tbuckley/cabot-search huggingface dataset:
Abstract 692: Antitumor activity of novel structure-based chemotherapeutic agent for the intervention of colorectal cancer
Authors: Aruna S. Jaiswal, Sanjeev Banerjee, Harekrushna Panda, Charles D. Bulkin, Tadahide Izumi, Fazlul H. Sarkar, David A. Ostrov, Satya Narayan
Journal: Cancer Research (2010)

Abstract Colorectal cancer is the second most common cause of cancer-related death in both men and women in the Western hemisphere. The success of treatment of colon cancer patients depends on matching the most effective therapeutic regimen with the characteristics of the individual patient. The primary challenge in achieving this goal is the heterogeneity of the disease. In the past 10 years, the overall survival of colon cancer patients has significantly improved with adjuvant trials of drugs; the recurrence rate over 5 years is still high. Thus, there is clearly an urgent need for the development of new chemotherapeutic drugs and strategies. The recent emerging concept to sensitize cancer cells to DNA-alkylating drugs is by inhibiting various proteins in the base excision repair (BER) pathway. We used structure-based molecular docking of DNA polymerase β (Pol-β) and identified a potent small molecular weight inhibitor (SMI), NSC-666715. We determined the specificity of this SMI for Pol-β by using in vitro activities of APE1, Fen1, DNA ligase I, and Pol-β-directed single nucleotide (SN)- and long-patch (LP)-BER. The binding specificity of NSC-666715 with Pol-β was also determined by using fluorescence anisotropy. The effect of NSC-666715 on the cytotoxicity of the DNA-alkylating drug, Temozolomide (TMZ), to colon cancer cells was determined by in vitro clonogenic and in vivo xenograft assays. The reduction in tumor growth was higher in the combination treatment relative to untreated or monotherapy treatment. NSC-666715 showed a high specificity for blocking Pol-β activity. It blocked Pol-β-directed SN- and LP-BER without affecting the activity of APE1, Fen1 and DNA ligase I. Fluorescence anisotropy data suggested that NSC-666715 directly and specifically interacts with Pol-β and interferes with binding to damaged DNA. NSC-666715 drastically induces the sensitivity of TMZ to colon cancer cells both in vitro and in vivo assays. The results further suggest that the disruption of BER by NSC-666715 negates its contribution to drug-resistance and bypasses other resistance factors, such as mismatch repair defects. Our findings provide the “proof-of-concept” for the development of highly specific and thus safer structure-based inhibitors for the prevention of tumor progression and/or treatment of colorectal cancer. Funded by NCI-NIH grants CA-097031 and CA-100247 to S.N. 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 692.
Eosinophil and Neutrophil Derived Mediators in Nasal Washes From Children Treated for Asthma
Authors: Patricia Jorge, Holliday T. Carper, Manuel Soto-Quiros, Lydiana Avila, Deborah D. Murphy, Joshua L. Kennedy, Thomas Platts-Mills, Peter W. Heymann
Journal: Journal of Allergy and Clinical Immunology (2013)
Abstract 3011: MicroRNA expression profiles in benign and aggressive canine mast cell tumors
Authors: Joelle M. Fenger, Tzu-yin Lin, Cristian Taccioli, Stefano Volinia, William C. Kisseberth, Cheryl A. London
Journal: Cancer Research (2010)

Abstract Introduction: MicroRNAs (miRNAs) are small non-coding RNAs (ncRNAs) 18-24 nucleotides in length that regulate gene expression primarily by targeting mRNAs according to the degree of complementarity with their 3’ untranslated region (UTR). MiRNAs are often dysregulated in cancer, suggesting they play a role in tumorigenesis. Canine mast cell tumors (MCT) are a common cutaneous tumor of dogs whose biological behavior varies from relatively benign disease that is cured with surgical excision to aggressive, locally invasive, highly metastatic disease that is poorly responsive even to multimodality therapy. We hypothesize that high grade MCTs possess a unique miRNA expression signature distinct from that found in benign MCTs and that this contributes to their aggressive behavior. In this study, we sought to determine which miRNAs are differentially expressed in benign and aggressive canine MCT. Methods: Total RNA was isolated by the Trizol (Invitrogen) method from 12 biologically low grade (surgical cure) and 12 biologically high grade (patient died from MCT disease). Mature miRNA expression analysis of preamplified cDNA was done using TaqMan Low Density Arrays (TLDAs), interrogating the expression profile of 378 miRNAs, 151 of whose mature sequences are 100% conserved between human and dog (Sanger miRBase release 12). Normalization was performed with the small nuclear RNA U6 and microRNA expression was calculated utilizing the comparative Ct method. Statistical analysis was performed with RealTime Statminer software (Integromics). P-values of &amp;lt;0.05 were considered statistically significant. Results: The expression of specific miRNAs was significantly different in biologically low grade and high grade MCTs. 51 miRNAs were differentially expressed in high grade versus low grade tumors (p&amp;lt;0.05). MiRNAs with known importance in human tumorigenesis, including several members of the miR 17-92 cluster (hsa-miR-17, −18a, −18b) and its paralog, the miR-106b-25 cluster (hsa-miR-106b, −93, −25) were significantly overexpressed in high grade tumors as compared to low grade tumors. Conclusion: Our findings indicate that specific miRNAs contribute to the biologically aggressive canine MCT phenotype. Hierarchical clustering revealed distinct miRNA expression signatures in high grade tumors compared to low grade tumors. Characterization of miRNA expression in canine MCTs will facilitate our understanding the biology of this disease and has the potential to identify diagnostic/prognostic factors and targets for therapeutic intervention. 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 3011.
Vaccinations and the Risk of Relapse in Multiple Sclerosis
Authors: Christian Confavreux, Samy Suissa, Patricia Saddier, Valérie Bourdès, Sandra Vukusic
Journal: New England Journal of Medicine (2001)

There has been some concern that vaccination may precipitate the onset of multiple sclerosis or lead to relapses. Since the recent hepatitis B vaccination program in France, there have been new reports of an increased risk of active multiple sclerosis after vaccination.
ULTRASOUND ACCELERATED THROMBOLYSIS IN PATIENTS WITH ACUTE PULMONARY EMBOLISM: A SYSTEMATIC REVIEW AND PROPORTION META-ANALYSIS
Authors: Ashraf Mostafa, Alexandros Briasoulis, Fayez Siddiqui, Tesfaye Telila, Sidakpal Panaich, Sagar Mallikethi Lepakshi Reddy, Luis Afonso, Cindy Grines
Journal: Journal of the American College of Cardiology (2016)
Evolution of affective and linguistic disambiguation under social eavesdropping pressures
Authors: Kevin B. Clark
Journal: Behavioral and Brain Sciences (2014)

Abstract Contradicting new dual-pathway models of language evolution, cortico-striatal-thalamic circuitry disambiguate uncertainties in affective prosody and propositional linguistic content of language production and comprehension, predictably setting limits on useful complexity of articulate phonic and/or signed speech. Such limits likely evolved to ensure public information is discriminated by intended communicants and safeguarded against the ecological pressures of social eavesdropping within and across phylogenetic boundaries.
Abstract 1680: Characterization of olanzapine glucuronidation: Potential role of the UGT2B10 codon 67 SNP in olanzapine metabolism
Authors: Kathryn K. Erickson, Philip Lazarus
Journal: Cancer Research (2010)

Abstract Olanzapine (OLZ) is an atypical antipsychotic with broad applications for cancer patients including treatment-resistant depression, psychiatric problems such as schizophrenia or bipolar disorder, and chemotherapy-induced nausea and vomiting. The half-life of OLZ varies widely between patients. The purpose of the present study was to determine the relative contribution of various UDP-glucuronosyltransferases (UGTs) that are known to metabolize OLZ and examine the role of functional UGT genetic variants as a potential determinant of OLZ metabolism. OLZ glucuronides were identified by ultra-pressure liquid chromatography (UPLC) and the UGTs exhibiting activity against OLZ were determined using homogenates of UGT-over-expressing HEK293 cell lines. Kinetic analysis was performed for active wild-type and variant UGTs. The clinical and physiological relevance of polymorphic active UGTs was examined by studying OLZ metabolism in 114 human liver microsomes and characterizing their glucuronidation activity via UPLC. One-Way ANOVA using Tukey's family error rate was used for pairwise comparisons between cell lines. Student's 2-sample t-test was used to compare human liver microsome glucuronidation data. UPLC analysis of cell line homogenate samples revealed three distinct glucuronidation products. We found that two UGT enzymes, UGT1A4 and UGT2B10, exhibit glucuronidation activity against OLZ. The enzymatic activity of UGT1A4 codon 24 and codon 48 variants against OLZ was significantly different from wild-type UGT1A4 (both p &amp;lt; 0.05). In addition, the UGT2B1067Tyr variant exhibited no glucuronidation activity against OLZ. Human liver microsomes homozygous for the UGT2B1067Tyr variant exhibited an 82% reduction in glucuronidation activity against OLZ (p&amp;lt;0.05). These data demonstrate the significance of a previously unrecognized UGT (UGT2B10) in OLZ excretion and the potential importance of a functional SNP at codon 67 of the UGT2B10 gene in the wide variability observed in OLZ metabolism between individuals. This could have an important impact on overall patient response/toxicity to OLZ. 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 1680.
Survival of patients with HCV cirrhosis and sustained virologic response is similar to the general population
Authors: Savino Bruno, Vito Di Marco, Massimo Iavarone, Luigi Roffi, Andrea Crosignani, Vincenza Calvaruso, Alessio Aghemo, Giuseppe Cabibbo, Mauro Viganò, Vincenzo Boccaccio, Antonio Craxí, Massimo Colombo, Patrick Maisonneuve
Journal: Journal of Hepatology (2016)
PWE-070 Outcomes following local excision of benign rectal lesions—network MDT results: Abstract PWE-070 Table 1
Authors: A R G Sheel, L Titu, P Skaife, S Slawik, P S Rooney
Journal: Gut (2012)

<h3>Introduction</h3> A regional Small and Early Rectal Cancer (SERC) MDT was established in 2008. In line with NICE guidance, all patients with stage 1 rectal cancer are referred, as well as benign lesions with a high clinical suspicion of malignancy. Historical evidence from St Mark9s has shown that most rectal cancers following Local excision (LE) develop in patients with incomplete adenoma excision. We aimed to establish outcomes of LE for benign lesions in our region, focusing on adequate treatment according to histology, adequacy and type of excision. <h3>Methods</h3> Observational study of the SERC MDT database. <h3>Results</h3> The SERC MDT processed 137 referrals (62 f: 75 m. Median age 77 (range 36–90)). There were 79 cases with benign histology at referral. Of 74 local excision (LE) procedures, 50 were performed for ultimately benign lesions. There was one attempted LE prior to MDT referral (asterisk). The case with incomplete excision of HGD was offered classical surgery. Histopathological examination of margins was not possible in 22 cases due to piecemeal excision. All patients entered an endoscopic surveillance programme. <h3>Conclusion</h3> The majority of the referrals to the SERC MDT are for benign lesions and we would recommend all suspicious lesions are referred in the first instance. Rates of complete excision of benign lesions can be improved. TEMS has a significantly higher complete excision rate compared to EMR. Long-term follow-up of patients with incomplete excision will be of interest. <h3>Competing interests</h3> None declared.
Survey Says Leading Firms Support Mammography
Authors: F. X. Mahaney
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Survey Says Leading Firms Support Mammography Get access Francis X. Mahaney, Jr. Francis X. Mahaney, Jr. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 21, 4 November 1992, Pages 1618–1619, https://doi.org/10.1093/jnci/84.21.1618 Published: 04 November 1992
Post-therapeutic Lymphedema: Scintigraphy Before and After Autologous Lymph Vessel Transplantation
Authors: Mayo Weiss, Ruediger Georg Hans Baumeister, Klaus Hahn
Journal: Clinical Nuclear Medicine (2002)

The function of lymphatic vessel grafts was proved in 12 patients with lymphedema of the upper extremity by visual and semiquantitative evaluation of a preoperative baseline study and scintigraphic follow-up data for a period of 8 years after microsurgical treatment. The transplantation site was an upper extremity. In 11 of 12 patients, lymphatic function improved after autologous lymphatic vessel transplantation compared with preoperative findings. This could be verified by a statistically significant decrease of the transport index (P < 0.01), clear demonstration of lymph nodes, and a less diffuse distribution pattern of the Tc-99m–labeled nanocolloids. In three patients, the vessel graft could be detected by scintigraphy. Lymphoscintigraphy combined with semiquantitative evaluation of lymphatic transport kinetics has been shown to be an easy and reliable method to assess lymphatic function before and after autologous lymph vessel transplantation.
Assessment of Silent Neuronal Injury Following Coronary Angiography and Intervention in Patients with Acute Coronary Syndrome
Authors: Ahmet Çağrı Aykan, Tayyar Gökdeniz, Hüseyin Bektaş, Faruk Boyacı, İlker Gül, Ezgi Kalaycıoğlu, Turhan Turan, Şükrü Çelik
Journal: Journal of the American College of Cardiology (2013)
Conferees Reach Agreement on NCI Budget For FY1992; Major Increase Approved
Authors: D. A. Tisevich
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Conferees Reach Agreement on NCI Budget For FY1992; Major Increase Approved Get access Dorothy A. Tisevich Dorothy A. Tisevich Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 22, 20 November 1991, Page 1610, https://doi.org/10.1093/jnci/83.22.1610 Published: 20 November 1991
Will NIH Patent Bid Cause "Land Rush"?
Authors: S. Jenks
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Will NIH Patent Bid Cause "Land Rush"? Get access Susan Jenks Susan Jenks Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 12, 17 June 1992, Pages 920–921, https://doi.org/10.1093/jnci/84.12.920 Published: 17 June 1992
PMO-186 Complication rates of colonoscopic removal of large colorectal polyps in a district general hospital: a retrospective audit
Authors: A Malik, J Gasem
Journal: Gut (2012)

<h3>Introduction</h3> Colonoscopic removal of large colorectal polyps, sessile or pedunculated, can pose a challenge. Techniques most commonly used are hot snare polypectomy or endoscopic mucosal resection using electrocautery snare. The bigger the size of the polyp greater the skill needed to avoid complications. The potential complications are bleeding and perforation. According to the British Society of Gastroenterology guidelines post polypectomy bleeding requiring transfusion should be &lt;1:100 (for &gt;1 cm polyps) and post polypectomy perforation rate should be &lt;1:500. <h3>Methods</h3> A retrospective audit was taken between the dates of October 2009 to October 2010 and included patients who had large polyps, defined as polyps equal to and &gt;20 mm in size, removed from the colorectal region by various colonoscopists during their routine colonoscopy lists in a district general hospital. The size of the polyp was confirmed from both the colonoscopy and histology report. <h3>Results</h3> In total 64 patients with large colorectal polyps were treated. Majorities were pedunculated (n=49) and the rest were sessile (n=15). In the group of patients who had pedunculated polyp, 29 were male and 20 were female with a mean age of 62.72 years. The average size of the polyp was 26.22 mm (range: 20–50). Snare polypectomy was performed for all pedunculated polyps. The colonoscopists were able to remove the polyp enbloc in 87.7% of patient (n=43) while in the rest polyps were removed piecemeal (n=6). There was no reported perforation or major bleeding requiring blood transfusion. Only 4 (8.1%) patients had minor bleeding which was successfully controlled during the procedure and no further intervention was required. Histologically, pedunculated polyps were 93.9 % villous or tubulvillous (n=46), 4.1% hamartomatous (n=2) and 2% benign leimyoma (n=1). In the group of patient who had sessile polyp, 10 were male while rest were female. There mean age was 71.93 years. The average size of the polyp was 33.67 mm (range: 20–55). Endoscopic mucosal resection was performed in all of them. The polyp was removed enbloc in only three cases (20%) while in rest it was removed piecemeal (n=12). There was no reported perforation or blood loss requiring blood transfusion. Only 1 (6.66%) of the patient had a minor bleeding which was controlled during the procedure. All 15 of sessile polyp were histological either villous or tubulovillous. <h3>Conclusion</h3> The complication rates of colonoscopic removal of large pedunculated and sessile polyps in a district general hospital are very low as evident from the data presented. Hence these procedures when performed by skilled colonoscopists are safe and can save the patient from major surgical procedures. <h3>Competing interests</h3> None declared.
PWE-282 The role of α-fetoprotein in hepatocellular carcinoma surveillance
Authors: S Jenks, S Hey, L Gibson, C Sturgeon, P Hayes, T Bird
Journal: Gut (2012)

<h3>Introduction</h3> The most efficient and cost-effective programme for HCC surveillance is the subject of ongoing debate. Current UK standard practice for HCC surveillance in high risk populations consists of 6 monthly ultrasound (US) and α-fetoprotein (AFP) measurement. However, the most recent international guidelines on HCC surveillance (AASLD) state that US alone is the most appropriate means of HCC surveillance.<sup>1 2</sup> To investigate the relative contributions of US and AFP to HCC surveillance we have performed a retrospective analysis of the records of consecutive cases of newly diagnosed HCC within two patient cohorts. <h3>Methods</h3> We retrospectively reviewed the electronic records of: (1) All 78 patients diagnosed with HCC in NHS Lothian between 1 January 2010 and 30 September 2011. (2) All 46 patients referred to the Scottish Liver Transplant Unit (SLTU) with HCC for liver transplant assessment from 1 January 2010 to 31 August 2011. Demographic details, mode of HCC detection and patient outcomes were recorded. Patients were identified as undergoing HCC surveillance if they were having 6 monthly US and AFP measurements. An elevated AFP was defined as &gt;6 kU/l. <h3>Results</h3> 36% (28/78) of the patients diagnosed with HCC in NHS Lothian were diagnosed through HCC surveillance. Of these 28 patients 39% (11/28) had the suspicion of HCC raised by AFP alone, 32% (9/28) were detected by both AFP and US and only 25% (7/28) were detected by US alone. 1 HCC was detected by CT scan. The overall sensitivity of AFP for detecting HCC in the surveillance group was 71% (20/28). 84% (36/43) of the SLTU cohort were diagnosed through regular HCC surveillance. 33% (12/36) by AFP alone, 25% (9/36) by US alone and 42% (15/36) by both AFP and US. 69% (25/36) had a raised AFP at HCC diagnosis. 76% (19/25) of patients with a raised AFP at diagnosis were offered potentially curative treatment. <h3>Conclusion</h3> In conclusion our data does not support the current AASLD guidelines stating US alone should be used for HCC surveillance. In both patient cohorts over a third of HCC cases detected through surveillance were identified by a rising AFP alone. Our results indicate AFP is therefore an important and effective addition to US. Additional refinement of how AFP levels are interpreted, in particular progressive rises in AFP, may enable increased sensitivity and specificity and further improve the efficacy of HCC surveillance. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Bruix J</b>, Sherman M. <i>Management of Hepatocellular Carcinoma: An Update</i>. 2010. http://www.aasld.org/practiceguidelines/ (accessed Feb 2011). 2. <b>Marrero Jorge A</b>, El-Serag Hashem B. Alpha-fetoprotein should be included in the hepatocellular carcinoma surveillance guidelines of the american association for the study of liver diseases. <i>Hepatology</i> 2011;<b>53</b>:1060–1.
Double-phase Tc-99m Sestamibi Scintimammography To Assess Angiogenesis and P-glycoprotein Expression in Patients With Untreated Breast Cancer
Authors: J H Yoon, H S Bom, H C Song, J H Lee, Y J Jaegal
Journal: Clinical Nuclear Medicine (1999)

This study evaluated the relation of Tc-99m sestamibi (MIBI) uptake and washout in untreated breast cancer with immunohistochemically determined angiogenesis and P-glycoprotein expression. Thirty-one patients with untreated breast cancer were studied prospectively. Tc-99m MIBI scintigraphy and immunohistochemical analyses of angiogenesis and P-glycoprotein expression were used to evaluate surgically removed tumor tissues. Anterior and both lateral planar images were acquired 10 and 180 minutes after intravenous injection of 740 MBq (20 mCi) Tc-99m MIBI. The tumor-to-normal breast ratio (T:N) and washout index (early T:N - late T:N divided by early T:N) were calculated. A significant correlation was found between angiogenesis and T:N at early and late images. Pearson's correlation coefficients and probability values were r = 0.54, P = 0.002 at early images and r = 0.47, P = 0.008 at late images. The T:N of both early and late images were not different among different groups of P-glycoprotein expression (P = 0.367 and P = 0.113, respectively), although the washout index was significantly different among the groups (P = 0.001). A strong correlation was found between the washout index and P-glycoprotein expression (r = 0.67, P < 0.01). Double-phase scintimammography to assess the early tumoral uptake and washout of Tc-99m MIBI can be used as a simple functional test for in vivo imaging of tumoral angiogenesis and P-glycoprotein expression in patients with untreated breast cancer.