TFF-1 Functions to Suppress Multiple Phenotypes Associated with Lung Cancer Progression.

Introduction: Trefoil Factor (TFF) is a member of a protein family comprised of three isoforms, of which TFF-1 exhibits antithetical functions; promotion or suppression of cell proliferation, survival and invasion, depending on the cancer type. However, the pathobiological function of TFF-1 in lung carcinoma has been still unclear.

Methods: We examined the expression and secretion of TFF-1 using cultured human lung carcinoma cells by immunoblotting, immunofluorescence, enzyme-linked immunosorbent assay and quantitative real-time PCR analyses.

Neural EGFL like 2 expressed in myoepithelial cells and suppressed breast cancer cell migration.

Breast tissue has a branching structure that contains double-layered cells, consisting primarily of luminal epithelial cells inside and myoepithelial cells outside. Ductal carcinoma in situ (DCIS) still has myoepithelial cells surrounding the cancer cells. However, myoepithelial cells disappear in invasive ductal carcinoma.

EphA2, a possible target of miR-200a, functions through the AKT2 pathway in human lung carcinoma.

We previously reported that miR-200a was highly up-regulated in lung carcinoma, exhibiting a copy number increase (CNI) of the AKT2 gene (AKT2+ group) in defined subsets, i.e., adenocarcinoma and early stages of carcinoma (pStage I/II).

The relation between anti-TGBFR1 immunohistochemical reaction and low Ki67, small tumor size and high estrogen receptor expression in invasive breast cancer.

Most breast cancers are derived from the luminal epithelium, which composes the inside of the breast ductal structure. Ductal carcinoma in situ (DCIS) leads to invasive ductal carcinoma, but noncancerous intraductal proliferative lesions are also a risk factor for ductal carcinoma. The transforming growth factor beta (TGFB) signaling pathway behaves as a tumor suppressor in the early stage of cancer, and conversely as a tumor growth factor in invasive stages in several cancers.

Screening of the copy number increase of in lung carcinoma by custom-designed MLPA.

Treatments for lung cancer include therapies targeting aberrant oncoproteins, but there remains a high medical need for novel therapies. Our previous studies showed that gene amplification/high-level polysomy of occurs in more than 10% of lung carcinomas. Here, we describe multiplex ligation-dependent probe amplification analysis (MLPA) as a high-throughput method to evaluate copy number increases (CNIs) of in lung carcinomas.

Amplicons in breast cancers analyzed by multiplex ligation-dependent probe amplification and fluorescence in situ hybridization.

Gene amplification is a common event in breast cancer, and identifies actual and potential targets of molecular therapy. The aim of the present study was to determine the amplification status of 22 genes that are reportedly frequently amplified in breast cancers. An archive of 322 formalin-fixed and paraffin-embedded invasive breast cancer tissues were screened by multiple ligation-dependent probe amplification (MLPA) and a total of 906 gene loci judged as 'gain' or 'amplified' was further confirmed to have been amplified based on fluorescence in situ hybridization (FISH).

Clinicopathological features of epiretinal membranes in eyes filled with silicone oil.

Purpose: The aim of this case series was to clarify the clinicopathological features of epiretinal membranes (ERMs) that developed in eyes after silicone oil (SO) tamponade to treat rhegmatog-enous retinal detachments (RRDs).

Patients And Methods: In the Department of Ophthalmology, Saitama Medical Center, Jichi Medical University, patients with idiopathic ERMs (23 eyes) and ERMs in eyes filled with SO (SO ERMs) after vitreous surgery to treat RRDs (nine eyes) were enrolled from July 2012 to March 2014. ERM tissues obtained intraoperatively were examined histopathologically.

Regulation of p27 by ubiquitin ligases and its pathological significance in human lung carcinomas.

Down-regulation of cyclin-dependent kinase inhibitor protein p27, due to enhanced degradation, is frequently observed in various cancers. The ubiquitin ligases that mediate this degradation have been identified as S-phase kinase-associated protein-2 (Skp2), Kip1 ubiquitylation-promoting complex (KPC), and p53-inducible protein with RING-H2 domain (Pirh2) as well. We investigated the correlation among expression of these 3 ligases and p27 status in surgical specimens of human lung carcinomas by immunohistochemical analysis.

Gene amplification of CCNE1, CCND1, and CDK6 in gastric cancers detected by multiplex ligation-dependent probe amplification and fluorescence in situ hybridization.

New and effective treatments for advanced gastric cancer are urgently needed. Cyclins E and D1 form a complex with cyclin-dependent kinase 2, 4, or 6 to regulate G1-S transition. The G1-S regulatory genes encoding cyclin E (CCNE1), cyclin D1 (CCND1), and CDK6 (CDK6) are frequently amplified in gastric cancer and may therefore influence molecularly targeted therapies against ERBB2 or EGFR when coamplified.

Loss of YAP1 defines neuroendocrine differentiation of lung tumors.

YAP1, the main Hippo pathway effector, is a potent oncogene and is overexpressed in non-small-cell lung cancer (NSCLC); however, the YAP1 expression pattern in small-cell lung cancer (SCLC) has not yet been elucidated in detail. We report that the loss of YAP1 is a special feature of high-grade neuroendocrine lung tumors. A hierarchical cluster analysis of 15 high-grade neuroendocrine tumor cell lines containing 14 SCLC cell lines that depended on the genes of Hippo pathway molecules and neuroendocrine markers clearly classified these lines into two groups: the YAP1-negative and neuroendocrine marker-positive group (n = 11), and the YAP1-positive and neuroendocrine marker-negative group (n = 4).

MicroRNAs associated with increased AKT gene number in human lung carcinoma.

MicroRNA (miRNA) expression profiles were examined in 3 groups of lung carcinomas that had been stratified by increases in AKT1 or AKT2 gene number. Microarray analysis using 2000 probes revealed 87 miRNAs that were up-regulated and 32 down-regulated miRNAs in carcinomas harboring amplification or high-level polysomy of the AKT1 (AKT1+), as well as 123 up-regulated and 83 down-regulated miRNAs in those of the AKT2 genes (AKT2+), in comparison with carcinomas harboring disomy of both (AKTd/d). In total, 182 miRNAs were up-regulated in AKT1+ or AKT2+, compared with AKTd/d.

Association between AKT1 Gene Polymorphism rs2498794 and Smoking-Related Traits with reference to Cancer Susceptibility.

To clarify the potential role of variability within and around the AKT1 gene in smoking behaviors, we performed a single-nucleotide polymorphism (SNP) analysis of the AKT1 gene in an elderly Japanese cohort. Genotypes of the rs2498794 SNP, which is located in the fifth intron region of the AKT1 gene, were marginally but significantly associated with smoking duration in the total 999 samples of former and current smokers. Interestingly, this SNP had a marginally significant association with individual cancer history (past and current), especially in groups with a shorter smoking duration (<44 years) and fewer cigarettes per day (≤20).

Diverse involvement of isoforms and gene aberrations of Akt in human lung carcinomas.

Emerging evidence confirms a central role of Akt in cancer. To evaluate the relative contribution of deregulated Akt and their clinicopathological significance in lung carcinomas, overexpression, activation of Akt and AKT gene increases were investigated. Immunohistochemical staining for 108 cases revealed overexpression of total Akt, Akt1, Akt2 and Akt3 in 61.

Epidemiological and pathobiological profiles of Clostridium perfringens infections: review of consecutive series of 33 cases over a 13-year period.

Background: Although Clostridium perfringens (C. perfringens) is well known as the causative agent of several forms of enteric disease, precise epidemiological and pathobiological aspects are still unknown.

Methods: We retrospectively reviewed the culture results of samples collected in our hospital from 2001 through 2013.

Semi-comprehensive analysis of gene amplification in gastric cancers using multiplex ligation-dependent probe amplification and fluorescence in situ hybridization.

The prognosis of patients with gastric carcinomas at an advanced stage still remains dismal, and therefore novel therapeutic modalities are urgently needed. Since the successful targeting of amplified ERBB2 with a humanized monoclonal antibody, the amplified genes of other receptor tyrosine kinases such as EGFR, FGFR2, and MET, as well as those of other cell regulator genes, are being considered as candidate targets of molecular therapy. The aim of the present study was to determine the amplification status of 26 genes, which are frequently amplified in solid cancers, in advanced gastric cancers.

Solitary fibrous tumor of the thymus with variegated epithelial components.

Solitary fibrous tumor is a rare mesenchymal neoplasm, characterized by peculiar histological features composed by the proliferation of spindle cells in "patternless pattern". Although it has been known to sometimes be accompanied by epithelioid cells, the presence of a well-formed epithelial structure is far more rare. We describe herein the case of a 60-year-old female with the radiological finding of a single nodular lesion in the anterior mediastinum.

Clonal profiling of mixed lobular and ductal carcinoma revealed by multiplex ligation-dependent probe amplification and fluorescence in situ hybridization.

A needle biopsy of a mass in the right breast of a 36-year-old woman revealed invasive ductal carcinoma (IDC), and approximately 20% of cancer cells showed unequivocal membranous staining with the HercepTest. After systemic therapy with trastuzumab and paclitaxel followed by FEC (fluorouracil + epirubicin + cyclophosphamide), a right mastectomy was performed. By histological and immunohistochemical examinations, the resected tumor consisted mainly of E-cadherin-negative invasive lobular carcinoma (ILC), and the rest was ERBB2-positive IDC; thus, the diagnosis was mixed ductal and lobular carcinoma.

Intratumoral heterogeneous amplification of ERBB2 and subclonal genetic diversity in gastric cancers revealed by multiple ligation-dependent probe amplification and fluorescence in situ hybridization.

A humanized monoclonal antibody against ERBB2 is used in neoadjuvant therapy for patients with gastric cancer. A critical factor in determining patient eligibility and predicting outcomes of this therapy is the intratumoral heterogeneity of ERBB2 amplification in gastric adenocarcinomas. The aims of this study are to assess the underlying mechanisms of intratumoral heterogeneity of ERBB2 amplification; to characterize the diversity of coamplified oncogenes such as EGFR, FGFR2, MET, MYC, CCND1, and MDM2; and to examine the usefulness of multiple ligation-dependent probe amplification (MLPA) in the semicomprehensive detection of these gene amplifications.

Significance of Akt activation and AKT gene increases in soft tissue tumors.

To clarify the aberrations of AKT genes, their protein products and clinicopathologic significance in bone and soft tissue tumors, expression profiles of total Akt, its isoforms and activated Akt, and increases in copy number of AKT1/AKT2 genes were examined. Immunohistochemical analysis in 77 cases revealed overexpression of total Akt, Akt1, Akt2, and phosphorylated Akt in 84.4%, 67.

Genetic aberrations as the targets of oncology research: Involvement of paraffin-embedded tissues.

Cancer is a complex and heterogeneous group of diseases which have been generally classified by their clinical and histopathological features. The genomes of cancer cells are altered by diverse mechanisms and these genetic aberrations lead to a variety of pathological changes. A number of technological advances have allowed us to analyze the cancer genome by various '-omics' techniques, and have accelerated the exploration for the primary genetic aberrations that drive cancer.

Utility of fluorescence in situ hybridization to detect MDM2 amplification in liposarcomas and their morphological mimics.

The atypical lipomatous tumor (ALT)/well-differentiated liposarcoma (WDLS) and the de-differentiated liposarcoma (DDLS) represent the most common category of liposarcomas. ALT/WDLSs and DDLSs are often difficult to distinguish from other tumors with similar morphological characteristics. In this study, we investigated whether the detection of amplified or overexpressed murine double-minute 2 (MDM2) can be a useful diagnostic ancillary aid.