Global ETD Search

601	ApoE3 mediated poly(butyl) cyanoacrylate nanoparticles containing curcumin: study of enhanced activity of curcumin against beta amyloid induced cytotoxicity using in vitro cell culture model Mulik, R.S., Monkkonen, J., Juvonen, R.O., Mahadik, K.R., Paradkar, Anant R January 2010 (has links) No / Beta amyloid plays a main role in the pathophysiology of Alzheimer's disease by inducing oxidative stress in the brain. Curcumin, a natural antioxidant, is known to inhibit beta amyloid and beta amyloid induced oxidative stress. However, low bioavailability and photodegradation are the major concerns for the use of curcumin. In the present study, we have formulated apolipoprotein E3 mediated poly(butyl) cyanoacrylate nanoparticles containing curcumin (ApoE3-C-PBCA) to provide photostability and enhanced cell uptake of curcumin by targeting. Prepared nanoparticles were characterized for particle size, zeta potential, entrapment efficiency and in vitro drug release. The entrapment of curcumin inside the nanoparticles was confirmed by X-ray diffraction analysis. Physicochemical characterization confirmed the suitability of the method of preparation. The photostability of curcumin was increased significantly in nanoparticles compared to plain curcumin. In vitro cell culture study showed enhanced therapeutic efficacy of ApoE3-C-PBCA against beta amyloid induced cytotoxicity in SH-SY5Y neuroblastoma cells compared to plain curcumin solution. Beta amyloid is known to induce apoptosis in neuronal cells, therefore antiapoptotic activity of curcumin was studied using flow cytometry assays. From all the experiments, it was found that the activity of curcumin was enhanced with ApoE3-C-PBCA compared to plain curcumin solution suggesting enhanced cell uptake and a sustained drug release effect. The synergistic effect of ApoE3 and curcumin was also studied, since ApoE3 also possesses both antioxidant and antiamyloidogenic activity. It was found that ApoE3 did indeed have activity against beta amyloid induced cytotoxicity along with curcumin. Hence, ApoE3-C-PBCA offers great advantage in the treatment of beta amyloid induced cytotoxicity in Alzheimer's disease. Alzheimer disease Amyloid beta-Peptides Apolipoprotein E3 Apoptosis Caspase 3/metabolism Cell cycle Cell line Curcumin Enbucrilate Flow cytometry Humans Models Nanoparticles Polymers Reactive oxygen species X-Ray diffraction REF 2014 Drug therapy Metabolism Physiology Chemistry Drug effects Beta amyloid Tumor Therapeutic use Theoretical Targeted nanoparticles
602	Resveratrol-mediated SIRT-1 interactions with p300 modulate receptor activator of NF-kappaB ligand (RANKL) activation of NF-kappaB signaling and inhibit osteoclastogenesis in bone-derived cells Shakibaei, M., Buhrmann, C., Mobasheri, A. January 2011 (has links) No / Resveratrol is a polyphenolic phytoestrogen that has been shown to exhibit potent anti-oxidant, anti-inflammatory, and anti-catabolic properties. Increased osteoclastic and decreased osteoblastic activities result in bone resorption and loss of bone mass. These changes have been implicated in pathological processes in rheumatoid arthritis and osteoporosis. Receptor activator of NF-kappaB ligand (RANKL), a member of the TNF superfamily, is a major mediator of bone loss. In this study, we investigated the effects of resveratrol on RANKL during bone morphogenesis in high density bone cultures in vitro. Untreated bone-derived cell cultures produced well organized bone-like structures with a bone-specific matrix. Treatment with RANKL induced formation of tartrate-resistant acid phosphatase-positive multinucleated cells that exhibited morphological features of osteoclasts. RANKL induced NF-kappaB activation, whereas pretreatment with resveratrol completely inhibited this activation and suppressed the activation of IkappaBalpha kinase and IkappaBalpha phosphorylation and degradation. RANKL up-regulated p300 (a histone acetyltransferase) expression, which, in turn, promoted acetylation of NF-kappaB. Resveratrol inhibited RANKL-induced acetylation and nuclear translocation of NF-kappaB in a time- and concentration-dependent manner. In addition, activation of Sirt-1 (a histone deacetylase) by resveratrol induced Sirt-1-p300 association in bone-derived and preosteoblastic cells, leading to deacetylation of RANKL-induced NF-kappaB, inhibition of NF-kappaB transcriptional activation, and osteoclastogenesis. Co-treatment with resveratrol activated the bone transcription factors Cbfa-1 and Sirt-1 and induced the formation of Sirt-1-Cbfa-1 complexes. Overall, these results demonstrate that resveratrol-activated Sirt-1 plays pivotal roles in regulating the balance between the osteoclastic versus osteoblastic activity result in bone formation in vitro thereby highlighting its therapeutic potential for treating osteoporosis and rheumatoid arthritis-related bone loss. Animals Bone marrow cells Metabolism Cell line Core binding factor Alpha 1 subunit Genetics Dogs Enzyme inhibitors Pharmacology Humans Mice Multiprotein complexes NF-kappa B Osteoclasts Osteoporosis Drug therapy RANK Ligand Rheumatic fever Signal transduction Drug effects Sirtuin 1 Stilbenes Up-regulation p300-CBP transcription factors REF 2014
603	Curcumin enhances the effect of chemotherapy against colorectal cancer cells by inhibition of NF-kappaB and Src protein kinase signaling pathways Shakibaei, M., Mobasheri, A., Lueders, C., Busch, F., Shayan, P., Goel, A. January 2013 (has links) No / OBJECTIVE: Development of treatment resistance and adverse toxicity associated with classical chemotherapeutic agents highlights the need for safer and effective therapeutic approaches. Herein, we examined the effectiveness of a combination treatment regimen of 5-fluorouracil (5-FU) and curcumin in colorectal cancer (CRC) cells. METHODS: Wild type HCT116 cells and HCT116+ch3 cells (complemented with chromosome 3) were treated with curcumin and 5-FU in a time- and dose-dependent manner and evaluated by cell proliferation assays, DAPI staining, transmission electron microscopy, cell cycle analysis and immunoblotting for key signaling proteins. RESULTS: The individual IC50 of curcumin and 5-FU were approximately 20 microM and 5 microM in HCT116 cells and 5 microM and 1 microM in HCT116+ch3 cells, respectively (p<0.05). Pretreatment with curcumin significantly reduced survival in both cells; HCT116+ch3 cells were considerably more sensitive to treatment with curcumin and/or 5-FU than wild-type HCT116 cells. The IC50 values for combination treatment were approximately 5 microM and 1 microM in HCT116 and 5 microM and 0.1 microM in HCT116+ch3, respectively (p<0.05). Curcumin induced apoptosis in both cells by inducing mitochondrial degeneration and cytochrome c release. Cell cycle analysis revealed that the anti-proliferative effect of curcumin and/or 5-FU was preceded by accumulation of CRC cells in the S cell cycle phase and induction of apoptosis. Curcumin potentiated 5-FU-induced expression or cleavage of pro-apoptotic proteins (caspase-8, -9, -3, PARP and Bax), and down-regulated anti-apoptotic (Bcl-xL) and proliferative (cyclin D1) proteins. Although 5-FU activated NF-kappaB/PI-3K/Src pathway in CRC cells, this was down-regulated by curcumin treatment through inhibition of IkappaBalpha kinase activation and IkappaBalpha phosphorylation. CONCLUSIONS: Combining curcumin with conventional chemotherapeutic agents such as 5-FU could provide more effective treatment strategies against chemoresistant colon cancer cells. The mechanisms involved may be mediated via NF-kappaB/PI-3K/Src pathways and NF-kappaB regulated gene products. Antineoplastic agents Therapeutic use Apoptosis Drug effects Blotting Western Cell line Tumor Colorectal neoplasms Drug therapy Enzymology Metabolism Pathology Curcumin Pharmacology Drug synergism Fluorouracil Humans Microscopy Electron Transmission NF-kappa B Antagonists & inhibitors Signal transduction src-Family Kinases REF 2014
604	Antitumor activity of a duocarmycin analogue rationalized to be metabolically activated by cytochrome P450 1A1 in human transitional cell carcinoma of the bladder Sutherland, Mark, Gill, Jason H., Loadman, Paul, Laye, Jonathan P., Sheldrake, Helen M., Illingworth, Nicola A., Alandas, Mohammed N., Cooper, Patricia A., Searcey, M., Pors, Klaus, Shnyder, Steven, Patterson, Laurence H. 01 October 2012 (has links) No / We identify cytochrome P450 1A1 (CYP1A1) as a target for tumor-selective drug development in bladder cancer and describe the characterization of ICT2700, designed to be metabolized from a prodrug to a potent cytotoxin selectively by CYP1A1. Elevated CYP1A1 expression was shown in human bladder cancer relative to normal human tissues. RT112 bladder cancer cells, endogenously expressing CYP1A1, were selectively chemosensitive to ICT2700, whereas EJ138 bladder cells that do not express CYP1A1 were significantly less responsive. Introduction of CYP1A1 into EJ138 cells resulted in 75-fold increased chemosensitivity to ICT2700 relative to wild-type EJ138. Negligible chemosensitivity was observed in ICT2700 in EJ138 cells expressing CYP1A2 or with exposure of EJ138 cells to CYP1B1- or CYP3A4-generated metabolites of ICT2700. Chemosensitivity to ICT2700 was also negated in EJ138-CYP1A1 cells by the CYP1 inhibitor alpha-naphthoflavone. Furthermore, ICT2700 did not induce expression of the AhR-regulated CYP1 family, indicating that constitutive CYP1A1 expression is sufficient for activation of ICT2700. Consistent with the selective activity by CYP1A1 was a time and concentration-dependent increase in gamma-H2AX protein expression, indicative of DNA damage, associated with the activation of ICT2700 in RT112 but not EJ138 cells. In mice-bearing CYP1A1-positive and negative isogenic tumors, ICT2700 administration resulted in an antitumor response only in the CYP1A1-expressing tumor model. This antitumor response was associated with detection of the CYP1A1-activated metabolite in tumors but not in the liver. Our findings support the further development of ICT2700 as a tumor-selective treatment for human bladder cancers. Animals Antineoplastic agents Biotransformation CHO cells Carcinoma Cell line Tumor Cell survival Cricetinae Cytochrome P-450 CYP1A1 Female Gene expression Humans Indoles Liver Maximum tolerated dose Mice Inbred BALB C Microsomes Pyrroles Tumor burden Urinary bladder neoplasms Xenograft model antitumor assays REF 2014 Metabolism Pharmacokinetics Pharmacology Transitional cell Drug therapy Enzymology Pathology Genetics
605	Patient and other factors influencing the prescribing of cardiovascular prevention therapy in the general practice setting with and without nurse assessment Mohammed, Mohammed A., El Sayed, C., Marshall, T. January 2012 (has links) No / Although guidelines indicate when patients are eligible for antihypertensives and statins, little is known about whether general practitioners (GPs) follow this guidance. To determine the factors influencing GPs decisions to prescribe cardiovascular prevention drugs. DESIGN OF STUDY: Secondary analysis of data collected on patients whose cardiovascular risk factors were measured as part of a controlled study comparing nurse-led risk assessment (four practices) with GP-led risk assessment (two practices). SETTING: Six general practices in the West Midlands, England. PATIENTS: Five hundred patients: 297 assessed by the project nurse, 203 assessed by their GP. MEASUREMENTS: Cardiovascular risk factor data and whether statins or antihypertensives were prescribed. Multivariable logistic regression models investigated the relationship between prescription of preventive treatments and cardiovascular risk factors. RESULTS: Among patients assessed by their GP, statin prescribing was significantly associated only with a total cholesterol concentration >/= 7 mmol/L and antihypertensive prescribing only with blood pressure >/= 160/100 mm Hg. Patients prescribed an antihypertensive by their GP were five times more likely to be prescribed a statin. Among patients assessed by the project nurse, statin prescribing was significantly associated with age, sex, and all major cardiovascular risk factors. Antihypertensive prescribing was associated with blood pressures >/= 140/90 mm Hg and with 10-year cardiovascular risk. LIMITATIONS: Generalizability is limited, as this is a small analysis in the context of a specific cardiovascular prevention program. CONCLUSIONS: GP prescribing of preventive treatments appears to be largely determined by elevation of a single risk factor. When patients were assessed by the project nurse, prescribing was much more consistent with established guidelines. Adult Aged Antihypertensive agents Cardiovascular diseases Drug therapy Nursing Prevention & control Communication Confidence intervals Decision making England Female General Practitioners Humans Logistic models Male Middle aged Nursing diagnosis Odds ratio Physician's practice patterns Physician-patient relations Practice guidelines as topic Prescribing Primary health care Risk assessment REF 2014

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