Vinorelbine Inhibits Angiogenesis and 95D Migration via Reducing Hypoxic Fibroblast Stromal Cell-Derived Factor 1 Secretion.

Vinorelbine inhibits angiogenesis and 95D migration via reducing hypoxic fibroblast stromal cell-derived factor 1 secretion.

Filed under: Drug and Alcohol Rehabilitation

Exp Biol Med (Maywood). 2012 Sep 3;
Fang D, Sun L, Lin S, Zhou L, Su N, Yuan S, Yu B

Tumor stroma plays a prominent role in cancer progression. Fibroblasts constitute a majority of the stromal cells in tumor, and yet the functional contributions of these cells to tumor angiogenesis and invasion are poorly understood, especially the anticancer drug interference to these processes. To estimate the effects of vinorelbine (VNR) on fibroblast-associated tumor invasion and angiogenesis, we evaluated the response of 95D and human umbilical vein endothelial cell (HUVEC) migration, tube formation in vitro, as well as capillary formation of rat thoracic aorta rings to hypoxic MRC-5 conditioned medium (CM) by VNR pretreatment. Our results demonstrated that VNR significantly inhibited 95D and HUVEC migration and angiogenesis induced by hypoxic MRC-5 cells. We also showed that hypoxic MRC-5 CM (Hypo-CM) had a higher level of stromal cell-derived factor 1 (SDF-1) secretion, while Hypo-CM up-regulated the CXCR4 expression in HUVECs and 95Ds. This increased activity of SDF-1/CXCR4 paracrine was clearly attenuated by VNR pretreatment. It was further found that pretreating HUVECs and 95Ds with AMD3100, a CXCR4 antagonist, markedly reversed the Hypo-CM promoting cell migration and angiogenesis, while adding exogenous SDF-1 attenuated the inhibition effects of CM collected from VNR-pretreated hypoxic MRC-5 (Hypo-CMV). These data indicate that VNR indirectly decreased 95D migration and angiogenesis through its effect on hypoxic MRC-5, via impacting SDF-1/CXCR4 paracrine, suggesting that VNR could interrupt the influence of fibroblasts on HUVECs and 95Ds to exert an anticancer role. Therefore, fibroblasts should be taken into consideration when evaluating and developing anticancer drugs.
HubMed – drug


Addressing patient alcohol use: a view from general practice.

Filed under: Drug and Alcohol Rehabilitation

J Prim Health Care. 2012; 4(3): 217-22
Mules T, Taylor J, Price R, Walker L, Singh B, Newsam P, Palaniyappan T, Snook T, Ruselan M, Ryan J, Santhirasegaran J, Shearman P, Watson P, Zino R, Signal L, Fougere G, Moriarty H, Jenkin G

General practitioners (GPs) have the potential to promote alcohol harm minimisation via discussion of alcohol use with patients, but knowledge of GPs’ current practice and attitudes on this matter is limited. Our aim was to assess GPs’ current practice and attitudes towards discussing alcohol use with their patients.This qualitative study involved semi-structured, face-to-face interviews with 19 GPs by a group of medical students in primary care practices in Wellington, New Zealand.Despite agreement amongst GPs about the importance of their role in alcohol harm minimisation, alcohol was not often raised in patient consultations. GPs’ usual practice included referral to drug and alcohol services and advice. GPs were also aware of national drinking guidelines and alcohol screening tools, but in practice these were rarely utilised. Key barriers to discussing alcohol use included its societal ‘taboo’ nature, time constraints, and perceptions of patient dishonesty.In this study there is a fundamental mismatch between the health community’s expectations of GPs to discuss alcohol with patients and the reality. Potential solutions to the most commonly identified barriers include screening outside the GP consultation, incorporating screening tools into existing software used by GPs, exploring with GPs the social stigma associated with alcohol misuse, and framing alcohol misuse as a health issue. As it is unclear if these approaches will change GP practice, there remains scope for the development and pilot testing of potential solutions identified in this research, together with an assessment of their efficacy in reducing hazardous alcohol consumption.
HubMed – drug


Vasostatin increases oxygenation of B16-F10 melanoma tumors and raises therapeutic efficacy of cyclophosphamide.

Filed under: Drug and Alcohol Rehabilitation

Acta Biochim Pol. 2012 Sep 3;
Cicho? T, Jarosz M, Smolarczyk R, Ogórek B, Matuszczak S, Wagner M, Mitrus I, Sochanik A, Jazowiecka-Rakus J, Szala S

One of the preconditions of effective anticancer therapy is efficient transfer of the therapeutic agent (chemotherapeutic) to tumor cells. Fundamental barriers making drug delivery and action difficult include underoxygenation, elevated interstitial pressure, poor and abnormal tumor blood vascular network and acidic tumor milieu. In this study we aimed at developing an optimized scheme of administering a combination of an angiogenesis-inhibiting drug (vasostatin) and a chemotherapeutic (cyclophosphamide) in the therapeutic treatment of mice bearing experimental B16-F10 melanoma tumors. We report that the strongest tumor growth inhibition was observed in mice that received two, three or four vasostatin doses in combination with one injection of cyclophosphamide (i.e., V2 + CTX, V3 + CTX or V4 + CTX schemes). Double administration of vasostatin increases oxygenation of B16-F10 tumors. On the other hand, its five-fold administration lowers tumor oxygenation, breaks down tumor vascular network (increasing hypoxia) and leads in consequence to death of cancer cells and appearance of necrotic areas in the tumor. A decreased cyclophosphamide dose in combination with two doses of vasostatin (V2 + CTX scheme) inhibits tumor growth similarly to a larger dose of cyclophosphamide alone.
HubMed – drug


Managing patients with multimorbidity: systematic review of interventions in primary care and community settings.

Filed under: Drug and Alcohol Rehabilitation

BMJ. 2012; 345: e5205
Smith SM, Soubhi H, Fortin M, Hudon C, O’Dowd T

To determine the effectiveness of interventions designed to improve outcomes in patients with multimorbidity in primary care and community settings.Systematic review.Medline, Embase, CINAHL, CAB Health, Cochrane central register of controlled trials, the database of abstracts of reviews of effectiveness, and the Cochrane EPOC (effective practice and organisation of care) register (searches updated in April 2011). ELIGIBILITY CRITERIA: Randomised controlled trials, controlled clinical trials, controlled before and after studies, and interrupted time series analyses reporting on interventions to improve outcomes for people with multimorbidity in primary care and community settings. Multimorbidity was defined as two or more chronic conditions in the same individual. Outcomes included any validated measure of physical or mental health and psychosocial status, including quality of life outcomes, wellbeing, and measures of disability or functional status. Also included were measures of patient and provider behaviour, including drug adherence, utilisation of health services, acceptability of services, and costs.Two reviewers independently assessed studies for eligibility, extracted data, and assessed study quality. As meta-analysis of results was not possible owing to heterogeneity in participants and interventions, a narrative synthesis of the results from the included studies was carried out.10 studies examining a range of complex interventions totalling 3407 patients with multimorbidity were identified. All were randomised controlled trials with a low risk of bias. Two studies described interventions for patients with specific comorbidities. The remaining eight studies focused on multimorbidity, generally in older patients. Consideration of the impact of socioeconomic deprivation was minimal. All studies involved complex interventions with multiple components. In six of the 10 studies the predominant component was a change to the organisation of care delivery, usually through case management or enhanced multidisciplinary team work. In the remaining four studies, intervention components were predominantly patient oriented. Overall the results were mixed, with a trend towards improved prescribing and drug adherence. The results indicated that it is difficult to improve outcomes in this population but that interventions focusing on particular risk factors in comorbid conditions or functional difficulties in multimorbidity may be more effective. No economic analyses were included, although the improvements in prescribing and risk factor management in some studies could provide potentially important cost savings.Evidence on the care of patients with multimorbidity is limited, despite the prevalence of multimorbidity and its impact on patients and healthcare systems. Interventions to date have had mixed effects, although are likely to be more effective if targeted at risk factors or specific functional difficulties. A need exists to clearly identify patients with multimorbidity and to develop cost effective and specifically targeted interventions that can improve health outcomes.
HubMed – drug


3,4-Dimethoxyphenyl bis-benzimidazole, a novel DNA topoisomerase inhibitor that preferentially targets Escherichia coli topoisomerase I.

Filed under: Drug and Alcohol Rehabilitation

J Antimicrob Chemother. 2012 Sep 3;
Bansal S, Sinha D, Singh M, Cheng B, Tse-Dinh YC, Tandon V

OBJECTIVES: Antibiotic resistance in bacterial pathogens is a serious clinical problem. Novel targets are needed to combat increasing drug resistance in Escherichia coli. Our objective is to demonstrate that 2-(3,4-dimethoxyphenyl)-5-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2yl]-1H-benzimidazole (DMA) inhibits E. coli DNA topoisomerase I more strongly than human topoisomerase I. In addition, DMA is non-toxic to mammalian cells at antibiotic dosage level. METHODS: In the present study, we have established DMA as an antibacterial compound by determining MICs, post-antibiotic effects (PAEs) and MBCs for different standard as well as clinical strains of E. coli. We have described the differential catalytic inhibitory mechanism of bis-benzimidazole, DMA, for human and E. coli topoisomerase I and topoisomerase II by performing different assays, including relaxation assays, cleavage-religation assays, DNA unwinding assays, ethidium bromide displacement assays, decatenation assays and DNA gyrase supercoiling assays. RESULTS: DMA significantly inhibited bacterial growth at a very low concentration, but did not affect human cell viability at higher concentrations. Activity assays showed that it preferentially targeted E. coli topoisomerase I over human topoisomerase I, topoisomerase II and gyrase. Cleavage-religation assays confirmed DMA as a poison inhibitor of E. coli topoisomerase I. This study illuminates new properties of DMA, which may be further modified to develop an efficient topoisomerase inhibitor that is selective towards bacterial topoisomerase I. CONCLUSIONS: This is the first report of a bis-benzimidazole acting as an E. coli topoisomerase I inhibitor. DMA is a safe, non-cytotoxic molecule to human cells at concentrations that are needed for antibacterial activity.
HubMed – drug



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Oakland rehab center for women faces eviction

Filed under: Drug and Alcohol Rehabilitation

An Oakland treatment center for women battling drug and alcohol addiction is facing eviction this week. Officials at Serenity House, located on San Pablo Avenue, said they have until Wednesday to pay $ 12,000 in back rent or be forced out. Serenity …
Read more on KTVU San Francisco


New drug, Vivitrol, helped woman finally kick her addiction

Filed under: Drug and Alcohol Rehabilitation

Vivitrol is the newest weapon in the war against the growing problem of opiate addiction, approved for that purpose by the Food and Drug Administration in 2010 after being OK'd for alcohol dependence in 2006. … I tried doctors, therapists, rehab. I …
Read more on Pittsburgh Post Gazette


Should Cannabis be Legalised?

Filed under: Drug and Alcohol Rehabilitation

As regards the damage to young brains, the chairman of the alcohol and drug rehab clinic where I work, Peter McCann, recently told me that "the male brain doesn't stop developing until the age of 28 so I don't see why it is only teenage brains that are …
Read more on Huffington Post UK (blog)


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