Yatsushi Nishi

Enhanced Expression of Endothelin B Receptor at Protein and Gene Levels in Human Cirrhotic Liver

Endothelin (ET) has been implicated in the regulation of hepatic microcirculation and development of portal hypertension. This study examined the localization of ETA receptor (ETAR) and ETB receptor (ETBR) in cirrhotic liver tissues from patients with hepatocellular carcinoma with hepatitis C-related cirrhosis, and normal liver samples from patients with metastatic liver carcinoma. Anti-ETAR and ETBR antibodies were used for immunohistochemistry and Western blot. Immunoelectron microscopy was conducted using immunoglobulin-gold and silver staining. For in situ hybridization (ISH), human ETAR and ETBR peptide nucleic acid probes were used with the catalyzed signal amplification system. In normal liver tissue, immunohistochemistry revealed that ETBR was predominantly expressed on hepatic sinusoidal lining cells, particularly on sinusoidal endothelial (SECs) and hepatic stellate cells (HSCs), and ETAR was scantily expressed. These findings were confirmed by Western blot and ISH. In cirrhotic liver tissue, overexpression of ETBR was demonstrated by Western blot and ISH. Morphometric analysis showed significant increase of ETBR expression on HSCs and SECs in cirrhotic liver, particularly on HSCs. ETAR expression was increased but remained low. Enhanced ETBR expression in cirrhosis may intensify the effect of endothelin on HSCs and increase hepatic microvascular tone.

Early gastric cancer frequently has high expression of KK-LC-1, a cancer-testis antigen

AIM To assess cancer-testis antigens (CTAs) expression in gastric cancer patients and examined their associations with clinicopathological factors. METHODS Eighty-three gastric cancer patients were evaluated in this study. Gastric cancer specimens were evaluated for the gene expression of CTAs, Kitakyushu lung cancer antigen-1 (KK-LC-1), melanoma antigen (MAGE)-A1, MAGE-A3 and New York esophageal cancer-1 (NY-ESO-1), by reverse transcription PCR. Clinicopathological background information, such as gender, age, tumor size, macroscopic type, tumor histology, depth of invasion, lymph node metastasis, lymphatic invasion, venous invasion, and pathological stage, was obtained. Statistical comparisons between the expression of each CTA and each clinicopathological background were performed using the χ2 test. RESULTS The expression rates of KK-LC-1, MAGE-A1, MAGE-A3, and NY-ESO-1 were 79.5%, 32.5%, 39.8%, and 15.7%, respectively. In early stage gastric cancer specimens, the expression of KK-LC-1 was 79.4%, which is comparable to the 79.6% observed in advanced stage specimens. The expression of KK-LC-1 was not significantly associated with clinicopathological factors, while there were considerable differences in the expression rates of MAGE-A1 and MAGE-A3 with vs without lymphatic invasion (MAGE-A1, 39.3% vs 13.6%, P = 0.034; MAGE-A3, 47.5% vs 18.2%, P = 0.022) and/or vascular invasion (MAGE-A1, 41.5% vs 16.7%, P = 0.028; MAGE-A3, 49.1% vs 23.3%, P = 0.035) and, particularly, MAGE-A3, in patients with early vs advanced stage (36.5% vs 49.0%, P = 0.044), respectively. Patients expressing MAGE-A3 and NY-ESO-1 were older than those not expressing MAGE-A3 and NY-ESO-1 (MAGE-A3, 73.7 ± 7.1 vs 67.4 ± 12.3, P = 0.009; NY-ESO-1, 75.5 ± 7.2 vs 68.8 ± 11.2, P = 0.042). CONCLUSION The KK-LC-1 expression rate was high even in patients with stage I cancer, suggesting that KK-LC-1 is a useful biomarker for early diagnosis of gastric cancer.

Signal detection of endothelin receptor subtypes in human cirrhotic liver by a new in situ hybridization method

Endothelin (ET) has been implicated in the regulation of hepatic microcirculation and development of portal hypertension, but the role of ET in cirrhosis of the liver has not yet been elucidated. We present here the application of peptide nucleic acid (PNA) probes in a fast and sensitive in situ hybridization (ISH) method for localizing the mRNA of endothelin receptor subtypes in formalin-fixed, paraffin-embedded sections of normal and cirrhotic human liver. The results of ISH using synthetic FITC-labeled PNA probes combined with the catalyzed signal amplification (CSA) system were compared with those using the standard detection system. It was indicated that the CSA-ISH protocol is more sensitive for the detection of mRNA target than the standard ISH protocol. Our results with CSA-ISH showed that the expression of mRNA for the endothelin B receptor was significantly upregulated in hepatic sinusoidal lining cells in cirrhotic human liver tissues compared to control normal liver tissue. Therefore, the CSA detection system may facilitate and enhance the use of in situ hybridization protocols, and CSA-ISH will be used as an important diagnostic technique in the future.

A Case Report of Intra-abdominal Desmoid Tumor Located in the Mesentery of the Colon.

腹腔内デスモイドの報告はまれである. 本邦では1970年以降, 我々の調べた限りでは39例の報告をみるにすぎない. 今回我々は結腸間膜より発生した腹腔内デスモイドの1例を経験したので, 若干の文献的考察を加え報告する.症例は51歳の女性で, 心窩部痛を主訴に来院した. 超音波検査, CT, MRI, 血管造影より間葉系腫瘍を疑い手術を施行した.腫瘍は9.5×9×8.5cm大, 重さ400g, 灰白色, 弾性硬で, 病理組織学的に腹腔内デスモイドと診断された.術後経過は良好で1年現在再発の徴候は認めていない.

Expression of KK-LC-1, a cancer/testis antigen, at non-tumour sites of the stomach carrying a tumour

Kita-Kyushu lung cancer antigen-1 (KK-LC-1) is a cancer/testis antigen (CTA) and predominant target for cancer immunotherapy. Our previous study indicated that KK-LC-1 was expressed in 82% of gastric cancers, and also in 79% of early stage of gastric cancers, with a correlation to Helicobacter pylori (H. pylori) infection. In addition, we found that KK-LC-1 was occasionally expressed at non-tumour sites of stomachs carrying tumours. Here, we investigated the characteristics of KK-LC-1 expression at non-tumour sites and the clinical utility of these phenomena. The gene expression of KK-LC-1 was detected at the non-tumour sites including pyloric glands. The most detectable corpus/gland subset had a KK-LC-1 expression rate of 77% in the pyloric gland of the lower corpus where H. pylori preferentially exists. KK-LC-1 expression rates were 67% or 32% with or without intestinal metaplasia, which also induced by H. pylori, respectively. Consequently, KK-LC-1 would be detected at the pre-cancerous condition of the stomach, and may be a useful marker to predict gastric cancer.

Detection of KK-LC-1 Protein, a Cancer/Testis Antigen, in Patients with Breast Cancer

Background: Kita-Kyushu lung cancer antigen-1 (KK-LC-1) is a cancer/testis antigen and predominant target for cancer immunotherapy. Its detection is only established based on gene expression. In this study, we established a monoclonal antibody against KK-LC-1 to detect its protein expression in formalin-fixed samples. Materials and Methods: The monoclonal antibody against KK-LC-1 was evaluated and the detection of KK-LC-1 between gene expression and protein expression was compared in patients with breast cancer. The monoclonal antibody clone 34B3, which we established, stained testicular germ cells positively. Results: The rates of detection of KK-LC-1 gene and protein expression were 11.8% and 52.9%, respectively. Protein expression was detected in all triple-negative breast cancer cases studied (n=8). Furthermore, KK-LC-1 was detected in all tumours without oestrogen receptor expression. Conclusion: This study indicated that KK-LC-1 expression was detected in breast cancer, especially in oestrogen receptor-negative subtypes.

Primary hepatic angiomyolipoma: immunohistochemistry and electron microscopic observations: a case report

BackgroundHepatic angiomyolipomas are a rare, benign group of mesenchymal tumors in the liver. Hepatic angiomyolipoma is sometimes misdiagnosed as hepatocellular carcinoma, and there is the possibility of a malignant transformation. Hence, the accurate diagnosis of this disorder is necessary.Case presentationA 64-year-old Japanese man was observed to have a space-occupying lesion of 15-mm diameter in the liver during a follow-up examination for a previously resected cecal carcinoma. He underwent lateral segmentectomy of the liver with a provisional diagnosis of hepatic metastatic recurrence of the carcinoma based on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging and diffusion-weighted imaging.ConclusionsWe have explored the combination of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging and histological examination to confirm our diagnosis of hepatic angiomyolipoma comprising an intimate mixture of numerous abnormal blood vessels, adipocytes, and epithelioid spindle cells of various sizes. Immunohistochemical examination revealed characteristic pathological findings associated with positive qualitative immunoreactions for human melanoma black 45 and desmin. Electron microscopic findings revealed the presence of melanosomes in the epithelioid cells. Diffusion-weighted imaging provides a more accurate diagnostic image with the characteristic macroscopic appearance of hepatic angiomyolipoma. Through immunohistochemistry and electron microscopy, we also show that this benign tumor comprises tissue elements.

A Case Report of Congenital Esophagobronchial Fistula with Esophageal Diverticulum.

食道憩室を伴った先天性食道気管支瘻の1例を経験した. 症例は53歳の男性で, 人間ドックで上部消化管造影を行ったところ, 食道憩室気管支瘻を認めた. これは, 胸部中部食道左側に憩室を認め, 憩室底より左肺下葉の気管支が造影されていた. 食道内視鏡では, 胸部食道に食道憩室があり底部に瘻孔開口部を認め, 気管支鏡では, 瘻管の開口部は確認できなかったが, 食道内チューブより色素を注入し左B6付近からの色素の流出を認めた手術は食道憩室と瘻管の切除を行った. 病理学的には, 瘻管の内腔の大部分は重層扁平上皮で被われ平滑筋を伴い, 辺縁の一部に多列線毛上皮が見られ, 両者には移行像も認められた.この疾患は本例を含め本邦では55例が報告されているが左気管支と交通する例は珍しく本例は8例めの報告である.