bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PL06-02: Viral-related malignancies affecting ethnic minorities and immigrant subpopulations in the United States
Authors: Ramos Juan Carlos 
Published: December 2010

Abstract
Viral-related malignancies occur disparately in ethnic minority populations in the United States. Recent demographics of HIV subjects enrolled in U.S. clinical trials reveal that AIDS-related malignancies mostly affect minorities in this country. Human herpes virus-8 (HHV-8) is the etiologic cause of Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion lymphoma (PEL). Epstein Barr virus (EBV) is often associated with aggressive AIDS-related lymphomas (ARLs), including diffuse large B-cell lymphoma (DLBCL) with immunoblastic features, Burkitt lymphoma, primary CNS lymphoma (PCNSL), and plasmablastic lymphoma. Human papilloma virus (HPV) causes cervical and anal cancers, which occur more frequently in HIV patients. Adult T-cell leukemia/lymphoma (ATLL) is a deadly disease which is rarely seen in the United States but commonly occurs in African descendant immigrants to the Eastern United States and South Florida from the Caribbean (particularly Haiti and Jamaica) where the virus in endemic. At the University of Miami we see and treat more patients with these illnesses combined than any other institution in the nation. About 10% of our ATLL patients are co-infected with HIV. We have been key participants in AIDS malignancy Consortium (AMC) lymphoma clinical trials, and under our viral oncology program we devote a number of translational and molecular studies towards the understanding the pathophysiology of these illnesses. In this section, the clinical spectrum, trends, biology, and treatment of AIDS-related malignancies and adult T-cell leukemia/lymphoma in the United States will be reviewed. Investigational therapies, disease models, and recent molecular findings from the analyses of these tumors using state of the art technologies will also be discussed.
Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):PL06-02.
Abstract PL08-03: Race and cancer treatment outcome: Roswell Park over 50 years
Authors: Marshall James R. 
Published: December 2010

Abstract
There is strong evidence that African Americans are at elevated cancer risk, compared to European Americans. In addition, it is generally accepted that African Americans face more aggressive disease, with poorer treatment outcome. Whether these differences reflect biologic factors inherent in lifestyle or genomic characteristics that affect risk and treatment outcome is not well understood. Racial differences in risk could reflect differences in exposure to environmental toxins, to diet, to physical activity or possibly obesity; they could reflect genetically determined physiologic or metabolic processes. Racial differences in treatment outcome could result from compliance with treatment directives, with stage at diagnosis, or with the quality of medical care or with the aggressiveness with which treatment is pursued; they could also be a product of genetically structured physiologic, metabolic or detoxification processes. Racial differences in quality of care could result from differences in the institutions from which African Americans and European Americans receive cancer care.
To the degree that the quality of medical care is largely a function of the institution from which care is delivered, holding the institution constant should eliminate or greatly lessen racial differences. A comparison of the treatment outcomes of African Americans and European Americans at Roswell Park should lessen the likelihood that treatment differences would affect survival differences. Treatment differences would in all likelihood be minimized within a single institution; they would be conditioned by the disease site and stage of disease, rather than by institution-specific preferences. In addition, within a single institution, disease site, along with stage at diagnosis, age and gender could be held constant.
We have used a number of patient data sets collected at Roswell Park over the past 50 years to compare treatment outcomes of African Americans and European Americans. We consider racial differences in mortality treated first as a dichotomy at 5 and at 10 years, and with the relative hazard of mortality examined by use of Cox proportional hazards analysis. We adjust for stage of disease at diagnosis, age and gender for comparison. We also consider effect modification by disease stage, age and gender.
Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):PL08-03.
Phase 1 First-in-Human Trial of the Vascular Disrupting Agent Plinabulin(NPI-2358) in Patients with Solid Tumors or Lymphomas
Authors: Mita Monica M. , Spear Matthew A. , Yee Lorrin K. , Mita Alain C. , Heath Elisabeth I. , Papadopoulos Kyriakos P. , Federico Kristine C. , Reich Steven D. , Romero Ofelia , Malburg Lisa , Pilat MaryJo , Lloyd G. Kenneth , Neuteboom Saskia T.C. , Cropp Gillian , Ashton Edward , LoRusso Patricia M. 
Published: December 2010

Abstract
Purpose: Plinabulin (NPI-2358) is a vascular disrupting agent that elicits tumor vascular endothelial architectural destabilization leading to selective collapse of established tumor vasculature. Preclinical data indicated plinabulin has favorable safety and antitumor activity profiles, leading to initiation of this clinical trial to determine the recommended phase 2 dose (RP2D) and assess the safety, pharmacokinetics, and biologic activity of plinabulin in patients with advanced malignancies.
Experimental Design: Patients received a weekly infusion of plinabulin for 3 of every 4 weeks. A dynamic accelerated dose titration method was used to escalate the dose from 2 mg/m2 to the RP2D, followed by enrollment of an RP2D cohort. Safety, pharmacokinetic, and cardiovascular assessments were conducted, and Dynamic contrast-enhanced MRI (DCE-MRI) scans were performed to estimate changes in tumor blood flow.
Results: Thirty-eight patients were enrolled. A dose of 30 mg/m2 was selected as the RP2D based on the adverse events of nausea, vomiting, fatigue, fever, tumor pain, and transient blood pressure elevations, with DCE-MRI indicating decreases in tumor blood flow (Ktrans) from 13.5 mg/m2 (defining a biologically effective dose) with a 16% to 82% decrease in patients evaluated at 30 mg/m2. Half-life was 6.06 ± 3.03 hours, clearance was 30.50 ± 22.88 L/h, and distributive volume was 211 ± 67.9 L.
Conclusions: At the RP2D of 30 mg/m2, plinabulin showed a favorable safety profile, while eliciting biological effects as evidenced by decreases in tumor blood flow, tumor pain, and other mechanistically relevant adverse events. On the basis of these results additional clinical trials were initiated with plinabulin in combination with standard chemotherapy agents. Clin Cancer Res; 16(23); 5892–99. ©2010 AACR.
Noninvasive Radiofrequency Field Destruction of Pancreatic Adenocarcinoma Xenografts Treated with Targeted Gold Nanoparticles
Authors: Glazer Evan S. , Zhu Cihui , Massey Katheryn L. , Thompson C. Shea , Kaluarachchi Warna D. , Hamir Amir N. , Curley Steven A. 
Published: December 2010

Abstract
Purpose: Pancreatic carcinoma is one of the deadliest cancers with few effective treatments. Gold nanoparticles (AuNP) are potentially therapeutic because of the safety demonstrated thus far and their physiochemical characteristics. We used the astounding heating rates of AuNPs in nonionizing radiofrequency (RF) radiation to investigate human pancreatic xenograft destruction in a murine model.
Experimental Design: Weekly, Panc-1 and Capan-1 human pancreatic carcinoma xenografts in immunocompromised mice were exposed to an RF field 36 hours after treatment (intraperitoneal) with cetuximab- or PAM4 antibody–conjugated AuNPs, respectively. Tumor sizes were measured weekly, whereas necrosis and cleaved caspase-3 were investigated with hematoxylin–eosin staining and immunofluorescence, respectively. In addition, AuNP internalization and cytotoxicity were investigated in vitro with confocal microscopy and flow cytometry, respectively.
Results: Panc-1 cells demonstrated increased apoptosis with decreased viability after treatment with cetuximab-conjugated AuNPs and RF field exposure (P = 0.00005). Differences in xenograft volumes were observed within 2 weeks of initiating therapy. Cetuximab- and PAM4-conjugated AuNPs demonstrated RF field–induced destruction of Panc-1 and Capan-1 pancreatic carcinoma xenografts after 6 weeks of weekly treatment (P = 0.004 and P = 0.035, respectively). There was no evidence of injury to murine organs. Cleaved caspase-3 and necrosis were both increased in treated tumors.
Conclusions: This study demonstrates a potentially novel cancer therapy by noninvasively inducing intracellular hyperthermia with targeted AuNPs in an RF field. While the therapy is dependent on the specificity of the targeting antibody, normal tissues were without toxicity despite systemic therapy and whole-body RF field exposure. Clin Cancer Res; 16(23); 5712–21. ©2010 AACR.
Gene Expression Profile Correlates with T-Cell Infiltration and Relative Survival in Glioblastoma Patients Vaccinated with Dendritic Cell Immunotherapy
Authors: Prins Robert M. , Soto Horacio , Konkankit Vera , Odesa Sylvia K. , Eskin Ascia , Yong William H. , Nelson Stanley F. , Liau Linda M. 
Published: December 2010

Abstract
Purpose: To assess the feasibility, safety, and toxicity of autologous tumor lysate–pulsed dendritic cell (DC) vaccination and toll-like receptor (TLR) agonists in patients with newly diagnosed and recurrent glioblastoma. Clinical and immune responses were monitored and correlated with tumor gene expression profiles.
Experimental Design: Twenty-three patients with glioblastoma (WHO grade IV) were enrolled in this dose-escalation study and received three biweekly injections of glioma lysate-pulsed DCs followed by booster vaccinations with either imiquimod or poly-ICLC adjuvant every 3 months until tumor progression. Gene expression profiling, immunohistochemistry, FACS, and cytokine bead arrays were performed on patient tumors and peripheral blood mononuclear cells.
Results: DC vaccinations are safe and not associated with any dose-limiting toxicity. The median overall survival from the time of initial surgical diagnosis of glioblastoma was 31.4 months, with a 1-, 2-, and 3-year survival rate of 91%, 55%, and 47%, respectively. Patients whose tumors had mesenchymal gene expression signatures exhibited increased survival following DC vaccination compared with historic controls of the same genetic subtype. Tumor samples with a mesenchymal gene expression signature had a higher number of CD3+ and CD8+ tumor-infiltrating lymphocytes compared with glioblastomas of other gene expression signatures (P = 0.006).
Conclusion: Autologous tumor lysate–pulsed DC vaccination in conjunction with TLR agonists is safe as adjuvant therapy in newly diagnosed and recurrent glioblastoma patients. Our results suggest that the mesenchymal gene expression profile may identify an immunogenic subgroup of glioblastoma that may be more responsive to immune-based therapies. Clin Cancer Res; 17(6); 1603–15. ©2010 AACR.
Acquired Resistance to EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Lung Cancer: Distinct Natural History of Patients with Tumors Harboring the T790M Mutation
Authors: Oxnard Geoffrey R. , Arcila Maria E. , Sima Camelia S. , Riely Gregory J. , Chmielecki Juliann , Kris Mark G. , Pao William , Ladanyi Marc , Miller Vincent A. 
Published: December 2010

Abstract
Purpose: Patients with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma develop acquired resistance to EGFR tyrosine kinase inhibitors (TKI) after a median of 10 to 16 months. In half of these cases, a second EGFR mutation, T790M, underlies acquired resistance. We undertook this study to examine the clinical course of patients harboring the T790M mutation following progression on TKI.
Experimental Design: EGFR-mutant lung cancer patients with acquired resistance to EGFR TKIs were identified as part of a prospective rebiopsy protocol in which postprogression tumor specimens were collected for molecular analysis. Postprogression survival and characteristics of disease progression were compared in patients with and without T790M.
Results: We identified T790M in the initial rebiopsy specimens from 58 of 93 patients (62%, 95% CI: 52–72). T790M was more common in biopsies of lung/pleura tissue and lymph nodes than in more distant sites (P = 0.014). Median postprogression survival was 16 months (interquartile range = 9–29 months); patients with T790M had a significantly longer postprogression survival (P = 0.036). Patients without T790M more often progressed in a previously uninvolved organ system (P = 0.014) and exhibited a poorer performance status at time of progression (P = 0.007).
Conclusions: Among patients with acquired resistance to EGFR TKIs, the presence of T790M defines a clinical subset with a relatively favorable prognosis and more indolent progression. Knowledge of T790M status is therefore important both for the clinical care of these patients and for the optimal design and interpretation of clinical trials in this setting. Clin Cancer Res; 17(6); 1616–22. ©2010 AACR.
24-hour time-dependent aspirin efficacy in patients with stable coronary artery disease
Authors: Vermillet Adeline , Boval Bernadette , Guyetand Carine , Petroni Thibaut , Dillinger Jean-Guillaume , Sideris Georgios , Sollier Claire Bal dit , Drouet Ludovic , Henry Patrick 
Published: December 2010

SummaryAspirin-induced cyclooxygenase (COX)-1 acetylation is irreversible and it is assumed that the platelet thromboxane-A2 aggregation pathway is inhibited for at least 24 hours (h) after aspirin ingestion. However, time course of biological efficacy of daily low-dose aspirin has rarely been assessed in patients with coronary artery disease (CAD). We aimed to assess the 24-h biological efficacy of daily low-dose aspirin in CAD patients. The peak and trough (2 h –24 h) effect of a chronic treatment with once daily dose aspirin were studied in 150 consecutive stable CAD patients. The main outcome measure was light transmission aggregometry (LTA) triggered with 0.5 mg/ml arachidonic acid (AA). In the last 47 consecutive patients, additional tests were conducted at 6, 12, 16, 20 h after last aspirin administration. 4.7% of the patients had significant aggregation (>20% maximal intensity LTA-AA) 2 h after aspirin ingestion and 24.7% at 24 h (p<0.0001). The more precise assessments in the last 47 patients showed that significant platelet aggregation progressively reappeared with time after aspirin intake (2 h – 4% of patients, 6 h – 4%, 12 h – 11%, 16 h – 16%, 20 h – 19% and 24 h – 28%). Concordant results were observed using production of thromboxane-B2 and other techniques evaluating AA-induced platelet aggregation/activation. No significant differences were found between lower (75–100 mg/day) and higher (>100 mg/day) dose aspirin. Such aspirin «resistance» at 24 h after ingestion was related to biological inflammatory markers, current smoking and diabetes. In conclusion, once daily aspirin does not provide stable 24-h antiplatelet protection in a significant proportion of CAD patients. Any biological assessment of aspirin efficacy should take time since last aspirin intake into consideration.
Association of plasma fibrinogen, C-reactive protein and G-455>A polymorphism with early atherosclerosis in the VITA Project cohort
Authors: Tosetto Alberto , Prati Patrizio , Baracchini Claudio , Manara Renzo , Rodeghiero Francesco 
Published: December 2010

SummaryWhile increased fibrinogen is associated with vascular events, only few data are available on its association with preclinical atherosclerosis. We aimed at evaluating the association between fibrinogen levels, fibrinogen polymorphism G-455>A and C-reactive protein and preclinical atherosclerosis in a population-based, cross-sectional study. A cohort of 2,580 subjects was enrolled. Fibrinogen was measured at time of original enrolment and at time of the second visit, when ultrasound examination of both left and right common carotid arteries was performed, together with evaluation of C-reactive protein (CRP) and of the fibrinogen G-455>A polymorphism. CRP and fibrinogen levels at baseline were the two variables mostly influencing fibrinogen levels at the follow-up visit (p<0.0001). Carriers of the H2H2 genotype of the G-455>A polymorphism had increased fibrinogen levels, particularly in association with increased CRP levels. Increased fibrinogen levels were independently associated with presence of carotid plaques, particularly in those subjects having a persistent increase of fibrinogen (odds ratio 1.98, 95% confidence interval 1.47–2.67). An association between the H2H2 genotype and presence of carotid plaques was observed only in a subgroup of subjects with CRP > 0.5 mg/dl. A persistent increase of plasma fibrinogen is associated with an increased risk of early atherosclerosis.
The monocyte transcriptome during pregnancy in multiple sclerosis: prominent expression of the Fc-receptor CD64
Authors: Neuteboom Rinze F , Verbraak Evert , Wierenga-Wolf Annet F , Voerman Jane SA , Meurs Marjan van , Swagemakers Sigrid M , Spek Peter J van de , Steegers Eric AP , Groot Christianne JM de , Laman Jon D , Hintzen Rogier Q 
Published: December 2010

Background: During the third trimester of pregnancy multiple sclerosis (MS) disease activity is reduced. It is not fully understood which factors mediate this disease amelioration. Objective: To study alterations of the monocyte transcriptome during pregnancy in MS patients, using a genomewide approach to identify differentially regulated genes. Methods: Women with MS and healthy controls were longitudinally studied, including a visit before pregnancy. Results: RNA-microarray analysis was performed in six patients. We found a significant increase of CD64 (Fc gamma receptor 1a, FcgR1a) during the third trimester compared with baseline, confirmed by RT-PCR in a group of ten patients. Analysis with Ingenuity software was performed using all genes expression of which was altered at least 1.5-fold in at least five out of six patients. Major networks that were altered during MS pregnancy were: cell-to-cell signalling and interaction, immune response, and cell signalling. From the genes selected for Ingenuity analysis, seven additional candidate genes, selected for their biological interest, were tested using RT-PCR in ten patients with MS and nine controls. We found an increased expression of JAK2 and STAT1 directly postpartum in patients with MS and in controls. Conclusion: The increased CD64 expression during pregnancy is indicative of enhanced innate immune functions.
The relationship between fatigue and other clinical features of multiple sclerosis
Authors: Mills Roger J , Young Carolyn A 
Published: December 2010

Background: There has been considerable debate regarding the precise relationships between fatigue in multiple sclerosis (MS) and disease-related factors, such as disability, sleep disturbance, depression, age and sex. Existing studies give conflicting information. Objective: To clarify such relationships in a large cross-sectional study, using a rigorously developed measurement tool which was based on a clear definition of fatigue. Method: A pack containing the Neurological Fatigue Index for MS Summary Scale, the Hospital Anxiety and Depression Scale, the Epworth Sleepiness Scale, the Multiple Sclerosis Impact Scale and questions regarding sleep and demographics was mailed to patients with MS attending two centres in the UK. All scale scores were converted to parametric measures using the Rasch measurement model. Both linear and non-linear relationships were sought. Results: Data from 635 respondents (52% response) were analysed. Fatigue was strongly related to the impact of MS. Fatigue was worse in those with progressive disease and clearly worsened once ambulation was affected. There was only weak correlation with anxiety and depression. Fatigue was not related to disease duration or patient age. There was an intimate but complex relation between fatigue and sleep. Fatigue levels were minimum at a nocturnal sleep duration of 7.5 h. Conclusion: Clear relationships were found between fatigue and disability, disease type and sleep. Further physiological enquiry and trials of drug treatment and sleep modulation might be guided by these clinical relationships.
A small-molecule inhibitor of D-cyclin transactivation displays preclinical efficacy in myeloma and leukemia via phosphoinositide 3-kinase pathway
Authors: Mao Xinliang , Cao Biyin , Wood Tabitha E. , Hurren Rose , Tong Jiefei , Wang Xiaoming , Wang Wenjie , Li Jie , Jin Yueping , Sun Wenxian , Spagnuolo Paul A. , MacLean Neil , Moran Michael F. , Datti Alessandro , Wrana Jeffery , Batey Robert A. , Schimmer Aaron D. 
Published: December 2010

AbstractD-cyclins are universally dysregulated in multiple myeloma and frequently overexpressed in leukemia. To better understand the role and impact of dysregulated D-cyclins in hematologic malignancies, we conducted a high-throughput screen for inhibitors of cyclin D2 transactivation and identified 8-ethoxy-2-(4-fluorophenyl)-3-nitro-2H-chromene (S14161), which inhibited the expression of cyclins D1, D2, and D3 and arrested cells at the G0/G1 phase. After D-cyclin suppression, S14161 induced apoptosis in myeloma and leukemia cell lines and primary patient samples preferentially over normal hematopoietic cells. In mouse models of leukemia, S14161 inhibited tumor growth without evidence of weight loss or gross organ toxicity. Mechanistically, S14161 inhibited the activity of phosphoinositide 3-kinase in intact cells and the activity of the phosphoinositide 3-kinases α, β, δ, and γ in a cell-free enzymatic assay. In contrast, it did not inhibit the enzymatic activities of other related kinases, including the mammalian target of rapamycin, the DNA-dependent protein kinase catalytic subunit, and phosphoinositide-dependent kinase-1. Thus, we identified a novel chemical compound that inhibits D-cyclin transactivation via the phosphoinositide 3-kinase/protein kinase B signaling pathway. Given its potent antileukemia and antimyeloma activity and minimal toxicity, S14161 could be developed as a novel agent for blood cancer therapy.