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Noriaki Ohuchi

Publications and source records attributed to Noriaki Ohuchi.

At least 19 recordsLinked to original sources
PubMed2006

Reduction in nonfluorescence state of quantum dots on an immunofluorescence staining.

Fluorescence quantum dots are widely used in immunofluorescence staining because of their intense and stable fluorescence. However, the nonfluorescence state of the quantum dots is their disadvantage. Here, the nonfluorescence state of the dots labeled to cells and tissues was suppressed. Cells and tissues where the receptor HER2 had been overexpressed were fixed and then labeled with anti-HER2 crosslinked with the dots. The intensity of the dots increased with the illumination time. The majority of the single dots were in the nonfluorescence state at beginning of the illumination period and the number of fluorescence dots observed increased with the illumination time. Living cells were also labeled with the anti-HER2-Qdots. Blinking and bleaching of the Qdots was effectively suppressed by adding beta-mercaptoethanol and glutathione. Therefore, the movement of the Qdots bound to cell membrane could be observed for long periods of time.

Animals↗
PubMed2006

Cost-effectiveness analysis of screening modalities for breast cancer in Japan with special reference to women aged 40-49 years.

Although the introduction of screening mammography in Japan would be expected to reduce mortality from breast cancer, the optimal screening modality in terms of cost-effectiveness remains unclear. We compared the cost-effectiveness ratio, defined as the cost required for a life-year saved, among the following three strategies: (1) annual clinical breast examination; (2) annual clinical breast examination combined with mammography; and (3) biennial clinical breast examination combined with mammography for women aged 30-79 years using a hypothetical cohort of 100 000. The sensitivity, specificity and early breast cancer rates were derived from studies conducted from 1995 to 2000 in Miyagi Prefecture. The treatment costs were based on a questionnaire survey conducted at 13 institutions in Japan. We used updated parameters that were needed in the analysis. Although the effectiveness of treatment in terms of the number of expected survival years was highest for annual combined modality, biennial combined modality had a higher cost-effectiveness ratio, followed by annual combined modality and annual clinical breast examination in all age groups. In women aged 40-49 years, annual combined modality saved 852.9 lives and the cost/survival duration was 3 394 300 yen/year, whereas for biennial combined modality the corresponding figures were 833.8 and 2 025 100 yen/year, respectively. Annual clinical breast examination did not confer any advantages in terms of effectiveness (815.5 lives saved) or cost-effectiveness (3 669 900 yen/year). While the annual combined modality was the most effective with respect to life-years saved among women aged 40-49 years, biennial combined modality was found to provide the highest cost-effectiveness.

Adult↗
PubMed2006

Expression of the steroid and xenobiotic receptor and its possible target gene, organic anion transporting polypeptide-A, in human breast carcinoma.

Steroid and xenobiotic receptor (SXR) or human pregnane X receptor (hPXR) has been shown to play an important role in the regulation of genes related to xenobiotic detoxification, such as cytochrome P450 3A4 and multidrug resistance gene 1. Cytochrome P450 enzymes, conjugation enzymes, and transporters are all considered to be involved in the resistance of breast carcinoma to chemotherapeutic or endocrine agents. However, the expression of SXR/hPXR proteins and that of its target genes and their biological or clinical significance have not been examined in human breast carcinomas. Therefore, we first examined SXR/hPXR expression in 60 breast carcinomas using immunohistochemistry and quantitative reverse transcription-PCR. We then searched for possible SXR/hPXR target genes using microarray analysis of carcinoma cells captured by laser microscissors. SXR/hPXR was detected in carcinoma tissues but not in nonneoplastic and stromal cells of breast tumors. A significant positive correlation was detected between the SXR/hPXR labeling index and both the histologic grade and the lymph node status of the carcinoma cases. Furthermore, in estrogen receptor-positive cases, SXR/hPXR expression was also positively correlated with expression of the cell proliferation marker, Ki-67. Microarray analysis showed that organic anion transporting polypeptide-A (OATP-A) was most closely correlated with SXR/hPXR gene expression, and both OATP-A mRNA and protein were significantly associated with SXR/hPXR in both breast carcinoma tissues and its cell lines. These results suggest that SXR/hPXR and its target gene, such as OATP-A, may play important roles in the biology of human breast cancers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

MRI accurately depicts underlying DCIS in a patient with Paget's disease of the breast without palpable mass and mammography findings.

Breast-conserving therapy must be carefully indicated among patients with Paget's disease of the breast, because the disease is often associated with an underlying in situ or invasive carcinoma, even when there are no palpable mass or mammography findings. We report a 52-year-old woman who complained of skin color change of her right nipple for 11 months. No mass was palpable in her breasts, and mammography did not show any density or calcification. Nipple biopsy revealed Paget's disease of the breast with ductal carcinoma in situ (DCIS) in the breast epithelium just beneath the nipple. Magnetic resonance imaging (MRI) of the breast demonstrated diffuse segmental enhancement in two different quadrants. According to the pattern of enhancement, the lesions depicted by MRI were diagnosed as an extensively spreading type of DCIS. Based on informed consent, the patient received a total mastectomy. The histopathological examination demonstrated non-invasive ductal carcinoma with comedo-necrosis. The histological mapping with subserial sectioning demonstrated an extent of the lesions that corresponded accurately to the lesions defined by MRI. We conclude that MRI may play an important role in selecting candidates for breast-conserving therapy out of those patients with mammary Paget's disease with no clinical evidence of an underlying breast carcinoma.

Biopsy↗
PubMed2005

Nano-sized fluorescent particles as new tracers for sentinel node detection: experimental model for decision of appropriate size and wavelength.

The concepts of made-to-order and low-invasiveness medicines are becoming widely accepted. A treatment for cancer, with minimum invasive surgery and without lymph nodes dissection based on sentinel lymph node (SN) navigation surgery, would adhere to these concepts. Dyes and/or radioisotopes are employed for SN detection in standard methods, however, each detection method has advantages and disadvantages. To make up for the disadvantages, we aimed at developing a new non-invasive method using fluorescent beads of uniform nano-size that could efficiently visualize SN from outside the body, and conducted experiments to determine the appropriate size and fluorescent wavelength. We examined various bead sizes and fluorescent wavelengths. The sizes were 20, 40, 100 and 200 nm. The fluorescent peak wavelengths of the beads were yellow-green (515 nm), dark red (680 nm), far red (720 nm) and infrared (755 nm). The beads were subcutaneously injected into the foot pad of the hind leg of a rat, and followed by laser scanning of the inguinal area for fluorescence observation. The beads exhibited different times for the fluorescence detection according to their sizes and wavelength. The 40 nm beads were considered to be the most appropriate size for SN detection in rats. The wavelength of near infrared was effective for avoiding attenuation by the tissue. In conclusion, we confirmed that uniformly nano-sized fluorescent beads have the potential to be an alternative to existing tracers in the detection of the SN in animal experiments if we select the appropriate particle size and wavelength.

Animals↗
PubMed2005

Sex steroid-producing enzymes in human breast cancer.

It is well known that sex steroids are involved in the growth of breast cancers, and the great majority of breast carcinomas express estrogen (ER), progesterone (PR), and androgen (AR) receptors. In particular, recent studies have demonstrated that estrogens and androgens are locally produced in breast carcinoma tissues, and total blockade of in situ estrogen production potentially leads to an improvement in prognosis of breast cancer patients. Therefore, it is important to obtain a better understanding of sex steroid-producing enzymes in breast carcinoma tissues. In this review, we summarize recent studies on the expression and regulation of enzymes related to intratumoral production of estrogens (aromatase, 17beta-hydroxysteroid dehydrogenase type 1 (17betaHSD1), and steroid sulfatase (STS) etc) and androgens (17betaHSD5 and 5alpha-reductase) in human breast carcinoma tissues, and discuss the biological and/or clinical significance of these enzymes. The cellular localization of aromatase in breast carcinoma tissues still remains controversial. Therefore, we examined localization of aromatase mRNA in breast carcinoma tissues by laser capture microdissection/real time-polymerase chain reaction. Aromatase mRNA expression was detected in both carcinoma and intratumoral stromal cells, and the expression level of aromatase mRNA was higher in intratumoral stromal cells than in carcinoma cells in the cases examined. We also examined an association among the immunoreactivity of enzymes related to intratumoral estrogen production and ERs in breast carcinoma tissues, but no significant association was detected. Therefore, the enzymes responsible for the intratumoral production of estrogen may not always be the same among breast cancer patients, and not only aromatase but also other enzymes such as STS and 17betaHSD1 may have important therapeutic potential as targets for endocrine therapy in breast cancer patients.

Breast Neoplasms↗
PubMed2005

Breast conserving surgery with primary volume replacement using a lateral tissue flap.

Breast conserving surgery (BCS) is now a standard surgical treatment for early breast cancer. The number of patients with tumors under 3 cm who underwent breast conserving surgery overtook the number of patients who underwent total mastectomy for the first time in Japan in 2003. We have been employing breast conserving surgery with primary reconstruction using a lateral tissue flap (LTF), and have performed breast conserving surgery for 266 patients from 1990 to 2002. The incidence of local relapse was 5.6%. Although we did not irradiate a low risk group of 101 patients, our method is not inferior to other reports in which all cases underwent irradiation. Primary reconstruction with LTF has three advantages. The first is that we can avoid poly-surgery for breast reconstruction. The second is that the volume of the graft is maintained longer than reconstruction with a musculo-cutaneous flap. The third is that patients can avoid allergic reactions or granulomas as seen with artificial prosthesies. In conclusion, breast conserving surgery with immediate volume replacement with a LTF is a reasonable surgical procedure and has the advantage of avoiding unnecessary surgical procedures for reconstruction and surgical invasion without delaying the diagnosis of local relapse. Moreover, an adequate assessment of risk can spare low risk groups irradiation.

Axilla↗
PubMed2005

Pathological aspects of core needle biopsy for non-palpable breast lesions.

Recently, the incidence of non-palpable or noninvasive breast cancer has increased. Consequently, criteria for choosing procedures to obtain pathological materials had changed. Fine needle aspiration biopsy cytology (FNA) and core needle biopsy (CNB) are both reliable procedures for detecting breast cancer. However, for non-palpable lesions, the diagnostic accuracy of CNB is higher. The main limits of FNA are the high rate of insufficient sampling and inability to determine invasiveness. CNB is an established alternative to surgical biopsy, and CNB can avoid excess surgical biopsies in a large number of patients. In addition to accurate histological diagnosis, there is interest in obtaining prognostic information from CNB, especially for patients being considered for preoperative (neoadjuvant) therapy. CNB provides useful information about histologic type and grade. However, an unavoidable problem of CNB is underestimation of invasion. On the other hand, there is good concordance in particular for estrogen receptor (ER) and progesterone receptor (PR) between CNB and surgical excision. Several aspects of CNB remains controversial, such as diagnosing papillary lesions by CNB, problems regarding tumor cell displacement after CNB, and management of lobular neoplasia (LN) on CNB.

Biopsy, Needle↗
PubMed2005

Long-term outcome of breast-conserving therapy for breast cancer.

PURPOSE: We present a retrospective analysis of long-term therapeutic results for patients treated in our institution to evaluate the efficacy of breast-conserving therapy (BCT). PATIENTS AND METHODS: The study population was 99 patients (102 breasts) with stage 0, I, and II breast cancer who underwent breast conservation therapy between April 1990 and November 1997. The entire breast was irradiated to a median dose of 50 Gy (range, 50-60 Gy) in 25-30 fractions. An additional 10 Gy in five fractions with 6-12 MeV electrons was given to 23 breasts (23%) with positive surgical margins. RESULTS: The 5-/10-year overall survival, cause-specific survival, relapse-free rate, local recurrence, and regional recurrence rates were 94.6/93.3%, 95.7/94.5%, 88.2/77.5%, 4.2/8.5%, and 2.0/6.3%, respectively. In both uni- and multivariate analyses, age < 40 years was a significant prognostic factor for local recurrence. No severe morbidity was observed. CONCLUSION: The long-term clinical outcome of BCT for early breast carcinoma patients in our department was favorable. Patient age <40 was the most important factor associated with an increased risk of local recurrence in the ipsilateral breast.

Adult↗
PubMed2004

Estrogen-related receptor alpha in human breast carcinoma as a potent prognostic factor.

Estrogen-related receptor alpha (ERRalpha) was identified as a gene related to estrogen receptor alpha (ERalpha) and belongs to a class of nuclear orphan receptors. ERRalpha binds to estrogen responsive element(s) (ERE) and is considered to be involved in modulation of estrogenic actions. However, biological significance of ERRalpha remains largely unknown. Therefore, we examined the expression of ERRalpha in human breast carcinoma tissues using immunohistochemistry (n = 102) and real-time reverse transcription-PCR (n = 30). ERRalpha immunoreactivity was detected in the nuclei of carcinoma cells in 55% of breast cancers examined, and relative immunoreactivity of ERRalpha was significantly (P = 0.0041) associated with the mRNA level. Significant associations were detected between ERalpha and ERE-containing estrogen-responsive genes, such as pS2 (P < 0.0001) and EBAG9/RCAS1 (P = 0.0214), in breast carcinoma tissues. However, no significant association was detected between ERalpha and pS2 (P = 0.1415) in the ERRalpha-positive cases (n = 56) or between ERalpha and EBAG9/RCAS1 (P = 0.8271) in the ERRalpha-negative group (n = 46). ERRalpha immunoreactivity was significantly associated with an increased risk of recurrence and adverse clinical outcome by both uni- (P = 0.0097 and P = 0.0053, respectively) and multi- (P = 0.0215 and P = 0.0118, respectively) variate analyses. A similar tendency was also detected in the group of breast cancer patients who received tamoxifen therapy after surgery. Results from our study suggest that ERRalpha possibly modulates the expression of ERE-containing estrogen-responsive genes, and ERRalpha immunoreactivity is a potent prognostic factor in human breast carcinoma.

Adult↗
PubMed2004

Identification and evaluation of 55 genetic variations in the BRCA1 and the BRCA2 genes of patients from 50 Japanese breast cancer families.

We sequenced approximately 23 kb genomic regions containing all the coding exons and their franking introns of two breast cancer susceptibility genes, BRCA1 and BRCA2, of 55 individuals from 50 unrelated Japanese breast cancer families. We identified 55 single-nucleotide polymorphisms (SNPs) (21 in BRCA1 and 34 in BRCA2) containing nine pathogenic protein-truncating mutations (four in BRCA1 and five in BRCA2 from ten patients). Among the remaining 46 SNPs, allele frequencies of 40 were examined in both the breast cancer patients and 28 healthy volunteers with no breast cancer family history by PCR-RFLP or by direct DNA sequencing. Twenty-eight SNPs were common and were also found in the healthy volunteers and/or a SNP database. The remaining 18 were rare (allele frequency <0.05) and were not found in the healthy volunteers and/or the database. The pathogenic significance of these coding SNPs (cSNPs) remains to be clarified. The SNP information from this study will be useful in the future genetic testing of both BRCA1 and BRCA2 genes in the Japanese population.

Alleles↗
PubMed2004

The increase of female breast cancer incidence in Japan: emergence of birth cohort effect.

During recent decades, breast cancer incidence has been increasing in Japan. According to the latest reports from several cancer registries in Japan, the breast has become the leading cancer site in female cancer incidence. To analyze the trend of breast cancer incidence in detail, we summarized female breast cancer incidence in Miyagi Prefecture, Japan during 1959-1997, and evaluated the period and cohort effect on breast cancer incidence using the age-period-cohort model. Age-specific and age-standardized rates have increased over successive calendar periods. Around 1980, an accelerated increase in these incidence rates took place. A full model including age, period and cohort was best fitted to the trend of incidence. In the model, the effects of period and cohort were statistically significant. The nonlinear effect for cohort indicates an increasing trend, beginning with the cohort in 1888-1897, and the nonlinear effect for period showed a clear increase in risk with calendar period. Furthermore, the full model including a linear component showed a steadily upward trend in the cohort effect. Based on our own epidemiologic studies previously conducted in Miyagi Prefecture, and other published reports, the cohort effect is likely to be related to the change in prevalence of women with risk factors such as low parity and insufficient breastfeeding. We believe that the emergence of the cohort effect is an important finding, although the period effect may also persist. The significant cohort effect may give a caution for continuous increase of breast cancer incidence in Japan.

Adult↗
PubMed2004

Collaboration of breast cancer clinic and genetic counseling division for BRCA1 and BRCA2 mutation family in Japan.

BACKGROUND: BRCA1 and BRCA2 mutations cause high breast cancer incidence rates as high as 80% Although prophylactic therapy is still controversial, several prophylactic therapies have been proposed and tried for BRCA1 and BRCA2 mutation carriers. Prophylactic surgery, chemo-prevention and precise screening have been proposed as prophylactic therapy. All BRCA1 and BRCA2 mutation carriers need knowledge about their disease and the countermeasures that are used to protect against onset of disease. Counseling plays an important role in this regard for people with genetic diseases. Therefore, collaboration between breast cancer clinics and genetic counseling services is the most important issue in clinical practice. Our group consists of three national universities and a general hospital. In this article we describe our trial to construct a clinical system against hereditary breast cancer as an interim report for the Japanese Ministry of Health, Labour and Welfare. PATIENTS AND METHODS: Twenty familial breast cancer patients were registered in this study. The whole sequence of BRCA1 and BRCA2 were analyzed. If pathological mutations were detected, their first degree families were introduced to the counseling division at each institute when candidates visited counseling divisions. RESULTS AND DISCUSSION: Four cases of a deleterious mutation in BRCA1 or BRCA2 were detected among 20 cases. Their first degree relatives are now under consideration for visiting counseling divisions. The clinical system described in this study should play a role to protect BRCA1 or BRCA2 mutation carriers in Japan.

Breast Neoplasms↗
PubMed2004

Ductal Carcinoma in situ and related lesions of the breast: recent advances in pathology practice.

The incidence of ductal carcinoma in situ (DCIS) of the breast has increased significantly in Japanese women. It comprises 14.1% (172/1216) of all primary breast cancers at our institute, and nowadays this histological type is familiar to the surgeons and pathologists of any institute. Several subclassifications have been published recently. Most based on nuclear atypia and the presence of comedonecrosis, and sometimes on the structures of the involved glands. These classifications are correlated with the biological behavior, tumor extent and the risk for local recurrences. The diagnostic accuracy of minimally invasive procedures (aspiration biopsy cytology/core needle biopsy) may differ between subclasses. Atypical ductal hyperplasia (ADH) and microinvasive ductal carcinomas are lesions which resemble but deviate from the DCIS spectrum. The incidence of ADH seems to be lower than in Western countries. Patients with ADH may have a risk for subsequent breast cancer, because ADH is frequently associated with contralateral breast carcinomas. Microinvasion should be treated with caution, but we could not find any metastatic foci in microinvasive ductal carcinomas (T1mic). Tentatively, ADH may be treated similarly to non-comedo (low-grade) DCIS cases, according to our limited clinical experience.

Breast Neoplasms↗
PubMed2004

Pathological evaluation of sentinel lymph nodes for breast cancer.

Recently, sentinel lymph node (SLN) biopsy has been employed to avoid unnecessary lymph node dissection, because SLN negativity for carcinoma metastases may imply an extremely low possibility of non-SLN involvement. Pathological evaluation is essential, but standardized procedures have not yet been determined. Intraoperative consultation, either by frozen section (multiple slices are desirable) or touch imprint cytology, are usually very useful. Their accuracy, however, is variable and depends on the procedures used, but specificity is characteristically 100%, and the missed metastatic focus is always quite minute. After fixation, multiple sections, immunohistochemistry, and their combination will be able to detect small metastatic foci more frequently. The clinical significance of small or submicro- or occult metastases have not yet been clarified, and further investigations are needed. If the SLN is positive for carcinoma metastases, both the procedure for detection and the size of the metastatic focus should be clarified on the pathological reports.

Axilla↗
PubMed2004

Biophoton detection as a novel technique for cancer imaging.

Biophoton emission is defined as extremely weak light that is radiated from any living system due to its metabolic activities, without excitation or enhancement. We measured biophoton images of tumors transplanted in mice with a highly sensitive and ultra-low noise CCD camera system. Cell lines employed for this study were AH109A, TE4 and TE9. Biophoton images of each tumor were measured 1 week after carcinoma cell transplantation to estimate the tumor size at week 1 and the biophoton intensity. Some were also measured at 2 and 3 weeks to compare the biophoton distribution with histological findings. We achieved sequential biophoton imaging during tumor growth for the first time. Comparison of microscopic findings and biophoton intensity suggested that the intensity of biophoton emission reflects the viability of the tumor tissue. The size at week 1 differed between cell lines, and the biophoton intensity of the tumor was correlated with the tumor size at week 1 (correlation coefficient 0.73). This non-invasive and simple technique has the potential to be used as an optical biopsy to detect tumor viability.

Animals↗
PubMed2004

Invasive micropapillary carcinoma of the breast: clinicopathological and immunohistochemical study.

Invasive micropapillary carcinoma (IMPCa) of the breast refers to a unique variant of invasive ductal carcinoma, but its biological behavior has not been elucidated well. We analyzed 16 IMPCa cases (10 pure type, six mixed type). The incidence of IMPCa was 1.0% of all primary breast carcinoma. High nuclear grade (75.0%), as well as poorly differentiated histological grade (81.3%), was frequently seen. Lymph node metastases were evident in 92.9% of the examined cases, and about half of them showed more than 10 positive nodes. Comparison between serially experienced invasive ductal carcinoma, not otherwise specified (IDC-NOS), revealed that both high nuclear grade and poor histological grade were significantly more frequent (P < 0001), there was a lower frequency of positive estrogen receptor/progesterone receptor (P < 0.05, P < 0.01), a higher frequency of HER-2 overexpression (P < 0.025), and more frequent lymph node metastases (P < 0.05) in IMPCa. The comparison between lymph node positive IDC-NOS did not show any statistically significant differences in frequency for positive p53, matrix metalloproteinase protein-2 (MMP-2), vascular endothelial growth factor (VEGF) or E-cadherin. However, IMPCa showed a significantly increased number of blood vessels counted by CD34 immunostains (P < 0.05). These results suggest that IMPCa is, at least, the same or more aggressive than lymph node positive cases of IDC-NOS. Hence, not only the high incidence of lymph node metastases but also distant, blood-borne metastases may be important.

Biomarkers, Tumor↗