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Shinzaburo Noguchi

Publications and source records attributed to Shinzaburo Noguchi.

At least 19 recordsLinked to original sources
PubMed2007

Connexin26 expression is associated with lymphatic vessel invasion and poor prognosis in human breast cancer.

PURPOSE: Cx26, which is a constituent of the connexin family, has recently been shown to promote metastasis through enhancing the vascular invasion in mouse melanoma cells. In this study, we have investigated whether or not Cx26 expression is associated with vascular invasion and recurrences in human breast cancers. EXPERIMENTAL DESIGN: Cx26 expression was studied in 152 invasive breast cancers by immunohistochemistry. In order to investigate the blood vessel invasion and lymphatic vessel invasion with precision, immunohistochemical staining of blood vessels and lymphatic vessels was carried out using anti-CD34 and anti-D2-40 antibodies, respectively. RESULTS: Cx26 was positive in 51.3% (78/152) of the breast tumors. A statistically significant association was observed between Cx26 expression and large tumor size (P = 0.013) or high histological grade (P = 0.043). Frequency of blood vessel invasion was higher in Cx26-positive tumors (5.1%, 4/78) than in Cx26-negative tumors (1.4%, 1/74) though not statistically significant (P = 0.210). Lymphatic vessel invasion was significantly (P = 0.001) more frequent in Cx26-positive tumors (39.7%) than in Cx26-negative tumors (14.9%). Patients with Cx26-positive tumors showed a significantly (P < 0.001) poorer prognosis than those with Cx26-negative tumors. Multivariate analysis showed that Cx26 (P < 0.05) expression was an independent prognostic factor. CONCLUSIONS: Cx26 expression is associated with lymphatic vessel invasion, large tumor size, high histological grade, and poor prognosis in human breast cancers. Cx26 seems to enhance the metastasis probably through promoting the lymphatic vessel invasion. Cx26 might be clinically useful as a new prognostic factor.

Antibodies, Monoclonal↗
PubMed2007

Clinicopathologic analysis of breast cancers with PIK3CA mutations in Japanese women.

PURPOSE: Somatic mutations of PIK3CA, which encodes the p110alpha catalytic subunit of phosphatidylinositol 3-kinase, have recently been shown to play an important role in the pathogenesis and progression of human breast cancers. In this study, the frequency of PIK3CA mutations and their relationship with clinicopathologic and biological variables were investigated in Japanese breast cancers. EXPERIMENTAL DESIGN: Mutational analysis of PIK3CA was done in 188 primary breast cancers of Japanese women. Relationship of these mutations with various clinicopathologic variables [histologic type, tumor size, histologic grade, lymph node status, estrogen receptor (ER)-alpha and progesterone receptor status, and prognosis], biological variables [phospho-AKT (pAKT) and HER2 expression determined by immunohistochemistry], and p53 mutation status was studied. RESULTS: Missense mutations of PIK3CA were found in 44 of 158 invasive ductal carcinomas, 4 of 10 invasive lobular carcinomas, 1 of 4 mucinous carcinomas, 2 of 2 squamous carcinomas, and 2 of 2 apocrine carcinomas, but no mutation was found in 12 noninvasive ductal carcinomas. PIK3CA-mutated tumors were found to be more likely to be ER-alpha positive (P < 0.05) and pAKT positive (P < 0.05). There was no significant association between PIK3CA mutations and p53 mutation status. PIK3CA mutations were significantly (P < 0.05) associated with a favorable prognosis, and multivariate analysis showed that PIK3CA mutation status was a significant (P < 0.05) prognostic factor independent of the other conventional prognostic factors. CONCLUSIONS: The frequency of PIK3CA mutations in Japanese breast cancers is similar to that of Caucasian breast cancers. Association of PIK3CA mutations with positive pAKT and positive ER-alpha suggests that PIK3CA mutations might exert their effects through activation of the phosphatidylinositol 3-kinase/AKT/ER-alpha pathway. PIK3CA mutations seem to have a potential to be used as an indicator of favorable prognosis.

Breast Neoplasms↗
PubMed2006

Dofequidar fumarate (MS-209) in combination with cyclophosphamide, doxorubicin, and fluorouracil for patients with advanced or recurrent breast cancer.

PURPOSE: To evaluate the efficacy and tolerability of dofequidar plus cyclophosphamide, doxorubicin, and fluorouracil (CAF) therapy in comparison with CAF alone, in patients with advanced or recurrent breast cancer. Dofequidar is a novel, orally active quinoline derivative that reverses multidrug resistance. PATIENTS AND METHODS: In this randomized, double-blind, placebo-controlled trial, patients were treated with six cycles of CAF therapy: 28 days/cycle, with doxorubicin (25 mg/m2) and fluorouracil (500 mg/m2) administered on days 1 and 8 and cyclophosphamide (100 mg orally [PO]) administered on day 1 through 14. Patients received dofequidar (900 mg PO) 30 minutes before each dose of doxorubicin. Primary end point was overall response rate (ORR; partial or complete response). In total, 221 patients were assessable. RESULTS: ORR was 42.6% for CAF compared with 53.1% for dofequidar + CAF, a 24.6% relative improvement and 10.5% absolute increase (P = .077). There was a trend for prolonged progression-free survival (PFS; median 241 days for CAF v 366 days for dofequidar + CAF; P = .145). In retrospectively defined subgroups, significant improvement in PFS in favor of dofequidar was observed in patients who were premenopausal, had no prior therapy, and were stage IV at diagnosis with an intact primary tumor. Except for neutropenia and leukopenia, there was no statistically significant excess of grade 3/4 adverse events compared with CAF. Treatment with dofequidar did not affect the plasma concentration of doxorubicin. CONCLUSION: Dofequidar + CAF was well tolerated and is suggested to have efficacy in patients who had not received prior therapy.

Adult↗
PubMed2006

Demonstration of adiponectin receptors 1 and 2 mRNA expression in human breast cancer cells.

Recently, we have shown that low adiponectin levels are significantly associated with an increased breast cancer risk. It seems to be very important to study the expression of adiponectin receptor 1 (AdipoR1) and receptor 2 (AdipoR2) in the human breast epithelial cells and breast cancer cells in order to clarify whether or not adiponectin exerts its effects directly on these cells. Expression of adiponectin, AdipoR1, and AdipoR2 mRNA was determined by RT-PCR assay using the RNA samples obtained from human breast cancer cell lines (MCF-7, T47D, SKBR3, and MDA-MB231), HMEC (primary culture of normal human mammary epithelial cells), adipose tissues (axilla) as well as breast cancer cells and normal breast epithelial cells selectively collected from breast cancer tissues by laser microdissection (LMD). Adiponectin mRNA expression was observed only in the adipose tissues. On the other hand, AdipoR1 and AdipoR2 mRNA expression was observed in all four breast cancer cell lines, HMEC, adipose tissues as well as breast cancer cells and normal breast epithelial cells selectively collected by LMD. In addition, AdipoR1 and AdipoR2 expression in both normal breast epithelial cells and breast cancer cells was confirmed by immunohistochemistry. These results suggest a possibility that adiponectin might modulate the growth of normal breast epithelial cells and breast cancer cells directly through AdipoR1 and AdipoR2 receptors, and that the association of low serum adiponectin levels with a high breast cancer risk might be explained, at least in part, by the direct effect of adiponectin on the breast epithelial cells.

Adiponectin↗
PubMed2006

A multi-class predictor based on a probabilistic model: application to gene expression profiling-based diagnosis of thyroid tumors.

BACKGROUND: Although microscopic diagnosis has been playing the decisive role in cancer diagnostics, there have been cases in which it does not satisfy the clinical need. Differential diagnosis of malignant and benign thyroid tissues is one such case, and supplementary diagnosis such as that by gene expression profile is expected. RESULTS: With four thyroid tissue types, i.e., papillary carcinoma, follicular carcinoma, follicular adenoma, and normal thyroid, we performed gene expression profiling with adaptor-tagged competitive PCR, a high-throughput RT-PCR technique. For differential diagnosis, we applied a novel multi-class predictor, introducing probabilistic outputs. Multi-class predictors were constructed using various combinations of binary classifiers. The learning set included 119 samples, and the predictors were evaluated by strict leave-one-out cross validation. Trials included classical combinations, i.e., one-to-one, one-to-the-rest, but the predictor using more combination exhibited the better prediction accuracy. This characteristic was consistent with other gene expression data sets. The performance of the selected predictor was then tested with an independent set consisting of 49 samples. The resulting test prediction accuracy was 85.7%. CONCLUSION: Molecular diagnosis of thyroid tissues is feasible by gene expression profiling, and the current level is promising towards the automatic diagnostic tool to complement the present medical procedures. A multi-class predictor with an exhaustive combination of binary classifiers could achieve a higher prediction accuracy than those with classical combinations and other predictors such as multi-class SVM. The probabilistic outputs of the predictor offer more detailed information for each sample, which enables visualization of each sample in low-dimensional classification spaces. These new concepts should help to improve the multi-class classification including that of cancer tissues.

Algorithms↗
PubMed2006

Possible involvement of CCT5, RGS3, and YKT6 genes up-regulated in p53-mutated tumors in resistance to docetaxel in human breast cancers.

BACKGROUND: Present study was aimed to investigate the relationship of p53 mutation status with response to docetaxel in breast cancers. In addition, attempts were made to identify the genes differentially expressed between p53-wild and p53-mutated breast tumors and to study their relationship with response to docetaxel. METHODS: Mutational analysis of p53 was done in 50 breast tumor samples obtained from primary breast cancer patients (n = 33) and locally recurrent breast cancer patients (n = 17) before docetaxel therapy. Response to docetaxel was evaluated clinically. Gene expression profiling (n = 2,412) was conducted by adapter-tagged competitive-PCR in 186 tumor samples, which were also analyzed in their p53 mutational status in order to identify the differentially expressed genes according to p53 mutation status and their relationship with response to docetaxel. RESULTS: Response rate of p53-mutated tumors (44%) was lower than that of p53-wild tumors (62%) though there was no statistical significance (P = 0.23). Of 2412 genes, mRNA expression of 13 genes was significantly different between p53-wild and p53-mutated tumors. Of these 13 genes, mRNA expression of CCT5, RGS3, and YKT6 was significantly up-regulated in p53-mutated tumors and associated with a low response rate to docetaxel. Treatment of MCF-7 cells with siRNA specific for CCT5, RGS3, or YKT6 resulted in a significant enhancement of docetaxel-induced apoptosis. CONCLUSIONS: CCT5, RGS3, and YKT6 mRNA expressions, which are up-regulated in p53-mutated breast tumors, might be implicated in resistance to docetaxel and clinically useful in identifying the subset of breast cancer patients who may or may not benefit from docetaxel treatment.

Antineoplastic Agents, Phytogenic↗
PubMed2006

Predictive factors for response to docetaxel in human breast cancers.

Docetaxel has come into wide use recently for the treatment of breast cancer in neoadjuvant, adjuvant and metastatic settings. Docetaxel binds to beta-tubulin and causes kinetic abnormalities in the dynamics of microtubules by increasing their polymerization and inhibiting their depolymerization, resulting in elevated levels of microtubule formation. During metaphase, defective spindle formation induced by docetaxel activates the mitotic checkpoint and leads to cell cycle arrest, culminating in apoptosis. However, docetaxel is not effective for all breast cancers. For example, in metastatic settings, the response rate to docetaxel reportedly ranges from 30 to 50%. It is therefore very important to develop a diagnostic method with high accuracy for the prediction of sensitivity to docetaxel in order to avoid unnecessary treatment. Currently it is impossible to identify, before the initiation of therapy, the patients for whom docetaxel will be effective. Various biological parameters have been studied clinically for their ability to predict response to docetaxel, such as parameters related to: (1) efflux (p-glycoprotein) and metabolism (CYP3A4); (2) beta-tubulin (somatic mutation of beta-tubulin and changes in beta-tubulin isotypes levels); (3) cell cycle (HER2, BRCA1 and Aurora-A); and (4) apoptosis (p53, BCL2 and thioredoxin). More recently, gene expression profiling techniques have been used for the development of a prediction model for response to docetaxel. In the present paper, clinical studies that have been conducted recently to identify predictive factors for response to docetaxel are reviewed together with a presentation of our recent work in this field.

Antineoplastic Agents, Phytogenic↗
PubMed2006

Association of GSTP1 CpG islands hypermethylation with poor prognosis in human breast cancers.

Glutathione S-transferase P1 (GSTP1) belongs to a family of phase II metabolic enzymes that can detoxify the carcinogens and cytotoxic drugs by conjugating them with glutathione. Relationship of GSTP1 CpG islands hypermethylation or GSTP1 protein expression with clinicopathological characteristics of breast cancers was studied. The CpG islands hypermethylation status of GSTP1 gene was studied by methylation specific primer assay and GSTP1 expression was studied by immunohistochemistry in primary breast cancers. Of 174 breast tumors, 24 (14%) were found to have GSTP1 CpG islands hypermethylation. A significant association was found between GSTP1 CpG islands hypermethylation and large tumor size (P < 0.01) or lymph node metastases (P < 0.05). Relapse-free survival (RFS) rates of patients with GSTP1 CpG islands hypermethylation were significantly poorer than those without it (5-year RFS rates; 60 vs. 86%, P < 0.01). Multivariate analysis showed that GSTP1 CpG islands hypermethylation status was a statistically significant prognostic factor being independent of other conventional prognostic factors. Immunohistochemical study showed that here was a significant association between GSTP1 CpG islands hypermethylation and loss of GSTP1 expression (P < 0.01) but that RFS rates of patients with GSTP1 positive tumors were not significantly different from those with GSTP1 negative tumors. GSTP1 CpG islands hypermethylation, but not GSTP1 protein expression, is associated with a poor prognosis of breast cancers, suggesting that GSTP1 CpG islands hypermethylation has a potential to serve as a clinically useful prognostic factor.

Breast Neoplasms↗
PubMed2006

Comparison of anastrozole versus tamoxifen as preoperative therapy in postmenopausal women with hormone receptor-positive breast cancer: the Pre-Operative "Arimidex" Compared to Tamoxifen (PROACT) trial.

BACKGROUND: The Pre-Operative "Arimidex" Compared to Tamoxifen (PROACT) study was a randomized, multicenter study comparing anastrozole with tamoxifen as a preoperative treatment of postmenopausal women with large, operable (T2/3, N0-2, M0), or potentially operable (T4b, N0-2, M0) breast cancer. The effect of preoperative endocrine therapy in patients scheduled for mastectomy or with inoperable tumors at baseline was also investigated. METHODS: Patients with hormone receptor-positive breast cancer received anastrozole (n = 228) or tamoxifen (n = 223) with or without chemotherapy for 12 weeks before primary surgery. RESULTS: Objective responses for anastrozole and tamoxifen occurred in 39.5% and 35.4% of patients, respectively (ultrasound measurements), and 50.0% and 46.2% of patients, respectively (caliper measurements). In hormonal therapy-only patients (n = 314), feasible surgery at baseline improved after 3 months in 43.0% of patients receiving anastrozole and 30.8% receiving tamoxifen (P = .04). In the intent-to-treat population, improvement in feasible surgery at baseline to actual surgery at 3 months was found to be numerically higher in the anastrozole group compared with the tamoxifen group, although this difference did not reach significance. Drug-related adverse events were reported in 20.2% and 18.1% of patients, respectively, in the anastrozole and tamoxifen groups. CONCLUSIONS: Anastrozole is an effective and well-tolerated preoperative therapy, producing clinically beneficial tumor downstaging and reductions in tumor volume. These effects enable more minimal surgical interventions in patients scheduled for mastectomy, and mastectomy in patients with previously inoperable tumors. Anastrozole appears to be at least as effective as tamoxifen in this setting, and more effective than tamoxifen in certain clinically relevant subgroups. Cancer 2006. (c) 2006 American Cancer Society.

Aged↗
PubMed2006

Quantitative analysis of aromatase mRNA expression derived from various promoters (I.4, I.3, PII and I.7) and its association with expression of TNF-alpha, IL-6 and COX-2 mRNAs in human breast cancer.

The purpose of the present study was to study the aromatase mRNA expression as well as promoter usage (I.4, I.3, PII and I.7) in axillary adipose tissue (AA), mammary adipose tissue (MA), breast tumor tissue (BT) and adjacent normal breast tissue (NB), and to study the relationship between aromatase mRNA expression and tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and cyclooxygenase (COX)-2 mRNA expression. BT (n=108), NB (n=54), AA (n=41) and MA (n=34) from patients with breast cancer were subjected to real-time PCR assays for the mRNA levels of aromatase, TNF-alpha, IL-6 and COX-2. We also studied the usage of promoters I.4, I.3, PII and the recently reported endothelial promoter I.7. Total aromatase mRNA levels were significantly up-regulated in BT as compared with NB, AA and MA. Proportion of promoter l.4-specific transcripts against the total transcripts was significantly decreased and that of promoter l.3- and l.7-specific transcripts was significantly increased in BT than NB, AA and MA. However, the amount of transcripts from all the 4 promoters was significantly up-regulated in BT than NB, AA and MA. Estrogen receptor-alpha (ER-alpha) positive tumors showed a higher percentage of promoter I.7 usage than ER-alpha negative tumors with a marginal significance (p=0.05), and tumor with high microvessel counts tended (p=0.06) to show a higher percentage of promoter I.7 usage than those with low microvessel counts. There was a significant association between aromatase mRNA levels and TNF-alpha, IL-6 or COX-2 mRNA levels in BT, AA and MA but not in NB. These results suggest that enhanced transcription of promoters l.4, I.3, PII and I.7 explains the up-regulation of aromatase mRNA levels in BT. It has also been suggested that angiogenesis might stimulate the growth of ER-alpha positive tumors through the enhanced transcription of aromatase from promoter I.7 in endothelial cells in BT, and that TNF-alpha, IL-6 and COX-2 might be implicated in the up-regulation of aromatase mRNA in BT, AA and MA but not in NB.

Adipose Tissue↗
PubMed2006

A phase I/II trial of a WT1 (Wilms' tumor gene) peptide vaccine in patients with solid malignancy: safety assessment based on the phase I data.

OBJECTIVE: We conducted a phase I study to investigate the safety of a weekly WT1 tumor vaccine therapy in patients with solid tumors that had been refractory to all other anti-cancer therapies. METHODS: Skin-test-negative patients were intradermally injected weekly for 12 weeks with 3.0 mg of an HLA-A*2402-restricted modified 9-mer WT1 peptide emulsified in Montanide ISA51 adjuvant. We estimated the Bayesian posterior probability of the occurrence of grade 3 or 4 toxicity when receiving the weekly WT1 vaccination. This analysis provided the basis for making a decision to terminate the phase I study and switch to phase II. Moreover, we performed an exploratory assessment of the anti-tumor effects of WT1 treatment. RESULTS: Ten patients received 114 vaccinations with WT1 on a weekly schedule. No grade 3 or 4 toxicities were observed. Based on the Bayesian approach, it was highly likely that the probability of grade 3 or 4 toxicity was below 20% (the posterior probability = 0.914). Fifteen grade 2 and two grade 1 toxicities were observed; all of these incidents, however, were determined by the Independent Data and Safety Monitoring Committee to be unrelated to the WT1 treatment. One patient exhibited a partial response; five additional patients had stable disease while receiving weekly WT1 treatment. CONCLUSION: This paper confirms that the potential toxicities of the treatment schedule of weekly WT1 vaccination are acceptable and suggested a potential anti-tumor effect. Consequently, we validated the decision to continue to the phase II trial.

Adolescent↗
PubMed2006

Quantitative analysis of aromatase, sulfatase and 17beta-HSD(1) mRNA expression in soft tissue metastases of breast cancer.

Expression of the estrogen-synthesizing genes aromatase, steroid sulfatase (STS) and 17beta-hydroxysteroid dehydrogenase type1 (17beta-HSD(1)) has been shown to be up-regulated in primary breast cancer tissue but their expression status in metastatic tumor tissue has yet to be determined. The mRNA expression levels of the three estrogen-synthesizing genes as well as of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and cyclooxygenase (COX)-2, all of which have been reported to up-regulate the estrogen-synthesizing genes, were determined by means of a real-time PCR assay in 100 primary breast cancer tissues and 15 soft tissue metastases. In addition, PCR-gel electrophoresis was used to determine the proportion (%) of promoter (l.4, l.3, Pll and l.7) usage of aromatase. Aromatase and STS mRNA levels were significantly (P=0.04 and P=0.03, respectively) higher in soft tissue metastases than in primary tumors, while 17beta-HSD(1) mRNA levels tended (P=0.09) to be higher. The proportions of the promoter usages were very similar for primary tumors and soft tissue metastases, and the mRNA levels of TNF-alpha, IL-6 and COX-2 were not significantly different. Levels of aromatase, STS and 17beta-HSD(1) mRNA are up-regulated in soft tissue metastases compared to those in primary tumors, suggesting that intra-tumoral estrogen synthesis may play a significant role in the growth stimulation of tumor cells in soft tissue metastases as in primary tumors. TNF-alpha, IL-6 and COX-2, on the other hand, are unlikely to be implicated in this up-regulation.

17-Hydroxysteroid Dehydrogenases↗
PubMed2006

High expression of leptin receptor mRNA in breast cancer tissue predicts poor prognosis for patients with high, but not low, serum leptin levels.

The association of mRNA expression levels of leptin receptors (long isoform: Lep-R(L) and short isoform: Lep-R(S)) in breast cancer tissue with patient prognosis was studied with special reference to the serum leptin level or the leptin mRNA level in tumor tissue. Lep-R(L), Lep-R(S) and leptin mRNA levels in breast cancer tissue (n = 91) were determined with a real-time PCR assay, and serum leptin levels in breast cancer patients (n = 67) with an enzyme-linked immunosorbent assay. Neither Lep-R(L) nor Lep-R(S) mRNA levels in tumor tissue were significantly associated with patient prognosis, but both intratumoral Lep-R(L) and Lep-R(S) mRNA high tumors were significantly (p < 0.01) associated with a poor prognosis. Multivariate analysis showed that a high level of both Lep-R (L) and Lep-R (S) mRNA in tumor tissue was a significant risk factor, independent of other risk factors. The subset analysis demonstrated that both intratumoral Lep-R(L) and Lep-R(S) mRNA high tumors were significantly associated with a poor prognosis for the subset of patients with high serum leptin or high intratumoral leptin mRNA levels but not in the subset of patients with low serum leptin or low intratumoral leptin mRNA levels. The association between both intratumoral Lep-R(L) and Lep-R(S) mRNA high tumors and a poor prognosis in the presence of high serum leptin or high intratumoral leptin mRNA levels seems to suggest that the leptin and Lep-R(L)/Lep-R(S) pathways are implicated in the growth stimulation of breast tumors. The well-established finding that obesity serves as a risk factor for relapse in breast cancer patients may thus be partially explained by the high serum leptin level seen in obese women.

Adult↗
PubMed2006

High expression of ubiquitin carboxy-terminal hydrolase-L1 and -L3 mRNA predicts early recurrence in patients with invasive breast cancer.

The present study investigated the mRNA expression level of ubiquitin c-terminal hydrolase (UCH)-L1 and -L3 in breast cancer tissue and aimed to elucidate its association with tumor characteristics and patient prognosis. UCH-L1 and UCH-L3 mRNA levels in invasive breast cancer (n = 100) were determined by a real-time polymerase chain reaction (PCR) assay and their relationship with various clinicopathological characteristics of breast tumors as well as patient prognosis were studied. UCH-L3 mRNA level was significantly upregulated in breast cancer tissue compared to adjacent normal breast tissue (P < 0.005), and UHC-L1 mRNA level also showed a non-significant increase in tumor tissue compared to adjacent normal breast tissue. Both UCH-L1 and UCH-L3 mRNA levels were significantly higher in high histological grade tumors than in low histological grade tumors (P < 0.001 and P < 0.005, respectively). High UCH-L1 mRNA level was significantly associated with negative estrogen receptor status (P < 0.05) and negative progesterone receptor status (P < 0.05). Patients with both UCH-L1 and UCH-L3 mRNA high tumors showed a significantly poorer prognosis than those in the UCH-L1 or UCH-L3 mRNA low group (P < 0.005). These observations that UCH-L3 mRNA level is upregulated in breast cancer tissue, and breast tumors with both UCH-L1 and UCH-L3 mRNA high expression are associated with a poor prognosis, suggest the possible involvement of UCH-L1 and UCH-L3 in the pathogenesis and progression of breast cancer.

Antigens, CD↗
PubMed2006

Clinical significance of class III beta-tubulin expression and its predictive value for resistance to docetaxel-based chemotherapy in gastric cancer.

Docetaxel, one of the most effective anticancer drugs for gastric cancer, targets beta-tubulin, the major protein in mitotic spindles. Eight isotypes of beta-tubulin, with tissue and organ-specific expression, have been identified in mammalian cells. We examined class III beta-tubulin expression in gastric cancer and assessed its relationship with sensitivity to docetaxel-based chemotherapy. A total of 115 paraffin-embedded gastric tumors were analyzed by immunohistochemistry for class III beta-tubulin expression. Twenty patients with advanced gastric cancer received preoperative docetaxel-based chemotherapy. Their biopsied specimens, obtained by endoscopy before chemotherapy were examined for class III beta-tubulin expression. The relationship between expression and chemosensitivity was assessed. Forty-two (36.4%) of 115 cases were confirmed to be positive for class III beta-tubulin expression. There was no association between clinicopathological status and prognosis. Among the patients positive for class III beta-tubulin expression, only 16.7% showed no response to chemotherapy, while 64.3% responded to the chemotherapy in the negative group. Our results suggest that class III beta-tubulin is a simple and useful predictive marker for the clinical response to docetaxel-based chemotherapy in gastric cancer.

Adult↗
PubMed2006

[Immediate breast reconstruction following to skin-sparing mastectomy].

Patients with breast cancer accompanied by extensive intraductal components or multiple tumors are not considered to be candidates for breast-conserving surgery. To improve post-operative quality of life of such patients, skin-sparing mastectomy with immediate reconstruction has been performed recently. We described our experience of skin-sparing mastectomy and areola-nipple-sparing mastectomy followed by immediate reconstruction with the use of a latissimus dorsi myocutaneous flap, a transverse rectus abdominis myocutaneous flap, and a deep inferior epigastric artery perforator flap. These operations appear to be oncologically safe when patients are selected carefully, and have a great benefit for the patients both aesthetically and psychologically.

Female↗
PubMed2006

[A phase-I clinical study of a combination therapy of vinorelbine and capecitabine in patients with advanced/recurrent breast cancer].

A phase-I clinical study of a combination therapy of vinorelbine and capecitabine was conducted in anthracycline- and taxane-pretreated patients with advanced/recurrent breast cancer. The objectives of this study in four medical institutions were to evaluate DLT (Dose Limiting Toxicity) and safety as primary endpoints, and tumor response and pharmacokinetics of vinorelbine as secondary endpoints. One 3-week course of treatment consisted of intravenous vinorelbine on Days 1 and 8 and oral capecitabine on Days 1 to 14, followed by a one-week rest. Vinorelbine was given at 20 mg/m(2) (Level 1) and 25 mg/m(2) (Level 2), and capecitabine was given at 1,650 mg/m(2)/day (in two divided doses, Levels 1 - 2). As the administration at each dose level in 3 patients did not cause DLT, 6 patients were additionally treated with vinorelbine at 25 mg/m(2) and capecitabine at 1,650 mg/m(2)/day (in two divided doses) to confirm safety. The major toxicities were bone marrow depression and gastrointestinal symptoms. In particular, the incidences of grade 3 or greater neutropenia (11 patients) and leukemia (10 patients) were high. They were reversible, however, and not severe enough to discontinue treatment. The response rate was 25.0% (3 PR/12). The combination with capecitabine did not affect the plasma pharmacokinetics of vinorelbine.

Aged↗