bluuebunny/crossref_metadata_2025_split huggingface dataset:
Susceptibility to glaucoma: differential comparison of the astrocyte transcriptome from glaucomatous African American and Caucasian American donors
Authors: Lukas Thomas J , Miao Haixi , Chen Lin , Riordan Sean M , Li Wenjun , Crabb Andrea M , Wise Alexandria , Du Pan , Lin Simon M , Hernandez M Rosario 
Published: July 2008

Abstract
Background
Epidemiological and genetic studies indicate that ethnic/genetic background plays an important role in susceptibility to primary open angle glaucoma (POAG). POAG is more prevalent among the African-descent population compared to the Caucasian population. Damage in POAG occurs at the level of the optic nerve head (ONH) and is mediated by astrocytes. Here we investigated differences in gene expression in primary cultures of ONH astrocytes obtained from age-matched normal and glaucomatous donors of Caucasian American (CA) and African American (AA) populations using oligonucleotide microarrays.

Results
Gene expression data were obtained from cultured astrocytes representing 12 normal CA and 12 normal AA eyes, 6 AA eyes with POAG and 8 CA eyes with POAG. Data were normalized and significant differential gene expression levels detected by using empirical Bayesian shrinkage moderated t-statistics. Gene Ontology analysis and networks of interacting proteins were constructed using the BioGRID database. Network maps included regulation of myosin, actin, and protein trafficking. Real-time RT-PCR, western blots, ELISA, and functional assays validated genes in the networks.

Conclusion
Cultured AA and CA glaucomatous astrocytes retain differential expression of genes that promote cell motility and migration, regulate cell adhesion, and are associated with structural tissue changes that collectively contribute to neural degeneration. Key upregulated genes include those encoding myosin light chain kinase (MYLK), transforming growth factor-β receptor 2 (TGFBR2), rho-family GTPase-2 (RAC2), and versican (VCAN). These genes along with other differentially expressed components of integrated networks may reflect functional susceptibility to chronic elevated intraocular pressure that is enhanced in the optic nerve head of African Americans.
Risk Factors for the Incidence of Breast Cancer: Do They Affect Survival From the Disease?
Authors: Barnett Gillian C. , Shah Mitul , Redman Karen , Easton Douglas F. , Ponder Bruce A.J. , Pharoah Paul D. P. 
Published: July 2008

Purpose Risk factors that influence the incidence of breast cancer may also affect survival after diagnosis. Methods Data from 4,560 women with invasive breast cancer who had taken part in the population-based Studies of Epidemiology and Risk Factors in Cancer Heredity (SEARCH) breast cancer study were used to investigate the influence on survival of variables related to pregnancy, menarche and menopause, prior use of exogenous hormones, height, weight, body mass index (BMI), smoking history, and alcohol intake. Results In univariate analyses, there was no association between prognosis and age at menarche and menopause, menopausal status at diagnosis, smoking history, or prior use of the oral contraceptive pill. Women whose most recent pregnancy was more than 30 years ago had a 35% reduced risk of dying (95% CI, 8% to 54%) compared with women who had a full-term pregnancy in the past 15 years, and the use of hormone replacement therapy for more than 4 years was associated with a similar risk reduction. BMI was associated with a 3% (95% CI, 1% to 4%) increase in mortality per unit increase. Improved prognosis was seen with increasing current alcohol consumption, with a 2% (95% CI, 1% to 3%) reduction in the risk of death per unit of alcohol consumed per week. Conclusion The apparent benefit of alcohol intake has not been described before, and our data need to be interpreted with some caution. However, our finding that an increase in BMI is associated with a poorer prognosis supports previously published data and suggests that advice on weight loss should be given to all obese patients with breast cancer.
Effect of Esthetic Outcome After Breast-Conserving Surgery on Psychosocial Functioning and Quality of Life
Authors: Waljee Jennifer F. , Hu Emily S. , Ubel Peter A. , Smith Dylan M. , Newman Lisa A. , Alderman Amy K. 
Published: July 2008

PurposeAlthough breast-conserving surgery (BCS) is often assumed to result in minimal deformity, many patients report postoperative breast asymmetry. Understanding the effect of asymmetry on psychosocial functioning is essential for patients to make an informed choice for surgery.Patients and MethodsAll women who underwent BCS at the University of Michigan Medical Center (Ann Arbor, MI) during a 4-year period were surveyed using a mailed questionnaire (N = 714; response rate = 79.5%). Women were queried regarding five aspects of psychosocial functioning: quality of life (QOL), depression, fear of recurrence, stigmatization, and perceived change in health status. Postoperative breast asymmetry was assessed using items from the Breast Cancer Treatment and Outcomes Survey. Multiple regression was used to examine the relationship between breast asymmetry and each outcome, controlling for age, time from surgery in years, race, education level, disease stage, surgical treatment, and the occurrence of postoperative complications.ResultsWomen with pronounced breast asymmetry were significantly more likely to feel stigmatized as a result of their breast cancer treatment (odds ratio [OR] = 4.58; 95% CI, 2.77 to 7.55) and less likely to report unchanged or improved health after treatment (OR = 0.43; 95% CI, 0.27 to 0.66). Minimal breast asymmetry was associated with higher QOL scores (86.3 v 82.4, P < .001). Finally, women with pronounced breast asymmetry were more likely to exhibit depressive symptoms (minimal asymmetry, 16.2%; moderate asymmetry, 18.0%; pronounced asymmetry, 33.7%, Wald test = 16.6; P = .002).ConclusionPronounced breast asymmetry after BCS is significantly correlated with poor psychosocial functioning. Identifying patients at risk for postoperative asymmetry at the time of consultation may allow for improved referral for supportive counseling, prosthetics, and reconstruction.
Novel Intraoperative Molecular Test for Sentinel Lymph Node Metastases in Patients With Early-Stage Breast Cancer
Authors: Julian Thomas B. , Blumencranz Peter , Deck Kenneth , Whitworth Pat , Berry Donald A. , Berry Scott M. , Rosenberg Anne , Chagpar Anees B. , Reintgen Douglas , Beitsch Peter , Simmons Rache , Saha Sukamal , Mamounas Eleftherios P. , Giuliano Armando 
Published: July 2008

PurposeAn accurate, intraoperative sentinel lymph node (SLN) test could decrease delayed axillary dissections. Molecular tests may be more sensitive than current intraoperative tests but historically have not been rapid enough and have not been properly validated. We present the results from a large, prospective evaluation of the first rapid molecular SLN test, the Breast Lymph Node (BLN) Assay.MethodsA beta trial (n = 304) to determine the threshold levels of mammaglobin and cytokeratin 19 correlating with metastasis greater than 0.2 mm and a validation trial (n = 416) to validate the threshold cutoffs were conducted. Alternating portions from each SLN were processed for histology and the BLN Assay.ResultsBLN Assay performance against extensive permanent-section histology verified by central pathology review was similar to that expected of standard permanent-section histology: sensitivity, 87.6%; specificity, 94.2%; positive predictive value, 86.2%; and negative predictive value (NPV), 94.9%. In 319 patients with both frozen-section hematoxylin and eosin results and BLN Assay results, the BLN Assay had higher sensitivity (95.6%) and NPV (98.2%) than frozen section (sensitivity, 85.6%; NPV, 94.5%). The assay can be performed in approximately 36 to 46 minutes for one to three nodes.ConclusionThe BLN Assay allows a rapid evaluation of 50% of each SLN. Comparison with permanent-section histology on adjacent node pieces evaluated by expert pathologists indicated that the BLN Assay was more sensitive than current intraoperative techniques while maintaining high specificity. These data indicate that the assay may be clinically useful for intraoperative or postoperative axillary lymph node dissection decisions.
Young Age at Diagnosis Correlates With Worse Prognosis and Defines a Subset of Breast Cancers With Shared Patterns of Gene Expression
Authors: Anders Carey K. , Hsu David S. , Broadwater Gloria , Acharya Chaitanya R. , Foekens John A. , Zhang Yi , Wang Yixin , Marcom P. Kelly , Marks Jeffrey R. , Febbo Phillip G. , Nevins Joseph R. , Potti Anil , Blackwell Kimberly L. 
Published: July 2008

Purpose Breast cancer arising in young women is correlated with inferior survival and higher incidence of negative clinicopathologic features. The biology driving this aggressive disease has yet to be defined. Patients and Methods Clinically annotated, microarray data from 784 early-stage breast cancers were identified, and prospectively defined, age-specific cohorts (young: ≤ 45 years, n = 200; older: ≥ 65 years, n = 211) were compared by prognosis, clinicopathologic variables, mRNA expression values, single-gene analysis, and gene set enrichment analysis (GSEA). Univariate and multivariate analyses were performed. Results Using clinicopathologic variables, young women illustrated lower estrogen receptor (ER) positivity (immunohistochemistry [IHC], P = .027), larger tumors (P = .012), higher human epidermal growth factor receptor 2 (HER-2) overexpression (IHC, P = .075), lymph node positivity (P = .008), higher grade tumors (P < .0001), and trends toward inferior disease-free survival (DFS; hazard ratio = 1.32; P = .094). Using genomic expression analysis, tumors arising in young women had significantly lower ERα mRNA (P < .0001), ERβ (P = .02), and progesterone receptor (PR) expression (P < .0001), but higher HER-2 (P < .0001) and epidermal growth factor receptor (EGFR) expression (P < .0001). Exploratory analysis (GSEA) revealed 367 biologically relevant gene sets significantly distinguishing breast tumors arising in young women. Combining clinicopathologic and genomic variables among tumors arising in young women demonstrated that younger age and lower ERβ and higher EGFR mRNA expression were significant predictors of inferior DFS. Conclusion This large-scale genomic analysis illustrates that breast cancer arising in young women is a unique biologic entity driven by unifying oncogenic signaling pathways, is characterized by less hormone sensitivity and higher HER-2/EGFR expression, and warrants further study to offer this poor-prognosis group of women better preventative and therapeutic options.
Analysis of Maryland Cancer Patient Participation in National Cancer Institute–Supported Cancer Treatment Clinical Trials
Authors: Baquet Claudia R. , Ellison Gary L. , Mishra Shiraz I. 
Published: July 2008

Purpose We examined the relationship of sociodemographic factors, urban/rural residence, and county-level socioeconomic factors on accrual of Maryland patients with cancer to National Cancer Institute (NCI) –sponsored cancer treatment clinical trials. Patients and Methods Data were analyzed for the period 1999 to 2002 for 2,240 Maryland patients with cancer accrued onto NCI-sponsored treatment trials. The extent to which Maryland patients with cancer and patients residing in lower socioeconomic and/or rural areas were accrued to cancer trials and were representative of all patients with cancer in Maryland was determined. Data were obtained from several sources, including NCI's Cancer Therapy Evaluation Program for Maryland patients with cancer in Cooperative Group therapeutic trials, Maryland Cancer Registry data on cancer incidence, and United States Census and the Department of Agriculture. Results For Maryland patients with cancer accrued onto NCI-sponsored treatment trials between 1999 and 2002, subgroups accrued at a higher rate included pediatric and adolescent age groups, white patients, female patients (for sex-specific tumors), patients with private health insurance, and patients residing in the Maryland National Capitol region. Moreover, between 1999 and 2002, there was an estimated annual decline (8.9% per year; P < .05) in the percentage of black patients accrued onto cancer treatment trials. Logistic regression models uncovered different patterns of accrual for female patients and male patients on county-level socioeconomic factors. Conclusion Results highlight disparities in the accrual of Maryland patients with cancer onto NCI-sponsored treatment trials based on patient age, race/ethnicity, geography of residence, and county-level socioeconomic factors. Findings provide the basis for development of innovative tailored and targeted educational efforts to improve trial accrual, particularly for the underserved.
Results of the First Phase I Clinical Trial of the Novel Ii-Key Hybrid Preventive HER-2/neuPeptide (AE37) Vaccine
Authors: Holmes Jarrod P. , Benavides Linda C. , Gates Jeremy D. , Carmichael Mark G. , Hueman Matthew T. , Mittendorf Elizabeth A. , Murray James L. , Amin Asna , Craig Dianna , von Hofe Eric , Ponniah Sathibalan , Peoples George E. 
Published: July 2008

PurposeHER-2/neu is overexpressed in breast cancer and is the source of immunogenic peptides. CD4+T-helper peptides for HER-2/neu are being evaluated in vaccine trials. The addition of Ii-Key, a four–amino-acid LRMK modification, increases vaccine potency when compared with unmodified class II epitopes. We present the results of the first human phase I trial of the Ii-Key hybrid HER-2/neu peptide (AE37) vaccine in disease-free, node-negative breast cancer patients.Patients and MethodsThe dose escalation trial included five dose groups, to determine safety and optimal dose of the hybrid peptide (100 μg, 500 μg, 1,000 μg) and granulocyte-macrophage colony-stimulating factor (GM-CSF; range, 0 to 250 μg). In the event of significant local toxicity, GM-CSF (or peptide in absence of GM-CSF) was reduced by 50%. Immunologic response was monitored by delayed-type hypersensitivity and [3H]thymidine proliferative assays for both the hybrid AE37 (LRMK-positive HER-2/neu:776-790) and AE36 (unmodified HER-2/neu:776-790).ResultsAll 15 patients completed the trial with no grade 3 to 5 toxicities. Dose reductions occurred in 47% of patients. In the second group (peptide, 500 μg; GM-CSF, 250 μg), all patients required dose reductions, prompting peptide-only inoculations in the third group. The vaccine induced dose-dependent immunologic responses in vitro and in vivo to AE37, as well as AE36.ConclusionThe hybrid AE37 vaccine seems safe and well tolerated with minimal toxicity if properly dosed. AE37 is capable of eliciting HER-2/neu–specific immune responses, even without the use of an adjuvant. This trial represents the first human experience with the Ii-Key modification, and to our knowledge, AE37 is the first peptide vaccine to show potency in the absence of an immunoadjuvant.
Obesity and Risk of Cancer in Postmenopausal Korean Women
Authors: Song Yun-Mi , Sung Joohon , Ha Mina 
Published: July 2008

PurposeTo evaluate an association between obesity, measured by body mass index (BMI; kg/m2), and risk of cancer at individual and all sites in postmenopausal women.MethodsA cohort of 170,481 postmenopausal Korean women who were age 40 to 64 years at baseline measurement of BMI was observed prospectively from 1994 to 2003 for cancer incidence. Multivariable adjusted proportional hazard models were used for evaluating the association.ResultsWomen with a BMI of 30 kg/m2or higher had a 23% higher risk of cancer than women with a BMI between 21.0 and 22.9 kg/m2(hazard ratio = 1.23; 95% CI, 1.08 to 1.41). According to the increase in BMI level, significant positive trends existed in cancers of colon, breast, corpus uteri, and kidney with hazard ratios of 1.05 (95% CI, 1.02 to 1.08), 1.07 (95% CI, 1.05 to 1.10), 1.13 (95% CI, 1.07 to 1.20), and 1.08 (95% CI, 1.02 to 1.15), respectively, for the increase of BMI by 1 kg/m2. When the analysis was limited to never-smokers, women with a BMI of 25 kg/m2or higher showed a significantly increased risk of cancers of the colon, breast, corpus uteri, and kidney and leukemia compared with the normal BMI (18.5 to 22.9 kg/m2) group.ConclusionAlthough variations exist between the individual cancer sites, obesity was associated with an overall increased risk of cancer in postmenopausal Korean women. To reduce the risk of cancer, active strategies to prevent obesity should be implemented in postmenopausal women.
Activity of Sunitinib in Patients With Advanced Neuroendocrine Tumors
Authors: Kulke Matthew H. , Lenz Heinz-Josef , Meropol Neal J. , Posey James , Ryan David P. , Picus Joel , Bergsland Emily , Stuart Keith , Tye Lesley , Huang Xin , Li Jim Z. , Baum Charles M. , Fuchs Charles S. 
Published: July 2008

PurposeStandard cytotoxic chemotherapy has limited efficacy in metastatic neuroendocrine tumor patients. Neuroendocrine tumors express vascular endothelial growth factor (VEGF) and its receptor (VEGFR). Sunitinib malate, an oral tyrosine kinase inhibitor, has activity against VEGFRs as well as platelet-derived growth factor receptors, stem-cell factor receptor, glial cell line–derived neurotrophic factor, and FMS-like tyrosine kinase-3. We evaluated the efficacy of sunitinib in a two-cohort, phase II study of advanced carcinoid and pancreatic neuroendocrine tumor patients.Patients and MethodsPatients were treated with repeated 6-week cycles of oral sunitinib (50 mg/d for 4 weeks, followed by 2 weeks off treatment). Patients were observed for response, survival, and adverse events. Patient-reported outcomes were assessed.ResultsAmong 109 enrolled patients, 107 received sunitinib (carcinoid, n = 41; pancreatic endocrine tumor, n = 66). Overall objective response rate (ORR) in pancreatic endocrine tumor patients was 16.7% (11 of 66 patients), and 68% (45 of 66 patients) had stable disease (SD). Among carcinoid patients, ORR was 2.4% (one of 41 patients), and 83% (34 of 41 patients) had SD. Median time to tumor progression was 7.7 months in pancreatic neuroendocrine tumor patients and 10.2 months in carcinoid patients. One-year survival rate was 81.1% in pancreatic neuroendocrine tumor patients and 83.4% in carcinoid patients. No significant differences from baseline in patient-reported quality of life or fatigue were observed during treatment.ConclusionSunitinib has antitumor activity in pancreatic neuroendocrine tumors; its activity against carcinoid tumors could not be definitively determined in this nonrandomized study. Randomized trials of sunitinib in patients with neuroendocrine tumors are warranted.
Severe Sequence-Specific Toxicity When Capecitabine Is Given After Fluorouracil and Leucovorin
Authors: Hennig Ivo M. , Naik Jay D. , Brown Sarah , Szubert Alex , Anthoney David A. , Jackson David P. , Melcher Alan M. , Crawford S. Michael , Bradley Christopher , Brown Julia M.B. , Seymour Matthew T. 
Published: July 2008

Purpose Options for single-agent fluoropyrimidine adjuvant therapy after bowel cancer resection include intravenous fluorouracil with leucovorin (FU/LV) or oral capecitabine. These treatments have similar efficacy but differ in convenience and toxicity. We therefore wished to compare their overall acceptability to patients. Patients and Methods Patients scheduled for adjuvant single-agent fluoropyrimidine therapy were randomly assigned to receive once-weekly FU/LV (425 mg/m2 FU, 45 mg LV) for 6 weeks, followed by two 3-week cycles of capecitabine (1,250 mg/m2 twice daily, days 1 through 14), or the same treatments but in reverse order. After 12 weeks, the patients were asked which treatment they preferred, and received the preferred treatment for an additional 12 weeks. The primary end point was patient preference. Results After 40 of the planned 74 patients had been randomly assigned, real-time adverse event monitoring led to early trial closure because of excess sequence-specific toxicity. Eleven of 14 patients (79%) receiving capecitabine as their second treatment experienced grade ≥ 3 toxicity. This compared with five of 18 patients (28%) receiving capecitabine as the first treatment, and no patients receiving FU/LV as the first treatment (zero of 16) or the second treatment (zero of 12). Similar imbalances were seen in the proportion of patients requiring interruption of treatment. Conclusion In chemotherapy-naïve patients, capecitabine produced more toxicity than FU/LV, but at levels in line with previously reported data. However, treatment with capecitabine after FU/LV caused markedly increased toxicity, indicating a sequence-specific interaction. The mechanism has not been determined, but interaction with intracellularly retained folate after FU/LV therapy is a possibility. Oncologists need to be aware of this risk if considering crossing patients over from FU/LV to capecitabine-based regimens.
Impact of Intensity-Modulated Radiation Therapy on Local Control in Primary Soft-Tissue Sarcoma of the Extremity
Authors: Alektiar Kaled M. , Brennan Murray F. , Healey John H. , Singer Samuel 
Published: July 2008

Purpose One of the concerns about intensity-modulated radiation therapy (IMRT) is that its tight dose distribution, an advantage in reducing RT morbidity to surrounding normal structures, might compromise tumor coverage. The purpose of this study is to determine if such concern is warranted in soft-tissue sarcoma (STS) of the extremity. Methods Between 02/02 and 05/05, 41 adult patients with primary STS of the extremity were treated with limb-sparing surgery and adjuvant IMRT. The margins were positive/within 1 mm in 21. Tumor size was more than 10 cm in 68% of patients and grade was high in 83%. Preoperative IMRT was given to 7 patients (50 Gy) and postoperative IMRT (median dose, 63 Gy) was given to 34 patients. Complete gross resection including periosteal stripping/bone resection was required in 11, and neurolysis/nerve resection in 24. Results With a median follow-up time of 35 months, two (4.8%) of 41 patients developed local recurrence. The 5-year actuarial local control rate was 94% (95% CI, 86% to 100%). The local control rate was also 94% for patients with negative or positive/close margin. Other prognostic factors such as age, size, and grade did not impact local control either. The 5-year distant control rate was 61% (95% CI, 45% to 76%) and the overall survival rate was 64% (95% CI, 45% to 84%). Conclusion IMRT in STS of the extremity provides excellent local control in a group of patients with high risk features. This suggests that the precision with which IMRT dose is distributed has a beneficiary effect in sparing normal tissue and improving local control.