Publications (11)18.7 Total impact
-
Article: High expression of ATP-binding cassette transporter ABCC11 in breast tumors is associated with aggressive subtypes and low disease-free survival.
[show abstract] [hide abstract]
ABSTRACT: ATP-binding cassette (ABC) transporters are membrane proteins that efflux various compounds from cells, including chemotherapeutic agents, and are known to affect multidrug resistance. Recent reports disagree on whether ABCC11 is a risk factor for breast tumorigenesis, but its expression in breast cancer is poorly investigated. We hypothesized that both frequency and expression levels of ABC transporters in breast tumors would vary by cancer subtype, and be associated with prognosis. Here, we constructed a tissue microarray breast tumor samples from 281 patients, and analyzed expressions of ABCB1, ABCC1, ABCC11, and ABCG2 immunohistochemically. Breast cancer subtypes were determined by immunohistochemistry of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). Protein expression was correlated to clinicopathological characteristics, clinical follow-up, and pathological complete response to neoadjuvant chemotherapy. The tissue microarray comprised 191 luminal A (68.0 %), 17 luminal B (6.0 %), 27 HER2 (9.6 %), and 46 triple-negative (16.4 %) samples. ABCC1 and ABCC11 expressions were associated with significantly shorter disease-free survival (P = 0.027 and P = 0.003, respectively). ABCC1, ABCC11, and ABCG2, but not ABCB1, were expressed significantly more, and more frequently, in aggressive subtypes. Patients with HER2+ and triple-negative tumor subtypes that expressed high levels of ABCC11 had significantly worse disease-free survival (P = 0.017 and P < 0.001, respectively). We have shown, for the first time, that ABCC1, ABCC11, and ABCG2 are highly expressed in aggressive breast cancer subtypes, and that tumor ABCC11 expression is associated with poor prognosis.Breast Cancer Research and Treatment 01/2013; · 4.43 Impact Factor -
Article: Unique mutation, accelerated mTOR signaling and angiogenesis in the pulmonary cysts of Birt-Hogg-Dubé syndrome.
[show abstract] [hide abstract]
ABSTRACT: Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder characterized by fibrofolliculomas, renal tumors and pulmonary cysts with repeated pneumothorax. This disorder is caused by mutations in the gene that encodes folliculin (FLCN). FLCN is known to be involved in the signaling of mammalian target of rapamycin (mTOR). We investigated the lung of a BHD patient who presented with a unique mutation. A 33-year-old woman visited our hospital due to repeated pneumothorax. Histopathologic study of the resected lung demonstrated multiple epithelial cysts. An increase of blood vessels was observed in the vicinity of subpleural cysts. Genomic DNA analysis revealed heterozygous mutation at the 3' end of intron 5 of the FLCN gene. Total mRNA and protein were extracted from the resected lung tissue. RT-PCR and sequence analysis demonstrated the production of exon 6-skipped FLCN mRNA. In Western blotting, the band intensities of phospho-mTOR, phospho-S6, phospho-Akt, hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) were increased in the BHD lung compared with normal lungs. Histopathologic analysis demonstrated strong immunostainings of mTOR signaling molecules in cyst-lining cells. Collective data indicates that dysregulation of mTOR signaling facilitates S6-mediated protein synthesis and HIF-1α-mediated angiogenesis, which may contribute to the development of pulmonary cysts in this disorder.Pathology International 01/2013; 63(1):45-55. · 1.62 Impact Factor -
Article: Breast cancer manifested by hematologic disorders.
[show abstract] [hide abstract]
ABSTRACT: Breast cancer is the most common type of cancer in women. However, it is very rarely manifested as hematologic disorders. A 35-year-old woman was admitted because of disseminated intravascular coagulation. Examinations revealed the presence of breast cancer in her left breast; therefore, paclitaxel was administered weekly. Although disseminated intravascular coagulation was controlled, pulmonary dysfunction due to lymphangitis carcinomatosa suddenly occurred 10 weeks after treatment. Pulmonary dysfunction was effectively treated with epirubicin and cyclophosphamide. Twenty-three weeks after treatment, the patient developed liver dysfunction accompanied with jaundice due to progressive metastatic lesions in the liver; liver dysfunction improved after the administration of vinorelbine. Subsequently, because of the recurrence of pulmonary dysfunction, rechallenge with epirubicin and cyclophosphamide was performed and was effective; however, this therapy was discontinued because of its adverse effects. She expired of liver failure 33 weeks after the occurrence of disseminated intravascular coagulation. Metastatic tumors in the bone marrow, lung, and liver showed different sensitivities to different anti-cancer agents. We report a case of breast cancer manifested by hematologic disorders which was treated by a sequential chemotherapy.Journal of thoracic disease. 12/2012; 4(6):650-4. -
Article: Preoperative endocrine therapy with goserelin acetate and tamoxifen in hormone receptor-positive premenopausal breast cancer patients.
[show abstract] [hide abstract]
ABSTRACT: BACKGROUND: The use of preoperative endocrine therapy for breast cancer has increased during the last decade. Although several studies have reported favorable response rates in postmenopausal women, its effectiveness in premenopausal women remains unknown. This study therefore aimed to evaluate the potential benefits of preoperative endocrine therapy in premenopausal women. METHODS: Fifty-three patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative invasive breast cancer were included in this study. Preoperative endocrine therapy with goserelin acetate and tamoxifen was administered for 3 months. Clinical evaluations were performed by ultrasonography before and after endocrine therapy. Pathological evaluations were performed using core biopsy and surgical specimens. Immunohistochemical evaluations of ER, progesterone receptor (PgR), HER2, and Ki-67 were performed before and after endocrine therapy. RESULTS: Partial response (PR) was observed in 23 % (12/53) and progressive disease (PD) in 2 % (2/53) of patients. Significant suppression of Ki-67 was observed following endocrine therapy in 90 % (47/52) of patients (P < 0.0001). Significant downregulation of PgR was observed after endocrine therapy (P = 0.0002), which tended to be correlated with clinical response (P = 0.058). CONCLUSIONS: Three months of preoperative endocrine therapy with goserelin acetate and tamoxifen was safe and effective in premenopausal patients with invasive breast cancer, with a 23 % PR rate. Changes in PgR and Ki-67 expression might be promising markers for endocrine responsiveness.Breast Cancer 11/2012; · 1.36 Impact Factor -
Article: Impacts and predictors of cytotoxic anticancer agents in different breast cancer subtypes.
[show abstract] [hide abstract]
ABSTRACT: Breast cancer is not a single entity. This study therefore aimed to identify differences in the impacts of anticancer agents and predictive factors between different breast cancer subtypes. A total of 234 patients with luminal (n = 109), luminal-HER2 (L-H, n = 29), HER-2 (n = 35), or triple negative (TN, n = 61) breast cancer subtypes were treated with standard neoadjuvant chemotherapy consisting of an anthracycline and/or taxane. Pathological response and prognosis were examined in each subtype. Expression levels of estrogen and progesterone receptors, HER-2, nuclear grade, MIB-1, p53, topoisomerase IIalpha (topoIIalpha), cytokeratin (CK) 5/6, and epidermal growth factor receptor (EGFR) were examined in association with quasipathological complete response (QpCR). QpCR rates were 9.1% (10/109) in luminal, 45% (13/29) in L-H, 37% (13/35) in HER2, and 54.1% (33/61) in TN. Non-QpCR patients showed significantly poorer 3-year disease-free survival than QpCR patients in TN, but not in patients with other subtypes. No factors were associated with QpCR in luminal patients. Patients with higher nuclear grade were more likely to achieve QpCR in L-H. The proliferative markers MIB-1 and topoIlalpha had opposite impacts on pathological response in HER-2 and TN. The QpCR rate was significantly higher in TN lacking CK5/6 and/or EGFR expression, defined as nonbasal subtype, compared with basal subtype (p = 0.049). Cytotoxic anticancer agents were associated with different responses in different breast cancer subtypes. Identifying basal-type cancer and further subdivision of nonbasal types is important for treating TN patients.Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics 01/2012; 20(2-3):71-9. · 1.30 Impact Factor -
Article: A human epidermal growth factor receptor 2 expression-based approach to neoadjuvant chemotherapy for operable breast cancer.
[show abstract] [hide abstract]
ABSTRACT: We investigated the pathological effects of neoadjuvant chemotherapy based on the human epidermal growth factor receptor 2 in operable breast cancer. This prospective clinical study was a pilot involving 63 female patients. Before surgery, patients with tumors overexpressing human epidermal growth factor receptor 2 received four cycles of 60 mg/m(2) anthracycline and 600 mg/m(2) cyclophosphamide every 3 weeks, whereas those whose tumors did not overexpress human epidermal growth factor receptor 2 received four cycles of 75 mg/m(2) docetaxel and 600 mg/m(2) cyclophosphamide every 3 weeks. A quasi-pathological complete response (i.e. absence of invasive tumor or only focal residual tumor cells) was the primary endpoint, with compliance and predictors for each regimen as secondary endpoints. If a quasi-pathological complete response was not achieved, then crossover to the alternative treatment was recommended. The quasi-pathological complete response rate was 36.5% (23 of 63) overall, 27.8% (5 of 18) for the anthracycline and cyclophosphamide regimen and 40.0% (18 of 45) for the docetaxel and cyclophosphamide regimen. Docetaxel and cyclophosphamide treatment induced a quasi-pathological complete response in most patients with triple-negative tumors (15 of 19). The relative dose intensity was 97.3% for the anthracycline and cyclophosphamide regimen and 96.6% for the docetaxel and cyclophosphamide regimen. Quasi-pathological complete response to the docetaxel and cyclophosphamide regimen was associated with low estrogen receptor and progesterone receptor expression and high MIB-1 and topoisomerase IIalpha expression, in univariate analyses, but only with low estrogen receptor expression in multivariate analysis. Selecting neoadjuvant chemotherapy regimens on the basis of individual human epidermal growth factor receptor 2 status improved efficacy, with docetaxel and cyclophosphamide treatment showing particular promise in tumors with the potential to be highly malignant.Japanese Journal of Clinical Oncology 03/2010; 40(7):620-6. · 1.78 Impact Factor -
Article: Hepatocellular carcinoma occurring in a young Crohn's disease patient.
[show abstract] [hide abstract]
ABSTRACT: Reported herein is a case of hepatocellular carcinoma (HCC) occurring in a 25-year-old Japanese man who was diagnosed with Crohn's disease (CD) at 14 years of age; treatment included predonisolone, azathioprine, and infliximab. The tumor was located in right upper lobe and the size was 8 cm in diameter; histology was poorly differentiated HCC with pleomorphic cellular changes. Adjacent normal liver showed no evidence of cirrhosis or viral hepatitis. Until now, only six cases of HCC arising in patients with CD have been reported in the English-language literature. Most of these patients had early onset of CD and HCC: none had cirrhosis or virus hepatitis. Most patients had a long disease history of CD and were being medicated with several immunosuppressive agents. Some factors associated with CD might indirectly or directly be related to the development of HCC in CD patients, although the possibility that these HCC occurred coincidentally in CD patients, including the present patient, cannot be ruled out. Accumulation of cases is necessary to evaluate the relationship between CD and HCC precisely.Pathology International 08/2009; 59(7):492-6. · 1.62 Impact Factor -
Article: Feasibility of AC/EC followed by weekly paclitaxel in node-positive breast cancer in Japan.
[show abstract] [hide abstract]
ABSTRACT: The feasibility and efficacy of adriamycin or epirubicin in combination with cyclophosphamide followed by weekly paclitaxel (AC/EC-weekly PAC) as adjuvant chemotherapy for breast cancer was investigated. Node-positive breast cancer was treated with AC/ EC-weekly PAC, namely AC at 60/600 mg/m(2) or EC at 90/600 mg/m(2) x4 at three-week intervals, followed by weekly PAC (80 mg/m(2)) x 12, namely four cycles of single weekly administration for three weeks followed by a one-week rest (3 x 4 PAC) or single weekly administration for 12 consecutive weeks (12 PAC). One hundred and three of 109 consecutive patients enrolled were analyzed, of whom 96 (93.2%) completed the regimen. Grade 3/4 neutropenia occurred in 52.4% receiving AC/EC, and 10.9% of 55 receiving 12 PAC but only 2.1% of 48 receiving 3 x 4 PAC. Neuropathy disorders occurred in more than half receiving PAC, which did not improve after one-week rest in 3 x 4 PAC. AC/EC-weekly PAC is feasible and without serious complications.Anticancer research 06/2009; 29(5):1515-20. · 1.73 Impact Factor -
Article: False-positive and false-negative cases of fine-needle aspiration cytology for palpable breast lesions.
[show abstract] [hide abstract]
ABSTRACT: Fine-needle aspiration cytology (FNA) is less traumatic and technically easy to apply to small breast tumors. A total of 382 cases of palpable breast lesions that had undergone fine needle aspiration and histopathologic diagnosis were reviewed with an emphasis on the rate of false positive diagnoses in benign breast lesions. A diagnosis of " malignant " was made in 98 of the 382 specimens (25.6%). The predictive value for malignancy was 97.9%. The sensitivity, specificity, and accuracy of FNA were 86.3%, 98.2%, and 93.2%, respectively, when the " suspicious " group was considered positive for malignancy. The histologic subtypes of the 4 false-positive cases were epithelial proliferative lesions, ductal or lobular hyperplasia. None of these 4 cases were definitely diagnosed as " malignant " by radiological studies. Four false-negative cases by FNA were suspicious for malignancy radiologically. There was no specific pathological subtype associated with false-negative status on FNA in this study. Palpable breast tumors can be definitively diagnosed based on a combination of physical examination, radiological studies and FNA, when the radiological studies concur with the diagnosis by FNA.Breast Cancer 02/2007; 14(4):388-92. · 1.36 Impact Factor -
Article: Prognostic significance of the number of positive lymph nodes in gallbladder cancer.
[show abstract] [hide abstract]
ABSTRACT: The aim of this study was to assess the prognostic impact of the number of lymph node metastases. The medical records of 33 patients with node-positive gallbladder cancer (GBC) treated at our institution from January 1985 through December 2002 were reviewed. There were 10 cases with a single node metastasis. The sites were as follows: the cystic duct node, the pericholedochal node, the retroportal node, the hilar node, the lymph node around the common hepatic artery, and the paraaortic node. According to the International Union Against Cancer (UICC) 5th edition, 5-year survival rates for the patients with pN1, pN2, and greater than pN2 were 19.2%, 10%, and 0%, respectively (not significant). Patients with a single node metastasis had a higher 5-year survival rate (33%) than patients with two or more lymph node metastases (0%; P < 0.05). There were no lymph node recurrences in patients with a single node metastasis. Number of positive nodes and liver metastasis were factors predictive of significantly worse survival. Rather than using the topographic classification, or even simply classifying whether nodal involvement is positive or negative, classification according to the number of positive nodes will contribute to establishing a more practically useful staging system.Journal of Gastrointestinal Surgery 10(7):999-1007. · 2.83 Impact Factor -
Article: Is lymph-node micrometastasis in gallbladder cancer a significant prognostic factor?
[show abstract] [hide abstract]
ABSTRACT: The purpose of our study was to investigate prognostic significance of lymph-node micrometastasis in gallbladder carcinoma. In total, 1,094 lymph nodes from 41 patients who had undergone radical resection with lymph-node dissection, including para-aortic lymph nodes were stained with hematoxylin and eosin (H&E) and immunostained with anti-cytokeratin 7/8 antibody. Micrometastasis in each lymph node was defined as tumor cells that were detectable only by immunohistochemical evaluation and were not detected by H&E staining. Metastases were detected in 163 lymph nodes (14.9%) by H&E staining. Micrometastases were found in 25 of the remaining lymph nodes (2.3%). Among 24 patients with lymph node metastasis based on the H&E staining, 12 had micrometastases. Of the 17 patients in whom lymph-node metastasis was not detected by the H&E staining, one was found to have micrometastasis. Micrometastasis correlated significantly with lymph node metastasis on H&E staining and pN (Tumor-Node-Metastasis 5th ed.). On multivariate analysis of data from 17 node-positive patients who underwent curative resection, micrometastasis and microscopic venous invasion were significant prognostic factors. Our findings suggest that micrometastasis might be traces of scatter of cancer cells to the whole body rather than an event in an initial stage of the metastasis.Hepato-gastroenterology 59(113):31-5. · 0.66 Impact Factor
Top co-authors
Top Journals
Institutions
-
2007–2013
-
Yokohama City University
Yokohama-shi, Kanagawa-ken, Japan
-
