Recovery of Immunoglobulin VJ Recombinations from Pancreatic Cancer Exome Files Strongly Correlates with Reduced Survival
AbstractWe assessed pancreatic cancer, lymphocyte infiltrates with a computational genomics approach. We took advantage of tumor-specimen exome files available from the cancer genome atlas to mine T- and B-cell immune receptor recombinations, using highly efficient, scripted algorithms established in several previous reports. Surprisingly, the results indicated that pancreatic cancer exomes represent one of the highest level yields for immune receptor recombinations, significantly higher than two comparison cancers used in this study, head and neck and bladder cancer. In particular, pancreatic cancer exomes have very large...
Source: Cancer Microenvironment - February 5, 2018 Category: Cancer & Oncology Source Type: research

Immunogenomics: A Negative Prostate Cancer Outcome Associated with TcR- γ/δ Recombinations
AbstractWe developed a scripted algorithm, based on previous, earlier editions of the algorithm, to mine prostate cancer exome files for T-cell receptor (TcR) recombination reads: Reads representing TcR gene recombinations were identified in 497 prostate cancer exome files from the cancer genome atlas (TCGA). As has been reported for melanoma, co-detection of productive TcR- α and TcR-β recombination reads correlated with an RNA expression signature representing T-cell exhaustion, particularly with high RNA levels for PD-1 and PD-L1, in comparison to several different control sets of samples. Co-detection of TcR-α and T...
Source: Cancer Microenvironment - January 22, 2018 Category: Cancer & Oncology Source Type: research

Positive Correlation between Matrix Metalloproteinases and Epithelial-to-Mesenchymal Transition and its Association with Clinical Outcome in Bladder Cancer Patients
AbstractInvolvement of matrix metalloproteinases (MMPs) in the pathogenesis of urothelial carcinoma elects them to be sensitive marker for clinical and prognostic implications. MMPs regulate tumor growth and invasion by inducing epithelial-to-mesenchymal transition (EMT) which is characterized by the complex reprogramming of epithelial cells and ultimately bring about major changes in the structural organization of bladder urothelium. The present study has been undertaken to evaluate the clinical relevance of MMPs in two distinct types of bladder cancer disease. Expression analysis of MMPs namely MMP-2, MMP-7, MMP-9 and EM...
Source: Cancer Microenvironment - January 18, 2018 Category: Cancer & Oncology Source Type: research

Three-Dimensional Cellular Arrangement in Epithelial Ovarian Cancer Cell Lines TOV-21G and SKOV-3 is Associated with Apoptosis-Related miRNA Expression Modulation
AbstractEpithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, and the lack of chemoresistance biomarkers contributes to the poor prognosis. Cancer stem cells (CSC) have been investigated in EOC to understand its relationship with chemoresistance and recurrence. In this context, in vitro cultivation-models are important tools for CSC studies. MicroRNAs (miRNAs) play key roles in cancer, CSC regulation and apoptosis. Thus, this study aims to evaluate the tumorsphere model as CSC-enrichment method in EOC studies and investigate apoptosis-related miRNAs in tumorspheres-derived EOC cell lines. TOV-21G and...
Source: Cancer Microenvironment - January 6, 2018 Category: Cancer & Oncology Source Type: research

The Impact of Microenvironment on the Synovial Sarcoma Transcriptome
AbstractSynovial sarcoma (SS) is initiated by at(X;18) chromosomal translocation and resultantSS18-SSX fusion oncogene. Only a few SS cell lines exist. None has been compared to its source tumor. In order to compare matched tumor and cell line pairs, we performed RNAseq on 3 tumor/cell line pairs from a genetically engineered mouse model of SS, as well as 2 pairs from human SS tumors. Transcriptomes of mouse tumors and derivative cell lines deviated significantly. Differentially expressed genes highlighted inflammatory infiltrates and metabolism. The same was found for the human tumor and cell line pairs. More was shared b...
Source: Cancer Microenvironment - December 1, 2017 Category: Cancer & Oncology Source Type: research

Correlation of Circulating CD64 + /CD163 + Monocyte Ratio and stroma/peri-tumoral CD163 + Monocyte Density with Human Papillomavirus Infected Cervical Lesion Severity
This study aimed to investigate circulating monocyte populations correlated with M2 phenotype density and its activity in HPV infected cervical lesions. HPV DNA was investigated in cervical tissues using PCR. High risk HPV E6/E7 mRNA was detected using in situ hybridization. CD163 immunohistochemical staining was performed for M2 macrophage. CD163 and Arg1 mRNA expression were detected using real-time PCR. Circulating monocyte subpopulations were analyzed using flow cytometry. CD163 and Arg1 mRNA expression were increased according to cervical lesion severity and corresponding with density of M2 macrophage in HSIL and SCC ...
Source: Cancer Microenvironment - December 1, 2017 Category: Cancer & Oncology Source Type: research

Upregulation of Treg-Related Genes in Addition with IL6 Showed the Significant Role for the Distant Metastasis in Colorectal Cancer
AbstractT helper 17 (Th17) and T regulatory (Treg) cytokines appear to be contributing greatly to colorectal cancer (CRC) development and progression. The aim of the current study was to investigate the expression ofFoxp3;IL10;TGFB1;IL17A;IL6 andNOS2 genes in tumor tissue, regional positive lymph nodes and distant metastasis obtained from 26 patients with advanced CRC. Quantitative real-time polymerase chain reaction (qPCR) was performed for mRNA detection by TaqMan gene expression assay. In distant metastasis,IL6 was strongly expressed, over 7.5 fold, followed by Treg-related genesFoxp3;IL10 andTGFB1 in contrast toIL17A a...
Source: Cancer Microenvironment - December 1, 2017 Category: Cancer & Oncology Source Type: research

SR 11302, an AP-1 Inhibitor, Reduces Metastatic Lesion Formation in Ex Vivo 4D Lung Cancer Model
AbstractActivator protein (AP) -1 is a transcription factor, plays important role in cell differentiation, proliferation and apoptosis. Analysis of tumor cells grown onex vivo 4D lung cancer model shows increase in components of AP-1, c-Fos and c-Jun in circulating tumor cells (CTC) compared to primary tumor. Our aim was to determine whether the AP-1 inhibitor SR11302 reduces metastatic lesion formation in the 4D model. Human lung cancer cell lines A549, H1299, and H460 were grown in the 4D model and treated with SR11302 (1  μM). We compared the number of cells in the metastatic site upon SR11302 treatment and number of ...
Source: Cancer Microenvironment - November 24, 2017 Category: Cancer & Oncology Source Type: research

Prognostic Prediction of Oral Squamous Cell Carcinoma by E-Cadherin and N-Cadherin Expression in Overall Cells in Tumor Nests or Tumor Cells at the Invasive Front
AbstractEpithelial-mesenchymal transition (EMT) is a significant process in the invasion and metastasis of cancers including oral squamous cell carcinoma (OSCC), and the cadherin switch has been identified as one of the hallmarks of EMT. The aim of the present study was to evaluate the significance of the cadherin switch in the prognosis of OSCC and generate a model for prognostic predictions. Seventy-six biopsy and/or initial surgical specimens from OSCC patients were immunohistochemically analyzed for the expression of E-cadherin and N-cadherin in either overall OSCC cells in tumor nests or in OSCC cells at the invasive ...
Source: Cancer Microenvironment - November 2, 2017 Category: Cancer & Oncology Source Type: research

Correlation of Circulating CD64 + /CD163 + Monocyte Ratio and stroma/peri-tumoral CD163 + Monocyte Density with Human Papillomavirus Infected Cervical Lesion Severity
This study aimed to investigate circulating monocyte populations correlated with M2 phenotype density and its activity in HPV infected cervical lesions. HPV DNA was investigated in cervical tissues using PCR. High risk HPV E6/E7 mRNA was detected using in situ hybridization. CD163 immunohistochemical staining was performed for M2 macrophage. CD163 and Arg1 mRNA expression were detected using real-time PCR. Circulating monocyte subpopulations were analyzed using flow cytometry. CD163 and Arg1 mRNA expression were increased according to cervical lesion severity and corresponding with density of M2 macrophage in HSIL and SCC ...
Source: Cancer Microenvironment - October 24, 2017 Category: Cancer & Oncology Source Type: research

Upregulation of Treg-Related Genes in Addition with IL6 Showed the Significant Role for the Distant Metastasis in Colorectal Cancer
AbstractT helper 17 (Th17) and T regulatory (Treg) cytokines appear to be contributing greatly to colorectal cancer (CRC) development and progression. The aim of the current study was to investigate the expression ofFoxp3;IL10;TGFB1;IL17A;IL6 andNOS2 genes in tumor tissue, regional positive lymph nodes and distant metastasis obtained from 26 patients with advanced CRC. Quantitative real-time polymerase chain reaction (qPCR) was performed for mRNA detection by TaqMan gene expression assay. In distant metastasis,IL6 was strongly expressed, over 7.5 fold, followed by Treg-related genesFoxp3;IL10 andTGFB1 in contrast toIL17A a...
Source: Cancer Microenvironment - September 3, 2017 Category: Cancer & Oncology Source Type: research

Expression Profiling of the MAP Kinase Phosphatase Family Reveals a Role for DUSP1 in the Glioblastoma Stem Cell Niche
AbstractThe dual specificity phosphatases (DUSPs) constitute a family of stress-induced enzymes that provide feedback inhibition on mitogen-activated protein kinases (MAPKs) critical in key aspects of oncogenic signaling. While described in other tumor types, the landscape of DUSP mRNA expression in glioblastoma (GB) remains largely unexplored. Interrogation of the REpository for Molecular BRAin Neoplasia DaTa (REMBRANDT) revealed induction (DUSP4, DUSP6), repression (DUSP2, DUSP7 –9), or mixed (DUSP1, DUSP5, DUSP10, DUSP15)DUSP transcription of select DUSPs in bulk tumor specimens. To resolve features specific to the tu...
Source: Cancer Microenvironment - August 18, 2017 Category: Cancer & Oncology Source Type: research

Effects of Vacuolar H + -ATPase Inhibition on Activation of Cathepsin B and Cathepsin L Secreted from MDA-MB231 Breast Cancer Cells
AbstractStudies indicate secreted cathepsins are involved in metastasis. V-ATPases, which are necessary for activating intracellular cathepsins, also play a role in metastasis and are targeted to the plasma membrane of metastatic breast cancer cells. We are interested in a connection between cell surface V-ATPases, activation of secreted cathepsins and the metastatic phenotype of MDA-MB231 cells. We investigated whether V-ATPase inhibition would reduce the activity of secreted cathepsin B and cathepsin L. Using cell lysates and conditioned media, we measured cathepsin B and L activity within and outside of the cells. We fo...
Source: Cancer Microenvironment - August 1, 2017 Category: Cancer & Oncology Source Type: research

Human Metaplastic Breast Carcinoma and Decorin
In this study, decorin immunoreactivity and the effect of adenoviral decorin cDNA (Ad-DCN) transduction were examined in MBC. Multiple immunohistochemical stainings were used to characterize a massive breast tumour derived from an old woman. Furthermore, three-dimensional (3D) explant cultures derived from the tumour were transduced with Ad-DCN to study the effect of the transduction on the explants. The MBC tumour was shown to be completely negative for decorin immunoreactivity demonstrating that the malignant cells were not able to synthesize decorin. Ad-DCN transduction resulted in a markedly altered cytological phenoty...
Source: Cancer Microenvironment - June 26, 2017 Category: Cancer & Oncology Source Type: research

Participation of Tumor-Associated Myeloid Cells in Progression of Amelanotic Melanoma (RMM Tumor Line) in F344 Rats, with Particular Reference to MHC Class II- and CD163-Expressing Cells
AbstractTumor progression is often influenced by infiltration of myeloid cells; depending on the M1- or M2-like activation status, these cells may have either inhibitory or promoting effects on tumor growth. We investigated the properties of tumor-associated myeloid cells in a previously established homotransplantable amelanotic melanoma (RMM tumor line) in F344 rats. RMM tumor nodules were allowed to reach the sizes of 0.5, 1, 2 and 3  cm, respectively. Immunohistochemistry and flow cytometry was performed for macrophage markers CD68 and CD163, and for the antigen-presenting cell marker, MHC class II. Although no signifi...
Source: Cancer Microenvironment - June 16, 2017 Category: Cancer & Oncology Source Type: research