Publications (7)21.09 Total impact
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Article: Immunohistochemistry-based cell cycle detection (iCCD): a novel system to visualize cell kinetics on formalin-fixed paraffin-embedded tissues.
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ABSTRACT: Carcinogenesis is widely believed to occur when regulatory systems governing cellular proliferation and differentiation are compromised. To date, various methods have been devised to determine cell cycle. However, these methods have not gained popularity in the diagnostic field. We developed a multiplex immunohistochemical method that can simultaneously stain cells in the G1 and S/G2/M phases and those undergoing apoptosis with the 3 markers Cdt1, geminin, and gamma H2A.X. The staining procedure can be performed using an autoimmunostainer. The nuclei of cells in the G1 phase stain red with the antibody for Cdt1, those in the S/G2/M phases stain blue with the antibody for geminin, and the nuclei of cells undergoing apoptosis stain brown with the antibody for H2A.X. The present method enables accurate cell cycle assessments using paraffin-embedded tissue specimens, which are superior to other forms of specimens in terms of morphologic observation.The American journal of surgical pathology 05/2012; 36(5):769-73. · 4.06 Impact Factor -
Article: Rapid multiplex immunohistochemistry using the 4-antibody cocktail YANA-4 in differentiating primary adenocarcinoma from squamous cell carcinoma of the lung.
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ABSTRACT: The current Food and Drug Administration-approved standard treatment for non-small cell carcinomas consists of carboplatin/taxol/avastin. However, nowadays more specialized protocols, depending on tumor subtype, are being used for lung cancer patients. Therefore, accurate differentiation between adenocarcinoma and squamous cell carcinoma is essential for the selection of appropriate therapies. We designed a rapid multiplex immunostaining method using a novel 4-antibody cocktail, YANA-4. This antibody cocktail consists of the following monoclonal antibodies: rabbit for thyroid transcription factor 1(TTF-1), mouse for napsin A, mouse l for p63, and rabbit for CK14. All procedures can be completed within 3 hours. This method labels the nuclei of adenocarcinomas as brown with TTF-1, and cytoplasm as blue with napsin A. Squamous cell carcinomas could be differentiated from adenocarcinomas with an inverse staining pattern: blue nuclei with p63 and brown cytoplasm with CK14. In this study, 97.4% (38 of 39) of adenocarcinomas showed brown nuclei (TTF-1) and/or blue cytoplasm (napsin A), with 4 cases showing positivity only for brown nuclei (TTF-1) and 1 case only for blue cytoplasm (napsin A). None of the squamous cell carcinoma cases showed these staining patterns. Positivity for blue nuclei (p63) and/or brown cytoplasm (CK14) was detected in 100% (25 of 25) of squamous cell carcinomas, with 1 case showing positivity only for brown cytoplasm (CK14) and 2 cases only for blue nuclei (p63). None of the adenocarcinoma cases showed these patterns. This rapid immunohistochemical method can thus be considered highly specific and sensitive for differentiating adenocarcinomas and squamous cell carcinomas.Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 03/2011; 19(6):509-13. · 1.63 Impact Factor -
Article: Oncogene-mediated human lung epithelial cell transformation produces adenocarcinoma phenotypes in vivo.
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ABSTRACT: It has been challenging to engineer lung adenocarcinoma models via oncogene-mediated transformation of primary cultured normal human cells. Although viral oncoprotein-mediated malignant transformation has been reported, xenografts derived from such transformed cells generally represent poorly differentiated cancers. Here, we demonstrate that the combined expression of multiple cellular factors induces malignant transformation in normal human lung epithelial cells. Although a combination of four genetic alterations, including hTERT overexpression, inactivation of the pRB and p53 pathways, and KRAS activation, is insufficient for normal human small airway epithelial cells to be fully transformed, expression of one additional oncogene induces malignant transformation. Notably, we have succeeded in reproducing human lung adenocarcinoma phenotypes in the flanks of nude mice by introducing an active form of PIK3CA, CYCLIN-D1, or a dominant-negative form of LKB1 in combination with the four genetic alterations above. Besides differentiated lung cancer, poorly differentiated cancer models can also be engineered by employing c-MYC as one of the genetic elements, indicating that histologic features and degree of differentiation of xenografts are controllable to some extent by changing the combination of genetic elements introduced. This is the first study reporting malignant transformation of normal lung epithelial cells in the absence of viral oncoproteins. We propose that our model system would be useful to identify the minimal and most crucial set of changes required for lung tumorigenesis, and that it would provide a broadly applicable approach for discovering attractive therapeutic targets.Cancer Research 03/2011; 71(7):2541-9. · 7.86 Impact Factor -
Article: Effect of chemical peeling on photocarcinogenesis.
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ABSTRACT: Chemical peeling is one of the dermatological treatments available for certain cutaneous diseases and conditions or improvement of cosmetic appearance of photo-aged skin. We assessed the photo-chemopreventive effect of several clinically used chemical peeling agents on the ultraviolet-irradiated skin of hairless mice. Chemical peeling was done using 35% glycolic acid dissolved in distilled water, 30% salicylic acid in ethanol, and 10% or 35% trichloroacetic acid in distilled water at the right back of ultraviolet-irradiated hairless mice every 2 weeks for glycolic acid, salicylic acid and 10% trichloroacetic acid, and every 4 weeks for 35% trichloroacetic acid for a total of 18 weeks after the establishment of photo-aged mice by irradiation with ultraviolet B range light three times a week for 14 weeks at a total dose of 6.66 J/cm(2) . Tumor formation was assessed every week. Skin specimens were taken from treated and non-treated area for evaluation under microscopy, evaluation of p53 expression and mRNA expression of cyclooxygenase-2. Serum level of prostaglandin E(2) was also evaluated. All types of chemical peeling reduced tumor formation in treated mice, mostly in the treated area but also in the non-treated area. Peeling suppressed retention of p53-positive abnormal cells and reduced mRNA expression of cyclooxygenase-2 in treated skin. Further, serum prostaglandin E(2) level was decreased in chemical peeling treated mice. These results indicate that chemical peeling with glycolic acid, salicylic acid and trichloroacetic acid could serve tumor prevention by removing photo-damaged cells.The Journal of Dermatology 10/2010; 37(10):864-72. · 1.49 Impact Factor -
Article: Preventive effect of chemical peeling on ultraviolet induced skin tumor formation.
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ABSTRACT: Chemical peeling is one of the dermatological treatments available for certain cutaneous diseases and conditions or improvement of cosmetic appearance of photoaged skin. We assessed the photochemopreventive effect of several clinically used chemical peeling agents on the ultraviolet (UV)-irradiated skin of hairless mice. Chemical peeling was done using 35% glycolic acid dissolved in distilled water, 30% salicylic acid in ethanol, 10% or 35% trichloroacetic acid (TCA) in distilled water at the right back of UV-irradiated hairless mice every 2 weeks in case of glycolic acid, salicylic acid, and 10% TCA and every 4 weeks in case of 35% TCA for totally 18 weeks after the establishment of photoaged mice by irradiation with UVA+B range light three times a week for 10 weeks at a total dose of 420 J/cm(2) at UVA and 9.6 J/cm(2) at UVB. Tumor formation was assessed every week. Skin specimens were taken from treated and non-treated area for evaluation under microscopy, evaluation of P53 expression, and mRNA expression of cyclooxygenase (COX)-2. Serum level of prostaglandin E(2) was also evaluated. All types of chemical peeling reduced tumor formation in treated mice, mostly in the treated area but also non-treated area. Peeling suppressed clonal retention of p53 positive abnormal cells and reduced mRNA expression of COX-2 in treated skin. Further, serum prostaglandin E(2) level was decreased in chemical peeling treated mice. These results indicate that chemical peeling with glycolic acid, salicylic acid, and TCA could serve tumor prevention by removing photodamaged cells.Journal of dermatological science 10/2010; 60(1):21-8. · 3.71 Impact Factor -
Article: Histiocytic sarcoma with two immunohistopathologically distinct populations.
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ABSTRACT: This report is a case of histiocytic sarcoma (HS), in which tumor cells consist of two immunohistopathologically distinct populations (A) oval CD68+lysozyme+CD163- cells and (B) abundant cytoplasm or spindle-shaped CD68+lysozyme-CD163+ cells. Cervical lymph node was infiltrated mainly by population (A), where chemotherapy was quite effective. On the other hand, vast majority of infiltrated tumor cells in the hilar lymph node belonged to population (B), in which the cells were resistant to chemo-radiotherapy. Considering the poor prognosis of HS, the expression of CD163 could be a marker for resistance to chemo-radiotherapy. It is also notable that CD163-negative stage of HS may exist and still be reactive for the treatment.International journal of hematology 10/2010; 92(4):642-6. · 1.17 Impact Factor -
Article: Progressive osteosclerosis and visceral calcification after cord blood transplantation.
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ABSTRACT: A 26-year-old woman, who successfully underwent umbilical cord blood transplantation for aplastic anemia 4 years previously, had suffered from hepatosplenic microabscesses caused by unidentifiable grocott stain-positive spores from immediately after the transplantation. At 51 months post-transplant, we attempted bone marrow biopsy from her posterior iliac crest, but failed to penetrate the cortical bone. X-ray of her spine and pelvis showed marked and diffuse osteosclerosis. Retrospective analysis of computed tomography revealed the gradual replacement of sternal, vertebral, and pelvic bone marrow with calcified tissues in addition to the dispersed calcification of the liver, spleen, and kidneys over the last 2 years. The bone mineral density of the lumbar spine had increased but not that of the femoral neck. Biomedical parameters for bone remodeling demonstrated enhanced bone formation as well as bone resorption and secondary hyperparathyroidism. Based on the past reports, we suggest that chronic fungal infection, which caused visceral calcification, induced the production of humoral factors for osteoblastic activation.International journal of hematology 02/2010; 91(3):542-5. · 1.17 Impact Factor
