New Philadelphia, PA, United States
New Philadelphia, PA, United States

The Wistar Institute is a biomedical center, with a focus on cancer research and vaccine development. It is located in the University City section of Philadelphia, Pa. Founded in 1892 as the first independent, nonprofit, biomedical research institute in the country, Wistar has held the Cancer Center designation from the National Cancer Institute since 1972. Wistar has more than thirty laboratories, which are home to three research programs: a gene expression and regulation program, a molecular and cellular oncogenesis program, and a tumor microenvironment and metastasis program. Wikipedia.


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Patent
Wistar Institute | Date: 2015-05-01

Pharmaceutical compositions for the treatment of cancer are provided. In one embodiment the composition comprises Gamitrinib and a P13K inhibitor selected from PX-866, AZD6482, LY294002. BEZ235, GSK458, GDCO941, ZSTK474, BKM120 and GSK2636771B. Methods of treating cancer are also provided. The present invention is based in part on the inventors discovery that combination therapy that targets mitochondria eliminates tumor adaptation induced by P13K inhibition, and improves clinical outcome in cancer.


Patent
Valley Health System and Wistar Institute | Date: 2017-04-05

The present invention relates to methods and systems for high risk screening, diagnosis, prognosis, and surveillance of lung cancer. Accordingly, in one aspect, the invention provides a method for diagnosing or evaluating whether a subject has, or is at risk of having, lung cancer such as NSCLS. The method comprises obtaining a first expression level of the AKAP4 gene of a population of cells from the blood of a test subject; and comparing the first expression level with a first predetermined reference value. A difference between the first expression level and first predetermined reference value correlates with a diagnosis or evaluation of a lung cancer.


Orom U.A.,Max Planck Institute for Molecular Genetics | Shiekhattar R.,Wistar Institute
Cell | Year: 2013

Enhancer-associated long noncoding RNAs act over long distances and across chromosomes to activate transcription at distal promoters. Here, we address the latest advances made toward understanding the role of long noncoding RNA expression and the involvement of these RNAs in enhancer function through association with protein factors and modulation of chromatin structure. © 2013 Elsevier Inc.


Talmadge J.E.,University of Nebraska Medical Center | Gabrilovich D.I.,Wistar Institute
Nature Reviews Cancer | Year: 2013

Tumour-induced granulocytic hyperplasia is associated with tumour vasculogenesis and escape from immunity via T cell suppression. Initially, these myeloid cells were identified as granulocytes or monocytes; however, recent studies have revealed that this hyperplasia is associated with populations of multipotent progenitor cells that have been identified as myeloid-derived suppressor cells (MDSCs). The study of MDSCs has provided a wealth of information regarding tumour pathobiology, has extended our understanding of neoplastic progression and has modified our approaches to immune adjuvant therapy. In this Timeline article, we discuss the history of MDSCs, their influence on tumour progression and metastasis, and the crosstalk between tumour cells, MDSCs and the host macroenvironment. © 2013 Macmillan Publishers Limited. All rights reserved.


Nishikura K.,Wistar Institute
Annual Review of Biochemistry | Year: 2010

One type of RNA editing converts adenosines to inosines (Aâ†'I editing) in double-stranded RNA (dsRNA) substrates. A→ RNA editing is mediated by adenosine deaminase acting on RNA (ADAR) enzymes. A→ RNA editing of protein-coding sequences of a limited number of mammalian genes results in recoding and subsequent alterations of their functions. However, A→ RNA editing most frequently targets repetitive RNA sequences located within introns and 5†and 3†untranslated regions (UTRs). Although the biological significance of noncoding RNA editing remains largely unknown, several possibilities, including its role in the control of endogenous short interfering RNAs (esiRNAs), have been proposed. Furthermore, recent studies have revealed that the biogenesis and functions of certain microRNAs (miRNAs) are regulated by the editing of their precursors. Here, I review the recent findings that indicate new functions for A→ editing in the regulation of noncoding RNAs and for interactions between RNA editing and RNA interference mechanisms. © 2010 by Annual Reviews. All rights reserved.


Lieberman P.M.,Wistar Institute
Science | Year: 2014

Fifty years after the discovery of Epstein-Barr virus and its association with cancer, a vaccine or therapy for the virus remains elusive.


Altieri D.C.,Wistar Institute
Seminars in Cell and Developmental Biology | Year: 2015

Although technically a member of the Inhibitor of Apoptosis (IAP) gene family, survivin has consistently defied assumptions, refuted predictions and challenged paradigms. Despite its more than 5500 citations currently in Medline, the biology of survivin has remained fascinatingly complex, its exploitation in human disease, most notably cancer, tantalizing, and its regulation of cellular homeostasis unexpectedly far-reaching. An inconvenient outsider that resists schemes and dogmas, survivin continues to hold great promise to unlock fundamental circuitries of cellular functions in health and disease. © 2015 Elsevier Ltd.


Murphy M.E.,Wistar Institute
Carcinogenesis | Year: 2013

The HSP70 family of heat shock proteins consists of molecular chaperones of approximately 70 kDa in size that serve critical roles in protein homeostasis. These adenosine triphosphatases unfold misfolded or denatured proteins and can keep these proteins in an unfolded, folding-competent state. They also protect nascently translating proteins, promote the cellular or organellar transport of proteins, reduce proteotoxic protein aggregates and serve general housekeeping roles in maintaining protein homeostasis. The HSP70 family is the most conserved in evolution, and all eukaryotes contain multiple members. Some members of this family serve specific organellar- or tissue-specific functions; however, in many cases, these members can function redundantly. Overall, the HSP70 family of proteins can be thought of as a potent buffering system for cellular stress, either from extrinsic (physiological, viral and environmental) or intrinsic (replicative or oncogenic) stimuli. As such, this family serves a critical survival function in the cell. Not surprisingly, cancer cells rely heavily on this buffering system for survival. The overwhelming majority of human tumors overexpress HSP70 family members, and expression of these proteins is typically a marker for poor prognosis. With the proof of principle that inhibitors of the HSP90 chaperone have emerged as important anticancer agents, intense focus has now been placed on the potential for HSP70 inhibitors to assume a role as a significant chemotherapeutic avenue. In this review, the history, regulation, mechanism of action and role in cancer of the HSP70 family are reviewed. Additionally, the promise of pharmacologically targeting this protein for cancer therapy is addressed. © The Author 2013. Published by Oxford University Press. All rights reserved.


Patent
Wistar Institute | Date: 2016-08-16

The present invention provides a small molecule treatment of diseases/conditions caused by a virus carrying a viral oncoprotein. In one embodiment, the virus which carries the viral oncoprotein is HPV. The small molecule useful herein includes thiadiazolin-3,5-dione compounds having an optionally substituted aryl group bound to one nitrogen atom of said thiadiazolin-3,5-dione compound. The small molecules may also be administered with a compound which inhibits binding of HPV E6 to p53. In one embodiment, the thiadiazolin-3,5-dione compound has formula (I), or a pharmaceutically acceptable salt, prodrug, solvate, or metabolite thereof, wherein R^(1 )and R^(2 )are defined herein.


A method of treating a mammalian subject with cancer comprises administering to said subject having a cancer, e.g., a metastatic or refractory cancer or tumor, a small molecule inhibitor of a target signaling molecule of the MEK/MAPK pathway that impairs T cell activation, and administering to said subject a molecule that induces T cell proliferation in the presence of said inhibitor. The combination of a small molecule inhibitor of a target of the MEK/MAPK pathway and the T cell proliferation inducer reduces the proliferation of the cancer and tumor cells in vivo. Compositions and kits including these components are also provided.

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