tbuckley/cabot-search huggingface dataset:
PWE-015 Experience from the first Newcastle endoscopic retrograde cholangiopancreatography and endoscopic ultrasound course for nurses
Authors: M K Nayar, L Hodgson, H Gray, G Nicholson
Journal: Gut (2010)

<h3>Introduction</h3> Endoscopic retrograde cholangiopancreatography and endoscopic ultrasound (ERCP and EUS, respectively) are complex endoscopic procedures requiring highly skilled nursing assistants. For these procedures to be performed safely and efficiently; regular training and teaching is essential. Currently there are no mandatory training courses in the region for these procedures despite the recognised need. The aim of the course was to address the basic principles of these complex endoscopic procedures and highlight recent developments in the field. <h3>Methods</h3> Fifty nurses working in endoscopy units around the country attended the first Newcastle ERCP and Endoscopic Ultrasound course for nurses (The Newcastle Upon Tyne Hospitals NHS Foundation Trust). They were surveyed at the end of the course using a detailed questionnaire. <h3>Results</h3> 50 delegates attended from eight institutions around the UK. 49 (98%) delegates completed the questionnaire. The average experience of the staff working in endoscopy was 5.5 years (range 0–20 years). 13/49 (26.5%) had previously attended some form of ERCP±EUS training. 42 (85.7%) delegates thought all nurses should attend similar course. 38 (77.5%) thought their knowledge was either basic or moderate prior to attending the course. 47 (95.9%) said that their knowledge had improved after the course. 31 (63.2%) thought their ability to assist during an ERCP/EUS either basic or moderate before the course 45 (91.8%) thought their ability to assist during ERCP/EUS had improved after the course. Confidence in assisting the Endoscopist with therapeutic procedures increased from 28 (57.1%) to 41 (83.6%) of attendees after the course. 42 (85.7%) of attendees agree all nurses should undergo a training course within the first year in post in the Endoscopy unit. <h3>Conclusion</h3> 1. Less than a third of the endoscopy nurses attending the course had attended some form of formal training course for either ERCP or EUS, despite a medium time working in Endoscopy of 5.5 years. 2. This course not only improved the knowledge and ability to assist during a therapeutic ERCP/EUS list but also improved the nurse9s confidence about these complex procedures. 3. More prospective surveys are required to address training issues for nurse assistants involved in ERCP and EUS.
Abstract 860: Effects of breastfeeding and oral contraception use on the risk of breast cancer recurrence: A multinational study
Authors: Teresa A. Lehman, Mohammed Shaik, Ramakrishna V. Modali, Borys Hrinczenko
Journal: Cancer Research (2015)

Abstract Introduction: Breastfeeding (BF) decreases and oral contraceptive (OCP) increases the incidence of breast cancer (BC). However, their role in the recurrence of breast cancer (rBC) has not been established. The aim of our study was to examine the association of maternal factors in the rBC. Methods: Data were obtained from the Global Epidemiological Study (GES), an IRB approved multinational biorepository and database to assess disease risk factors. Pts provided their personal history, age, BMI, age of first pregnancy, BF, number of children breastfed, radiation exposure (RE), years of OCP use, benign breast disease (BD), hysterectomy, hormone replacement therapy (HRT) and rBC. The t-test and chi-square test were used for continuous and categorical variables, respectively. The association [adjusted odds ratio (aOR)] between rBC and each risk factor was obtained using logistic regression after adjusting for all the variables including stage of cancer. Results: A total of 2546 patients were surveyed, of which 218 patients had rBC later in life. The average age of pts with recurrence was 54 yrs and those without rBC was 56 yrs. Of the total, 73.5% had BF, 25% had used OCP, 17.3% used HRT, 5.6% had RE, 16.6% had a hysterectomy, and 16% had BD. In multivariate analysis, age, BF, OCP and RE each had significant impacts on the rBC. Pts who did not BF had a 3-fold increased risk of recurrence compared to those who breastfed at least 3 children [aOR of 2.9 (1.7-4.9)]. Pts who did not use OCPs were 53% less likely to have rBC compared to those who used OCPs [aOR of 0.47 (0.32-0.69)]. A statistically significant dose-effect for number of children breastfed and rBC, and years of OCPs usage and rBC was found. BMI, HRT, hysterectomy, BD, and age at first pregnancy did not have an effect on rBC. Conclusion: Our study suggests that breastfeeding decreases the risk of recurrence of breast cancer, while OCP usage increases the risk of recurrence of breast cancer. Further studies are needed to validate our results. Predictors of recurrence of breast cancer (rBC)Variablesβ EstimateAdjusted OR (CI)p-valueAge0.0221.02 (1.008-1.03)0.002Breastfed (BF, none vs. &amp;gt;3 children)1.062.9 (1.7-4.9)&amp;lt;0.0001Breastfed (BF, &amp;lt; 3 vs. &amp;gt; 3 children)0.742.09 (1.2-3.5)0.006Oral Contraceptive use (OCP, no vs. yes)-0.7430.47 (0.32-0.69)0.0001Radiation exposure (RE, no vs. yes)-1.310.26 (0.16- 0.13)&amp;lt;0.0001HRT (no vs. yes)0.41.49 (0.96-2.3)0.07 Citation Format: Teresa A. Lehman, Mohammed Shaik, Ramakrishna V. Modali, Borys Hrinczenko. Effects of breastfeeding and oral contraception use on the risk of breast cancer recurrence: A multinational study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 860. doi:10.1158/1538-7445.AM2015-860
Phase I open-label, dose-escalation study of ANA773 tosylate, an oral prodrug of a toll-like receptor-7 agonist, in patients with advanced solid tumors.
Authors: G. A. Daniels, W. E. Carson, A. C. Mita, K. L. Kendra, M. H. Rahimy, D. W. Inman, J. R. Appleman, J. L. Freddo, D. G. McNeel
Journal: Journal of Clinical Oncology (2011)

2524 Background: ANA773 is an oral prodrug of a small molecule, TLR7-selective agonist which has demonstrated pharmacological activity in preclinical studies. In a study in healthy volunteers, dose-related increases in markers of interferon-alpha dependent responses (e.g. oligoadenylate synthetase (OAS), neopterin, and OAS1 and other Interferon Stimulated Gene mRNAs) were observed after administration of ANA773 with little or no increase in circulating IFN-alpha. This study aimed to determine the MTD, pharmacodynamics (PD), pharmacokinetics (PK), and anti-tumor activity in pts with advanced cancer. Methods: Phase I dose escalation in pts with advanced solid tumors. Pts were treated with ANA773 dosed orally every other day for 14 days followed by a 14 day rest period, on continuous 28-day cycles. A minimum of 3 pts were enrolled at each dose level. Endpoints included safety, PK, biomarkers of immune activation and tumor response by RECIST. Results: 20 pts have been treated at 5 dose levels (50, 100, 200, 400, and 800mg QOD). ANA773 was well tolerated; the MTD was not reached in this trial. CTC grade 1-2 AEs considered possibly treatment related included fatigue, nausea, diarrhea, headaches, vomiting and weight loss. One pt had gr 3 fatigue. One pt had DLT; a pt with malignant melanoma experienced grade 3 neutropenia at 800mg QOD and was dose reduced to 600mg QOD starting in cycle 2. This pt achieved a PR and continued treatment for 19 cycles. 4 pts had stable disease (SD): adenocystic carcinoma (13 cycles), prostatic carcinoma (6 cycles), uveal melanoma (7 cycles) and uveal melanoma (11 cycles). PK analysis indicates that exposure to the active TLR7 agonist is dose proportional. At 400 and 800 mg QOD an increased expression for interferon-responsive genes (OAS1, ISG15, IFIT1 and IFI27) was demonstrated in PBMCs. Consistent with ongoing TLR7 activation, substantial induction of all four genes occurred on D13. Conclusions: ANA773 was well tolerated in pts with advanced solid tumors. Continued clinical development is supported by the early evidence for its activity, including evidence of TLR7 agonist-mediated pharmacology and responses observed in pts with melanoma.
Abstract 3128: MicroRNA-mediated reprogramming of myeloid cells by targeting TGFβ signaling and its associated molecular network
Authors: Suman K. Vodnala
Journal: Cancer Research (2015)

Abstract Tumor derived soluble factors result in accumulation of Gr-1+CD11b+ immature myeloid cells at tumor site and premetastatic organ. These cells are known to promote tumor progression and metastasis. Gr-1+CD11b+ immature myeloid cells and tumor-associated macrophages display a type 2 phenotype (M2) and produce immune suppressive cytokines including TGFβ. We have previously shown that immature myeloid cells are vicious producers of TGFβ ligand and express high levels of TGFβR2 receptor for eliciting immune suppressive function. Specific deletion of TGFβR2 in myeloid cells resulted in increased antitumor immunity and decreased metastasis in the lungs of cancer mouse models. microRNAs (miRs) are abundant class of small non-coding RNAs that have recently emerged as powerful epigenetic regulators of gene expression in pathophysiological conditions. One of the critical properties of miR is to target a large number of genes frequently within the context of a network, making them very efficient in regulating distinct biological cell processes. In the current project, we have identified three miRs that target myeloid TGFβR2 associated molecular network including p38 and cAMP pathways, which are critical in type 2 cytokine production. We have successfully transduced bone marrow stem cells with lentivirus expressing these miRs driven by a myeloid specific promoter CD11b. Transplantation of these modified bone marrow into lethally irradiated mice decreased breast cancer metastasis. The underlying mechanisms involve the reduction in type 2 cytokines such as IL-4, IL-10 and IL-13 and activation of IFN producing CD8 cytotoxic lymphocytes. Interestingly, the miRNAs are also differentially regulated by TGFβ signaling in TGFβR2+/+ and TGFβR2−/− myeloid cells, suggesting a feedback loop between TGFβ and miRNA. These results demonstrate that the candidate miRNA can reprogram tumor-associated myeloid cells by altering the cytokine milieu and enhance host antitumor immunity. Our work points out that endogenous miRNA targeting myeloid TGFβ signaling and its molecular network provides an important therapeutic option. Note: This abstract was not presented at the meeting. Citation Format: Suman K. Vodnala. MicroRNA-mediated reprogramming of myeloid cells by targeting TGFβ signaling and its associated molecular network. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3128. doi:10.1158/1538-7445.AM2015-3128
Abstract 3017: Ribonucleotide reductase promotes uracil-mediated genome instability in tumor progression
Authors: Chih-Wei Chen, Ning Tsao, Yun Yen, Christine E. Lehman, Yuh-Hwa Wang, Chian-Feng Chen, Tse-Hsiang Wu, Sui-Chih Tien, Ming-Hsiang Lee, Zee-Fen Chang
Journal: Cancer Research (2015)

Abstract The elevation of RRM2A subunit of ribonucleotide reductase (RNR) has been shown oncogenic and associated with human cancers. However, the molecular mechanism of RRM2A in cancer promotion is unclear. In this study, we investigated whether RNR-mediated dUTP formation is involved in promoting genome instability. Since dUTP is degraded by dUTPase, we analyzed the expression of RRM2A and dUTPase in clinical samples from colorectal and breast cancer patients. The results revealed that high RRM2A and low dUTPase in tumors are correlated with poorer survival. In cancer cell lines that express high level of RRM2A and dUTPase, knockdown of dUTPase increases genome instability. Conversely, overexpression of dUTPase reduces genome stress in cancer cells expressing high RRM2A and low dUTPase. In non-tumorigenic cells, overexpression of RRM2A increases replication stress and genome instability accompanied by higher levels of 53BP1 foci and increased breaks at AT-rich fragile sites bound by 53BP1. Thymidine supplement in growth medium or co-expression of dUTPase was able to reduce RRM2A-mediated replication stress and 53BP1 foci. We further provide evidence that RRM2A promotes replication stress and error prone-translesion synthesis dependent on uracil DNA glycosylase. These results suggest that up-regulation of RRM2A in tumor cells increases uracil-mediated replication stress to promote genome instability. Therefore, high RRM2A/low dUTPase context confers tumor genome evolution advantage, correlating with poorer prognosis. Citation Format: Chih-Wei Chen, Ning Tsao, Yun Yen, Christine E. Lehman, Yuh-Hwa Wang, Chian-Feng Chen, Tse-Hsiang Wu, Sui-Chih Tien, Ming-Hsiang Lee, Zee-Fen Chang. Ribonucleotide reductase promotes uracil-mediated genome instability in tumor progression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3017. doi:10.1158/1538-7445.AM2015-3017
Ad-ISF35 Intratumoral Administration Induces a Bystander Effect and Immune-Mediated Tumor Rejection with a Safe Vector Biodistribution and Toxicology Profile In a NHL Mouse Model.
Authors: Johanna Melo-Cardenas, Mauricio Urquiza, Robier Aguillon-Prada, Thomas J. Kipps, Januario E Castro
Journal: Blood (2010)
Abstract 15472: Impact of the Use of Fractional Flow Reserve (FFR) on the Coronary Revascularization Strategy : Insights from a Large French Multicenter FFR Registry (R3F)
Authors: Eric van Belle, Thomas Cuisset, Gilles Rioufol, Christophe Pouillot, Emmanuel Teiger, Didier Barreau, Michel Hanssen, Loic Belle, Cyril Besnard, Christophe Bretelle, Patrick Dupouy
Journal: Circulation (2010)

Background: Recent data suggest that fractional flow reserve (FFR) is useful in guiding coronary revascularization. There is however currently no large report of its impact on the decision of coron...
Treatment of Patients up to 60 Years with High Risk AML: Final Results of the AML SHG-Hannover 01/99 Trial.
Authors: Jürgen Krauter, Gerhard Heil, Dieter Hoelzer, Oliver G. Ottmann, Hans Martin, Michael Lubbert, Jurgen Finke, Wolfgang F.W. Heit, Walter Fiedler, Lothar Kanz, Gunter Schlimok, Hartmut H. Kirchner, Aruna Raghavachar, Wolfram Brugger, Arnold Ganser
Journal: Blood (2006)
Activity of cabozantinib (XL184) in advanced ovarian cancer patients (pts): Results from a phase II randomized discontinuation trial (RDT).
Authors: R. J. Buckanovich, R. Berger, A. Sella, B. I. Sikic, X. Shen, D. A. Ramies, D. C. Smith, I. B. Vergote
Journal: Journal of Clinical Oncology (2011)

5008 Background: Cabozantinib (Cabo) is an oral, potent inhibitor of MET and VEGFR2. MET over-expression has been observed in advanced ovarian cancer (OC). Anti-VEGF pathway agents have shown clinical benefit in pts w/ OC. Simultaneous targeting of the MET and VEGF signaling pathways with Cabo may therefore be a promising treatment strategy. Methods: Epithelial OC pts with progressive measurable disease (mRECIST) received Cabo at 100 mg qd PO over a 12 wk Lead-in stage. Up to 2 prior regimens are allowed for platinum-resistant (R), and up to 3 prior regimens for platinum-sensitive (S) pts. Tumor response was assessed every 6 wks. Treatment ≥ wk 12 was based on response: pts with PR continued open-label Cabo, pts with SD were randomized to Cabo vs placebo, and pts with PD discontinued. Primary endpoint was ORR per mRECIST in the Lead-in stage, and progression free survival (PFS) in the randomized period. Accrual in any cohort could be halted for either high rates of ORR or PD. Results: Accrual was halted at 68 pts based on an observed high rate of clinical activity. The median number of prior systemic treatments was 2. Most common related AEs ≥Grade 3 were hand-foot syndrome (10%), diarrhea (8%) and fatigue (4%). Dose reductions and permanent discontinuations for AEs occurred in 43% and 10% of pts, respectively. Of 51 pts evaluable for mRECIST RR at 12 wks, 28 are R, 17 are S, and 6 have unknown status. mRECIST RR at 12 wks: overall = 12/51(24%), R = 5/28(18%); S= 5/17(29%). Five additional PRs await confirmation. The overall DCR (PR+SD) at wk 12 is 58% (30/51). After a median f/u of 4 mos (range: 1 to 11 mos), the median duration of response and median PFS have not been reached. CA125 responses (assessed by GCIG criteria) in 40 pts with ≥1 post-baseline result: 7/40 (18%). Median maximum increase in hemoglobin (Hb) in anemic pts (Hb < 11 g/dL) was 1.9 g/dL (N=8 in pts w/ ≥ 6 wk f/u; range, 1.1-3.2 g/dL). All maximum Hb changes occurred w/in the first 12 wks. Randomization in this cohort was halted & pts unblinded due to observed efficacy. Conclusions: Cabo exhibits clinical activity in ovarian cancer pts with advanced disease, regardless of prior platinum status, as reflected by high rates of response.
Severity, Frequency, and Risk Factors for Oral Mucositis after BEAM High-Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation and Preliminary Results with Palifermin Versus Best Supportive Care.
Authors: Eva-Susanne Strobel, Kris Bauchmüller, Gabriele Ihorst, Monika Engelhardt
Journal: Blood (2006)
Attenuation of Apoptosis-Stimulating Protein of p53-2 (ASPP2) Promotes IL-3-Independent Growth and Enhances Cytogenetic Abnormalities after Gamma-Irradiation in Mouse Hematopoietic Cells - Mimicking Early Leukemogenesis of Therapy-Associated Human AML
Authors: Kerstin Maria Kampa-Schittenhelm, Ulrike Mau-Holzmann, Lothar Kanz, Charles Lopez, Marcus M Schittenhelm
Journal: Blood (2015)
Abstract 2846: Ultrasensitive detection of actionable subclones in chronic myeloid leukemia
Authors: Michael W. Schmitt, Bella Aminov, Jerald P. Radich, Lawrence A. Loeb
Journal: Cancer Research (2015)

Abstract Targeted Abl inhibitors such as imatinib have vastly improved survival in chronic myeloid leukemia (CML). However resistance occurs in many patients, most frequently due to point mutations in the Abl kinase. At the time of diagnosis, resistance mutations may already exist in a small fraction of the malignant cells. Second-generation inhibitors have been developed which can overcome specific resistance mutations. Identification of pre-existing resistance mutations would thus have important therapeutic implications, as it could inform which therapy would result in the most durable response in a given patient. Prior searches for pre-existing Abl mutations in CML have used methods such as allele-specific PCR or next-generation DNA sequencing; these methods are prone to background errors resulting in frequent false positive mutations. For example, next-generation sequencing has an error rate of 0.1%-1%, which results in a large number of erroneous mutations that obscure true variants. Enrichment of the Abl gene is also a major limitation. Nearly all prior reports have used PCR amplification for dozens of cycles to enrich the Abl gene prior to mutation detection; this process introduces thousands of PCR errors which make differentiation of true mutations from artifactual mutations challenging. We have developed a protocol for DNA sequencing, Duplex Sequencing, that separately tags and sequences each of the two strands of single DNA molecules. True mutations are present at the same position in both strands and are complementary, while PCR or sequencing errors occur in only one of the strands and are not scored. Duplex Sequencing has a calculated error rate of less than one artifactual mutation per billion nucleotides sequenced. To apply Duplex Sequencing to the Abl oncogene, we established a new, extremely efficient targeted capture approach that utilizes sequential rounds of capture with biotinylated DNA probes. This protocol results in &amp;gt;1,000,000 fold enrichment, with up to 99.8% of reads corresponding to the Abl gene. Duplex Sequencing was carried out at high depth (&amp;gt;100,000 fold), resulting in an average of 2,000 duplex reads per nucleotide position. The estimated accuracy for mutation identification was 99.9999%. We are in the process of sequencing samples from CML at the time of diagnosis and relapse to assay for drug resistance mutations below the limit of detection of conventional assays. Our approach could be extended to any targeted molecular agent for which mutation of the target confers resistance to the drug. Citation Format: Michael W. Schmitt, Bella Aminov, Jerald P. Radich, Lawrence A. Loeb. Ultrasensitive detection of actionable subclones in chronic myeloid leukemia. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2846. doi:10.1158/1538-7445.AM2015-2846
Abstract 613: Copy number variations distinguish lung adenocarcinomas from squamous cell carcinomas
Authors: Kai Song, Guangqiang Zheng, Luc Girard, Ignacio I. Wistuba, Jack A. Roth, Carmen Behrens, Milind B. Suraokar, John D. Minna, Adi F. Gazdar
Journal: Cancer Research (2015)

Abstract Purpose To develop a molecular based classification of non-small cell lung carcinomas based on genome wide copy number variations (CNVs). Background For a number of clinical and biologic reasons, the accurate classification of non small cell lung carcinoma (NSCLC) into adenocarcinoma (ADC) and squamous cell carcinoma (SCC) is essential. DNA based tests, which are not currently used, are more robust when applied to formalin fixed paraffin embedded tissues. Materials and Methods TCGA Dataset: The Cancer Genome Atlas project (TCGA) level 3 CNVs data (Affymetrix Genome-Wide Human SNP Array 6.0) of resected ADC (n = 241) and SCC (n = 210) patients were utilized as a Training set along with 1091 non malignant lung samples. SPORE Patient Dataset: The UT Lung SPORE cohort consists of 248 resected lung cancers (168 ADC and 74 SCC samples) run with the Agilent 244K Human Genome CGH Microarray. Molecular signature identification based on the morphologic subclassification of NSCLC: We used statistical algorithms to identify potential CNV biomarkers and combined them with known amplified oncogenes to identify 28 CNV signature genes that were highly correlated with histological classification. Identification of CNV classifier genes. The CNV signature genes were identified through the following four sequential steps: 1) Paired t-test. 2) Elastic Net. 3) Partial lease squares algorithm. 4) Naive Bayes classifier. Results: The 28 gene CNV signature accurately separated squamous cell carcinomas from adenocarcinomas in the Training and Validation sets as well as distinguished tumors from non-malignant tissues (Table 1). Table 1. The classification results between ADC and SCC DataSensitivitySpecificityAccuracyADC vs SCCTraining set (TCGA)0.940.870.91Validation set (SPORE)0.870.840.86Tumor vs Non-malignantADC0.910.960.94SCC0.970.980.98 Conclusions: A 28 gene CNV signature distinguished lung adenocarcinomas from squamous cell carcinomas with great accuracy (86-91%) and the lung tumor samples can be distinguished from the non-malignant lung samples with an accuracy of 94-98%. Citation Format: Kai Song, Guangqiang Zheng, Luc Girard, Ignacio I. Wistuba, Jack A. Roth, Carmen Behrens, Milind B. Suraokar, John D. Minna, Adi F. Gazdar. Copy number variations distinguish lung adenocarcinomas from squamous cell carcinomas. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 613. doi:10.1158/1538-7445.AM2015-613
Neutralization of Tumor-Derived Soluble Glucocorticoid-Induced TNF-Related Protein (GITR) Ligand Present in Cancer Patient Sera Increases Anti-Tumor Reactivity of NK Cells.
Authors: Katrin M. Baltz, Matthias Krusch, Tina Baessler, Anita Bringmann, Lothar Kanz, Peter Brossart, Helmut R. Salih
Journal: Blood (2007)