Subject(s)
Bisoprolol/administration & dosage , Defibrillators , Electric Countershock , Isolated Noncompaction of the Ventricular Myocardium , Pregnancy Complications, Cardiovascular , Tachycardia, Ventricular , Adrenergic beta-1 Receptor Antagonists/administration & dosage , Adult , Cardiotocography/methods , Cesarean Section/methods , Echocardiography/methods , Electric Countershock/instrumentation , Electric Countershock/methods , Electrocardiography, Ambulatory/methods , Female , Humans , Isolated Noncompaction of the Ventricular Myocardium/complications , Isolated Noncompaction of the Ventricular Myocardium/diagnosis , Isolated Noncompaction of the Ventricular Myocardium/physiopathology , Magnetic Resonance Imaging, Cine/methods , Pregnancy , Pregnancy Complications, Cardiovascular/diagnosis , Pregnancy Complications, Cardiovascular/physiopathology , Pregnancy Outcome , Stroke Volume , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/etiologyABSTRACT
Melanoma is the most deadly type of skin cancer, constituting annually â¼ 75% of all cutaneous cancer-related deaths due to metastatic spread. Currently, because of metastatic spread, there are no effective treatment options for late-stage metastatic melanoma patients. Studies over the past two decades have provided insight into several complex molecular mechanisms as to how these malignancies evade immunological control, indicating the importance of immune escape or suppression for tumor survival. Thus, it is essential to develop innovative cancer strategies and address immune obstacles with the goal of generating more effective immunotherapies. One important area of study is to further elucidate the role and significance of myeloid-derived suppressor cells (MDSCs) in the maintenance of the tumor microenvironment. These cells possess a remarkable ability to suppress immune responses and, as such, facilitate tumor growth. Thus, MDSCs represent an important new target for preventing tumor progression and escape from immune control. In this study, we investigated the role of MDSCs in immune suppression of T cells in an antigen-specific B16 melanoma murine system utilizing a novel synthetic tyrosinase (Tyr) DNA vaccine therapy in both prophylactic and therapeutic models. This Tyr vaccine induced a robust and broad immune response, including directing CD8 T-cell infiltration into tumor sites. The vaccine also reduced the number of MDSCs in the tumor microenvironment through the downregulation of monocyte chemoattractant protein 1, interleukin-10, CXCL5 and arginase II, factors important for MDSC expansion. This novel synthetic DNA vaccine significantly reduced the melanoma tumor burden and increased survival in vivo, due likely, in part, to the facilitation of a change in the tumor microenvironment through MDSC suppression.
Subject(s)
Cancer Vaccines/immunology , Melanoma/immunology , Melanoma/therapy , Monophenol Monooxygenase/immunology , Myeloid Cells/immunology , Vaccines, DNA/immunology , Animals , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Cancer Vaccines/administration & dosage , Cytokines/metabolism , Disease Models, Animal , Female , Humans , Immunity, Cellular , Immunity, Humoral , Immunization , Immunomodulation , Melanoma/genetics , Melanoma/mortality , Melanoma/pathology , Melanoma/prevention & control , Melanoma, Experimental , Mice , Monophenol Monooxygenase/antagonists & inhibitors , Monophenol Monooxygenase/genetics , Myeloid Cells/metabolism , T-Cell Antigen Receptor Specificity , Tumor Burden/immunology , Tumor Microenvironment , Vaccines, DNA/administration & dosageABSTRACT
INTRODUCTION: In order to determine the development of the prevalence of HIV infection in rural Western Uganda, data of epidemiological studies conducted in 2001 and 2007 were compared to study data from 1993. METHODS: In 2001 (n = 466) and in 2007 (n = 486), one group each of clinically healthy pregnant women of a local prenatal care department were enrolled in the study and anonymously screened for HIV-1. For both groups, informed consent was obtained prior to enrolment. Testing for HIV was done by enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blot. In addition, age and antibodies against syphilis were determined as risk factors of HIV infection. RESULTS: The seroprevalence of HIV-1 infection did not decrease significantly over this time period, dropping from 28.3 to 25.1% between 2001 and 2007, but the prevalence of syphilis antibodies decreased from 27.9 to 11.1%. The data of 2001 and 2007 were compared to a third cohort from 1993, in which 21.5% of pregnant women were HIV-1-positive and 31.1% were Treponema pallidum hemagglutination assay (TPHA)-positive. CONCLUSION: The current prevalence of HIV-1 infection in Uganda is still high and there is a need for further promotion of HIV prevention and control services.
