bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuropsychological Outcome in Chemotherapy-Only–Treated Children With Acute Lymphoblastic Leukemia
Authors: Jansen Nathalie C.A.J. , Kingma Annette , Schuitema Arnout , Bouma Anke , Veerman Anjo J.P. , Kamps Willem A. 
Published: June 2008

Purpose To evaluate neuropsychological functioning over time in children treated for acute lymphoblastic leukemia (ALL) with chemotherapy only. Patients and Methods Forty-nine consecutive patients (median age at first assessment, 6.8 years; range, 4.0 to 11.8 years) treated with intrathecal and systemic chemotherapy were included in a nationwide, prospective-longitudinal, sibling-controlled study. Patients and siblings completed three extensive neuropsychological assessments: at diagnosis, 3 to 6 months after completion of (2-year) treatment and 4.5 years after diagnosis. Assessments included measures of learning, memory, attention, speed, executive functioning, visual-constructive functioning, and fine-motor functioning. Multilevel analyses were applied to evaluate patients' performances over time and to compare patients to 29 siblings (median age of siblings at first assessment, 8.2 years; range, 4.5 to 12.6 years) and to normative data. Results No major differences were found in neuropsychological performance between patients and siblings, with both groups performing mainly in the normal range. The patient group as a whole, however, scored significantly lower than the siblings on complex fine-motor functioning at the last evaluation. Large practice effects were found for both patients and siblings in four of 11 tasks. Patients who uttered physical complaints (ie, pain and/or tiredness) at the first pretreatment assessment scored significantly lower than siblings on attention and speed at the last two evaluations. Conclusion Despite intensive and potentially neurotoxic treatment, no evident negative, neuropsychological late effects were found 4.5 years after diagnosis, except for effects on complex fine-motor functioning. Both the large practice effects observed and the poorer performances on sustained attention for patients with physical complaints should be reckoned with in prospective, longitudinal neuropsychological research in children.
ERCC5 Is a Novel Biomarker of Ovarian Cancer Prognosis
Authors: Walsh Christine S. , Ogawa Seishi , Karahashi Hisae , Scoles Daniel R. , Pavelka James C. , Tran Hang , Miller Carl W. , Kawamata Norihiko , Ginther Charles , Dering Judy , Sanada Masashi , Nannya Yasuhito , Slamon Dennis J. , Koeffler H. Phillip , Karlan Beth Y. 
Published: June 2008

Purpose To identify a biomarker of ovarian cancer response to chemotherapy. Patients and Methods Study participants had epithelial ovarian cancer treated with surgery followed by platinum-based chemotherapy. DNA and RNA were isolated from frozen tumors and normal DNA was isolated from matched peripheral blood. A whole-genome loss of heterozygosity (LOH) analysis was performed using a high-density oligonucleotide array. Candidate genomic areas that predicted enhanced response to chemotherapy were identified with Cox proportional hazards methods. Gene expression analyses were performed through microarray experiments. Candidate genes were tested for independent effects on survival using Cox proportional hazards models, Kaplan-Meier survival curves, and the log-rank test. Results Using a whole-genome approach to study the molecular determinants of ovarian cancer response to platinum-based chemotherapy, we identified LOH of a 13q region to predict prolonged progression-free survival (PFS; hazard ratio, 0.23; P = .006). ERCC5 was identified as a candidate gene in this region because of its known function in the nucleotide excision repair pathway, the unique DNA repair pathway that removes platinum-DNA adducts. We found LOH of the ERCC5 gene locus and downregulation of ERCC5 gene expression to predict prolonged PFS. Integration of genomic and gene expression data shows a correlation between 13q LOH and ERCC5 gene downregulation. Conclusion ERCC5 is a novel biomarker of ovarian cancer prognosis and a potential therapeutic target of ovarian cancer response to platinum chemotherapy.
Risk of Cancer byATMMissense Mutations in the General Population
Authors: Dombernowsky Sarah Louise , Weischer Maren , Allin Kristine Højgaard , Bojesen Stig Egil , Tybjjrg-Hansen Anne , Nordestgaard Børge Grønne 
Published: June 2008

PurposeTruncating and missense mutations in the ATM gene, which cause insufficient DNA damage surveillance, allow damaged cells to proceed into mitosis, which eventually results in increased cancer susceptibility. We tested the hypotheses that ATM Ser49Cys and ATM Ser707Pro heterozygosity increase the risk of cancer overall, of breast cancer, and of 26 other cancer subtypes in the general population.Patients and MethodsWe genotyped 10,324 individuals from the Danish general population who were observed prospectively for 36 years, during which 2,056 developed cancer.ResultsMultifactorially adjusted hazard ratios for ATM Ser49Cys heterozygotes versus noncarriers were 1.2 (95% CI, 0.9 to 1.5) for cancer overall, 0.8 (95% CI, 0.3 to 2.0) for breast cancer, 4.8 (95% CI, 2.2 to 11) for melanoma, 2.3 (95% CI, 1.1 to 5.0) for prostate cancer, and 3.4 (95% CI, 1.1 to 11) for cancer of the oral cavity/pharynx. Multifactorially adjusted hazard ratios for ATM Ser707Pro heterozygotes versus noncarriers were 0.8 (95% CI, 0.6 to 1.2) for cancer overall, 0.6 (95% CI, 0.2 to 1.6) for breast cancer, 10 (95% CI, 1.1 to 93) for thyroid/other endocrine tumors, and 2.7 (95% CI, 1.0 to 7.6) for cancer of corpus uteri.ConclusionATM missense mutations do not increase the risk of cancer overall or of breast cancer in the general population; however, we observed in exploratory analyses that ATM missense mutations may be associated with an increased risk of other cancer subtypes. As we did multiple comparisons, some of these findings could represent chance findings rather than real phenomena.
Circulating 25-Hydroxyvitamin D Levels and Survival in Patients With Colorectal Cancer
Authors: Ng Kimmie , Meyerhardt Jeffrey A. , Wu Kana , Feskanich Diane , Hollis Bruce W. , Giovannucci Edward L. , Fuchs Charles S. 
Published: June 2008

PurposeHigher plasma 25-hydroxyvitamin D3(25(OH)D) levels are associated with a decreased incidence of colorectal cancer, but the influence of plasma 25(OH)D on the outcome of patients with established colorectal cancer is unknown.Patients and MethodsWe prospectively examined the association between prediagnosis 25(OH)D levels and mortality among 304 participants in the Nurses' Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS) who were diagnosed with colorectal cancer from 1991 to 2002. Participants diagnosed within 2 years of blood collection were excluded. Patients were observed until death, June 2005 (NHS), or January 2005 (HPFS), whichever came first. The primary end point was overall mortality. Cox proportional hazards models were used to calculate hazard ratios (HR) adjusted for other risk factors for cancer survival.ResultsHigher plasma 25(OH)D levels were associated with a significant reduction in overall mortality (P for trend = .02). Compared with the lowest quartile, participants in the highest quartile had an adjusted HR of 0.52 (95% CI, 0.29 to 0.94) for overall mortality. A trend toward improved colorectal cancer–specific mortality was also seen (HR = 0.61; 95% CI, 0.31 to 1.19). The results remained unchanged after excluding patients diagnosed within 5 years of blood collection (P for trend = .04); the multivariate HR for overall mortality comparing extreme quartiles was 0.45 (95% CI, 0.19 to 1.09).ConclusionAmong patients with colorectal cancer, higher prediagnosis plasma 25(OH)D levels were associated with a significant improvement in overall survival. Further study of the vitamin D pathway and its influence on colorectal carcinogenesis and cancer progression is warranted.
Phase II Trial of Docetaxel With Rapid Androgen Cycling for Progressive Noncastrate Prostate Cancer
Authors: Rathkopf Dana , Carducci Michael A. , Morris Michael J. , Slovin Susan F. , Eisenberger Mario A. , Pili Roberto , Denmeade Samuel R. , Kelsen Moshe , Curley Tracy , Halter Melinda , Collins Connie , Fleisher Martin , Heller Glenn , Baker Sharyn D. , Scher Howard I. 
Published: June 2008

Purpose We evaluated rapid androgen cycling in combination with docetaxel for men with progressive noncastrate prostate cancers. Patients and Methods Noncastrate patients with ≤ 6 months of hormone therapy were eligible. Cohort 1 (62 patients) received six 28-day cycles of docetaxel (75 mg/m2), leuprolide, and 7 days of topical testosterone. Cohort 2 (38 patients) received nine 21-day cycles of docetaxel (70 mg/m2), leuprolide, and 3 days of testosterone. The primary end point was the proportion of patients at 18 months who achieved noncastrate testosterone levels (> 150 ng/dL) and an undetectable prostate-specific antigen (PSA; ≤ 0.05, ≤ 0.5, or ≤ 2.0 ng/mL with prior prostatectomy, radiation therapy, or no definitive therapy, respectively). Cytochrome P450 3A4 (CYP3A4) activity and docetaxel pharmacokinetics were evaluated. Results A higher proportion of patients achieved the undetectable PSA outcome at 18 months in cohort 2 relative to cohort 1 (13% v 0%). The 16% incidence of febrile neutropenia was higher than that observed in patients was castration-resistant disease, which may have been related to a 50% reduction in overall docetaxel clearance in the noncastrate group. There was no alteration in CYP3A4 activity (P = .87) or docetaxel clearance (P = .88) between cycles. Conclusion The undetectable PSA end point allows for a rapid screening of interventions for further study. Increasing the number of docetaxel cycles after a shorter period of testosterone repletion, and a longer duration of testosterone depletion, increased the proportion of men who achieved an undetectable PSA. The higher-than-expected incidence of febrile neutropenia may have been related to the reduced overall docetaxel clearance in patients with noncastrate versus castrate testosterone levels.
One Hundred Years After “Carcinoid”: Epidemiology of and Prognostic Factors for Neuroendocrine Tumors in 35,825 Cases in the United States
Authors: Yao James C. , Hassan Manal , Phan Alexandria , Dagohoy Cecile , Leary Colleen , Mares Jeannette E. , Abdalla Eddie K. , Fleming Jason B. , Vauthey Jean-Nicolas , Rashid Asif , Evans Douglas B. 
Published: June 2008

Purpose Neuroendocrine tumors (NETs) are considered rare tumors and can produce a variety of hormones. In this study, we examined the epidemiology of and prognostic factors for NETs, because a thorough examination of neither had previously been performed. Methods The Surveillance, Epidemiology, and End Results (SEER) Program registries were searched to identify NET cases from 1973 to 2004. Associated population data were used for incidence and prevalence analyses. Results We identified 35,618 patients with NETs. We observed a significant increase in the reported annual age-adjusted incidence of NETs from 1973 (1.09/100,000) to 2004 (5.25/100,000). Using the SEER 9 registry data, we estimated the 29-year limited-duration prevalence of NETs on January 1, 2004, to be 9,263. Also, the estimated 29-year limited-duration prevalence in the United States on that date was 103,312 cases (35/100,000). The most common primary tumor site varied by race, with the lung being the most common in white patients, and the rectum being the most common in Asian/Pacific Islander, American Indian/Alaskan Native, and African American patients. Additionally, survival duration varied by histologic grade. In multivariate analysis of patients with well-differentiated to moderately differentiated NETs, disease stage, primary tumor site, histologic grade, sex, race, age, and year of diagnosis were predictors of outcome (P < .001). Conclusion We observed increased reported incidence of NETs and increased survival durations over time, suggesting that NETs are more prevalent than previously reported. Clinicians need to be become familiar with the natural history and patterns of disease progression, which are characteristic of these tumors.
Stem Cell–Related “Self-Renewal” Signature and High Epidermal Growth Factor Receptor Expression Associated With Resistance to Concomitant Chemoradiotherapy in Glioblastoma
Authors: Murat Anastasia , Migliavacca Eugenia , Gorlia Thierry , Lambiv Wanyu L. , Shay Tal , Hamou Marie-France , de Tribolet Nicolas , Regli Luca , Wick Wolfgang , Kouwenhoven Mathilde C.M. , Hainfellner Johannes A. , Heppner Frank L. , Dietrich Pierre-Yves , Zimmer Yitzhak , Cairncross J. Gregory , Janzer Robert-Charles , Domany Eytan , Delorenzi Mauro , Stupp Roger , Hegi Monika E. 
Published: June 2008

Purpose Glioblastomas are notorious for resistance to therapy, which has been attributed to DNA-repair proficiency, a multitude of deregulated molecular pathways, and, more recently, to the particular biologic behavior of tumor stem-like cells. Here, we aimed to identify molecular profiles specific for treatment resistance to the current standard of care of concomitant chemoradiotherapy with the alkylating agent temozolomide. Patients and Methods Gene expression profiles of 80 glioblastomas were interrogated for associations with resistance to therapy. Patients were treated within clinical trials testing the addition of concomitant and adjuvant temozolomide to radiotherapy. Results An expression signature dominated by HOX genes, which comprises Prominin-1 (CD133), emerged as a predictor for poor survival in patients treated with concomitant chemoradiotherapy (n = 42; hazard ratio = 2.69; 95% CI, 1.38 to 5.26; P = .004). This association could be validated in an independent data set. Provocatively, the HOX cluster was reminiscent of a “self-renewal” signature (P = .008; Gene Set Enrichment Analysis) recently characterized in a mouse leukemia model. The HOX signature and EGFR expression were independent prognostic factors in multivariate analysis, adjusted for the O-6-methylguanine-DNA methyltransferase (MGMT) methylation status, a known predictive factor for benefit from temozolomide, and age. Better outcome was associated with gene clusters characterizing features of tumor-host interaction including tumor vascularization and cell adhesion, and innate immune response. Conclusion This study provides first clinical evidence for the implication of a “glioma stem cell” or “self-renewal” phenotype in treatment resistance of glioblastoma. Biologic mechanisms identified here to be relevant for resistance will guide future targeted therapies and respective marker development for individualized treatment and patient selection.
Risk of Prostate Cancer Recurrence in Men Treated With Radiation Alone or in Conjunction With Combined or Less Than Combined Androgen Suppression Therapy
Authors: D'Amico Anthony V. , Chen Ming-Hui , Renshaw Andrew A. , Loffredo Brittany , Kantoff Philip W. 
Published: June 2008

Purpose We determined the risk of recurrence in men enrolled on a randomized trial for prostate cancer who were treated with radiation therapy (RT) alone or in conjunction with combined or less than combined androgen suppression therapy (AST). Patients and Methods Between 1995 and 2001, 206 men with localized but unfavorable-risk adenocarcinoma of the prostate were randomly assigned to receive RT or RT and AST, which was defined as 6 months of both a luteinizing hormone-releasing hormone agonist and an antiandrogen. A post–random assignment hypothesis that was generated by multivariable Cox regression analyses was used to evaluate whether the risk of prostate-specific antigen (PSA) recurrence was significantly associated with months of antiandrogen use; regression analysis adjusted for known prognostic factors, comorbidity score, and medications that can elevate liver function tests sufficiently to necessitate discontinuation of the antiandrogen. Results After a median follow-up of 8.2 years (interquartile range,7.0 to 9.5 years), 81 men sustained PSA recurrence. An increasing PSA level (P < .001); Gleason score of 8, 9, or 10 (P < .001); and clinical category T2 disease (P = .005) were significantly associated with an increased risk of recurrence. However, recurrence risk was significantly decreased (adjusted hazard ratio, 0.81; 95% CI, 0.72 to 0.92; P = .001) with each additional month of antiandrogen use after analysis was adjusted for these known prognostic factors. Conclusion Men with localized but unfavorable-risk prostate cancer who were treated with RT and 6 months of planned combined AST appear to have an increased risk of recurrence when treated with less than as compared with 6 months of the antiandrogen.
Minimal Residual Disease Values Discriminate Between Low and High Relapse Risk in Children With B-Cell Precursor Acute Lymphoblastic Leukemia and an Intrachromosomal Amplification of Chromosome 21: The Austrian and German Acute Lymphoblastic Leukemia Berlin-Frankfurt-Münster (ALL-BFM) Trials
Authors: Attarbaschi Andishe , Mann Georg , Panzer-Grümayer Renate , Röttgers Silja , Steiner Manuel , König Margit , Csinady Eva , Dworzak Michael N. , Seidel Markus , Janousek Dasa , Möricke Anja , Reichelt Carsten , Harbott Jochen , Schrappe Martin , Gadner Helmut , Haas Oskar A. 
Published: June 2008

Purpose We aimed to identify relapse predictors in children with a B-cell precursor acute lymphoblastic leukemia (ALL) and an intrachromosomal amplification of chromosome 21 (iAMP21), a novel genetic entity associated with poor outcome. Patients and Methods We screened 1,625 patients who were enrolled onto the Austrian and German ALL–Berlin-Frankfurt-Münster (ALL-BFM) trials 86, 90, 95, and 2000 with ETV6/RUNX1-specific fluorescent in situ hybridization probes, and we identified 29 patient cases (2%) who had an iAMP21. Minimal residual disease (MRD) was quantified with clone-specific immunoglobulin and T-cell receptor gene rearrangements. Results Twenty-five patients were good responders to prednisone, and all achieved remission after induction therapy. Eleven patients experienced relapse, which included eight who experienced relapse after cessation of front-line therapy. Six-year event-free and overall survival rates were 37% ± 14% and 66% ± 11%, respectively. Results of MRD analysis were available in 24 (83%) of 29 patients: nine (37.5%) belonged to the low-risk, 14 (58.5%) to the intermediate-risk, and one (4%) to the high-risk group. MRD results were available in 8 of 11 patients who experienced a relapse. Seven occurred among the 14 intermediate-risk patients, and one occurred in the high-risk patient. Conclusion The overall and early relapse rates in the BFM study were lower than that in a previous United Kingdom Medical Research Council/Childhood Leukemia Working Party study (38% v 61% and 27% v 47%, respectively), which might result from more intensive induction and early reintensification therapy in the ALL-BFM protocols. MRD values were the only reliable parameter to discriminate between a low and high risk of relapse (P = .02).
Acylated Ghrelin Inhibits Spontaneous Luteinizing Hormone Pulsatility and Responsiveness to Naloxone But Not That to Gonadotropin-Releasing Hormone in Young Men: Evidence for a Central Inhibitory Action of Ghrelin on the Gonadal Axis
Authors: Lanfranco Fabio , Bonelli Lorenza , Baldi Matteo , Me Elisa , Broglio Fabio , Ghigo Ezio 
Published: June 2008

Context: Recent evidence suggests that ghrelin exerts a negative modulation on the gonadal axis. Ghrelin was reported to suppress LH secretion in both animal and human models. Moreover, acylated ghrelin (AG) also decreases the LH responsiveness to GnRH in vitro.
Objective: The objective of the study was to evaluate the effects of AG infusion on spontaneous and stimulated gonadotropin secretion.
Design, Participants, and Intervention: In seven young healthy male volunteers (age mean ± sem 26.4 ± 2.6 yr), we evaluated LH and FSH levels every 15 min during: 1) iv isotonic saline infusion; 2) iv saline followed by AG; LH and FSH response to GnRH (100 μg iv as a bolus), 3) alone and 4) during AG infusion; LH and FSH response to naloxone (0.1 mg/kg iv as a slow bolus), 5) alone and 6) during AG infusion.
Results: Significant LH but not FSH pulses were recorded in all subjects under saline infusion. AG infusion inhibited LH levels [area under the curve(240–480): 415.8 ± 69.7 mIU/ml·min during AG vs. 744.6 ± 120.0 mIU/ml·min during saline, P &lt; 0.02] and abolished LH pulsatility. No change in FSH secretion was recorded. The LH and FSH responses to GnRH during saline were not affected by AG administration. However, AG inhibited the LH response to naloxone [area under the curve (120–210): 229.9 ± 39.3 mIU/ml·min during AG vs. 401.1 ± 44.6 mIU/ml·min during saline, P &lt; 0.01]. FSH levels were not modified by naloxone alone or in combination with AG.
Conclusions: AG inhibits both spontaneous LH pulsatility and the LH response to naloxone. Because AG does not affect the LH response to GnRH, these findings indicate that the ghrelin system mediates central inhibition of the gonadal axis.
Homozygous Mutation G539R in the Gene for P450 Oxidoreductase in a Family Previously Diagnosed as Having 17,20-Lyase Deficiency
Authors: Hershkovitz Eli , Parvari Ruthi , Wudy Stefan A. , Hartmann Michaela F. , Gomes Larissa G. , Loewental Neta , Miller Walter L. 
Published: June 2008

Context: Very few patients have been described with isolated 17,20-lyase deficiency who have had their mutations in P450c17 (17α-hydroxylase/17,20-lyase) proven by DNA sequencing and in vitro characterization of the mutations. Most patients with 17,20-lyase deficiency have mutations in the domain of P450c17 that interact with the electron-donating redox partner, P450 oxidoreductase (POR).Objective: Our objective was to clarify the genetic and functional basis of isolated 17,20-lyase deficiency in familial cases who were previously reported as having 17,20-lyase deficiency.Patients: Four undervirilized males of an extended Bedouin family were investigated. One of these has previously been reported to carry mutations in the CYP17A1 gene encoding P450c17 causing isolated 17,20-lyase deficiency.Methods: Serum hormones were evaluated before and after stimulation with ACTH. Urinary steroid metabolites were profiled by gas chromatography-mass spectrometry. Exons 1 and 8 of CYP17A1 previously reported to harbor mutations in one of these patients and all 15 coding exons of POR were sequenced.Results: Gas chromatography-mass spectrometry (GC-MS) urinary steroid profiling and serum steroid measurements showed combined deficiencies of 17,20-lyase and 21-hydroxylase. Sequencing of exons 1 and 8 of CYP17A1 in two different laboratories showed no mutations. Sequencing of POR showed that all four patients were homozygous for G539R, a previously studied mutation that retains 46% of normal capacity to support the 17α-hydroxylase activity but only 8% of the 17,20-lyase activity of P450c17.Conclusion: POR deficiency can masquerade clinically as isolated 17,20-lyase deficiency.