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.

AIMTo assess cancer-testis antigens (CTAs) expression in gastric cancer patients and examined their associations with clinicopathological factors.METHODSEighty-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.RESULTSThe 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).CONCLUSIONThe 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.

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.

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.Breast cancer is the most frequently diagnosed cancer in women. It is also a predominant cause of mortality (1). However, standard therapies for breast cancer have not reduced mortality. New therapies against breast cancer, especially triple-negative breast cancer (TNBC), that cannot be applicable for hormone and HER2 therapy, are needed. A recent study indicated that inhibitors of immune checkpoints such as programmed death (PD)-1/PD ligand-1 interaction can restore the immune response of cytotoxic T-lymphocytes (CTLs) to tumour-associated antigens and have been successfully established as a new cancer therapy (2).Several tumour-associated antigens have been identified in various human cancer types (3). These antigens are classified into four categories, excluding extrinsic viral antigens, as follows: cancer/testis antigens (CTAs), differentiation antigens, amplification or overexpression antigens, and tumour-specific mutated antigens recently defined as neo-antigens. CTAs are especially attractive targets for immunotherapy because they are not at all, or minimally expressed in normal tissues except for the testis, but are aberrantly expressed in a range of human cancer types (4). Therefore, immune targeting of these antigens is thought to have negligible adverse side-effects.Kita-Kyushu lung cancer antigen-1 (KK-LC-1), also known as CT83 and CXORF61, is a CTA that has epitope peptides recognised by CTLs. When CTLs against KK-LC-1 accumulate predominantly among tumour-infiltrating lymphocytes, adaptive immunotherapy using such lymphocytes leads to a good response (5). KK-LC-1 maps to chromosome Xq23, and is not expressed in normal tissues except for the testis, but is expressed in 33% of non-small cell lung cancer (6, 7). Furthermore, KK-LC-1 was found to be expressed in 82% and 75% of patients with gastric cancer (10) and TNBC (8,9).Almost all studies about KK-LC-1 screening have evaluated its gene expression. Although some reports used polyclonal antibody (pAb) against KK-LC-1 (9, 10), we...

Abstract. Background/Aim: Our previous study indicatedthat Kita-kyushu