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Li Q.,Cancer Therapy and Research Center
Frontiers in bioscience (Landmark edition) | Year: 2013

Type III interferons (IFNs), a new type IFN family consisting of 3 IFN-lambdas, have been identified through a homology search. They include IFN-lambda1, IFN-lambda2 and IFN-lambda3, which are also named as interleukin (IL)-29, IL-28A and IL-28B, respectively. The receptor complex of IFN-lambdas is composed of the IL-10 receptor beta (IL-10Rbeta) and a novel IL-28 receptor alpha (IL-28Ralpha). The signal transductions of type III IFNs seem to be similar to those of type I IFNs. Both type I and III IFNs activate Janus activated kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway and transcribe a number of IFN-associated genes. Various types of viruses induce expressions of type III IFNs as well as type I IFNs; however, the biological functions of type III IFNs could be distinct from those of type I IFNs partly because of the tissue-restricted expression of the type III receptor complexes. In this review, we encapsulate recent understandings about type III IFNs in particular the anti-tumor effects, and discuss possible mechanisms and a potential use for cancer therapy.

Curiel T.J.,Cancer Therapy and Research Center
Drug Resistance Updates | Year: 2012

Multidrug resistance (MDR) renders cancer cells relatively invulnerable to treatment with many standard cytotoxic anti-cancer agents. Cancer immunotherapy could be an important adjunct for other strategies to treat MDR positive cancers, as resistance to immunotherapy generally is unrelated to mechanisms of resistance to cytotoxic agents. Immunotherapy to combat MDR positive tumors could use any of the following strategies: direct immune attack against MDR positive cells, using MDR as an immune target to deliver cytotoxic agents, capitalization on other immune properties of MDR positive cells, or conditional immunotoxins expressed under MDR control. Additional insights into the immunogenic potential of some cytotoxic agents can also be brought to bear on these strategies. This review will highlight key concepts in cancer immunotherapy and illustrate immune principles and strategies that have been or could be used to help destroy MDR positive tumor cells, either alone or in rational combinations. © 2012 Elsevier Ltd.

Barontini M.,Center for Endocrinological Investigations | Dahia P.L.M.,Cancer Therapy and Research Center
Best Practice and Research: Clinical Endocrinology and Metabolism | Year: 2010

von Hippel-Lindau disease (VHL) disease increases susceptibility to several malignancies, including renal cell carcinoma, haemangioblastomas of the central nervous system or retina and phaeochromocytomas. The VHL tumour suppressor gene, responsible for the disease, encodes for a major regulator of the hypoxic response by targeting the transcription factor hypoxia inducible factor (HIF) for degradation. In this review, we present a synopsis of clinical features of the disease and emphasise unique aspects of VHL syndrome in the paediatric population. Genotype-phenotype associations based on the risk of phaeochromocytoma have pointed to the existence of additional, HIF-independent functions of VHL that remain underexplored. We also examine the progress on these pleiotropic roles of VHL, which contribute to explain clinical features of VHL disease. These advances have important translational implications and are likely to offer a new host of therapeutic options to individuals affected by the disease in the future. © 2010 Elsevier Ltd. All rights reserved.

Cardenas E.,University of Texas at San Antonio | Ghosh R.,University of Texas at San Antonio | Ghosh R.,Cancer Therapy and Research Center
Biochemical Pharmacology | Year: 2013

It appears that the story on vitamin E and its role in human health remains incomplete. It is apparent that vitamin E supplementation involves many variables, some of which include its uptake from the intestine, the preference for α-tocopherol, transport by tocopherol specific proteins and lipid transporters and the differential metabolism of different vitamin E isoforms. The fundamental differences within population genetics can have significant implications for the effect that dietary supplementation might have on human health. When evaluating the efficacy of vitamin E prophylactic or therapeutic use in previous and future studies, it is critical to consider dosage to be administered, form of vitamin E and source (such as whether from synthetic or purified from natural sources). Further studies are needed to determine the effects of all vitamin E isoforms on cell growth, tumorigenicity, to clarify its possible use as an adjuvant to existing chemotherapeutics. The Alpha-Tocopherol, Beta Carotene (ATBC) Cancer Prevention Study Group and Selenium and Vitamin E Cancer Prevention Trial (SELECT) studies along with the numerous studies of vitamin E should help guide the next chapter of vitamin E research. © 2013 Elsevier Inc. All rights reserved.

Zhang B.,Cancer Therapy and Research Center
Cancer Research | Year: 2010

The promise of cancer immunotherapy has not been translated into clinical successes, in large part because of tumor-associated immune suppression that blocks effective antitumor immunity. Recent findings show a tumor-induced immunosuppressive mechanism, whereby tumor-derived CD73 functions as an ecto-enzyme to produce extracellular adenosine, which promotes tumor growth by limiting antitumor T-cell immunity via adenosine receptor signaling. Results with small molecule inhibitors, or monoclonal antibodies targeting CD73 in murine tumor models, suggest that targeted CD73 therapy is an important alternative and realistic approach to effective control of tumor growth. In particular, it helps T-cell-based therapy by enhancing the adaptive immune response machinery, which may increase the function of tumor-infiltrating T lymphocytes, and subsequently lead to improved survival in cancer patients. ©2010 AACR.

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