220 research outputs found
A therapy resistant myelodysplastic syndrome characterized by the presence of the rare reciprocal translocation t(3;12)(q26.2;p13)
No full textLow dose 2-CdA schedule activity in splenic marginal zone lymphomas.
No full textSplenic Marginal Zone Lymphoma (SMZL) is a rare clinicopathological entity among marginal zone lymphomas. SMZL is an indolent lymphoma usually treated by splenectomy. A subset of patients is characterized by a more aggressive clinical course and poor prognosis. Treatment of these cases and second-line therapy for relapsed patients have not been yet identified. We report 10 cases treated with cladribrine (5 mg/m(2)/week) for six courses. Six patients (60%) achieved partial response, two patients (20%) achieved a complete response and the two remaining patients did not respond and died as a result of progression of the disease. The treatment was well tolerated. A total of 60% of the patients had an overall survival rate of 48 months and 24 months progression-free-survival was achieved by 37% with a median time of progression-free-survival of 17 months. Interestingly, in addition to a relevant percentage of hematological remission, some patients also experienced a molecular remission. We conclude that this treatment is safe and well tolerated and is able to induce a substantial number of responses. Our results suggest that this schedule is well tolerated and could be an useful alternative to splenectomy
FROM REFUSE DERIVED FUEL (RDF) TO NH3: A KEY PATHWAY FOR THE SUSTAINABILITY AND SECURITY OF THE FOOD PRODUCTION CHAIN
No full textMatch unrelated bone marrow transplantation in a case of high risk myelodysplastic syndrome treated with azacitidine and concomitant 1alpha-25-dihydroxyvitamin D3, as differentiating agent.
No full textBortezomib and liposomal doxorubicin are highly effective in obtaining the best possible response before autologous transplant for multiple myeloma
No full textRole of low-dose 2-CdA in refractory or resistant lymphoplasmocytic lymphoma
No full textCladribrine (2-CdA), a purine analogue active on both dividing and resting lymphocytes, plays an important role in the treatment of indolent lymphoproliferative malignancies such as Hairy Cell Leukemia (HCL), Chronic Lymphocytic Leukemia (CLL), Lymphoplasmocytic Lymphoma (LPL), Waldenström's Macroglobulinemia (WM). With the aim of evaluating the efficacy and toxicity of low dose 2-CdA, 15 lymphoplasmocytic lymphoma patients, not eligible for more aggressive or standard therapies, because of age or poor performance status, were treated with the drug at a dose of 5 mg/m2, once a week for six total courses. All patients showed disease progression. Fourteen patients were valuable for response. In eleven out of these 14 (85.7%) disease progression stopped, with 21% having good hematological responses (one CR and two PR). The treatment was generally well tolerated, without serious infectious events. This schedule may be appropriate for the management of patients where the aim of the treatment is control of disease progression
Biomarker-driven optimal designs for patient enrollment restriction
No full textThe rapidly developing field of personalized medicine is giving the opportunity to treat patients with a specific regimen according to their individual demographic, biological, or genomic characteristics, known also as biomarkers. While binary
biomarkers simplify subgroup selection, challenges arise in the presence of continuous ones, which are often categorized based on data-driven quantiles. In the context of binary response trials for treatment comparisons, this paper proposes a method for determining the optimal cutoff of a continuous predictive biomarker to discriminate between sensitive and insensitive patients, based on their relative risk. We derived the optimal design to estimate such a cutoff, which requires a set of equality constraints that involve the unknown model parameters and the patients’ biomarker values and are not directly attainable. To implement the optimal design, a novel covariate-adjusted response-adaptive randomization is introduced, aimed at sequentially minimizing the Euclidean distance between the current allocation and the optimum. An extensive simulation study shows the performance of the proposed approach in terms of estimation efficiency and
variance of the estimated cutoff. Finally, we show the potential severe ethical impact of adopting the data-dependent median to identify the subpopulations
Proteomic analysis of pancreatic endocrine tumor cell lines treated with the histone deacetylase inhibitor trichostatin A
No full textEffects of the histone-deacetylases inhibitor trichostatin A (TSA) on the growth of three different
human pancreatic endocrine carcinoma cell lines (CM, BON, and QGP-1) have been assessed via
dosage-dependent growth inhibition curves. TSAdetermined strong inhibition of cell growth with
similar IC50 values for the different cell lines: 80.5 nM(CM), 61.6 nM(BON), and 86 nM(QGP-1),
by arresting the cell cycle in G2/M phase and inducing apoptosis. 2DE and nano-RP-HPLC-ESIMS/
MS analysis revealed 34, 33, and 38 unique proteins differentially expressed after TSA treatment
in the CM, BON, and QGP-1 cell lines, respectively. The most important groups of modulated
proteins belong to cell proliferation, cell cycle, and apoptosis classes (such as peroxiredoxins 1
and 2, the diablo protein, and HSP27). Other proteins pertain to processes such as regulation of
gene expression (nucleophosmin, oncoprotein dek), signal transduction (calcium-calmodulin),
chromatin, and cytoskeleton organization (calgizzarin, dynein, and lamin), RNA splicing
(nucleolin, HNRPC), and protein folding (HSP70). The present data are in agreement with previous
proteomic analyses performed on pancreatic ductal carcinoma cell lines (Cecconi, D. et al.,
Electrophoresis 2003; Cecconi, D. et al., J. Proteome Res. 2005) and place histone-deacetylases inhibitors
among the potentially most powerful drugs for the treatment of pancreatic tumor
Robustness of the Sequential Efficient Design for Identifying a Target Subpopulation
No full textPrecision medicine is an innovative approach for tailoring treatments based on individual characteristics or biomarkers. Enrichment is a main strategy in the development of clinical trials for precision medicine as it “is the prospective use of any patient characteristic to select a study population in which detection of a drug effect (if one is, in fact, present) is more likely than it would be in an unselected population.” (FDA, 2019) [ 1]. Although a binary biomarker can be used to stratify the subjects, the situation is more complex if a continuous
biomarker is associated with patient responses. Recently Baldi Antognini et al. [ 2] provided the optimal allocations for inference on the threshold of a continuous biomarker and proposed a new Covariate-Adaptive
procedure, called the Sequential Efficient Design (SED), to implement these designs sequentially. In this paper we push forward the results by exploring the robustness of the SED under possible deviation from the
linearity assumption of the response-biomarker relationship, taking also into account comparisons with the permuted block design
Pre-eclampsia: From Etiology and Molecular Mechanisms to Clinical Tools. A Review of the Literature
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