bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2766: Multicenter pharmacokinetic evaluation of ON 01910. Na, a novel broad-spectrum anticancer agent, in Phase I single agent clinical trials in patients with solid tumors
Authors: Maniar Manoj , Mani Sridhar , Ghalib Mohammed H. , Roboz John , Ohnuma Takao , Advani Suresh , Rao Raghunadh , Doval D , Acharya Manmohan , O'Rourke Edward , Wilhelm Francois , Holland James F. , Taft David 
Published: February 2011

Abstract
Introduction: ON 01910. Na is an anti-cancer agent with demonstrated activity against both solid tumors and hematological cancers. The purpose of this research was to evaluate the effect of dose and administration schedule on ON 01910. Na pharmacokinetics (PK) in advanced, heavily pre-treated solid tumor patients. Methods: Data was collected in three Phase I protcols conducted in the US and in India covering a wide range of doses and intraveous infusion schedules: Protocol 1 (50-1375 mg/m2/day over 72 h); Protocol 2 (250 – 4450 mg/m2/day over 24 h) and Protocol 3 (2400-3200 mg over 2, 4 or 8 h). In several patients, pharmacokinetics were evaluated for more than 1 dosing cycle. Plasma samples were collected pre-dose and up to 72 hours post-infusion. ON 01910. Na plasma levels were determined by a validated LC/MS/MS method. Results: Ninety-five data sets from 81 patients were evaluated in this study. ON 01910. Na showed biphasic elimination from the plasma, regardless of dose and administration schedule. The functional half-life of ON 01910. Na, estimated from the initial decline of plasma levels following infusion termination, was less than 2 hours. This was confirmed in data from patients receiving prolonged infusions as ON. 01910. Na approached steady state levels within several hours after dose initiation. As noted in the table below, ON. 01910. Na clearance was lower at higher drug dosing rates. There were no differences in drug pharmacokinetics among the infusion schedules. Conclusion: The pharmacokinetics of ON 01910. Na is dose dependent. A continuous IV infusion would be recommended to treat patients because of its short plasma half-life and rapid clearance. Systemic drug exposure is not affected by type of dosing (flat dosing vs. BSA adjusted). No significant differences were noted between the PK profiles of patients in the US centers and the patients in the India centers.Effect of Dosing Rate on Clearance of ON 01910. NaDosing Rate (mg/m2/hr)NClearance (L/hr/m2)0-25189.3 ± 4.725-501610.0 ± 5.050-75209.2 ± 3.175-10065.5 ± 2.6100-200126.2 ± 3.8200-40083.3 ± 1.6400-800112.5 ± 1.8800-125041.9 +/− 0.47
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2766.
Abstract 2768: Development of a tubulin fractionation assay for the evaluation of “on target” activity of tubulin targeting agents in clinical PBMC samples
Authors: Matthews Clayton A. , Bibby David , Leske Annabell F. , Harvey Andrew J. , Kremmidiotis Gabriel 
Published: February 2011

Abstract
The novel agent, BNC105, is a tubulin polymerization inhibitor which acts as a vascular disruption agent (VDA). BNC105 exhibits 100-fold selectivity for activated endothelial cells compared to quiescent endothelial cells, providing a large differential between effects on cancer vasculature and normal vasculature. We developed a tubulin fractionation assay that enables evaluation of tubulin polymerisation changes in peripheral blood mononuclear cell samples (PBMCs) obtained from patients treated with BNC105. The assay capitalizes on the mass differences between polymerized and depolymerised tubulin to separate each fraction in a density gradient by ultracentrifugation. Experimental conditions during the extraction process were optimised to maintain the polymerisation state of tubulin. This optimisation was carried out in cell lines and PBMCs from healthy volunteers. Critical parameters include temperature, GTP concentration, DMSO concentration, pH, and buffer density. Tubulin monomer and polymer extracts were resolved using SDS-PAGE and transferred onto nitrocellulose membranes followed by detection using βI tubulin specific antibodies. The tubulin bands were analysed by densitometry and normalized to an actin loading control. Following exposure of cell lines or PBMCs to tubulin polymerisation inhibitors for a period of 60 minutes, the depolymerised tubulin fraction increased, while the polymerised tubulin fraction decreased. Conversely, exposure to tubulin polymerizing agents caused a greater proportion of tubulin to appear in the polymerized fraction. We used this method to evaluate the tubulin polymerisation status in PBMC samples obtained from cancer patients treated with BNC105. Samples were obtained prior to dosing and at 1, 2, 3-5, 7, and 24 hours post-dosing. Based on the data obtained, BNC105 treatment caused an 80% reduction in the polymerised tubulin fraction at the 1, 2 and 3-5 hour sampling time points. The amount of tubulin in the polymerised fraction returned to pre-dose levels by the 7 hour post-dose time point. The pharmacokinetic profile of BNC105 shows a steep curve reaching Cmax at around 20 minutes post-administration, followed by plasma clearance with no BNC105 detectable after the 7 hour time point. The pharmacokinetics of BNC105 supports our tubulin depolymerisation data with respect to response time and the subsequent recovery period. These results were reproducible, and have shown a similar pattern in all patients tested to date.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2768.
Abstract 2771: Clinical outcomes and prognostic factors in 83 patients with pancreatic cancer treated in phase I clinical trials at M.D. Anderson Cancer Center
Authors: Tsimberidou Apostolia M. , Vaklavas Christos , Wen Sijin , Hong David , Wheler Jennifer , Ng Chaan S. , Naing Aung , Uehara Cynthia , Wolff Robert , Kurzrock Razelle 
Published: February 2011

Abstract
Introduction. The outcomes of patients with pancreatic cancer treated on early-phase clinical trials have not been systematically analyzed. The purpose of this study was to report the presenting characteristics and outcomes of patients with locally advanced or metastatic pancreatic cancer treated on phase I clinical trials at a single institution.
Patients and Methods. We reviewed the records of consecutive patients with metastatic pancreatic cancer who were treated in the Phase I Clinical Trials Program at The University of Texas M. D. Anderson Cancer Center from November 2004 to March 2009. Data recorded and analyzed included survival, response, and disease characteristics.
Results. Eighty-three patients were identified. The median age was 62 years (range, 39-81). There were 40 men and 43 women. The most common metastatic sites were liver (54% of patients), lung (51%), lymph nodes (37%), and peritoneum and omentum (24%). The median number of prior therapies was 2 (range, 0-7). Thirty-two (39%) patients had a history of pancreatectomy. Sixty-seven (81%) patients had ≥1 comorbidity. Of 78 patients evaluable for response, 2 (3%) had a partial response (PR), and 10 (13%) had stable disease (SD) for ≥4 months. With a median follow-up for survivors of 3.7 months, the median survival from presentation in the Phase I Clinic was 5.0 months (95% CI, 3.3-6.2). The median overall survival from diagnosis was 22.1 months (95% CI, 17.9-26.5). The median time to treatment failure (TTF) was 1.5 months (95% CI, 1.3-1.8). In multivariate analysis, independent factors associated with lower rates of PR or SD were liver metastases (p = 0.001) and PS greater than 0 (p = 0.01) (Table 3). Independent factors associated with shorter survival were liver metastases (p = 0.007), calcium ≤ 8.4 mg/nL (p = 0.015), and elevated serum levels of CEA (&gt;6 ng/mL; p = 0.005). Independent factors associated with shorter TTF were history of smoking (p = 0.009), liver metastases (p = 0.001), serum bilirubin levels &gt;1 mg/dL (p = 0.007), and &gt;1 prior therapy (p = 0.002).
Conclusions. The median survival in the current study (5 months) compares favorably to the median survival reported with best supportive care (3 months). Our results suggest that phase I clinical trials offer a reasonable therapeutic approach for patients with advanced pancreatic cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2771.
Abstract 2780: Mammographic density and breast cancer tumor characteristics in the Multiethnic Cohort Study
Authors: Conroy Shannon M. , Pagano Ian , Kolonel Laurence N. , Maskarinec Gertraud 
Published: February 2011

Abstract
Mammographic density (MD), a strong risk factor for breast cancer, may reflect proliferation of breast epithelial and stromal cells in response to cumulative exposure to endogenous and exogenous hormones. Whether MD predicts subtypes of breast cancer defined by expression of the estrogen (ER+) and/or progesterone (PR+) receptor is unclear. Because factors associated with higher MD are associated with ER+PR+ breast cancers, we hypothesized that women with higher percent MD (dense breast tissue area to total breast area) would have a higher risk for ER+PR+ and a lower risk for ER-PR- breast cancers as compared to women with lower percent MD. In a nested case-control study, we compared the MD of 667 controls and 607 breast cancer cases among women of Caucasian, Japanese and Native Hawaiian ancestry in the Hawaii component of the Multiethnic Cohort Study. A reader blinded to disease status performed computer assisted density assessment on prediagnostic mammograms. Receptor status for breast cancers was obtained from the statewide Hawaii Tumor Registry. Tumors were classified into ER+PR+ (n=341), ER-PR- (n=50), ER+PR-/ER-PR+ (n=64) and unstaged/unknown (n=152). Mean density values were computed for women with more than one mammogram and modeled using polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) while adjusting for confounders. Mean percent MD was significantly greater for ER+PR+, but not for ER-PR- breast cancers compared to controls after adjusting for age: 37.3%, 28.9%, versus 29.4%, respectively. The overall ORs for a 10% increase in percent MD were similar for all breast cancer cases and for ER+PR+ and ER+PR-/ER-PR+ cancer subtypes: 1.22 (95% CI, 1.14-1.30), 1.25 (95% CI, 1.16-1.35) and 1.23 (95% CI, 1.07-1.42), respectively. Percent MD was not found to be a predictor for ER-PR- subtypes (OR for a 10% increase = 1.00, 95% CI, 0.84, 1.18). Our findings indicate that within a multiethnic population, women with higher MD have an increased risk for ER+PR+, but not ER-PR- breast cancer. Breast cancer subtypes are suspected to have diverse etiologies that respond to different treatments. Our findings support specific models of hormone-related triggers for the increased breast cancer risk associated with MD. Research supported by NCI grants: R37CA54281, R01CA85265 and R25CA90956.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2780.
Abstract 2801: Circulating 25-hydroxyvitamin D and risk of pancreatic cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP)
Authors: Stolzenberg-Solomon Rachael Z. , Jacobs Eric J. , Arslan Alan A. , Qi Dai , Patel Alpa V. , Kolonel Laurence N. ,   for the Vitamin D Pooling Project Investigators.
Published: February 2011

Abstract
Results from epidemiologic studies examining pancreatic cancer risk and vitamin D intake or 25-hydroxyvitamin D [25(OH) D] concentrations have been inconsistent. For most people, more than 90% of their vitamin D status is produced endogenously from exposure of the skin to solar ultra-violet B (UVB) light (280-320 nm) resulting in cutaneous production of precursors to 25(OH)D. 25(OH)D is the major circulating vitamin D metabolite in humans and is also considered the best indicator of vitamin D status from both sun exposure and diet. Therefore, we conducted a pooled nested case-control study of participants from 8 cohorts within the Vitamin D Pooling Project-Rarer Cancer Consortium (VDPP) to test whether pre-diagnostic circulating 25(OH)D concentrations were associated with the development of incident pancreatic cancer. In total, 952 incident pancreatic adenocarcinoma cases occurred among participants (average follow-up 6.5 years). Controls (n=1333) were matched to each case by cohort, age, sex, race, date of blood draw, and follow-up time. Circulating vitamin D levels were measured using the DiaSorin LIAISON 25(OH)D TOTAL assay or an older DiaSorin radioassay. We used conditional logistic regression to calculate smoking-, body mass index-, and diabetes-adjusted odds ratios (OR) and 95% confidence intervals (CI) for pancreatic cancer. Clinically relevant cut-points were compared to adequate status (defined as 50 to &lt;75nmol/L) as the reference. No significant associations were apparent for deficient or inadequate status. However, high 25(OH)D concentration (&gt; 100 nmol/L) was associated with a significant 2-fold increase in pancreatic cancer risk overall (OR=2.12, 95% CI 1.23-3.71). No statistically significant associations were observed for deficient (&lt;25.0 nmol/L) or inadequate (25.0 to &lt;37.5 nmol/L) status overall or in stratified models. This association was observed in smokers and non-smokers, and both men and women, although it was slightly stronger in men. Given this result, recommendations to increase vitamin D concentrations in healthy individuals for the prevention of cancer should be carefully considered.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2801.
Abstract 2805: A pooled investigation of circulating 25-hydroxyvitamin D and non-Hodgkin lymphoma: The Cohort Consortium Vitamin D Pooling Project of Rarer Cancers
Authors: Purdue Mark P. , Freedman D. Michal , Gapstur Susan M. , Helzlsouer Kathy J. , Laden Francine , Lim Unhee , Maskarinec Gertraud , Rothman Nathaniel , Shu Xiao-Ou , Stevens Victoria L. , Zeleniuch-Jacquotte Anne , Albanes Demetrius , Bertrand Kimberly , Weinstein Stephanie J. , Yu Kai , Irish Lonn , Horst Ronald L. , Bolton Judith Hoffman , Giovannucci Edward L. , Kolonel Laurence N. , Snyder Kirk , Willett Walter , Arslan Alan A. , Hayes Richard B. , Zheng Wei , Zhang Yong Bing , Hartge Patricia 
Published: February 2011

Abstract
Findings from several epidemiologic studies suggest that exposure to solar ultraviolet radiation may be associated with a reduced risk of non-Hodgkin lymphoma (NHL). These observations have led to speculation that vitamin D may protect against lymphomagenesis. To investigate this hypothesis, the authors conducted a pooled investigation of circulating 25-hydroxyvitamin D [25(OH)D] and subsequent NHL risk within ten cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Prediagnostic samples of serum or plasma from 1,353 cases and 1,778 controls were assayed for 25(OH)D by immunoassay at a single laboratory. Odds ratios (ORs) and 95% confidence intervals (CIs) relating categories of 25(OH)D concentration with NHL risk were calculated using conditional logistic regression models, with 50-&lt;75 nmol/L used as the reference category. Analyses of common NHL histologic subtypes were performed using polytomous regression modeling.
Overall, no evidence of association with NHL risk was observed for either low 25(OH)D concentration (&lt;25 nmol/L: OR 1.08, 95% CI 0.78-1.50) or high concentration (≥100 nmol/L: OR 0.86, 95% CI 0.57-1.27), and a test for trend was not statistically significant (P = 0.68).
Analyses of other measures of 25(OH)D {continuous log[25(OH)D], categories of 25(OH)D using sex/cohort/season-specific cutpoints, categories of season-adjusted residuals of predicted 25(OH)D} were similarly null, as were results from stratified analyses and investigations of histologic subtypes of NHL. These findings do not support the hypothesis that elevated circulating 25(OH)D levels are associated with reduced NHL risk. Future research investigating the biologic basis for the sunlight-NHL association should consider alternative mechanisms, such as immunologic effects.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2805.
Abstract 2821: Dietary lycopene and prostate cancer risk in the NIH-AARP Diet and Health Study
Authors: Watters Joanne , Park Yikyung , Hollenbeck Albert , Schatzkin Arthur , Albanes Demetrius 
Published: February 2011

Abstract
In the U.S., tomatoes and tomato products contribute almost all dietary intake of lycopene, a carotenoid with antioxidant properties. Some studies have shown reduced prostate cancer risk with diets high in lycopene or tomato-rich foods (e.g., pizza), yet others have not. Despite numerous investigations, there is no consensus concerning the relationship between lycopene and prostate cancer risk. We examined the relation between dietary lycopene and risk of prostate cancer within the National Institutes of Health (NIH)-AARP Diet and Health Study, a large prospective cohort investigation of dietary and environmental cancer risk factors among men aged 50-71 upon enrollment in 1995-1996 (n=292,482). Cox proportional hazards regression models with hazard ratios (HR) and 95% confidence intervals (95% CI) were adjusted for age, race, education, height, body mass index, physical activity, family history of prostate cancer, diabetes, prostate-specific antigen testing, digital rectal examination, total energy, α-tocopherol, calcium, α-linolenic acid, selenium, red meat, and fish. There were 15,229 nonadvanced and 1,889 advanced incident prostate cancers identified through 2003 and 510 fatal prostate cancers through 2005. The median intake of dietary lycopene was 2.5 mg/day in the lowest quintile and 14.9 mg/day in the highest quintile of intake. Total lycopene consumption was associated with a slight reduction in risk of nonadvanced prostate cancer (HR= 0.93, 95% CI: 0.88 − 0.99), but there was no association with advanced or fatal prostate cancers. Similar patterns were observed for total tomato consumption. No individual tomato-rich food affected nonadvanced prostate cancer risk. Pizza was associated with a 15% reduction in advanced prostate cancers (95% CI: 0.72 − 1.00) and a 33% reduction in fatal prostate cancers (95% CI: 0.47 − 0.96), whereas salsa consumption was associated with a 28% increase in advanced prostate cancers (95% CI: 1.10 − 1.48). Considering the overall null association between lycopene intake and advanced prostate cancer, it is possible other constituents in these foods may be affecting cancer risk; alternatively, these results for specific foods may be due to chance. Overall, these data suggest that dietary lycopene may be associated with minimal reductions in nonadvanced prostate cancer risk.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2821.
Abstract 2829: Recreational physical activity and epithelial ovarian cancer risk in the California Teachers Study
Authors: Lu Yani , Sullivan-Halley Jane , Chang Ellen T. , Henderson Katherine D. , Lacey James , Ma Huiyan , Bernstein Leslie 
Published: February 2011

Abstract
Background: It has been hypothesized that physical activity may reduce the risk of ovarian cancer by influencing sex hormones, body fat, and frequency of ovulation. However, epidemiologic studies have provided inconsistent results.
Methods: We explored the association between recreational physical activity and epithelial ovarian cancer risk in 106,270 women ages 22 to 84 years old when they joined the prospective California Teachers Study in 1995-1996. Information on strenuous and moderate physical activities from high school through age 54 years or age at cohort entry if younger than 54, and sedentary behavior one year before cohort entry was collected by self-administered questionnaire. Follow-up through 2007 identified 431 women with incident invasive epithelial ovarian cancer. Multivariable adjusted Cox proportional hazards modeling was used to compute hazard rate ratios (RR) and 95% confidence intervals (CI).
Results: Long-term recreational physical activity level was not associated with epithelial ovarian cancer risk, although a slightly lower risk was observed among women with high activity levels (average activity &gt; 3 hrs/wk) (RR=0.81, 95%CI=0.61-1.08) relative to those with low activity levels (P for trend=0.20). Physical activity at different life periods, including the 3 years before cohort entry, also indicated a similar, statistically non-significant lower risk of epithelial ovarian cancer. No associations were observed for sedentary behavior one year before cohort entry.
Conclusion: Overall, results from this study did not suggest a strong inverse association between recreational physical activity and epithelial ovarian cancer risk. Furthermore, sedentary behavior characterized by sitting time in the year prior to cohort entry was not a predictor of ovarian cancer risk.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2829.