bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allele Imbalance, or Loss of Heterozygosity, in Normal Breast Epithelium of Sporadic Breast Cancer Cases and BRCA1 Gene Mutation Carriers Is Increased Compared With Reduction Mammoplasty Tissues
Authors: Larson Pamela S. , Schlechter Benjamin L. , de las Morenas Antonio , Garber Judy E. , Cupples L. Adrienne , Rosenberg Carol L. 
Published: November 2005

Purpose Normal-appearing breast epithelium can contain genetic abnormalities, including allele imbalance (AI), also referred to as loss of heterozygosity. Whether abnormalities are associated with cancer or cancer risk is unknown. Patients and Methods We performed a miniallelotype, using 20 microsatellites, on each of 460 histologically normal, microdissected breast terminal ducto-lobular units (TDLUs) from three groups of women: sporadic breast cancer patients (SP; n = 18), BRCA1 gene mutation carriers (BRCA1; n = 16), and controls undergoing reduction mammoplasty (RM; n = 18). We analyzed the results using Fisher's exact tests, logistic regression, and generalized estimating equations. Results AI was increased three-fold in SP and BRCA1 groups compared with RM. Both the number of TDLUs with AI increased (eight [5%] of 162 in the RM group compared with 24 [15%] of 162 in the SP and 22 [16%] of 136 in the BRCA1 groups; P = .0150), and the proportion of patients with AI increased (five [28%] of 18 in the RM group compared with 15 [83%] of 18 in the SP and 13 [81%] of 16 in the BRCA1 groups; P = .0007). The adjusted odds ratios (OR) for AI in TDLU increased in SP (OR = 15.5) and BRCA1 (OR = 13.7) patients compared with RM (P = .0025). This result was particularly evident on chromosome 17q (P = .0393), where more AI was seen in BRCA1 (OR = 12.4) than in SP (OR = 4.9) patients or RM controls. Conclusion Increased prevalence of AI in normal-appearing epithelium is associated with breast cancer and increased breast cancer risk. The increased prevalence may reflect dysregulation, even in normal-appearing epithelium, of genomic processes contributing to cancer development. The clinical significance of genetic alterations in the subset of controls remains to be determined.
Phase I Study of the Sequential Combination of Interleukin-12 and Interferon Alfa-2b in Advanced Cancer: Evidence for Modulation of Interferon Signaling Pathways by Interleukin-12
Authors: Eisenbeis Charles F. , Lesinski Gregory B. , Anghelina Mirela , Parihar Robin , Valentino Daniel , Liu Jing , Nadella Padma , Sundaram Poongothai , Young Donn C. , Sznol Mario , Walker Michael J. , Carson William E. 
Published: November 2005

PurposeTo evaluate the safety of sequentially administered recombinant (r) human (h) interleukin-12 (IL-12) and interferon alfa-2b (IFN-α-2b) in patients with advanced cancer and to determine the effects of endogenously produced IFN-γ on Janus kinase-signal transducer and activator of transcription (Jak-STAT) signal transduction in patient peripheral-blood mononuclear cells (PBMCs).Patients and MethodsForty-nine patients with metastatic cancer received rhIL-12 on day 1 and IFN-α-2b on days 2 to 6 of either a 14-day (n = 43) or a 7-day treatment cycle (n = 6). rhIL-12 was initially administered subcutaneously at a dose of 100 ng/kg, whereas IFN-α-2b was escalated from 1 to 10 million units (MU) in cohorts of three patients (1, 3, 5, 7, or 10 MU). rhIL-12 was subsequently administered intravenously (IV) in escalating doses (100 to 500 ng/kg) to achieve greater IFN-γ production. Peripheral blood was drawn for measurement of plasma IFN-γ and the induction of Jak-STAT signal transduction in PBMCs.ResultsNo IL-12–or IFN-α–related dose-limiting toxicities were observed. There were no responses in 41 assessable patients. Five patients exhibited stable disease lasting 6 months or longer while on therapy. Optimal induction of IFN-γ by IL-12 occurred after an IV dose of 250 ng/kg. Patient PBMCs exhibited increased levels of STAT1 after IL-12 administration. The peak level of IFN-γ achieved with IL-12 therapy correlated with the peak level of intracellular STAT1 in patient PBMCs (r = 0.38, P = .021).ConclusionThe combination of rhIL-12 and IFN-α-2b can be administered sequentially with minimal toxicity. IV administration of rhIL-12 modulates IFN-α–induced Jak-STAT signal transduction in patient PBMCs.
Health Behaviors of Cancer Survivors: Examining Opportunities for Cancer Control Intervention
Authors: Bellizzi Keith M. , Rowland Julia H. , Jeffery Diana D. , McNeel Timothy 
Published: November 2005

Purpose A population-based investigation was conducted to examine the prevalence of health behaviors (smoking, alcohol use, physical activity, and cancer screening) of cancer survivors by age, time since diagnosis, and cancer site. Understanding health behaviors of survivors is imperative, as many survivors are living longer and are at risk for cancer recurrence, second cancers, and complications from treatment. Methods Using the National Health Interview Survey, this study examined the prevalence of smoking and alcohol use as well as whether cancer survivors (n = 7,384) are meeting current recommendations for physical activity and cancer screening compared with noncancer controls (n = 121,347). Results Cancer survivors are similar to controls with respect to smoking status and alcohol consumption after adjusting for group differences. However, younger survivors (18 to 40 years) are at greater risk for continued smoking than controls. Survivors are 9% more likely to meet physical activity recommendations compared with controls. χ2 tests indicate no significant differences in smoking, alcohol consumption, and physical activity by time since diagnosis, but differences by cancer site exist. Female cancer survivors are 34% and 36% more likely to meet mammogram and Papanicolaou smear screening recommendations, respectively, compared with controls. Similar screening patterns were found for prostate-specific antigen screening in men. Conclusion This study provides benchmark approximations of the prevalence of risky health behaviors of survivors by time since diagnosis and cancer site. As part of the collective effort to reduce late effects of cancer treatment, oncologists may be in the best position to offer initial guidance for promoting healthy lifestyle behaviors among cancer survivors.
Wnt5a Expression Is Associated With the Tumor Proliferation and the Stromal Vascular Endothelial Growth Factor—An Expression in Non–Small-Cell Lung Cancer
Authors: Huang Cheng-long , Liu Dage , Nakano Jun , Ishikawa Shinya , Kontani Keiichi , Yokomise Hiroyasu , Ueno Masaki 
Published: November 2005

Purpose The Wnt gene family encodes the multifunctional signaling glycoproteins. We performed the present study to investigate the clinical significance of Wnt5a expression in non–small-cell lung cancer (NSCLC). Patients and Methods One hundred twenty-three patients with NSCLC who had undergone resection were investigated. Real-time quantitative reverse transcriptase polymerase chain reaction was performed to evaluate the Wnt5a gene expression. Immunohistochemistry was performed to investigate the Wnt5a protein expression, the Ki-67 proliferation index, tumor angiogenesis, and the expression of beta-catenin and vascular endothelial growth factor-A (VEGF-A). Results Wnt5a gene expression in squamous cell carcinoma was significantly higher than that in adenocarcinoma (P < .0001). There was a significant correlation between the normalized Wnt5a gene expression ratio and the intratumoral Wnt5a protein expression (r = 0.729; P < .0001). The intratumoral Wnt5a expression was significantly correlated with the Ki-67 proliferation index (r = 0.708; P < .0001). In contrast, no correlation was observed between the intratumoral Wnt5a expression and tumor angiogenesis. Furthermore, the intratumoral Wnt5a expression was significantly correlated with the stromal expression of beta-catenin (r = 0.729; P < .0001) and VEGF-A (r = 0.661; P < .0001). In addition, the stromal VEGF-A expression was also correlated with Ki-67 proliferation (r = 0.627; P < .0001). Cox regression analyses demonstrated Wnt5a status to be a significant prognostic factor for NSCLC patients (P = .0193), especially for patients with squamous cell carcinomas (P = .0491). Conclusion The present study revealed that an overexpression of Wnt5a could produce more aggressive NSCLC, especially in squamous cell carcinomas, during tumor progression.
Ixabepilone (Epothilone B Analogue BMS-247550) Is Active in Chemotherapy-Naive Patients With Hormone-Refractory Prostate Cancer: A Southwest Oncology Group Trial S0111
Authors: Hussain Maha , Tangen Catherine M. , Lara Primo N. , Vaishampayan Ulka N. , Petrylak Daniel P. , Colevas A. Dimitrios , Sakr Wael A. , Crawford E. David 
Published: November 2005

Purpose The epothilones are a new class of tubulin-polymerizing agents with activity in taxane-sensitive and resistant tumor models. We evaluated ixabepilone (BMS-247550) in patients with metastatic hormone-refractory prostate cancer (HRPC). Methods Eligible patients had chemotherapy-naive metastatic HRPC, a Zubrod performance status of 0 to 2, and adequate organ function. All patients received BMS-247550 at 40 mg/m2 over 3 hours every 3 weeks. The primary end point was proportion of patients achieving a prostate-specific antigen (PSA) response. Results Forty-eight patients with metastatic HRPC were registered. Forty-two patients were eligible, with a median age of 73 years and a median PSA level of 111 ng/mL; 78% had bone-only or bone and soft tissue metastases, and 88% had objective radiologic disease progression at registration. Grade 3 and 4 adverse events (AEs) occurred in 16 and three patients, respectively. All grade 4 toxicities were neutropenia or leukopenia. The most frequent grade 3 AEs were neuropathy (eight patients), hematologic toxicity (seven patients), flu-like symptoms, and infection (five patients each). There were no grade 3/4 thrombocytopenia or grade 5 AEs. There were 14 confirmed PSA responses (33%; 95% CI, 20% to 50%); 72% of PSA responders had declines greater than 80%, and two patients achieved an undetectable PSA. The estimated median progression-free survival is 6 months (95% CI, 4 to 8 months), and the median survival is 18 months (95% CI, 13 to 24 months). Conclusion Ixabepilone has demonstrated activity in patients with chemotherapy-naive metastatic HRPC. Major toxicities were neutropenia and neuropathy. Further testing to define its activity relative to standard therapy is warranted.
Chemotherapy and Cardiotoxicity in Older Breast Cancer Patients: A Population-Based Study
Authors: Doyle John J. , Neugut Alfred I. , Jacobson Judith S. , Grann Victor R. , Hershman Dawn L. 
Published: November 2005

Purpose Adjuvant chemotherapy, especially with anthracyclines, is known to cause acute and chronic cardiotoxicity in breast cancer patients. We studied the cardiac effects of chemotherapy in a population-based sample of breast cancer patients aged ≥ 65 years with long-term follow-up. Patients and Methods In the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we analyzed treatments and outcomes among women ≥ 65 years of age who were diagnosed with stage I to III breast cancer from January 1, 1992 to December 31, 1999. Propensity scores were used to control for baseline heart disease (HD) and other known predictors of chemotherapy, and Cox proportional hazards models were used to estimate the risk of cardiomyopathy (CM), congestive heart failure (CHF), and HD after chemotherapy. Results Of 31,748 women with stage I to III breast cancer, 5,575 (18%) received chemotherapy. Chemotherapy was associated with younger age, fewer comorbidities, hormone receptor negativity, multiple primary tumors, and advanced disease. Patients who received chemotherapy were less likely than other patients to have pre-existing HD (45% v 55%, respectively; P < .001). The hazard ratios for CM, CHF, and HD for patients treated with doxorubicin (DOX) compared with patients who received no chemotherapy were 2.48 (95% CI, 2.10 to 2.93), 1.38 (95% CI, 1.25 to 1.52), and 1.35 (95% CI, 1.26 to 1.44), respectively. The relative risk of cardiotoxicity among patients who received DOX compared with untreated patients remained elevated 5 years after diagnosis. Conclusion When baseline HD was taken into account, chemotherapy, especially with anthracyclines, was associated with a substantially increased risk of CM. As the number of long-term survivors grows, identifying and minimizing the late effects of treatment will become increasingly important.
Temporal and Geographic Variation in the Use of Hematopoietic Growth Factors in Older Women Receiving Breast Cancer Chemotherapy: Findings From a Large Population-Based Cohort
Authors: Du Xianglin L. , Lairson David R. , Begley Charles E. , Fang Shenying 
Published: November 2005

Purpose Hematopoietic growth factors have played a major role in preventing infection and shortening the duration of neutropenia in patients receiving cancer chemotherapy. Little information is available on how these growth factors are used in patients with cancer outside the clinical trial setting. We performed descriptive and exploratory analyses on the patterns and correlates of the use of hematopoietic growth factors in community-dwelling elderly patients. Patients and Methods We identified 5,843 women from the Surveillance, Epidemiology, and End Results (SEER)–Medicare-linked data cohorts who were diagnosed with breast cancer at age 65 or older in 1992 to 1999 from the 11 SEER areas and received chemotherapy. Results Overall, 17.3% of the elderly women with breast cancer chemotherapy received filgrastim and 6.8% received epoetin. The use of the growth factors increased significantly over time from 1992 to 1999 (P < .001 for trend). Compared with patients diagnosed in 1992 to 1994, patients diagnosed in 1998 to 1999 were more than five times and 65 times more likely to receive filgrastim and epoetin, respectively, after controlling for other factors such as age and comorbidity. There also was substantial geographic variation in the use of hematopoietic growth factors, ranging from 10.6% in Seattle to 22.9% in Atlanta. Significant predictors of growth factors included patient age, race, tumor stage, and comorbidity. Conclusion There were substantial temporal and geographic variations in the use of hematopoietic growth factors among patients receiving chemotherapy for breast cancer. The nationwide and population-based Medicare claims provide potential for examining the effectiveness, medical costs, and cost effectiveness of hematopoietic growth factors in the community.
Costs and Cost Effectiveness of a Health Care Provider–Directed Intervention to Promote Colorectal Cancer Screening Among Veterans
Authors: Wolf Michael S. , Fitzner Karen A. , Powell Eowyn F. , McCaffrey Kathryn R. , Pickard A. Simon , McKoy June M. , Lindenberg Julia , Schumock Glen T. , Carson Kenneth R. , Ferreira M. Rosario , Dolan Nancy C. , Bennett Charles L. 
Published: November 2005

Purpose Colorectal cancer screening is underused, particularly in the Veterans Affairs (VA) population. In a randomized controlled trial, a health care provider–directed intervention that offered quarterly feedback to physicians on their patients' colorectal cancer screening rates led to a 9% increase in colorectal cancer screening rates among veterans. The objective of this secondary analysis was to assess the cost effectiveness of the colorectal cancer screening promotion intervention. Methods Providers in the intervention arm attended an educational workshop on colorectal cancer screening and received confidential feedback on individual and group-specific colorectal cancer screening rates. The primary end point was completion of colorectal cancer screening tests. Sensitivity analyses investigated cost-effectiveness estimates varying the data collection methods, costs of labor and technology, and the effectiveness of the intervention. Results Rates of colorectal cancer screening for the intervention versus control arms were 41.3% v 32.4%, respectively (P < .05). The incremental cost-effectiveness ratio was $978 per additional veteran screened based on feedback reports generated from manual review of records. However, if feedback reports could be generated from information technology systems, sensitivity analyses indicate that the cost-effectiveness estimate would decrease to $196 per additional veteran screened. Conclusion An intervention based on quarterly feedback reports to physicians improved colorectal cancer screening rates at a VA medical center. This intervention would be cost effective if relevant data could be generated by existing information technology systems. Our findings may have broad applicability because a 2005 Medicare initiative will provide the VA electronic medical record system as a free benefit to all US physicians.
Role of Chemotherapy and the Receptor Tyrosine Kinases KIT, PDGFRα, PDGFRβ, and Met in Large-Cell Neuroendocrine Carcinoma of the Lung
Authors: Rossi Giulio , Cavazza Alberto , Marchioni Alessandro , Longo Lucia , Migaldi Mario , Sartori Giuliana , Bigiani Nazzarena , Schirosi Laura , Casali Christian , Morandi Uliano , Facciolongo Nicola , Maiorana Antonio , Bavieri Mario , Fabbri Leonardo M. , Brambilla Elisabeth 
Published: November 2005

Purpose Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a relatively uncommon, high-grade neuroendocrine tumor sharing several features with small-cell lung carcinoma (SCLC) but currently considered as a variant of non-SCLC and accordingly treated with poor results. Little is known about the optimal therapy of LCNEC and the possible therapeutic molecular targets. Patients and Methods We reviewed 83 patients with pure pulmonary LCNEC to investigate their clinicopathologic features, therapeutic strategy, and immunohistochemical expression and the mutational status of the receptor tyrosine kinases (RTKs) KIT, PDGFRα, PDGFRβ, and Met. Results LCNEC histology predicted a dismal outcome (overall median survival, 17 months) even in stage I patients (5-year survival rate, 33%). LCNEC strongly expressed RTKs (KIT in 62.7% of patients, PDGFRα in 60.2%, PDGFRβ in 81.9%, and Met in 47%), but no mutations were detected in the exons encoding for the relevant juxtamembrane domains. Tumor stage and size (≥ 3 cm) and Met expression were significantly correlated with survival. At univariate and multivariate analysis, SCLC-based chemotherapy (platinum-etoposide) was the most important variable correlating with survival, both in the adjuvant and metastatic settings (P < .0001). Conclusion Pulmonary LCNEC represents an aggressive tumor requiring multimodal treatment even for resectable stage I disease, and LCNEC seems to respond to adjuvant platinum-etoposide–based chemotherapy. Patients who received this therapy had the best survival rate. Despite our failure in finding mutational events in the tested RTKs, the strong expression of KIT, PDGFRα, PDGFRβ, and Met in tumor cells suggests an important role of these RTKs in LCNEC, and these RTKs seem to be attractive therapeutic targets.
Genomic and Protein Expression Profiling Identifies CDK6 As Novel Independent Prognostic Marker in Medulloblastoma
Authors: Mendrzyk Frank , Radlwimmer Bernhard , Joos Stefan , Kokocinski Felix , Benner Axel , Stange Daniel E. , Neben Kai , Fiegler Heike , Carter Nigel P. , Reifenberger Guido , Korshunov Andrey , Lichter Peter 
Published: November 2005

PurposeMedulloblastoma is the most common malignant brain tumor in children. Despite multimodal aggressive treatment, nearly half of the patients die as a result of this tumor. Identification of molecular markers for prognosis and development of novel pathogenesis-based therapies depends crucially on a better understanding of medulloblastoma pathomechanisms.Patients and MethodsWe performed genome-wide analysis of DNA copy number imbalances in 47 medulloblastomas using comparative genomic hybridization to large insert DNA microarrays (matrix-CGH). The expression of selected candidate genes identified by matrix-CGH was analyzed immunohistochemically on tissue microarrays representing medulloblastomas from 189 clinically well-documented patients. To identify novel prognostic markers, genomic findings and protein expression data were correlated to patient survival.ResultsMatrix-CGH analysis revealed frequent DNA copy number alterations of several novel candidate regions. Among these, gains at 17q23.2-qter (P < .01) and losses at 17p13.1 to 17p13.3 (P = .04) were significantly correlated to poor prognosis. Within 17q23.2-qter and 7q21.2, two of the most frequently gained chromosomal regions, confined amplicons were identified that contained the PPM1D and CDK6 genes, respectively. Immunohistochemistry revealed strong expression of PPM1D in 148 (88%) of 168 and CDK6 in 50 (30%) of 169 medulloblastomas. Overexpression of CDK6 correlated significantly with poor prognosis (P < .01) and represented an independent prognostic marker of overall survival on multivariate analysis (P = .02).ConclusionWe identified CDK6 as a novel molecular marker that can be determined by immunohistochemistry on routinely processed tissue specimens and may facilitate the prognostic assessment of medulloblastoma patients. Furthermore, increased protein-levels of PPM1D and CDK6 may link the TP53 and RB1 tumor suppressor pathways to medulloblastoma pathomechanisms.
Adverse Effects of Preoperative Radiation Therapy for Rectal Cancer: Long-Term Follow-Up of the Swedish Rectal Cancer Trial
Authors: Birgisson Helgi , Påhlman Lars , Gunnarsson Ulf , Glimelius Bengt 
Published: November 2005

Purpose To analyze the occurrence of subacute and late adverse effects in patients treated with preoperative irradiation for rectal cancer. Patients and Methods The study population included 1,147 patients randomly assigned to preoperative radiation therapy or surgery alone in the Swedish Rectal Cancer Trial conducted 1987 through 1990. Patient data were matched against the Swedish Hospital Discharge Register to identify patients admitted to hospital after the primary treatment of the rectal cancer. Patients with known residual disease were excluded, and patients with a recurrence were censored 3 months before the date of recurrence. Relative risks (RR) with 95% CIs were calculated. Results Irradiated patients were at increased risk of admissions during the first 6 months from the primary treatment (RR = 1.64; 95% CI, 1.21 to 2.22); these were mainly for gastrointestinal diagnoses. Overall, the two groups showed no difference in the risk of admissions more than 6 months from the primary treatment (RR = 0.95; 95% CI, 0.80 to 1.12). Regarding specific diagnoses, however, RRs were increased for admissions later than 6 months from the primary treatment in irradiated patients for unspecified infections, bowel obstruction, abdominal pain, and nausea. Conclusion Gastrointestinal disorders, resulting in hospital admissions, seem to be the most common adverse effect of short-course preoperative radiation therapy in patients with rectal cancer. Bowel obstruction was the diagnosis of potentially greatest importance, which was more frequent in irradiated than in nonirradiated patients.