1,720,971 research outputs found
Heterogeneous prognostic impact of 9q+ deletions in patients with chronic myelogenous leukemia
No full textPolymorphic variation at the STAT5 locus is associated with the response of CML patients to interferon alpha
No full textCharacterization of two new imatinib-responsive fusion genes generated by disruption of PDGFRB in eosinophilia-associated chronic myeloproliferative disorders
No full textIrinotecan and capecitabine as second-line treatment after failure for first-line infusional 24-h 5-fluorouracil/folinic acid in advanced colorectal cancer: a phase II study
No full textThe efficacy of combination therapy with irinotecan and capecitabine has been demonstrated for the first-line treatment of metastatic colorectal cancer (MCRC). The aim of this trial was to evaluate the efficacy and safety of this combination in MCRC as second-line treatment after failure of 24-h infusional 5-fluorouracil (5-FU24h) and folinic acid (FA). Patients pre-treated with 5-FU24h/FA were recruited at two institutions to receive 6xweekly irinotecan 70 mg/m2 and capecitabine (1000 mg/m2 b.i.d. days 1-14 and 22-35). Courses were repeated on day 50. In elderly patients (>65 years) a 20% dose reduction of both drugs was scheduled. Twenty-eight patients [M/F 20/8; median age 65 years (range 44-79); median ECOG score 1] were enrolled. The most frequent sites of metastases were liver, n=20, lymph nodes and lungs, n=10, respectively. Half of the patients had two or more metastatic sites. A total of 71 treatment courses (median 2, range 1-8) were administered. Main toxicities [worst per patient (%); CTC grade 1/2/3/4] were: anaemias 18/14/-/-; leukocytopenia 11/21/-/-; thrombocytopenia 11/-/-/-; diarrhea 18/36/21/-; nausea/vomiting 43/29/4/-; mucositis 4/11/-/-; alopecia 7/25/-/-; hand-foot syndrome 7/21/-/-; fatigue 14/14/-/-; renal insufficiency (caused by diarrhea and exsiccosis) -/-/-/7. Dose intensity in the first course was [median/mean (%)]: irinotecan 92/83; capecitabine 88/82. Twenty-three patients are evaluable for response analysis (five did not complete the first course): three patients showed partial remissions (13%) and 11 patients had stable disease (48%). Median time to progression was 3.0 months for the total population (range 1.4-17.3) and 6.5 months for responders (partial response plus no change). Seventy-four percent of the patients received a third-line therapy. Overall survival was 15.7 months calculated from the start of study treatment. Second-line therapy with irinotecan and capecitabine yielded a tumor control in 61% of patients with MCRC. Efficacy and toxicity data are comparable to 5-FU/irinotecan combinations, although the likelihood of severe diarrhea appears to be higher with capecitabine/irinotecan
A polymorphism associated with STAT3 expression and response of chronic myeloid leukemia to interferon alpha
No full textInterferon alpha (IFN) induces variable responses in chronic myeloid leukemia (CML), with 8-30% of early chronic phase cases achieving a complete cytogenetic response. We hypothesized that polymorphic differences in genes encoding IFN signal transduction components might account for different patient responses. We studied 174 IFN-treated patients, of whom 79 achieved less than 35% Philadelphia-chromosome (Ph) positive metaphases (responders) and 95 failed to show any cytogenetic response (more than 95% Ph-positive metaphases; non-responders). We compared 17 single nucleotide polymorphisms (SNPs) at IFNAR1, IFNAR2, JAK1, TYK2, STAT1, STAT3 and STAT5a/b between the two groups and found a significant difference for rs6503691, a SNP tightly linked to STAT5a, STAT5b and STAT3 (minor allele frequency 0.16 for non-responders; 0.06 for responders, P=0.007). Levels of STAT3 mRNA correlated with rs6503691 genotype (P<0.001) as assessed by real time quantitative PCR and therefore we conclude that rs6503691 is associated with the STAT3 expression levels and response of CML patients to IF
Pegylated liposomal doxorubicin and mitomycin C in combination with infusional 5-fluorouracil and sodium folinic acid in the treatment of advanced gastric cancer: results of a phase II trial
No full textMitomycin C (MMC) in combination with infusional 5-fluorouracil (5-FU) is a well-tolerated active combination therapy for advanced gastric cancer. Pegylated liposomal doxorubicin (Caelyx) has been combined with this regimen in a phase I study exhibiting promising activity in patients with upper gastrointestinal tumors. In the present study, we investigated activity and tolerability of this three-drug regimen in patients with gastric cancer. Patients with advanced or metastatic gastric cancer were recruited to receive weekly infusional 5-FU (2000 mg/m2) mixed with sodium folinic acid (FA; 500 mg/m2) in one pump (days 1, 8, 15, 22, 29, 36). On days 1 and 29, Caelyx (20 mg/m2) was given as a 1-h, and MMC (7 mg/m2) was applied as bolus injection on days 8 and 36. Treatment courses were repeated on day 57. Twenty-seven patients with a median age of 66 years were recruited in a single center; 56% had histologically proven peritoneal carcinomatosis and 26 patients are evaluable for toxicity. Common Toxicity Criteria of the National Cancer Institute grade 3 toxicity was recorded in 34% of the patients (anemia 12%, leukocytopenia 8%, febrile neutropenia 4%, thrombocytopenia 12%, nausea 15%, diarrhea 8% and mucositis 4%). One patient developed hemolytic-uremic syndrome. One complete (5%) and eight partial responses (42%) were observed in 19 patients evaluable for response according to WHO criteria. Seven patients had no change (37%) and three (16%) progressive disease. Six patients with peritoneal carcinomatosis not amenable to WHO response assessment had progression-free intervals between 8 and 21 months. Median survival for all patients was 14.7 months and median time to progression was 8.4 months. We conclude that this new three-drug combination regimen yields a promising overall response rate (47%) in patients with gastric cancer despite the inclusion of a majority of elderly patients at moderate or high risk of death in this trial. Its safety and good tolerability as established in the phase I trial was confirmed
Diagnosis and monitoring of residual disease by quantitative RT-PCR in eosinophilia-associated myeloproliferative disorders with rearrangements of PDGFRA and PDGFRB
No full textIn eosinophilia-associated myeloproliferative disorders with rearrangements of PDGFRA or PDGFRB, molecular diagnosis of the respective fusion genes and monitoring of minimal residual disease (MRD) during treatment with imatinib are compromised by the heterogeneity of the fusion partners. We therefore sought to establish a rapid and reliable quantitative RT-PCR assay (RQ-PCR) using the LightCycler technology for the detection and quantification of PDGFR fusion transcripts by universal amplification of regions which are located downstream to known breakpoint cluster regions within PDGFRA exon 12 and between intron 9 and 11 of PDGFRB. Diagnostic analyses were performed in cDNAs derived from bone marrow or peripheral blood samples of 39 patients (pts) with FIP1L1-PDGFRA (n=31), BCR-PDGFRA (n=1), CDK5RAP2-PDGFRA (n=1), H4-PDGFRB (n=2), ETV6-PDGFRB (n=2), GIT2-PDGFRB (n=1) and GPIAP1-PDGFRB (n=1) fusion genes (36m, 3f, median age 56 ys, range 20 – 73). Except in FIP1L1-PDGFRA positive cases, all patients revealed involvement of chromosome bands 4q12 (PDGFRA) or 5q31–33 (PDGFRB) in chromosomal aberrations identified by conventional cytogenetics. As external standards for quantification, serial dilutions of plasmids containing normal PDGFRA and PDGFRB sequences were employed. ABL transcripts were quantified as internal control and results were expressed as ratios PDGFRA/ABL or PDGFRB/ABL. A cut-off point for overexpression of PDGFRA and PDGFRB (mean+/–2SD) was determined by analysis of a series of 30 healthy volunteers. In healthy individuals, PDGFRA is expressed at very low levels if at all, whereas PDGFRB is expressed at comparable levels to ABL. Serial dilutions of the FIP1L1-PDGFRA positive EOL1 cell line in HL60 cells and of mRNAs derived from patients with known fusion genes (FIP1L1-PDGFRA and H4-PDGFRB) in control mRNA revealed an assay sensitivity of up to 1:1,000 for both fusion genes which was two logs lower than the sensitivity of the specific nested RT-PCRs (1:100,000). At diagnosis, all pts with PDGFR fusion genes showed significantly increased transcript levels compared to healthy controls. The transcript levels ranged within 4 orders of magnitude for PDGFRA (ratio PDGFRA/ABL 0.03–51) and one order of magnitude for PDGFRB fusion genes (ratio PDGFRB/ABL 190–1350). Serial quantification for MRD monitoring during treatment with imatinib has been performed in 21 pts with PDGFRA (100–400 mg/d) and 5 pts with PDGFRB (400mg/d) fusion genes, respectively. In PDGFRA cases, RQ-PCR for PDGFRA transcripts became negative in 21 of 21 patients after a median of 13 weeks (range, 8–67) which was confirmed by fusion gene specific nested RT-PCR in 19 of 21 cases after a median of 21 weeks (range, 28–67). In PDGFRB cases, RQ-PCR for PDGFRB became negative in 4 of 5 patients after a median of 44 weeks (range 16–72 weeks) which was confirmed by fusion gene specific nested RT-PCR in 1 of 5 patients after 40 weeks. We conclude that the universal quantification of regions which are located downstream to known breakpoint cluster regions of PDGFRA and PDGFRB is a sensitive and reliable assay for the routine screening of constitutive activation of PDGFRA or PDGFRB and for monitoring of residual disease during treatment with tyrosine kinase inhibitors
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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