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981.
Angiogenesis is important for tumor growth and metastasis. CLT1 (CGLIIQKNEC), a peptide that binds to tumor interstitial spaces
in the presence of fibrin-fibronectin, has structural similarity to the anti-angiogenic β-sheet peptides anastellin and anginex.
This similarity is reflected in the ability of CLT1 to form co-aggregates with fibronectin that induce an unfolded protein
response and cause autophagic cell death in proliferating endothelial cells. CLT1 cytotoxicity is mediated at least in parts
by a novel CLT1 binding protein, Chloride Intracellular Channel 1 (CLIC1), which promotes internalization of CLT1-fibronectin
co-aggregates in a mechanism that depends on the LIIQK amino acid sequence of CLT1. LIIQK encompasses amino acid residues
relevant for CLT1 binding to CLIC1 and in addition, facilitates the formation of CLT1-fibronectin co-aggregates, which in
turn promote translocation of CLIC1 to the endothelial cell surface through ligation of integrin αvβ3. Paralleling the in
vitro results, we found that CLT1 co-localizes with CLIC1 and fibronectin in angiogenic blood vessels in vivo, and that CLT1
treatment inhibited angiogenesis and tumor growth. Our findings show that CLT1 is a new anti-angiogenic compound, and its
mechanism of action is to form co-aggregates with fibronectin, which bind to angiogenic endothelial cells through integrins,
become internalized through CLIC1 and elicit a cytotoxic unfolded protein response. The simple structure and high potency
of CLT1 make it a potentially useful compound for anti-angiogenic treatments. 相似文献
982.
Parvaiz A. Koul Umar Hafiz Khan Rafi A. Jan Ajaz N. Koul Abdul Baseer Qadri 《Indian Journal of Rheumatology》2012,7(3):167-168
A young female with known Behcet's disease presented with skin lesions over lower limbs. The lesions were biopsied and found to be pyoderma gangrenosum. The lesions responded to oral steroids for 6 weeks. 相似文献
983.
984.
985.
BackgroundAll renin arises from prorenin. The proportion of renin relative to prorenin could influence overall renin-angiotensin-aldosterone activity. We sought to determine whether prorenin levels were related to extracellular volume, as reflected by the levels of plasma renin activity (PRA), and to aldosterone.MethodsWe analyzed plasma levels of prorenin, renin, and aldosterone, as well as their interactions, in 129 young blacks and whites.ResultsBlacks had lower plasma renin concentration (PRC) and PRA, but had prorenin levels similar to whites (69 pg/ml in blacks vs. 62 pg/ml in whites, P = 0.41). As a result, the renin-to-total renin ratio was significantly lower in blacks (11.5% in blacks as compared to 19.8% in whites; P = 0.0001). Because prorenin also resides in tissues including the adrenal where it can bind to a specific receptor to generate angiotensin II, we examined the relationship of prorenin levels to plasma aldosterone concentrations (PAC). While a positive association between PRC and PAC was found in both blacks and whites, PAC was positively related to prorenin in whites (P = 0.04) but negatively in blacks, an observation that we hypothesize was due to reduced prorenin-to-renin conversion in blacks.ConclusionsWe observed a disproportionately high level of prorenin in blacks. These high circulating prorenin levels however do not result in greater adrenal angiotensin II and aldosterone production in healthy young blacks.American Journal of Hypertension 2012; doi:10.1038/ajh.2012.83. 相似文献
986.
987.
Nicholls SJ Gordon A Johannson J Ballantyne CM Barter PJ Brewer HB Kastelein JJ Wong NC Borgman MR Nissen SE 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》2012,26(2):181-187
Background
Considerable interest has focused on the development of therapies that target the functionality of high-density lipoproteins (HDL). Upregulation of endogenous synthesis of the major protein on HDL particles, apolipoprotein A-I (apoA-I), represents a novel approach to generation of new HDL particles. The Study of Quantitative Serial Trends in Lipids with Apolipoprotein A-I Stimulation (SUSTAIN, NCT01423188) study aims to evaluate the lipid efficacy, safety and tolerability of an apoA-I inducer (RVX-208). The ApoA-I Synthesis Stimulation and Intravascular Ultrasound for Coronary Atheroma Regression Evaluation (ASSURE, NCT01067820) study aims to evaluate the effect of RVX-208 on plaque burden. 相似文献988.
989.
Jan Cincibuch Miroslav Myslive?ek Bohuslav Melichar ?estmír Neoral Iva Metelková Michaela Zezulová Hana Procházková-?tudentová Patrik Flodr Miloslava Zlevorová René Aujesky Karel Cwiertka 《World journal of gastroenterology : WJG》2012,18(35):4962-4966
Metastases of esophageal carcinoma to the skeletal muscle are rare, but the incidence may be increasing because of better diagnosis resulting from widespread use of positron emission tomography/computed tomography (PET/CT). A cohort of 205 patients with esophageal carcinoma treated at our center who had PET/CT between 2006 and 2010 was retrospectively evaluated for the presence of skeletal muscle metastases. Four patients had skeletal muscle metastases of esophageal carcinoma, including two patients with squamous cell carcinoma. In another patient with squamous cell carcinoma of the esophagus and synchronous skeletal muscle metastases, muscle metastases were subsequently shown to be related to second primary pancreatic adenocarcinoma. In all cases, skeletal muscle metastases were the first manifestation of systemic disease. In three patients palliation was obtained with the combination of external beam radiation therapy, systemic chemotherapy or surgical resection. Skeletal muscle metastases are a rare complication of esophageal carcinoma. 相似文献
990.