Sumiko Maeda

LAT1 acts as a crucial transporter of amino acids in human thymic carcinoma cells

L-type amino acid transporter 1 (LAT1, SLC7A5) incorporates essential amino acids into cells. Recent studies have shown that LAT1 is a predominant transporter in various human cancers. However, the function of LAT1 in thymic carcinoma remains unknown. Here we demonstrate that LAT1 is a critical transporter for human thymic carcinoma cells. LAT1 was strongly expressed in human thymic carcinoma tissues. LAT1-specific inhibitor significantly suppressed leucine uptake and growth of Ty82 human thymic carcinoma cell lines, suggesting that thymic carcinoma takes advantage of LAT1 as a quality transporter and that LAT1-specific inhibitor might be clinically beneficial in therapy for thymic carcinoma.

Tumor-related gene expression levels in thymic carcinoma and Type B3 thymoma

BackgroundThymic carcinoma (TC) is a rare type of malignant neoplasm that develops in the anterior mediastinum and associated with poor prognosis. Type B3 thymoma (B3) occasionally demonstrates malignant tumor characteristics, especially in the advanced stage. We investigated the expressions of tumor-related genes in resected TC and B3 specimens.MethodsTC and B3 specimens resected from 1999 through 2012 were investigated. Tumor segments were collected from the specimens by micro-dissection to extract mRNA, then RT-PCR was performed according to Dannenberg’s tumor profile method for semi-quantitation of tumor-related gene mRNA. To compare with other types of cancer, data from lung cancer (LC) cases in our database were also examined.ResultsThe gene expression levels of thymidylate synthase were significantly higher in TC and B3 as compared to LC specimens (p < 0.02), while no difference were observed between TC and B3 tumors. The ratio of folypolyglutamyl synthase (FPGS) to gamma-glutamyl hydrolase (GGH) mRNA was significantly lower in TC than in B3 (p < 0.05), with lower FPGS/GGH in those tumors related to overall survival. Also, the gene expression of vascular endothelial growth factor (VEGF) was significantly higher in TC as compared to B3 (p = 0.04), with higher VEGF gene expression in TC and B3 specimens related to overall survival of affected patients. Epidermal growth factor receptor (EGFR) expression was significantly higher in B3 as compared to both TC and LC specimens (p < 0.01). However, there were no EGFR gene mutations detected in any of the specimens.ConclusionsThese results indicate that elevated expressions of the tumor-related genes FPGS/GGH and VEGF are correlated with malignancy of TC and B3 tumors. Additional examinations will be necessary to investigate their chemosensitivity.

Nontuberculous mycobacterial and Aspergillus infections among cadaveric lung transplant recipients in Japan

BACKGROUND Lung transplantation is an effective treatment modality for respiratory failure. Chronic lung infections, including infections caused by nontuberculous mycobacteria (NTM) and Aspergillus, are difficult to control, and uncontrolled infections are relative contraindications for lung transplantation. However, few reports have documented the incidence and outcome of these infections in lung transplant recipients. METHODS To quantify the incidence and outcomes of colonization and disease caused by NTM and aspergillosis in recipients before and after lung transplantation, we reviewed the medical records and microbiology data from 240 consecutive cadaveric lung transplant recipients between 2000 and 2014. RESULTS Before lung transplantation, NTM and Aspergillus species were isolated from five (2.1%) and six (2.5%) patients, respectively, out of the total 240 recipients. All patients with NTM infection received treatment, resulting in culture conversion. They had no recurrence after lung transplantation. All patients with aspergillosis received treatment, one of whom had recurrence after lung transplantation. Over a median follow-up period of 3.3 years, NTM species were isolated after transplantation from eight of 240 patients (3.3%). Five of these patients met the criteria for NTM disease, and four of them received treatment. Four patients survived without a worsening of NTM disease. Over the same median follow-up period, Aspergillus species were isolated from seven of 240 patients (2.9%), six of whom received treatment. CONCLUSIONS Isolation of NTM or Aspergillus species from lung transplant recipients is uncommon. Adequate pre-transplant control and post-transplant management of NTM and Aspergillus infections allows for safe lung transplantation.

Mitosis count and number of cancer cells in cases of primary pulmonary adenocarcinoma: Correlations among phosphorylated histone 3, number of cancer cells, nuclear grade, pathologic features and prognosis: Mitosis count in lung adenocarcinoma

Immunohistochemistry findings for the phosphorylated form of histone 3 (pHH3) have been shown to be a reliable mitosis‐specific marker. We evaluated the correlation between pHH3‐stained mitotic figures (PHMFs) and clinical outcome, and compared the results with findings for numbers of PHMFs and cancer cells. The primary tumor was obtained from 113 patients with pulmonary adenocarcinomas (≤2 cm maximum dimension). All specimens were stained with pHH3, then the number of cancer cells in each was determined. Cases with a cancer‐cell index ≥1000 showed worse recurrence‐free survival as compared to those with a value <1000 (P < 0.001). Also, cases with a pHH3 index ≥0.27 showed worse recurrence‐free survival as compared to <0.27 (P = 0.001) and cases with a pHH3/cancer‐cell index ≥0.001 showed worse recurrence‐free survival as compared to <0.001 (P = 0.002). Multivariate analysis demonstrated that pHH3/cancer‐cell index was significantly correlated with prognosis, but not Ki‐67 index. The number of cancer cells was also strongly correlated with progression of Noguchis classification and WHO pathologic type. pHH3/cancer‐cell index was correlated with prognosis, and those were useful for prognostic evaluation of pulmonary adenocarcinoma patients. Furthermore, cancer cell number was correlated with Noguchis classification and WHO pathologic type.

Advanced Lung Cancer Inflammation Index Predicts Outcomes of Patients with Pathological Stage IA Lung Adenocarcinoma Following Surgical Resection

Purpose: The correlation of advanced cancer with inflammation and/or nutrition factors is well known. Recently, the advanced lung cancer inflammation index (ALI) was developed as a new prognostic tool for patients with advanced lung cancer. In this study, we examined whether ALI results are correlated with prognosis of patients with early stage lung adenocarcinoma who undergo lung resection. Methods: From January 2009 to December 2014, 544 patients underwent lung resection due to primary lung cancer at Dokkyo Medical University Hospital, of whom 166 with pathological stage IA lung adenocarcinoma were retrospectively investigated in this study. ALI was calculated as follows: Body Mass Index (BMI; kg/m2) × albumin (g/dL)/neutrophil- to-lymphocyte ratio (NLR). Results: Multivariate analysis revealed that gender, red cell distribution width (RDW), NLR, and ALI were parameters significantly correlated with overall survival (OS). Patients with an ALI value less than 22.2 had an inferior 5-year OS rate as compared to those with a value of 22.2 or higher (p <0.001) as well as an inferior 5-year recurrence-free survival (RFS) rate (p <0.001). Conclusion: Low ALI was correlated with poor prognosis in patients with stage IA lung adenocarcinoma. Those with an ALI value less than 22.2 should be carefully followed regardless of cancer stage.

Association of Perioperative Redox Balance on Long-Term Outcome in Patients Undergoing Lung Resection

PURPOSE We examined whether redox balance during the perioperative period is associated with long-term survival of patients after undergoing lung resection. METHODS Patients who underwent surgery for lung cancer from January to June 2013 at our institution were investigated. Serum was collected during the operation, and on postoperative day (POD) 3 and 7, and the levels of derivatives of reactive oxygen metabolites (d-ROMs) and biologic antioxidant potential (BAP) were measured. RESULTS In all, 21 patients (69 ± 7 years old) were enrolled, of whom 9 underwent video-assisted thoracoscopic surgery. Comorbidities in the patients included chronic obstructive pulmonary disease in eight and idiopathic pulmonary fibrosis in five. d-ROM values on POD 3 and 7 were significantly increased as compared to those obtained during the operation (p <0.001), whereas BAP did not change after surgery. Patients with a value below a d-ROM cutoff value of 327 during the operation showed significantly superior 3-year overall survival as compared to those with a value above the cutoff (87.5% vs. 20.0%, p <0.001). CONCLUSION In the present patients, surgical stress caused an increase in d-ROM during the postoperative course. The d-ROM value obtained during the operation was correlated with long-term survival following resection for lung cancer.