Search

Masaoka stage I type A thymomas rarely recur. We report the case of an 82-year-old man who developed endobronchial metastasis after thymothymectomy for Masaoka stage I type A thymoma. Twenty years after surgery, the patient developed bloody sputum, and chest computed tomography revealed a neoplasm obstructing the right upper lobe bronchus of the lung with enlarged mediastinal lymph nodes. He underwent right upper lobectomy and mediastinal lymph node dissection. Although preoperative pathological diagnosis was squamous cell carcinoma of the lung, postoperative histopathology revealed endobronchial metastasis of the thymoma. Nine years later, at age 89, the patient is alive and well.

BackgroundLOX family members are reported to play pivotal roles in cancer. Unlike their enzymatic activities in collagen cross-linking, their precise cancer functions are unclear. We revealed that LOXL4 is highly upregulated in breast cancer cells, and we thus sought to define an unidentified role of LOXL4 in breast cancer.MethodsWe established the MDA-MB-231 sublines MDA-MB-231-LOXL4 mutCA and -LOXL4 KO, which stably overexpress mutant LOXL4 that loses its catalytic activity and genetically ablates the intrinsic LOXL4 gene, respectively. In vitro and in vivo evaluations of these cells’ activities of cancer outgrowth were conducted by cell-based assays in cultures and an orthotopic xenograft model, respectively. The new target (s) of LOXL4 were explored by the MS/MS analytic approach.ResultsOur in vitro results revealed that both the overexpression of mutCA and the KO of LOXL4 in cells resulted in a marked reduction of cell growth and invasion. Interestingly, the lowered cellular activities observed in the engineered cells were also reflected in the mouse model. We identified a novel binding partner of LOXL4, i.e., annexin A2. LOXL4 catalyzes cell surface annexin A2 to achieve a cross-linked multimerization of annexin A2, which in turn prevents the internalization of integrin β-1, resulting in the locking of integrin β-1 on the cell surface. These events enhance the promotion of cancer cell outgrowth.ConclusionsLOXL4 has a new role in breast cancer progression that occurs via an interaction with annexin A2 and integrin β-1 on the cell surface.

Congenital lobar emphysema (CLE) is defined as the hyperinflation of pulmonary lobes due to obstruction of the flow of air via a known or unknown etiology, which causes pressure symptoms in the adjacent organs. CLE is mainly diagnosed in the neonatal period, and very few adult cases have been reported. Here we report a 34-year-old male with muscular dystrophy who was diagnosed with CLE on examination. He underwent a right lower lobectomy via 3-portal completely video-assisted thoracoscopic surgery, and his symptoms improved. Thoracoscopic surgery helped preserve the respiratory muscles and led to the improvement of respiratory function in this patient.

Pulmonary enteric adenocarcinoma (PEAC) is a rare subtype of lung cancer that should be differentiated from colorectal cancer metastasis. Little is known about its genetic background. An 84-year-old male with adenocarcinoma of the lung underwent left upper lobectomy. The histology of the surgical specimen was suggestive of PEAC. Gastrointestinal and colorectal fiberscopy revealed no evidence of colorectal cancer. Next-generation sequencing of the tumor identified a G469V substitution in serine/threonine-protein kinase B-raf (BRAF). Based on the higher prevalence of the G469 substitution in BRAF-mutant lung adenocarcinoma than in BRAFmutant colorectal cancer, the tumor likely originated from the lung. Identification of mutational genotype may be of some help in distinguishing PEAC from the lung metastasis of colorectal cancer.

Renal dysfunction is a long-term complication associated with an increased mortality after lung transplantation (LT). We investigated the association of single-nucleotide polymorphisms (SNPs) with the development of renal dysfunction after LT using a Japanese-specific SNP array. First, eligible samples of 34 LT recipients were genotyped using the SNP array and divided into two groups, according to the presence of homozygous and heterozygous combinations of mutant alleles of the 162 renal-related SNPs. To identify candidate SNPs, the renal function tests were compared between the two groups for each SNP. Next, we investigated the association between the candidate SNPs and the time course of changes of the estimated glomerular filtration rate (eGFR) in the 99 recipients until 10 years after the LT. Delta eGFR was defined as the difference between the postoperative and preoperative eGFR values. Eight SNPs were identified as the candidate SNPs in the 34 recipients. Validation analysis of these 8 candidate SNPs in all the 99 recipients showed that three SNPs, namely, rs10277115, rs4690095, and rs792064, were associated with significant changes of the Delta eGFR. Pre-transplant identification of high-risk patients for the development of renal dysfunction after LT based on the presence of these SNPs might contribute to providing personalized medicine.

Additional file 1: Table S1. List of 41 genes selected based on the signal-to-noise statistic. Table S2. Genes expressed differentially by more than twofold, in moderate and severe fibrotic samples compared to control lung samples. Table S3. List of 46 kinases having clinically available inhibitors.

Additional file 2: Fig. S1. a Clustering analysis of three samples from IPF case 2. b Clustering analysis of two samples from IPF case 3. c Signal-to-noise weighted-voting score based on 41 genes from IPF case 1. Fig. S2. Immunohistochemistry of ERBB4. Scale bar = 200 ��m. Fig. S3. Expression of the 40 selected genes encoding kinases having clinically available kinase inhibitors in IPF cases 4 (a) and 5 (b).

Additional file 8. Online Resource 8. Kaplan-Meier estimates of relapse-free survival.

Additional file 1. Online Resource 1. The exclusion criteria.

Additional file 7. Online Resource 7. Kaplan-Meier estimates of overall survival.

Additional file 5. Online Resource 5. The criteria for cessation of the protocol treatment.

Additional file 2: Fig. S1. Oct4a and Oct4b transcript variants are not expressed in adult murine somatic tissues, Fig. S2 Expression of SPP1C in normal human adult tissues, Fig. S3 Criteria for evaluation of OCT4/SPP1 transcript expression analysis for clinical tumour samples, Fig. S4–1 Uncropped full-length gel images related to Fig. 1a (hOCT4A), Fig. S4–2 Uncropped full-length gel images related to Fig. 1a (OCT4Bv), Fig. S4–3 Uncropped full-length gel images related to Fig. 1a (GAPDH), Fig. S4–4 Uncropped full-length gel images related to Fig. 1c, Fig. S5–1 Uncropped full-length gel images related to Fig. 2a, Fig. S5–2 Uncropped full-length gel images related to Fig. 2b, Fig. S5–3 Uncropped full-length gel images related to Fig. 2c (OCT4A, OCT4Bv), Fig. S5–4 Uncropped full-length gel images related to Fig. 2c (SPP1all, SPP1C), Fig. S5–5 Uncropped full-length gel images related to Fig. 2c (GAPDH), Fig. S6–1 Uncropped full-length gel images related to Fig. S1a, Fig. S6–2 Uncropped full-length gel images related to Fig. S1b, Fig. S7 Uncropped full-length gel images related to Fig. S2 (SPP1C), Fig. S8–1 Uncropped full-length gel images related to Fig. S3 (OCT4A, OCT4Bv), Fig. S8–2 Uncropped full-length gel images related to Fig. S3 (SPP1all, SPP1C), Fig. S8–3 Uncropped full-length gel images related to Fig. S3 (GAPDH)

Additional file 1: Table S1. Cell lines used in this study, Table S2. RNA resources used for analysis, Table S3. PCR primer sets for RT-PCR and qPCR, Table S4. Analysis of DNA variations according to sequencing analysis, Table S5. Summary of clinical data and OCT4/SPP1 expression analysis.

Figure S3. Molecular profiles of EGFR compound mutations. (A) In patients with the G719X compound mutation, five genes were highly induced while six genes were significantly repressed. In total, 11 genes were significantly altered in patient with the G719X compound mutation, while only 3 genes were significantly repressed in patient with the L858R compound mutation and 6 genes were altered in patient with the Ex19del compound mutation. (B) All the five significantly induced genes were unique for patient with the G719X compound mutation, while three out of six significantly down-regulated genes were overlapped with those of patient with the Ex19del compound mutation. (C)We performed GSEA using hallmark gene sets, revealing that several gene sets were correlated with the patient with the G719X compound mutation. (PDF 168 kb)

Figure S1. Patients population. Of 531 patients without any treatment before surgery, 415 (78%) were diagnosed as having adenocarcinoma. Based on clinical tests, 169 patients were diagnosed as EGFR-mutation positive. Of the 169 EGFR-mutation positive adenocarcinomas, 64 adenocarcinoma specimens were randomly selected and sequenced with MBS. (PDF 315 kb)

Figure S2. EGFR uncommon mutations detected by targeted sequencing. All the uncommon EGFR mutations detected in 7 cases were confirmed by direct sequencing. ECD, Extra-cellular Domain. (PDF 1223 kb)

Malignant mesothelioma (MM) is a highly aggressive tumor with a dismal prognosis. The incidence of MM is increasing as a result of widespread exposure to asbestos. As for the molecular alterations that occur in MM, chromosome alterations including homo-deletion of the P16 and P14 genes located in the 9p21 are well known. Mutations are rare in the P53 and Ras genes, which are frequently present in epithelial solid tumors. However, mutations are frequently present in the neurofi bromatosis type 2 gene. Epigenetic alterations including DNA methylation have been found in the MM, the profi le of which is diff erent from that of lung cancer, although differential diagnosis is sometimes clinically difficult. As in other malignant tumors, genes that are related to immortalization, proliferation, metastasis, angiogenesis, and anti-apoptosis are also overexpressed in MM, contributing to its malignant phenotype. It is of interest that simian virus 40 has been implicated to be one of the causative factors of MM in western countries. Although the causative role of asbestos is well-known in MM, much less information is available for MM than for other malignant tumors regarding the molecular alterations that occur in the disease. In terms of future tasks, it will be necessary to apply the knowledge that is learned about molecular alterations to clinical practice and to further elucidate the pathogenesis of MM with extensive research.

Dry pleural dissemination in non-small cell lung cancer, defined as solid pleural metastasis of lung cancer without pleural eff usion, is a condition occurring in T4 lung cancer. Positron emission tomography (PET) has been reported to be useful for the diagnosis and staging of lung cancer. It has been reported that positive findings on PET scans of indeterminate pleural abnormalities at computed tomography (CT) are sensitive to malignancy. We encountered two cases of dry small pleural dissemination of adenocarcinoma of the lung preoperatively detected by PET/CT. A 75-year-old man and a 66-year-old man underwent CT scan, which demonstrated solitary tumor in the lung, an enlarged mediastinal lymph node, and a small pleural nodule less than 10 mm in size, all of which were positive findings on the fluorine 18 fluorodeoxyglucose (FDG) PET portion of an integrated PET/CT. Both patients underwent thoracoscopic biopsy of the dry pleural nodule revealing dissemination of adenocarcinoma of the lung (T4). Whereas histological thoracoscopic diagnosis remains mandatory before planning treatment, our cases may suggest that PET/CT will be useful as a screening modality for dry pleural dissemination of lung cancer.