B-cell chronic lymphocytic leukemia (B-CLL) follows heterogeneous clinical courses, and several biological parameters need to be added to the current clinical staging systems to predict which patients will experience an indolent or an aggressive outcome. This study analyzed CD38 expression by flow cytometry and soluble APO1/Fas (sAPO1/Fas), Bcl-2 (sBcl-2), and CD23 (sCD23) proteins by immunoenzymatic methods to evaluate their effect on the clinical course of 168 unselected B-CLL patients. Intermediate/high risk modified Rai stages were characterized by a higher CD38 ؉ B-cell number (P ؍ .0002) and higher sCD23 levels (P < .0001). Moreover, CD38 ؉ B-cell percentages were significantly and directly associated both with  2 -microglobulin and sCD23 concentrations (P < .0001 and P ؍ .002, respectively). Both a higher tumor burden (lymphadenopathy/splenomegaly) and a lymphocyte doubling time less than 12 months were significantly associated with higher CD38 ؉ percentages (P < .0001 and P ؍ .0001, respectively). With regard to clinical outcome, progression-free survival was significantly longer (75% versus 37% at 5 years; P ؍ .00006) in patients with lower CD38 ؉ B-cell percentages. Furthermore, the risk of partial or no response to fludarabine increased with increasing CD38 expression (P ؍ .003), and a shorter overall survival (50% versus 92% at 8 years; P < .00001) characterized patients with more than 30% CD38 ؉ B-cell number. The predictive value of CD38 expression was maintained among the patients within the Rai intermediate risk group and was confirmed in multivariate analysis. Thus, the percentage of CD38 ؉ B cells appears to be an accurate predictor of clinical outcome and therefore could be used to indicate when more novel chemotherapeutic approaches are needed. , and CD19 and negative for surface CD22 and FMC7. 2 These cells overexpress the Bcl-2 gene product and are resistant to apoptosis; however, examining the relative levels of this antiapoptotic protein has not been particularly helpful in predicting clinical outcome. 3,4 The clinical course of patients with B-CLL can be quite variable, with many patients surviving for prolonged periods without any therapy, whereas others succumb rapidly despite aggressive treatment. 5 Although the 2 major staging systems have provided valuable information in addressing this clinical heterogeneity, 6,7 they have been unable to predict an indolent or aggressive course within the intermediate risk category. For this reason, several parameters such as lymphocyte doubling time (LDT), 8 serum levels of  2 -microglobulin, 9 soluble CD23 (sCD23), 10 serum thymidine kinase levels, 11 bone marrow histology, 12 and cytogenetic abnormalities 13 have been added to the current staging systems to differentiate prognostic subsets.Despite having several characteristics of naive B cells, such as sequences of V H genes in germline configuration (unmutated), B-CLL cells have been shown to have somatically mutated immunoglobulin variable region genes in at least half of the case...
SummaryBackground The rationale for combining anticancer drugs has not been applied consistently to use of intravesical agents for treatment of superficial bladder cancer, for which immunotherapeutic BCG and chemotherapeutic mitomycin seem to be a potentially effective combination. We aimed to do a prospective, randomised comparison of BCG alone with that of sequential BCG and electromotive mitomycin in patients with stage pT1 bladder cancer.Methods After transurethral resection and multiple biopsies, 212 patients with stage pT1 bladder cancer were randomly assigned to: 81 mg BCG infused over 120 min once a week for 6 weeks (n=105); or to 81 mg BCG infused over 120 min once a week for 2 weeks, followed by 40 mg electromotive mitomycin (intravesical electric current 20 mA for 30 min) once a week as one cycle for three cycles (n=107). Complete responders underwent maintenance treatment: those assigned BCG alone had one infusion of 81 mg BCG once a month for 10 months, and those assigned BCG and mitomycin had 40 mg electromotive mitomycin once a month for 2 months, followed by 81 mg BCG once a month as one cycle for three cycles. The primary endpoint was disease-free interval; secondary endpoints were time to progression; overall survival; and disease-specific survival. Analyses were done by intention to treat. This trial has been submitted for registration at the US National Cancer Institute website http://clinicaltrials.gov. Findings
SUMMARYBackground: Antibiotic-associated diarrhoea can be attributed in part to imbalances in intestinal microflora. Therefore, probiotic preparations are used to prevent this diarrhoea. However, although several trials have been conducted, no conclusive evidence has been found of the efficacy of different preparations, e.g. Lactobacillus spp. and Saccharomyces spp. Aim: To conduct a meta-analysis of the data in the literature on the efficacy of probiotics in the prevention of antibiotic-associated diarrhoea. Methods: A literature search was performed of electronic databases, Abstract Books and single paper references. Data were also obtained from the authors. Only placebo-
Cellular interactions with the extracellular matrix are important factors in the development and progression of many types of cancer. Originally characterized as a member of the so-called dystrophin-glycoprotein complex in muscle sarcolemma, dystroglycan (DG) is a transmembrane glycoprotein expressed in a wide variety of tissues at the interface between the basement membrane and cell membrane linking the extracellular matrix to the intracellular cytoskeleton.
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