tbuckley/cabot-search huggingface dataset:
Surgery followed by concurrent use of uracil-tegafur (UFUR), leucovorin and radiotherapy for patients with locally advanced rectal cancer
Authors: C. H. Hsieh, T. C. Hsu, K. H. Chang, H. H. Hsu, C. K. Liu, S. K. Hung, Y. L. Lai, Y. J. Chen
Journal: Journal of Clinical Oncology (2005)

3739 Background: This prospective, nonrandomized study was conducted to test the efficacy and toxicity of post-operative concurrent chemoradiation therapy (CCRT) using Uracil-Tegafur (UFUR), and leucovorin (LV) for locally advanced rectal cancer patients. Methods: From February 2001 through November 2004, 17 patients with stage II or III rectal cancer (adenocarcinoma) were enrolled in the study. All received curative resection, post-operative CCRT and regular followed up. Combination of oral UFUR 200 - 250 mg/m2/d and leucovorin 45 - 60 mg/d was given 7 days a week during and after RT course. Forty-five Gy of whole pelvis irradiation followed by 14.4 Gy of local boost to tumor bed was delivered in 33 fractions. The end points were disease-free, overall survival and toxicity. Results: Of the 17 patients, seven were male and 10 were female. The median age was 54 year old (ranged from 42 to 86 year old). The median and mean radiation dose were 59.4 Gy and 57.7 Gy, respectively (ranged from 50.4 Gy to 59.4 Gy). During CCRT, there was no treatment-related death. The mean survival was 36 months. The 3-year overall survival and disease-free survival rate were 68.1% and 43.9%, respectively. Four patients (23.5%) developed local failure and 8 (47.0%) patients developed distance metastasis. The 3-year local control and distant metastasis control rate were 68.1% and 49.9%, respectively. The most common side effects were gastro-intestinal toxicities (diarrhea, nausea and vomiting), dermatitis, fatigue, and hematological toxicities (anemia, leukopenia, and thrombocytopenia). No grade 4 toxicity was observed. Three (17.6%) patients suffered from diarrhea greater than grade 2. One (5.9%) patient suffered from grade 3 fatigue and vomiting but tolerable. Skin toxicity was less than grade 3. One (5.9%) patient experienced grade 3 anemia and no grade 3 leukopenia and thrombocytopenia was noted. Conclusions: The post-operative use of oral UFUR, leucovorin during and after RT provides a promising survival and local control rate with acceptable toxicity in patients with locally advanced rectal cancer. A randomized trial of this combination treatment is warranted. No significant financial relationships to disclose.
Endoscopic choledochoenterostomy using a new blunt-ended endoscopic ultrasound-guided access device
Authors: J. Romagnuolo
Journal: Endoscopy (2011)

During wire manipulation in duct access procedures, conventional endoscopic ultrasound (EUS) needles can shear their wire coating ([Fig. 1]), as has been previously well documented in vascular procedures [1] [2] [3], thereby leaving a foreign body in the duct and/or making it difficult to retract the wire into the needle. The needle can also potentially cause trauma to the duct wall.
IMPACT OF TIMING FROM BLOOD SAMPLING TO PHARMACODYNAMIC ASSESSMENT ON MEASURES OF PLATELET REACTIVITY IN PATIENTS TREATED WITH P2Y12 RECEPTOR INHIBITORS
Authors: Fabiana Rollini, Francesco Franchi, Kamaldeep Singh, Jung Rae Cho, Mona Bhatti, Christopher DeGroat, Jenny Hu, Niti Aggarwal, Zeina Alobaidi, Estela Thano, Elisabetta Ferrante, Martin Zenni, Theodore Bass, Dominick Angiolillo
Journal: Journal of the American College of Cardiology (2016)
Abstract 1373: Preclinical activity of axitinib and its associated change of serum biomarkers in nasopharyngeal carcinoma (NPC)
Authors: Edwin Pun Hui, Vivian WY Lui, Connie WC Hui, Cecilia PY Lau, Herbert HF Loong, Cesar SC Wong, Eric CH Wong, Anthony TC Chan
Journal: Cancer Research (2012)

Abstract Background: We have previously demonstrated promising activity of sunitinib, a multi-targeted tyrosine kinase inhibitor (TKI) against vascular endothelial growth factor (VEGF) receptor, platelet-derived growth factor receptor (PDGFR), c-kit and RET, in preclinical models of NPC (Invest New Drugs 2011:1123-31). However, the significant host related toxicity encountered in a phase 2 clinical trial of NPC patients has limited its clinical efficacy (Ann Oncol 2011:1280-7). Axitinib is a highly selective TKI of VEGF receptor 1, 2 and 3. Selectively targeting a single growth factor receptor pathway provides the potential to rationally adjust dosages and combine drugs directed at specific parts of the pathway to minimize toxicity and achieve the optimum therapeutic benefit. Methods: In vitro cytotoxicity of axitinib was evaluated by MTT assay in five NPC cell lines (C666-1, CNE-2, HK1-LMP1, HNE-1, HONE-1-EBV). In vivo activity was tested in two representative NPC xenograft models (CNE-2 and HK1-LMP1). We also studied treatment induced changes in tumor histology, microvessel density (MVD) and murine serum biomarkers. Results: All NPC cell lines tested except C666-1 were sensitive to axitinib with IC50 of 0.8-7 µM and maximum growth inhibition of 45-87%. In vivo, axitinib demonstrated significant tumor growth inhibition (fractional tumor volume reduction of 32-63% for axitinib treated mice versus 0-10% for vehicle control), reduced MVD and induced extensive tumor necrosis with no significant host toxicity in mice. There were significant increases in serum murine-derived VEGF and SDF-1α and decrease of sVEGFR-2 in axitinib treated tumor bearing mice as compared to vehicle treated controls. Conclusion: Axitinib demonstrated potent in vitro and in vivo activity in NPC preclinical models. Host derived serum proteins may serve as potential biomarkers of drug activity. A phase 2 clinical trial of axitinib in NPC is on-going (NCT01249547) to validate these findings in patients. Acknowledgement: supported by a direct grant (2041496) from CUHK. Axitinib was provided by Pfizer Inc. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1373. doi:1538-7445.AM2012-1373
Metabolic Changes in the Embden-Meyerhof Pathway During Development of Rat Hepatoma
Authors: M. Görlich, E. Heise, M. Binder
Journal: JNCI Journal of the National Cancer Institute (1965)

Hepatomas were induced in rats by daily feeding of 10 mg of diethylnitrosamine per kg of body weight. Hepatomas occurred between 95 and 120 days after treatment was begun. During carcinogenesis, alterations in respiration and aerobic and anaerobic glycolysis were studied. Respiration decreased slowly, aerobic glycolysis intermittently increased, and anaerobic glycolysis increased rapidly in the last stages of carcinogenesis. Proteolytic activation of fructose-1,6-diphosphatase (FDPase) and glucose-6-phosphatase (G6Pase) was possible but diminished almost to zero at the end of carcinogenesis. The relations between processes of natural activation in vivo and possible proteolytic activation in vitro are discussed. With deoxyglucose as substrate, the penetration of this sugar into the cells and the relation between its phosphorylation and dephosphorylation were measured. It was found that penetration and effective phosphorylation increased during carcinogenesis. The alterations of the Michaelis-Menten constant (Km) of normal and proteolytic activated FDPase were studied. The relation of increased Km during carcinogenesis to equilibrium between catabolism and anabolism of glucose is discussed.
NEUROPEPTIDE Y AS AN INDICATOR OF SUCCESSFUL REDUCTION OF SYMPATHETIC NERVOUS ACTIVITY AFTER RENAL SYMPATHETIC DENERVATION
Authors: Oliver Doerr, Christoph Liebetrau, Helge Mollmann, Luise Gaede, Christian Troidl, Jens Wiebe, Jedrzej Hoffmann, Sandra Voss, Timm Bauer, Christian Hamm, Holger Nef
Journal: Journal of the American College of Cardiology (2015)
AGE DIFFERENCES IN THE ASSOCIATION BETWEEN GAIT SPEED AND ENDOTHELIAL FUNCTION IN PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION
Authors: Hiroyuki Suzuki, Yasushi Matsuzawa, Masaaki Konishi, Naoki Nakayama, Toshiaki Ebina, Masami Kosuge, Kiyoshi Hibi, Satoshi Umemura, Kazuo Kimura
Journal: Journal of the American College of Cardiology (2015)
PWE-059 Single Dose Endoscopic Thrombin Injection for Acute Variceal Bleeding
Authors: M Smith, M Widlak, N Fisher, S Ishaq
Journal: Gut (2013)

<h3>Introduction</h3> Endoscopic Human Thrombin injection appears a technically simple yet efficacious alternative to cyanoacrylate for gastric varices with fewer complications from studies to date, but data remains limited. We evaluated the outcomes of patients following single thrombin injection treatment for acute bleeding from oesophageal and gastric varices. <h3>Methods</h3> Retrospective review of patients receiving endoscopic human thrombin injection (Tisseel Baxter Intl Inc.) for active bleeding from varices at a UK centre 2011–2012. <h3>Results</h3> 15 patients (67% male, mean age 56 (SD 10)), received human thrombin injection for actively bleeding varices. Mechanism of portal hypertension was alcoholic cirrhosis in 12 patients (80%), extra-hepatic in 3 (20%). Extrahepatic portal hypertension was due to cancer, portal vein thrombosis and splenic vein thrombosis respectively. Mean MELD was 15 (SD 6). Childs grade was A, B, C in 6%, 47% and 47% respectively. Bleeding varices were identified as gastric in 13 patients (87%), oesophageal in 2 (13%). These 2 cases were not amenable to further banding due to band-induced fibrosis. Gastric varices were classified as: GOV1 4 (31%), GOV2 6 (46%), IGV1 3(31%). There were co-existing oesophageal varices in 9 of 13 (69%), of which 3 were banded in addition but not actively bleeding. Mean thrombin dose used was 1125IU (range 500–2000). Immediate haemostasis was achieved in all 15 cases. Propanolol was commenced post endoscopy in 14 (93%) patients and maintained at a mean dose of 80mg/day (SD 35, range 20–160). Median follow up time was 129 days (range 9–753). No patient received TIPSS or liver transplantation. Rebleeding occurred in 3 (20%) patients, at 14, 43 and 299 days respectively. All 3 patients died following rebleeding (2 declined treatment, 1 pre-hospital arrest). There were 7 deaths in total during the study period, the remainder due to liver failure (2), pneumonia (1), metastatic cancer (1). Cumulative survival at 1, 3, 6, 12 months was 73%, 59%, 59%, and 50% respectively. <h3>Conclusion</h3> Single dose thrombin injection in our series appears to be a safe, easily administered and effective endoscopic therapy for acutely bleeding oesophagogastric varices. Mortality however remains high due to their underlying liver disease. <h3>Disclosure of Interest</h3> None Declared.
P234AAV-mediated cardiac transfer of the desmin cDNA ameliorates progression of cardiomyopathy in desmin-deficient mice
Authors: M Heckmann, R Bauer, A Jungmann, KH Strucksberg, R Schroeder, HA Katus, OJ Mueller
Journal: Cardiovascular Research (2014)

Background: Desmin is a type III intermediate filament which plays a central role in maintaining the structural integrity of cardiac and skeletal muscle cells. Mutations in the desmin coding gene are associated with a heterogeneous phenotype involving cardiomyopathies, cardiac conduction disease and myopathy. Desminopathies are most commonly diagnosed in adults in their mid 30s and show a progressive course, with cardiac involvement as the most important factor limiting prognosis. As of today, only symptomatic treatment is available for patients. Similar to patients with distinct defects in the desmin gene, knockout mice develop dilative cardiomyopathy compared to wildtype littermates.
PTU-184 Defining and treating a positive circumferential resection margin in oesophageal and gastro-oesophageal junctional cancer
Authors: J R O'Neill, N Stephens, V Save, H Phillips, H M Kamel, A G Robertson, P J Driscoll, S Paterson-Brown
Journal: Gut (2012)

<h3>Introduction</h3> A positive circumferential resection margin (CRM) has been implicated with poorer prognosis in oesophageal and gastro-oesophageal junctional (OGJ) cancer. The Royal College of Pathologists (RCP) defines a margin as positive if tumour cells are present within 1 mm. In contrast, the College of American Pathologists (CAP) only defines a margin as positive if tumour cells are observed at the margin. The equivalence of the systems is not clear and the impact of adjuvant treatment has not been assessed. <h3>Aims</h3> To compare the prognostic ability of the RCP and CAP systems in a cohort from a single UK centre and to determine if adjuvant radiotherapy offers a survival benefit for CRM positive patients. <h3>Methods</h3> Patients with a “T3” adenocarcinoma or squamous cell carcinoma of the oesophagus or OGJ undergoing potentially curative resection between 1994 and 2010 were identified from a prospective database. Resection specimens were reviewed and the CRM was measured to ± 0.1 mm by a consultant pathologist. Univariate, multivariate and propensity score matching analyses (PSMA) were performed. <h3>Results</h3> A total of 226 patients were included. Cox regression demonstrated patient sex (p=0.009), tumour differentiation (p=0.015), nodal (N) stage (p&lt;0.001) and CRM group (p=0.045) were independently predictive of prognosis. Patients were grouped into CRM of 0 mm (CAP+ve, n=47), CRM &gt;0 mm but &lt;1 mm (RCPCRM, n=83) and CRM ≥1 mm (CRM-ve, n=96). Median survivals (95% CIs) were significantly different across groups (p=0.019) with CAP+ve = 18 months (13.0 to 23.0), RCPCRM = 28 months (18.6 to 37.3) and CRM-ve = 33 months (25.8 to 40.2). A trend for poorer survival was noted for the CAP+ve vs the RCPCRM group (p=0.073) although there was heterogeneity in N stage across groups. PSMA demonstrated no residual survival difference between CAP+ve and RCPCRM groups when other prognostic variables were controlled. Significant selection bias was observed for patients undergoing adjuvant radiotherapy. PSMA was applied to assess the treatment effect. Patients undergoing adjuvant radiotherapy (n=23) showed significantly improved survival when compared to controls (n=23) matched for sex, pre-operative treatment, N stage, histology and differentiation (p=0.04). <h3>Conclusion</h3> The survival difference between CAP+ve and RCPCRM groups could be explained by existing prognostic variables. The CAP and RCP systems therefore appear equivalent in our cohort. In selected patients with a CRM &lt;1 mm, adjuvant radiotherapy may be of benefit and a prospective randomised trial is indicated. <h3>Competing interests</h3> None declared.
Abstract P4-09-17: Case-Matching Study Comparing Outcome of Unilateral and Synchronous Bilateral Breast Cancer
Authors: A Nichol, R Yerushalmi, S Tyldesley, M Lesperance, C Bajdik, C Speers, K Gelmon, I. Olivotto
Journal: Cancer Research (2010)

Abstract Background: Several retrospective studies have demonstrated worse outcomes for patients with synchronous bilateral breast cancer (SBBC) compared to unilateral breast cancer. This study aimed to determine whether SBBC outcomes can be estimated accurately from the characteristics of the higher-risk cancer. Material and Methods: In the province of British Columbia, Canada, women newly diagnosed with invasive breast cancer between 1989 and 2000, without metastatic or inflammatory presentation, were identified: 207 with SBBC (&amp;lt; 2 months apart) and 15,497 with unilateral breast cancer. Their breast cancer-specific survival (BCSS) outcomes were compared. Using 10-year BCSS estimates, the higher-risk cancer of each SBBC was determined. The priority sequence of matching of the prognostic and predictive variables was: positive lymph node number, primary tumor size, age, grade, lymphovascular invasion status, estrogen receptor status, type of local therapy, margin status, treating clinic, diagnosis year and systemic therapy use. A software program was employed on the 15,497-case cohort to select three unilateral cases that matched the maximum number of variables for the higher-risk cancer of each SBBC case, thereby generating a matched 621-case unilateral cohort. Results: At a median follow-up of 10.2 years, the 10-year BCSS was significantly lower for the SBBC cohort, 71% (95%CI 63 — 77) than for the 15,497-case unilateral cohort, 81.1% (95%CI 80.5 — 81.8) (p &amp;lt; 0.001). However, the SBBC cohort had significantly higher median age and stage at presentation. After the matching, there was no significant difference for the eleven variables between the SBBC cohort and the 621-case unilateral cohort. The 10-year BCSS was 71% (95%CI 63-77) for the SBBC cohort and 74% (95%CI 69-77) for the matched 621-case unilateral cohort. Discussion: BCSS was similar between the SBBC cohort and the unilateral cohort matched to the higher-risk SBBC. Therefore, the outcome of women with SBBC is best estimated from their higher-risk cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-09-17.
Intravenously Administered ACTH
Authors: Albert E. Renold, Peter H. Forsham, J. Maisterrena, George W. Thorn
Journal: New England Journal of Medicine (1951)

SAYERS and his co-workers1 demonstrated that large doses of ACTH administered intravenously over one half hour disappeared rapidly from the blood stream in two normal subjects, while giving rise to maximum but transient adrenal cortical stimulation. Gordon2 first drew attention to the fact that the administration of ACTH in a continuous intravenous drip led to sustained adrenal cortical stimulation in human subjects, and he emphasized that relatively small quantities of ACTH were required. This was identical with the experience of Ingle,3 who was able to produce greatly enlarged adrenal cortices in rats given small quantities of ACTH over a number . . .
FRI0549 Sleqol is responsive to changes in health-related quality of life due to treatment in systemic lupus erythematosus
Authors: K. P. Leong, J. C.-W. Tan, B. Y. H. Thong, T. Y. Lian, E. T. Koh, K. O. Kong, W. G. Law, H. H. Chng, G. Y. L. Chan, F. L.-A. Chia, J. W. L. Tan, H. S. Howe
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Various generic quality-of-life QoL (QoL) scales such as MOS 36-Item Short-Form Health Survey (SF-36) and disease-specific ones such as systemic lupus erythematosus QoL (SLEQOL) have been used to study the QoL of lupus patients. Most of the studies are cross-sectional and, consequently, information about the responsiveness of such instruments is scant. <h3>Objectives</h3> We studied the responsiveness of SLEQOL and SF-36 in lupus patient as they receive new drug treatment. <h3>Methods</h3> We selected patients from our prospective SLE registry who were prescribed new medications. We studied the differences in the QoL at study visits just before and just after the introduction of azathioprine, oral cyclophosphamide, intravenous cyclophosphamide, danazol, cyclosporine A, mycophenolate or hydroxychloroquine in an intention-to-treat manner. We collected clinical data and scores from SF-36, SLEQOL, Rheumatology Attitudes Index (RAI), SLE Disease Activity Index (SLEDAI) and revised Systemic Lupus Activity Measure (SLAM-R). <h3>Results</h3> There were 216 SLE patients (with 194 females) with 303 new drug initiations. The mean age was 36.23 ± 11.78 years. The mean age of diagnosis was 27.65 ± 10.34 years. Using SLEQOL, we found that the use of IV cyclophosphamide, mycophenolate and azathioprine is associated with significant improvements in QoL, in contrast to oral cyclophosphamide, cyclosporin A, danazol and hydroxychloroquine. IV cyclophosphamide is associated with improvement in the physical functioning, activities and self-image domains of SLEQOL, mycophenolate in the treatment and self-image domains and azathioprine in the activities and mood domains. SF-36 reflected QoL change with the use of IV cyclophosphamide (general health domain) and mycophenolate (physical functioning and role physical). <h3>Conclusions</h3> SLEQOL is responsive to the changes in QoL of SLE patients as they receive new medications. It distinguishes the differential effects on QoL of the various drugs. Different domains of the SLEQOL and SF-36 improved with the various medications. SLEQOL may be useful as an outcome measure in SLE clinical trials. <h3>Disclosure of Interest</h3> None Declared
Three-Phase Bone Imaging in the Early Diagnosis of Osteochondritis Dissecans of the Patella
Authors: Rakesh Kumar, Shivshankaran Dilip, Ajit K. Padhy, Rajesh Malhotra, Arun Malhotra, Sriram Machineni, Raju Sharma
Journal: Clinical Nuclear Medicine (1998)

A 16-year-old boy had a history of pain in the left knee for 6 months. On examination, mild tenderness was elicited over the left patella. A clinical diagnosis of chondromalacia patellae was made. Results of roentgenograms of both knees and diagnostic arthroscopy were normal. Three-phase bone imaging suggested osteochondritis dissecans of the patella, and the diagnosis was confirmed by MRI. These interesting images highlight the role of three-phase bone scintigraphy in early diagnosis, especially when routine roentgenograms and arthroscopic evaluations fail to delineate the problem.
Valvular Heart Disease and Acquired Type 2A von Willebrand Syndrome
Authors: William B. Hillegass, Nita A. Limdi
Journal: JAMA Cardiology (2016)

Joseph L. Blackshear, MD; Chad W. McRee, MD; Robert E. Safford, MD, PhD; Peter M. Pollak, MD; Mark E. Stark, MD; Colleen S. Thomas, MS; Candido E. Rivera, MD; Ewa M. Wysokinska, MD; Dong Chen, MD, PhD
Abstract P5-05-04: Intraductal delivery of RNAi-based therapeutics to gene targets identified through computational systems modeling
Authors: A Brock, S Krause, H Li, M Kowalski, J Collins, D Ingber
Journal: Cancer Research (2012)

Abstract We utilize a computational systems biology approach to identify gene targets with the potential to serve as targets for therapeutic RNAi. Inferred gene regulatory network models were constructed using whole transcriptome expression profiling for progressive stages of mammary tumorigenesis in FVB C3(1)-SV40Tag mice. These computational models predicted key mediator transcription factors that are critical for hyperplasia and ductal filling in the early stages of disease progression. Putative mediator transcription factors were targeted by RNAi first in a mammary spheroid assay. Based on their ability to restore lumen formation and normal apical-basal polarization to mammary tumor cells, two transcription factors, Hoxa1 and Hoxb13, were selected for validation in vivo. siRNA targeting each of these transcription factors was formulated with lipidoid nanoparticles and delivered to the mammary gland via intraductal injection. Silencing Hoxa1 resulted in a significant reduction in tumor incidence in FVB C3(1)-SV40Tag. This represents a novel strategy to achieve localized silencing of a target gene in the mammary epithelium. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-05-04.