The apelin­apelin receptor signaling pathway in fibroblasts is involved in tumor growth via p53 expression of cancer cells.

Cancer­associated fibroblasts (CAFs) are pivotal in tumor progression. TP53­deficiency in cancer cells is associated with robust stromal activation. The apelin­apelin receptor (APJ) system has been implicated in suppressing fibroblast­to­myofibroblast transition in non­neoplastic organ fibrosis. The present study aimed to elucidate the oncogenic role of the apelin­APJ system in tumor fibroblasts. APJ expression and the effect of APJ suppression in fibroblasts were investigated for p53 status in cancer cells using human cell lines (TP53­wild colon cancer, HCT116, and Caco­2; TP53­mutant colon cancer, SW480, and DLD­1; and colon fibroblasts, CCD­18Co), resected human tissue samples of colorectal cancers, and immune­deficient nude mouse xenograft models. The role of exosomes collected by ultracentrifugation were also analyzed as mediators of p53 expression in cancer cells and APJ expression in fibroblasts. APJ expression in fibroblasts co­cultured with p53­suppressed colon cancer cells (HCT116sh p53 cells) was significantly lower than in control colon cancer cells (HCT116sh control cells). APJ­suppressed fibroblasts treated with an antagonist or small interfering RNA showed myofibroblast­like properties, including increased proliferation and migratory abilities, via accelerated phosphorylation of Sma­ and Mad­related protein 2/3 (Smad2/3). In addition, xenografts of HCT116 cells with APJ­suppressed fibroblasts showed accelerated tumor growth. By contrast, apelin suppressed the upregulation of phosphorylated Smad2/3 in fibroblasts. MicroRNA 5703 enriched in exosomes derived from HCT116sh p53 cells inhibited APJ expression, and inhibition of miR­5703 diminished APJ suppression in fibroblasts caused by cancer cells. APJ suppression from a specific microRNA in cancer cell­derived exosomes induced CAF­like properties in fibroblasts. Thus, the APJ system in fibroblasts in the tumor microenvironment may be a promising therapeutic target.

Pyogenic granuloma originating in the pulmonary artery.

We herein report an unreported case of pyogenic granuloma that originated in the pulmonary artery. A 38-year-old man was urgently hospitalized with dyspnea and back pain. He had been on hemodialysis for 2 years due to chronic renal failure. We performed contrast-enhanced computed tomography and detected a mass occluding the left main pulmonary artery. The maximum standardized uptake value (SUVmax) of 18F-fluorodeoxy glucose (FDG) in the mass was 4.1. We made a tentative diagnosis of pulmonary artery tumor, and planned an operation. We performed median sternotomy and left anterolateral thoracotomy. As the tumor had not reached the bottom of the left pulmonary artery, we first performed left upper lobectomy. We then performed resection of the pulmonary artery tumor under cardiopulmonary bypass and reconstructed the pulmonary artery with self-pericardium. The pathological diagnosis was pyogenic granuloma. To our knowledge, pyogenic granuloma originating in the pulmonary artery has never been reported before.

Long-Term Zinc Supplementation Improves Liver Function and Decreases the Risk of Developing Hepatocellular Carcinoma.

Zinc plays a pivotal role in various zinc enzymes, which are crucial in the maintenance of liver function. Patients with chronic liver diseases (CLDs) usually have lower concentrations of zinc, which decrease further as liver fibrosis progresses. Whether long-term zinc supplementation improves liver function and reduces the risk of hepatocellular carcinoma (HCC) development remains unknown. Two hundred and sixty-seven patients with CLDs who received a zinc preparation (Zn-group; 196 patients), or who did not receive zinc (no Zn-treatment group; 71 patients), were retrospectively analyzed in this study. The Zn-group was divided into 4 groups according to their serum Zn concentrations at 6 months after the start of Zn treatment. Liver function significantly deteriorated in the no Zn-treatment group, while no notable change was observed in the Zn-group. The cumulative incidence rates of events and HCC at 3 years were observed to be lower in the Zn-group (9.5%, 7.6%) than in the no Zn-treatment group (24.9%, 19.2%) (p < 0.001). According to serum Zn concentrations, the cumulative incidence rates of events and HCC were significantly decreased in patients with Zn concentrations ≥ 70 µg/dL (p < 0.001). Zinc supplementation appears to be effective at maintaining liver function and suppressing events and HCC development, especially among patients whose Zn concentration is greater than 70 µg/dL.

[Right Atrial Approach for the Surgical Repair of Delayed Ventricular Septal Rupture].

Ventricular septal rupture(VSR) after acute myocardial infarction(AMI) is a rare and serious complication that is associated with extremely high mortality. Delayed VSR is particularly uncommon and is difficult to diagnose and treat. A 68-year-old man presented with dyspnea on effort. Coronary angiography revealed subtotal occlusion of the right coronary artery(RCA) with collateral circulation to the chronically and totally occluded left anterior descending artery (LAD). Elective stenting of the RCA was successfully performed for a recent MI of the RCA, while percutaneous coronary intervention(PCI) in the LAD ended in failure. At 21 days after the 1st PCI, the patient developed acute heart failure with new pansystolic murmur. Cardiac catheterization showed a left to right ventricular shunting without new coronary artery lesions. Fortunately, the hemodynamic status was stable, and we could perform elective surgical repair by right atrial approach. Simultaneously, a left internal thoracic artery bypass to the LAD was performed. The postoperative course was uneventful. The patient is currently doing well at 5 years after the operation.

NY-ESO-1 expression and its serum immunoreactivity in esophageal cancer.

PURPOSE: NY-ESO-1, a member of the cancer/testis antigen (CTA) family, elicits humoral and cellular immune responses in patients with advanced cancer. Unresectable or metastatic esophageal carcinoma patients do not benefit from the present multimodality treatment regimens in terms of survival. The objectives of this study were to analyze the antibody response to NY-ESO-1 antigen in patients with esophageal cancer and to determine the potential of NY-ESO-1 for use in tumor-specific immunotherapy. METHODS: Serum from 69 patients with esophageal cancer was investigated for antibody production against NY-ESO-1 by Western blot analysis. Also analyzed by immunohistochemistry were 56 tissue samples from these patients for NY-ESO-1 protein expression. RESULTS: NY-ESO-1 protein expression was found in 18 of 56 (32%) esophageal carcinomas. Serum immunoreactivity specific for NY-ESO-1 was found in 9 patients (13%) of whom 8 were in the advanced stage (stages III and IV). There was no relationship between clinicopathologic features and serum immunoreactivity for NY-ESO-1. NY-ESO-1 protein expression was detected in three of five antibody-positive patients whose tissue was available for analysis. Survival analysis showed no significant difference between antibody-positive and antibody-negative patient groups. CONCLUSIONS: A humoral immune response to NY-ESO-1 antigen was established in patients with advanced esophageal cancer. NY-ESO-1 is a good candidate for vaccine-based immunotherapy for advanced esophageal carcinoma.

Development of a novel monoclonal antibody recognizing basal cells of human squamous epithelia.

The basal layer of the epithelium is usually thought to contain stem or progenitor cell populations. In order to analyze its biological characteristics, we attempted to produce novel monoclonal antibodies recognizing basal cells of the human esophageal epithelium. Hybridomas were generated from fusions between spleen cells of ddY mice immunized with esophageal epithelial cells (EECs) cultured at low calcium concentrations. A clone, NJ-E-H10, producing a monoclonal antibody (moAb) reacting with basal cells of human esophageal epithelia, was selected for its staining pattern on frozen sections of the epithelia. The immunoreactivities of NJ-E-H10 were detected in the cytoplasm of basal cells predominantly located in the interpapillary zones of the epithelia. In the primary culture of EECs, immunoreactive cells were present at the marginal area of the growing colonies, where EECs extend their cytoplasm and migrate out of the colonies. Immunoelectron microscopy demonstrated the immunoreactivities of the moAb NJ-E-H10 around the intermediate filaments of basal cells, but not on the filaments themselves. In the human skin, NJ-E-H10 positive cells were also observed in the basal layer of the epidermis as well as in keratinocytes in the outer layer of the outer root sheath in hair follicles and myoepitheial cells in the sweat glands. Since the distribution of NJ-E-H10 immunoreactivities differs from that reported by hitherto-known antibodies, the MoAb NJ-E-H10 is considered a new marker for clarifing the biological properties of the basal cell compartment in stratified epithelia.