90Yttrium-Ibritumomab Tiuxetan Consolidation of First Remission in Advanced-Stage Follicular Non-Hodgkin Lymphoma: Updated Results After a Median Follow-Up of 7.3 Years From the International, Randomized, Phase III First-Line Indolent Trial.

PURPOSE Updated results are presented after a median follow-up of 7.3 years from the phase III First-Line Indolent Trial of yttrium-90 ((90)Y) -ibritumomab tiuxetan in advanced-stage follicular lymphoma (FL) in first remission. PATIENTS AND METHODS Patients with CD20(+) stage III or IV FL with complete response (CR), unconfirmed CR (CRu), or partial response (PR) after first-line induction treatment were randomly assigned to (90)Y-ibritumomab consolidation therapy (rituximab 250 mg/m(2) days -7 and 0, then (90)Y-ibritumomab 14.8 MBq/kg day 0; maximum 1,184 MBq) or no further treatment (control). Primary end point was progression-free survival (PFS) from date of random assignment. Results For 409 patients available for analysis ((90)Y-ibritumomab, n = 207; control, n = 202), estimated 8-year overall PFS was 41% with (90)Y-ibritumomab versus 22% for control (hazard ratio [HR], 0.47; P < .001). For patients in CR/CRu after induction, 8-year PFS with (90)Y-ibritumomab was 48% versus 32% for control (HR, 0.61; P = .008), and for PR patients, it was 33% versus 10% (HR, 0.38; P < .001). For (90)Y-ibritumomab consolidation, median PFS was 4.1 years (v 1.1 years for control; P < .001). Median time to next treatment (TTNT) was 8.1 years for (90)Y-ibritumomab versus 3.0 years for control (P < .001) with approximately 80% response rates to second-line therapy in either arm, including autologous stem-cell transplantation. No unexpected toxicities emerged during long-term follow-up. Estimated between-group 8-year overall survival rates were similar. Annualized incidence rate of myelodysplastic syndrome/acute myeloblastic leukemia was 0.50% versus 0.07% in (90)Y-ibritumomab and control groups, respectively (P = .042). CONCLUSION (90)Y-ibritumomab consolidation after achieving PR or CR/CRu to induction confers 3-year benefit in median PFS with durable 19% PFS advantage at 8 years and improves TTNT by 5.1 years for patients with advanced FL.

Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial--SAKK 44/00-CECOG/PAN.1.3.001.

PURPOSE: To compare clinical benefit response (CBR) and quality of life (QOL) in patients receiving gemcitabine (Gem) plus capecitabine (Cap) versus single-agent Gem for advanced/metastatic pancreatic cancer. PATIENTS AND METHODS: Patients were randomly assigned to receive GemCap (oral Cap 650 mg/m(2) twice daily on days 1 through 14 plus Gem 1,000 mg/m(2) in a 30-minute infusion on days 1 and 8 every 3 weeks) or Gem (1,000 mg/m(2) in a 30-minute infusion weekly for 7 weeks, followed by a 1-week break, and then weekly for 3 weeks every 4 weeks) for 24 weeks or until progression. CBR criteria and QOL indicators were assessed over this period. CBR was defined as improvement from baseline for >or= 4 consecutive weeks in pain (pain intensity or analgesic consumption) and Karnofsky performance status, stability in one but improvement in the other, or stability in pain and performance status but improvement in weight. RESULTS: Of 319 patients, 19% treated with GemCap and 20% treated with Gem experienced a CBR, with a median duration of 9.5 and 6.5 weeks, respectively (P < .02); 54% of patients treated with GemCap and 60% treated with Gem had no CBR (remaining patients were not assessable). There was no treatment difference in QOL (n = 311). QOL indicators were improving under chemotherapy (P < .05). These changes differed by the time to failure, with a worsening 1 to 2 months before treatment failure (all P < .05). CONCLUSION: There is no indication of a difference in CBR or QOL between GemCap and Gem. Regardless of their initial condition, some patients experience an improvement in QOL on chemotherapy, followed by a worsening before treatment failure.

A multiplicity of factors contributes to selective RNA polymerase III occupancy of a subset of RNA polymerase III genes in mouse liver.

The genomic loci occupied by RNA polymerase (RNAP) III have been characterized in human culture cells by genome-wide chromatin immunoprecipitations, followed by deep sequencing (ChIP-seq). These studies have shown that only ∼40% of the annotated 622 human tRNA genes and pseudogenes are occupied by RNAP-III, and that these genes are often in open chromatin regions rich in active RNAP-II transcription units. We have used ChIP-seq to characterize RNAP-III-occupied loci in a differentiated tissue, the mouse liver. Our studies define the mouse liver RNAP-III-occupied loci including a conserved mammalian interspersed repeat (MIR) as a potential regulator of an RNAP-III subunit-encoding gene. They reveal that synteny relationships can be established between a number of human and mouse RNAP-III genes, and that the expression levels of these genes are significantly linked. They establish that variations within the A and B promoter boxes, as well as the strength of the terminator sequence, can strongly affect RNAP-III occupancy of tRNA genes. They reveal correlations with various genomic features that explain the observed variation of 81% of tRNA scores. In mouse liver, loci represented in the NCBI37/mm9 genome assembly that are clearly occupied by RNAP-III comprise 50 Rn5s (5S RNA) genes, 14 known non-tRNA RNAP-III genes, nine Rn4.5s (4.5S RNA) genes, and 29 SINEs. Moreover, out of the 433 annotated tRNA genes, half are occupied by RNAP-III. Transfer RNA gene expression levels reflect both an underlying genomic organization conserved in dividing human culture cells and resting mouse liver cells, and the particular promoter and terminator strengths of individual genes.

Chemisorption of group-III metals on the Si(111) and Ge(111) surfaces: An ab initio study

Chemisorption of group-III metal adatoms on Si(111) and Ge(111) has been studied through the ab initio Hartree-Fock method including nonempirical pseudopotentials and using cluster models to simulate the surface. Three different high-symmetry sites (atop, eclipsed, and open) have been considered by using X4H9, X4H7, and X6H9 (X=Si,Ge) cluster models. In a first step, ideal surface geometries have been used. Metal-induced reconstruction upon chemisorption has also been taken into account. Equilibrium distances, binding energies, and vibrational frequencies have been obtained and compared with available experimental data. From binding-energy considerations, the atop and eclipsed sites seem to be the most favorable ones and thus a coadsorption picture may be suggested. Group-III metals exhibit a similar behavior and the same is true for Si(111) and Ge(111) surfaces when chemisorption is considered.

Genomic Study of RNA Polymerase II and III SNAP(c)-Bound Promoters Reveals a Gene Transcribed by Both Enzymes and a Broad Use of Common Activators.

SNAP(c) is one of a few basal transcription factors used by both RNA polymerase (pol) II and pol III. To define the set of active SNAP(c)-dependent promoters in human cells, we have localized genome-wide four SNAP(c) subunits, GTF2B (TFIIB), BRF2, pol II, and pol III. Among some seventy loci occupied by SNAP(c) and other factors, including pol II snRNA genes, pol III genes with type 3 promoters, and a few un-annotated loci, most are primarily occupied by either pol II and GTF2B, or pol III and BRF2. A notable exception is the RPPH1 gene, which is occupied by significant amounts of both polymerases. We show that the large majority of SNAP(c)-dependent promoters recruit POU2F1 and/or ZNF143 on their enhancer region, and a subset also recruits GABP, a factor newly implicated in SNAP(c)-dependent transcription. These activators associate with pol II and III promoters in G1 slightly before the polymerase, and ZNF143 is required for efficient transcription initiation complex assembly. The results characterize a set of genes with unique properties and establish that polymerase specificity is not absolute in vivo.

Desempenho de novos clones de seringueira: III. seleções promissoras para a região de Votuporanga, Estado de São Paulo

É apresentado o resultado da primeira seleção de 25 clones de seringueira (Hevea brasiliensis (Willd. ex Adr. de Juss.) Müell. Arg.), a maior parte constituída de introduções de diferentes origens. Após multiplicados, foram avaliados em experimentos do tipo pequena escala, obedecendo ao delineamento de blocos ao acaso, instalado na Estação Experimental de Votuporanga, SP. Os caracteres avaliados foram: produção de borracha seca, vigor expresso pelo perímetro do caule, espessura de casca e número de anéis de vasos laticíferos. Com relação à produção de borracha seca, destacaram-se os clones IAN 3156, IAC 40, 7/6, 3/5 e 3/1, produzindo 124%, 105%, 27%, 26% e 19% superiores em relação ao RRIM 600, recomendando-se seu plantio em pequena escala na região de Jaú. Caracteres secundários tais como o vigor, espessura de casca e número de anéis de vasos laticíferos dos clones testados são também discutidos. Sugere-se sua avaliação em experimentos do tipo grande escala com o objetivo de avaliar, além da produção, outros caracteres secundários para futuras recomendações no Estado de São Paulo.

Defining the RNA polymerase III transcriptome: Genome-wide localization of the RNA polymerase III transcription machinery in human cells.

Our view of the RNA polymerase III (Pol III) transcription machinery in mammalian cells arises mostly from studies of the RN5S (5S) gene, the Ad2 VAI gene, and the RNU6 (U6) gene, as paradigms for genes with type 1, 2, and 3 promoters. Recruitment of Pol III onto these genes requires prior binding of well-characterized transcription factors. Technical limitations in dealing with repeated genomic units, typically found at mammalian Pol III genes, have so far hampered genome-wide studies of the Pol III transcription machinery and transcriptome. We have localized, genome-wide, Pol III and some of its transcription factors. Our results reveal broad usage of the known Pol III transcription machinery and define a minimal Pol III transcriptome in dividing IMR90hTert fibroblasts. This transcriptome consists of some 500 actively transcribed genes including a few dozen candidate novel genes, of which we confirmed nine as Pol III transcription units by additional methods. It does not contain any of the microRNA genes previously described as transcribed by Pol III, but reveals two other microRNA genes, MIR886 (hsa-mir-886) and MIR1975 (RNY5, hY5, hsa-mir-1975), which are genuine Pol III transcription units.

Evaluation des résultats du traitement chirurgical des luxations acromio-claviculaires de type III selon un score cinématique

Introduction : Le traitement des entorses acromio-claviculaires (AC) est aujourd'hui encore controversé. Les luxations AC avec lésion du fascia delto-trapézoidale (grade IV, V et VI) sont généralement traitées par une chirurgie de stabilisation. A l'inverse les entorses sans luxation de la clavicule (grade I et II) sont traitées conservativement avec de bons résultats. Il reste une interrogation concernant le traitement des luxations AC sans lésion du fascia delto-trapézoidale (grade III). Le but de notre étude est d'évaluer les résultats du traitement chirurgical des entorses AC de grade III selon un score cinématique. Matériel et Méthode : 30 patients avec une entorse AC de grade III ont été opérés d'une stabilisation de la clavicule entre 2003 et 2011 par le service d'Orthopédie et traumatologie du CHUV. Tous ont été cliniquement évalués selon le score de Constant. L'évaluation cinématique a été effectuée à l'aide d'un iPod touch, fixé sur l'humérus. Cet outil de mesure, décrit et validé par l'EPFL, prend en considération l'accélération et la vitesse angulaire du membre supérieur pour 7 différents mouvements des deux bras. L'évaluation cinématique a été effectuée en comparant le côté opéré par rapport au côté sain selon 2 scores (RAV et P) provenant de ces variables. Les scores RAV et P sont calculés par l'application installée sur l'iPod touch, ils sont donnés en pourcentage par rapport à l'épaule saine. Nous avons défini un score de Constant relatif de plus de 60 et un score cinématique de plus de 75% comme satisfaisant. Résultats : Nous avons revus dix patients avec un recul moyen de 36 mois (6 à 72 mois) d'un âge moyen de 42 ans (27 à 62 ans). Le score de Constant moyen est de 75.9 ± 21.7. Le score P moyen est de 89.3% ± 23.4 et le score RAV moyen est de 91.8% ± 15.8 (tab.1). Quatre sujets obtiennent un excellent score de Constant pour le bras opéré, 2 sujets obtiennent un bon score et un sujet obtient un score moyen, tandis que 3 sujets obtiennent un mauvais score. Huit patients obtiennent un score cinématique satisfaisant alors que nous observons 2 résultats non satisfaisants. Les mauvais résultats tant cliniques que cinématiques ont été observés chez des patients travailleurs de force, nécessitant d'effectuer des mouvements de l'épaule au-dessus du niveau du buste. Discussion et Conclusion : Sur la base d'une évaluation clinique et cinématique, le traitement chirugical des entorses AC de grade III donne des résultats satisfaisants. Notre étude ne comportant pas de groupe contrôle et notre série étant non homogène, avec un nombre limité de sujet, nous ne pouvons conclure que le traitement chirurgical est le traitement le mieux adapté aux patients avec une entorse acromio-claviculaires de type III. Nous recommandons toutefois un traitement chirugical chez les patients actifs, et les patients exerçant un métier avec nécessité de mobilisation de l'épaule au dessus du buste. Un travail manuel lourd représente un facteur de mauvais pronostic.

Radiotherapy and temozolomide for newly diagnosed glioblastoma: recursive partitioning analysis of the EORTC 26981/22981-NCIC CE3 phase III randomized trial.

PURPOSE: The European Organisation for Research and Treatment of Cancer and National Cancer Institute of Canada trial on temozolomide (TMZ) and radiotherapy (RT) in glioblastoma (GBM) has demonstrated that the combination of TMZ and RT conferred a significant and meaningful survival advantage compared with RT alone. We evaluated in this trial whether the recursive partitioning analysis (RPA) retains its overall prognostic value and what the benefit of the combined modality is in each RPA class. PATIENTS AND METHODS: Five hundred seventy-three patients with newly diagnosed GBM were randomly assigned to standard postoperative RT or to the same RT with concomitant TMZ followed by adjuvant TMZ. The primary end point was overall survival. The European Organisation for Research and Treatment of Cancer RPA used accounts for age, WHO performance status, extent of surgery, and the Mini-Mental Status Examination. RESULTS: Overall survival was statistically different among RPA classes III, IV, and V, with median survival times of 17, 15, and 10 months, respectively, and 2-year survival rates of 32%, 19%, and 11%, respectively (P < .0001). Survival with combined TMZ/RT was higher in RPA class III, with 21 months median survival time and a 43% 2-year survival rate, versus 15 months and 20% for RT alone (P = .006). In RPA class IV, the survival advantage remained significant, with median survival times of 16 v 13 months, respectively, and 2-year survival rates of 28% v 11%, respectively (P = .0001). In RPA class V, however, the survival advantage of RT/TMZ was of borderline significance (P = .054). CONCLUSION: RPA retains its prognostic significance overall as well as in patients receiving RT with or without TMZ for newly diagnosed GBM, particularly in classes III and IV.

Institution de Jonas, év. d'Orléans.

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