Desmoid Tumor and Silicone Breast Implant Surgery: Is There Really a Connection? A Literature Review.

BACKGROUND: Desmoid tumors are borderline tumors of the connective tissue, arising in the musculo-aponeurotic stromal elements. A desmoid tumor (DT) has an infiltrative and locally aggressive growth pattern and usually does not metastasize; however, it has a high recurrence and complication rate. DT located in the breast (BDT) represents a rare extra-abdominal form. Recently, the presence of breast silicone implants was suggested by several researchers as a risk factor for developing BDT. OBJECTIVES: The goal of this review is to investigate the possible correlation between BDT and breast implant surgery. METHODS: We conducted a literature review of BDT-reported cases, associated with breast implant surgery. RESULTS: The search revealed 36 cases of BDT associated with silicone breast implants. CONCLUSIONS: Based on the reviewed data, the incidence of BDT following breast implant surgery is lower than BDT in the general population. At the moment, a possible association between breast implants and the development of breast desmoid tumors cannot be unequivocally confirmed. A world registry with accurate documentation of each case of BDT associated with breast implant surgery should be performed for future investigation. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .

HIV-1 Vpr transactivates LTR-directed expression through sequences present within -278 to -176 and increases virus replication in vitro.

Human immunodeficiency virus type 1 (HIV-1) Vpr, a 14-kDa virion-associated protein, plays an important role in the viral life cycle. Using a panel of truncated HIV-1 LTR-CAT constructs and Vpr expression plasmid, we have identified sequences from nucleotide -278 to -176 in LTR as Vpr-mediated transactivation domain. This region includes the glucocorticoid response element (GRE) in HIV-1 LTR. Transactivation by Vpr was noted with the HIV-1 LTR reporter constructs containing CAT or luciferase. A similar effect was also observed with a construct in which the GRE motif was linked to CAT. Studies involving Vpr mutants identified that helical domains I and III, and amino acid residues at G75 and C76, are responsible for GRE-mediated LTR transactivation. The transactivation function of Vpr is independent of its cell cycle arrest activity. Further, viral replication studies indicated that Vpr-mediated increase in viral replication is directly correlated with the ability of Vpr to transactivate HIV-1 LTR. The results presented here demonstrate that Vpr activates HIV-1 LTR through the host GR pathway and suggest that an intact GRE in the LTR is critical for Vpr activity.

HIV-1 viral protein R (Vpr) regulates viral replication and cellular proliferation in T cells and monocytoid cells in vitro.

Among the putative accessory genes of HIV-1, the 96-amino-acid virion-associated vpr gene product has been described to have several novel biological activities. These include cytoplasmic-to-nuclear translocation, which empowers HIV to infect and replicate in non-dividing cells and to increase viral replication, particularly in macrophages. Along with these viral effects, we found that HIV-1 Vpr induces dramatic biological changes in the target cells of HIV infection, including induction of changes in transcriptional patterns, morphological changes, and complete inhibition of proliferation, which collectively was termed differentiation. These changes occur in the absence of other viral gene products, suggesting that Vpr mediates its proviral effects partially or perhaps solely through modulation of the state of the target cell rather than directly on the virus. The inhibition of proliferation in T cell lines has been extended by several groups to demonstrate that the inhibition of proliferation is through G2 cell cycle arrest, further supporting the idea that Vpr acts directly on cellular targets. We have recently described a role for Vpr in modulating the glucocorticoid pathway, which is involved in the regulation of the state of the cell, in cytoplasmic-to-nuclear translocation, and in modulation of host cell transcription. It is important to note that certain anti-glucocorticoid compounds modulate Vpr activity in vitro. These results support the idea that the host cell contains specific receptor molecule(s) through which Vpr mediates its activity. Consequently, Vpr represents a unique target for anti-HIV drug development and has significance for HIV-1 disease progression.

HIV-1 viral protein R (Vpr) as a regulator of the target cell.

Among the putative 'accessory genes' of HIV-1, the 96 amino acid virion-associated Vpr gene product has been described to have several novel biological activities. These include cytoplasmic-to-nuclear translocation thus empowering HIV to infect and replicate in nondividing cells and to function to increase viral replication, particularly in monocytes. Along with these viral effects, we describe the dramatic biological changes induced by HIV-1 Vpr in the target cells of HIV infection including induction of changes in transcriptional patterns and complete inhibition of proliferation which collectively is termed differentiation. These changes occur in the absence of other viral gene products and suggest that Vpr mediates its proviral effects partially or perhaps solely through modulation of the state of the target cell rather than directly on the virus. The inhibition of proliferation in T-cell lines has been proposed by several groups to demonstrate that the inhibition of proliferation specifically arrests the cell cycle further supporting the notion that Vpr activity is directed at cellular targets. We have recently described a role for Vpr in modulating the glucocorticoid pathway, a pathway involved in the regulation of the state of the cell in cytoplasmic-to-nuclear translocation and in the modulation of host cell transcription. Importantly, certain antiglucocorticoids have been shown to modulate Vpr activity in vitro. These results demonstrate that the cell contains specific receptor(s) molecule(s) through which Vpr mediates its activity and that these molecules have implications for cell biology in general. These results collectively demonstrate that Vpr represents a unique target for anti-HIV drug development and has significance for HIV-1 disease progression.