Integrative Omics Approaches to Identify New Therapeutic Cancer Targets

CCR Grand Rounds Kimberly Stegmaier, M.D., Professor of Pediatrics at Harvard Medical School and the Ted Williams Chair at Dana-Farber Cancer Institute, has advanced the application of genomics to drug and protein target discovery for pediatric cancers. She is the Vice Chair for Pediatric Oncology Research, co-director of the Pediatric Hematologic Malignancy Program and an attending physician providing clinical care in Pediatric Oncology at the Dana-Farber Cancer Institute and Boston Children ’ s Hospital. Dr. Stegmaier is also an Institute Member of the Broad Institute of Harvard and MIT. She has served as a Council Member with the Society for Pediatric Research from 2013-2016 and now as the Chair for the American Association for Cancer Research (AACR) Pediatric Cancer Working Group. The Stegmaier Lab develops and integrates chemical and functional genomic approaches to identify new protein targets and small-molecule modulators of malignancy with an eye toward clinical translation. The laboratory has focused on pediatric malignancies notable for an aberrancy of differentiation and/or oncogenic activation of transcription factors: the acute leukemias, neuroblastoma and Ewing sarcoma. Multiple clinical trials have resulted from her laboratory ’ s research. Dr. Stegmaier is the recipient of numerous awards such as the Joanne Levy, M.D., Memorial Award for Outstanding Achievement from the American Society of Hematology, the Society for Pediatric Research Young Invest...
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Abstract Medicinal plants are boundless source of raw materials for the pharmaceutical. Identification of natural compounds from medicinal plant is helpful in the discovery of novel therapeutic agents. Tylophora pauciflora is a medicinal plant, which possess many biological activities such as antioxidant activity, anti-inflammatory activity and anti cancer activity. There is no GC-MS analysis reported on this plant. Thus, the present study is aimed to identify the present of phyto-chemical compounds from ethanolic extract of Tylophora pauciflora using GC-MS analysis. Results, the extract possess totally 14 bioacti...
Source: Bioinformation - Category: Bioinformatics Authors: Tags: Bioinformation Source Type: research
We reported 96 hydroxamic compounds optimized using hydrogen-donors, hydrophobic and electron withdrawing groups followed by molecular docking studies. The optimized compounds show good LibDock score and H-bond interaction in the active site of HDAC2. We selected 20 compounds as the best HDAC2 inhibitors based on the LibDock score, binding energy and hydrogen bonding. ADMET predictions on these compounds show good absorption, BBB penetration and no liver toxicity. We subsequently report four compounds selected as best HDAC2 inhibitors based on the LibDock, binding energy, H-bonding and ADMET properties. PMID: 31312074 [PubMed]
Source: Bioinformation - Category: Bioinformatics Authors: Tags: Bioinformation Source Type: research
Abstract Gut microbiota and their metabolites play a vital role in colon health and disease. Accumulating evidence suggests that the gut microbiota contributes to the risk of colorectal cancer (CRC). However, the role of a specific microbial community together with their metabolites contributing to the risk, initiation and progression of CRC is still unknown. Hence, we used a Bayesian Networks in combination with the IDA (Intervention calculus when the DAG is absent) to generate a graphical model that allows causal relationships to be inferred from observational data. Results from the analysis of publically availa...
Source: Bioinformation - Category: Bioinformatics Authors: Tags: Bioinformation Source Type: research
Single cell surgery such as manipulation or removal of subcellular components or/and organelles from single cells is increasingly used for the study of diseases and their causes in precision medicine. This paper presents a robotic surgery system to achieve automated organelle biopsy of single cells with dimensions of less than 20 μm in diameter. The complexity of spatial detection of the organelle position is reduced by patterning the cells using a microfluidic chip device. A sliding mode nonlinear controller is developed to enable extraction of organelles, such as the mitochondria and the nucleus, from single cell...
Source: IEEE Transactions on Biomedical Engineering - Category: Biomedical Engineering Source Type: research
The objective of this paper is to investigate the detectability of breast tumors having various histological types in excised breast tissues of total mastectomy. The tumor images measured by a portable impulse-radio-ultra-wideband (IR-UWB)-radar-based breast cancer detector are compared with both pathological images and images of dedicated breast positron emission tomography. It is found that the detector can detect invasive-ductal-carcinomas and extensive intraductal component in the dense breast. The density of the breast has a correlation to the effective permittivity derived from the reconstructed confocal images. The ...
Source: IEEE Transactions on Biomedical Engineering - Category: Biomedical Engineering Source Type: research
Conclusion: The results suggest that utilizing simple color- and textural-based features from visual inspection with acetic acid and visual inspection with Lugol's iodine images may provide unbiased automation of cervigrams. Significance: This would enable automated, expert-level diagnosis of cervical pre-cancer at the point of care.
Source: IEEE Transactions on Biomedical Engineering - Category: Biomedical Engineering Source Type: research
Abstract A significant obstacle to the study of human cancer biology and the testing of human specific immunotherapeutics is the paucity of translational models that recapitulate both the growth of human tumors and the functionality of human immune systems. Humanized mice engrafted with human hematopoietic stem cells (HSC) and patient-derived xenografts (PDX) enable preclinical investigation of the interactions between the human immune system and human cancer. We use immunodeficient non-obese diabetic (NOD, scid, gamma) NSG™ or NSG™-SGM3 mice as hosts for establishment of human immunity following HSC i...
Source: Mol Biol Cell - Category: Molecular Biology Authors: Tags: Methods Mol Biol Source Type: research
Abstract Experimental animal tumor models have been broadly used to evaluate anticancer drugs in the preclinical setting. They have also been widely applied for drug target discovery and validation, which usually follows four experimental strategies: first, assess the roles of putative drug targets using in vivo tumorigenicity and tumor growth kinetics assays of transplanted tumors, engineered through gain-of-function (GOF) by overexpressing transgene or knock-in (KI) or loss-of-function by gene silencing using knockdown (KD) or knockout (KO) or mutation via mutagenesis procedures; second, similarly genetically en...
Source: Mol Biol Cell - Category: Molecular Biology Authors: Tags: Methods Mol Biol Source Type: research
This study aimed to compare cancer incidence and trends in survival for children diagnosed in Japan and England, using population‐based cancer registry data. The analysis was based on 5,192 children with cancer (age 0‐14 years) from six prefectural cancer registries in Japan and 21,295 children diagnosed in England during 1993‐2010. Differences in incidence rates between the two countries were measured with Poisson regression models. Overall survival was estimated using the Kaplan‐Meier method. Incidence rates for Hodgkin lymphoma, renal tumours, and Ewing sarcomas in England were more than twice as high as those i...
Source: Cancer Science - Category: Cancer & Oncology Authors: Tags: Original Article Source Type: research
In this study, we reviewed 25 patients diagnosed with a spinal metastasis of unknown primary who presented with low back pain or acute-onset neurologic deficits and underwent operative treatment.
Source: World Neurosurgery - Category: Neurosurgery Authors: Tags: Original Article Source Type: research
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