摘要:

Although the signal transducer and activator of transcription (STAT) proteins were originally discovered through the study of interferon-induced responses, a large number of cytokines and growth factors have been found to activate STATs. In addition to the fundamental role of STAT pathways in normal cell signaling, accumulating evidence is defining a critical role for STATs in oncogenesis. STAT family members are constitutively activated by various oncoproteins in transformed cells and are found activated in a wide variety of human tumors, including breast cancer and diverse blood malignancies. This review discusses recent progress in understanding how aberrant activation of STAT signaling pathways participates in malignant progression of human cancers. Current evidence indicates that one mechanism by which STATs contribute to oncogenesis involves prevention of programmed cell death, or apoptosis, thereby conferring a survival advantage and, potentially, resistance to chemotherapy. These advances identify STATs as novel molecular targets for development of promising therapeutics against human cancers that harbor activated STAT proteins.

ISSN:1040-8746    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Retinoids (vitamin A and related molecules) are biologic agents that have demonstrated, in preclinical and clinical models, potent activity in the prevention and treatment of a variety of malignancies. Presented in this article is a review of recent clinical studies and correlative laboratory findings that advance our understanding of the biologic basis for the use of retinoids in cancer prevention and treatment.

ISSN:1040-8746    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Combination anti-retroviral therapy for HIV disease has profoundly altered the nature of the AIDS epidemic. Mitigating the impact of an uncontrollable decline in immune function is no longer the focal point for AIDS therapy, but has evolved to an emphasis on maximizing the potential for immune regeneration. Improved control of HIV replication has diminished, albeit unevenly, the frequency of AIDS-related malignancies and has altered the focus of hematologic and oncologic interventions in HIV disease. Now, with adoptive cellular therapies and the genetic engineering of cells in the clinical arena, the potential for cellular therapeutics in enhancing immune restoration is being tested. These approaches are based on better understanding of the immunobiology of HIV and its impact on hematopoietic tissues.

ISSN:1040-8746    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The epidemiology of AIDS-related Kaposi’s sarcoma (KS) predicted that a nonubiquitous sexually transmitted agent was central to its etiology. An assessment of Hill’s criteria for causality reveals there is now sufficient evidence to declare Kaposi’s sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8, a necessary, albeit not sufficient, cause of KS. The most compelling evidence comes from longitudinal studies presented in the past year that demonstrate that KSHV infection temporally precedes and is independently associated with AIDS-related KS even after adjustment for other potential etiologic factors. In the United States and Northern Europe, many studies have now shown that KSHV can be sexually transmitted among homosexual men, but determining specific routes of sexual transmission is methodologically challenging, and initial results are conflicting. Data are also emerging that demonstrate nonsexual modes of transmission. Spread via renal allograft appears to occur, and in endemic areas of Europe and Africa, nonsexual horizontal and perhaps vertical spread are the dominant modes of transmission.

ISSN:1040-8746    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

AIDS-lymphoma is a heterogeneous disease that most likely results from the complex interaction of several contributing factors, including chronic antigenic activation of B lymphocytes, dysregulated cytokine and co-stimulatory networks, infection with potentially oncogenic viruses (human herpesvirus-8 [HHV-8], Epstein-Barr virus), and accumulation of secondary genetic mutations. Cytokines are believed to play an important role in the immunologic decline that favors opportunistic infection and malignancy in advanced HIV infection. Recent work has provided some evidence that cytokine therapy can partially reverse the immune dysregulation seen in AIDS. This suggests that cytokines are likely to have an important role in both the pathogenesis and treatment or prevention of AIDS-lymphoma.

ISSN:1040-8746    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The clinical and pathologic characteristics of Hodgkin’s disease as they are diagnosed in patients with HIV infection differ from those of the general population. In fact, a higher frequency of unfavorable histologic subtypes, advanced stage, and poor therapeutic outcome have been reported in the HIV setting. Complete response rate after chemotherapy ranges from approximately 45% to 70%, although the disease-free survival is very short, and the median overall survival is only 18 months. The survival of these patients may be improved by the optimal combination of antineoplastic and antiretroviral treatment with the support of hematologic growth factors. However, new strategies of therapeutic intervention must be explored.

ISSN:1040-8746    

出版商:OVID    

年代:1999

数据来源: OVID