Temsirolimus in the treatment of relapsed and/or refractory mantle cell lymphoma

Patients with mantle cell lymphoma (MCL) have a poor prognosis; consequently, new therapeutic approaches, such as rapamycin and its derivates, mammalian target of rapamycin (mTOR) inhibitors, are warranted. Temsirolimus (also known as CCI-779), a dihydroester of rapamycin, in MCL cell lines inhibited mTOR, downregulated p21 and v-Raf, and induced autophagy. The first clinical trial in MCL patients was performed using 250 mg of temsirolimus weekly for 6–12 cycles. The overall response rate was 38%; the median time to progression was 6.5 months, median overall survival was 12 months, and the median duration of response was 6.9 months. At lower dose (25 mg/week), the overall response rate was 41%, median overall survival was 14 months, and time to progression was 6 months. In another trial, 162 patients were randomly assigned to receive temsirolimus at 2 different doses (175 mg/week for 3 weeks, then 75 mg or 25 mg/week) or a treatment chosen by the investigator among the most frequently adopted single agents for treatment of relapsed MCL. Patients treated with 175/75 mg of temsirolimus had significantly higher response rates and longer progression-free survival than those treated with investigator’s choice therapy. These data support the use of mTOR inhibitors for the treatment of MCL, probably in combination with other agents, such as antiangiogenic drugs or histone acetylase inhibitors

Self help groups in a city of Tuscany: Reconstruction of the second generation model of work for professionals and services

This study is part of a more extensive project aimed to investigate the effectiveness of self-help group participation in improving quality of life in mental disease. The study is taking place in the Tuscany Region, in Italy. In the first qualitative step of analysis researchers are interested in describing the specific features of the psychiatric self-help movement in Tuscany, comparing different realities, networks, kind of groups. Therefore, our aim is to collect exhaustive information to describe how self-help system work in different provinces at the present moment. The implementation of groups for psychiatric problems is quite young in Italy.  Because of a lack of specific regulation in the directives of the Italian health care system, every local service has implemented groups differently, sometimes enhancing, sometimes dismissing them. Prato, near Florence, is one of the more interesting context for the birth of psychiatric self-help movement in the region: public health services improved groups since early 90’s, it was one of the first self-help reality linked to services in the entire region. Now we are in a “second generation” of professionals, and the original meaning of groups seems to be transformed, sometimes misunderstood. Our objectives of study head us toward an in depth analysis of self-help phenomenon in Prato

Self help groups in a city of Tuscany: Reconstruction of the second generation model of work for professionals and services

This study is part of a more extensive project aimed to investigate the effectiveness of self-help group participation in improving quality of life in mental disease. The study is taking place in the Tuscany Region, in Italy. In the first qualitative step of analysis researchers are interested in describing the specific features of the psychiatric self-help movement in Tuscany, comparing different realities, networks, kind of groups. Therefore, our aim is to collect exhaustive information to describe how self-help system work in different provinces at the present moment. The implementation of groups for psychiatric problems is quite young in Italy.  Because of a lack of specific regulation in the directives of the Italian health care system, every local service has implemented groups differently, sometimes enhancing, sometimes dismissing them. Prato, near Florence, is one of the more interesting context for the birth of psychiatric self-help movement in the region: public health services improved groups since early 90’s, it was one of the first self-help reality linked to services in the entire region. Now we are in a “second generation” of professionals, and the original meaning of groups seems to be transformed, sometimes misunderstood. Our objectives of study head us toward an in depth analysis of self-help phenomenon in Prato

Arsenic trioxide and ascorbic acid interfere with the BCL2 family genes in patients with myelodysplastic syndromes: an ex-vivo study.

BACKGROUND: Arsenic Trioxide (ATO) is effective in about 20% of patients with myelodysplasia (MDS); its mechanisms of action have already been evaluated in vitro, but the in vivo activity is still not fully understood. Since ATO induces apoptosis in in vitro models, we compared the expression of 93 apoptotic genes in patients’ bone marrow before and after ATO treatment. For this analysis, we selected 12 patients affected by MDS who received ATO in combination with Ascorbic Acid in the context of the Italian clinical trial NCT00803530, EudracT Number 2005-001321-28. METHODS: Real-time PCR quantitative assays for genes involved in apoptosis were performed using TaqMan® Assays in 384-Well Microfluidic Cards “TaqMan® Human Apoptosis Array”. Quantitative RT-PCR for expression of EVI1 and WT1 genes was also performed. Gene expression values (Ct) were normalized to the median expression of 3 housekeeping genes present in the card (18S, ACTB and GAPDH). RESULTS: ATO treatment induced up-regulation of some pro-apoptotic genes, such as HRK, BAK1, CASPASE-5, BAD, TNFRSF1A, and BCL2L14 and down-regulation of ICEBERG. In the majority of cases with stable disease, apoptotic gene expression profile did not change, whereas in cases with advanced MDS more frequently pro-apoptotic genes were up-regulated. Two patients achieved a major response: in the patient with refractory anemia the treatment down-regulated 69% of the pro-apoptotic genes, whereas 91% of the pro-apoptotic genes were up-regulated in the patient affected by refractory anemia with excess of blasts-1. Responsive patients showed a higher induction of BAD than those with stable disease. Finally, WT1 gene expression was down-regulated by the treatment in responsive cases. CONCLUSIONS: These results represent the basis for a possible association of ATO with other biological compounds able to modify the apoptotic pathways, such as inhibitors of the BCL2 family

Kaluza-Klein bundles and manifolds of exceptional holonomy

We show how in the presence of RR two-form field strength the conditions for preserving supersymmetry on six- and seven-dimensional manifolds lead to certain generalizations of monopole equations. For six dimensions the string frame metric is Kaehler with the complex structure that descends from the octonions if in addition we assume F^{(1,1)}=0. The susy generator is a gauge covariantly constant spinor. For seven dimensions the string frame metric is conformal to a G_2 metric if in addition we assume the field strength to obey a selfduality constraint. Solutions to these equations lift to geometries of G_2 and Spin(7) holonomy respectively.Comment: LaTeX, 13 page

Estratégias de manejo para maximizar o rendimento potencial do arroz irrigado no Rio Grande do Sul.

bitstream/item/33565/1/documento-153.pd

An Immunoenzyme Linked Assay (ELISA) for the Detection of Antibodies to Truncated Glycoprotein D (tgD) of Bovine Herpesvirus-1

Bovine herpesvirus-1 (BHV-1) is responsible for a variety of clinical signs. It is widespread in cattle and causes severe economic losses (Castrucci et al., 2002a, b). To prevent the infection several live and inactivated vaccines are commonly used. However, due to their short-term immunity and incomplete protection, new vaccine strategies have been proposed such as genetic vaccination (Babiuk et al., 1999). With this aim a DNA vaccine, with a plasmid expressing the tgD glycoprotein, known to be responsible for the virus antigenicity and consequent immunogenicity (Castrucci et al., 2004; Gupta et al., 1998), has been investigated. In the present study, the ELISA reaction was performed in order to detect specific antibodies in calves vaccinated with a DNA vaccine using the pcDNA3.1-tgD plasmid

Bluetongue disease

Bluetongue (BT) is a noncontagious OIE-listed disease of domestic and wild ruminants caused by a virus (Bluetongue virus—BTV) of the Orbivirus genus within the family Reoviridae and transmitted by biting midges of the genus Culicoides. BT is a considerable socioeconomic concern and of major importance for the international trade of animals and animal products. In the past, BT endemic areas were considered those between latitudes 40 °N and 35 °S; however, BT has spread far beyond this traditional range. BTV has multiple serotypes and these serotypes exist in a complex network of serological cross-relationships, varying from partial to no protection between heterologous strains. This chapter summarizes several aspects of BT and BTV with particular emphasis for BTV epidemiology in Sahelian Africa