Biomedical subjects

Yutaka Yamamoto

Publications and source records attributed to Yutaka Yamamoto.

At least 19 recordsLinked to original sources

PubMed2006

Reduced expression of the breast cancer metastasis suppressor 1 mRNA is correlated with poor progress in breast cancer.

PURPOSE: It is well established that breast cancer metastasis suppressor 1 (BRMS1) suppresses metastasis of breast cancer in animal models without affecting the growth of the primary tumor. It has also been shown to suppress the metastasis of tumors derived from breast and melanoma cell lines. However, its clinical importance for breast cancer patients remains undetermined. This prompted us to investigate its expression level in breast cancer patients to clarify its clinical significance. EXPERIMENTAL DESIGN: The level of expression of BRMS1 mRNA was assessed by LightCycler quantitative real-time reverse transcription-PCR in 161 cases of invasive carcinoma of the breast. Associations between BRMS1 mRNA expression and various clinicopathologic factors were sought. RESULTS: It was found that BRMS1 mRNA was expressed at significantly higher levels in patients>50 years of age, with tumor size<2 cm, or with progesterone receptor-positive and HER2-negative tumors. No differences were found between BRMS1 mRNA expression and axillary lymph node metastasis and histologic grade groups. Patients with high levels of expression of BRMS1 mRNA have a better prognosis than those with low expression. Univariate and multivariate prognostic analysis showed that BRMS1 mRNA is an independent prognostic factor for disease-free survival in breast cancer. CONCLUSIONS: These results provide clinical evidence to support the notion that BRMS1 is a breast carcinoma metastasis suppressor gene. Our results also suggest that measuring BRMS1 expression will help to identify those breast cancer patients with worse disease-free survival.

Adult↗

PubMed2006

Additive antitumor effect of concurrent treatment of 4-hydroxy tamoxifen with 5-fluorouracil but not with doxorubicin in estrogen receptor-positive breast cancer cells.

PURPOSE: The sequential addition of tamoxifen (TAM) to chemotherapy seems superior to its concurrent addition in patients with breast cancer. This study was conducted to clarify the hypothesis that there are differential interactions among TAM and chemotherapeutic agents. METHODS: Estrogen receptor (ER)-alpha-positive or -negative breast cancer cells were treated with 4-hydroxy TAM (4OHT), 5-fluorouracil (FU) and/or doxorubicin (Dox). Changes in the expression levels of genes related to sensitivity and resistance to TAM, 5-FU or Dox were tested. RESULTS: Concurrent treatment of 4OHT with 5-FU but not with Dox additively inhibited the growth of ER-alpha-positive cells. 5-FU did not change the expression levels of any tested genes related to either sensitivity or resistance to TAM. Although Dox did not change the expression levels of any genes related to the sensitivity to TAM, Dox significantly increased the expression levels of some genes related to TAM resistance, Eph A-2, ER-beta, Fos and vascular endothelial growth factor. 4OHT significantly decreased thymidilate synthase (TS) activity. CONCLUSIONS: Although the antitumor effect of concurrent 4OHT and 5-FU was additive, that of concurrent 4OHT and Dox was less than additive in ER-alpha-positive cells. The increased expression of genes related to TAM resistance by Dox might be responsible for the interaction. Decreased TS activity by 4OHT might increase the antitumor activity of 5-FU. These findings may provide a preclinical rationale for concurrent use with 5-FU and TAM.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Comparative study on the efficacy of AmBisome and Fungizone in a mouse model of pulmonary aspergillosis.

OBJECTIVES: The aim of this study was to evaluate the efficacy and tissue concentration of AmBisome and Fungizone in murine pulmonary aspergillosis, and to investigate the localization of AmBisome at the infection site. METHODS: Mice were infected intratracheally with Aspergillus fumigatus. A single dose of each of the antifungals was administered intravenously 4 h after infection. The efficacy of the antifungal treatment was assessed by the pulmonary fungal burden at 20 h post-treatment and the survival time over 1 month. The pulmonary amphotericin B (AMB) concentration was measured until 48 h after administration. The distribution of AmBisome in the lung was evaluated using rhodamine-labelled AmBisome and an anti-AMB antibody. RESULTS: AmBisome at a dose of > or =1 mg/kg significantly prolonged the survival time of infected mice compared with the control group. At the maximum tolerated dose, 10 mg/kg AmBisome exhibited greater efficacy than 1 mg/kg Fungizone in terms of increasing survival and reducing the fungal burden. The pulmonary AMB concentration of 10 mg/kg AmBisome was higher than that of 1 mg/kg Fungizone. Tissue distribution analysis showed that AmBisome was localized at the infection site in the lung, and this might explain the potent in vivo efficacy in this infection model. CONCLUSIONS: AmBisome is localized at the infection site in the lung and consequently may fully exhibit its in vivo activity. The efficacy of AmBisome is superior to that of Fungizone against pulmonary aspergillosis.

Amphotericin B↗

PubMed2006

Additive antitumor effects of gefitinib and imatinib on anaplastic thyroid cancer cells.

PURPOSE: Anaplastic thyroid cancer (ATC) is one of the most aggressive malignancies. Although multidisciplinary treatments have been introduced, patients with this disease rarely survive longer than 1 year. These findings prompted us to investigate the antitumor activity of molecular targeting agents in thyroid cancer cells. METHODS: Two tyrosine kinase inhibitors, gefitinib and imatinib, were tested in a poorly differentiated thyroid cancer cell line, KTC-1, and two ATC cell lines, KTC-2 and KTC-3. RESULTS: All cell lines expressed not only a target molecule of gefitinib, HER1, but also a cognate receptor, HER2. They also expressed target molecules of imatinib, c-ABL and platelet-derived growth factor receptors at various levels. Both agents had modest antitumor activity in these cell lines. Combined treatment with gefitinib and imatinib led to an additional antitumor effect. Each agent induced apoptosis and their combined treatment enhanced apoptosis associated with the down-regulation of antiapoptotic proteins, Bcl-2 and Bcl-xL. Moreover, their combined treatment additionally inhibited the growth of KTC-3 xenografts in nude mice. CONCLUSIONS: These are the first findings to suggest that both gefitinib and imatinib have antitumor activity against ATC cells and that their combined use has greater activity than either drug alone.

Animals↗

PubMed2006

Successful treatment of malignant fibrous histiocytoma originating in the chest wall: report of a case.

Malignant fibrous histiocytoma (MFH) rarely originates in the chest wall, so its clinical features are not well defined. We report a case of MFH that recurred locally 3 years after primary resection. The patient, a 59-year-old woman, underwent wide excision, and is alive without recurrence 7 months after the operation. We reviewed the clinical features and treatment strategies of the total 39 cases of MFH originating in the chest wall reported from Japan. The fact that all patients who underwent wide excision with negative margins at the primary operation were alive without recurrence at the time of each report, despite a local recurrence rate as high as 40%, shows the importance of this operative strategy. Thus, early diagnosis of MFH of the chest wall is essential for improving the outcome of these patients. Neoadjuvant chemotherapy plus radiation therapy may be worthwhile for patients with advanced disease.

Female↗

PubMed2006

Evaluation of antifungal pharmacodynamic characteristics of AmBisome against Candida albicans.

A liposomal formulation of Amphotericin B (AmBisome), with small unilamellar vesicles containing amphotericin B, shows characteristic pharmacokinetics as liposomes, and in consequence, has different pharmacological activity and toxicity from amphotericin B deoxycholate (Fungizone). In this study, we evaluated the antifungal pharmacodynamic characteristics of AmBisome against Candida albicans using the in vitro time-kill method and murine systemic infection model. A time-kill study indicated that the in vitro fungicidal activities of AmBisome and Fungizone against C. albicans ATCC 90029 increased with increasing drug concentration. For in vivo experiments, leucopenic mice were infected intravenously with the isolate 4 hr prior to the start of therapy. The infected mice were treated for 24 hr with twelve dosing regimens of AmBisome administered at 8-, 12-, 24-hr dosing intervals. Correlation analysis between the fungal burden in the kidney after 24 hr of therapy and each pharmacokinetic/pharmacodynamic parameter showed that the peak level/MIC ratio was the best predictive parameter of the in vivo outcome of AmBisome. These results suggest that AmBisome, as well as Fungizone, has concentration-dependent antifungal activity. Furthermore, since AmBisome can safely achieve higher concentrations in serum than Fungizone, AmBisome is thought to have superior potency to Fungizone against fungal infections.

Amphotericin B↗

PubMed2006

Pharmaceutical evaluation of cultivated Glycyrrhiza uralensis roots in comparison of their antispasmodic activity and glycycoumarin contents with those of licorice.

In China, the collection of wild Glycyrrhiza uralensis, one of the raw materials of Chinese licorice, has been restricted to prevent desertification. To compensate for the reduced supply of wild Glycyrrhiza plants, cultivation programs of G. uralensis have been initiated in eastern Inner Mongolia. The goal of the present study was to compare the chemical and pharmacological properties of cultivated G. uralensis roots to those of licorice prepared from wild Glycyrrhiza plants. The antispasmodic effect of boiled water extract of 4-year-old cultivated G. uralensis roots and licorice on carbachol-induced contraction in mice jejunum was similar (ED(50): 134+/-21 microg/ml vs. 134+/-16 microg/ml). In addition, glycycoumarin content, which is an antispasmodic and species-specific ingredient of G. uralensis, was similar when comparing the boiled water extracts of 4-year-old cultivated roots and licorice (0.10+/-0.02% vs. 0.10+/-0.06%). These data suggest that cultivated G. uralensis roots may be an adequate replacement for the generation of licorice in the context of the restriction of wild Glycyrrhiza plant collection.

Animals↗

PubMed2006

A case report of paraneoplastic neurological syndrome associated with occult breast cancer.

Paraneoplastic syndromes are the rarest neurological complications in patients with breast cancer. Here, we present a case of occult breast cancer presenting as paraneoplastic sensory neuropathy. A 47-year-old woman developed progressive upper and lower extremity weaknesses with paresthesia and gait ataxia. Multiple cerebrospinal fluid (CSF) analyses and magnetic resonance image (MRI) scans of her brain and spine offered no diagnosis. Although no paraneoplastic antibodies were found, paraneoplastic neurological syndrome was suspected after examination by the neurologist eliminated other possibilities. Her mammogram demonstrated pleomorphic calcifications. Although local and systemic therapies were given, no significant improvement in the neurologic condition was found.

Biopsy, Needle↗

PubMed2006

Development of fluorescence-linked immunosorbent assay for high throughput screening of interferon-gamma.

BACKGROUND: Human interferon-gamma (hIFN-gamma) is produced by lymphocytes and has a variety of biological properties. Measurement of hIFN-gamma is widely used for various immunological responses for allergic or autoimmune diseases. Enzyme-linked immunosorbent assay (ELISA) is an established immunoassay used to quantify cellular metabolites or cytokines. ELISA requires many incubation and wash steps and is not practically suitable for screening large numbers of samples. METHODS: We have developed a fluorescence-linked immunosorbent assay (FLISA) method for the detection of hIFN-gamma. We measured the 50% inhibitory concentration (IC50) value of the hIFN-gamma production by interleukin (IL)-18 binding protein and anti-IL-18 monoclonal antibody. The IC50 described by FLISA was compared with that by ELISA. RESULTS: We developed a new system for measuring hIFN-gamma using Allophycocyanine (APC) fluorescent protein and compared it with the previous method using Cy5.5. The proposed FLISA had a smaller coefficient of variation than ELISA, and the means of coefficient of variation using the same samples measured by ELISA and FLISA were, respectively, 11.1% and 3.8%, suggesting that the edge effect often giving non-specific results may be smaller in FLISA than in ELISA. CONCLUSIONS: The improved FLISA system proposed is ideally suited for efficient measurements of hIFN-gamma. This homogeneous and multiplex method will be a powerful tool for high throughput screening for drug discovery research.

Antibodies, Monoclonal↗

PubMed2006

[Two cases of stage IV breast cancer with severe hypercalcemia].

Case 1: A 34-year-old woman,who had a right breast cancer with axillary lymph node metastasis and multiple bone metastases, was referred to our clinic. She developed paralysis of lower extremities and disorder of the bladder and rectum due to metastasis to the thoracic vertebra, and also had renal dysfunction due to severe hypercalcemia and hemorrhagic cystitis. Correcting the serum calcium level with intravenous infusion, elcatonin, pamidronate and betamethasone, she underwent radiation therapy for the vertebral metastasis. The first hormonal therapy (leuprorelin/exemestane) had been effective for about 4 months, however the second hormonal therapy (leuprorelin/tamoxifen) was not effective. Chemotherapy with paclitaxel (80 mg/m(2), day 1, 8, 15, every 4 weeks) brought about a stable general condition and a normal level of serum calcium with zoledronate in the ninth month of treatment. Case 2: A 32-year-old woman, who had a right breast cancer with multiple bone metastases and axillary and hilar lymph node metastases, came to our clinic, complaining of nausea due to severe hypercalcemia. After successful correction of hypercalcemia by the intravenous infusion and administration of elcatonin, pamidronate and dexamethasone, the hormonal therapy(goserelin/tamoxifen) caused rapid re-elevation of serum calcium and tumor marker, so that a tumor flare was suspected. After 3 cycles of EC therapy (EPI 90 mg/m(2), CPM 600 mg/m(2), every 3 weeks), 2 cycles of paclitaxel therapy (80 mg/m(2), day 1, 8, 15, every 4 weeks) brought about tumor reduction and the normal level of serum calcium. After 7 cycles of paclitaxel therapy,the hormonal therapy (goserelin/tamoxifen) proved effective for several months. To achieve tumor reduction and stabilize the serum calcium level, we need to start immediately the treatment of breast cancer with severe hypercalcemia, considering the general condition of the patient.

Adult↗

PubMed2006

[Localized amyloidosis of the ureter: a case report].

A 46-year-old female was referred to our hospital with a complaint of left flank pain. Ultrasongraphy and computed tomography demonstrated a left hydronephroureter due to stenosis with a ureteral mass in the left lower ureter. Retrograde pyelography revealed severe stricture of left lower ureter and brushing cytology showed papanicolaou class III. Ureteral tumor was suspected and left nephroureterectomy with partial cystectomy was performed. Histopathological diagnosis was amyloidosis of the left ureter. There was no evidence of secondary or systemic amyloidosis. Finally, we diagnosed her with localized amyloidosis of the left ureter. Localized amyloidosis of the ureter is a relatively rare condition, and this is the 55th case reported in the Japanese literature.

Amyloidosis↗

PubMed2006

[Clinical evaluation of urinary NMP22 (nuclear matrix protein 22) bladder chek in the detection of patients with bladder cancer].

The clinical usefulness of the nuclear matrix protein 22 (NMP22) Bladder Chek test as a novel urine marker in the detection of patients with bladder cancer was evaluated in comparison with the urinary NMP22 enzyme-linked immunosorbent assay (ELISA) and urinary cytology. A total of 40 patients with pathologically proven bladder cancer voided urine specimen before treatment. The urine samples were divided for NMP22 Bladder Chek test, NMP22 ELISA, and urinary cytology. In the 40 patients with bladder cancer, the overall positive rate was 62.5% for the NMP22 Bladder Chek test, 55% for the NMP22 ELISA test, and 27.5% for urine cytology. There was a significant difference between NMP22 Bladder Chek, NMP22 ELISA and cytology. The positive rate with the NMP22 Bladder Chek and NMP22 ELISA was higher in the patients with high grade and large-size (1 cm < or =) tumor. In 40 patients presenting with microhematuria without urothelial cancer, the false positive rate 12.5, 10, and 0% for NMP22 Bladder Chek, NMP22 ELISA, and urinary cytology. No significant difference was found with the test. In conclusion, the urine NMP22 Bladder Chek test provided a higher positive rate than the NMP22 ELISA test and urinary cytology. Therefore, the NMP22 Bladder Chek test may be clinically more useful as a tumor marker for the diagnosis of bladder cancer.

Adult↗

PubMed2006

[Inflammatory pseudotumor of the urinary bladder: a case report].

A 65-year-old female was referred to our hospital with a complaint of urinary retention and macrohematuria. Ultrasongraphy, computed tomography, magnetic resonance imaging and cystoscopy revealed a 2 x 2 cm broad-based nonpapillary bladder tumor localized in the anterior wall of the urinary bladder. The clinical diagnosis was an invasive bladder tumor and transurethral resection of bladder tumor carried out for pathological investigation. Finally, we diagnosed it as inflammatory pseudotumor of urinary bladder. No local recurrence was seen 12 months after surgery. Inflammatory pseudotumor of urinary bladder is a relatively rare condition, and this is the 52nd case reported in the Japanese literature.

Aged↗

PubMed2006

[Early effect of non-surgical treatment using betamethasone valerate ointment for phimosis in childhood].

We evaluated the early efficacy of non-surgical treatment using 0.07% betamethasone valerate ointment on, 34 boys with phimosis between January 2001 and June 2005. Patients were treated with 0.07% betamethasone valerate ointment applied to the distal aspect of the prepuce every other day for 2-6 weeks. During the treatment period, patients were instructed to retract the foreskin to penis root without overstraining. The overall success rate was 94.1% and therapeutic effects were observed in 58.8% of the patients in two weeks. There were no medical side effects. Treatment using betamethasone valerate ointment is very effective, easy and safe. We recommend this treatment for patients with phimosis and/or those with recurring balanoposthitis.

Anti-Inflammatory Agents↗

PubMed2006

[Adjuvant doxorubicin and cyclophosphamide followed by weekly paclitaxel for Japanese women with node-positive breast cancer: a multi-institutional feasibility study in a variety of practice settings in Kyushu].

We evaluated the feasibility of doxorubicin plus cyclophosphamide (AC) followed by weekly paclitaxel (wT) as adjuvant therapy for node-positive breast cancer in a variety of practice settings. Forty-seven patients received AC at either doses of 40 mg/m(2)+400 mg/m(2) (A(40)C(400), 33 patients) or 50 mg/m(2)+500 mg/m(2) (A(50)C(500), 14 patients) every 3 weeks for 4 cycles followed by wT at a dose of 80 mg/m(2)for 12 cycles with a week pause after 3 consecutive weekly administrations. Mean relative dose-intensities were 98.8% for A(40)C(400), 90.7% for wT after A(40)C(400), 91.3% for A(50)C(500), and 89.2% for wT after A(50)C(500). Grade 4 toxicity included neutropenia (3.0% for A(40)C(400), 14.3% for A(50)C(500)). Grade 3 toxicity included neutropenia (18.2% for A(40)C(400), 28.6% for A(50)C(500), 6.7% for wT), thrombocytopenia (2.2% for wT), nausea/vomiting (6.1% for A(40)C(400)), anorexia (3.0% for A(40)C(400), 2.2% for wT), fatigue (3.0% for A(40)C(400)), AST/ALT elevation (7.1% for A(50)C(500)), allergic reaction (4.4% for wT). There were six (12.8%) treatment discontinuations, including two allergic reactions to paclitaxel. AC followed by wT can be administered safely in the community at doses of 50 mg/m(2), 500 mg/m(2), and 80 mg/m(2), respectively,with minimal toxicity.

Adult↗

PubMed2006

[Therapeutic efficacy of capecitabine on advanced and recurrent breast cancer with special reference to time to progression].

We investigated 29 patients with advanced and recurrent breast cancers who underwent capecitabine therapy in the department. Patients'backgrounds: 41-89 years of age (median, 57 years of age). Advanced breast cancers, 5; recurrent breast cancers, 24. PS< or =2 in 18 cases and PS 3< or =in 11 cases. Eighty-six percent of patients were positive for ER and/or PgR. Multiorgan metastases occurred in 22 cases; bone metastases, 22 cases; lymph node metastases, 12 cases; skin metastases, 11 cases; lung metastases, 10 cases. The rate of patients who received chemotherapy was 93%, and the rate of those who received endocrinotherapy was 90%. Therapeutic response rate was CR in 1 case, PR in 5 cases, long SD in 5 cases, SD in 10 cases and PD in 8 cases, indicating a response rate of 20.7% and a clinical benefit rate of 37.9%. Time to progression (TTP) was 1-15 months (the median time, 4 months). Overall survival time (OS) was 2-23 months (median length, 12 months). OS was significantly longer in patients who had therapeutic effects than in patients with no such effects. TTP was significantly longer in patients who had therapeutic effects and in those who had longer SD than in patients with no such effects. OS was significantly longer in patients who had TTP of 6 months or longer. Clinical benefit (presence vs. absence) and PS (< or =2 vs. 3< or =) were independent factors affecting TTP. Capecitabine is expected to prolong the length of survival in patients who are able to continue treatment for 6 months or longer.

Adult↗

PubMed2006

[A clinical study of renal pelvic and ureteral cancer].

We investigated the clinicopathological features of 52 patients with transitional cell carcinoma of renal pelvic and/or ureter who underwent surgical treatment at Tokyo Medical University Hachioji Medical Center from April, 1992 to June, 2005. The patitents consisted of 38 males and 14 females, ranging from 29 to 86 years old with a median age of 68 years old. The mean follow-up period was 39 months. Pathologicaly, 32 cases were less than pT2 and 20 cases were pT3. Findings of lymphatic and venous invasion were present in 10 and 8 cases, respectively. The infiltration pattern (INF) of gamma was observed in 9 cases. The overall cause-specific survival rate was 95.8% at 1 year, 87.7% at 3 years and 80.6% at 5 years, respectively. According to univariate analysis, the high stage of tumor, the presence of lymphatic and/or venous invasion, the inclusion of infiltration pattern of gamma and positive reginonal lymph nodes indicated a significantly poor prognosis. On the other hand, multivariate analysis using Cox proportional hazards regression revealed the presence of infiltration pattern of gamma as the most significant predictor of survival.

Adult↗

PubMed2005

Molecular mechanism of a temperature-sensitive phenotype in peroxisomal biogenesis disorder.

Peroxisomal biogenesis disorders include Zellweger syndrome and milder phenotypes, such as neonatal adrenoleukodystrophy (NALD). Our previous study of a NALD patient with a marked deterioration by a fever revealed a mutation (Ile326Thr) within a SH3 domain of PEX13 protein (Pex13p), showing a temperature-sensitive (TS) phenotype in peroxisomal biogenesis. Clinical TS phenotypes also have been reported in several genetic diseases, but the molecular mechanisms still remain to be clarified. The immunofluorescent staining with anti-Pex13p antibody also revealed TS phenotype of the I326T mutant protein itself in the patient cells. Protease digestion of the recombinant Pex13p-SH3 domain showed an increase of protease susceptibility, suggesting a problem of mutant protein fold. Conformational analyses against urea denaturation using urea gradient gel electrophoresis or fluorescence emission from tryptophan residue revealed that the mutant protein should be easily unfolded. Far-UV circular dichroism (CD) spectra demonstrated that both wild-type and the mutant protein have antiparallel beta-sheets as their secondary structure with slightly different extent. The thermal unfolding profiles measured by CD showed a marked lower melting temperature for I326T protein compared with that of wild-type protein. Analysis of the protein 3D-structure indicated that the Ile326 should be a core residue for folding kinetics and the substitution of Ile326 by threonine should directly alter the kinetic equilibrium, suggesting a marked increase of the unfolded molecules when the patient had a high fever. Structural analyses of the protein in the other genetic diseases could provide an avenue for better understanding of genotype-phenotype correlations.

Amino Acid Motifs↗