls. These genetic polymorphisms were further analyzed in their association with breast cancer risk by a case-control study using the population-based breast cancers (n=143) and healthy controls (n=155), which showed that carriers of the variant allele Met at codon 507 are significantly associated with the increased risk of breast cancer (adjusted odds ratio=2.05, 95% confidential interval=1.01-4.16) in postmenopausal women and that the other genetic polymorphisms are not associated with breast cancer risk. These results suggest that BARD1 mutations are responsible for, if any, a very small number of familial breast cancers. Genetic polymorphism of BARD1 (Val/Met 507) could be useful in the selection of postmenopausal women at a high risk for developing breast cancer.

Breast Neoplasms↗

PubMed2003

Prediction of response to docetaxel by quantitative analysis of class I and III beta-tubulin isotype mRNA expression in human breast cancers.

PURPOSE: The relationship of intratumoral mRNA levels of class I and III beta-tubulin isotypes with clinical response to docetaxel has been studied in breast cancer patients. EXPERIMENTAL DESIGN: Expression of class I and class III beta-tubulin mRNA levels was determined by a real-time PCR in breast cancer tissues obtained from 39 patients with locally advanced breast cancers (n = 26) or locally recurrent breast cancers (n = 13) before docetaxel treatment. RESULTS: Class I beta-tubulin mRNA levels of responders [6.58 +/- 1.43 (x10(2)), mean +/- SE] were significantly (P = 0.002) lower than those of nonresponders [14.97 +/- 2.95 (x10(2))], and class III beta-tubulin mRNA levels of responders (1.38 +/- 0.40) were also significantly (P = 0.003) lower than those of nonresponders (7.43 +/- 2.77). Breast cancers were divided into four groups according to the expression status of class I and class III beta-tubulin isotype mRNA, i.e., the class I-high/class III-high group (n = 13), the class I-high/class III-low group (n = 7), the class I-low/class III-high group (n = 7), and the class I-low/class III-low group (n = 12). The class I-high/class III-high group showed a very low response rate (15%), whereas the class I-low/class III-low group showed a very high response rate (75%). The class I-high/class III-low group and the class I-low/class III-high group showed intermediate response rates of 57% and 43%, respectively. CONCLUSIONS: These results demonstrate that high expression of class I and class III beta-tubulin isotype mRNA is significantly associated with docetaxel resistance, and determination of class I and class III beta-tubulin isotype mRNA levels would be useful in the prediction of response to docetaxel.

Adult↗

PubMed2003

Association of CYP17 genetic polymorphism with intra-tumoral estradiol concentrations but not with CYP17 messenger RNA levels in breast cancer tissue.

The variant allele(1931C) of CYP17 (1931C/T), which is one of the key enzymes involved in estrogens synthesis, has been shown to be associated with breast cancer risk. Since this variant allele creates an additional putative Sp-1 binding site (CCACC) in the promoter region, it is speculated that it enhances the transcription of CYP17, leading to the enhanced estrogens synthesis in breast tumors. CYP17 messenger RNA (mRNA) expression could be detected in all the normal breast (n=51) and tumor tissues (n=67) by a real-time polymerase chain reaction but CYP17 mRNA expression was not significantly different between the variant allele carriers and non-carriers. In addition, no significant correlation was observed between CYP17 mRNA and E2 levels in tumors, indicating an unimportant role of CYP17 in in situ synthesis of E2. On the other hand, intra-tumoral E2 levels were significantly (P=0.025) higher in the variant allele carriers (127.2+/-11.0 pg/g) than non-carriers (88.2+/-8.5 pg/g). Since it has been previously reported that serum E2 levels are higher in variant allele carriers than non-carriers, it is speculated that the higher intra-tumoral E2 levels in the variant allele carriers might be ascribed to the higher serum E2 levels.

Adult↗

PubMed2003

Randomized controlled trial comparing oral doxifluridine plus oral cyclophosphamide with doxifluridine alone in women with node-positive breast cancer after primary surgery.

PURPOSE: We compared the therapeutic usefulness of doxifluridine (5'-DFUR) alone and a combination of 5'-DFUR plus cyclophosphamide (CPM), both of which are considered effective against advanced and recurrent breast cancer, to determine which treatment is more beneficial as postoperative adjuvant chemotherapy. PATIENTS AND METHODS: A total of 1,131 women with node-positive primary breast cancer were randomly assigned after primary surgery to receive 5'-DFUR alone or 5'-DFUR plus CPM. All patients initially received 5'-DFUR in an oral dose of 1,200 mg/d for 4 weeks, starting 4 weeks after surgery. Chemotherapy was then not given for 2 weeks. Patients in the 5'-DFUR group subsequently received five 4-week cycles of treatment consisting of oral 5'-DFUR (1,200 mg/d) for the first 2 weeks and no chemotherapy for the next 2 weeks. Those assigned to the 5'-DFUR plus CPM group also received oral CPM 100 mg/d for the first 2 weeks and no chemotherapy for the next 2 weeks. Women 50 years or older concurrently received 20 mg/d of tamoxifen for 2 years in both groups. RESULTS: Of the 1,088 eligible women, 546 were assigned to receive 5'-DFUR alone and 542 were assigned to receive 5'-DFUR plus CPM. Overall disease-free survival was significantly better in women who received 5'-DFUR plus CPM than in those who received 5'-DFUR alone (log-rank test, P =.021). Toxic effects occurred in 20.0% of patients (109 of 546) in the 5'-DFUR group and 32.3% of patients (175 of 542) in the 5'-DFUR plus CPM group (chi(2) test, P <.001). CONCLUSION: Combination therapy with 5'-DFUR plus CPM is more effective in preventing recurrence than 5'-DFUR alone.

Administration, Oral↗

PubMed2003

Intradermal radioisotope injection is superior to subdermal injection for the identification of the sentinel node in breast cancer patients.

BACKGROUND AND OBJECTIVES: The purpose of the present study was to evaluate whether the intradermal injection of radiocolloids would improve the identification rate of sentinel nodes over the subdermal injection in breast cancer patients. METHODS: Sentinel node biopsy was performed in T2 breast cancer patients with clinically negative nodes, using subdermal or intradermal injection of radioisotopes with the peritumoral dye injection. We used Tc-99m tin colloid, with a larger particle size (0.4-5 microm), rather than sulfur colloid and colloidal albumin. RESULTS: The initial 55 patients underwent subdermal injection of radiocolloids; the next 61 patients underwent intradermal injection of radiocolloids for sentinel node biopsy. The detection rate of sentinel nodes was significantly (P = 0.048) higher in the intradermal injection group (61/61, 100%) than in the subdermal injection group (51/55, 92.7%). False-negative rates were comparable between the two groups. Lymphoscintigraphy visualized the sentinel nodes significantly (P < 0.0001) more often in the intradermal injection group (59/61, 96.7%) than in the subdermal injection group (20/54, 37.0%). CONCLUSIONS: A significantly higher identification rate of sentinel node biopsy and lymphoscintigraphy can be achieved by intradermal injection of Tc-99m tin colloid with a large particle size than by subdermal injection.

Axilla↗

PubMed2003

Skin-sparing mastectomy and immediate reconstruction with a deep inferior epigastric perforator flap.

BACKGROUND: It is important for breast reconstruction after mastectomy to recreate immediately good breast symmetry with an adequate amount of soft tissue. METHODS: Eight patients with breast cancer underwent skin-sparing mastectomy and immediate reconstruction with a deep inferior epigastric perforator flap. This operative technique, and the results, advantages, and disadvantages of the technique were assessed. RESULTS: Seven patients had stage IIA disease, and one patient had stage I disease. An arc-shaped incision was made just at the lateral border of the breast in all patients. Three patients had a separate periareolar incision, and one had a circumferential nipple incision. There was 100% flap survival, and good breast symmetry was achieved in all patients. No major perioperative complications occurred in this series. A small amount of fat necrosis occurred in one flap. One patient had slight abdominal bulging. Minor wound-healing problems at the lateral breast skin envelope occurred in two patients. CONCLUSION: These data indicate that skin-sparing mastectomy and immediate reconstruction with a DIEP flap is a reliable and safe technique. This method is a potentially useful surgical technique, which has achieved very promising results.

Adult↗

PubMed2003

Current status of endocrine therapy for breast cancer.

Endocrine therapy is usually indicated prior to chemotherapy as the first line therapy for metastatic breast cancer patients because of its milder toxicity. Patients who respond to a first-line endocrine therapy have a high chance of responding to a second-line endocrine therapy, and thus the responders to a first-line endocrine therapy would better be treated with second or third-line endocrine therapy. In the adjuvant setting, tamoxifen (antiestrogen) has been proven to improve the prognosis of both pre- and postmenopausal estrogen receptor positive breast cancer patients, and goserelin (LH-RH agonist) has been proven to improve prognosis in premenopausal women comparable to chemotherapy (CMF). Very recently, preliminary results have indicated that anastrozole (aromatase inhibitor) is superior to tamoxifen as adjuvant treatment for estrogen receptor positive postmenopausal breast cancer patients. In addition, the recent success of tamoxifen in a chemoprevention trial seems to have ushered in a new era wherein prevention of breast cancer is much more emphasized than treatment of established breast cancer.

Algorithms↗

PubMed2003

Absence of beta-tubulin gene mutation in gastric carcinoma.

BACKGROUND: Effective chemotherapy for advanced gastric cancer is yet to be established. Taxanes, novel anticancer drugs which bind to beta-tubulin and prevent disruption of microtubules, are newly approved and promising agents for advanced and recurrent gastric cancer. To predict the chemoresistance to a taxan in gastric cancer, we examined the genetic mutations of the beta-tubulin gene. METHODS: Fifty pairs of gastric tumor and normal mucosa tissues were obtained from operations and the genomic DNA was extracted from each specimen. The four exons of the beta-tubulin gene were amplified for DNA mutations by single-strand conformation polymorphism (SSCP) methods and sequencing analysis. RESULTS: Nine (18%) of 50 patients with gastric cancer had two kinds of silent variations of the beta-tubulin gene in exon 4. Three kinds of intronic variations were detected in exons 1, 2, and 3. However, no genetic alterations that would change the beta-tubulin protein structure were detected in any of the 50 gastric tumors. CONCLUSION: Our findings indicate that mutations of the beta-tubulin gene, which might be a contraindication for chemotherapy based on taxans, were very rare events in gastric cancer.

Aged↗

PubMed2003

Polymorphisms of estrogen synthesizing and metabolizing genes and breast cancer risk in Japanese women.

Recent success of chemoprevention with tamoxifen has opened a new era wherein prevention of breast cancer is much more emphasized than treatment of established breast cancer. Since tamoxifen has been shown to reduce the risk of estrogen receptor (ER)-positive, but not ER-negative, breast cancer in the chemoprevention trial (P-1), it seems to be important to develop risk factors for ER-positive breast cancer in order to select the candidates for chemoprevention more appropriately. Estrogens, the major risk factors for breast cancer, are speculated to affect breast cancer risk through ER, thus, genetic polymorphisms of the genes involved in the estrogens biosynthesis and metabolism are expected as risk factors for ER-positive breast cancer. Significance of polymorphisms of the genes involved in estrogens biosynthesis (CYP17, CYP19) and metabolism (CYP1A1, CYP1B1, COMT) in modulating the susceptibility to breast cancer is reviewed. The ethnic difference of the variant allele frequencies between Caucasian women and Asian women is also discussed.

Aromatase↗

PubMed2003

Increased expression of BRCA1 mRNA predicts favorable response to anthracycline-containing chemotherapy in breast cancers.

Clinical significance of BRCA1 and BRCA2 mRNA levels in tumor tissues as predictors of response to anthracycline-containing chemotherapy was studied in breast cancer patients. Fifty-one patients with locally advanced breast tumors (n = 43) or locally recurrent tumors (n = 8) underwent tumor biopsy and were treated with CE (cyclophosphamide (600 mg/m2) plus epirubicin (60 mg/m2), q3w). BRCA1 and BRCA2 mRNA levels in the tumors were determined by a real-time PCR assay, and the expression of p53 and erbB2 in tumors was determined by immunohistochemistry. BRCA1 mRNA levels (1.317 +/- 0.277, mean +/- S.E.) of responders were significantly (p < 0.05) higher than those (0.609 +/- 0.097) of non-responders but there was no significant difference in BRCA2 mRNA levels between responders (1.590 +/- 0.326) and non-responders (1.586 +/- 0.410). Tumors were dichotomized into the BRCA1 mRNA levels high and low group according to the cut-off value of 0.55. Response rate (65%) of tumors with high BRCA1 mRNA levels was significantly (p < 0.05) higher than that (32%) of tumors with low BRCA1 mRNA levels. There was no significant association between response to CE and the expression of p53 or erbB2. Positive predictive value, negative predictive value, and diagnostic accuracy of BRCA1 mRNA determination in the prediction of response to CE were 65, 68, and 67%, respectively. These results suggest a possibility that BRCA1 mRNA levels in tumor tissues might be useful in the prediction of response to CE treatment in breast cancer patients.

Antibiotics, Antineoplastic↗