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1.  Inflammation as well as angiogenesis may participate in the pathophysiology of brain radiation necrosis 
Journal of Radiation Research  2014;55(4):803-811.
Radiation necrosis (RN) after intensive radiation therapy is a serious problem. Using human RN specimens, we recently proved that leaky angiogenesis is a major cause of brain edema in RN. In the present study, we investigated the same specimens to speculate on inflammation's effect on the pathophysiology of RN. Surgical specimens of symptomatic RN in the brain were retrospectively reviewed by histological and immunohistochemical analyses using hematoxylin and eosin (H&E) staining as well as immunohistochemical staining for VEGF, HIF-1α, CXCL12, CXCR4, GFAP, CD68, hGLUT5, CD45, IL-1α, IL-6 TNF-α and NF-kB. H&E staining demonstrated marked angiogenesis and cell infiltration in the perinecrotic area. The most prominent vasculature was identified as thin-walled leaky angiogenesis, i.e. telangiectasis surrounded by prominent interstitial edema. Two major cell phenotypes infiltrated the perinecrotic area: GFAP-positive reactive astrocytes and CD68/hGLUT5-positive cells (mainly microglias). Immunohistochemistry revealed that CD68/hGLUT5-positive cells and GFAP-positive cells expressed HIF-1α and VEGF, respectively. GFAP-positive cells expressed chemokine CXCL12, and CD68/hGLUT5-positive cells expressed receptor CXCR4. The CD68/hGLUT5-positive cells expressed pro-inflammatory cytokines IL-1α, IL-6 and TNF-α in the perinecrotic area. VEGF caused leaky angiogenesis followed by perilesional edema in RN. GFAP-positive cells expressing CXCL12 might attract CXCR4-expressing CD68/hGLUT5-positive cells into the perinecrotic area. These accumulated CD68/hGLUT5-positive cells expressing pro-inflammatory cytokines seemed to aggravate the RN edema. Both angiogenesis and inflammation might be caused by the regulation of HIF-1α, which is well known as a transactivator of VEGF and of the CXCL12/CXCR4 chemokine axis.
PMCID: PMC4100008  PMID: 24676944
brain radiation necrosis; CXCL12/CXCR4 chemokine axis; inflammation; microglia; pro-inflammatory cytokine
2.  A Case of Eccrine Porocarcinoma: Usefulness of Immunostain for S-100 Protein in the Diagnoses of Recurrent and Metastatic Dedifferentiated Lesions 
Annals of Dermatology  2013;25(3):348-351.
Eccrine porocarcinoma is a rare malignant tumor. Immunostain for S-100 protein, in addition to epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA), is described to be useful in the diagnosis. Herein, we report a case of eccrine porocarcinoma with immunostain for S-100 protein which was useful in diagnoses of recurrent and metastatic lesions. The primary lesion in the left inguinal region was excised, but it recurred on the same site 14 months after the resection. The recurrent lesion showed epithelioid melanocytic findings. Three months later, metastasis to the lungs was found. Since these recurrent and metastatic lesions were dedifferentiated, typical histologic findings of eccrine porocarcinoma disappeared in biopsied specimens. Nevertheless, scattered immunoreactive cells for S-100 protein were maintained in these dedifferentiated lesions. S-100 protein positive cells could be an aid to diagnose, even if histologic findings of recurrent and metastatic lesions have changed by dedifferentiation.
PMCID: PMC3756201  PMID: 24003279
Eccrine porocarcinoma; Immunohistochemistry; S100 proteins
3.  Establishment and characterization of a cell line (NOMH-1) originating from a human endometrioid adenocarcinoma of the ovary 
Cell lines are very useful for clinical and basic research. Thus far, only 11 reports have documented the characteristics of ovarian endometrioid adenocarcinoma cell lines in the literature. Due to the scarcity of information, the establishment of an ovarian malignant tumor cell line with distinctive characteristics is particularly important to study this disease. Thus, this study was undertaken to establish and characterize a new human endometrioid adenocarcinoma cell line of the ovary.
The cell line NOMH-1 was established from an ovarian tumor of a 44-year-old woman. Features of the cell line studied included morphology, chromosome analysis, heterotransplantation, tumor markers, and chemosensitivity.
This cell line has been growing well for 232 months and subcultured more than 50 times. Monolayer cultured cells were polygonal in shape, showing a pavement-like arrangement and a tendency to stack without contact inhibition. They exhibited a human karyotype with a modal chromosomal number in the hypertriploid range. The cells could be transplanted into the subcutis of nude mice and produced tumors resembling the original tumor. NOMH-1 cells expressed both CEA and CA19-9 which were identified immunohistochemically in the original tumor and the heterotransplanted tumor. The cells were sensitive to paclitaxel, an agent commonly used in the treatment of gynecological cancers.
NOMH-1 is the first ovarian endometrioid adenocarcinoma cell line in which CEA and CA19-9 expression have been defined. This newly established cell line should be useful for investigating the characteristics of ovarian endometrioid adenocarcinoma.
PMCID: PMC3568727  PMID: 23379414
Endometrioid adenocarcinoma; Ovary; Cell line; Chemosensitivity; MTT assay; Tumor marker
4.  Pulmonary tumor thrombotic microangiopathy caused by gastric cancer 
Annals of Thoracic Medicine  2012;7(3):168-169.
Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal cancer-related pulmonary complication with rapidly progressing dyspnea, and occasionally induces sudden death. Here, we describe a postmortem-diagnosed PTTM case caused by gastric cancer, with the complaint of progressing dyspnea for 5 days.He did not have any abdominal symptoms or cancer history. PTTM should be considered in patients with rapidly worsening respiratory conditions, even if there is no cancer history.
PMCID: PMC3425052  PMID: 22924078
Dyspnea; gastric cancer; PTTM
5.  Intraductal Lipid-Rich Carcinoma of the Breast with a Component of Glycogen-Rich Carcinoma 
Journal of Breast Cancer  2012;15(1):135-138.
We report a rare case of intraductal lipid-rich carcinoma of the breast with a component of glycogen-rich carcinoma. An impalpable tumor that was revealed by mammography and magnetic resonance imaging was excised. Histologic examination showed vacuolated neoplastic cells in the mammary ducts, and electron microscopy confirmed lipid droplets in the cytoplasm. The coexistence of glycogen-rich carcinoma was shown. Lipid-rich carcinoma that is coexistent with glycogen-rich carcinoma is rare, and most lipid-rich carcinomas are invasive. Intraductal lipid-rich carcinoma is difficult to detect without echography or mammography.
PMCID: PMC3318167  PMID: 22493642
Breast carcinoma; Glycogen; Immunohistochemistry; Lipid
6.  Clinicopathological analysis of recurrence patterns and prognostic factors for survival after hepatectomy for colorectal liver metastasis 
BMC Surgery  2010;10:27.
Hepatectomy is recommended as the most effective therapy for liver metastasis from colorectal cancer (CRCLM). It is crucial to elucidate the prognostic clinicopathological factors.
Eighty-three patients undergoing initial hepatectomy for CRCLM were retrospectively analyzed with respect to characteristics of primary colorectal and metastatic hepatic tumors, operation details and prognosis.
The overall 5-year survival rate after initial hepatectomy for CRCLM was 57.5%, and the median survival time was 25 months. Univariate analysis clarified that the significant prognostic factors for poor survival were depth of primary colorectal cancer (≥ serosal invasion), hepatic resection margin (< 5 mm), presence of portal vein invasion of CRCLM, and the presence of intra- and extrahepatic recurrence. Multivariate analysis indicated the presence of intra- and extrahepatic recurrence as independent predictive factors for poor prognosis. Risk factors for intrahepatic recurrence were resection margin (< 5 mm) of CRCLM, while no risk factors for extrahepatic recurrence were noted. In the subgroup with synchronous CRCLM, the combination of surgery and adjuvant chemotherapy controlled intrahepatic recurrence and improved the prognosis significantly.
Optimal surgical strategies in conjunction with effective chemotherapeutic regimens need to be established in patients with risk factors for recurrence and poor outcomes as listed above.
PMCID: PMC2949597  PMID: 20875094
7.  Precore mutant hepatitis B virus-associated fulminant hepatitis during infliximab therapy for rheumatoid arthritis 
Clinical Rheumatology  2010;32(Suppl 1):47-49.
A 73-year-old female, who suffered from rheumatoid arthritis for 10 years, developed precore mutant hepatitis B virus-associated fulminant hepatitis after 1 year of infliximab therapy and subsequent methotrexate withdrawal. We emphasize the importance of preemptive antiviral therapy before starting infliximab administration and withdrawing immunosuppressive drugs.
PMCID: PMC3594820  PMID: 20379839
Fulminant hepatitis; HBV; Infliximab; MTX; Rheumatoid arthritis

Results 1-7 (7)