In the HAART era Kaposi's sarcoma (KS) remains the second most frequent tumor in HIV-infected patients worldwide, and it has become the most common cancer in Sub-Saharan Africa. In western countries the risk for KS in men having sex with men (MSM) is 5 to 10 times higher compared to other groups of individuals practicing other HIV-risk behaviors. Patients with KS in Sub-Saharan Africa have very high tumor burdens and rapid disease progression with a diminished life expectancy of less than 6 months. KS lesions are comprised of both distinctive spindle cells of endothelial origin and a variable inflammatory infiltrate, which suggests that KS may result from reactive hyperproliferation induced by chronic inflammation, and therefore it is not a true neoplasm. KS has a variable clinical course ranging from very indolent forms, requiring no or minimal therapy, to a rapidly progressive disease. Treatment decisions must take into consideration the extent and the rate of tumor growth, patient's symptoms, immune system conditions and concurrent HIV-related complications. Several different therapeutic options are available but the optimal therapy is still unclear. Highly Active Antiretroviral Therapy (HAART) including protease inhibitors (PI) may represent the first treatment step for slowly progressive disease; chemotherapy (CT) plus HAART is indicated for visceral and/or rapidly progressive disease, whereas maintenance (M)-HAART after systemic chemotherapy may be an effective anti-KS measure after debulking CT. The angiogenic nature of KS makes it particularly suitable for therapies based on targeted agents such as metalloproteinase inhibitors, angiogenesis inhibitors and tyrosine kinase inhibitors. The aim of this article is to provide an up-to-date review of the current status and perspectives of AIDS-related KS in the HAART era.
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"The gastrointestinal system can be affected by multicentric lesions observed from oral cavity, oropharynx and esophagus to the perianal area, including organs like pancreas, liver and other organs like, lungs and tests. It is estimated that almost half of patients with AIDS and KS may present with associated visceral lesions . Of the four variants, the epidemic form most commonly involves the oral cavity . "
"In any case, the connection between P-TEFb-dependent and HMGA1-dependent signaling via 7SK RNA which we uncovered here represents a new molecular switch (Figure 10). The role that P-TEFb and 7SK RNA play in Tat-dependent HIV transcription (24,66–69) thereby might also provide a molecular explanation for the HIV-associated B-cell lymphoma and Kaposi sarcoma incident rates (70–73). Increased titration of nuclear 7SK RNA into Tat-dependent transcription regulatory complexes will, according to our observations, directly increase HMGA1 activity. "
[Show abstract][Hide abstract]ABSTRACT: Non-coding (nc) RNAs are increasingly recognized to play important regulatory roles in eukaryotic gene expression. The highly
abundant and essential 7SK ncRNA has been shown to negatively regulate RNA Polymerase II transcription by inactivating the
positive transcription elongation factor b (P-TEFb) in cellular and Tat-dependent HIV transcription. Here, we identify a more
general, P-TEFb-independent role of 7SK RNA in directly affecting the function of the architectural transcription factor and
chromatin regulator HMGA1. An important regulatory role of 7SK RNA in HMGA1-dependent cell differentiation and proliferation
regulation is uncovered with the identification of over 1500 7SK-responsive HMGA1 target genes. Elevated HMGA1 expression
is observed in nearly every type of cancer making the use of a 7SK substructure in the inhibition of HMGA1 activity, as pioneered
here, potentially useful in therapy. The 7SK-HMGA1 interaction not only adds an essential facet to the comprehension of transcriptional
plasticity at the coupling of initiation and elongation, but also might provide a molecular link between HIV reprogramming
of cellular gene expression-associated oncogenesis.
Full-text · Article · Nov 2010 · Nucleic Acids Research
[Show abstract][Hide abstract]ABSTRACT: The coupling coefficient and resonant frequency shift of dual
modes induced by the internal perturbation are obtained theoretically
for a general circular resonator. They are used for the design of a
two-stage BPF together with the external Q also theoretically derived.
The frequency and the appearance condition of the intrinsic attenuation
poles at both sides of the passband are analyzed in a simple form