236 research outputs found
Basic fibroblast growth factor mediates the growth and angiogenic activity of AIDS-Kaposi’s sarcoma (KS)-derived spindle cells and synergises with HIV-1 Tat protein in inducing KS-like lesions in mice.
No full text
Basic FGF induces lesions in mice resembling KS, and antisense oligonucleotides against this cytokine inhibit the growth and angiogenic activity of KS spindle cells.
No full textBlastic plasmacytoid dendritic cell neoplasm in children: diagnostic features and clinical implications
No full textBlock of AIDS-Kaposi's sarcoma (KS) cell growth, angiogenesis, and lesion formation in nude mice by antisense oligonucleotide targeting basic fibroblast growth factor. A novel strategy for the therapy of KS
No full textKaposi's sarcoma (KS) is the most frequent tumor of HIV-1-infected individuals (AIDS-KS). Typical features of KS are proliferating spindle-shaped cells, considered to be the tumor cells of KS, and endothelial cells forming blood vessels. Basic fibroblast growth factor (bFGF), a potent angiogenic factor, is highly expressed by KS spindle cells in vivo and after injection in nude mice it induces vascular lesions closely resembling early KS in humans. Similar lesions are induced by inoculating nude mice with cultured spindle cells from AIDS-KS lesions (AIDS-KS cells) which produce and release bFGF. Here we show that phosphorothioate antisense (AS) oligonucleotides directed against bFGF mRNA (ASbFGF) inhibit both the growth of AIDS-KS cells derived from different patients and the angiogenic activity associated with these cells, including the induction of KS-like lesions in nude mice. These effects are due to the block of the production of bFGF which is required by AIDS-KS cells to enter the cell cycle and which, after release, mediates angiogenesis. The effects of ASbFGF are specific, dose dependent, achieved at low (0.1-1 microM), nontoxic, oligomer concentrations, and are reversed by the addition of bFGF to the cells, suggesting that ASbFGF oligomers are promising drug candidates for KS therapy
Activation of the mTOR Pathway in Primary Medullary Thyroid Carcinoma and Lymph Node Metastases.
No full textUnderstanding the molecular pathogenesis of medullary thyroid carcinoma (MTC) is prerequisite to the design of targeted therapies for patients with advanced disease.We studied by immunohistochemistry the phosphorylation status of proteins of the RAS/MEK/ERK and PI3K/AKT/mTOR pathways in 53 MTC tissues (18 hereditary, 35 sporadic), including 51 primary MTCs and 2 cases with only lymph node metastases (LNM). We also studied 21 autologous LNMs, matched to 21 primary MTCs. Staining was graded on a 0 to 4 scale (S score) based on the percentage of positive cells. We also studied the functional relevance of the mTOR pathway by measuring cell viability, motility, and tumorigenicity upon mTOR chemical blockade.Phosphorylation of ribosomal protein S6 (pS6), a downstream target of mTOR, was evident (S ≥ 1) in 49 (96\%) of 51 primary MTC samples. This was associated with activation of AKT (phospho-Ser473, S > 1) in 79\% of cases studied. Activation of pS6 was also observed (S ≥ 1) in 7 (70\%) of 10 hereditary C-cell hyperplasia specimens, possibly representing an early stage of C-cell transformation. It is noteworthy that 22 (96\%) of 23 LNMs had a high pS6 positivity (S ≥ 3), which was increased compared with autologous matched primary MTCs (P = 0.024). Chemical mTOR blockade blunted viability (P < 0.01), motility (P < 0.01), and tumorigenicity (P < 0.01) of human MTC cells.The AKT/mTOR pathway is activated in MTC, particularly, in LNMs. This pathway sustains malignant features of MTC cell models. These findings suggest that targeting mTOR might be efficacious in patients with advanced MTC. Clin Cancer Res; 18(13); 3532-40. ©2012 AACR
Effects of Nicotine Pharmacology and Stimulus Expectancies on Withdrawal and Attentional Processing
No full textSmoking is a major public health issue in the United States. People smoke for different reasons many of which go beyond the simple pharmacology of nicotine. The current study sought to clarify the independent and potentially interactive effects of nicotine pharmacology and smoking expectancies on self-reported withdrawal symptoms and sustained attention. To this end, the study employed a mixed design with a modified balanced placebo component, as well as repeated assessments (pre-smoking vs. post-smoking) of the Wisconsin Smoking Withdrawal Scale and the Rapid Visual Information Processing task. This design created four groups of participants split by instructional set (told high-dose nicotine cigarette vs. told low-dose nicotine cigarette) and actual nicotine dose (low-dose vs. high-dose). For subjective measures of withdrawal, results indicated that expectancies, but not nicotine pharmacology, were associated with the alleviation of symptoms. Individuals expecting to receive a low-dose nicotine cigarette reported lower levels of withdrawal compared to those expecting to receive a high-dose nicotine cigarette. For sustained attention, nicotine pharmacology, but not expectancy, was associated with facilitated performance. Participants who received a high-dose nicotine cigarette exhibited decreased reaction times on the RVIP task. No interactions of expectancies and pharmacology were noted for withdrawal or sustained attention. The current findings underscore the importance of non-nicotinic factors in the maintenance of smoking behavior, particularly with regard to subjective perception of withdrawal symptoms. Though preliminary, these results suggest that modem smoking cessation techniques should take into account sensory factors that go beyond the pharmacological effects of nicotine addiction.Psycholog
Neutrophil Recruitment by Intradermally Injected Neutrophil Attractant/Activation Protein-1
No full textNeutrophil attractant/activation protein-1 (NAP-l) is a recently described cytokine that attracts neutrophils, but not monocytes or eosinophils. This leukocyte specificity is not absolute, in that NAP-1 attracts basophils and small numbers of lymphocytes. Our purpose was to determine in vivo effects of NAP-1, and to compare them to the reported action of the complement attractant, C5a. Intradermal injection into normal human subjects of 40 μ1 of NAP-l, over a concentration range of 4 × 10-8 M to10-6 M, caused no symptoms or signs such as wheal-and-flare, itching, induration, or tenderness. However, biopsies of injection sites showed perivascular neutrophil infiltration as early as 30 rain, which increased at 1 and 3h. The mean number of neutrophils per mm2 of dermis for 15 biopsies taken 3h after intradermal injection of 2 × 10-7 M or 100-6 M NAP-1 was 164 ± 41; the response to saline or a NAP-1 inactive fragment was 5 or less. Intradermal NAP-1 did not cause basophil or lymphocyte infiltration. Consistent with the absence of a wheal-and-flare, acid toluidine blue-stained sections showed no evidence of mast cell degranulation, in contrast to previously reported results with C5a. Thus, the predominant response by human subjects to intradermal NAP-1 was neutrophil accumulation in proximity to dermal blood vessels
A study of the aquaculture industry in Texas to assist in establishing aquaculture as a course offering in agricultural science and technology, final report.
No full text64 p.No abstract availablehttp://gbic.tamug.edu/request.ht
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