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Novel Treatment Modalities (novel + treatment_modality)
Selected AbstractsHER2 Is Frequently Over-expressed in Ovarian Clear Cell Adenocarcinoma: Possible Novel Treatment Modality Using Recombinant Monoclonal Antibody against HER2, TrastuzumabCANCER SCIENCE, Issue 11 2002Masaki Fujimura Ovarian clear cell adenocarcinoma (CCA) is generally chemo-resistant. Recently the poor prognosis and resistance to chemotherapeutic agents of HER2/neu over-expressing tumors have become clear. Thus, we investigated the expression level of HER2 in surgically resected CCA and ovarian serous adenocarcinoma, endometrioid adenocarcinoma, and mucinous adenocarcinoma specimens, as well as CCA cell lines, by an immunohistochemical method. HER2 was over-expressed in 42.9% of CCA (P=0.026, vs. ovarian serous adenocarcinoma), 20.8% of ovarian serous adenocarcinoma, 23.1% of ovarian endometrioid adenocarcinoma, and 30.0% of mucinous adenocarcinoma specimens. Three CCA cell lines, RMG-1, HAC-II and KK were also positively stained for HER2. A flow-cytometric study of HER2 revealed 7.2-, 6.4- and 4.5-fold greater expression of HER2 than that of normal mammary gland, respectively. Trastuzumab, a humanized recombinant monoclonal antibody against HER2 significantly and dose-dependently reduced the growth of CCA cell lines in vitro. The extent of the inhibitory effect of trastuzumab was dependent on the expression level of HER2. Trastuzumab also dose-dependently inhibited the growth of xenografted RMG-1 tumor. The survival period of trastuzumab-treated mice was longer than that of the control group. From these findings, trastuzumab appears to be a candidate as a treatment modality for HER2 over-expressing ovarian CCA. [source] Islet adaptation to insulin resistance: mechanisms and implications for interventionDIABETES OBESITY & METABOLISM, Issue 1 2005B. Ahrén Abstract:, Insulin sensitivity and insulin secretion are reciprocally related such that insulin resistance is adapted by increased insulin secretion to maintain normal glucose and lipid homeostasis. The relation between insulin sensitivity and secretion is curvilinear and mathematically best described as a hyperbolic relation. Several potential mediators have been suggested to be signals for the beta cells to respond to insulin resistance such as glucose, free fatty acids, autonomic nerves, fat-derived hormones and the gut hormone glucagon-like peptide-1 (GLP-1). Failure of these signals or of the pancreatic beta cells to adequately adapt insulin secretion in relation to insulin sensitivity results in inappropriate insulin levels, impaired glucose intolerance (IGT) and type 2 diabetes. Therefore, treatment of IGT and type 2 diabetes should aim at restoring the normal relation between insulin sensitivity and secretion. Such treatment includes stimulation of insulin secretion (sulphonylureas, repaglinide and nateglinide) and insulin sensitivity (metformin and thiazolidinediones), as well as treatment aimed at supporting the signals mediating the islet adaptation (cholinergic agonists and GLP-1). Both, for correct understanding of diabetes pathophysiology and for development of novel treatment modalities, therefore, the non-linear inverse relation between insulin sensitivity and secretion needs to be acknowledged. [source] Atrial fibrillation: insights from clinical trials and novel treatment optionsJOURNAL OF INTERNAL MEDICINE, Issue 6 2007Y. Blaauw Abstract., Blaauw Y, Crijns HJGM (University Hospital Maastricht, Maastricht, The Netherlands). Atrial fibrillation: insights from clinical trials and novel treatment options (Review). J Intern Med 2007; 262: 593,614. Atrial fibrillation (AF) is the most common encountered sustained arrhythmia in clinical practice. The last decade the result of large ,rate' versus ,rhythm' control trials have been published that have changed the current day practise of AF treatment. It has become clear that rate control is at least equally effective as a rhythm control strategy in ameliorating morbidity as well as mortality. Moreover, in each individual patient the risk of thromboembolic events should be assessed and antithrombotic treatment be initiated. There have also been great advances in understanding the mechanisms of AF. Experimental studies showed that as a result of electrical and structural remodelling of the atria, ,AF begets AF'. Pharmacological prevention of atrial electrical remodelling has been troublesome, but it seems that blockers of the renin angiotensin system, and perhaps statins, may reduce atrial structural remodelling by preventing atrial fibrosis. Clinical studies demonstrated that the pulmonary veins exhibit foci that can act as initiator and perpetuator of the arrhythmia. Isolation of the pulmonary veins using radiofrequency catheter ablation usually abolishes AF. The most promising advances in the pharmacological treatment of AF include atrial specific antiarrhythmic drugs and direct thrombin inhibitors. In the present review we will describe the results of recent experimental studies, discuss the latest clinical trials, and we will focus on novel treatment modalities. [source] Endocannabinoids and liver disease , reviewLIVER INTERNATIONAL, Issue 5 2005Ezra Gabbay Abstract: Aims: Endocannabinoids are endogenous compounds that bind to the same receptors as tetrahydrocannabinol, the active component in marijuana and hashish. They have been found to have many physiological and patho-physiological functions, including mood alteration, control of feeding and appetite, motor and co-ordination activities, analgesia, immune modulation and gut motility. In this review we aim to elucidate current knowledge as to their role in liver physiology and disease. Methods: The major findings published to date concerning endocannabinoids and liver disease are described, and their implications with regard to understanding disease mechanisms, and the development of new treatments is considered. Results: Recently, endocannabinoids have been implicated in the hemodynamic alterations occurring in cirrhosis. These changes appear to be mediated via specific cannabinoid receptors (CB1) on splanchnic and hepatic vascular endothelium. Plasma levels of endocannabinoids also seem to be elevated in hepatitis, and are involved in apoptosis of hepatocytes by a membrane mechanism not related to a specific receptor. Other studies suggest a beneficial role for cannabinoids in reducing the inflammation of experimental hepatitis. In an animal model of acute hepatic failure, both endocannabinoids and the antagonist to the CB1 receptor have been found to have a beneficial effect on neurological and cognitive function. Conclusions: Endocannabinoids appear to be involved in several aspects of acute and chronic liver disease, including vascular changes, modulation of inflammatory process and neurological function, Further research may provide new insights into the pathophysiology of liver disease, as well as a basis for novel treatment modalities. [source] Gastrointestinal stromal tumors (GISTs): a reviewAPMIS, Issue 2 2009SONJA E. STEIGEN Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms in the gastrointestinal tract, which, over the last 10 years, have emerged from a poorly understood neoplasm to a well-defined tumor entity exhibiting particular molecular abnormalities and for which promising novel treatment modalities have been developed. GISTs probably arise from the precursor cell of the interstitial cell of Cajal, express KIT tyrosine kinase in most of the cases and harbor mutations of importance for individualized treatment. The molecular targets for therapeutic interventions are not only of importance for the treatment of GIST patients but also useful for in the development of novel drug modalities and new strategies in basic cancer therapy. [source] Topical aminolaevulinic acid-photodynamic therapy for the treatment of acne vulgaris: a study of clinical efficacy and mechanism of actionBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2004B. Pollock Summary Background, ,Acne affects 83,95% of 16-year-olds of both sexes, and many seek help from a clinician. Emerging problems with conventional acne treatments, specifically antibiotic resistance of Propionibacterium acnes and fears over the safety and tolerance of oral isotretinoin, create a demand for novel treatment modalities in acne. Objectives, To study the efficacy of aminolaevulinic acid-photodynamic therapy (ALA-PDT) in the treatment of acne and to identify the mode of action, looking specifically at the effects on surface numbers of P. acnes and on sebum excretion. Methods, ,Ten patients (nine men and one woman, age range 16,40 years) with mild to moderate acne on their backs were recruited. Each patient's back was marked with four 30-cm2 areas of equal acne severity. Each site was then randomly allocated to either ALA-PDT treatment, light alone, ALA alone or an untreated control site. At baseline, numbers of inflammatory and noninflammatory acne lesions were counted, sebum excretion measured by Sebutapes (CuDerm, Dallas, TX, U.S.A.) and surface P. acnes swabs performed. ALA cream (20% in Unguentum Merck) was applied under occlusion to the ALA-PDT and ALA alone sites for 3 h. Red light from a diode laser was then delivered to the ALA-PDT and light alone sites (635 nm, 25 mW cm,2, 15 J cm,2). Each patient was treated weekly for 3 weeks. At each visit acne lesion counts were performed and 3 weeks following the last treatment sebum excretion rates and P. acnes swabs were repeated. Results, There was a statistically significant reduction in inflammatory acne lesion counts from baseline after the second treatment at the ALA-PDT site but not at any of the other sites. No statistically significant reduction in P. acnes numbers or sebum excretion was demonstrated at any sites including the ALA-PDT site. Conclusions, ALA-PDT is capable of clinically improving acne. An alternative mode of action for ALA-PDT other than direct damage to sebaceous glands or photodynamic killing of P. acnes is suggested from the results of this study. [source] Enhanced killing of B lymphoma cells by granulocyte colony-stimulating factor-primed effector cells and Hu1D10 , a humanized human leucocyte antigen DR antibodyBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2002Bernhard Stockmeyer Summary. Antibody-based approaches have become a novel treatment modality for lymphoma patients. Humanized 1D10 (Hu1D10; Remitogen) is among the antibodies that are currently under evaluation in phase II clinical trials in lymphoma patients. The 1D10 antibody is directed against a polymorphic epitope on the ,-chain of human leucocyte antigen (HLA) class II. We found expression of the 1D10 epitope on B cells and monocytes from approximately 50% of healthy donors. Analyses of 1D10 expression on malignant cells revealed that approximately half of the HLA class II-positive haematological malignancies expressed the 1D10 epitope. In whole blood antibody-dependent cellular cytotoxicity (ADCC) assays, Hu1D10 was more effective than rituxan in killing malignant ARH-77 B cells. Interestingly, Hu1D10-mediated lymphoma cell lysis was significantly enhanced when blood from granulocyte colony-stimulating factor (G-CSF)-treated patients was compared with blood from healthy controls. Analyses of the relevant effector cell populations revealed that Fc,RI (CD64)-positive polymorphonuclear cells were critical for enhanced Hu1D10-mediated lymphoma killing during G-CSF therapy, while the same effector cell population induced only marginal lysis with rituxan. Furthermore, Hu1D10 was highly effective in inducing apoptosis in primary lymphoma cells from B chronic lymphocytic leukaemia patients. These preclinical results form the basis for a phase I/II clinical trial of Hu1D10 in combination with G-CSF. [source] | ||||||||||