Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apigenin is a plant flavonoid that is thought to play a role in the prevention of carcinogenesis. However, its mechanism of action has not yet been elucidated. Because of the importance of angiogenesis in tumor growth, we investigated the effect of apigenin on endothelial and smooth-muscle cells in an in vitro model. Apigenin markedly inhibited the proliferation, and, to a lesser degree, the migration of endothelial cells, and capillary formation in vitro, independently of its inhibition of hyaluronidase activity. In contrast, it strongly stimulated vascular smooth-muscle-cell proliferation. The molecular mechanisms of apigenin activity were analyzed in these 2 types of cells. Our results show that apigenin inhibits endothelial-cell proliferation by blocking the cells in the G(2)/M phase as a result of the accumulation of the hyperphosphorylated form of the retinoblastoma protein. Apigenin stimulation of smooth-muscle cells was attributed to the reduced expression of 2 cyclin-dependent kinase inhibitors, p21 and p27, which negatively regulate the G(1)-phase cyclin-dependent kinase.
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PMID:Apigenin inhibits endothelial-cell proliferation in G(2)/M phase whereas it stimulates smooth-muscle cells by inhibiting P21 and P27 expression. 1069 50

Extracts of Aesculus hippocastanum (horse chestnut) seed have been used in the treatment of chronic venous insufficiency, edema, and hemorrhoids. Most of the beneficial effects of horse chestnut are attributed to its principal component beta-escin or aescin. Recent studies suggest that beta-escin may possess anti-inflammatory, anti-hyaluronidase, and anti-histamine properties. We have evaluated the chemopreventive efficacy of dietary beta-escin on azoxymethane-induced colonic aberrant crypt foci (ACF). In addition, we analyzed the cell growth inhibitory effects and the induction of apoptosis in HT-29 human colon cancer cell line. To evaluate the inhibitory properties of beta-escin on colonic ACF, 7-week-old male F344 rats were fed experimental diets containing 0%, 0.025%, or 0.05% beta-escin. After 1 week, the rats received s.c. injections of azoxymethane (15 mg/kg body weight, once weekly for 2 weeks) or an equal volume of normal saline (vehicle). Rats were continued on respective experimental diets and sacrificed 8 weeks after the azoxymethane treatment. Colons were evaluated histopathologically for ACF. Administration of dietary 0.025% and 0.05% beta-escin significantly suppressed total colonic ACF formation up to approximately 40% (P < 0.001) and approximately 50% (P < 0.0001), respectively, when compared with control diet group. Importantly, rats fed beta-escin showed dose-dependent inhibition (approximately 49% to 65%, P < 0.0001) of foci containing four or more aberrant crypts. To understand the growth inhibitory effects, HT-29 human colon carcinoma cell lines were treated with various concentrations of beta-escin and analyzed by flow cytometry for apoptosis and cell cycle progression. Beta-escin treatment in HT-29 cells induced growth arrest at the G1-S phase, which was associated with the induction of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1), and this correlated with reduced phosphorylation of retinoblastoma protein. Results also indicate that beta-escin inhibited growth of colon cancer cells with either wild-type or mutant p53. This novel feature of beta-escin, a triterpene saponin, may be a useful candidate agent for colon cancer chemoprevention and treatment.
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PMID:Beta-escin inhibits colonic aberrant crypt foci formation in rats and regulates the cell cycle growth by inducing p21(waf1/cip1) in colon cancer cells. 1681 4

Pigment epithelium-derived factor (PEDF) is a multifunctional serpin with antitumorigenic, antimetastatic, and differentiating activities. PEDF is found within tissues rich in the glycosaminoglycan hyaluronan (HA), and its amino acid sequence contains putative HA-binding motifs. We show that PEDF coprecipitation with glycosaminoglycans in media conditioned by human retinoblastoma Y-79 cells decreased after pretreatments with hyaluronidase, implying an association between HA and PEDF. Direct binding of human recombinant PEDF to highly purified HA was demonstrated by coprecipitation in the presence of cetylpyridinium chloride. Binding of PEDF to HA was concentration-dependent and saturable. The PEDF-HA interactions were sensitive to increasing NaCl concentrations, indicating an ionic nature of these interactions and having affinity higher than PEDF-heparin. Competition assays showed that PEDF can bind heparin and HA simultaneously. PEDF chemically modified with fluorescein retained the capacity for interacting with HA but lacked heparin affinity, suggesting one or more distinct HA-binding regions on PEDF. The HA-binding region was examined by site-directed mutagenesis. Single-point and cumulative alterations at basic residues within the putative HA-binding motif K189A/K191A/R194A/K197A drastically reduced the HA-binding activity without affecting heparin- or collagen I binding of PEDF. Cumulative alterations at sites critical for heparin binding (K146A/K147A/R149A) decreased HA affinity but not collagen I binding. Thus these clusters of basic residues (BXBXXBXXB and BX3AB2XB motifs) in PEDF are functional regions for binding HA. In the spatial PEDF structure they are located in distinct areas away from the collagen-binding site. The HA-binding activity of PEDF may contribute to deposition in the extracellular matrix and to its reported antitumor/antimetastatic effects.
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PMID:Pigment epithelium-derived factor binds to hyaluronan. Mapping of a hyaluronan binding site. 1880 95

Ophthalmic pediatric regional anesthesia has been widely described, but infrequently used. This review summarizes the available evidence supporting the use of conduction anesthesia in pediatric ophthalmic surgery. Key anatomic differences in axial length, intraocular pressure, and available orbital space between young children and adults impact conduct of ophthalmic regional anesthesia. The eye is near adult size at birth and completes its growth rapidly while the orbit does not. This results in significantly diminished extraocular orbital volumes for local anesthetic deposition. Needle-based blocks are categorized by relation of the needle to the extraocular muscle cone (ie, intraconal or extraconal) and in the cannula-based block, by description of the potential space deep to the Tenon capsule. In children, blocks are placed after induction of anesthesia by a pediatric anesthesiologist or ophthalmologist, via anatomic landmarks or under ultrasonography. Ocular conduction anesthesia confers several advantages for eye surgery including analgesia, akinesia, ablation of the oculocardiac reflex, and reduction of postoperative nausea and vomiting. Short (16 mm), blunt-tip needles are preferred because of altered globe-to-orbit ratios in children. Soft-tip cannulae of varying length have been demonstrated as safe in sub-Tenon blockade. Ultrasound technology facilitates direct, real-time visualization of needle position and local anesthetic spread and reduces inadvertent intraconal needle placement. The developing eye is vulnerable to thermal and mechanical insults, so ocular-rated transducers are mandated. The adjuvant hyaluronidase improves ocular akinesia, decreases local anesthetic dosage requirements, and improves initial block success; meanwhile, dexmedetomidine increases local anesthetic potency and prolongs duration of analgesia without an increase in adverse events. Intraconal blockade is a relative contraindication in neonates and infants, retinoblastoma surgery, and in the presence of posterior staphylomas and buphthalmos. Specific considerations include pertinent pediatric ophthalmologic topics, block placement in the syndromic child, and potential adverse effects associated with each technique. Recommendations based on our experience at a busy academic ophthalmologic tertiary referral center are provided.
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PMID:Regional Anesthesia for Pediatric Ophthalmic Surgery: A Review of the Literature. 3067 53