Biomedical subjects

Mamoru Fukuda

Publications and source records attributed to Mamoru Fukuda.

At least 19 recordsLinked to original sources

PubMed2007

Ductal carcinoma in situ: correlations between high-resolution magnetic resonance imaging and histopathology.

PURPOSE: The aim of this retrospective study was to determine and correlate contrast-enhanced areas and multiple internal dark dots and lines on high-resolution magnetic resonance imaging (HR-MRI) with findings in surgical specimens of ductal carcinoma in situ (DCIS) and to evaluate the ability of HR-MRI to detect DCIS lesions and clarify HR-MRI features characteristic of DCIS. MATERIALS AND METHODS: This study retrospectively reviewed 11 patients diagnosed with DCIS who had undergone HR-MRI. Pathological findings and results of HR-MRI were compared, and causes of periductal enhancements were analyzed. RESULTS: In all patients, HR-MRI using microscopic coils revealed ductally, segmentally, or regionally enhanced areas containing multiple dark dots and lines, representing local enhancement of stroma adjacent to the mammary duct containing DCIS. Neovascularization, infiltration of inflammatory cells, and focal edema occurred in enhanced periductal stroma. Poorly enhanced linear or dot-like structures correlated with dilated mammary ducts displaying necrosis and tumor impaction. CONCLUSION: DCIS was successfully depicted on HR-MRI using a microscopy coil in all 11 cases. Ductal, segmental, or regional areas of enhancement with multiple dark dots and lines on HR-MRI corresponded to mammary glands containing DCIS with periductal enhancement.

Adult↗

PubMed2007

Diagnostic accuracy of high-resolution MRI using a microscopy coil for patients with presumed DCIS following mammography screening.

PURPOSE: To prospectively evaluate the accuracy of high-resolution (HR)-MRI as a secondary examination in women with abnormal calcifications detected on mammography. MATERIALS AND METHODS: We used a 4.7-cm microscopy coil to acquire HR-MRI signal data. We examined 52 women with breast lesions preoperatively using HR-MRI and vacuum-assisted core needle biopsy. The lesions were suspicious of malignancy, classified as category 3-5 on mammography (Breast Imaging Reporting and Data System [BI-RADS]), and without a palpable mass. All visualized suspicious lesions were correlated with histological findings. We compared the HR-MRI and pathological findings and calculated the sensitivity, specificity, and accuracy. RESULTS: We compared the breast HR-MRI results with the gold standard of pathological results for studies of malignancy (DCIS and invasive cancer), and found a sensitivity of 88.5%, specificity of 92.3%, and accuracy of 90.4%. The positive predictive value (PPV) was 92%, and the negative predictive value (NPV) was 88.9%. When breast MRI was compared with pathological results for studies that diagnosed DCIS only, the results revealed a sensitivity of 88.6%, specificity of 88.2%, accuracy of 88.5%, PPV of 93.9%, and NPV of 78.9%. CONCLUSION: HR-MRI using a microscopy coil is a useful, reliable, safe, and minimally invasive procedure that is a good choice for secondary assessment of abnormal calcification in the breast.

Adult↗

PubMed2006

Floating hot-melt extruded tablets for gastroretentive controlled drug release system.

The purpose of this study was to investigate the influence of sodium bicarbonate on the physicochemical properties of controlled release hot-melt extruded (HME) tablets containing Eudragit RS PO and/or Eudragit E PO. Acetohydroxamic acid and chlorpheniramine maleate were used as model drugs. Sodium bicarbonate was incorporated into the tablet formulations and the drug release properties and buoyancy in media for HME tablets and directly compressed (DC) tablets were investigated. The HME tablets prepared from the powder blend containing both Eudragit RS PO and sodium bicarbonate exhibited sustained release properties and the tablets floated on the surface of the media for 24 h. The cross-sectional morphology of the HME tablets showed a porous structure since CO(2) gas was generated due to the thermal decomposition of sodium bicarbonate in the softened acrylic polymers at elevated temperature during the extrusion process. In contrast, all DC tablets prepared in this study showed no buoyancy and rapid drug release in the dissolution media. The drug release rate from floating HME tablets was controlled by both the incorporation of Eudragit E PO into the matrix tablet and the diameter of the die used in the extrusion equipment. The drug release profiles and buoyancy of the floating HME tablets were stable when stored at 40 degrees C/75%RH for 3 months.

Algorithms↗

PubMed2006

[Parathyroid cancer].

Explore the source record for details and available documents.

Diagnosis, Differential↗

PubMed2006

A truncated splice variant of human BARD1 that lacks the RING finger and ankyrin repeats.

BARD1 is a crucial partner of the breast and ovarian tumor suppressor BRCA1 required for ubiquitin ligase activity and for reciprocal stabilization in cells. We report here an alternatively spliced human BARD1 mRNA variant (BARD1DeltaRIN) isolated from a HeLa cell cDNA library. It is characterized by deletion of exons 2-6 that encode most of the RING finger domain and the entire span of ankyrin repeats. DeltaRIN transcript was detected in all breast cancer-cell lines studied although its protein expression level was low. DeltaRIN does not interact with BRCA1, whereas it interacts with and colocalizes with CstF-50 to cytoplasmic dots. Hence, a deletion variant of BARD1 occurs in cells and may play a distinct role with CstF-50.

Amino Acid Sequence↗

PubMed2006

Properties of sustained release hot-melt extruded tablets containing chitosan and xanthan gum.

The aim of this study was to investigate the influence of pH, buffer species and ionic strength on the release mechanism of chlorpheniramine maleate (CPM) from matrix tablets containing chitosan and xanthan gum prepared by a hot-melt extrusion process. Drug release from hot-melt extruded (HME) tablets containing either chitosan or xanthan gum was pH and buffer species dependent and the release mechanisms were controlled by the solubility and ionic properties of the polymers. All directly compressed (DC) tablets prepared in this study also exhibited pH and buffer species dependent release. In contrast, the HME tablets containing both chitosan and xanthan gum exhibited pH and buffer species independent sustained release. When placed in 0.1N HCl, the HME tablets formed a hydrogel that functioned to retard drug release in subsequent pH 6.8 and 7.4 phosphate buffers even when media contained high ionic strength, whereas tablets without chitosan did not form a hydrogel to retard drug release in 0.1N HCl. The HME tablets containing both chitosan and xanthan gum showed no significant change in drug release rate when stored at 40 degrees C for 1 month, 40 degrees C and 75% relative humidity (40 degrees C/75% RH) for 1 month, and 60 degrees C for 15 days.

Chemistry, Pharmaceutical↗

PubMed2006

Studies on the constituents of the leaves of Baccharis dracunculifolia (Asteraceae) and their cytotoxic activity.

A new sesquiterpene, named baccharisketone (1), and a new monoterpene, p-methoxythymol acetate (2), were isolated from the leaves of Baccharis dracunculifolia along with seventeen known compounds (3-19). The structures of the new compounds were determined by spectroscopic means. The growth inhibitory activity of the isolated compounds against leukemia cells (L 1210) was tested and three terpene phenols (4, 6, 17) and five sesquiterpene alcohols (8, 10, 11, 13, 16) were found to exhibit strong cytotoxic activity.

Baccharis↗

PubMed2006

Intraductal papilloma: features on MR ductography using a microscopic coil.

OBJECTIVE: The purpose of this study was to describe the features of intraductal papilloma on MR ductography using a microscopic coil. CONCLUSION: Intraductal papilloma appeared in most cases as a well-circumscribed mass with early enhancement and delayed washout associated with a dilated duct, predominantly showing signal hyperintensity on T1- and T2-weighted imaging.

Adult↗

PubMed2005

Down-regulation of BRCA1-BARD1 ubiquitin ligase by CDK2.

BRCA1, a breast and ovarian tumor suppressor, is a phosphoprotein whose cellular expression level is regulated in a cell cycle-dependent manner. BRCA1 interacts with BARD1 to generate significant ubiquitin ligase activity which catalyzes nontraditional Lys-6-linked polyubiquitin chains. However, it is not clear how the activity is regulated and how this affects BRCA1's multiple cellular functions. Here we show that the ubiquitin ligase activity of BRCA1-BARD1 is down-regulated by CDK2. During the cell cycle, BARD1 expression can largely be categorized into three patterns: moderately expressed in a predominantly unphosphorylated form in early G(1) phase, expressed at low levels in both phosphorylated and unphosphorylated forms during late G(1) and S phases, and highly expressed in its phosphorylated form during mitosis coinciding with BRCA1 expression. CDK2-cyclin A1/E1 and CDK1-cyclin B1 phosphorylate BARD1 on its NH(2) terminus in vivo and in vitro. Intriguingly, the BRCA1-BARD1-mediated in vivo ubiquitination of nucleophosmin/B23 (NPM) and autoubiquitination of BRCA1 are dramatically disrupted by coexpression of CDK2-cyclin A1/E1, but not by CDK1-cyclin B1. The inhibition of ubiquitin ligase activity is not due to the direct effect of the kinases on BARD1 because an unphosphorylatable mutant of BARD1, S148A/S251A/S288A/T299A, is still inhibited by CDK2-cyclin E1. Alternatively, BRCA1 and BARD1 are likely exported to the cytoplasm and their expressions are remarkably reduced by CDK2-cyclin E1 coexpression. Recognizing the importance of cyclin E1 overexpression in breast cancer development, these results suggest a CDK2-BRCA1-NPM pathway that coordinately functions in cell growth and tumor progression pathways.

BRCA1 Protein↗

PubMed2005

Ultrasonographic findings of invasive lobular carcinoma differentiation of invasive lobular carcinoma from invasive ductal carcinoma by ultrasonography.

BACKGROUND: Although controversy exists, invasive lobular carcinoma (ILC) differs in its high frequency of microscopically positive margins after conservative therapy compared to invasive ductal carcinoma (IDC). If ILC could be recognized by imaging modalities, it would provide important information for surgeons. We tried to confirm whether it is possible to distinguish ILC from other invasive carcinomas by ultrasonography (US). METHODS: A total of 81 histologically confirmed cases of IDC, including 26 cases of papillotubular carcinoma, 28 cases of solid-tubular carcinoma and 27 cases of scirrhous carcinoma, as well as 24 cases of ILC were selected and retrospectively studied with regard to the features of mass lesions on US examination. RESULTS: The sensitivities of US for papillotubular carcinoma, solid-tubular carcinoma, scirrhous carcinoma and ILC were 88.5%, 100%, 92.6% and 91.7% respectively. We could divide invasive breast cancer into two groups by US findings. One group had a low frequency of malignant findings and consisted of papillotubular and solid-tubular carcinomas, and the other group had a high frequency of malignant findings and consisted of scirrhous carcinomas and ILC. However, there were no statistical differences between papillotubular carcinoma and solid-tubular carcinoma or between scirrhous carcinoma and ILC with regard to the US findings. CONCLUSIONS: Scirrhous carcinoma, the most common type of IDC, and ILC are difficult to distinguish by US. Therefore it is difficult to separate ILC from IDC by US.

Adult↗

PubMed2005

[Application of sentinel node navigation surgery to prostate cancer].

A sentinel node (SN) validation study using a radioactive tracer and back-up extended pelvic lymph node (LN) dissection was performed in 40 patients with non-metastatic prostate cancer (PCa). The results of the study were favorable, with sensitivity, specificity, and accuracy of SN biopsies revealed 90%, 100%, and 97.5%, respectively. Although 1 patient had false negative LNs, the SN concept was still validated because extensive LN metastasis disrupted the physiological lymphatic flow in this case. Based on our promising results to date, we examined the utility of SN navigation surgery (SNNS) in patients with LN metastasis probability of 10% or less on Partin tables. Endoscopic minilaparotomy surgery, established by Kihara et al., was applied to our SN biopsies in 9 patients with clinically localized PCa. SNs were successfully resected in 7 of these patients. Limited pelvic LN dissection was performed in 3 patients, including 1 patient with LN metastasis. SN biopsy and radical prostatectomy were performed via a 5-cm lower abdominal incision. In summary, endoscopic minilaparotomy SNNS is a less invasive form of radical surgery for PCa that offers accurate diagnosis of LN status.

Endoscopy↗

PubMed2005

[Cancer screening].

The purpose of cancer screening is to widen the difference between morbidity and mortality of the target cancer. Since 1983 cancer screening has been supported by the Japanese government. Initially it covered gastric and cervical cancer with lung, breast and endometrial cancers supported from 1987 and colorectal cancer in 1992. Since 1998 support for cancer screening has been transferred to local government. It is generally accepted that the uptake of screening services is too low. Estimates for Japan suggest that at best 30% of the eligible population accept the services. In other parts of the world screening is more widely accepted, for example, 67% for breast cancer and 79% for cervical screening in the USA. Barriers within Japan for increasing screening are complex and include, legal, ethical, financial, technical infrastructure, data related matters and the level of understanding and education of the general public. In 2000 the MHLW conducted an evaluation of cancer screening in terms of usefulness and effectiveness. It concluded that fair or better evidence for reduction in mortality existed for cervical cancer (cytology), breast cancer (mammography with clinical examination for women aged > or = 50 years), colorectal cancer (faecal occult blood test), gastric cancer, lung cancer and liver cancer. As a step towards improving screening services and their uptake by the general public a new Research Centre for Cancer Prevention and Screening was established at the National Cancer Centre in October 2003. This and other initiatives will build on the progress of the past 20 years but it is generally agreed that there is still have a long way to go.

Adult↗

PubMed2005

[Sentinel lymph node concept in prostate cancer].

Endoscopy↗

PubMed2005

Fusion of SPECT and multidetector CT images for accurate localization of pelvic sentinel lymph nodes in prostate cancer patients.

OBJECTIVE: The present study was performed to investigate the feasibility of fusion of images obtained by SPECT and multidetector CT (MDCT) for the accurate localization of sentinel lymph nodes in prostate cancer patients. METHODS: To facilitate the fusion of both SPECT and CT images, a pelvic MDCT scan was performed with 3 markers of small plastic bullets attached to the skin over the bilateral iliac crests and the ventral midline at the same height. SPECT was performed after the same locations were marked with needle caps containing (99m)Tc-pertechnetate. The images were superimposed by use of free software (MRIcro). The results of hot lymph node detection with fusion images were compared with those of surgery. RESULTS: The images could be successfully superimposed for all 11 patients examined. Surgeons accurately confirmed 27 (87.1%) of 31 regional lymph nodes on fusion images. CONCLUSION: Fusion of SPECT and MDCT images is useful for the precise localization of sentinel lymph nodes in prostate cancer patients.

Aged↗

PubMed2005

Structural inhomogeneity in mammography quality control phantoms detected by refraction-enhanced synchrotron radiation imaging.

Synchrotron radiation imaging with the refraction-enhancement mode visualized structural inhomogeneities in phantoms used for image quality control of mammography. Eight phantoms were examined, all of which were manufactured in the United States and approved by the American College of Radiology as dedicated phantoms. In addition to fiber- and mass-mimicking test objects, each phantom has 5 groups of calcification specks of various sizes. Synchrotron radiation (SR) imaging was performed at Spring-8, a synchrotron radiation facility in Japan. Images were obtained with monochromatic 20-keV x-ray beams, a radiation field of 15 mm X 26 mm at a sample plane, a CCD camera with a resolution of 6 micrometers as a detector, and a sample-to-detector distance of 10 to 11 m. Two hundred and forty specks were evaluated in total in the SR images, and the surrounding area of each speck was also included. Evaluation of the images showed that 14 crack-like structures were depicted near specks, and there were 62 specks with attached void(s) or air bubble(s). Refraction-enhanced SR imaging sensitively detected structural inhomogeneities and abnormalities in phantoms which were implicitly agreed to have a homogeneous matrix and test objects without foreign substances. A possible manufacturing-dependent quality issue was identified. The effect of inhomogeneities detected by SR imaging on visual scoring of specks could not be identified in the tested phantoms; this should be assessed on images of other phantoms in a future study.

Mammography↗

PubMed2004

Nucleophosmin/B23 is a candidate substrate for the BRCA1-BARD1 ubiquitin ligase.

The breast and ovarian tumor suppressor BRCA1 forms a heterodimeric RING-type ubiquitin ligase with BARD1 to catalyze untraditional Lys-6-linked polyubiquitin chains. It is not clear how the BRCA1-BARD1 ligase regulates various cellular processes such as DNA repair, cell-cycle progression, transcriptional regulation, and centrosome duplication. Here we report that BRCA1-BARD1 catalyzes the polyubiquitination of nucleolar phosphoprotein nucleophosmin/B23 (NPM). Two different mass spectrometry screens for protein ubiquitinated by BRCA1-BARD1 both identified NPM. NPM interacts with N-terminal fragments of BRCA1 and BARD1 in a manner dependent upon BRCA1-BARD1 heterodimer formation. NPM colocalizes with BRCA1 and BARD1 in mitotic cells suggesting the possibility of NPM regulation by BRCA1-BARD1 during mitosis. BRCA1-BARD1 catalyzes the ubiquitination of NPM in vitro and in vivo, and BRCA1-BARD1 co-expression in cells causes NPM stabilization rather than degradation. This is consistent with the notion that this ligase catalyzes untraditional polyubiquitin chains. Given the many overlapped functions between NPM and BRCA1, we propose that NPM is a strong candidate as a substrate of the BRCA1-BARD1 ubiquitin ligase.

Animals↗

PubMed2004

Ubiquitin and breast cancer.

The regulation of protein stability by the ubiquitin-proteasome pathway is a critical issue central to the comprehension of the molecular basis of carcinogenesis. However, ubiquitin modification of target substrates signals many cellular processes other than proteolysis that are also important for the development of cancer. It is noteworthy that many proteins studied by clinical breast cancer researchers are involved in these ubiquitin pathways. This review summarizes recent works on such proteins including cyclins, CDK inhibitors, and the SCF in cell cycle control; the breast and ovarian cancer suppressor BRCA1-BARD1; ErbB2/HER2/Neu and its ubiquitin ligase c-Cbl or CHIP; and the estrogen receptor and its downstream target Efp. Understanding these pathways may provide some hints toward developing diagnostic tools and treatments for breast cancer patients.

BRCA1 Protein↗

PubMed2004

A multicenter phase II study of docetaxel 60 mg/m2 as first-line chemotherapy in patients with advanced or recurrent breast cancer.

PURPOSE: Docetaxel is an active agent as first-line chemotherapy in patients with advanced breast cancer at a dosage of 100 mg/m2. However, the efficacy of this agent as a first-line drug when used at a lower dosage is unclear. This study was performed to evaluate the clinical efficacy and safety of 60 mg/m2 docetaxel for the treatment of breast cancer. PATIENTS AND METHODS: This study enrolled 23 patients with advanced and/or metastatic breast cancer, who had not been treated with an anthracycline or taxane previously. Treatment with docetaxel was continued in patients showing a response until there was evidence of disease progression or unacceptable toxicity. RESULTS: Among 20 fully evaluated patients, the overall response rate was 50.0% and the median time to progression was 31 weeks. The most commonly observed adverse events were neutropenia (78.2%) and fatigue (60.9%). Fluid retention occurred in only 8.7% of the patients. Adverse events did not cause discontinuation of the treatment. CONCLUSION: Docetaxel achieved good disease control with mild adverse events in first-line treatment at a dosage of 60 mg/m2.

Adult↗