To assess the toxicity and activity of oral thalidomide in Kaposi's sarcoma (KS) in a phase II dose-escalation study.
Human immunodeficiency virus (HIV)-seropositive patients with biopsy-confirmed KS that progressed over the 2 months before enrollment received an initial dose of 200 mg/d of oral thalidomide in a phase II study. The dose was increased to a maximum of 1,000 mg/d for up to 1 year. Anti-HIV therapy was maintained during the study period. Toxicity, tumor response, immunologic and angiogenic factors, and virologic parameters were assessed.
Twenty patients aged 29 to 49 years with a median CD4 count of 246 cells/mm(3) (range, 14 to 646 cells/mm(3)) were enrolled. All patients were assessable for toxicity, and 17 for response. Drowsiness in nine and depression in seven patients were the most frequent toxicities observed. Eight (47%; 95% confidence interval [CI], 23% to 72%) of the 17 assessable patients achieved a partial response, and an additional two patients had stable disease. Based on all 20 patients treated, the response rate was 40% (95% CI, 19% to 64%). The median thalidomide dose at the time of response was 500 mg/d (range, 400 to 1,000 mg/d). The median duration of drug treatment was 6.3 months, and the median time to progression was 7.3 months.
Oral thalidomide was tolerated in this population at doses up to 1,000 mg/d for as long as 12 months and was found to induce clinically meaningful anti-KS responses in a sizable subset of the patients. Additional studies of this agent in KS are warranted.
"In addition to its antiangiogenic effect, an immunomodulatory function is also a potential mechanism of the anticancer activity of thalidomide. To date, the effectiveness of thalidomide for treating neoplastic disorders has been confirmed in diseases such as multiple myeloma (11) and Kaposi’s sarcoma (12). In addition, thalidomide has been tentatively used for the treatment of advanced hepatocellular carcinoma (13–16). "
[Show abstract][Hide abstract] ABSTRACT: Liver regeneration is an angiogenesis-associated phenomenon. The present study investigated the influence of thalidomide, an antiangiogenic agent, on vascular endothelial growth factor (VEGF) expression and liver regeneration after 70% partial hepatectomy (PH) in rats. PH was performed on 50 rats dosed with either thalidomide (100 mg/kg) or a vehicle (controls) by intragastric administration. Serial changes in hepatic microcirculation were evaluated by laser Doppler flowmetry. The VEGF expression in liver tissue was assessed by immunohistochemical study and western blot analysis. Following hepatectomy, the liver regeneration rate increased markedly and reached a peak at 96 h in the two groups. Thalidomide did not affect the overall restoration of liver mass, although a delay in cell proliferation was observed. Prior to PH, the liver microcirculation in rats treated with thalidomide for 2 days was comparatively less than that in their corresponding controls; however, no significant difference between the groups was detected at any time-point following PH. Western blotting showed that the expression of VEGF was upregulated by hepatectomy and the expression levels in the two groups were equal at all studied time-points. The immunohistochemical staining revealed a waved pattern of VEGF expression which advanced from the periportal to pericentral area in both groups, but a slower advancement was detected in thalidomide-treated rats. In conclusion, thalidomide exerted no significant effects on the expression of VEGF and did not impair the overall restoration of liver mass in a rat model of PH-induced liver regeneration, providing supportive evidence for its use as an adjunct treatment modality for liver cancers.
"In our cohort, complete regression of lymph nodes and symptoms was observed in 91% of patients and was maintained after discontinuation of treatment with a 2-year PFS of 60% after a median followup of almost 2 years, comparing favourably with rituximab alone (Gerard et al, 2007; Bower et al, 2011). Despite small numbers, the low risk of KS reactivation could be thalidomide-related , as has been previously reported (Little et al, 2000). The duration of maintenance with thalidomide in MCD patients following rituximab-thalidomide combination therapy should be explored in a prospective trial. "
"While the enantiomers can interconvert (racemize) in vivo , their pathogenic mechanisms are still not understood. Recently, thalidomide has been considered as a potential drug for various diseases such as autoimmune diseases, AIDS, Hansen’s disease, and some cancers [87, 88]. "
[Show abstract][Hide abstract] ABSTRACT: Aptamers are single-stranded DNA or RNA oligonucleotides, which are able to bind with high affinity and specificity to their target. This property is used for a multitude of applications, for instance as molecular recognition elements in biosensors and other assays. Biosensor application of aptamers offers the possibility for fast and easy detection of environmental relevant substances. Pharmaceutical residues, deriving from human or animal medical treatment, are found in surface, ground, and drinking water. At least the whole range of frequently administered drugs can be detected in noticeable concentrations. Biosensors and assays based on aptamers as specific recognition elements are very convenient for this application because aptamer development is possible for toxic targets. Commonly used biological receptors for biosensors like enzymes or antibodies are mostly unavailable for the detection of pharmaceuticals. This review describes the research activities of aptamer and sensor developments for pharmaceutical detection, with focus on environmental applications.
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