tbuckley/cabot-search huggingface dataset:
Abstract 13083: Cocooning of Cardiac Stem Cells Within Hydrogel Microcapsules Supplemented With Integrin-binding Proteins Promotes Cell Survival and Post Ischemic Cardiac Function
Authors: Audrey Mayfield, Everad Tilokee, Brian McNeill, Bu-Khanh Lam, Marc Ruel, Erik J Suuronen, David W Courtman, Duncan J Stewart, Darryl R Davis
Journal: Circulation (2013)
A pilot study of low-dose capecitabine plus trastuzumab as first-line treatment for patients older than 75 years with HER2-positive advanced gastric cancer.
Authors: Sun Jin Sym, Young Saing Kim, Inkeun Park, Hee Kyung Ahn, Junshik Hong, Jinny Park, Eun Kyung Cho, Jae Hoon Lee, Woon Ki Lee, Min Chung, Hyung-Sik Kim, Dong Bok Shin
Journal: Journal of Clinical Oncology (2014)

165 Background: Elderly patients often present with concomitant co-morbidities and age-associated physiologic problems, such as impaired organ function and functional changes that make the selection of optimal treatment difficult. We report the treatment outcome in 13 elderly patients with HER2-positve advanced gastric cancer who treated with low-dose capecitabine plus trastuzumab. Methods: Patients older than 75 years with gastric cancer were eligible for inclusion if their tumors showed overexpression of HER2 protein by immunohistochemistry (IHC) (3+) or gene amplification by FISH and IHC 2+. Capecitabine 1000 mg/m 2 was given orally twice a day for 14 days followed by a 1-week rest. Trastuzumab was given by intravenous infusion as a dose of 8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks. Chemotherapy was given every 3 weeks for eight cycles. Results: Between December 2011 and July 2013, 13 consecutive patients (IHC 3+;7, IHC 2+ and FISH+;6) with a median age of 79 years (range, 75-92 years) were enrolled in this study. ECOG PS was 0/1/2:1/7/5, respectively. A total of 54 cycles of capecitabine plus trastuzumab were administered (median, three cycles; range, 2-8 cycles). Of the 12 patients with measurable lesions, the overall response rate was 41.6% (95% CI, 13.7 to 69.5%). Disease control was achieved in 75.0% of patients. Median progression-free survival was 8.2 months (95% CI, 2.5-13.7 months) and median overall survival was 10.9 months (95% CI, 1.4-20.4 months). Grade 3-4 toxicities were stomatitis (7.6%) and anemia (7.6%). No treatment-related deaths and symptomatic congestive heart failure were observed. Conclusions: Our findings suggest that low-dose capecitabine plus trastuzumab is effective and well tolerated in elderly patients with advanced HER2-positive gastric cancer who are considered ineligible for combination chemotherapy. Prospective trials investigating this regimen in elderly patients with advanced gastric cancer are warranted. Clinical trial information: Gachon University IRB.
Abstract 17932: Diabetic Cardiomyopathy in Mice is Characterized by Defects in Myocyte Turnover Measured by Microdosing of 14C-Labeled Thymidine
Authors: Yingnan Bai, Borghetti Giulia, Alex Matsuda, Antonio Cannatá, Andrea Sorrentino, Maria V Caballero, Todd Pankratz, Eric Guarin, Polina Goichberg, Annarosa Leri, Marcello Rota, Mark Seymour, Piero Anversa, Junbo Ge, Jan Kajstura
Journal: Circulation (2013)

Insulin-dependent diabetes mellitus was induced in mice by streptozotocin administration (175 mg/kg bw). Blood glucose was measured daily and when it reached 450 mg/dl, ~5-7 days later, 300 pCi 14C-thymidine was given intramuscularly to label forming cardiomyocytes. Control mice were similarly treated. This protocol results in a pulse labeling of replicating cells, since thymidine disappears from the circulation in less than one hour; the half-life of this nucleotide is ~15 minutes. Control and diabetic mice were sacrificed at 1, 3, 5, 10, 20, 30, 60, and 90 days after the injection of 14C-thymidine and the heart was collected. Left ventricular myocytes were isolated by enzymatic digestion, purified by differential centrifugation, and the DNA was extracted for the measurement of the kinetics of 14C concentration by Accelerator Mass Spectrometry. This is the only methodology that allows the assessment of trace-amount of 14C in the DNA. In non-diabetic control hearts, 14C concentration in the myocyte DNA in...
Population pharmacokinetics of imatinib in children and adults
Authors: E. Chatelut, A. Pétain, J. Azard, D. Kattygnarath, C. Delbaldo, B. Geoerger, M. Barrois, S. Séronie-Vivien, A. Lecesne, G. Vassal
Journal: Journal of Clinical Oncology (2008)

2526 Background: The aim of this study was to explore the impact of several demographic, biological and pharmacogenetic covariates on imatinib and its main metabolite (CGP74588) disposition. Methods: Thirty three children included in a phase 2 study and thirty four adults with gastrointestinal stromal tumor received 340 mg/m² and 400 mg imatinib, respectively. Plasma imatinib and CGP74588 concentrations observed on day 1 and at steady-state were analyzed by population pharmacokinetic method (NONMEM) to evaluate the impact of age, body weight (BW), age, sex, albuminemia (ALB), plasma alpha1-acid glycoprotein (AGP), and several polymorphisms corresponding to ABCB1, ABCG2, CYP3A4, CYP3A5, AGP (pharmacogenetic data available in 46/67 patients). Results: Analysis of the whole data set (67 patients) showed that apparent clearance (CL/F) of imatinib was positively correlated with BW and ALB, and negatively with AGP. By considering these three covariates, the inter-individual variability on CL/F decreased from 47% to 19%. Apparent volume of distribution of imatinib was positively correlated with BW, and negatively with AGP. Apparent clearance of CGP74588 was similarly dependent on both BW and AGP, and significantly lower (30% reduction) at steady-state. By adding genotype status to the final covariate imatinib model, a 22% reduction in CL/F was observed in heterozygous compared to wild-type patients corresponding to ABCG2 421C>A (p<0.05). Conclusions: By considering morphological and biological covariates, a unique covariate model could be used to describe accurately imatinib pharmacokinetics in patients from 2 to 84 years-old. Morphological and biological characteristics have a stronger influence than pharmacogenetics on imatinib pharmacokinetics. Beside the impact of BW, those of AGP and ALB suggest the importance of protein-binding phenomenon and liver functions on imatinib disposition. No significant financial relationships to disclose.
Immune Monitoring Technology Primer: protein microarray (‘seromics’)
Authors: Jianda Yuan, Ena Wang, Bernard A. Fox
Journal: Journal for ImmunoTherapy of Cancer (2016)

Protein microarrays are used to identify targets of drugs, small molecules, and enzyme substrates that may be modified in numerous ways such as by phosphorylation or methylation, to detect protein binding properties, investigate protein-protein interactions, and to define protein-based biomarkers in
CA19-9 and surgical margin status (SMS) associations with local-regional (LRF) and distant failure (DF) in patients (Pts) with pancreatic cancer: RTOG 9704 secondary analysis.
Authors: William Regine, Kathryn A. Winter, Ivan Kessel, Yuhchyau Chen, James A. Fugazzi, Eric Donald Donnelly, Thomas A. DiPetrillo, Samir Narayan, John Peter Plastaras, Rakesh Gaur, Guila Delouya, John H. Suh, Joshua E. Meyer, Michael G. Haddock, Mukund S. Didolkar, Gilbert D. A. Padula, David B Johnson, John Parker Hoffman, Christopher H. Crane
Journal: Journal of Clinical Oncology (2015)

347 Background: 9,704 was the first phase 3 pancreatic cancer trial to validate the prognostic value of postresection CA19-9 for overall survival (OS), with values &gt; 90/180 associated with worse OS. All pts received adjuvant gemcitabine or 5-FU and chemo-radiotherapy (RT). This analysis evaluates patterns of disease failure. Methods: SMS was negative, positive, or unknown. CA19-9 was analyzed at cut points 90, 180 and continuously. LRF and DF were estimated by cumulative incidence and Gray’s test compared. Cox hazard models were used for multivariate analyses (MVA) and included treatment, tumor site, size and nodal status. To adjust for multiple comparisons a p-value &lt; 0.01 is statistically significant and 0.01 to &lt; 0.05 a trend. Results: 538 pts accrued, with 451 eligible and analyzable for SMS and 385 for CA19-9. For CA19-9, 132 (34%) were Lewis Antigen negative (no CA19-9 expression), 200 (52%) &lt; 90 and 220 (57%) &lt; 180. 188 (42%) had negative margins, 152 (34%) positive and 111 (25%) unknown (i.e., no margin comment in path report; shown to have outcomes similar to negative margin pts). Pts with CA19-9 ≥ 180 were more likely to have tumors ≥ 3 cm and pts with positive SMS more likely to have KPS 60 - 80, T3/T4, or N1 disease. On univariate analysis (UVA) CA19-9 cut at 90 was associated with significant increases in both LRF (trend) and DF; in the gemcitabine arm this was seen in DF, not in LRF; in the 5-FU arm it was seen in both. Results were similar at the 180 cut point and continuously. SMS on UVA was not associated with increase in LRF/DF; see Table. On MVA, CA19-9 &gt; 90 was significantly associated with LRF and DF; positive SMS showed only a trend for DF. Conclusions: Postresection CA19-9 has significant association with both LRF and DF not seen with SMS. These findings support continued use of RT in trials and consideration of dose intensification among pts with elevated postresection CA19-9. Grants: NCI U10, CA21661, CA37422, CA180868, CA180822. Clinical trial information: 0000000. [Table: see text]
EAP in advanced gastric cancer.
Authors: B G Taal, W W ten Bokkel Huinink, H Franklin, S Rodenhuis
Journal: Journal of Clinical Oncology (1990)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1990.8.5.939 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2332776 EAP in advanced gastric cancer. B G TaalxB G TaalSearch for articles by this author , W W ten Bokkel HuininkxW W ten Bokkel HuininkSearch for articles by this author , H FranklinxH FranklinSearch for articles by this author , S RodenhuisxS RodenhuisSearch for articles by this author https://doi.org/10.1200/JCO.1990.8.5.939 First Page PDF © 1990 by American Society of Clinical Oncology
Pembrolizumab (MK-3475) in patients (pts) with extensive-stage small cell lung cancer (SCLC): Preliminary safety and efficacy results from KEYNOTE-028.
Authors: Patrick Alexander Ott, Maria Elena Elez Fernandez, Sandrine Hiret, Dong-Wan Kim, Rebecca Anne Moss, Tammy Winser, Sammy Yuan, Jonathan D. Cheng, Bilal Piperdi, Janice M. Mehnert
Journal: Journal of Clinical Oncology (2015)

7502 Background: Treatment options for pts with SCLC that progresses on platinum-based chemotherapy are limited. Pembrolizumab, an anti–PD-1 monoclonal antibody designed to block the interaction between PD-1 and its ligands PD-L1 and PD-L2, has shown antitumor activity in multiple advanced malignancies, including non-small cell lung cancer. We assessed the safety and efficacy of pembrolizumab in pts with PD-L1+SCLC. Methods: KEYNOTE-028 (ClinicalTrials.gov, NCT02054806) is an ongoing multicohort, phase Ib study of pembrolizumab in pts with PD-L1+ advanced solid tumors. Key eligibility criteria for the SCLC cohort include: confirmed, measurable disease; PD-L1 expression in ≥ 1% of cells in tumor nests or PD-L1+ bands in stroma as assessed by IHC at a central laboratory; failure of standard therapy; and absence of autoimmune disease or interstitial lung disease. Pembrolizumab 10 mg/kg is given every 2 wk for up to 2 y or until confirmed progression or unacceptable toxicity. Primary end points are safety, tolerability, and response assessed per RECIST v1.1 by investigator review every 8 wk for the first 6 mo and every 12 wk thereafter. Results: Of the 135 pts with SCLC screened, 37 (27%) had PD-L1+ tumors. Seventeen pts were enrolled from March 2014 through January 2015 (59% men; median age, 62 y; 59% ECOG PS 1). One pt was misenrolled and did not receive pembrolizumab. All 16 treated pts received prior platinum and etoposide. 9 pts (53%) experienced a drug-related AE (DRAE); only 1 pt had a grade ≥ 3 DRAE. There were no treatment-related deaths or discontinuations due to DRAEs. Four of 16 (25%) evaluable pts had a partial response. One (7%) pt had stable disease, resulting in a disease control rate of 31%. Six (37%) pts had progressive disease as their best response, and 5 pts had no assessment at the time of analysis. Responses are durable, with all responders on treatment for 16+ wks with ongoing response. Conclusions: Pembrolizumab is generally well tolerated and has promising antitumor activity in pts with PD-L1+ SCLC who have progressed on prior platinum-based therapy. Enrollment in the SCLC cohort of KEYNOTE-028 is ongoing. Clinical trial information: NCT02054806.
Interactions between antioxidant gene variants and dietary antioxidant intake for asthma outcomes in children – Food for thought?
Authors: Steve Turner, Jon Ayres, Colin Palmer, Anil Mehta, Somnath Mukhopadhyay, Graham Devereux
Journal: European Respiratory Journal (2014)

Introduction. We tested the hypothesis that there is an interaction between reduced antioxidant dietary exposures and genetically determined susceptibility to oxidant stress for adverse asthma outcomes in children.  Methods. Respiratory questionnaire, food frequency questionnaire (FFQ), Paediatric Asthma Quality of Life Questionnaire (PAQLQ) and Children9s Asthma Control Test (CACT) were completed by children with asthma. Exposures of interest were energy-adjusted intake of vitamins C and E, carotenoids and selenium; a composite score (0 to 4) for antioxidant exposure was derived. DNA was extracted, GST variants were determined; a susceptibility score (0-3) for oxidant stress was derived. The primary outcome was a recent exacerbation and secondary outcomes were CACT and PAQLQ scores.  Results. DNA and FFQ details were obtained in 450 children, mean age 10.3 years and 58% male. The risk for exacerbation, but not reduced CACT or PAQLQ scores, was concordant with increasing number of GST mutants (risk with no mutation 0.6 [95% CI 0.3, 0.9] compared to 2 or 3 mutations). There was no consistent association between individual antioxidant exposure or the dietary antioxidant exposure score and asthma outcomes. There was no interaction between reduced exposure to the dietary antioxidants measured and increased genetically determined antioxidant susceptibility for asthma exacerbation.  Conclusion. Whilst our study was underpowered to detect an interaction of small magnitude, we found no evidence of a large effect of a gene-environment interaction between genetically-determined oxidant susceptibility and reduced dietary oxidant exposure for the outcomes.
Comparison of the incidence of peripheral neuropathy (PN) with eribulin versus ixabepilone (IXA) in metastatic breast cancer (MBC) patients: A randomized phase II study.
Authors: Linda T. Vahdat, Agustin Garcia, Charles L. Vogel, Christine M. Pellegrino, Deborah L. Lindquist, Joseph A. Sparano, Prashanth Gopalakrishna, Nicholas Iannotti
Journal: Journal of Clinical Oncology (2012)

121 Background: Eribulin mesylate is approved for patients (pts) with MBC who have previously received ≥2 chemotherapeutic regimens for metastatic disease including an anthracycline and taxane in either the adjuvant or metastatic setting. This study compared incidence and severity of neuropathy adverse events (AEs) in pts receiving eribulin or IXA. Methods: Pts (locally recurrent/MBC; prior taxane therapy; ≥1 prior chemotherapy for advanced disease; pre-existing neuropathy Grade 0 [n=51] or 1 [n=53]) were randomized to receive 1.4 mg/m 2 eribulin mesylate (2–5-min intravenous (IV), Days 1 and 8 of a 21-day cycle) or 40 mg/m 2 IXA (3 h IV, Day 1 of a 21-day cycle). The primary objective was to compare incidence of neuropathy AEs by CTCAE grade. Secondary objectives: severity of neuropathy AEs by CTCAE grade, patient neurotoxicity questionnaire (PNQ), and vibration sensitivity using Vibration Perception Threshold (VPT); time to onset of treatment-emergent neuropathy (TEN); efficacy; safety and tolerability. Results: Incidences ofPN and TEN (all grades) with eribulin (n=51) versus (vs) IXA (n=50) were 31.3% vs 44.0%, p=0.1632 and 33.3% vs 48.0%, p=0.1284, respectively. Severity (grade ≥3) was numerically lower with eribulin than IXA (PN: 9.8% vs 20.0%; TEN: 9.8% vs 22.0%). No significant differences were seen in baseline to worst PNQ scores. Median worst post-baseline VPT scores were lower with eribulin than IXA (index finger: 2.3 vs 2.4 vibration units [vu]; great toe: 7.75 vs 8.6 vu). Median time to onset of TEN was earlier with IXA (11.6 weeks [wks]) than eribulin (35.9 wks). TEAEs were comparable. Median treatment duration was 15.0 wks (eribulin) and 10.5 wks (IXA). Reasons for discontinuation (eribulin vs IXA): TEN (3.9% vs 18.0%); any TEAE (11.8% vs 32.0%); progressive disease (68.6% vs 48.0%). Objective response and clinical benefit rates were 15.4% vs 5.8% and 26.9% vs 19.2% for eribulin and IXA, respectively. Conclusions: Although not statistically significant, neuropathy AEs were less common with eribulin than IXA. Eribulin was associated with longer time to onset of TEN and fewer discontinuations due to neuropathy and other toxicities.
Abstract P4-04-13: Cancer-derived miR-105 promotes tumor invasion and destroys the natural barriers against metastasis
Authors: Shizhen Emily Wang, Weiying Zhou, Miranda Y Fong, Yongfen Min, Pengnian Charles Lin
Journal: Cancer Research (2015)

Abstract Cancer-secreted miRNAs are emerging mediators of cancer–host crosstalk. In this study, we set out to identify cancer-derived miRNAs that participate in cancer metastasis by adapting the niche cells. We show that miR-105, which is characteristically expressed and secreted by metastatic breast cancer cells, is a potent regulator of migration through targeting the tight junction protein ZO-1. In epithelial and endothelial monolayers, exosome-mediated transfer of cancer-secreted miR-105 efficiently destroys tight junctions and the integrity of these natural barriers against metastasis. Overexpression of miR-105 in non-metastatic cancer cells induces metastasis and vascular permeability in distant organs, whereas intervention of miR-105 in highly metastatic tumors alleviates this effect. By testing clinical specimens from breast cancer patients, we further show that miR-105 can be detected in the circulation at the pre-metastatic stage, and its levels in the blood and tumor are associated with ZO-1 expression and metastatic progression in early-stage breast cancer. Our results demonstrate for the first time the dual roles of miR-105 in inducing the migratory potential of cancer cells as well as destroying the epithelial and endothelial barriers in the cancer niche by targeting the cellular tight junctions. In breast cancer patients, increased levels of miR-105 in the circulation can be detected at the pre-metastatic stage and predict the occurrence of metastasis. Anti-miR-105 treatment suppresses metastasis and abolishes the systemic effect of tumor-derived miR-105 on niche adaptation. Therefore, these pre-clinical observations strongly suggest clinical applications of miR-105 as a predictive or early-diagnostic blood-borne marker as well as a therapeutic target for breast cancer metastasis. Citation Format: Shizhen Emily Wang, Weiying Zhou, Miranda Y Fong, Yongfen Min, Pengnian Charles Lin. Cancer-derived miR-105 promotes tumor invasion and destroys the natural barriers against metastasis [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-04-13.
The usefulness of point-of-care-testing for C-reactive protein in lower respiratory tract infection/acute cough
Authors: Elena Andreeva, Hasse Melbye
Journal: European Respiratory Journal (2012)

Background: Respiratory tract infections and acute cough are too frequently treated with antibiotics. Point of care test (POCT) for C-reactive protein (CRP) has in one study been shown to significantly reduce antibiotic prescribing for lower respiratory tract infections (LRTI) without compromising recovery.

Aim: The aim of the study was to evaluate the effect of using the CRP test in general practice patients with LRTI on the prescription of antibiotics, referral to radiography, and the outcome of the patients.

Methods: Open randomised clinical trial; patients with LRTI/acute cough were included. CRP-test was carried out before treatment was decided in the intervention group, with the use of Afinion test system (Axis Shield). Frequency of prescribing antibiotics and referral to radiography were main outcome measures.

Results: Altogether, 179 patients were included, 101 in the intervention group tested by POCT for CRP and 78 in the control group. No significant difference in age, gender, co-morbidity, symptoms and chest findings was found between intervention and the control groups. In the intervention group antibiotics prescribing rate was significantly lower, 37.6%, than in the control group, 60.2%, (p=0.005). Referral to chest X-ray examination was also significantly lower in the intervention group, 55.4%, than in the control group, 76% (p<0.01). Two weeks after start of treatment the recovery rate (% fully or almost recovered) was 92% and 93%, respectively.

Conclusion: CRP testing may reduce unnecessary antibiotic prescribing and referral to radiography in patients with LRTI and acute cough without compromising recovery.
Hormonal induction followed by rapid hormonal cycling for prostate cancer (PC): the MEN's Cycle
Authors: L. T. Nordquist, N. Sauter, M. Morris, O. Smaletz, K. Konopelski, A. Delacruz, G. Heller, H. I. Scher
Journal: Journal of Clinical Oncology (2004)

4609 Background: Continuous androgen deprivation (AD) is a standard therapy for systemic PC. Rapid cyclic AD and androgen repletion (AR) after a 1 month induction with castration was shown to be feasible. This trial explores a longer induction period followed by rapid cyclic AD and AR in patients (pts) with limited prior hormone exposure. Methods: Eligible pts had a rising PSA after surgery or radiation, or radiographic metastases, and ≤ 6 months of prior hormone exposure. Treatment consisted of a 3 month induction (GnRH analog monthly & bicalutamide x 1 month) followed by monthly cycles of AR (topical testosterone (T) daily x 7 days) and AD (GnRH analog monthly). A PSA of ≤1ng/ml after induction was required to proceed with cycling. PSA and T levels were monitored post ablation (troughs) and post repletion (peaks). The primary endpoint was the proportion of pts with serially declining PSA troughs after 6 cycles. Treatment failures were defined as 3 sequential increases in PSA troughs prior to 6 cycles. Results: 23 pts were enrolled (5 pts: rising PSA only; 18 pts: metastatic disease). The median baseline PSA was 63ng/ml (2.6–546). The median baseline T level was 383ng/dl (181–654). All cycling pts achieved T levels within the normal reference range during AR and castrate troughs during AD. 5 pts (22%) did not achieve a PSA of ≤1ng/ml after induction and did not cycle. 3 pts were inevaluable. Of the 15 evaluable pts who cycled, 6 pts met the primary endpoint and 3 pts are still being evaluated at < 6 cycles. 6 pts were treatment failures (all continued standard AD off study, of whom 5 pts had further PSA declines). No pt progressed radiographically. Common toxicities included grade 1 fatigue and hot flashes. Conclusion: Rapid hormonal cycling using a 3 month induction is feasible, well-tolerated, and successive declines in the PSA troughs can be achieved. Some pts did show evidence of AD resistance within 3 months by not achieving a PSA of ≤1ng/ml after induction. Based on these results, we have designed a phase II clinical trial using rapid hormonal cycling with no induction in combination with docetaxel in pts with limited prior hormone exposure. Support: CCPP, CA05826, Prostate Cancer Foundation No significant financial relationships to disclose.