tbuckley/cabot-search huggingface dataset:
Abstract LB-321: Changing the route of immunization determines outcome in immunotherapy of experimental brain tumors: Translation in development
Authors: Anna C. Darabi, Emma Sande'n, Sofia Eberstål, Shorena Janelidze, Edward Visse, Peter Siesjö
Journal: Cancer Research (2010)

Abstract Introduction: Based on our previous experimental result we have performed a clinical trial at the Lund University Hospital, with immunotherapy using IFN transduced autologous tumor cells for intradermal (i.d.) immunizations in adult patients with glioblastoma multiforme. Eight patients have been treated with an increase in overall survival by more than six months as compared to age-matched controls. The trial has shown that the therapy has no side effects and that an immune activation can be detected. Current experimental results show that by changing the route of immunization from i.d. to sub-cutaneous (s.c.) immunization, a substantial increase in survival time of animals is seen. The mechanisms behind this are now under investigation. Experimental Procedures: We are currently investigating the therapeutic efficacy of i.d. or s.c. administerd IFN transduced irradiated tumor cells (N32-IFNγ) against intra cerebral tumors in the rat glioma model (N32) syngeneic with the Fisher 344 rat. The rats are immunized day 1, 15 and day 29 after tumor inoculation. The induction of the immune response is studied by tracing irradiated CFDA-SE stained tumor cells from the immunization site (i.d. or s.c.) to secondary lymphoid organs using immuno-histochemistry. The immune response is studied at different time-points after the first and after the third immunization. Preliminary Results: S.c. immunization with N32-IFNγ cured 53% of the tumor bearing animals compared to i.d. immunization where only 6% of the rats survived for 100 days, when the study was finalized. After the first immunization, tumor cell debris can be traced to inguinal lymph nodes of i.d. immunized animals, but not of s.c. immunized animals. After the third immunization tumor debris is found in inguinal lymph nodes both after i.d. and s.c. immunization. No other secondary lymphoid tissues tested contain tumor debris. Mononuclear phagocytes expressing MHC class II are responsible for engulfing tumor cells at the immunization site of both i.d. and s.c. immunized animals. Cells that strongly express the enzyme cyclooxygenase-2, the rate-limiting enzyme for production of prostaglandine E2, are seen after s.c. immunization but not after i.d. immunization. Further studies are ongoing to reveal possible differences in kinetics and antigen presenting cells. Conclusions: To our knowledge, no systematic comparison has been performed between different immunization routes using whole tumor cells as immunogen. If these results are further confirmed, the route of immunization will be altered from i.d. to s.c. in future clinical trials. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-321.
Optimal Pinhole Techniques for Preoperative Localization with Tc-99m MIBI for Primary Hyperparathyroidism
Authors: I A Ho Shon, P J Roach, E J Bernard, L W Delbridge
Journal: Clinical Nuclear Medicine (2001)

Technetium-99m-labeled 2-methoxyisobutylisonitrile (Tc-99m MIBI) has been used extensively to localize parathyroid adenomas before operation. Imaging techniques vary widely, and the aim of this study was to determine the optimal time of delayed imaging and the value of routine correlative pertechnetate thyroid imaging.In this study, preoperative parathyroid localization was performed using pinhole anterior and oblique images (15 minutes and 2 and 4 hours after injection) with correlative pertechnetate thyroid images. Ninety-seven patients underwent dual- or triple-phase Tc-99m MIBI imaging and correlative pertechnetate thyroid imaging before surgery. Two nuclear medicine physicians blinded to the surgical findings interpreted all available images and various Tc-99m MIBI image combinations at 15 minutes alone; 15 minutes and 2 hours, 15 minutes and 4 hours; and 15 minutes and 2 and 4 hours each with and without correlative pertechnetate thyroid imaging.Ninety parathyroid adenomas were detected in 86 patients. The optimal results were achieved with 15-minute and 2- and 4-hour Tc-99m-MIBI images, with correlative thyroid scans resulting in a sensitivity rate of 88%. Fifteen-minute and 2-hour Tc-99m-MIBI images and correlative thyroid scans and 15-minute and 4-hour Tc-99m MIBI images and correlative thyroid scans produced similar results (sensitivity rate, 86% and 83%, respectively; P = not significant). Compared with all Tc-99m MIBI image combinations alone, the addition of the routine correlative thyroid scan significantly improved sensitivity and also improved reporter confidence in 45% of studies.Of the pinhole techniques compared, 15-minute and 2-hour Tc-99m MIBI images with correlative thyroid scanning may be the preferred imaging protocol, because this yields results similar to imaging for as long as 4 hours after injection in a shorter, more logistically acceptable imaging time.
NK CELLS FROM GLIOMA-BEARING MICE TREATED WITH TEMOZOLOMIDE ARE ENRICHED FOR GENES RELATED TO MULTI-DRUG RESISTANCE AND CHEMOTAXIS
Authors: S. Pellegatta, S. Pessina, G. Cantini, D. Kapetis, E. Cazzato, G. Finocchiaro
Journal: Neuro-Oncology (2014)

BACKGROUND: Chemotherapy can influence the immune response by inducing immunogenic death of tumor cells or modulating tumor microenvironment (Galluzzi et al. 2012). The limitations of chemotherapy and immunotherapy as single therapeutic modalities have generated considerable interest in combinatorial strategies (Zitvogel L et al 2008). Here we focused on understanding the molecular mechanisms directly induced by temozolomide (TMZ), the standard chemotherapeutic agent for glioblastoma, that can activate immune cells. METHODS: We studied the in vivo effects of TMZ on immune cells by treating mice 9 days after intracranial implantation of GL261 gliomas with intraperitoneal injections of TMZ (5 mg/kg) or vehicle (control mice) for 5 days. Mice were sacrificed 20 hours after treatment on days 1 to 5: tumor and peripheral blood were harvested and analyzed by flow cytometry. RESULTS: Trafficking of NK1.1+ CD3- NK cells in blood, but not of CD8+ T cells, and their homing ability into the brain significantly increased in TMZ-treated mice on day 12 after the second administration of TMZ. At this early time point TMZ led to a significant enrichment of CD11b(low) CD27(high) and CD11b(high) CD27(high) subsets. Microarray analysis revealed differentially expressed genes represented in different clusters of which chemotaxis, cell cycle, multidrug resistance and anti-apoptosis were predominantly up-regulated in blood-derived NK cells isolated from TMZ-treated compared to control mice. We focused validation experiments on genes related to multidrug resistance and chemotaxis. Chemotaxis was assayed using the in vitro transwell system confirming that the migration ability of NK cells from treated mice significantly increased by 3-fold compared with controls. Increased expression of three ATP transporter genes was confirmed by real time PCR (2.6-fold higher than controls, P = 0.006). Five days after the end of the treatment we found an enrichment of CD11(high) CD27(low), the most potent effector subset of NK cells (Chiossone et al 2009). In agreement, IFN-gamma production evaluated by flow cytometry and the in vitro cytotoxic activity of NK cells from TMZ-treated mice were higher than that of NK cells from control mice. CONCLUSIONS: Our results support the idea that NK cells can be resistant to chemotherapy (Lowdell 2003; MacDonald HR et al 1995). In particular at early time points TMZ leads to an enrichment of NK cells with migratory function, in the later phase TMZ leads to an increase of NK cells promoting cytotoxic ability. SECONDARY CATEGORY: Preclinical Experimental Therapeutics.
A RANDOMIZED COMPARISON OF TRANSRADIAL CORONARY INTERVENTION USING 6.5-FR SHEATHLESS GUIDE CATHETER VERSUS 6-FR GLIDE SHEATH
Authors: Makoto Saigan, Kazunori Horie, Daisuke Togashi, Masaki Miyasaka, Takashi Matsumoto, Tsuyoshi Isawa, Norio Tada, Mie Sakurai, Taku Honda
Journal: Journal of the American College of Cardiology (2016)
Countercurrent Exchange of Heat in the Dog Kidney
Authors: AsbjöRN RöED, KNUT AUKLAND
Journal: Circulation Research (1969)

The mechanisms of renal heat clearance were studied in anesthetized dogs by recording renal venous and cortical temperatures during step changes of arterial blood temperature induced by infusion of 0.9% saline of room temperature into the renal artery. The venous thermodilution curves were well described by a three-exponential function with average rate constants: k 1 = 10.4 min -1 , k 2 = 2.2 min -1 , and k 3 = 0.59 min -1 , and intercepts at 34%, 44%, and 22%, respectively. The various components were interpreted as follows: The slow component mainly represents heat conduction from inner medullary and perirenal tissue as shown by extrarenal temperature recording and by calculating the heat distribution volume. Local cortical recordings showed that cortex is not a homogeneous compartment, and k 2 reflects an average cortical heat clearance, k 1 is much higher than blood flow per gram of tissue in any kidney region and results from heat exchange between intrarenal arteries and veins. The arteriovenous diffusion of heat explains the higher temperatures observed in the cortex and the renal medulla than in renal venous blood. The arteriovenous thermodilution technique is unsuited for local and total renal blood flow measurements, because of countercurrent diffusion and heat exchange witli perirenal tissue.
866 ALS-2200, A NOVEL ONCE-DAILY NUCLEOTIDE HCV POLYMERASE INHIBITOR, DEMONSTRATED POTENT ANTIVIRAL ACTIVITY IN TREATMENT-NAÏVE PATIENTS WITH COMPENSATED CIRRHOSIS OR GENOTYPE 2–4 CHRONIC HEPATITIS C
Authors: P. Marcellin, S. Popa, A. Streinu-Cercel, N. Boyer, D. Dospinoiu, A. Patat, N. Ghicavii, V. Garg, R.S. Kauffman, M. Koziel, M.J. Tong, S. Chanda, Q. Zhang, C. Westland, L. Beigelman, L.M. Blatt, J. Fry
Journal: Journal of Hepatology (2013)
Abstract 5407: Inhibitory Raf-1 phosphorylations at Ser-43 and Ser-259 are induced in vitamin K1 enhancement of Sorafenib-mediated HCC cell growth inhibition
Authors: Ziqiu Wang, Meifang Wang, Brian I. Carr
Journal: Cancer Research (2010)

Abstract Sorafenib, a multi-kinase inhibitor, is an FDA-approved agent for treatment of human hepatocellular carcinoma (HCC). However, tumor shrinkage is minor. K vitamins can activate protein kinase A (PKA), which in turn can mediate inhibitory Raf phosphorylation. We developed a new strategy to combine naturally occurring K vitamins with Sorafenib to treat HCC, and found that K vitamins were able to enhance the inhibition of HCC cell growth in vitro and in vivo by Sorafenib. To explore the mechanisms involved, we examined the role of Raf-1 kinase, because it has been reported that Sorafenib inhibits tumor cell growth as a direct inhibitor of Raf, whereas vitamin K2 can induce PKA activity, which is a Raf-1 upstream kinase. We found that while lower doses of vitamin K1 (10 μM) or Sorafenib (2.5 μM) alone slightly induced Raf-1 phosphorylation at both Ser-43 and Ser-259 in Hep3B cells, combination vitamin K1 plus Sorafenib treatment resulted in strong Raf-1 phosphorylation at these two Raf-inhibitory serine residues. Raf-1 protein kinase activity assay showed that lower concentrations of vitamin K1 or Sorafenib alone had little, if any effects on Raf-1 activity, combination vitamin K1 plus Sorafenib at the same low concentrations significantly inhibited Raf-1 activity, judged by strong inhibition of MEK, and of ERK phosphorylation, its down stream targets. Since Raf-1 phosphorylation at Ser-43 and Ser-259 can be regulated by either PKA or Akt kinase, we examined the effects of both vitamin K1 and Sorafenib on their phosphorylation. Although both vitamin K1 and Sorafenib alone induced PKA phosphorylation, no synergistic phosphorylation effects on PKA were found using the combination. However, vitamin K1 enhanced Sorafenib-induced Akt phosphorylation, which was associated with enhanced c-Met tyrosine phosphorylation at Tyr-1349, a known phospho-Akt regulator. Our data suggest that enhanced inhibitory Raf-1 phosphorylation at Ser-43 and Ser-259 may play a central role in vitamin K1 plus Sorafenib synergy in inhibiting HCC cell growth. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5407.
Atypical clinical presentation of typical endoscopic finding of Bouveret’s syndrome
Authors: V. Prachayakul, P. Aswakul, U. Kachintorn
Journal: Endoscopy (2011)

Bouveret’s syndrome is a rare but recognizable condition which was first reported by Leon Bouveret in 1896 [1]. This syndrome is a clinical syndrome of gastric outlet obstruction due to gallstone impaction. Cappell et al. characterized the symptoms of Bouveret’s syndrome: patients, usually older than 70 years, presented with abdominal pain (71 %), nausea, and vomiting (87 %), hematemesis (15 %), anorexia (13 %), and weight loss (14 %) [2]. Endoscopic investigation would show a cholecystoduodenal (or, rarely, choledochoduodenal) fistula, which was the complication of gallstone impaction together with adhesion at the gallbladder bed or impairment of vascular supply to the gallbladder wall.
FRI0139 Inflammatory cell infiltrates in the heart of patients with coronary artery disease with and without inflammatory rheumatic disease: a biopsy study.
Authors: J. K. Andersen, I. L. Kvelstad, K. Mikkelsen, I. Oma, T. Veel, S. M. Almdahl, M. H. Liang, T. Ø. Førre, M. W. Fagerland, I. Hollan
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic rheumatic diseases (SRDs) are associated with increased cardiovascular (CV) morbidity due to accelerated atherosclerosis. However, SRDs are also associated with cardiac vasculitis that may contribute to the increased CV risk. In the Feiring Heart Biopsy Study (FHBS) a high occurrence of inflammatory cell infiltrates (ICI) in the aorta of patients with coronary artery disease (CAD) and SRD were found and therefore we wanted to examine if this patient group also had a high occurrence of inflammation in the heart. <h3>Objectives</h3> To examine the occurrence and extent of ICI and small vessel vasculitis in all layers of the right atrium (epicardium, myocardium and endocardium) in patients with CAD with and without SRDs. <h3>Methods</h3> We examined biopsies from the right atrium taken in a standardized way during coronary artery bypass grafting from the edge of the openings for cannulation due to extracorporeal circulation from patients with and without SRD (matched for age, sex and acute coronary syndrome) included in FHBS (Hollan I, 2007). A 3-µm thick section from each paraffin fixed specimen was stained by hematoxylin and eosin and examined by light microscopy in a blinded manner. The number and extent of ICIs in the three layers of the heart wall were semi-quantified. <h3>Results</h3> <h3>Conclusions</h3> In patients with CAD, vasculitis was not observed, but the occurrence of ICIs in the right atrium was high, mostly localized around small vessels. The ICIs occured in the epicardium, and the occurrence and extent of epicardial ICIs was similar in SRD and non-SRD patients. In the myocardium and endocardium, the ICIs occurred in a low frequency, and in the non-SRD group only (but the difference was not statistically significant). In theory, the observed ICIs might be secondary to or independent of cardiovascular disease (CVD), but the inflammation might also contribute to CAD by compromising of the function of epicardial coronary arteries. Interestingly, abnormalities in epicardium (increased mass of epicardial adipose tissue) are related to CV prognosis, and we propose that inflammation in the epicardium might be of particular importance. Our findings do not support the hypothesis that inflammation in the heart including small vessel cardiac vasculitis is more common in SRD than non-SRD patients. However, this possibility cannot be completely ruled out as the number of examined specimens were small, taken from apparently healthy tissue, and the right atrium was the only site sampled. <h3>Disclosure of Interest</h3> None Declared
997 TUMOR RESPONSE EVALUATION ACCORDING TO MRECIST CRITERIA IN PATIENTS WITH HEPATOCELLULAR CARCINOMA TREATED WITH TACE-DRUG ELUTING BEADS
Authors: A.L. Chagas, L. Kikuchi, N.S. Freitas, A.C.B. Santos, R.S.S.M. Alencar, C.M. Tani, A.M. Moreira, M.S. Rocha, L.A.C. D'Albuquerque, F.C. Carnevale, F.J. Carrilho
Journal: Journal of Hepatology (2012)
Cephalexin in Patients with Renal Disease
Authors: Jeanne A. Linquist, Jaleel Y. Siddiqui, Ian M. Smith
Journal: New England Journal of Medicine (1970)

Cephalexin was administered to patients with renal impairment to study kinetics and devise a basis for predictable therapy in uremia. The mean peak serum level of 24 μg milliliter was independent of renal function. Peak levels occurred at 30 minutes after 500 mg orally in normal subjects and were undetectable by four hours. In severe renal failure, peak levels occurred at four to eight hours, and detectable levels for 72 hours. The mean half-life of cephalexin on hemodialysis was 6.3 hours as compared to 30.8 hours without dialysis. A fitted regression line describes the relation between the half-life and creatinine clearance so that if one value is known, the corresponding function may be read and dosage modified individually. The dosage frequency suggested is every 48 to 60 hours with a creatinine clearance of 0–4 ml per minute, every 24 hours for one of 5 to 15 ml per minute and every eight to 12 hours for one of 16 to 30 ml per minute. No modification is necessary at creatinine clearances above 30 ml per minute.
Is faster better? Operative duration in emergent appendicectomy
Authors: R. D'cruz, E. McDermott
Journal: International Journal of Surgery (2015)

Methods A retrospective study of 271 patients who had undergone appendicectomy from 1 January 2013 to 31 December 2013 was conducted. Data that includes time of presentation to Emergency Department, presenting complaint, diagnostic investigations, time of operation, length of hospital stay and complications were collected. These patients were subsequently put into categories based on the duration of appendicectomy i.e.  90 mins.
QUANTITATIVE ASSESSMENT OF VARIOUS HEPATOBILIARY DISEASES WITH Tc-99m-DISIDA.
Authors: A. Susan
Journal: Clinical Nuclear Medicine (1986)

Gilbert, Marsha Eklem, Shakuntala Krishnamurthy, Gerbail T. Krishnamurthy, David A. Lieberman, Emmet B. Keeffe, VA Medical Center and Oregon Health Sciences University, Portland, OR.
Abstract 46: COSMIC: Enhancing the analysis of whole somatic mutant tumor genomes
Authors: Simon A. Forbes, Nidhi Bindal, Chai Yin Kok, Mingming Jia, Kenric Leung, Prasad Gunasekaran, Sally Bamford, Charlotte Cole, Jon Teague, Michael R. Stratton, Peter Campbell, P Andrew Futreal
Journal: Cancer Research (2011)

Abstract COSMIC, the Catalogue Of Somatic Mutations In Cancer (http://www.sanger.ac.uk/cosmic), is a comprehensive web resource for the investigation of somatic mutations in human cancer with data curated and centrally combined from a variety of sources. Currently, point mutation data have been manually curated from the scientific literature on 89 genes, together with full mutation details on a further 57 fusion gene pairs (Release v50, Nov 2010), defined as known cancer genes in the Cancer Gene Census (http://www.sanger.ac.uk/genetics/CGP/Census). Further, in collaboration with the IARC TP53 database, COSMIC now contains the somatic mutation data for the key p53 tumor suppressor gene. Details of many large candidate gene screens, together spanning almost 20,000 genes have also been curated from three sources, the scientific literature, the Cancer Genome Project labs at the Sanger Institute, UK (CGP), and The Cancer Genome Atlas (TCGA) web portal. Finally, COSMIC now presents the results of 48 whole-genome screens, detailing 2689 genomic rearrangements, 1661 coding mutations and 55,440 non-coding mutations. The COSMIC website is designed to allow easy and intuitive browsing of this data, in isolation or various combinations. As the amount and variability of data has increased, the methods of acquiring and interacting with the data have been enhanced. The COSMIC website now provides mining capabilities, with numerous specialization filters, graphically presenting selected data. A more extensive mining tool is the COSMIC Biomart, allowing selection of data using any definitions found in the COSMIC system. With the increasing significance of genomic data in cancer, COSMIC has integrated with the two largest genome browsers, the Ensembl system and the UCSC cancer genomics browser; links are available from and to Ensembl, whilst per-tissue summaries are provided graphically in the UCSC browser. In addition, COSMIC has integrated its own genome browser, a version of ‘Gbrowse’, which provides custom genomic views of the majority of COSMIC data, together with CONAN copy number graphs, within the context of full genome annotations. Looking to the future, much novel global cancer genomics data will soon be made available via the ICGC data coordination centre. COSMIC is well placed to utilize this as a major new source of mutation information, maintaining COSMIC's position as a central resource in human cancer genetics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 46. doi:10.1158/1538-7445.AM2011-46