bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5158: Serological autoantibody profiling in bladder cancer using protein arrays
Authors: Orenes-Piñero Esteban , Herrera Emilia , Rico Daniel , Barderas Rodrigo , Gonzalez-Pisano David , Casal Ignacio , Algaba Ferran , Palou Joan , Urrutia Manuel , Navajo Jose , Sanchez Lydia , Sanchez-Carbayo Marta 
Published: May 2019

Abstract
Cancer cells might release at least part of their contents into the blood stream directly or through extracellular fluids upon cell damage or death. Cancer proteins not present in non-neoplastic cell subpopulations might then elicit a host immune response. The serum autoantibody repertoire from cancer patients might therefore, be exploited for the identification of tumor-associated antigens (TAAs). The recognition that human tumors stimulate the production of autoantibodies against such autologous cellular proteins (TAAs) has opened the door to the possibility that autoantibodies could be translated into serological tools for early diagnosis and/or disease management. In this report, we attempt at exploring the serum proteome of patients with bladder cancer using protein arrays. The serum autoantibody profiles of 18 patients with bladder cancer and 6 control specimens including cases affected with other neoplasias, benign urological diseases and healthy individuals was investigated using protein arrays containing more than 12,000 proteins. Data analyses included T-test as well as clustering strategies using the Prospector and CIMMiner softwares. Supervised clustered heatmaps served to highlight identified biological differences among autoantibody profiles arrays of bladder cancer cases and controls. Moreover, protein expression patterns of the identified immunogenic TAAs were assessed by immunohistochemistry on tissue microarrays (n=92). Supervised clustering analysis segregated bladder cancer patients from controls. A panel of 171 autoantibodies was identified to be differentially expressed in bladder cancer patients as compared to control individuals in a significant manner. Bladder cancer TAAs included proteins involved in cell proliferation, signal transduction, apoptosis, DNA-binding and transcription factors, among others. Immunohistochemical analyses on tissue arrays served to validate the increased protein expression of identified TAAs in bladder tumors. Moreover they revealed the relevance of expression patterns of proteins such as clusterin for bladder cancer diagnostics, staging and outcome prognosis. Protein expression patterns of clusterin were significantly associated with clinico-pathological variables such as tumor size (P=0.034), T1 substaging (P=0.013) or progression into muscle invasive disease (P=0.020). Thus, the novel application of high-throughput protein arrays for serum autoantibody profiling is providing critical information not only to identify TAAs candidate biomarkers for bladder cancer diagnostics and potential immunological therapeutic targets, such as clusterin, but also to further characterize bladder cancer progression.
Abstract 5537: Surgical resection and survival in octagenarians and younger age cohorts of patients diagnosed with non-small cell lung cancer.
Authors: Dillman Robert O , Zusman Douglas R , Joyo Colin I 
Published: May 2019

Abstract
Background and Purpose: As life expectancy has increased, and more former smokers are surviving into old age, an increasing proportion of newly diagnosed patients with non-small cell lung cancer (NSCLC) are over the age of 80 years. This has led to questions regarding the appropriateness of subjecting elderly patients with newly diagnosed NSCLC, to surgical resection, even if they have only localized disease. Patients and Methods: The Hoag Cancer Center data base was used to identify patients with non-small lung cancer diagnosed during 2000-2006, who underwent a surgical resection at Hoag Hospital. Actuarial survival curves were generated for each age cohort. Results: Of 1293 total patients, 17.2% were 80 years of age or older, 36.1% age 70-79, 29.2% age 60-69, 12.9% age 50-59, and 4.6% &lt; 50 years of age. Surgical resections of primary lung cancer included 400 lobectomies, 59 wedge resections, and 23 pneumonectomies. There was a strong correlation (.954) between older age and a higher proportion of male patients. There was also a difference in the proportional distribution of histologies by age group (p=.0005) primarily because of a .973 inverse correlation between older age and adenocarcinoma histology, which was the predominant histology in all age groups. There also were differences in the stage distribution of cases by age (p&lt;.0001), primarily because of a .961 correlation between older age and localized disease, and conversely, a .989 inverse correlation with distant metastatic disease. The proportion of the 482 patients undergoing surgery did not differ significantly among all cohorts (p=0.62), but a somewhat smaller proportion of patients age 80 or older underwent surgical resection of their primary lung cancer (31.7%) compared to patients less than 80 years of age (31.7% vs 38.5%, p=.046). Only 48/75 (64.0%) of patients age 80 or older with localized NSCLC underwent surgical resection compared to 254/306 (83.0%) for patients younger than age 80 (p=.0003). There was a similar trend for patients who had regionally advanced disease: 18/52 (34.6%) of patients age 80 or older underwent surgical resection versus 124/251 (49.4%) for patients less than age 80 (p=.052). Actuarial survival curves for patients revealed observed 5-year survival rates of 62%, 53%, 63%, 63%, and 79% from oldest to youngest cohort. Conclusion: A smaller proportion of patients 80 years of age or older underwent surgery compared to those less than 80 years of age, but survival for octogenarians with newly diagnosed NSCLC, who were selected to undergo surgical resection, was comparable to younger age groups. Older patients should not be denied potentially curative surgery simply because of age.
Abstract 555: Gene expression differences in primary breast tumors from African American and Caucasian women.
Authors: Field Lori A , Love Brad , Deyarmin Brenda , Kane Jennifer , Hooke Jeffrey A , Ellsworth Rachel E , Shriver Craig D 
Published: May 2019

Abstract
Background: Incidence of breast cancer varies across ethnic groups. Overall incidence is highest among Caucasian women (CW); however, incidence in women younger than 40 as well as mortality is highest among African American women (AAW). Although socioeconomic disparities are often blamed for these differences, AAW are more likely than CW to present with large, aggressive tumors with poor prognostic features such as estrogen receptor negativity, triple negative phenotype, and lymph node involvement, suggesting that molecular factors may also contribute to the younger age of onset and worse outcomes in AAW. In the present study, we have compared primary breast tumors from AAW and CW by gene expression profiling to identify differentially expressed genes that may explain why diagnosis at a young age, aggressive tumor biology and lower survival are more prevalent in AAW than CW with breast cancer.
Materials and Methods: Breast tumor specimens were obtained from 26 pairs of age and stage-matched AAW and CW enrolled in the Clinical Breast Care Project (CBCP). Tumor cells were isolated by laser microdissection (Leica) and RNA isolated using the RNAqueous Micro kit (Ambion). RNA was amplified and labeled with biotin-11-UTP using two rounds of amplification with the MessageAmp II aRNA Amplification kit (Ambion). Fragmented aRNA was hybridized to the HG U133A 2.0 array (Affymetrix). A Mann-Whitney U test was used to identify differentially expressed genes (p ≤ 0.001).
Results: Sixty-five genes were differentially expressed between AAW and CW. Twenty-eight genes were more highly expressed in AAW, including SOS1, TSPO, and PSPH, while 37genes had lower expression in AAW, including ZNF228, SCAMP4, and PSD3.
Discussion: These results support a model in which molecular factors influence breast cancer onset, progression and prognosis in AAW. Genes with higher expression in tumors from AAW function in steroid, fatty acid, and serine biosynthesis, signal transduction, cell proliferation and adhesion, and cytoskeleton organization and biogenesis. Functions of genes with lower expression in AAW tumors include regulation of transcription, vesicular transport, iron metabolism, signal transduction, and extracellular matrix organization and biogenesis. These results suggest that breast tumors from AAW and CW differ at the gene expression level and that these differences may be responsible for the more aggressive clinical features of breast tumors in AAW compared to CW.
Abstract 5568: Elevated interleukin-12 is a plasma marker of poor prognosis in stage III melanoma patients
Authors: Chun Yun S , Wang Yuling , Vo Amy H , Liu Huey , Wang Daniel Y , Gershenwald Jeffrey E , Cormier Janice N , Ross Merrick I , McClain Dana M , Schacherer Christopher W , Reveille John D , Lee Jeffrey E 
Published: May 2019

Abstract
Background: The heterodimeric cytokine interleukin-12 (IL-12) can both induce and suppress cellular immunity; the IL-12 p40 subunit is also a component of IL-23, which can promote tumor growth. IL-12 plasma levels have been reported to rise with age. Since survival in melanoma patients also depends on age, we investigated the relationship between IL-12, age and survival in a large cohort of melanoma patients.
Methods: Melanoma patients underwent blood draw for determination of combined IL-12-p40 levels by ELISA. Clinical data was obtained from a prospective database. AJCC stage of disease, age and overall survival (OS) were determined from the date of blood draw.
Results: Plasma IL-12 levels were determined in 658 patients (445 stages I-II, 150 stage III, 63 stage IV). IL-12 levels rose with age, with mean levels of 75, 84, 96 and 112 pg/ml in ages &lt;40, 40-59, 60-79 and ≥80 yr, respectively (p=0.012). After median follow-up of 13 mo, age was confirmed as a predictor of shorter OS on univariate analysis (p=0.009). However, in a multivariate model, while both advanced stage (p&lt;0.0001) and elevated IL-12 (p=0.006) were independent predictors of shorter OS, age (p=0.339) was not. Stage-specific analysis demonstrated that the association between IL-12 and OS was limited to patients with regional metastasis (stage III, table). The risk of death among stage III patients with elevated IL-12 (&gt; 150 pg/ml) was &gt;4-fold greater than that of patients with normal IL-12. Furthermore, the association of elevated IL-12 with OS in stage III patients was independent of the extent of regional disease.
Conclusions: An elevated plasma level of IL-12 is an independent predictor of poor prognosis in melanoma patients with regional metastasis. The association between IL-12 and advanced age could help explain the link between age and poorer prognosis in melanoma. Elevated IL-12 may be a marker of an immunosuppressive, tumor-promoting response in melanoma patients.
Prognostic factorUnivariate PMultivariate PHazard ratio (95% CI)Gender (M v. F)0.461--Age (yr)0.0300.349-Extent of disease (stage III A v. B v. C)0.0310.031Elevated IL-12 (&gt; 150 pg/ml)0.0010.0044.763 (1.660-13.669)
Abstract LB-139: Efficacy, safety, and changes in blood markers following sunitinib monotherapy in patients with advanced hepatocellular carcinoma: Experience from a multidisciplinary Phase II study
Authors: Pavlickova Petra , Vogt Peter K. 
Published: May 2019

Abstract
Patients with advanced hepatocellular carcinoma (HCC) have a very poor prognosis. HCC is a highly vascular tumor with increased levels of angiogenic factors, including VEGF and VEGFR2. Sunitinib is an oral multitargeted receptor tyrosine kinase inhibitor with activity against VEGFR2, PDGFRβ, and c-KIT. We performed a multidisciplinary Phase II study to evaluate the efficacy, toxicity, and changes in angiogenic parameters following sunitinib administration in patients with advanced HCC. Eligibility criteria included unresectable or metastatic measurable HCC. Patients were treated with sunitinib at 37.5 mg po qd on a standard 4 weeks on, 2 weeks off regimen (6 weeks/cycle). Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was performed to assess changes in tumor permeability. Plasma markers were assayed by multiplex protein array. In a subset of patients, viable circulating endothelial cells (CECs) and circulating progenitor cells (CPCs) were evaluated by flow cytometry in fresh whole blood samples at days 1, 15, 29, 57, 85, and 133. The primary endpoint of the study was progression-free survival (PFS). The targeted 34 patients have been enrolled: median age=63 (range 30-81); M/F=29/5; ECOG 0/1=15/19; CLIP 1/2/3=13/12/9. The treatment was generally well tolerated. Grade 3/4 toxicities included SGOT/SGPT (18/9%), neutropenia (12%), lymphopenia (15%), thrombocytopenia (12%), fatigue (9%), hand-foot syndrome (6%), rash (6%), hyperbilirubinemia (6%), and ataxia/disequilibrium (3%). One patient had a partial response and 10 patients had stable disease of at least 12 weeks. The median PFS was 4.0 months (95% CI: 2.8-7.0) and the median overall survival was 10 months (95% CI: 7.5-not estimable). Following 2 weeks of sunitinib administration, the mean tumor permeability (Ktrans) decreased by an average of 40% from the baseline. Sunitinib decreased sVEGFR2 levels and increased PlGF and VEGF levels in most patients. Interim analyses suggested that sunitinib treatment increase the number of CECs at day 15. The number of CPCs was significantly decreased by sunitinib at days 15, 29, and 57 compared to baseline (P&lt;0.01). Sunitinib administered in the current dose schedule can be safely given with close monitoring in the majority of HCC patients. Preliminary evidence of antitumor activity was observed. Changes in functional parameters on DCE-MRI were seen following sunitinib administration. Complete data on VEGF, PlGF, bFGF, and sVEGFR2 in plasma, CECs, and CPCs– and their correlation with changes in DCE-MRI and clinical response– will be presented.
Abstract LB-141: The Adenoma Prevention with Celecoxib (APC) trial: Five-year efficacy and safety results
Authors: Bertagnolli Monica M. , Zauber Ann G. , Hawk Ernest T 
Published: May 2019

Abstract
The APC Trial was a placebo-controlled randomized study of celecoxib for prevention of sporadic adenomas in high risk patients. This study showed that, after 3 years of treatment, patients taking 200 mg of celecoxib bid had 33% fewer adenomas and 57% fewer advanced lesions, and patients taking 400 mg of celecoxib bid had 45% fewer adenomas and 66% fewer advanced lesions. This study also found that celecoxib use was associated with a small but significant increase in cardiovascular risk. After completing the 3 year treatment study, APC trial enrollees were offered participation in a 2 year off treatment observational study during which additional safety and efficacy data were collected. Colonoscopies at 5 years after initiating study treatment were performed on 639 patients, and showed a cumulative advanced adenoma incidence of 0.125 in patients taking 200 mg bid celecoxib, and 0.158 in patients taking 400 mg celecoxib bid, compared to 0.212 for patients on placebo (41% and 25% reductions, respectively, P&lt;0.0001). Investigator reported, non-adjudicated selected cardiovascular events occurred 35 times in 676 patients randomized to placebo, 45 times in 683 patients randomized to celecoxib 200 mg bid, and 46 times in 669 patients randomized to 400 mg celecoxib bid. This selected category of events included all reports of myocardial infarction or ischemia, death from any cause, cerebrovascular disease, cardiovascular therapeutic procedures, or venous thrombosis or thromboembolism. One third of APC Trial participants used cardioprotective aspirin, and year 5 colonoscopy data showed increased adenoma incidence and severity in this subset, suggesting the presence of more aggressive disease in aspirin users. These data, together with additional new placebo-controlled analyses of celecoxib cardiovascular safety, suggest that chemoprevention with celecoxib may be safe and effective for some high risk colorectal adenoma patients.
Abstract LB-203: Phase I/II study of the androgen receptor antagonist MDV3100 in castration-resistant prostate cancer
Authors: Scher Howard I. , Beer Thomasz , Higano Celestia S , Danila Daniel C , Shelkey Julia , Hirmand Mohammed , Hung David , Morris Michael J , Larson Steve M , Sawyers Charles L 
Published: May 2019

Abstract
Introduction: Overexpression of the androgen receptor (AR) is believed to contribute to the progression of CRPC. MDV3100 is a small molecule AR antagonist with a novel mechanism of action that blocks nuclear translocation of AR, DNA binding, and has no agonist activity when AR is overexpressed. MDV3100 has been shown to be effective in preclinical models of CRPC. In July 2007, a multi-center first-in-man Phase 1-2 trial was initiated to determine safety, pharmacokinetics (PK), and antitumor activity including effects on prostate-specific antigen (PSA), bone and soft tissue metastases, and in selected pts fluorodeoxyglucose (FDG) and fluorodihydrotestosterone (FDHT) uptake by positron emission tomography (PET).
Methods: Pts were administered MDV3100 orally, once daily, starting at 30 mg with sequential escalations in cohorts of 3 pts. Enrollment was expanded at 60 mg and above to include up to 12 chemotherapy-naïve and 12 post-chemotherapy pts, once the safety of a dose was established. PK parameters for the dose-escalation cohorts were estimated using a 2-compartment model.
Results: 85 pts have been enrolled to date on doses up to 240 mg. 21 pts at 60 mg, and 22 pts at 150 mg have been followed for 12+ and 8+ weeks respectively. MDV3100 has been well-tolerated without dose-limiting toxicity. PK were dose-linear with a half-life of approximately one week. At doses of 30, 60, 150, and 240 mg, geometric mean steady state Cmax values were 2.8, 6.1, 17.3, and 23.7 µg/mL and AUC24hr were 61, 120, 361, and 480 µg*hr/mL, respectively. Effective AR blockade by MDV3100 has been shown by PSA declines and by PET findings. Evaluation at the 12 week timepoint for 21 pts at 60 mg showed 9 pts (43%) had &gt;50% decline in PSA from baseline. To date, 8 pts have had FDG and FDHT PET at baseline of whom 4 have had 1 or more follow-up scans. All 8 had abnormal FDHT accumulation at baseline while 4 of 4 with follow-up scans had no FDHT accumulation.
Conclusions: MDV3100 is a novel AR antagonist in clinical investigation. The observed PSA declines are consistent with the inhibition of AR signaling. The inhibition of FDHT accumulation demonstrates receptor blockade in vivo. MDV3100 has been well-tolerated to date and appears to be a promising candidate for the treatment of CRPC. Pt follow-up and dose escalation are continuing. The analysis of the association between PSA declines and clinical outcomes is ongoing and will be reported at a future date.
Abstract LB-204: Results of a Phase 3 trial evaluating safety and efficacy of specific immunotherapy, recombinant idiotype (Id) conjugated to KLH (Id-KLH) with GM-CSF, compared to non-specific immunotherapy, KLH with GM-CSF, in patients with follicular non-Hodgkin's lymph
Authors: Levy Ronald , Robertson M J , Ganjoo K , Leonard J , Vose J , Denney Dan 
Published: May 2019

Abstract
Introduction: MyVax® personalized immunotherapy consists of the tumor-specific Id protein, produced using molecular methods, conjugated to Keyhole limpet hemocyanin (KLH) and administered in a series of sc immunizations with GM-CSF.
Methods: This is a multi-center, randomized, blinded, controlled trial examining the safety and efficacy of MyVax compared to a control immunotherapy in patients with previously untreated follicular non-Hodgkin's lymphoma (fNHL). Patients received 8 cycles of CVP followed by a 6-month rest period. Patients who maintained at least a partial response for 6 months post CVP were randomized to receive MyVax or control immunotherapy in a 2:1 ratio. All patients received GM-CSF at each immunization and for the next 3 days. Patients received a series of 7 immunizations over 24 weeks. Sera for Id- and KLH-specific humoral immune response (IR) assays were collected prior to, during, and for 1 year following immunization.
Results: 287 patients were randomized and 278 patients received at least one immunization. Anti-Id IRs were observed in 41.0% of evaluable patients. No statistical difference in PFS and time to subsequent anti-lymphoma therapy (SALT) was seen in the patients who received MyVax compared to those who received the control immunotherapy. Both arms of the study have an apparent plateau of PFS &gt;30% at 5 years. A highly statistically significant improvement in PFS (P=0.0017) was seen in patients mounting an anti-Id immune response (IR+) vs. IR- patients with &gt;2-fold increase (39.7 vs 18.1 months) in PFS. The IR+ patients show a statistically significant improvement in PFS over the control immunotherapy patients while there is not a statistically significant difference in PFS between the IR patients and the control immunotherapy patients. The degree of clinical benefit correlates with the titer of the anti-Id IRs, but not with the titer of the anti-KLH IRs. High risk FLIPI patients did as well as the other patients in both PFS and SALT. Clinical response improvements were observed on both arms post immunization.
Conclusions: There was no difference in PFS between the patients receiving specific immunotherapy versus those receiving control immunotherapy. As previously reported in Phase II trials, fNHL patients mounting anti-Id IRs have a significantly improved clinical outcome.