bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor Thymidylate Synthase 1494del6 Genotype As a Prognostic Factor in Colorectal Cancer Patients Receiving Fluorouracil-Based Adjuvant Treatment
Authors: Dotor Emma , Cuatrecases Miriam , Martínez-Iniesta María , Navarro Matilde , Vilardell Felip , Guinó Elisabeth , Pareja Laura , Figueras Agnés , Molleví David G. , Serrano Teresa , de Oca Javier , Peinado Miguel A. , Moreno Víctor , Germà Josep Ramón , Capellá Gabriel , Villanueva Alberto 
Published: March 2006

PurposeThe purpose of this study was to analyze the value of germline and tumor thymidylate synthase (TS) genotyping as a prognostic marker in a series of colorectal cancer patients receiving adjuvant fluorouracil (FU) -based treatment.Patients and MethodsOne hundred twenty-nine colorectal cancer patients homogeneously treated with FU plus levamisole or leucovorin in the adjuvant setting were included. TS enhancer region, 3R G > C single nucleotide polymorphism (SNP), and TS 1494del6 polymorphisms were assessed in both fresh-frozen normal mucosa and tumor. Mutational analyses of TS and allelic imbalances were studied in all primary tumors and in 18 additional metachronic metastases. TS protein immunostaining was assessed in an expanded series of 214 tumors. Multivariate Cox models were adjusted for stage, differentiation, and location.ResultsTumor genotyping (frequency of allelic loss, 26%) showed that the 3R/3R genotype was associated with a better outcome (hazard ratio [HR] = 0.38; 95% CI, 0.16 to 0.93; P = .020 for the recessive model). 3R G > C SNP genotyping did not add prognostic information. Tumor TS 1494del6 allele (frequency of allelic loss, 36%) was protective (for each allele with the deletion, based on an additive model, HR = 0.42; 95% CI, 0.22 to 0.82; P = .0034). Both polymorphisms were in strong linkage disequilibrium (D' = 0.71, P < .001), and the 3R/–6 base pair (bp) haplotype showed a significant overall survival benefit compared with the most prevalent haplotype 2R/+6bp (HR = 0.42; 95% CI, 0.20 to 0.85; P = .017). No TS point mutation was detected in primary tumors or metastases. TS protein immunostaining was not associated with survival or any of the genotypes analyzed.ConclusionTumor TS 1494del6 genotype may be a prognostic factor in FU-based adjuvant treatment of colorectal cancer patients.
High WT1 Expression After Induction Therapy Predicts High Risk of Relapse and Death in Pediatric Acute Myeloid Leukemia
Authors: Lapillonne Hélène , Renneville Aline , Auvrignon Anne , Flamant Cyril , Blaise Annick , Perot Christine , Lai Jean-Luc , Ballerini Paola , Mazingue Françoise , Fasola Sylvie , Dehée Axelle , Bellman Françoise , Adam Mircéa , Labopin Myriam , Douay Luc , Leverger Guy , Preudhomme Claude , Landman-Parker Judith 
Published: March 2006

Purpose To determine whether minimal residual disease (MRD) measured by Wilms' tumor gene 1 (WT1) expression is a prognostic marker in pediatric acute myeloid leukemia (AML), we quantified WT1 transcript by real-time quantitative-polymerase chain reaction in 92 AML at diagnosis and during follow-up. Patients and Methods Patients (median age, 6 years; cytogenetics, favorable 27%, intermediate 59%, poor 13%) were treated between 1995 and 2002 and enrolled in Leucémie aiguë Myéloblastique Enfant (LAME) 89/91, LAME 99 pilot study and Acute Promyelocytic Leukemia French collaborative protocols. With a median follow-up of 26 months, event-free survival was 56% with a standard deviation (SD) of 5% and overall survival of 62.5% with an SD of 6%. WT1 copy number was normalized by TATA box binding protein gene transcripts and expressed as WT1/TBP × 1,000 ratio. Median WT1 ratio in normal patient controls was 12 (range, 0 to 57). A level over two SD than normal bone marrow controls (ie, WT1 ratio > 50), was considered as significant overexpression. Results At diagnosis, WT1 overexpression was detected in 78% of patients (72 of 92 patients; median copy ratio, 2231). The WT1 values were significantly higher (P = .01) in favorable cytogenetics and lower (P < .0001) in M5-FAB subtype, 11q23 rearrangements (P < .001), and infants (P = .003) and demonstrate a strong correlation with fusion transcript AML1-ETO, PML-RARα expression. After induction treatment, WT1 ratio was analyzed in 46 of 72 patients and found above 50 in nine of 36 patients and five of 25 patients at D35-50 and 3 to 5 months, respectively. WT1 ratio > 50 after induction is an independent prognostic risk factor of relapse (P = .002) and death (P = .02). Conclusion WT1 quantification is an informative molecular marker for MRD in pediatric AML and is now performed as prospective analysis in ELAM02 protocol.
Survival Prediction in Patients With Glioblastoma Multiforme by Human Telomerase Genetic Variation
Authors: Wang Luo , Wei Qingyi , Wang Li-E , Aldape Kenneth D. , Cao Yumei , Okcu M. Fatih , Hess Kenneth R. , El-Zein Randa , Gilbert Mark R. , Woo Shiao Y. , Prabhu Sujit S. , Fuller Greg N. , Bondy Melissa L. 
Published: March 2006

Purpose Glioblastoma multiforme (GBM) is the most common and aggressive glioma with the poorest survival. Use of biomarkers for screening patients with GBM may be used to modify treatments and improve outcomes. The level of human telomerase (hTERT) expression is an independent predictor of outcome of many cancers, and a functional variant of hTERT MNS16A (shorter tandem repeats or short [S] allele) is associated with increased hTERT mRNA expression. We investigated whether hTERT MNS16A variant genotype predicted survival in GBM patients. Patients and Methods We genotyped hTERT MNS16A in 299 GBM patients using polymerase chain reaction and determined hTERT genotype by classifying the DNA band of 243 or 272 base pairs (bp) as S allele and 302 or 333 bp as long (L) allele. We compared overall survival using Kaplan-Meier estimates and equality of survival distributions using the log-rank test, and we computed univariate and multivariate Cox proportional hazards models to estimate the effects of selected variables. Results Overall survival differed significantly by hTERT MNS16A genotype, with median survivals of 25.1, 14.7, and 14.6 months for the SS, SL, and LL genotypes, respectively. Compared with the SS genotype, the hazard ratios for the SL and LL genotypes were 1.69 and 1.87, respectively, after adjustment for other factors. Multivariate Cox regression analysis showed an independent statistically significant association between the hTERT MNS16A variant genotype and outcome. Conclusion A functional hTERT MNS16A genotype is a potential biomarker for assessment of survival outcome of GBM. Larger studies are needed to verify these findings.
Human Telomere Reverse Transcriptase Expression Predicts Progression and Survival in Pediatric Intracranial Ependymoma
Authors: Tabori Uri , Ma Jing , Carter Michael , Zielenska Maria , Rutka James , Bouffet Eric , Bartels Ute , Malkin David , Hawkins Cynthia 
Published: March 2006

Purpose Pediatric intracranial ependymomas are a heterogeneous group of neoplasms with unpredictable clinical and biologic behavior. As part of ongoing studies to identify potential biologic and therapeutic markers, we analyzed the role of human telomere reverse transcriptase (hTERT; the catalytic subunit of telomerase) expression as a prognostic marker for this disease. Patients and Methods Primary intracranial ependymomas that were resected at our institution between 1986 and 2004 were identified through the pathology and oncology databases. A tissue array was constructed from the patient samples and hTERT expression was evaluated by immunohistochemistry. Twenty-one samples were also analyzed for telomerase activity (telomerase repeat amplification protocol assay). Results Eighty-seven tumors from 65 patients were analyzed. Five-year progression-free survival was 57% (SEM, 12%) and 21% (SEM, 8%) for hTERT-negative and hTERT-positive tumors, respectively (P = .002). Five-year overall survival was 84% (SEM, 7%) and 41% (SEM, 7%) for hTERT-negative and hTERT-positive tumors, respectively (P = .001). There was good correlation between telomerase activity and hTERT expression (κ = 0.637). Multivariate analysis revealed hTERT expression to be the single most important predictor of survival of all known pathologic, clinical, and treatment factors (hazard ratio, 60.4; 95% CI, 6.4 to 561). All four patients with hTERT-negative tumors at relapse are still alive, with median follow-up of 11.2 years. Conclusion In this study, hTERT expression was the strongest predictor of outcome and was independent of other clinical and pathologic prognostic markers. It represents a simple and reliable biologic prognostic factor for intracranial ependymomas. These results should be confirmed in larger prospective trials.
Skip Metastases in Osteosarcoma: Experience of the Cooperative Osteosarcoma Study Group
Authors: Kager Leo , Zoubek Andreas , Kastner Ulrike , Kempf-Bielack Beate , Potratz Jenny , Kotz Rainer , Exner G. Ulrich , Franzius Christiane , Lang Susanna , Maas Rainer , Jürgens Heribert , Gadner Helmut , Bielack Stefan 
Published: March 2006

Purpose The outlook for patients with osteosarcoma who present with synchronous regional bone metastases (skip metastases), either in the primary bone site or transarticular, is considered to be extremely poor. This study was conducted to further investigate the prognostic implication of skip metastases in osteosarcoma. Patients and Methods The authors retrospectively analyzed the collected data of 1,765 consecutive patients with newly diagnosed high-grade osteosarcoma of bone who were registered in the neoadjuvant Cooperative Osteosarcoma Study Group studies and identified 24 patients (1.4%) with unequivocally proven skip metastases. All 24 patients were treated by an aggressive surgical approach coupled with polychemotherapy. Demographic, diagnostic, tumor, and treatment-related variables and response and survival data were analyzed. Results Skip metastases were identified preoperatively in 11 of 24 patients by bone scan, eight of 22 patients by plain x-ray, 15 of 18 patients by magnetic resonance imaging, and five of 10 patients by computed tomography. A complete surgical remission (CSR) of all clinically detectable tumor sites was achieved in 22 of 24 patients during front-line therapy. With a median follow-up time of 4.4 years (8 years for survivors) from diagnosis, 12 patients were alive, all of whom were in continuous CSR. Survival did correlate with location of skip metastases and histologic response to neoadjuvant chemotherapy. Conclusion Synchronous regional bone metastases are rare in osteosarcoma, and preoperative detection relies on appropriate diagnostic imaging. Aggressive multimodal therapy holds the promise to achieve prolonged survival, especially in patients in whom these metastases occur within the same bone as the primary lesion and whose tumors respond well to chemotherapy.
Translocation Carcinomas of the Kidney After Chemotherapy in Childhood
Authors: Argani Pedram , Laé Marick , Ballard Edgar T. , Amin Mahul , Manivel Carlos , Hutchinson Brian , Reuter Victor E. , Ladanyi Marc 
Published: March 2006

Purpose Children who survive cancer are at more than 19-fold increased risk of developing another malignancy. Renal cell carcinoma (RCC) occurring as a secondary malignancy is uncommon. Translocation RCC, bearing TFE3 or TFEB gene fusions, are recently recognized entities for which risk factors have not been identified. Patients and Methods We describe the clinical, pathologic, cytogenetic, and molecular data on six translocation RCCs that arose in five young patients who had received chemotherapy. Results The ages at time of diagnosis of the RCC ranged from 6 to 22 years. Histologically, these tumors showed typical features previously described for translocation RCCs. At the molecular level, three tumors contained the ASPL-TFE3 fusion, two contained Alpha-TFEB, and one contained PRCC-TFE3. The intervals between chemotherapy and the diagnosis of RCC ranged from 4 to 13 years. The indications for the antecedent chemotherapy were varied and included acute promyelocytic leukemia, acute myeloid leukemia with t(9;11), bilateral Wilms' tumor, systemic lupus erythematosus, and conditioning regimen of bone marrow transplant for Hurler's syndrome. Only the latter patient had also received radiation. Hence, among 39 genetically confirmed translocation RCCs in our personal experience, six (15%) have arisen in patients who had received cytotoxic chemotherapy. Conclusion Cytotoxic chemotherapy may predispose to the development of renal translocation carcinomas.
Randomized Trial of Peer Counseling on Reproductive Health in African American Breast Cancer Survivors
Authors: Schover Leslie R. , Jenkins Rosell , Sui Dawen , Adams Jennifer Harned , Marion Michelle S. , Jackson Karen Eubanks 
Published: March 2006

Purpose We designed a peer counseling program to improve sexual function, increase knowledge about reproductive health, and decrease menopausal symptoms and infertility-related distress for African American breast cancer survivors. Patients and Methods Women were randomly assigned to immediate counseling or a 3-month waitlist. Three peer counselors conducted a 3-session intervention using a detailed workbook. Questionnaires at baseline, after the waitlist period, at posttreatment, and at 3-month follow-up assessed spirituality, sexual function, menopause symptoms, emotional distress, relationship satisfaction, fertility concerns, and knowledge about reproductive health and breast cancer. At the postcounseling assessment, women rated the workbook, their counselor, and the program. Results Of 93 women screened, 60 women (65%) enrolled in the study. Women who completed counseling (80%; N = 48) had a mean age of 49 years (standard deviation [SD], 8 years) and a mean follow-up of 4.5 years (SD, 3.8 years) since cancer diagnosis. Almost all rated the workbook as very easy to understand (94%) and their counselor as very knowledgeable (96%) and very skillful (98%). Eighty-one percent rated the program as “very useful to me.” Immediate counseling and waitlist groups did not differ at baseline in psychologic adjustment, nor did scores change during the waitlist period. Therefore, the groups were combined in analyzing outcomes. Knowledge of reproductive issues improved significantly from baseline to 3-month follow-up (P < .0001), as did emotional distress (P = .0047) and menopause symptoms (P = .0128). Sexually dysfunctional women became less distressed (P = .0167). Conclusion Women valued the Sisters Peer Intervention in Reproductive Issues After Treatment program highly and found it relevant. The program had positive effects on knowledge and target symptoms.
Role of Radiotherapy in Supratentorial Primitive Neuroectodermal Tumor in Young Children: Results of the German HIT-SKK87 and HIT-SKK92 Trials
Authors: Timmermann Beate , Kortmann Rolf-Dieter , Kühl Joachim , Rutkowski Stefan , Meisner Christof , Pietsch Torsten , Deinlein Frank , Urban Christian , Warmuth-Metz Monika , Bamberg Michael 
Published: March 2006

Purpose To assess the outcome of young children with supratentorial primitive neuroectodermal tumor (stPNET) treated by intensive postoperative chemotherapy alone compared with treatment with chemotherapy and delayed radiotherapy (RT). Patients and Methods From 1987 to 1992, children younger than 3 years of age with stPNET were enrolled in the HIT-SKK87 trial in Germany and Austria. After surgery, low-risk patients received maintenance chemotherapy before RT. In high-risk patients, intensive induction chemotherapy was followed by maintenance chemotherapy until delayed RT was initiated. In the following trial, HIT-SKK92 methotrexate-based chemotherapy was applied. In children with complete remission after three cycles, therapy was finished without irradiation. Otherwise, radiotherapy or salvage chemotherapy was administered. Results Twenty-nine children were eligible (age, 3.0 to 37.0 months). All children received chemotherapy. In 15 children, no RT was administered. Four children had tumor progression during chemotherapy and underwent irradiation. In 10 patients, RT was given after chemotherapy. Overall survival (OS) and progression-free survival (PFS) rates after 3 years were 17.2% and 14.9%, respectively. Twenty-four children relapsed (13 at the tumor site only, three at distant site, and eight at both local and distant sites). Positive impact on survival was observed in children with complete resection but without statistical significance. Administration of RT was the only significant predictive factor for OS and PFS. Only one child not having RT survived. Conclusion Outcome of infants and babies with stPNET is unsatisfactory. Omission of RT jeopardizes survival, even if intensive chemotherapy is applied. We suggest to limit any delay of RT to a maximum of 6 months even in young children.
White Race As a Risk Factor for Hypothyroidism After Treatment for Pediatric Hodgkin's Lymphoma
Authors: Metzger Monika L. , Hudson Melissa M. , Somes Grant W. , Shorr Ron I. , Li Chin-Shang , Krasin Matthew J. , Shelso John , Pui Ching-Hon , Howard Scott C. 
Published: March 2006

Purpose Hypothyroidism frequently occurs after treatment for pediatric Hodgkin's lymphoma, but race has not been investigated as a risk factor for this delayed toxicity. The aim of this study was to determine whether race is an independent risk factor for hypothyroidism in survivors of pediatric Hodgkin's lymphoma. Patients and Methods To identify differences between black and white patients in the development of hypothyroidism after treatment for Hodgkin's lymphoma, we conducted a retrospective study of consecutively treated pediatric patients with newly diagnosed Hodgkin's lymphoma treated at St Jude Children's Research Hospital (Memphis, TN) from January 1980 through December 2002. Clinical or biochemical hypothyroidism was defined by an above normal thyroxine-stimulating hormone concentration or by the need for thyroid hormone replacement therapy. Results The 461 patients (388 white patients, 73 black patients) where followed for a median of 11.3 years (range, 1.8 to 24.9 years). Hypothyroidism developed in 196 (43%) of 461 patients after a median of 2.9 years (range, 0.7 to 11.3 years) after diagnosis of Hodgkin's lymphoma. Hypothyroidism developed in 47% of white patients but in only 21% of black patients (hazard ratio = 2.7; 95% CI, 1.6 to 4.6). After adjusting for other risk factors for hypothyroidism (thyroid radiation dose, sex, and nodular sclerosis histology), the risk of hypothyroidism in white patients was 2.5 times (95% CI, 1.5 to 4.3 times) the risk in black patients (P < .001). Conclusion White patients have a higher risk of hypothyroidism after neck irradiation for pediatric Hodgkin's lymphoma than black patients.
Linking Ligand-Induced Alterations in Androgen Receptor Structure to Differential Gene Expression: A First Step in the Rational Design of Selective Androgen Receptor Modulators
Authors: Kazmin Dmitri , Prytkova Tatiana , Cook C. Edgar , Wolfinger Russell , Chu Tzu-Ming , Beratan David , Norris J. D. , Chang Ching-yi , McDonnell Donald P. 
Published: March 2006

AbstractWe have previously identified a family of novel androgen receptor (AR) ligands that, upon binding, enable AR to adopt structures distinct from that observed in the presence of canonical agonists. In this report, we describe the use of these compounds to establish a relationship between AR structure and biological activity with a view to defining a rational approach with which to identify useful selective AR modulators. To this end, we used combinatorial peptide phage display coupled with molecular dynamic structure analysis to identify the surfaces on AR that are exposed specifically in the presence of selected AR ligands. Subsequently, we used a DNA microarray analysis to demonstrate that differently conformed receptors facilitate distinct patterns of gene expression in LNCaP cells. Interestingly, we observed a complete overlap in the identity of genes expressed after treatment with mechanistically distinct AR ligands. However, it was differences in the kinetics of gene regulation that distinguished these compounds. Follow-up studies, in cell-based assays of AR action, confirmed the importance of these alterations in gene expression. Together, these studies demonstrate an important link between AR structure, gene expression, and biological outcome. This relationship provides a firm underpinning for mechanism-based screens aimed at identifying SARMs with useful clinical profiles.
Activation of the Blue Opsin Gene in Cone Photoreceptor Development by Retinoid-Related Orphan Receptor β
Authors: Srinivas Maya , Ng Lily , Liu Hong , Jia Li , Forrest Douglas 
Published: March 2006

AbstractColor vision requires the expression of opsin photopigments with different wavelength sensitivities in retinal cone photoreceptors. The basic color visual system of mammals is dichromatic, involving differential expression in the cone population of two opsins with sensitivity to short (S, blue) or medium (M, green) wavelengths. However, little is known of the factors that directly activate these opsin genes and thereby contribute to the S or M opsin identity of the cone. We report that the orphan nuclear receptor RORβ (retinoid-related orphan receptor β) activates the S opsin gene (Opn1sw) through binding sites upstream of the gene. RORβ lacks a known physiological ligand and activates the Opn1sw promoter modestly alone but strongly in synergy with the retinal cone-rod homeobox factor (CRX), suggesting a cooperative means of enhancing RORβ activity. Comparison of wild-type and mutant lacZ reporter transgenes showed that the RORβ-binding sites in Opn1sw are required for expression in mouse retina. RORβ-deficient mice fail to induce S opsin appropriately during postnatal cone development. Photoreceptors in these mice also lack outer segments, indicating additional functions for RORβ in photoreceptor morphological maturation. The results identify Opn1sw as a target gene for RORβ and suggest a key role for RORβ in regulating opsin expression in the color visual system.
Anti-Transglutaminase Antibody Assay of the Culture Medium of Intestinal Biopsy Specimens Can Improve the Accuracy of Celiac Disease Diagnosis
Authors: Carroccio Antonio , Di Prima Lidia , Pirrone Giuseppe , Scalici Calogero , Florena Ada M , Gasparin Maurizio , Tolazzi Giuseppe , Gucciardi Antonino , Sciumè Carmelo , Iacono Giuseppe 
Published: March 2006

Abstract
Background: We measured anti-transglutaminase (anti-tTG) antibody in the culture medium of intestinal biopsy specimens from patients with suspected celiac disease (CD) and evaluated the relationship between antibody production and severity of intestinal mucosal damage.
Methods: We performed diagnostic testing for CD on 273 consecutive patients. In addition to routine histologic evaluation of duodenal biopsy specimens, we assayed anti-tTG antibodies in serum and in the culture medium of duodenal biopsy specimens.
Results: CD was diagnosed in 191 of the 273 patients. Sensitivity and specificity of the serum anti-endomysium (EmA) and anti-tTG assays were 83% and 85% and 99% and 95%, respectively, and both had 88% diagnostic accuracy. EmA and anti-tTG assayed in the culture medium had 98% sensitivity, 100% specificity, and 98% diagnostic accuracy (vs serum assays; P &lt;0.0001). Twenty-nine CD patient specimens (16%) were negative for serum anti-tTG and EmA; for 24 of these patients, anti-tTG assay of the culture medium was positive. The CD patients whose biopsy specimens were positive for serum antibodies showed the following intestinal histologies: total villous atrophy, 35%; severe villous atrophy, 25%; mild atrophy, 25%; villi with no atrophy but with increased intraepithelial lymphocytes, 15%. None of the CD patients whose specimens were negative for serum antibodies showed total or severe villous atrophy; 77% had mild villous atrophy, and 23% had no villous atrophy but had increased intraepithelial lymphocyte counts. Mild villous atrophy was also seen in specimens from ∼15% of patients without CD.
Conclusion: Anti-tTG assay of the culture medium of biopsy specimens can improve the accuracy of CD diagnosis in patients negative for serum antibodies.