Pathway Pharmaceuticals | Date: 2015-03-02
The present invention provides improved systems, methods and software for determining a pathway activation strength in old subjects relative to young subjects of the same species, the method including collecting young subject transcriptome data and old subject transcriptome data for one species to evaluate pathway activation strength (PAS) and down-regulation strength for a plurality of biological pathways, mapping the plurality of biological pathways for the activation strength and down-regulation strength from old subject samples relative to young subject samples to form a pathway cloud map and providing a gero-protective rating for each of a plurality of drugs in accordance with a drug rating for minimizing signaling pathway cloud disturbance (SPCD) in the pathway cloud map of the one species to provide a ranking of the gero-protective drugs.
Aliper A.M.,Johns Hopkins University |
Csoka A.B.,Vision Genomics LLC |
Csoka A.B.,Howard University |
Buzdin A.,Johns Hopkins University |
And 8 more authors.
Aging | Year: 2015
For the past several decades, research in understanding the molecular basis of human aging has progressed significantly with the analysis of premature aging syndromes. Progerin, an altered form of lamin A, has been identified as the cause of premature aging in Hutchinson-Gilford Progeria Syndrome (HGPS), and may be a contributing causative factor in normal aging. However, the question of whether HGPS actually recapitulates the normal aging process at the cellular and organismal level, or simply mimics the aging phenotype is widely debated. In the present study we analyzed publicly available microarray datasets for fibroblasts undergoing cellular aging in culture, as well as fibroblasts derived from young, middle-age, and old-age individuals, and patients with HGPS. Using GeroScope pathway analysis and drug discovery platform we analyzed the activation states of 65 major cellular signaling pathways. Our analysis reveals that signaling pathway activation states in cells derived from chronologically young patients with HGPS strongly resemble cells taken from normal middle-aged and old individuals. This clearly indicates that HGPS may truly represent accelerated aging, rather than being just a simulacrum. Our data also points to potential pathways that could be targeted to develop drugs and drug combinations for both HGPS and normal aging. © Aliper et al.
Spirin P.V.,RAS Engelhardt Institute of Molecular Biology |
Lebedev T.D.,RAS Engelhardt Institute of Molecular Biology |
Orlova N.N.,RAS Engelhardt Institute of Molecular Biology |
Gornostaeva A.S.,RAS Engelhardt Institute of Molecular Biology |
And 10 more authors.
Leukemia | Year: 2014
The t(8;21)(q22;q22) rearrangement represents the most common chromosomal translocation in acute myeloid leukemia (AML). It results in a transcript encoding for the fusion protein AML1-ETO (AE) with transcription factor activity. AE is considered to be an attractive target for treating t(8;21) leukemia. However, AE expression alone is insufficient to cause transformation, and thus the potential of such therapy remains unclear. Several genes are deregulated in AML cells, including KIT that encodes a tyrosine kinase receptor. Here, we show that AML cells transduced with short hairpin RNA vector targeting AE mRNAs have a dramatic decrease in growth rate that is caused by induction of apoptosis and deregulation of the cell cycle. A reduction in KIT mRNA levels was also observed in AE-silenced cells, but silencing KIT expression reduced cell growth but did not induce apoptosis. Transcription profiling of cells that escape cell death revealed activation of a number of signaling pathways involved in cell survival and proliferation. In particular, we find that the extracellular signal-regulated kinase 2 (ERK2; also known as mitogen-activated protein kinase 1 (MAPK1)) protein could mediate activation of 23 out of 29 (79%) of these upregulated pathways and thus may be regarded as the key player in establishing the t(8;21)-positive leukemic cells resistant to AE suppression.
Makarev E.,Johns Hopkins University |
Cantor C.,Boston University |
Cantor C.,Retrotope |
Zhavoronkov A.,Johns Hopkins University |
And 6 more authors.
Aging | Year: 2014
Age-related macular degeneration (AMD) is a major cause of blindness in older people and is caused by loss of the central region of the retinal pigment epithelium (RPE). Conventional methods of gene expression analysis have yielded important insights into AMD pathogenesis, but the precise molecular pathway alterations are still poorly understood. Therefore we developed a new software program, "AMD Medicine", and discovered differential pathway activation profiles in samples of human RPE/choroid from AMD patients and controls. We identified 29 pathways in RPE-choroid AMD phenotypes: 27 pathways were activated in AMD compared to controls, and 2 pathways were activated in controls compared to AMD. In AMD, we identified a graded activation of pathways related to wound response, complement cascade, and cell survival. Also, there was downregulation of two pathways responsible for apoptosis. Furthermore, significant activation of pro-mitotic pathways is consistent with dedifferentiation and cell proliferation events, which occur early in the pathogenesis of AMD. Significantly, we discovered new global pathway activation signatures of AMD involved in the cell-based inflammatory response: IL-2, STAT3, and ERK. The ultimate aim of our research is to achieve a better understanding of signaling pathways involved in AMD pathology, which will eventually lead to better treatments.
Aliper A.M.,Johns Hopkins University |
Frieden-Korovkina V.P.,HiBiotechnology LLC |
Buzdin A.,Pathway Pharmaceuticals |
Roumiantsev S.A.,Russian National Research Medical University |
And 2 more authors.
Oncotarget | Year: 2014
In solid cancers, myeloid derived suppressor cells (MDSC) infiltrate (peri)tumoral tissues to induce immune tolerance and hence to establish a microenvironment permissive to tumor growth. Importantly, the mechanisms that facilitate such infiltration or a subsequent immune suppression are not fully understood. Hence, in this study, we aimed to delineate disparate molecular pathways which MDSC utilize in murine models of colon or breast cancer. Using pathways enrichment analysis, we completed interactome maps of multiple signaling pathways in CD11b+/Gr1(high/low) MDSC from spleens and tumor infiltrates of mice with c26GM colon cancer and tumor infiltrates of MDSC in 4T1 breast cancer. In both cancer models, infiltrating MDSC, but not CD11b+ splenic cells, have been found to be enriched in multiple signaling molecules suggestive of their enhanced proliferative and invasive phenotypes. The interactome data has been subsequently used to reconstruct a previously unexplored regulation of MDSC cell cycle by the c-myc transcription factor which was predicted by the analysis. Thus, this study represents a first interactome mapping of distinct multiple molecular pathways whereby MDSC sustain cancer progression.
Pathway Pharmaceuticals | Date: 2016-01-28
The present invention provides systems, methods and software predicting a clinical outcome of a patient having a disorder the method including the steps of providing a drug score database (DSD) based on pathway activation strengths (PASs) for a plurality of biological pathways associated with the drug in the treatment of the disorder and comparing the pathway activation strengths of the plurality of biological pathways of the patient with the drug score database to provide a predictive indication if the patient is a responder or non-responder to the drug; and repeating these steps for a plurality of drugs thereby predicting a clinical outcome to the plurality of drugs of the patient to the disorder.
Pathway Pharmaceuticals | Date: 2016-01-28
The present invention provides systems, methods and software predicting a clinical outcome of a patient having breast cancer, the method including the steps of providing a drug score database (DSD) based on pathway activation strengths (PASs) for a plurality of biological pathways associated with the drug in the treatment of the disorder and comparing the pathway activation strengths of the plurality of biological pathways of the patient with the drug score database to provide a predictive indication if the patient is a responder or non-responder to the drug; and repeating these steps for a plurality of drugs thereby predicting a clinical outcome to the plurality of drugs of the patient to the breast cancer.
Pathway Pharmaceuticals | Date: 2014-12-30
Scientific apparatus and instruments for image analysis, namely, computer hardware and software for medical imaging apparatus; calculating machines, data processing equipment and computers; pre-recorded digital media devices featuring information in the field of oncology; computer hardware; computer software and firmware for genomic analysis of cancer for the purpose of treating cancer; downloadable software for genomic analysis of cancer for the purpose of treating cancer via the internet; downloadable electronic publications in the nature of books in the field of oncology; downloadable electronic software for genomic analysis of cancer and featuring printouts in the field of oncology for the purpose of treating cancer; computer program, namely, software for targeted treatment of cancer by genomic analysis of cancer and determining optimal targeted cancer drugs and drug combinations for personalized medicine; computer software for determining optimal targeted cancer drugs and drug combinations for personalized medicine. Scientific and technological services, namely, research and design in the field of computer software for determining optimal targeted cancer drugs and drug combinations for personalized medicine; technical laboratory research in the fields of biology, biotechnology, pharmacy, and medicine; engineering work in connection with science, medical and scientific research to facilitate the discovery of the causes, prevention, treatment and cure of cancer; medical laboratories; providing laboratory research services in the field of medical diagnostic and prognosis testing; providing reagent and assay sample testing and diagnostic services for others in the field of medical science and research related thereto; providing temporary use of non-downloadable computer software for targeted treatment of cancer by genomic analysis of cancer and determining optimal targeted cancer drugs and drug combinations for personalized medicine; industrial analysis and research services; design and development of computer hardware and software; computer programming; installation, maintenance and repair of computer software; computer software consultancy services; design, drawing and commissioned writing for the compilation of web sites; creating, maintaining and hosting the web sites of others; new product design services; scientific research services in the field of oncology genetic testing for medical purposes; providing medical and scientific research information in the field of personalized medicine; medical and scientific research services in the field of cancer treatment and diagnosis; providing a web site featuring technology that enables physicians to generate, manage and exchange medical information and documents regardless of medical organization or geographic location; providing medical and scientific research information in the field of clinical trials; providing medical and scientific research information in the field of pharmaceuticals and clinical trials; providing an interactive web site that enables users to enter, access, track, monitor and generate health and medical information and reports; medical and scientific research services in the field of disease diagnosis, treatment, and monitoring. Medical services; veterinary services; medical analysis, namely, medical diagnosis and treatment of cancer for persons; pharmaceutical advice; medical services, namely, targeted medical treatment of cancer for patients; medical diagnostic services, namely, analyzing genomic information, creating a diagnosis, and applying genomic information to patient care all for medical testing for diagnostic purposes; providing health care information via telephone and the Internet; providing information in the field of the diagnostic, prophylactic, and therapeutic properties of pharmaceuticals; healthcare services for treating cancers; providing online information services in the field of medicine, namely, providing information on the clinical problems and different stages of various forms of cancer and instructions on how to access diagnostic and therapeutic approaches to cancer; consulting services in the fields of medical testing for diagnostic or treatment purposes; maintaining files and records concerning the medical condition of individuals; maintaining patient medical records and files; maintaining personal medical history records and files; medical information; providing a web site featuring medical information; providing medical information; providing medical information, consultancy and advisory services; providing an internet-based database of patient medical information where patients can inquire about medical issues and procedures from other patients and can relay information about their medical experiences for support and community; providing an on-line, patient-initiated, patient-authorized, fee-for-service, medical profile and medical record analysis service designed to provide patients with custom tailored information about the range of possible diagnoses and therapies associated with a defined set of symptoms; providing on-line medical record analysis services designed to provide patients with custom tailored information about the range of possible diagnoses and therapies associated with a defined set of symptoms and/or genetic profile.
News Article | April 16, 2014
Pathway Pharmaceuticals, a Hong Kong-based personalized medicine company that helps medical professionals make more informed decisions when selecting cancer therapies, received a seed funding from Deep Knowledge Ventures. The amount of the deal was not disclosed. Led by Anton Buzdin, PHD, DSC, CEO, Pathway Pharmaceuticals has just launched its service to medical professionals worldwide, which tests the effects of drugs that are approved by national regulatory agencies on gene expression in patient tumor biopsies. Its OncoFINDER™ tool uses advanced algorithms to predict drug efficacy by comparing the gene expression data of tumor biopsies to a large sample of data from healthy tissue collected over 7 years. This information can also be used to analyze the efficacy of treatments currently in clinical trials and in the laboratory. The company also has operations in the United States, Russia and the United Kingdom.