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Long-term Response (long-term + response)
Selected AbstractsLeft Ventricular Lead Proximity to an Akinetic Segment and Impact on Outcome of Cardiac Resynchronization TherapyJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2006DANIEL ARZOLA-CASTANER M.D. Background: Previous studies report that the optimal pacing site for cardiac resynchronization therapy (CRT) is along the left ventricular (LV) lateral and postero-lateral (PL) wall. However, little is known regarding whether pacing over an akinetic site impacts the contractile response and long-term outcome from CRT. Methods and Results: A total of 38 patients with ischemic cardiomyopathy were studied for their acute hemodynamic and 12-month clinical response to CRT. The intraindividual percentage change in dP/dt (%,dP/dt), over baseline, was derived from the mitral regurgitation (MR) Doppler profile with CRT on versus off. Two-dimensional echocardiography was used for myocardial segmentation and determinination of akinetic sites. LV lead implant site was determined using angiographic and radiographic data and categorized as being "on" (group 1) or "off" (group 2) an akinetic site. Long-term response was measured as a combined endpoint of hospitalization for heart failure and/or all cause mortality at 12 months. Time to primary endpoint was estimated by the Kaplan-Meier method. Clinical characteristics and acute hemodynamic response was similar in both (group 1 [n = 14]; %,dP/dt 48.8 ± 67.4% vs group 2 [n = 24]; %,dP/dt 32.2 ± 40.1%, P = 0.92). No difference in long-term outcome was observed (P = 0.59). In contrast, lead placement in PL or mid-lateral (ML) positions was associated with a better acute hemodynamic response when compared to antero-lateral (AL) positions (PL, %,dP/dt 45.7 ± 50.7% and ML, %,dP/dt 45.1 ± 58.8% vs AL, %,dP/dt 2.9 ± 30.9%, respectively, P = 0.014). Conclusion: LV lead proximity to an akinetic segment does not impact acute hemodynamic or 12-month clinical response to CRT. [source] Long-term outcome of non-fistulizing (ulcers, stricture) perianal Crohn's disease in patients treated with infliximabALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2009G. BOUGUEN Summary Background, In Crohn's disease, anal ulcers and stricture can be disabling. Aim, To evaluate long-term outcome of non-fistulizing perianal Crohn's disease under infliximab. Methods, The medical records of 99 patients with non-fistulizing perianal Crohn's disease at first infliximab infusion were reviewed. Complete responses (ulcer healing or stricture regression) after induction infliximab therapy and at the maximal follow-up were assessed. Results, Ninety-four patients (94.9%) had ulcers, 22 (22.2%) had stricture and 31 (31.3%) had draining perianal fistulas at first infliximab infusion. After infliximab induction therapy, 40/94 (42.5%) patients with ulcers, 4/22 (18.2%) with stricture and 10/31 (32.2%) with fistulas had a complete response. Eight patients were lost to follow-up. After a median follow-up of 175 weeks (range, 13,459), complete response rates for ulcers, stricture and fistulas were 72.3% (68/94), 54.5% (12/22) and 54.8% (20/31) respectively. Long-term response for cavitating ulcer was positively associated with concomitant immunosuppressant use (P = 0.017) and older age (P = 0.049). Among the 12 patients with complete regression of stricture, 6 patients also had anal dilatation. Complete response was associated with perianal pain relief and disappearance of soiling. Three patients with ulcers developed an anal abscess. Conclusions, Infliximab therapy may be effective in inducing and maintaining response for ulcers. [source] Long-term responses of zooplankton to invasion by a planktivorous fish in a subarctic watercourseFRESHWATER BIOLOGY, Issue 1 2009PER-ARNE AMUNDSEN Summary 1.,Introduced or invading predators may have strong impacts on prey populations of the recipient community mediated by direct and indirect interactions. The long-term progression of predation effects, covering the invasion and establishment phase of alien predators, however, has rarely been documented. 2.,This paper documents the impact of an invasive, specialized planktivorous fish on its prey in a subarctic watercourse. Potential predation effects on the crustacean plankton, at the community, population and individual levels, were explored in a long-term study following the invasion by vendace (Coregonus albula). 3.,Over the 12-year period, the density and species richness of zooplankton decreased, smaller species became more abundant and Daphnia longispina, one of the largest cladocerans, was eliminated from the zooplankton community. 4.,Within the dominant cladocerans, including Daphnia spp., Bosmina longispina and Bosmina longirostris, the body size of ovigerous females and the size at first reproduction decreased after the arrival of the new predator. The clutch sizes of Daphnia spp. and B. longirostris also increased. 5.,Increased predation pressure following the vendace invasion induced many effects on the crustacean zooplankton, and we document comprehensive and strong direct and indirect long-term impacts of an introduced non-native predator on the native prey community. [source] Usefulness and Limitation of Dobutamine Stress Echocardiography to Predict Acute Response to Cardiac Resynchronization TherapyECHOCARDIOGRAPHY, Issue 1 2010F.R.C.P.C., Mario Sénéchal M.D. Background: It has been hypothesized that a long-term response to cardiac resynchronization therapy (CRT) could correlate with myocardial viability in patients with left ventricular (LV) dysfunction. Contractile reserve and viability in the region of the pacing lead have not been investigated in regard to acute response after CRT. Methods: Fifty-one consecutive patients with advanced heart failure, LV ejection fraction , 35%, QRS duration > 120 ms, and intraventricular asynchronism , 50 ms were prospectively included. The week before CRT implantation, the presence of viability was evaluated using dobutamine stress echocardiography. Acute responders were defined as a ,15% increase in LV stroke volume. Results: The average of viable segments was 5.8 ± 1.9 in responders and 3.9 ± 3 in nonresponders (P = 0.03). Viability in the region of the pacing lead had an excellent sensitivity (96%), but a low specificity (56%) to predict acute response to CRT. Mitral regurgitation (MR) was reduced in 21 patients (84%) with acute response. The presence of MR was a poor predictor of response (sensibility 93% and specificity 17%). However, combining the presence of MR and viability in the region of the pacing lead yields a sensibility (89%) and a specificity (70%) to predict acute response to CRT. Conclusion: Myocardial viability is an important factor influencing acute hemodynamic response to CRT. In acute responders, significant MR reduction is frequent. The combined presence of MR and viability in the region of the pacing lead predicts acute response to CRT with the best accuracy. (Echocardiography 2010;27:50-57) [source] An Echocardiographic Analysis of the Long-Term Effects of Carvedilol on Left Ventricular Remodeling, Systolic Performance, and Ventricular Filling Patterns in Dilated CardiomyopathyECHOCARDIOGRAPHY, Issue 7 2005Peter S. Rahko M.D. Background: The long-term clinical benefit of beta blockade is well recognized, but data quantifying long-term effects of beta blockade on remodeling of the left ventricle (LV) is limited. Methods: This consecutive series evaluates the long-term response of the LV to the addition of carvedilol to conventional therapy for dilated cardiomyopathy. There were 33 patients who had a LV ejection fraction <45%, LV enlargement and symptomatic heart failure. Quantitative Doppler echocardiography was performed at baseline 6, 12, 24, and 36 months after initiation of carvedilol to evaluate LV ejection fraction, LV volume, wall stress, mass, regional function, and diastolic performance. Results: Compared to baseline there was a significant and sustained reduction in end-systolic volume and end-systolic wall stress with a corresponding improvement in LV ejection fraction. The LV mass did not decline but relative wall thickness increased toward normal. An analysis of regional wall motion responses showed an improvement in all areas, particularly the apical, septal, and lateral walls that was significantly more frequent in patients with a nonischemic etiology. Filling patterns of the LV remained abnormal throughout the study but changed with therapy suggesting a decline in filling pressures. These changes were sustained for 3 years. Conclusion: (1) The addition of carvedilol to conventional therapy for a dilated cardiomyopathy significantly improves LV ejection fraction and reduces LV end-systolic volume and wall stress for at least 3 years, (2) the response to 6 months of treatment predicts the long-term response, (3) the typical response is partial improvement of the LV, complete return to normal size, and function is uncommon, and (4) abnormalities of LV filling persist in virtually all patients throughout the course of treatment. [source] Effect of intravenous immunoglobulin on cerebellar ataxia and neuropathic pain associated with celiac diseaseEUROPEAN JOURNAL OF NEUROLOGY, Issue 12 2008N. Souayah Background:, Cerebellar syndrome and small fiber neuropathy may complicate celiac disease (CD) and may be resistant to a strict gluten-free diet. Methods:, Case series. Results:, We report three patients with biopsy-proven CD who developed cerebellar ataxia and neuropathic pain despite strict adherence to a gluten-free diet. A small fiber neuropathy was suggested by skin biopsy findings in two patients. All patients' symptoms, including small fiber neuropathy symptoms, responded to treatment with intravenous immunoglobulin (IVIG). Discontinuation of IVIG in two patients resulted in worsened ataxia that reversed after resumption of IVIG. Conclusion:, Intravenous immunoglobulin may be effective in treating cerebellar ataxia and small fiber neuropathy associated with CD, suggesting an immune pathogenesis. Further prospective, controlled studies are necessary to determine the long-term response to IVIG or other immunomodulation therapy. [source] Long-term desmopressin response in primary nocturnal enuresis: open-label, multinational studyINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 1 2009H. Lottmann Summary Background:, Primary nocturnal enuresis (PNE) is a distressing condition, particularly in severe cases (, 3 wet nights/week). A prevalent pathophysiological mechanism, especially in monosymptomatic PNE (PMNE), is commonly believed to be an insufficient increase in night-time release of antidiuretic hormone. Desmopressin, a synthetic analogue of antidiuretic hormone, has been shown to reduce the number of wet nights experienced by PMNE patients in several controlled trials. Aim: This study was performed to evaluate desmopressin treatment in the real-life clinical setting and was a large-scale, 6-month investigation of efficacy and safety in patients with severe PNE. Predictive factors for desmopressin response were also evaluated. A total of 744 children aged 5 years and above from four countries were involved in the study. Results: At baseline, patients had a median of 6 wet nights/week; at 6 months, 41% of patients had experienced , 50% reduction in the mean number of wet nights. Long-term desmopressin treatment was consistently well-tolerated across all ages, with 5% of patients experiencing any treatment-related adverse events. The strength of treatment response was associated with nocturnal diuresis (p < 0.0001) and age (p = 0.0167) in logistic regression analyses. Compliance and dosage were also associated with response and more patients experienced , 50% reduction in wet nights after 6 months' treatment than earlier in the study, suggesting the value of persistent treatment. Conclusion: This study shows that long-term desmopressin treatment in the clinical setting is effective and well-tolerated in PNE patients of 5 years and upwards. Early improvements in bedwetting of any appreciable magnitude may be rewarding, may facilitate compliance and enable good long-term response. [source] Curcumin-induced apoptosis in ovarian carcinoma cells is p53-independent and involves p38 mitogen-activated protein kinase activation and downregulation of Bcl-2 and survivin expression and Akt signaling,MOLECULAR CARCINOGENESIS, Issue 1 2010Jane L. Watson Abstract New cytotoxic agents are urgently needed for the treatment of advanced ovarian cancer because of the poor long-term response of this disease to conventional chemotherapy. Curcumin, obtained from the rhizome of Curcuma longa, has potent anticancer activity; however, the mechanism of curcumin-induced cytotoxicity in ovarian cancer cells remains a mystery. In this study we show that curcumin exhibited time- and dose-dependent cytotoxicity against monolayer cultures of ovarian carcinoma cell lines with differing p53 status (wild-type p53: HEY, OVCA429; mutant p53: OCC1; null p53: SKOV3). In addition, p53 knockdown or p53 inhibition did not diminish curcumin killing of HEY cells, confirming p53-independent cytotoxicity. Curcumin also killed OVCA429, and SKOV3 cells grown as multicellular spheroids. Nuclear condensation and fragmentation, as well as DNA fragmentation and poly (ADP-ribose) polymerase-1 cleavage in curcumin-treated HEY cells, indicated cell death by apoptosis. Procaspase-3, procaspase-8, and procaspase-9 cleavage, in addition to cytochrome c release and Bid cleavage into truncated Bid, revealed that curcumin activated both the extrinsic and intrinsic pathways of apoptosis. Bax expression was unchanged but Bcl-2, survivin, phosphorylated Akt (on serine 473), and total Akt were downregulated in curcumin-treated HEY cells. Curcumin also activated p38 mitogen-activated protein kinase (MAPK) without altering extracellular signal-regulated kinase 1/2 activity. We conclude that p53-independent curcumin-induced apoptosis in ovarian carcinoma cells involves p38 MAPK activation, ablation of prosurvival Akt signaling, and reduced expression of the antiapoptotic proteins Bcl-2 and survivin. These data provide a mechanistic rationale for the potential use of curcumin in the treatment of ovarian cancer. © 2009 Wiley-Liss, Inc. [source] Impact of rising CO2 on emissions of volatile organic compounds: isoprene emission from Phragmites australis growing at elevated CO2 in a natural carbon dioxide spring,PLANT CELL & ENVIRONMENT, Issue 4 2004P. A. SCHOLEFIELD ABSTRACT Isoprene basal emission (the emission of isoprene from leaves exposed to a light intensity of 1000 µmol m,2 s,1 and maintained at a temperature of 30 °C) was measured in Phragmites australis plants growing under elevated CO2 in the Bossoleto CO2 spring at Rapolano Terme, Italy, and under ambient CO2 at a nearby control site. Gas exchange and biochemical measurements were concurrently taken. Isoprene emission was lower in the plants growing at elevated CO2 than in those growing at ambient CO2. Isoprene emission and isoprene synthase activity (IsoS) were very low in plants growing at the bottom of the spring under very rich CO2 and increased at increasing distance from the spring (and decreasing CO2 concentration). Distance from the spring did not significantly affect photosynthesis making it therefore unlikely that there is carbon limitation to isoprene formation. The isoprene emission rate was very quickly reduced after rapid switches from elevated to ambient CO2 in the gas-exchange cuvette, whereas it increased when switching from ambient to elevated CO2. The rapidity of the response may be consistent with post-translational modifications of enzymes in the biosynthetic pathway of isoprene formation. Reduction of IsoS activity is interpreted as a long-term response. Basal emission of isoprene was not constant over the day but showed a diurnal course opposite to photosynthesis, with a peak during the hottest hours of the day, independent of stomatal conductance and probably dependent on external air temperature or temporary reduction of CO2 concentration. The present experiments show that basal emission rate of isoprene is likely to be reduced under future elevated CO2 levels and allow improvement in the modelling of future isoprene emission rates. [source] Polymorphisms in the ,1A -adrenoceptor gene do not modify the short- and long-term efficacy of ,1 -adrenoceptor antagonists in the treatment of benign prostatic hyperplasiaBJU INTERNATIONAL, Issue 4 2006CHAIDIR A. MOCHTAR OBJECTIVE To determine whether a common single nucleotide polymorphism (SNP) in the ADRA1A gene encoding the ,1A -adrenoceptor modifies the short- and long-term efficacy of ,1 -adrenoceptor antagonists in the treatment of benign prostatic hyperplasia (BPH). PATIENTS AND METHODS For 254 patients with BPH and/or lower urinary tract symptoms who received ,1 -adrenergic antagonists for ,,3 months, the ADRA1A genotype at position 1475 of the coding region was determined. The patients' short-term response to treatment was determined for four outcome measures, i.e. the International Prostate Symptom Score (IPSS), the IPSS quality-of-life score, peak urinary flow rate, and obstruction grade, stratified by genotype. Eventual BPH-related invasive therapy was used as the outcome for assessing the long-term response to treatment. Genetic variants at positions 834, 896, 898 and 1831 were too rare to be considered in the analysis. RESULTS There were no significant differences for the genotype strata in three of the four outcome measures. Patients with the CC genotype responded significantly better in quality-of-life perception than patients with the CT or TT genotype. There were also no significant differences in the risk of BPH-related invasive therapy among the three genotypes. CONCLUSIONS The 1475C,T SNP in the ADRA1A gene does not modify the short- and long-term efficacy of ,1 -adrenoceptor antagonists for treating BPH. There was a small effect on perceived quality of life but this was not reflected in other variables that measured the treatment response more directly. [source] Climate change in the Arctic: using plant functional types in a meta-analysis of field experimentsFUNCTIONAL ECOLOGY, Issue 1 2002C. F. Dormann Summary 1,The effects of global climate change are predicted to be strongest in the Arctic. This, as well as the suitability of tundra as a simple model ecosystem, has led to many field experiments investigating consequences of simulated environmental change. 2,On the basis of 36 experiments reviewed here, minor light attenuation by clouds, small changes in precipitation, and increases in UV-B radiation and atmospheric CO2 concentrations will not affect arctic plants in the short term. However, temperature elevation, increases in nutrient availability and major decreases in light availability will cause an immediate plant-growth response and alter nutrient cycling, possibly creating positive feedbacks on plant biomass. The driver of future change in arctic vegetation is likely to be increased nutrient availability, arising for example from temperature-induced increases in mineralization. 3,Arctic plant species differ widely in their response to environmental manipulations. Classification into plant functional types proved largely unsatisfactory for generalization of responses and predictions of effects. 4,Nevertheless, a few generalizations and consistent differences between PFTs were detected. Responses to fertilization were the strongest, particularly in grasses. Shrubs and grasses were most responsive to elevated temperature. 5,Future studies should focus on interactive effects of environmental factors, investigate long-term responses to manipulations, and incorporate interactions with other trophic levels. With respect to plant functional types, a new approach is advocated, which groups species according to their responses to environmental manipulations. [source] Regulation of intracellular cyclic GMP levels in olfactory sensory neuronsJOURNAL OF NEUROCHEMISTRY, Issue 1 2005Cheil Moon Abstract Cyclic AMP is the primary second messenger mediating odorant signal transduction in mammals. A number of studies indicate that cyclic GMP is also involved in a variety of other olfactory signal transduction processes, including adaptation, neuronal development, and long-term cellular responses in the setting of odorant stimulation. However, the mechanisms that control the production and degradation of cGMP in olfactory sensory neurons (OSNs) remain unclear. Here, we investigate these mechanisms using primary cultures of OSNs. We demonstrate that odorants increase cGMP levels in intact OSNs in vitro. Different from the rapid and transient cAMP responses to odorants, the cGMP elevation is both delayed and sustained. Inhibition of soluble guanylyl cyclase and heme oxygenase blocks these odorant-induced cGMP increases, whereas inhibition of cGMP PDEs (phosphodiesterases) increases this response. cGMP PDE activity is increased by odorant stimulation, and is sensitive to both ambient calcium and cAMP concentrations. Calcium stimulates cGMP PDE activity, whereas cAMP and protein kinase A appears to inhibit it. These data demonstrate a mechanism by which odorant stimulation may regulate cGMP levels through the modulation of cAMP and calcium level in OSNs. Such interactions between odorants and second messenger systems may be important to the integration of immediate and long-term responses in the setting odorant stimulation. [source] Photodynamic Therapy for the Treatment of Intranasal Tumors in 3 Dogs and 1 CatJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 5 2003Michael D. Lucroy Three dogs and 1 cat with intranasal tumors were treated with pyropheophorbide-a-hexyl ether-based photodynamic therapy (PDT). PDT was well tolerated by all the animals, and no adverse effects from photosensitizer injection, such as cutaneous photosensiti-zation, were observed. Facial swelling was observed in all animals after each PDT treatment but resolved spontaneously within 72 hours after treatment. All animals had a decrease in severity of epistaxis, frequency of sneezing, and amount of nasal discharge after PDT. Clinical signs were controlled for variable time, although long-term responses were comparable with radiation therapy in 2 animals. This small case series demonstrates another application for PDT in veterinary medicine. On the basis of these findings, further studies are warranted to define the role of PDT in the management of intranasal tumors in dogs and cats. [source] Short- and long-term modulation of the lutein epoxide and violaxanthin cycles in two species of the Lauraceae: sweet bay laurel (Laurus nobilis L.) and avocado (Persea americana Mill.)PLANT BIOLOGY, Issue 3 2008R. Esteban Abstract Short- and long-term responses of the violaxanthin (V) and lutein epoxide (Lx) cycles were studied in two species of Lauraceae: sweet bay laurel (Laurus nobilis L.) and avocado (Persea americana L.). The Lx content exceeded the V content in shade leaves of both species. Both Lx and V were de-epoxidised on illumination, but only V was fully restored by epoxidation in low light. Violaxanthin was preferentially de-epoxidised in low light in L. nobilis. This suggests that Lx accumulates with leaf ageing, partly because its conversion to lutein is limited in shade. After exposure to strong light, shade leaves of avocado readjusted the total pools of ,- and ,-xanthophyll cycles by de novo synthesis of antheraxanthin, zeaxanthin and lutein. This occurred in parallel with a sustained depression of Fv/Fm. In Persea indica, a closely related but low Lx species, Fv/Fm recovered faster after a similar light treatment, suggesting the involvement of the Lx cycle in sustained energy dissipation. Furthermore, the seasonal correlation between non-reversible Lx and V photoconversions and pre-dawn Fv/Fm in sun leaves of sweet bay supported the conclusion that the Lx cycle is involved in a slowly reversible downregulation of photosynthesis analogous to the V cycle. [source] Radioembolization with selective internal radiation microspheres for neuroendocrine liver metastases,CANCER, Issue 5 2008Julie King MPH Abstract BACKGROUND. There are limited effective treatment options available and a poor 5-year survival for patients with inoperable neuroendocrine liver metastases (NETLMs). In this study, the authors prospectively assessed the safety and efficacy of treatment with yttrium 90 (90Y) radioactive microspheres for patients with unresectable NETLMs. METHODS. Radioactive 90Y resin microspheres (selective internal radiation [SIR-Spheres]) were administered through a temporarily placed percutaneous hepatic artery catheter concomitantly with a 7-day systemic infusion of 5-fluorouracil to patients with progressive, unresectable NETLMs. Patients were monitored prospectively, and the response to treatment was measured by using cancer markers and tumor size on computed tomography imaging studies. RESULTS. Thirty-four patients (22 men) with a mean age 61 years (range, 32-79 years) who had unresectable NETLMs were treated between December 2003 and December 2005. The mean (±standard error) follow-up was 35.2 ± 3.2 months. The site of the primary neuroendocrine tumor was the bronchus in 1 patient, the medullary thyroid in 2 patients, gastrointestinal in 15 patients, the pancreas in 8 patients, and of unknown origin in 8 patients. The tumors were classified as vipoma (1 tumor), somatostatinoma (1 tumor), glucagonoma (2 tumors), large cell (3 tumors), carcinoid (25 tumors), and of unknown origin (2 tumors). Complications after 90Y radioembolization included abdominal pain, which was mild to severe; nausea and fever; and lethargy that lasted from 1 week to 1 month. Two patients developed biopsy-proven radiation gastritis, 1 patient developed a duodenal ulcer, and there was 1 early death from liver dysfunction and pneumonia. Subjective changes from recorded baseline hormone symptoms were reported every 3 months. Symptomatic responses were observed in 18 of 33 patients (55%) at 3 months and in 16 of 32 patients (50%) at 6 months. Radiologic liver responses were observed in 50% of patients and included 6 (18%) complete responses and 11 (32%) partial responses, and the mean overall survival was 29.4 ± 3.4 months). In patients who had evaluable chromogranin A (CgA) marker levels, there was a fall in CgA marker levels after 90Y radioembolization in 19 patients (26%) at 1 month, in 19 patients (41%) at 3 months, in 15 patients (43%) at 6 months, in 11 patients (42%) at 12 months, in 8 patients (38%) at 24 months, and in 3 patients (46%) at 30 months. CONCLUSIONS. In this open study of 34 patients, the results demonstrated that radioembolization with 90Y resin microspheres can achieve relatively long-term responses in some patients with nonresectable NETLMs. Cancer 2008. © 2008 American Cancer Society. [source] Pegylated liposomal doxorubicin-efficacy in patients with recurrent high-grade gliomaCANCER, Issue 6 2004Peter Hau M.D. Abstract BACKGROUND Doxorubicin exhibits high efficacy in malignant glioma cell cultures. Nonetheless, as a standard formulation, doxorubicin has not been used clinically, due to poor penetration of the blood-brain barrier. Furthermore, doxorubicin is known to induce tumor resistance genes. To address both of these issues, the authors investigated the use of pegylated liposomal doxorubicin (CaelyxÔ; Essex Pharma, Munich, Germany) alone (Trial 1) and in combination with tamoxifen (Trial 2) in two sequentially performed nonrandomized prospective Phase II trials involving patients with recurrent high-grade glioma. METHODS Twenty patients were included in each trial. Progression-free survival at 6 months (PFS-6) and toxicity were the primary endpoints. Expression of the tumor resistance proteins multidrug resistance protein 1 (MDR-1) and multiple resistance protein (MRP) was evaluated by immunohistochemical methods and by sestamibi,single-photon emission computed tomography (SPECT). RESULTS The overall response rate (including cases of disease stabilization) was 40% in both Trial 1 and Trial 2. PFS-6 was 15%, and the median time to disease progression was 17 weeks. It is noteworthy that 40% of patients with Grade III tumors had long-term responses, which lasted for up to 3 years. There was no significant difference between Trial 1 and Trial 2 in terms of efficacy. Both regimens were well tolerated, with the main side effect being palmoplantar erythrodysesthesia. The authors found no correlation between clinical response and expression of tumor resistance genes or between clinical response and SPECT data. CONCLUSIONS Pegylated liposomal doxorubicin administered alone or in combination with tamoxifen is safe and moderately effective in patients with recurrent high-grade glioma. None of the putative predictors for response that were evaluated proved to be significant in this setting. Cancer 2004. © 2004 American Cancer Society. [source] | ||||||||||||||||||||||