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Poor Responders (poor + responder)
Selected AbstractsEvaluating budesonide efficacy in nasal polyposis and predicting the resistance to treatmentCLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2009F. C. P. Valera Summary Background Cell resistance to glucocorticoids is a major problem in the treatment of nasal polyposis (NP). Objectives The objectives of this study were to observe the effect of budesonide on the expression of IL-1,, TNF-,, granulocyte macrophage-colony stimulating factor, intercellular adhesion molecule (ICAM)-1, basic fibroblast growth factor, eotaxin-2, glucocorticoid receptor (GR)-,, GR-,, c-Fos and p65 in nasal polyps and to correlate their expression to clinical response. Methods Biopsies from nasal polyps were obtained from 20 patients before and after treatment with topical budesonide. Clinical response to treatment was monitored by a questionnaire and nasal endoscopy. The mRNA levels of the studied genes were measured by real-time quantitative (RQ)-PCR. Results There was a significant decrease in the expression of TNF-, (P<0.05), eotaxin-2 (P<0.05) and p65 (P<0.05) in NP after treatment. Poor responders to glucocorticoids showed higher expression of IL-1, (3.74 vs. 0.14; P<0.005), ICAM-1 (1.91 vs. 0.29; P<0.05) and p65 (0.70 vs. 0.16; P<0.05) before treatment. Following treatment, IL-1, (4.18 vs. 0.42; P<0.005) and GR-, (0.95 vs. 0.28; P<0.05) mRNA expression was higher in this group. Conclusion Topical budesonide reduced the expression of TNF-,, eotaxin-2 and p65. Poor responders to topical budesonide exhibit higher levels of IL-1,, ICAM-1 and nuclear factor (NF)-,B at diagnosis and higher expression of both IL-1, and GR-, after treatment. These results emphasize the anti-inflammatory action of topical budesonide at the molecular level and its importance in the treatment of NP. Nevertheless, IL-1,, ICAM-1 and NF-,B may be associated with primary resistance to glucocorticoids in NP, whereas higher expression of GR-, in poor responders only after glucocorticoid treatment may represent a secondary drug resistance mechanism in this disease. [source] The hemodynamic response to medical treatment of portal hypertension as a predictor of clinical effectiveness in the primary prophylaxis of variceal bleeding in cirrhosisHEPATOLOGY, Issue 5 2000Carlo Merkel In the prevention of variceal rebleeding, it is already established that hemodynamic response to drug treatment (decrease in hepatic venous pressure gradient [HVPG] to 12 mm Hg or by >20%) is predictive of clinical effectiveness. In primary prophylaxis very few clinical data are available. We assessed the role of the hemodynamic response to beta-blockers or beta-blockers plus nitrates in predicting clinical efficacy of prophylaxis. A total of 49 cirrhotic patients with varices at risk of bleeding, without prior variceal bleeding, were investigated by hepatic vein catheterization before and after 1 to 3 months of chronic treatment with nadolol or nadolol plus isosorbide mononitrate, and were followed during treatment for up to 5 years. A total of 30 patients (61%) were good hemodynamic responders, and among them in 12 (24%) HVPG was ,12 mm Hg during treatment. During treatment 9 patients had variceal bleeding: 7 were poor responders and 2 were good responders. The probability of bleeding at 3 years of follow-up was significantly higher in poor responders (41%) than in good responders (7%; P = .0008). No patient reaching an HVPG of 12 mm Hg or less during treatment had variceal bleeding during follow-up. Cox's regression analysis showed that poor hemodynamic response was the main factor predicting bleeding (, = 1.91; SE(,) = 0.80; P = .01). During follow-up 11 patients died of hepatic causes. Survival was related to Child-Pugh class and to initial value of HVPG, according to Cox's analysis. In conclusion, the assessment of hemodynamic response to drugs in terms of HVPG is the best predictor of efficacy of prophylaxis of variceal bleeding in patients treated with beta-blockers or beta-blockers plus nitrates. [source] Molecular characterization of the response to chemotherapy in conventional osteosarcomas: Predictive value of HSD17B10 and IFITM2INTERNATIONAL JOURNAL OF CANCER, Issue 4 2009Sébastien Salas Abstract The therapy regimen of high-grade osteosarcoma includes chemotherapy followed by surgical resection and postoperative chemotherapy. The degree of necrosis following definitive surgery remains the only reliable prognostic factor and is used to guide the choice of postoperative chemotherapy. The aim of this study was to find molecular markers able to classify patients with an osteosarcoma as good or poor responders to chemotherapy before beginning treatment. Gene expression screening of 20 nonmetastatic high-grade osteosarcoma patients was performed using cDNA microarray. Expression of selected relevant genes was validated using QRT-PCR. Immunohistochemistry on tissue microarrays sections of 73 biopsies was performed to investigate protein expression. Fluorescent in situ hybridization was performed for RPL8 gene. We have found that HSD17B10 gene expression was up-regulated in poor responders and that immunohistochemistry expression of HSD17B10 on biopsy before treatment was correlatedto response to chemotherapy. Other results include correlationof IFITM2, IFITM3, and RPL8 gene expression to chemotherapy response. A statistical correlation was found between polysomy 8 or gain of RPL8 and good response to chemotherapy. These data suggest that HSD17B10, RPL8, IFITM2, and IFITM3 genes are involved in the response to the chemotherapy and that HSD17B10 may be a therapeutic target. RPL8 and IFITM2 may be useful in the assessment at diagnosis and for stratifying patients taking part in randomized trials. © 2009 UICC [source] Genetic imbalances revealed by comparative genomic hybridization in osteosarcomasINTERNATIONAL JOURNAL OF CANCER, Issue 4 2002Toshifumi Ozaki Abstract Osteosarcomas are the most frequent bone sarcomas. The molecular chromosomal aberrations in osteosarcomas were analyzed by comparative genomic hybridization (CGH). We studied 47 frozen tumors (41 primary samples, 6 relapses) in osteosarcoma patients registered in the Cooperative Osteosarcoma Study (COSS) protocol. Genomic imbalances were detected in 40 of 41 primary tumors and 6 of 6 relapsed tumors. Gains were more frequent than losses (ratio of 1.3:1). The median number of changes was 16 and 12 in primary and relapsed osteosarcomas, respectively. The median number of aberrations in primary high-grade osteosarcomas (17.0) was significantly higher than in low- or intermediate-grade osteosarcoma subtypes (3.0) (p = 0.038). The most frequent gains included 8q, 1p21-p31 and 1q21-q24, and the most frequent losses were 10q, 5q and 13q. High-level gains were observed on 8q23-q24, 17p13 and 1q21-q24. A gain of 19p (p < 0.001) or loss of 9p (p = 0.027) was more frequent in poor responders than in good responders. Univariate analysis revealed that patients with primary metastases (p = 0.002), poor histologic responses (p = 0.005), high-level gains of 19p (p = 0.012) or losses of 13q14 (p = 0.042) had significantly lower event-free survival (EFS), whereas patients with a loss of 5q (p = 0.007) or a loss of 10q21-22 (p = 0.017) had significantly higher EFS than patients without these aberrations. Multivariate analysis demonstrated that primary metastasis, loss of 13q14 and loss of 5q were independent prognostic factors. The findings of our study seem to be useful for evaluating the prognosis of patients and may finally lead to treatment strategies based on genetic background of osteosarcoma. © 2002 Wiley-Liss, Inc. [source] Original Contribution: Hyperandrogenism does not predispose patients to photoepilatory treatment failure: a single-center reviewJOURNAL OF COSMETIC DERMATOLOGY, Issue 3 2010MSc Derm, Marisa Taylor MBBS Summary Studies have suggested that patients with PCOS tend to be more treatment resistant to light-mediated depilation compared with their non-PCOS counterparts. We conducted a retrospective assessment of 29 hirsute patients treated between January 2006 and February 2007 to assess whether those with unsatisfactory hair clearance after treatment with intense pulsed light (IPL) were predominantly hyperandrogenic. The number of IPL sessions was also recorded for those patients failing to improve on treatment. Seventy-six percent had satisfactory hair clearance where hyperandrogenic patients dominated. All patients required an average of six treatments before discharge. Eighty-eight percent of poor responders were normoandrogenic. Our hyperandrogenic cohort appeared more responsive to IPL than the normoandrogenic patients. From our observations, the presence of hyperandrogenism does not indicate treatment resistance. This standpoint is unique and warrants a randomized trial directly comparing the two groups to investigate whether a positive or negative relationship actually exists. [source] | ||||||||||