• Title/Summary/Keyword: biological pathways

Search Result 703, Processing Time 0.02 seconds

OrCanome: a Comprehensive Resource for Oral Cancer

  • Bhartiya, Deeksha;Kumar, Amit;Singh, Harpreet;Sharma, Amitesh;Kaushik, Anita;Kumari, Suchitra;Mehrotra, Ravi
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.17 no.3
    • /
    • pp.1333-1336
    • /
    • 2016
  • Oral cancer is one of the most prevalent cancers in India but the underlying mechanisms are minimally unraveled. Cancer research has immensely benefited from genome scale high throughput studies which have contributed to expanding the volume of data. Such datasets also exist for oral cancer genes but there has been no consolidated approach to integrate the data to reveal meaningful biological information. OrCanome is one of the largest and comprehensive, user-friendly databases of oral cancer. It features a compilation of over 900 genes dysregulated in oral cancer and provides detailed annotations of the genes, transcripts and proteins along with additional information encompassing expression, inhibitors, epitopes and pathways. The resource has been envisioned as a one-stop solution for genomic, transcriptomic and proteomic annotation of these genes and the integrated approach will facilitate the identification of potential biomarkers and therapeutic targets.

Integrated Bioinformatics Approach Reveals Crosstalk Between Tumor Stroma and Peripheral Blood Mononuclear Cells in Breast Cancer

  • He, Lang;Wang, Dan;Wei, Na;Guo, Zheng
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.17 no.3
    • /
    • pp.1003-1008
    • /
    • 2016
  • Breast cancer is now the leading cause of cancer death in women worldwide. Cancer progression is driven not only by cancer cell intrinsic alterations and interactions with tumor microenvironment, but also by systemic effects. Integration of multiple profiling data may provide insights into the underlying molecular mechanisms of complex systemic processes. We performed a bioinformatic analysis of two public available microarray datasets for breast tumor stroma and peripheral blood mononuclear cells, featuring integrated transcriptomics data, protein-protein interactions (PPIs) and protein subcellular localization, to identify genes and biological pathways that contribute to dialogue between tumor stroma and the peripheral circulation. Genes of the integrin family as well as CXCR4 proved to be hub nodes of the crosstalk network and may play an important role in response to stroma-derived chemoattractants. This study pointed to potential for development of therapeutic strategies that target systemic signals travelling through the circulation and interdict tumor cell recruitment.

MicroRNAs: Biogenesis, Roles for Carcinogenesis and as Potential Biomarkers for Cancer Diagnosis and Prognosis

  • Kavitha, Nowroji;Vijayarathna, Soundararajan;Jothy, Subramanion Lachumy;Oon, Chern Ein;Chen, Yeng;Kanwar, Jagat Rakesh;Sasidharan, Sreenivasan
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.15 no.18
    • /
    • pp.7489-7497
    • /
    • 2014
  • MicroRNAs (miRNAs) are short non-coding RNAs of 20-24 nucleotides that play important roles in carcinogenesis. Accordingly, miRNAs control numerous cancer-relevant biological events such as cell proliferation, cell cycle control, metabolism and apoptosis. In this review, we summarize the current knowledge and concepts concerning the biogenesis of miRNAs, miRNA roles in cancer and their potential as biomarkers for cancer diagnosis and prognosis including the regulation of key cancer-related pathways, such as cell cycle control and miRNA dysregulation. Moreover, microRNA molecules are already receiving the attention of world researchers as therapeutic targets and agents. Therefore, in-depth knowledge of microRNAs has the potential not only to identify their roles in cancer, but also to exploit them as potential biomarkers for cancer diagnosis and identify therapeutic targets for new drug discovery.

Synthesis and Biological Evaluation of Tetrapeptide Ketones as Reversible 20S Proteasome Inhibitors

  • Latif, Muhammad;Jung, Myoung Eun;Lee, Kwangho;Choi, Gildon
    • Bulletin of the Korean Chemical Society
    • /
    • v.35 no.12
    • /
    • pp.3571-3575
    • /
    • 2014
  • Proteasome, a multicatalytic protease complex, has been validated as a promising therapeutic target in oncology. Carfilzomib (Kyprolis$^{(R)}$), a tetrapeptide epoxyketone, irreversibly inhibits the chymotrypsin-like (CT-L) activity of the proteasome and has been recently approved for multiple myeloma treatment by FDA. A chemistry effort was initiated to discover the compounds that are reversibly inhibit the proteasome by replacing the epoxyketone moiety of carfilzomib with a variety of ketones as reversible and covalent warheads at the C-terminus. The newly synthesized compounds exhibited significant inhibitory activity against CT-L activity of the human 20S proteasome. When the compounds were tested for cancer cell viability, 14-8 was found to be most potent in inhibiting Molt-4 acute lymphoblastic leukemia cell line with a $GI_{50}$ of $4.4{\mu}M$. Cytotoxic effects of 14-8 were further evaluated by cell cycle analysis and Western blotting, demonstrating activation of apoptotic pathways.

Differential Gene Expression Analysis in K562 Human Leukemia Cell Line Treated with Benzene

  • Choi, Sul-Ji;Kim, Ji-Young;Moon, Jai-Dong;Baek, Hee-Jo;Kook, Hoon;Seo, Sang-Beom
    • Toxicological Research
    • /
    • v.27 no.1
    • /
    • pp.43-48
    • /
    • 2011
  • Even though exposure to benzene has been linked to a variety of cancers including leukemia, the detailed molecular mechanisms relevant to benzene-induced carcinogenesis remain to be clearly elucidated. In this study, we evaluated the effects of benzene on differential gene expression in a leukemia cell line. The K562 leukemia cell line used in this study was cultured for 3 h with 10 mM benzene and RNA was extracted. To analyze the gene expression profiles, a 41,000 human whole genome chip was employed for cDNA microarray analysis. We initially identified 6,562 genes whose expression was altered by benzene treatment. Among these, 3,395 genes were upregulated and 3,167 genes were downregulated by more than 2-fold, respectively. The results of functional classification showed that the identified genes were involved in biological pathways including transcription, cell proliferation, the cell cycle, and apoptosis. These gene expression profiles should provide us with further insights into the molecular mechanisms underlying benzene-induced carcinogenesis, including leukemia.

Neuroprotective Effect of Taurine against Oxidative Stress-Induced Damages in Neuronal Cells

  • Yeon, Jeong-Ah;Kim, Sung-Jin
    • Biomolecules & Therapeutics
    • /
    • v.18 no.1
    • /
    • pp.24-31
    • /
    • 2010
  • Taurine, 2-aminoethanesulfonic acid, is an abundant free amino acid present in brain cells and exerts many important biological functions such as anti-convulsant, modulation of neuronal excitability, regulation of learning and memory, anti-aggressiveness and anti-alcoholic effects. In the present study, we investigated to explore whether taurine has any protective actions against oxidative stress-induced damages in neuronal cells. ERK I/II regulates signaling pathways involved in nitric oxide (NO) and reactive oxygen species (ROS) production and plays a role in the regulation of cell growth, and apoptosis. We have found that taurine significantly inhibited AMPA induced cortical depolarization in the Grease Gap assays using rat cortical slices. Taurine also inhibited AMPA-induced neuronal cell damage in MTT assays in the differentiated SH-SY5Y cells. When the neuronal cells were treated with $H_2O_2$, levels of NO were increased; however, taurine pretreatment decreased the NO production induced by $H_2O_2$ to approximately normal levels. Interestingly, taurine treatment stimulated ERK I/II activity in the presence of AMPA or $H_2O_2$, suggesting the potential role of ERK I/II in the neuroprotection of taurine. Taken together, taurine has significant neuroprotective actions against AMPA or $H_2O_2$ induced damages in neuronal cells, possibly via activation of ERK I/II.

Convergence of Cancer Metabolism and Immunity: an Overview

  • Van Dang, Chi;Kim, Jung-whan
    • Biomolecules & Therapeutics
    • /
    • v.26 no.1
    • /
    • pp.4-9
    • /
    • 2018
  • Cancer metabolism as a field of research was founded almost 100 years ago by Otto Warburg, who described the propensity for cancers to convert glucose to lactate despite the presence of oxygen, which in yeast diminishes glycolytic metabolism known as the Pasteur effect. In the past 20 years, the resurgence of interest in cancer metabolism provided significant insights into processes involved in maintenance metabolism of non-proliferating cells and proliferative metabolism, which is regulated by proto-oncogenes and tumor suppressors in normal proliferating cells. In cancer cells, depending on the driving oncogenic event, metabolism is re-wired for nutrient import, redox homeostasis, protein quality control, and biosynthesis to support cell growth and division. In general, resting cells rely on oxidative metabolism, while proliferating cells rewire metabolism toward glycolysis, which favors many biosynthetic pathways for proliferation. Oncogenes such as MYC, BRAF, KRAS, and PI3K have been documented to rewire metabolism in favor of proliferation. These cell intrinsic mechanisms, however, are insufficient to drive tumorigenesis because immune surveillance continuously seeks to destroy neo-antigenic tumor cells. In this regard, evasion of cancer cells from immunity involves checkpoints that blunt cytotoxic T cells, which are also attenuated by the metabolic tumor microenvironment, which is rich in immuno-modulating metabolites such as lactate, 2-hydroxyglutarate, kynurenine, and the proton (low pH). As such, a full understanding of tumor metabolism requires an appreciation of the convergence of cancer cell intrinsic metabolism and that of the tumor microenvironment including stromal and immune cells.

Identification and Function Prediction of Novel MicroRNAs in Laoshan Dairy Goats

  • Ji, Zhibin;Wang, Guizhi;Zhang, Chunlan;Xie, Zhijing;Liu, Zhaohua;Wang, Jianmin
    • Asian-Australasian Journal of Animal Sciences
    • /
    • v.26 no.3
    • /
    • pp.309-315
    • /
    • 2013
  • MicroRNAs are a class of endogenous small RNAs that play important roles in post-transcriptional gene regulation by directing degradation of mRNAs or facilitating repression of target gene translation. In this study, three small RNA cDNA libraries from the mammary gland tissues of Laoshan dairy goats (Capra hircus) were constructed and sequenced, individually. Through Solexa high-throughput sequencing and bioinformatics analysis, we obtained 50 presumptive novel miRNAs candidates, and 55,448 putative target genes were predicted. GO annotations and KEGG pathway analyses showed the majority of target genes were involved in various biological processes and metabolic pathways. Our results discovered more information about the regulation network between miRNAs and mRNAs and paved a foundation for the molecular genetics of mammary gland development in goats.

Inhibition of the expression on MMP-2, 9 and morphological changes via human fibrosarcoma cell line by 6,6'-bieckol from marine alga Ecklonia cava

  • Zhang, Chen;Li, Yong;Shi, Xiujuan;Kim, Se-Kwon
    • BMB Reports
    • /
    • v.43 no.1
    • /
    • pp.62-68
    • /
    • 2010
  • Matrix Metalloproteinases (MMPs) are a family of zinc-endopeptidases which can degrade extracellular matrix (ECM) components and play important roles in a variety of biological and pathological processes. 6,6'-bieckol isolated and characterized from an edible marine brown alga Ecklonia cava (EC), according to the comprehensive spectral analysis of MS and NMR data. Here the influence of 6,6'-bieckol on expressions of MMPs was examined by zymography and western blot analysis via human fibrosarcoma cell line (HT1080). It is shown that 6,6'-bieckol significantly down regulated the expressions of MMP-2 and -9 in dose-dependent manner. The influence of 6,6'-bieckol on the cell viability and cell behavior of HT1080 cells were also investigated, our dates shown that it suppressed the migration and 3D culture in HT1080 cells. Meanwhile, we explored several signal pathways which may contribute to this process, and found the suppressing of MMPs expressions in HT1080 cells might be due to the suppression of NF-${\kappa}B$ signal pathway.

Estimating Neuro-Pathway from Visual and Somatosensory Evoked Potential (유발전위를 이용한 뇌의 시감각 및 체성감각 인지영역 추정기술)

  • 배병훈;김동우
    • Journal of Biomedical Engineering Research
    • /
    • v.15 no.4
    • /
    • pp.481-488
    • /
    • 1994
  • In this paper a study of neuro-pathway estimation based on visual and somatosensory evoked potential is given. The evoked potentials which are caused by visual and somatosensory stimulation are detected by an average method. The forward problem that is estimating a scalp potential from a given electrical source in the brain is solved by using a triple concentric spherical shell model of the head and a single current dipole model of the neuron activity. The inverse problem which calculates a source position is solved by a least square fit between the model predicted potential and a given evoked potential measurement. The similarities between estimated sensory neuro-pathways and physiological brain function regions are verified.

  • PDF