3 results on '"Block, Timothy"'
Search Results
2. Changes in the Glycosylation of Kininogen and the Development of a Kininogen-Based Algorithm for the Early Detection of HCC.
- Author
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Wang M, Sanda M, Comunale MA, Herrera H, Swindell C, Kono Y, Singal AG, Marrero J, Block T, Goldman R, and Mehta A
- Subjects
- Aged, Carcinoma, Hepatocellular metabolism, Female, Humans, Liver Neoplasms metabolism, Male, Middle Aged, Sensitivity and Specificity, United States, alpha-Fetoproteins analysis, Algorithms, Biomarkers, Tumor analysis, Carcinoma, Hepatocellular diagnosis, Early Detection of Cancer methods, Kininogens analysis, Liver Neoplasms diagnosis
- Abstract
Background: Hepatocellular carcinoma (HCC) has the greatest increase in mortality among all solids tumors in the United States related to low rates of early tumor detection. Development of noninvasive biomarkers for the early detection of HCC may reduce HCC-related mortality. Methods: We have developed an algorithm that combines routinely observed clinical values into a single equation that in a study of >3,000 patients from 5 independent sites improved detection of HCC as compared with the currently used biomarker, alpha-fetoprotein (AFP), by 4% to 20%. However, this algorithm had limited benefit in those with AFP <20 ng/mL. To that end, we have developed a secondary algorithm that incorporates a marker, fucosylated kininogen, to improve the detection of HCC, especially in those with AFP <20 ng/mL and early-stage disease. Results: The ability to detect early-stage AFP-negative (AFP <20 ng/mL) HCC increased from 0% (AFP alone) to 89% (for the new algorithm). Glycan analysis revealed that kininogen has several glycan modifications that have been associated with HCC, but often not with specific proteins, including increased levels of core and outer-arm fucosylation and increased branching. Conclusions: An algorithm combining fucosylated kininogen, AFP, and clinical characteristics is highly accurate for early HCC detection. Impact: Our biomarker algorithm could significantly improve early HCC detection and curative treatment eligibility in patients with cirrhosis. Cancer Epidemiol Biomarkers Prev; 26(5); 795-803. ©2017 AACR ., (©2017 American Association for Cancer Research.)
- Published
- 2017
- Full Text
- View/download PDF
3. Substance abuse, HIV-1 and hepatitis.
- Author
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Parikh N, Nonnemacher MR, Pirrone V, Block T, Mehta A, and Wigdahl B
- Subjects
- Acquired Immunodeficiency Syndrome immunology, Acquired Immunodeficiency Syndrome mortality, Acquired Immunodeficiency Syndrome transmission, Blood immunology, Blood virology, Bone Marrow immunology, Bone Marrow virology, Brain immunology, Brain virology, Coinfection, Disease Progression, Female, HIV Seropositivity immunology, HIV Seropositivity mortality, HIV Seropositivity transmission, Hepatitis B immunology, Hepatitis B mortality, Hepatitis B transmission, Hepatitis C immunology, Hepatitis C mortality, Hepatitis C transmission, Humans, Male, Substance Abuse, Intravenous immunology, Substance Abuse, Intravenous mortality, United States epidemiology, Acquired Immunodeficiency Syndrome epidemiology, HIV Seropositivity epidemiology, HIV-1 immunology, Hepatitis B epidemiology, Hepatitis C epidemiology, Substance Abuse, Intravenous epidemiology
- Abstract
During the course of human immunodeficiency virus type 1 (HIV-1) disease, the virus has been shown to effectively escape the immune response with the subsequent establishment of latent viral reservoirs in specific cell populations within the peripheral blood (PB) and associated lymphoid tissues, bone marrow (BM), brain, and potentially other end organs. HIV-1, along with hepatitis B and C viruses (HBV and HCV), are known to share similar routes of transmission, including intravenous drug use, blood transfusions, sexual intercourse, and perinatal exposure. Substance abuse, including the use of opioids and cocaine, is a significant risk factor for exposure to HIV-1 and the development of acquired immune deficiency syndrome, as well as HBV and HCV exposure, infection, and disease. Thus, coinfection with HIV-1 and HBV or HCV is common and may be impacted by chronic substance abuse during the course of disease. HIV- 1 impacts the natural course of HBV and HCV infection by accelerating the progression of HBV/HCV-associated liver disease toward end-stage cirrhosis and quantitative depletion of the CD4+ T-cell compartment. HBV or HCV coinfection with HIV-1 is also associated with increased mortality when compared to either infection alone. This review focuses on the impact of substance abuse and coinfection with HBV and HCV in the PB, BM, and brain on the HIV-1 pathogenic process as it relates to viral pathogenesis, disease progression, and the associated immune response during the course of this complex interplay. The impact of HIV-1 and substance abuse on hepatitis virus-induced disease is also a focal point.
- Published
- 2012
- Full Text
- View/download PDF
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