Home About us Contact
|
Home About us Contact | ||
|
|
||
Combination Strategies (combination + strategy)
Selected AbstractsChemInform Abstract: Synthesis of Enantiomerically Pure Cycloalkenols via Combination Strategy of Enzyme-Catalyzed Reaction and RCM Reaction.CHEMINFORM, Issue 14 2008Han Shi-Hui Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Review article: gene therapy, recent developments and future prospects in gastrointestinal oncologyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2010Y. Touchefeu Aliment Pharmacol Ther 2010; 32: 953,968 Summary Background, Gene therapy consists of the introduction of genetic material into cells for a therapeutic purpose. A wide range of gene therapy vectors have been developed and used for applications in gastrointestinal oncology. Aim, To review recent developments and published clinical trials concerning the application of gene therapy in the treatment of liver, colon and pancreatic cancers. Methods, Search of the literature published in English using the PubMed database. Results, A large variety of therapeutic genes are under investigation, such as tumour suppressor, suicide, antiangiogenesis, inflammatory cytokine and micro-RNA genes. Recent progress concerns new vectors, such as oncolytic viruses, and the synergy between viral gene therapy, chemotherapy and radiation therapy. As evidence of these basic developments, recently published phase I and II clinical trials, using both single agents and combination strategies, in adjuvant or advanced disease settings, have shown encouraging results and good safety records. Conclusions, Cancer gene therapy is not yet indicated in clinical practice. However, basic and clinical advances have been reported and gene therapy is a promising, new therapeutic approach for the treatment of gastrointestinal tumours. [source] Antimalarial drugs , host targets (re)visitedBIOTECHNOLOGY JOURNAL, Issue 3 2006Margarida Cunha-Rodrigues Abstract Every year, forty percent of the world population is at risk of contracting malaria. Hopes for the erradication of this disease during the 20th century were dashed by the ability of Plasmodium falciparum, its most deadly causative agent, to develop resistance to available drugs. Efforts to produce an effective vaccine have so far been unsuccessful, enhancing the need to develop novel antimalarial drugs. In this review, we summarize our knowledge concerning existing antimalarials, mechanisms of drug-resistance development, the use of drug combination strategies and the quest for novel anti-plasmodial compounds. We emphasize the potential role of host genes and molecules as novel targets for newly developed drugs. Recent results from our laboratory have shown Hepatocyte Growth Factor/MET signaling to be essential for the establishment of infection in hepatocytes. We discuss the potential use of this pathway in the prophylaxis of malaria infection. [source] Phase II study of the histone deacetylase inhibitor MGCD0103 in patients with previously treated chronic lymphocytic leukaemiaBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2009Kristie A. Blum Summary MGCD0103, an orally available class I histone deacetylase (HDAC) inhibitor, was examined for pre-clinical activity in chronic lymphocytic leukaemia (CLL). A phase II clinical trial was performed, starting at a dose of 85 mg/d, three times per week. Dose escalation to 110 mg or the addition of rituximab was permitted in patients without a response after two or more cycles. MGCD0103 demonstrated pre-clinical activity against CLL cells with a LC50 (concentration lethal to 50%) of 0·23 ,mol/l and increased acetylation of the HDAC class I specific target histone H3. Twenty-one patients received a median of two cycles of MGCD0103 (range, 0,12). All patients had previously received fludarabine, 33% were fludarabine refractory, and 71% had del(11q22·3) or del(17p13·1). No responses according to the National Cancer Institutes 1996 criteria were observed. Three patients received 110 mg and four patients received concomitant rituximab, with no improvement in response. Grade 3,4 toxicity consisted of infections, thrombocytopenia, anaemia, diarrhoea, and fatigue. HDAC inhibition was observed in six out of nine patients on day 8. Limited activity was observed with single agent MGCD0103 in high risk patients with CLL. Future investigations in CLL should focus on broad HDAC inhibition, combination strategies, and approaches to diminish constitutional symptoms associated with this class of drugs. [source] A randomized clinical trial of energy conservation for patients with cancer-related fatigueCANCER, Issue 6 2004Andrea M. Barsevick D.N.Sc. Abstract BACKGROUND The efficacy of energy conservation and activity management (ECAM) for fatigue reduction and maintenance of functional performance has never been evaluated in adults with cancer who are undergoing treatment. METHODS A randomized clinical trial compared an ECAM intervention with a control intervention focused on nutrition. Individuals initiating chemotherapy, radiotherapy, or concurrent therapy for cancer were randomized to receive either the semistructured ECAM intervention (n = 200) or the control intervention (n = 196). Participants in each group participated in 3 telephone sessions with an oncology nurse during the first 5 weeks of treatment. Data on fatigue and limitation of functioning were obtained before cancer treatment and at two follow-up points that coincided with times of high fatigue for each type of treatment. The outcomes of interest included perception of fatigue and functional performance. RESULTS A repeated-measures analysis of covariance using the type of cancer treatment as a covariate revealed a significant study group,by-time interaction indicating that the ECAM group experienced a greater decrease in fatigue over time compared with the control group (F2,544 = 4.5; P = 0.01). The intervention was not associated with changes in overall functional performance. CONCLUSIONS Individuals who received the ECAM intervention derived a modest but significant benefit from it. To achieve a more robust clinical benefit from the intervention, it may be necessary to manage other key symptoms in addition to fatigue. Research is needed to examine symptom clusters or combinations associated with negative outcomes as well as combination strategies for symptom management. Cancer 2004. © 2004 American Cancer Society. [source] Interpreting clinical trials of diabetic dyslipidaemia: new insightsDIABETES OBESITY & METABOLISM, Issue 3 2009A. S. Wierzbicki Current treatment guidelines highlight the importance of aggressive lipid-modifying therapy in reducing cardiovascular risk in patients with type 2 diabetes. Statins are established as the cornerstone of dyslipidaemia management in diabetic patients, based on their efficacy in lowering levels of low-density lipoprotein cholesterol (LDL-C). However, statins fail to address the high residual cardiovascular risk in treated patients, some of which may be attributable to low HDL cholesterol (HDL-C) and elevated triglycerides and to a preponderance of small, dense LDL particles, indicating the need for further intervention. Fibrates are effective against all components of atherogenic dyslipidaemia associated with type 2 diabetes. Clinical studies, most notably the Fenofibrate Intervention and Event Lowering in Diabetes, indicate that fibrates, most likely in combination with a statin, have a secondary role in reducing cardiovascular risk in patients with type 2 diabetes, particularly in those without prior cardiovascular disease or patients with low HDL-C. Results are awaited from the ongoing Action to Control Cardiovascular Risk in Diabetes trial to fully evaluate the outcome benefits of this combination strategy. [source] Pro-apoptotic therapy with the oligonucleotide GenasenseTM (oblimersen sodium) targeting Bcl-2 protein expression enhances the biological anti-tumour activity of rituximabBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2004Jeyanthi Ramanarayanan Summary New strategies have evolved in the treatment of patients with non-Hodgkin's lymphoma (NHL). Anti-sense oligonucleotides (ASO) and monoclonal antibody (mAb) therapy, though proven to be safe and effective, have not demonstrated to be curative when used as single agents. We tested an innovative combination strategy involving various mAbs and ASO against Bcl-2 (G3139) in aggressive preclinical models. G3139, under optimal transfection conditions, decreased the proliferation rate of lymphoma cells by 60,75% when compared with controls. In addition, apoptosis was demonstrated in Raji (25%) and DHL-4 cells (30%) treated with Genasense following downregulation of Bcl-2 protein. Downregulation of Bcl-2 by G3139 was associated with a higher degree of rituximab-associated, complement-mediated cytotoxicity and antibody dependent cellular cytotoxicity when compared with rituximab alone-treated controls. In vivo studies in severe combined immunodeficiency (SCID) mice clearly demonstrated synergistic activity between G3139 and rituximab. Treatment of lymphoma-bearing SCID mice with G3139 for two consecutive days prior to each rituximab dose resulted in better disease control and survival than treatment with either agent alone or controls. Our findings suggest that Bcl-2 downregulation by G3139, followed by the administration of rituximab is an efficient anti-tumour strategy associated with improved survival in lymphoma-bearing SCID mice. [source] | ||||||||||