tbuckley/cabot-search huggingface dataset:
Enhancing cancer clinical trials access: Impact and outcomes of a community-centered pilot education and advocacy program.
Authors: M. Michaels, N. Blakeney, A. Britton, L. Swords, N. Bitow, B. Gibbs, S. Yeun, B. Rytkonen, R. Goodman, S. L. Jarama
Journal: Journal of Clinical Oncology (2010)

e16555 Background: Although cancer clinical trials (CCTs) help achieve progress in cancer care, trial participation among adult cancer patients remains at only 3%, with rates lower among minorities and the medically underserved. Enhanced community engagement can lead to greater awareness, access, and ultimately, patient accrual. Methods: The Education Network to Advance Cancer Clinical Trials (ENACCT) launched a 3-year, community-centered Pilot Education Program (PEP) in 3 communities nationwide to increase knowledge among community leaders (CLs), health care providers (HCPs) and CCT staff, improve access, and increase patient inquiries about trials. Additionally, local sites worked addressed policy barriers to enhance access. PEP impact was evaluated using web-based surveys, interviews, focus groups and field observation. Results: Seventy-five trainers were recruited among CLs (n = 53) and HCPs (n = 22). PEP trained 926 CLs (66% minority), 461 HCPs (62% nurses) and 61 CCTs staff. Additionally 4,000 individuals were reached through community presentations and 49,000 educational palm cards distributed. Among evaluation respondents, community leader trainees had favorable attitudes and beliefs about CCTs at first assessment and over time, with increased intention to talk to others. Health care provider trainees had more favorable attitudes and beliefs regarding their role in referral to CCTs at posttest compared to baseline. CCT staff indicated increased understanding of patient challenges to CCTs participation and intention to advocate for implementation of cultural and linguistically appropriate service standards (CLAS) within their institution. Site initiatives to address access barriers included implementation of consent short forms, Six Sigma quality improvement measures to enhance recruitment processes and city-wide symposia on CCTs reaching CLs and HCPs. To date, 3,027 website sessions and 88 unique patient profiles have been created with a national CCTs matching service associated with PEP. Conclusions: Findings from ENACCT's PEP suggest community-centered interventions can be an effective means of enhancing cancer clinical trials participation. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca Lilly
Adjuvant CMFP versus CMFP plus tamoxifen versus observation alone in postmenopausal, node-positive breast cancer patients: three-year results of an Eastern Cooperative Oncology Group study.
Authors: S G Taylor, L A Kalish, J E Olson, F Cummings, J M Bennett, G Falkson, D C Tormey, P P Carbone
Journal: Journal of Clinical Oncology (1985)

After mastectomy, 265 postmenopausal patients with node-positive breast cancer were stratified according to pathologic nodal status and estrogen-receptor (ER) status and randomized to receive either 12 cycles of cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP), or CMFP plus tamoxifen (CMFPT), or observation alone. Patients entered the study between March 1978 and July 1981. Cox regression analysis indicated that, compared to observation alone, chemotherapy (CMFP and CMFPT groups combined) led to a significant reduction in relapses by the end of the first year of study in every examined prognostic subgroup. However, after the first year the relapse-free survival curves of all treatment groups tended to merge, so that by three years 52% of the observation group and 51% of the chemotherapy groups remained disease free. Chemotherapy continued to show a significantly superior relapse-free survival rate for three years only in the subgroup of patients with ER-negative tumors (the subgroup with the largest relapse-free survival advantage at one year). The addition of tamoxifen produced no benefit or harm in any prognostic subcategory examined. ER status was prognostically important for predicting early relapse only in those patients not receiving chemotherapy, due to the greater effectiveness of this chemotherapy to prevent early relapse in the ER-negative subgroup. Treatment has had no early effect on survival. As breast cancer continues to recur even after ten or more years, later relapse patterns may alter these results.
The combination of trastuzumab and vinorelbine as a atractive regimen in overexpressing metastatic breast cancer patients
Authors: I. Glogowska, A. Jagiello-Gruszfeld, R. Sienkiewicz-Kozlowska, S. Jaczewska, E. Szombara, T. Pienkowski
Journal: Journal of Clinical Oncology (2005)

3212 Background: Trastuzumab (T) and vinorelbine (V) combination has previously shown as a interesting regimen for Her-2 positive metastatic breast cancer (mbc) patients(pts). It is retrospective analysis of the efficacy and safety T/V combination in Her-2 positive mbc treated in two polish centers. Methods: Between February 2002 and May 2004, 45 women were treated with weekly combination of T and V. Median age 50 (range 35–73), median of metastatic sites 2, median of visceral metastases -1. In all pts overexpression Her-2 3+ (39) or FISH positive (6) were confirmed. 14 pts had not received any chemotherapy for metastatic disease (subgroup A), 12 pts were previously treated by 1 line of chemotherapy for mbc (subgroup B), 19 pts by 2 or more line of chth (subgroupC). In 18pts antracycline because of mbc were used. In 24 cases V was administrated as first combination with T, in 21 as second or third (after combination of docetaxel or cisplatin).T and V were administrated weekly (V-30mg/m2 in 19 pts, 25mg/m2 - 26 pts). Pts were assessed for toxicites and reassessed for response every 8 weeks until progression. Results: The overall response was obtained in 17 pts (38%): in subgroup A-5pts, B-4pts, C-8pts. Median time of treatment duration in responders was 23 weeks. There was no significant differences of results in subroups A,B,C. SD was observed in 22pts. We noted 2 cases of PD during treatment. In the median follow-up 29 weeks (r 2–119) PD was noted in22 pts with mTTP 20 weeks (r 3–111).15pts are still receiving treatment. The regimen was well tolerated. WHO 3–4 grade(G) neutropenia was observed in 17 pts (with 2 cases of infections G3), G3 anaemia in 1pt. There was one case of severe cardiotoxicity in our group -congestive heart failure G3 after 9 weeks therapy, required end of treatment with Herceptin. Toxicites (main hematologic) required vinorelbine dose reduction from 30mg/m2 to 25mg/m2 in 89 cycles (11%) and from 25mg/m2 to 20mg/m2 in 48 cycles (6%).There were 71cycles (9%) of V omitted from 823 planed. Conclusions: This analysis confirm that combination of vinorelbine and trastuzumab is active and well tolerated regimen in Her-2 positive mbc pts, even pretreated by one or more line systemic therapy. No significant financial relationships to disclose.
Abstract 19221: Rates of Arterial Revascularization in Patients Treated with Vorapaxar vs. Placebo in the TRA 2{degrees}P-TIMI 50 Trial
Authors: Erin A Bohula May, Marc P Bonaca, Benjamin M Scirica, Joao Morais, Markku Nieminen, Sabina A Murphy, Eugene Braunwald, David A Morrow
Journal: Circulation (2012)

Vorapaxar is a selective antagonist of protease-activated receptor (PAR)-1 that potently blocks platelet activation by thrombin. Thrombin signaling also influences vascular endothelial and smooth m...
Patient-Level DNA Damage and Repair Pathway Profiles and Prognosis After Prostatectomy for High-Risk Prostate Cancer
Authors: Joseph R. Evans, Shuang G. Zhao, S. Laura Chang, Scott A. Tomlins, Nicholas Erho, Andrea Sboner, Matthew J. Schiewer, Daniel E. Spratt, Vishal Kothari, Eric A. Klein, Robert B. Den, Adam P. Dicker, R. Jeffrey Karnes, Xiaochun Yu, Paul L. Nguyen, Mark A. Rubin, Johann de Bono, Karen E. Knudsen, Elai Davicioni, Felix Y. Feng
Journal: JAMA Oncology (2016)

A substantial number of patients diagnosed with high-risk prostate cancer are at risk for metastatic progression after primary treatment. Better biomarkers are needed to identify patients at the highest risk to guide therapy intensification.To create a DNA damage and repair (DDR) pathway profiling method for use as a prognostic signature biomarker in high-risk prostate cancer.A cohort of 1090 patients with high-risk prostate cancer who underwent prostatectomy and were treated at 3 different academic institutions were divided into a training cohort (n = 545) and 3 pooled validation cohorts (n = 232, 130, and 183) assembled for case-control or case-cohort studies. Profiling of 9 DDR pathways using 17 gene sets for GSEA (Gene Set Enrichment Analysis) of high-density microarray gene expression data from formalin-fixed paraffin-embedded prostatectomy samples with median 10.3 years follow-up was performed. Prognostic signature development from DDR pathway profiles was studied, and DDR pathway gene mutation in published cohorts was analyzed.Biochemical recurrence-free, metastasis-free, and overall survival.Across the training cohort and pooled validation cohorts, 1090 men were studied; mean (SD) age at diagnosis was 65.3 (6.4) years. We found that there are distinct clusters of DDR pathways within the cohort, and DDR pathway enrichment is only weakly correlated with clinical variables such as age (Spearman ρ [ρ], range, -0.07 to 0.24), Gleason score (ρ, range, 0.03 to 0.20), prostate-specific antigen level (ρ, range, -0.07 to 0.10), while 13 of 17 DDR gene sets are strongly correlated with androgen receptor pathway enrichment (ρ, range, 0.33 to 0.82). In published cohorts, DDR pathway genes are rarely mutated. A DDR pathway profile prognostic signature built in the training cohort was significantly associated with biochemical recurrence-free, metastasis-free, and overall survival in the pooled validation cohorts independent of standard clinicopathological variables. The prognostic performance of the signature for metastasis-free survival appears to be stronger in the younger patients (HR, 1.67; 95% CI, 1.12-2.50) than in the older patients (HR, 0.77; 95% CI, 0.29-2.07) on multivariate Cox analysis.DNA damage and repair pathway profiling revealed patient-level variations and the DDR pathways are rarely affected by mutation. A DDR pathway signature showed strong prognostic performance with the long-term outcomes of metastasis-free and overall survival that may be useful for risk stratification of high-risk prostate cancer patients.
Criteria of tumor response used in clinical trials of chemotherapy.
Authors: K Tonkin, D Tritchler, I Tannock
Journal: Journal of Clinical Oncology (1985)

We have studied 61 published reports of trials of cancer chemotherapy to evaluate the criteria for tumor response that were used and the adequacy of their description in the publication. Our sample comprised recent articles published in three major journals that addressed the influence of chemotherapy on patients with recurrent or metastatic colorectal cancer, non-small cell lung cancer, and head and neck cancer. Incomplete information was sought through a questionnaire mailed to the senior author of each paper, and 48 of them responded. We conclude that: no article contained all of the information required to define precisely criteria for tumor responses; criteria for tumor response are variable; and differences in response criteria contribute to the wide variation in reported rates of tumor response. Meaningful intercomparison of clinical trials will require the establishment of uniform criteria for assessing and reporting the response of tumors to chemotherapy.
Abstract 12251: Galectin-3 as a Predictor of Myocardial Fibrosis in Kawasaki Disease
Authors: Fujito Numano, Chisato Shimizu, Susan J Fernandez, Matthew Vejar, Andrea Salgado, Adriana H Tremoulet, John B Gordon, Jane C Burns, Lori B Daniels
Journal: Circulation (2014)

Background: Kawasaki disease (KD) is a self-limited, acute vasculitis of young children and the etiology remains unknown. Coronary artery aneurysms (CAA) are the most significant complication, but histologic examination of autopsies and biopsies of KD patients has revealed myocarditis and myocardial fibrosis (MF) in most cases. Galectin-3 (Gal-3) is a matricellular protein that plays a multifunctional role in inflammation, fibrosis, and cell differentiation, and is expressed by fibroblasts and inflammatory cells including macrophages, activated T cells, and dendritic cells. Gal-3 is recognized as a cardiac fibrosis marker associated with heart failure and cardiovascular events. Gal-3 plays a role in adhesion and migration of inflammatory and fibroblastic cells. We postulated that Gal-3 may be involved in myocarditis and MF in KD. Methods: Plasma Gal-3 levels were determined by ELISA in 63 pediatric (PKD) and 91 adult KD (AKD) subjects, 7 age-similar pediatric healthy controls (HC) and 69 age-similar adult...
Role of the serine protease-like HGF β-chain in Met binding and signaling
Authors: Robert A. Lazarus, Daniel Kirchhofer, Mark Peek, Michael T. Lipari, Karen L. Billeci, Lydia Santell, Paul Moran, Charles Eigenbrot, Christian Wiesmann
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

4500 

Hepatocyte growth factor (HGF), a plasminogen-related growth factor, is the ligand for Met, a receptor tyrosine kinase implicated in development, tissue regeneration and invasive tumor growth. HGF acquires signaling activity only upon proteolytic cleavage of single-chain HGF into its α/β-heterodimer, similar to zymogen activation of structurally related serine proteases. Although both chains are required for activation, only the α-chain binds Met with high affinity. Recently, we reported that the protease-like HGF β-chain binds to Met with low affinity (Stamos et al. (2004) EMBO J. 23, 2325-2335) and that mutational analysis defined a functional Met binding site on HGF β that bears remarkable resemblance to the active site region of serine proteases (Kirchhofer et al. (2004) J. Biol. Chem. 279, 39915-39924). Additional mutagenesis of the β-chain at residues distinct from those in direct contact with the Met Sema domain shows that purified 2-chain HGF mutants also result in impaired Met phosphorylation (A549 human lung carcinoma cells), cell migration (MDA-MB-435 human breast carcinoma cells) and cell proliferation (BxPC3 human pancreatic adenocarcinoma cells). This suggests that additional allosterically linked regions may be involved in the signaling process. Furthermore, antibodies directed toward the HGF β-chain or the HGF α-chain result in inhibition of Met phosphorylation in A549 cells. These antibodies also inhibit proliferation in BxPC3 cells and BaF3 murine lymphoid cells. Implications for dimerization mechanisms of HGF-dependent Met receptor activation and signaling are presented.
Phase II study of 5-florouracil/leucovorin in combination with paclitaxel and oxaliplatin in 1st line treatment for patients with advanced gastric cancer (AGC)
Authors: R. Lin, N. Fan, Q. Chen, Z. Guo, X. Wang, L. Chen, J. Liu
Journal: Journal of Clinical Oncology (2008)

15678 Background: Primary results of semimonthly 5-florouracil/leucovorin combined with paclitaxel and oxaliplatin (POF) in 1st and 2nd line treatment of AGC have been presented at ASCO 2007. Here we report this regimen in 1st line treatment efficacy for AGC. Methods: Patients chosen with histologically proven diagnosis of adenocarcinoma of the stomach or gastroesophageal junction, locally advanced (i.e., unresectable) or metastatic disease previously untreated. The chemotherapy regimen was comprised of a 3-hour infusion of 135 mg/m2 of paclitaxel followed by oxaliplatin 85 mg/m2 and LV 400 mg/m2, administered simultaneously as a 2-hour infusion, then continued a 46-hour infusion of FU 2.4 g/m2 using an ambulatory pump. Treatment was continued until disease progressed, unacceptable toxicity, or patient choice. Results: Twenty-seven patients were enrolled onto this study in our center between September 19, 2005 and December 31, 2006. The median patient age was 57 years (range, 26 to 77 years), 21 were males and 6 were females. All patients received the chemotherapy between at least two cycles and maximum twelve cycles with a median of six. Twenty-one patients had measurable lesions. Four CRs, eight PRs and seven SDs were observed. At a median follow-up of 610 days, the median survival was 348 days. Frequent grade 3 to 4 toxicities were: neutropenia (29.6%), stomatitis (7.4%), nausea (7.4%), vomiting (7.4%), hepatic dysfunction (3.7%), paresthesia (18.5%). No treatment-related death occurred. Conclusions: POF regimen appears to be of well efficacy and is well tolerated in patients with AGC. Currently, this regimen is being tested in the phase III trial (POF v.s. IF) involving patients with AGC on the basis of well result. No significant financial relationships to disclose.
A pilot study to evaluate response and angiogenesis after treatment with bevacizumab in patients with inflammatory breast cancer
Authors: S. B. Wedam, J. A. Low, X. Yang, C. Chow, A. Berman, R. Eulate, D. Danforth, S. M. Hewitt, S. M. Steinberg, S. M. Swain
Journal: Journal of Clinical Oncology (2004)

578 Background: Inflammatory breast cancer (IBC) is an aggressive form of breast cancer associated with vascular and lymphatic invasion. Previously untreated IBC patients received bevacizumab (BV), a recombinant humanized monoclonal antibody to VEGF, to evaluate endothelial cell proliferation (CD31/Ki67), tumor cell proliferation (Ki67), tumor microvessel density (MVD), VEGF, and vascular permeability (k21) on dynamic contrast enhanced MRI (dMRI). Methods: Treatment consisted of BV alone for cycle (C) 1 (15mg/m2 on day 1) followed by six cycles of BV (15mg/m2) with doxorubicin (50mg/m2) and docetaxel (75mg/m2) q3wk and G-CSF in C2–7. Following mastectomy and radiation, BV was given for eight more cycles with hormonal therapy for ER+ pts. Tumor core biopsies and dMRI were obtained at baseline, after C1, 4, 7. Results: Sixteen pts enrolled received 125 cycles of treatment. Pts: Stage III 87.5% and IV 12.5%, ER+ 38%, Her2 positive 12.5%. Post-chemo, thirteen pts (3 too early to evaluate): 8PRs, 1PR unconfirmed, 1PD. A decrease in CD31/Ki67 was seen after BV treatment alone (-1% median change, p=0.031). There were no decreases in Ki67 or MVD after BV alone (p=0.97 and 0.70) or BV and chemotherapy (p=0.23 and 0.85). There were significant decreases in k21 after treatment (n=12), with a median change of -53% (p=0.019) after C1, -70% (p=0.001) after C4, and -56% (p=0.008) after C7. In patients with PR there were trends towards a decrease in VEGF after C1(-57% median change, p=0.09) and decrease in Ki67 after C4/C7 (-57% median change, p=0.09). There were no correlations between k21and CD31/Ki67 index, Ki67, or VEGF after BV alone (n=11); but a trend towards a correlation between VEGF and k21 after BV and chemotherapy (r=0.62, p=0.10). Most common grade 3/4 toxicities (n=16): neutropenia (63%), diarrhea (25%), HTN (25%), and febrile neutropenia (19%). Conclusions: Preliminary results revealed a decrease in vascular permeability on dMRI and endothelial cell proliferation with BV treatment alone. In responding pts, there were trends toward a decrease in VEGF after BV and tumor cell proliferation after BV and chemotherapy. No significant financial relationships to disclose.
Chemotherapy-associated steroid use and its effect on blood glucose, nephro-, and other toxicity of chemotherapy for non-diabetic oncological patients
Authors: X. Yan, P. Wong, G. DelPriore, J. Bottino
Journal: Journal of Clinical Oncology (2009)

e20721 Background: Gynecologic cancer chemotherapy regimen include prechemotherapy, intrachemotherapy, and postchemotherapy administration of glucocorticoid steroids, which introduce the risk of hyperglycemia. Some studies have suggested that hyperglycemia is associated with increased chemotherapy toxicity. We evaluated the effects of dexamethasone as part of ovarian cancer and cervical cancer chemotherapy on blood glucose and its subsequent effect on nephrotoxicity in non-diabetic patients. Methods: We conducted a retrospective chart review of patients diagnosed with ovarian cancer and cervical cancer and received steroids as part of their chemotherapy during 2006–2008. Subjects who had elevated glucose detected at any time during treatment were compared with controls who had normal glucose levels. Pre- and post treatment serum BUN, creatinine, and blood glucose level were obtained. Results: 17 non-diabetic patients who received cisplatin or paclitaxel or both were studied (median age 50 years; range 42–60); All of the patients received 10 -20 mg of DEX intravenously before cisplatin/taxol. Glucose was only mildly elevated in 4 patients (110–200 mg/dl). None of the four cases with elevated glucose levels had any toxicity. One of the eight controls (12.5%) had elevation of creatinine. In all of the 17 patients, only one had evidence of mild nephrotoxicity, however her median blood glucose was not elevated while on therapy. Conclusions: This preliminary study did not show that current steroid regimens prescribed with chemotherapy have a significant overall effect on glucose elevation and subsequent increased nephrotoxicity of chemotherapy. Additional patients will be presented. No significant financial relationships to disclose.
Preferential inhibition of Sp1 expression in growing tumors by mithramycin-A (MIT) directly correlates with its potent antiangiogenic effects in human carcinoid xenograft model
Authors: K. Xie, Z. Jia, J. Zhang, L. Wang, Q. Li, X. Le, J. C. Yao
Journal: Journal of Clinical Oncology (2007)

15041 Background: MIT, also known as aureolic acid and plicamycin (Mithracin), is an aureolic acid-type polyketide produced by various soil bacteria of the genus Streptomyces. Previous studies have shown that MIT exhibits antitumor activity. In the present study, we examine the antiangiogenic effect of MIT and its underlying mechanisms. Methods: Cohorts of 10 athymic BALB/c nude mice were implanted with 1.5 million human H727 carcinoid cells. Mice were treated with subcutaneous or intraperitoneal 0.2 mg/kg of mithramycin twice weekly once implanted tumor reached 4 mm in size. Results: Both subcutaneous and intraperitoneal MIT significantly suppressed the growth of carcinoid cells in nude mouse models (median tumor weight in PBS, s.c., i.p. groups 790 mm 3 vs 280 mm 3 , 480 mm 3 ; P &lt; 0.01). We also evaluated the Sp1 expression in growing tumors and various organs. We found that the liver expressed the highest level of Sp1 among normal organs (including liver, stomach, large intestine, and small intestine, spleen, kidney, brain and lymph node). However, Sp1 expression in the growing tumors was more than 10 times higher than that in a normal liver. Treatment with MIT reduced the Sp1 expression in the tumors, while no discernible effect on Sp1 expression in normal tissues was observed. This is the first demonstration that MIT selectively inhibited the Sp1 expression in the growing tumors. Consistent with the expression of Sp1, a substantial suppression of VEGF, PDGF, EGFR, and IGFR expression was evident. Finally, treatment with MIT reduced the microvessel formation in tumors by 80% (MVD count; P &lt; 0.01). This antiangiogenic activity was confirmed by in vitro tubulogenesis assay and in vivo Matrigel plug assay. Conclusions: Collectively, our studies strongly indicate that MIT is a potent antiangiogenic agent and its mechanism of action involved suppression of Sp1 expression and its consequent downregulation of its downstream targets including VEGF, PDGF, EGFR, and IGFR that are key to tumor angiogenesis. No significant financial relationships to disclose.
Gene expression of antimicrobial peptides in colonic mucosa of patients with inflammatory bowel disease before and after first infliximab treatment.
Authors: I. Arijs, K. Lemaire, R. Quintens, L. Van Lommel, P. Leemans, Kristel Van Steen, G. De Hertogh, G. Van Assche, S. Vermeire, K. Geboes, F. Schuit, P. Rutgeerts
Journal: Gut (2008)