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Deepak Reddy Gade, Amareswararao Makkapati, Rajesh Babu Yarlagadda, Godefridus J Peters, B S Sastry, V V S Rajendra Prasad
Overexpression of P-glycoprotein (P-gp) leads to the emergence of multidrug resistance (MDR) in cancer treatment. Acridones have the potential to reverse MDR and sensitize cells. In the present study, we aimed to elucidate the chemosensitization potential of acridones by employing various molecular modelling techniques. Pharmacophore modeling was performed for the dataset of chemosensitizing acridones earlier proved for cytotoxic activity against MCF7 breast cancer cell line. Gaussian-based QSAR studies also performed to predict the favored and disfavored region of the acridone molecules...
February 24, 2018: Computational Biology and Chemistry
Suzanne Grant, Bruce Guthrie
Patient safety is an increasing concern for health systems internationally. The majority of administrative work in UK general practice takes place in the context of organisational routines such as repeat prescribing and test results handling, where high workloads and increased clinician dependency on administrative staff have been identified as an emerging safety issue. Despite this trend, most research to date has focused on the redistribution of the clinical workload between doctors, nurses and allied health professionals within individual care settings...
March 2, 2018: Social Science & Medicine
Marcela Ewing, Peter Naredi, Chenyang Zhang, Jörgen Månsson
Background: Many patients with common cancers are late diagnosed. Objectives: Identify consultation profiles and clinical features in patients with the seven most common cancers, who had consulted a general practitioner (GP) frequently before their cancer diagnosis. Methods: A case-control study was conducted in Region Västra Götaland, Sweden. A total of 2570 patients, diagnosed in 2011 with prostate, breast, colorectal, lung, gynaecological and skin cancers including malignant melanoma, and 9424 controls were selected from the Swedish Cancer Register and a regional health care database...
March 13, 2018: Family Practice
Milad Moloudizargari, Esmaeil Mortaz, Mohammad Hossein Asghari, Ian M Adcock, Frank A Redegeld, Johan Garssen
Omega-3 polyunsaturated fatty acids (PUFAs) have well established anti-cancer properties. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are among this biologically active family of macromolecules for which various anti-cancer effects have been explained. These PUFAs have a high safety profile and can induce apoptosis and inhibit growth of cancer cells both in vitro and in vivo , following a partially selective manner. They also increase the efficacy of chemotherapeutic agents by increasing the sensitivity of different cell lines to specific anti-neoplastic drugs...
February 20, 2018: Oncotarget
Yaming Xi, Zhuanzhen Ma, Hao Zhang, Maowen Yuan, Lina Wang
The aim of the present study was to investigate the cytotoxic effect and multi-drug resistance (MDR) of Clostridium difficile toxin A (TcdA) on K562/A02 cells, and understand its underlying molecular pathways. K562/A02 cells were treated with TcdA at different concentrations for 24, 48 and 72 h, and the inhibition effect and drug resistance of TcdA on K562/A02 cell proliferation was assessed by methyl thiazolyl tetrazolium colorimetric assay. Furthermore, cell cycle-apoptosis was analyzed by flow cytometry, P-glycoprotein (P-gp) expression was determined by western blot analysis and caspase-3 activity was measured using a caspase-3 activity kit...
April 2018: Oncology Letters
María Paula Ceballos, Giulia Decándido, Ariel Darío Quiroga, Carla Gabriela Comanzo, Verónica Inés Livore, Florencia Lorenzetti, Flavia Lambertucci, Lorena Chazarreta-Cifre, Claudia Banchio, María de Luján Alvarez, Aldo Domingo Mottino, María Cristina Carrillo
Sirtuins (SIRTs) 1 and 2 deacetylases are overexpressed in hepatocellular carcinoma (HCC) and are associated with tumoral progression and multidrug resistance (MDR). In this study we analyzed whether SIRTs 1 and 2 activities blockage was able to affect cellular survival and migration and to modulate p53 and FoxO1 acetylation in HepG2 and Huh7 cells. Moreover, we analyzed ABC transporters P-glycoprotein (P-gp) and multidrug resistance-associated protein 3 (MRP3) expression. We used cambinol and EX-527 as SIRTs inhibitors...
March 12, 2018: Toxicology Letters
Annebel R De Vleeschauwer, Xiaocui Zhou, David J Lefebvre, Annabelle Garnier, Fleur Watier, Charly Pignon, Sandrine A Lacour, Stephan Zientara, Labib Bakkali-Kassimi, Kris De Clercq, Bernard Klonjkowski
Vaccination is a key element in the control of foot-and-mouth disease (FMD). The majority of the antigenic sites that induce protective immune responses are localized on the FMD virus (FMDV) capsid that is formed by four virus-encoded structural proteins, VP1 to VP4. In the present study, recombinant canine adenovirus type 2 (CAV2)-based FMD vaccines, Cav-P1/3C R° and Cav-VP1 R°, respectively expressing the structural P1 precursor protein along with the non-structural 3C protein or expressing the structural VP1 protein of the FMDV strain O/FRA/1/2001, were evaluated as novel vaccines against FMD...
March 12, 2018: Vaccine
Samuel Johnson, Sharmala Thuraisingam, John Furler, Jo-Anne Manski Nankervis
Insulin initiation is often delayed in primary care partly because of clinician concerns about the additional clinical work. This study describes health services usage (HSU) pre- and post-insulin initiation in people with type 2 diabetes and out-of-target glycaemic levels. Secondary analysis of participant data from the Stepping Up randomised controlled trial of a model of care for insulin initiation in general practice was undertaken. For 142 people who commenced insulin, HSU in the 6 months prior was compared to that in the 12 months following insulin initiation...
March 16, 2018: Australian Journal of Primary Health
Wen-Zhao Sun, Dan-Dan Zhang, Ying-Lin Peng, Li Chen, De-Hua Kang, Bin Wang, Xiao-Wu Deng
BACKGROUND: Conventional phantom-based planar dosimetry (2D-PBD) quality assurance (QA) using gamma pass rate (GP (%)) is inadequate to reflect clinically relevant dose error in intensity-modulated radiation therapy (IMRT), owing to a lack of information regarding patient anatomy and volumetric dose distribution. This study aimed to evaluate the dose distribution accuracy of IMRT delivery for nasopharyngeal carcinoma (NPC), which passed the 2D-PBD verification, using a measurement-guided 3D dose reconstruction (3D-MGR) method...
March 15, 2018: Radiation Oncology
John K Fallon, Nicole Houvig, Catherine L Booth-Genthe, Philip C Smith
Information is needed on the expression of transporters in lung to inform drug development and therapeutic decisions. Much of the information currently available is from semiquantitative gene expression or immunometric densitometry studies reported in the literature. NanoLC-MS/MS (MRM mode) isotope dilution targeted quantitative proteomics was used here to quantify twelve selected transporters in fresh human lung membrane fraction samples and in the membrane fraction of selected immortalized human lung epithelial cell line samples...
February 22, 2018: Journal of Pharmaceutical and Biomedical Analysis
Kimberley Lau, Joseph Wilkinson, Ram Moorthy
OBJECTIVE: Following the announcement of the NHS Cancer Plan in 2000, anyone suspected of having cancer has to be seen by a specialist within two weeks of referral. Since this introduction, studies have shown that only 6.3-14.6% of 2-week referrals were diagnosed with a head and neck cancer and that majority of the cancer diagnoses were via other referral routes. These studies suggest that the referral scheme is not currently cost effective. Our aim is to develop a scoring system that determines the risk of head and neck cancer in a patient, which can then be used to aid GP referrals...
March 15, 2018: Clinical Otolaryngology
J H C de Roo, T M Bosch, A van Rhijn, R Del Canho
BACKGROUND: Medication is not always delivered in a safe dosing format. Up to 33% of medication errors can be attributed to confusing packaging or labelling. CASE DESCRIPTION: A 6-year-old boy with ADHD, for which he was being treated with methylphenidate and pipamperone drops, was brought to the A&E department with signs of severe encephalopathy. He had apparently been given pipamperone in streams rather than in drops in the previous months. The pipamperone level in his blood was raised to toxic levels...
2018: Nederlands Tijdschrift Voor Geneeskunde
Hiroyuki Hattori, Kosei Yamauchi, Siaw Onwona-Agyeman, Thoru Mitsunaga
BACKGROUND: Grains of Paradise (GP) is the seed of Aframomum melegueta, which is widely distributed throughout West Africa and has been used as a spice and a folk remedy for a long time. The anti-obesity effect by GP intake was demonstrated in our previous report. In this present study, we tried to isolate some compounds in GP and clarify the anti-obesity mechanism. RESULTS: Ten vanilloid compounds were determined. Among ten vanilloids, 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-ol and 1-(4'-hydroxy-3'-methoxyphenyl)-3-octen-5-one were determined as novel compounds and 6-gingerol, 6-paradol, and 6-shogaol were identified as the major constituents in GP extract...
March 15, 2018: Journal of the Science of Food and Agriculture
Helen Benson, Cherie Lucas, Walter Kmet, Shalom I Benrimoj, Kylie Williams
Background Team based care has been used internationally to improve the delivery of best practice primary health care. The WentWest General Practice Pharmacist Project, involving the integration of pharmacists within general practice teams, was commissioned to improve medication management of general practice patients. A particular focus of the project was the performance of medication review to allow the detection and resolution of drug related problems (DRPs). Objective The objectives of this 6-month study (October 2016-March 2017) were to: (1) identify and classify the DRPs detected as a result of pharmacist activities within a general practice primary care setting...
March 14, 2018: International Journal of Clinical Pharmacy
Suzanne M Beecher, Cillian Keogh, Claragh Healy
INTRODUCTION: General practitioners (GPs) require the necessary skills to identify potentially malignant skin lesions and refer patients in an appropriate and timely manner. We examined the impact of a single consultant delivered education session to GP trainees on their diagnosis of common skin lesions. METHODS: A prospective analysis of baseline knowledge was assessed using a photographic questionnaire. A dedicated education session was delivered by a consultant plastic surgeon...
March 14, 2018: Irish Journal of Medical Science
Robert Munashe Maweni, Nicholas Sunderland, Zahra Rahim, Emmanuella Odih, Jins Kallampallil, Thomas Saunders, Srikanth Akunuri
BACKGROUND: Hypertensive urgency is defined as a severely elevated systolic blood pressure (SBP) of ≥ 180 mmHg and/or diastolic blood pressure (DBP) of ≥ 120 mmHg, in the absence of end organ damage. It is known that there are racial differences in prevalence and severity of hypertension but there is a dearth of studies looking at hypertensive urgency in Black populations living in Europe. AIMS: We sought to define the clinical characteristics of Black patients presenting with hypertensive urgency, in order to better define the risks and complications this growing population of patients faces...
March 14, 2018: Irish Journal of Medical Science
Burak Ozgür, Lasse Saaby, Kristine Langthaler, Birger Brodin
The presented data are related to the research article entitled "Characterization of the IPEC-J2 MDR1 (iP-gp) cell line as a tool for identification of P-gp substrates" by Ozgur et al. (2017) [1]. This data report describes the challenges of investigating the concentration-dependent transport of P-glycoprotein (P-gp) substrates with relatively low aqueous solubility. Thus, we provide solubility data on two prototypical P-gp substrates, digoxin and rhodamine 123, representing P-gp substrates with a relatively low- and high-aqueous solubility, respectively...
February 2018: Data in Brief
Haruhiko Tokuda, Gen Kuroyanagi, Takashi Onuma, Yukiko Enomoto, Tomoaki Doi, Hiroki Iida, Takanobu Otsuka, Shinji Ogura, Toru Iwama, Kumi Kojima, Osamu Kozawa
It has been previously reported that HSP27 is released from platelets in type 2 diabetes mellitus (DM) patients according to phosphorylation. In the present study, we investigated the effect of ristocetin, a glycoprotein (GP)Ib/IX/V activator, on the release of HSP27 and the effect of anti-platelet agents, such as acetylsalicylic acid (ASA), on this release. Forty-six patients with type 2 DM were recruited, and classified into two groups depending on administration of anti-platelet agents, resulting in 31 patients without these agents (control group) and 15 patients with them (anti-platelet group)...
April 2018: Biomedical Reports
Hyun-Jung Moon, Hak-Bong Kim, Su-Hoon Lee, So-Eun Jeun, Chi-Dug Kang, Sun-Hee Kim
NSAIDs (non-steroidal anti-inflammatory drugs) have potential use as anticancer agents, either alone or in combination with other cancer therapies. We found that NSAIDs including celecoxib (CCB) and ibuprofen (IBU) significantly potentiated the cytotoxicity of Hsp90 inhibitors in human multidrug-resistant (MDR) cells expressing high levels of mutant p53 (mutp53) protein and P-glycoprotein (P-gp), and reversed Hsp90 inhibitor resistance caused by activation of heat shock factor 1 (HSF1) and by up-regulation of heat shock proteins (Hsps) and P-gp...
February 16, 2018: Oncotarget
Chao Liu, Quan Gong, Ting Chen, Juan Lv, Zhiping Feng, Pengjie Liu, Zhiyong Deng
Multidrug resistance (MDR) is an obstacle for cancer chemotherapy. It was reported that 20(S)-ginsenoside Rg3 (hereafter Rg3) was able to regulate MDR in mouse leukemia cells. The present study investigated the effect of Rg3 on the MDR of A549 lung cancer cells. A cell viability assay revealed that Rg3 treatment increased cisplatin (DDP) cytotoxicity in DDP resistant A549 cells (A549/DDP). Furthermore, Rg3 increases the antitumor effect of DDP on A549/DDP xenograft mice. The expression of MDR-mediated proteins, including P-glycoprotein (P-gp), multidrug resistance-associated protein (MPR1) and lung resistance protein 1 (LPR1), was detected in tumor tissue of A549/DDP xenograft mice...
April 2018: Oncology Letters
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