bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aberrant DNA methylation in pediatric patients with acute lymphocytic leukemia
Authors: Garcia‐Manero Guillermo , Jeha Sima , Daniel Jerry , Williamson Jason , Albitar Maher , Kantarjian Hagop M. , Issa Jean‐Pierre J. 
Published: February 2003

AbstractBACKGROUNDAberrant methylation of promoter‐associated cystosine‐guanine (CpG) islands is an epigenetic modification of DNA frequently observed in adult patients with acute lymphocytic leukemia (ALL). This epigenetic modification has been associated with gene silencing, malignant transformation, and aging. It is not known whether there are epigenetic differences between pediatric patients and adult patients with ALL.METHODSTo investigate the methylation characteristics of pediatric patients with ALL and to determine whether DNA methylation can explain prognostic or biologic differences between pediatric and adult patients, the authors analyzed the methylation status of 7 promoter‐associated CpG islands in 16 pediatric patients with ALL and compared them with the methylation characteristics of a cohort of adult patients with ALL. The genes analyzed included the estrogen receptor gene (ER), multidrug resistance gene 1 (MDR1), p15, C‐ABL, CD10, p16, and p73.RESULTSThe mean methylation densities of ER, MDR1, CD10, p15, and C‐ABL were 25.4%, 16.4%, 5.23%, 4.24%, and 4%, respectively. P16 was methylated in 11.7% of patients, and p73 was methylated in 17.6% of patients. One patient (6.2%) had methylation of 0 genes, 15 patients (93.7%) had methylation of ≥ 1 gene, and 4 patients (25%) had methylation of 3–4 genes. Methylation of all these genes was < 2% (or methylation specific polymerase chain reaction negative) in nonneoplastic tissues. A significant inverse correlation was observed between methylation of CD10 and CD10 expression. No differences were observed between the methylation characteristics of pediatric patients and adult patients.CONCLUSIONSThe results indicate that DNA methylation is common in pediatric patients with ALL and that methylation of the genes studied does not account for prognostic differences between pediatric patients and adult patients with ALL. Cancer 2003;97:695–702. © 2003 American Cancer Society.DOI 10.1002/cncr.11090
Detection of chromosomal aneusomy by fluorescence in situ hybridization for patients with nipple discharge
Authors: Yamamoto Daigo , Senzaki Hideto , Nakagawa Hiroyuki , Okugawa Homa , Gondo Hideki , Tanaka Kanji 
Published: February 2003

AbstractBACKGROUNDBreast carcinoma and precancer are believed to start in the lining of the milk duct or lobule. Ductography and fiberoptic ductoscopy (FDS) are used to identify abnormal intraductal lesions, although it is difficult to distinguish malignant from benign cases. Therefore, we studied the clinical usefulness of fluorescence in situ hybridization (FISH) analysis of a numerical aberration of chromosomes (aneusomy) using ductal lavage from patients with nipple discharge.METHODSWe applied ductography and FDS to 90 women who had nipple discharge. Ductal lavages obtained from patients with positive ductography and/or FDS findings were subjected to cytology and FISH analysis using centromere probes for chromosomes 1, 11, and 17. Patients with samples that showed aneusomy in at least one of the three chromosomes were diagnosed as positive.RESULTSHistologic evaluation revealed 54 benign lesions and six malignancies. The sensitivity, specificity, and diagnostic accuracy were 33.3%, 88.9%, and 83.3%, respectively, for cytology and 100%, 100%, and 100%, respectively, for FISH.CONCLUSIONThe results demonstrated that FISH has a diagnostic accuracy comparable to cytology. This technique has 100% specificity is making a definitive diagnosis of malignancy in patients with indeterminate cytologic results, suggesting that FISH diagnosis can be a good adjunct to cytology. Cancer 2003;97:690–4. © 2003 American Cancer Society.DOI 10.1002/cncr.11091
Titration of serum p53 antibodies in 1085 patients with various types of malignant tumors
Authors: Shimada Hideaki , Ochiai Takenori , Nomura Fumio 
Published: February 2003

AbstractBACKGROUNDThere have been very few large‐scale, multiinstitutional studies of surveillance of serum p53 antibodies (S‐p53 Abs) in patients with various malignant tumors.METHODSA highly specific, quantitative enzyme‐linked immunosorbent assay (ELISA) kit was developed and used to evaluate the efficiency of detecting p53 Abs. A cut‐off value was established by analyzing sera from 205 healthy volunteers as reference individuals. Sera from 1085 patients with various types of primary malignant tumors were studied for the presence of S‐p53 Abs before treatment. Sera from 34 patients were selected randomly for a competition assay to ensure that antibodies were specific to p53 protein. Carcinoembryonic antigen (CEA) was assessed to compare its positive rate with the positive rate of S‐p53 Abs.RESULTSThe median value of S‐p53 Abs in healthy control individuals was 0.33 U/mL (range, 0.0–4.39 U/mL). Based on reference values that were calculated using parametric determination of the lower 0.95 fraction of the reference distribution in healthy control individuals, the cut‐off value was determined as 1.3 U/mL. Two hundred twenty‐one of 1085 patients (20.4%) were positive for S‐p53 Abs. The highest relevance of S‐53 Abs was associated with head and neck carcinoma (32%), followed by esophageal carcinoma (30%), colorectal carcinoma (24%), and carcinoma of the uterus (23%). The positive rate for S‐p53 Abs was higher compared with the positive rate for CEA in patients with squamous cell carcinoma.CONCLUSIONSSurveillance of S‐p53 Abs is useful in detecting various types of malignant tumors, particular in patients with squamous cell carcinoma. Cancer 2003;97:682–9. © 2003 American Cancer Society.DOI 10.1002/cncr.11092
R‐Ras promotes tumor growth of cervical epithelial cells
Authors: Rincón‐Arano Héctor , Rosales Ricardo , Mora Nancy , Rodriguez‐Castañeda Armando , Rosales Carlos 
Published: February 2003

AbstractBACKGROUNDR‐Ras is 55% identical to H‐Ras. However, these two oncogenes seem to have different tumor‐transforming potential. R‐Ras induced cell transformation in fibroblasts but not in other cell types. R‐Ras also reportedly induces a more invasive phenotype in breast epithelial cells through integrin activation. The authors studied the mechanisms whereby R‐Ras induces a malignant phenotype.METHODSDominant negative (R‐Ras43N) and constitutively active (R‐Ras87L) mutants of R‐Ras were stably transfected into human cervical epithelium C33A cells. Transfected cells were analyzed for adhesion, cell spreading, migration, and growth in culture and in nude mice. The activity of extracellular signal‐regulated kinase (ERK) and phosphatidylinositol 3‐kinase (PI 3‐K) also was determined by Western blot analysis and by in vitro kinase assays.RESULTSR‐Ras87L‐transfected cells, but not R‐Ras43 N‐transfected cells, had a higher growth rate in nude mice and in culture compared with control cells. None of the transfected C33A cells showed an increase in cell adhesion to fibronectin or collagen I, nor did they show an increment of β1 integrin affinity. However, cells that expressed R‐Ras87L, but not cells that expressed R‐Ras 43N, presented a marked increase in cell spreading and migration through collagen‐coated membranes. Increases in cell proliferation, spreading, and migration induced by R‐Ras87L were inhibited by the PI 3‐K inhibitor LY294002. In addition, PI 3‐K activity, but not ERK activity, was increased only in cells that expressed R‐Ras87L.CONCLUSIONSThese data suggest that the oncogene R‐Ras promotes tumor growth of cervical epithelial cells and increases their migration potential over collagen through a pathway that involves PI 3‐K. Cancer 2003;97:575–85. © 2003 American Cancer Society.DOI 10.1002/cncr.11093
Endocrine and cardiovascular late effects among adult survivors of childhood brain tumors
Authors: Gurney James G. , Kadan‐Lottick Nina S. , Packer Roger J. , Neglia Joseph P. , Sklar Charles A. , Punyko Judy A. , Stovall Marilyn , Yasui Yutaka , Nicholson H. Stacy , Wolden Suzanne , McNeil Dawn E. , Mertens Ann C. , Robison Leslie L. 
Published: February 2003

AbstractBACKGROUNDSurvivors of childhood brain tumors (CBTs) are at high risk for a variety of late adverse effects. Most research on long‐term effects of CBTs has been comprised of single‐institution case series without comparison groups. Research on CBT late effects often is focused on neurologic and sensory outcomes, with less emphasis on other potential targets such as the endocrine and circulatory systems. The current study was conducted to contrast the incidence of endocrine and cardiovascular conditions among CBT survivors as a function of treatment and to determine the risk of occurrence of these conditions relative to a sibling comparison group.METHODSAs part of the Childhood Cancer Survivor Study (CCSS), treatment data were collected from medical records and self‐reported late effects were ascertained from a survey questionnaire of 1607 CBT patients who survived their disease for 5 or more years. For comparison purposes, questionnaire data were also collected from 3418 randomly selected siblings of participants in CCSS.RESULTSOne or more endocrine conditions were reported by 43% of CBT survivors. Compared with siblings, CBT survivors had a significantly increased risk of late‐onset (≥ 5 years postdiagnosis) hypothyroidism (relative risk [RR] = 14.3; 95% confidence interval [95% CI] 9.7–21.0), growth hormone deficiency (RR = 277.8; 95% CI 111.1–694.9), the need for medications to induce puberty (RR = 86.1; 95% CI 31.1–238.2), and osteoporosis (RR = 24.7; 95% CI 9.9–61.4). One or more cardiovascular conditions were reported by 18% of CBT survivors, with an elevated late‐onset risk for stroke (RR = 42.8; 95% CI 16.7–109.8), blood clots (RR = 5.7; 95% CI 3.2–10.0), and angina‐like symptoms (RR = 2.0; 95% CI 1.5–2.7). Very few late effects were evident among those treated with surgery only, but risks were consistently elevated for those treated with radiation and surgery, and higher still for those who also received adjuvant chemotherapy.CONCLUSIONSChildhood brain tumor survivors are at a significantly increased risk for several adverse endocrine and cardiovascular late effects, particularly if they were treated with radiation and chemotherapy. Lifetime medical surveillance and follow‐up for potential toxicities are necessary because treatment‐related complications may occur many years after therapy. Cancer 2003;97:663–73. © 2003 American Cancer Society.DOI 10.1002/cncr.11095
Frequency of gastrointestinal involvement and its clinical significance in mantle cell lymphoma
Authors: Romaguera Jorge E. , Medeiros L. Jeffrey , Hagemeister Frederick B. , Fayad Luis E. , Rodriguez Maria A. , Pro Barbara , Younes Anas , McLaughlin Peter , Goy Andre , Sarris Andreas H. , Dang Nan H. , Samaniego Felipe , Brown H. M. , Gagneja Harish K. , Cabanillas Fernando 
Published: February 2003

AbstractBACKGROUNDThe reported frequency of gastrointestinal (GI) tract involvement in patients with mantle cell lymphoma (MCL) is 15–30%. However, this figure most likely is an underestimate because most patients with MCL involving the GI tract previously reported were examined endoscopically only if they had GI tract symptoms. The impact of endoscopic assessment on the management of MCL patients is unknown.METHODSFrom March 1998 to May 2001 baseline upper and lower endoscopy of the GI tract was performed in consecutive untreated patients with MCL as part of a prospective therapeutic trial. Biopsies were performed on abnormal as well as macroscopically normal mucosa. Endoscopy was repeated during treatment and as part of follow‐up evaluations.RESULTSOnly 26% of patients presented with GI symptoms at the time of diagnosis. MCL was present histologically in the lower GI tract of 53 of 60 patient (88%) and in the upper GI tract of 28 of 58 patients (43%). Microscopic evidence of MCL was found in 84% of patients with normal visual (macroscopic) findings by lower endoscopy and in 45% of patients with macroscopically normal findings by upper endoscopy. Despite this high frequency of GI tract involvement, the use of upper and lower endoscopy with biopsies in this group of patients resulted in changes in clinical management in only three (4%) patients.CONCLUSIONSGastrointestinal tract involvement was found to be present in most patients with MCL, usually at a microscopic level involving macroscopically normal mucosa. The use of aggressive staging evaluation of the GI tract was found to have little impact on patient management decisions in the current study. Cancer 2003;97:586–91. © 2003 American Cancer Society.DOI 10.1002/cncr.11096
A prospective study on glioblastoma in the elderly
Authors: Brandes Alba A. , Vastola Francesca , Basso Umberto , Berti Franco , Pinna Giampietro , Rotilio Antonino , Gardiman Marina , Scienza Renato , Monfardini Silvio , Ermani Mario 
Published: February 2003

AbstractBACKGROUNDElderly patients (age > 65 years) with glioblastoma multiforme frequently are excluded from clinical studies, and prospective trials for patients with this age group do not exist to date.METHODSThe authors conducted a prospective trial in 79 consecutive elderly patients with glioblastoma who underwent surgery and received radiotherapy (59.44 grays in 33 fractions; Group A; n = 24 patients) or received the same radiotherapy plus adjuvant chemotherapy with procarbizine, lomustine, and vincristine (PCV; lomustine 110 mg/m2 on Day 1, procarbazine 60 mg/m2 on Days 8–21, and vincristine 1.4 mg/m2 on Days 8 and 29 every 42 days; Group B; n = 32 patients), or received the same radiotherapy plus adjuvant temozolomide (150 mg/m2 for 5 days every 28 days; Group C; n = 22 patients).RESULTSThe median time to disease progression (TTP) and median survival MST were 7.2 months (95% confidence interval [95%CI], 6.34–8.64) and 12.5 months (95%CI, 11.6–14.8), respectively. The TTP was significantly better for Group C compared with Groups A and B (10.7 months vs. 5.3 months and 6.9 months, respectively; P = 0.0002). Karnofsky performance status (KPS) (P < 0.001) and temozolomide (P < 0.001) were the only independent prognostic factors. Overall survival was better in Group C compared with Group A (14.9 months vs. 11.2 months; P = 0.002), but there were no statistical differences found between Groups A and B or between Groups B and C. Only KPS (P < 0.001) was predictive of overall survival, even if temozolomide chemotherapy was very close to the significance level (P = 0.058). Hematologic Grade 3–4 toxicity was higher with the PCV chemotherapy regimen compared with the temozolomide chemotherapy regimen.CONCLUSIONSAge alone should not preclude appropriate treatment in elderly patients with good performance status, for whom definitive radiation therapy and adjuvant chemotherapy with temozolomide is advised. Cancer 2003;97:657–62. © 2003 American Cancer Society.DOI 10.1002/cncr.11097
Treatment options for patients with acute myeloid leukemia with a matched sibling donor
Authors: Sung Lillian , Buckstein Rena , Doyle John J. , Crump Michael , Detsky Allan S. 
Published: February 2003

AbstractBACKGROUNDThe role of allogeneic bone marrow transplantation (BMT) in the consolidation of young adults with acute myeloid leukemia (AML) with matched sibling donors (MSD) is controversial. Although BMT is associated with increased event free survival compared with intensive chemotherapy (CT) consolidation, BMT also is associated with increased treatment‐related mortality and likely decreased quality of life and life expectancy in patients who do not develop recurrent disease.METHODSThe authors used decision analysis to compare three strategies for maximizing quality‐adjusted life years (QALYs) in patients with AML in first remission with an MSD:BMT All,BMT None(consolidation CT only), or BMT in high‐risk patients, as defined by baseline cytogenetic testing (Teststrategy). A second decision‐analysis tree was then constructed that compared BMT with CT specifically for patients with intermediate cytogenetics.RESULTSUsing expected QALYs as the outcome measure, theTest,BMT All, andBMT Nonestrategies were associated with 20.10 QALYs, 19.63 QALYs, and 18.38 QALYs, respectively. Thus, theTeststrategy, with CT for low‐risk patients and BMT for intermediate risk and high‐risk patients, was expected to be the optimal strategy. In the intermediate cytogenetic decision analysis, although the expected QALY for BMT recipients was higher compared with CT recipients (19.78 QALYs vs. 18.75 QALYs), because of uncertainty in variable estimates, the optimal choice was less clear.CONCLUSIONSCT consolidation is a reasonable option for patients with AML who have favorable cytogenetics, even if an MSD is available. This model provides a framework from which patients with AML and their physicians can make decisions about consolidation therapy. Cancer 2003;97:592–600. © 2003 American Cancer Society.DOI 10.1002/cncr.11098
The predictive value of longitudinal neuropsychologic assessment in the early detection of brain tumor recurrence
Authors: Armstrong Carol L. , Goldstein Bram , Shera David , Ledakis George E. , Tallent Emily M. 
Published: February 2003

AbstractBACKGROUNDNeuropsychologic tests are widely used to predict the course of progressive neurologic diseases, and recent research has demonstrated the specificity of cognitive measures, even in relatively diffuse diseases. However, the cognitive effects of brain tumors of similar histology and location are known to be highly variable. The authors used the specificity of cognitive function principle to compare two models for the early detection of low‐grade brain tumor recurrence prior to detection with clinically scheduled neuroimaging.METHODSTo test the feasibility of these prediction models, 34 patients with supratentorial, low‐grade brain tumors prospectively were administered serial comprehensive neuropsychologic examinations; 11 patients developed recurrent tumors during the series and 23 patients did not. A general model based on tests sensitive to malignancy and white matter disease was compared with a tumor‐specific model based on indices related to each patient's tumor locus. A Cox proportional hazards model was used to identify the predictor variables that significantly changed immediately prior to recurrence.RESULTSOnly the tumor‐specific model achieved statistical significance (P < 0.02). A tumor‐specific index decline of 1 standard deviation indicated a 5–fold increase in the probability of tumor recurrence.CONCLUSIONSAlthough this method needs to be tested with more frequent and regular observations and with a larger sample, these results provide evidence of the feasibility of the subject‐specific model as a predictor of recurrence. The evidence of the predictive value of a tumor‐specific model is consistent with studies that identify only limited, brain structure‐specific cognitive decline from broad neuropsychologic batteries. Cancer 2003;97:649–56. © 2003 American Cancer Society.DOI 10.1002/cncr.11099
Cytotoxic/natural killer cell cutaneous lymphomas
Authors: Santucci Marco , Pimpinelli Nicola , Massi Daniela , Kadin Marshall E. , Meijer Chris J. L. M. , Müller‐Hermelink Hans Konrad , Paulli Marco , Wechsler Janine , Willemze Rein , Audring Heike , Bernengo Maria Grazia , Cerroni Lorenzo , Chimenti Sergio , Chott Andreas , Díaz‐Pérez José L. , Dippel Edgard , Duncan Lyn M. , Feller Alfred C. , Geerts Marie‐Louise , Hallermann Christian , Kempf Werner , Russell‐Jones Robin , Sander Christian , Berti Emilio 
Published: February 2003

AbstractBACKGROUNDCutaneous lymphomas expressing a cytotoxic or natural killer (NK) cell phenotype represent a group of lymphoproliferative disorders for which there is currently much confusion and little consensus regarding the best nomenclature and classification.METHODSThis study analyzes 48 cases of primary cutaneous lymphoma expressing cytotoxic proteins and/or the NK cell marker, CD56. These cases were collected for a workshop of the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Task Force, to better clarify the clinical, morphologic, and phenotypic features of these uncommon tumors.RESULTSSeveral categories with different clinical and pathologic features were delineated: 1) aggressive, CD8+, epidermotropic, cytotoxic T‐cell lymphoma; 2) mycosis fungoides, cytotoxic immunophenotype variant; 3) subcutaneous panniculitis‐like T‐cell lymphoma; 4) NK/T‐cell lymphoma, nasal type; 5) CD4+, NK cell lymphoma; 6) blastoid NK cell lymphoma; (7) intravascular NK‐like lymphoma; and 8) cytotoxic, peripheral T‐cell lymphoma.CONCLUSIONSOur data show that primary cutaneous cytotoxic/NK cell lymphomas include distinct groups of diseases, clinically, histologically, and biologically. Because the finding of a cytotoxic phenotype often has prognostic significance, the routine use of cytotoxic markers in the diagnosis and classification of cutaneous lymphomas should be expanded. Cancer 2003;97:610–27. © 2003 American Cancer Society.DOI 10.1002/cncr.11107
Moderate sun exposure and nevus counts in parents are associated with development of melanocytic nevi in childhood
Authors: Wiecker Tine Sander , Luther Heike , Buettner Petra , Bauer Jürgen , Garbe Claus 
Published: February 2003

AbstractBACKGROUNDMelanocytic nevi have been identified as the most important risk factor for cutaneous melanoma. Sun exposure, sunburns, and light pigmentation have been found to be associated with their development in childhood. To the authors' knowledge, nevus proneness of parents and the exact type of ultraviolet (UV) exposure have not yet been investigated in this context. The authors' objective was to determine independent risk factors and their impact for nevus development in childhood.METHODSThe current study was conducted by two university departments of dermatology in 49 public nursery schools in Stuttgart, Germany and in 38 public nursery schools in Bochum, Germany. The cross‐sectional study included 1812 children aged 2–7 years and their parents. Total body nevus counts in children, assessment of pigmentary features, and nevus counts on the arms of parents were performed. Parents underwent a standardized interview concerning national origin and lifestyle features, as well as habits and magnitude of sun exposure of children. Analysis was performed by multivariate linear regression analysis and by multiple logistic regression analysis.RESULTSThe number of nevi was found to steadily increase with age from a median of 3 at age 2 years to 19 at age 7 years (P < 0.0001). High numbers of nevi in children were associated with the number of weeks on sunny holidays, outdoor activities at home, skin type, facial freckling, ethnicity of parents, and the number of nevi on the arms of parents. Previously experienced sunburns failed significance (P = 0.0620).CONCLUSIONSThe authors found a strong association between nevus development in children and the number of parental moles, which most likely points to an inherited factor. Moderate sun exposure such as outdoor activities during a German summer without sunburns seemed to be sufficient for induction of melanocytic nevi. The authors believe that these findings will have direct impact on concepts for preventive strategies. Cancer 2003;97:628–38. © 2003 American Cancer Society.DOI 10.1002/cncr.11114