Abstract 949: PathSeq: A comprehensive computational tool for pathogen discovery by deep sequencing of human cancer tissues

Spectrometric-based surface-enhanced laser desorption/ionization ProteinChip (SELDI-TOF) facilitates rapid and easy analysis of protein mixtures and is often exploited to define potential diagnostic markers from sera. However, SELDI-TOF is a relatively insensitive technique and unable to detect circulating proteins at low levels even if they are differentially expressed in cancer patients. Therefore, we applied this technology to study tissues from renal cell carcinomas (RCC) in comparison to healthy controls. We found that different biomarkers are identified from tissues than those previously identified in serum, and that serum markers are often not produced by the tumors themselves at detectable levels, reflecting the nonspecific nature of many circulating biomarkers. We detected and characterized αB-crystallin as an overexpressed protein in RCC tissues and showed differential expression by immunohistochemistry. We conclude that SELDI-TOF is more useful for the identification of biomarkers that are synthesized by diseased tissues than for the identification of serum biomarkers and identifies a separate set of markers. We suggest that SELDI-TOF should be used to screen human cancer tissues to identify potential tissue-specific proteins and simpler and more sensitive techniques can then be applied to determine their validity as biomarkers in biological fluids.

Download Full-text

MicroRNA-219-5p Represses the Proliferation, Migration, and Invasion of Gastric Cancer Cells by Targeting the LRH-1/Wnt/β-Catenin Signaling Pathway

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504016x14768374457986 ◽

2017 ◽

Vol 25 (4) ◽

pp. 617-627 ◽

Cited By ~ 27

Author(s):

Chunsheng Li ◽

Jingrong Dong ◽

Zhenqi Han ◽

Kai Zhang

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Cell Lines ◽

Human Cancer ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Human Gastric Cancer ◽

Gastric Cancer Cells ◽

Cancer Tissues

MicroRNAs (miRNAs) are reportedly involved in gastric cancer development and progression. In particular, miR-219-5p has been reported to be a tumor-associated miRNA in human cancer. However, the role of miR-219-5p in gastric cancer remains unclear. In this study, we investigated for the first time the potential role and underlying mechanism of miR-219-5p in the proliferation, migration, and invasion of human gastric cancer cells. miR-219-5p was found to be markedly decreased in gastric cancer tissues and cell lines compared with adjacent tissues and normal gastric epithelial cells. miR-219-5p mimics or anti-miR-219-5p was transfected into gastric cancer cell lines to overexpress or suppress miR-219-5p expression, respectively. Results showed that miR-219-5p overexpression significantly decreased the proliferation, migration, and invasion of gastric cancer cells. Conversely, miR-219-5p suppression demonstrated a completely opposite effect. Bioinformatics and luciferase reporter assays indicated that miR-219-5p targeted the 3′-untranslated region of the liver receptor homolog-1 (LRH-1), a well-characterized oncogene. Furthermore, miR-219-5p inhibited the mRNA and protein levels of LRH-1. LRH-1 mRNA expression was inversely correlated with miR-219-5p expression in gastric cancer tissues. miR-219-5p overexpression significantly decreased the Wnt/β-catenin signaling pathway in gastric cancer cells. Additionally, LRH-1 restoration can markedly reverse miR-219-5p-mediated tumor suppressive effects. Our study suggests that miR-219-5p regulated the proliferation, migration, and invasion of human gastric cancer cells by suppressing LRH-1. miR-219-5p may be a potential target for gastric cancer therapy.

Download Full-text

Characterization of Gene Expression Patterns among Artificially Developed Cancer Stem Cells Using Spherical Self-Organizing Map

Cancer Informatics ◽

10.4137/cin.s39839 ◽

2016 ◽

Vol 15 ◽

pp. CIN.S39839 ◽

Cited By ~ 13

Author(s):

Akimasa Seno ◽

Tomonari Kasai ◽

Masashi Ikeda ◽

Arun Vaidyanath ◽

Junko Masuda ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Cancer Stem Cells ◽

Human Cancer ◽

Expression Patterns ◽

Embryonic Stem ◽

Culture Conditions ◽

Self Organizing Map ◽

Cancer Tissues ◽

Self Organizing

We performed gene expression microarray analysis coupled with spherical self-organizing map (sSOM) for artificially developed cancer stem cells (CSCs). The CSCs were developed from human induced pluripotent stem cells (hiPSCs) with the conditioned media of cancer cell lines, whereas the CSCs were induced from primary cell culture of human cancer tissues with defined factors ( OCT3/4, SOX2, and KLF4). These cells commonly expressed human embryonic stem cell (hESC)/hiPSC-specific genes ( POU5F1, SOX2, NANOG, LIN28, and SALL4) at a level equivalent to those of control hiPSC 201B7. The sSOM with unsupervised method demonstrated that the CSCs could be divided into three groups based on their culture conditions and original cancer tissues. Furthermore, with supervised method, sSOM nominated TMED9, RNASE1, NGFR, ST3GAL1, TNS4, BTG2, SLC16A3, CD177, CES1, GDF15, STMN2, FAM20A, NPPB, CD99, MYL7, PRSS23, AHNAK, and LOC152573 genes commonly upregulating among the CSCs compared to hiPSC, suggesting the gene signature of the CSCs.

Download Full-text

Deep sequencing of the TP53 gene reveals a potential risk allele for non–small cell lung cancer and supports the negative prognostic value of TP53 variants

Tumor Biology ◽

10.1177/1010428317694327 ◽

2017 ◽

Vol 39 (2) ◽

pp. 101042831769432 ◽

Cited By ~ 10

Author(s):

Christophe Deben ◽

Jolien Van den Bossche ◽

Nele Van Der Steen ◽

Filip Lardon ◽

An Wouters ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Deep Sequencing ◽

Cell Lung Cancer ◽

Prognostic Value ◽

Human Cancer ◽

Tp53 Gene ◽

Small Cell ◽

Small Cell Lung ◽

Tp53 Mutations

The TP53 gene remains the most frequently altered gene in human cancer, of which variants are associated with cancer risk, therapy resistance, and poor prognosis in several tumor types. To determine the true prognostic value of TP53 variants in non–small cell lung cancer, this study conducted further research, particularly focusing on subtype and tumor stage. Therefore, we determined the TP53 status of 97 non–small cell lung cancer adenocarcinoma patients using next generation deep sequencing technology and defined the prognostic value of frequently occurring single nucleotide polymorphisms and mutations in the TP53 gene. Inactivating TP53 mutations acted as a predictor for both worse overall and progression-free survival in stage II–IV patients and patients treated with DNA-damaging (neo)adjuvant therapy. In stage I tumors, the Pro-allele of the TP53 R72P polymorphism acted as a predictor for worse overall survival. In addition, we detected the rare R213R (rs1800372, minor allele frequency: 0.0054) polymorphism in 7.2% of the patients and are the first to show the significant association with TP53 mutations in non–small cell lung cancer adenocarcinoma patients (p = 0.003). In conclusion, Our findings show an important role for TP53 variants as negative predictors for the outcome of non–small cell lung cancer adenocarcinoma patients, especially for TP53 inactivating mutations in advanced stage tumors treated with DNA-damaging agents, and provide the first evidence of the R213R G-allele as possible risk factor for non–small cell lung cancer.

Download Full-text

Clinical significance of ERas oncogene on cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.15083 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 15083-15083

Author(s):

K. Yasuda ◽

M. Yashiro ◽

T. Sawada ◽

M. Ohira ◽

K. Hirakawa

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Es Cells ◽

Cancer Cell Lines ◽

Colorectal Cancers ◽

Breast Cancers ◽

Cancer Tissues

15083 Background: Embryonic stem (ES) cells are pluripotent cells derived from early mammalian embryos. When ES cells are subcutaneously injected into immunodeficient or isogenic mice, a teratoma is formed within a few weeks. This tumor is composed of all three germ layers in a disorganized fashion. Thus there could be some common molecular mechanisms shared by ES cells and somatic cancer cells. The ERas oncogene is a recently identified gene that supports the tumorigenic growth of ES cells by producing a constitutively active Ras protein. There have been no report about expression of ERas oncogene on cancer cells until now. The aim of this study is to investigate expression and clinical significance of ERas oncogene on cancer cell lines and clinical cancer tissues. Methods: A panel of 35 human cancer cell lines, 5 normal cell lines, and 20 patiants with gastric cancer tissues were used in this study. ERas mRNA expression was examined by reverse transcription-polymerase chain reaction. The effect of the DNA methyl transferase inhibitor, 5-aza-2’- deoxycitydine on the ERas expression was analyzed. Methylation of CpG islands of ERas promoter lesion was investigated using bisulfate-directsequence analysis. Results: Expression of ERas mRNA was not found in any normal cells. In contrast, ERas mRNA was found in 15 of 35 cancer cell lines, including 8 of 15 gastric cancers, 4 of 7 colorectal cancers, 2 of 6 pancreas cancers, 1 of 3 breast cancers and none of esophageal cancers. Eras mRNA was found in all gastric cancer tissues, but not normal tissues. 5-aza-2’-deoxycytidine treatment at 2, 5, and 10μM for 24 h resulted in ERas expression in 10 of 20 cancer cell lines with respect to the silencing of ERas, including 7 of 7 gastric cancers, 1 of 3 colorectal cancers and 2 of 3 breast cancers. Methylation of CpG island were found in the cancer cell lines without ERas expression, but not in these with ERas expression. Conclusions: ERas oncogene is associated with the carcinogenesis pathway in human cancer. Eras might be useful marker for cancer diagnosis. No significant financial relationships to disclose.

Download Full-text

Cell Transfer Therapy for Cancer: Past, Present, and Future

Journal of Immunology Research ◽

10.1155/2014/525913 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 14

Author(s):

Xiaoling Qian ◽

Xian Wang ◽

Hongchuan Jin

Keyword(s):

Dendritic Cells ◽

T Lymphocytes ◽

Nk Cells ◽

Human Cancer ◽

Tumor Infiltrating Lymphocytes ◽

Cell Transfer ◽

Human Cancer Cells ◽

Cancer Tissues ◽

Infiltrating Lymphocytes

Cell transfer therapy for cancer has made a rapid progress recently and the immunotherapy has been recognized as the fourth anticancer modality after operation, chemotherapy, and radiotherapy. Lymphocytes used for cell transfer therapy include dendritic cells, natural killer (NK) cells, and T lymphocytes such as tumor-infiltrating lymphocytes (TILs) and cytotoxic T lymphocytes (CTLs). In vitro activated or engineered immune cells can traffic to cancer tissues to elicit persistent antitumor immune response which is very important especially after immunosuppressive treatments such as chemotherapy. In this review, we overviewed recent advances in the exploration of dendritic cells, NK cells, and T cells for the treatment of human cancer cells.

Download Full-text