tbuckley/cabot-search huggingface dataset:
Abstract P2-05-15: Assessment of Notch Signaling Pathway Components as Biomarkers for Triple Negative Breast Cancer: Comparison of Triple Negative Breast Cancer Cell Lines and Human Breast Cancer Samples.
Authors: A Zlobin, R Olsauskas-Kuprys, S Hodge, M O'Toole, C Ersahin, C Osipo
Journal: Cancer Research (2012)

Abstract Background: Treatment options for patients presenting with TNBC are limited, primarily because there is no approved targeted therapy available. Canonical breast cancer targets such as estrogen receptor and HER2/neu proteins are absent in TNBC. Furthermore, there is an urgent need to uncover biomarkers in this disease in light of its costly treatment as compared to non-TNBC treatment and, more importantly, its poor prognosis as evidenced by aggressive tumor metastasis and high patient mortality. While Notch-1 target gene expression has been reported to be linked to various types of malignancies, we propose that since Notch signaling pathway is involved in cancer cell proliferation and survival it could be a likely oncogenic driver and possible target in certain TNBC patients. Methods: Human TNBC cell lines BT-549, MDA-MB-231, and MDA-MB-468 were used to measure endogenous relative mRNA transcript levels of Notch genes and gene targets by means of real time PCR. In addition, the RNA from formalin-fixed, paraffin-embedded specimen from women-diagnosed with TNBC who had undergone breast surgery was also analyzed for comparable gene expression for similar targets following Laser capture micro-dissection. Results: The in vitro results show that mRNA transcripts of Notch-4, Deltex-1, Hes-1 and -Hes5, as well as upstream Notch regulator PEA3 targets IL-8 and MMP-9 were increased in MDA-MB-468 and BT-549 cells as compared to MDA-MB-231 cells (n = 3–5). In the clinical sample specimens, Notch-1, Jagged-1, and Hes-5 genes were up-regulated, while the Notch-4 gene was down-regulated in TNBC patients as compared to normal control specimens from reduction mammoplasty (n = 4). Conclusions: Our data present the heterogeneity of TNBC disease. They also indicate that the Notch signaling pathway is up-regulated in certain TNBC cell lines and human TNBC breast cancer tissue. Lastly, these results suggest that some components of Notch signaling may be viable biomarkers to better predict Notch activity for future therapeutic interventions using Notch inhibitors. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-15.
TCTAP C-156 Successful Percutaneous Coronary Intervention Treatment of Left Main Coronary Artery Malperfusion Due to Type A Acute Aortic Dissection
Authors: Soichiro Enomoto, Toshihiro Tamura, Yoshihisa Nakagawa, Yusuke Yoshikawa
Journal: Journal of the American College of Cardiology (2015)
Abstract 2713: The Pten and p53 tumor suppressors cooperate to constrain the PI3K/mTOR pathway activation.
Authors: Pixu Liu, Hailing Cheng, Lynn Symonds, Erbo Xu, Sauveur-Michel Maira, Emmanuelle di Tomaso, Thomas Roberts, Jean Zhao
Journal: Cancer Research (2013)

Abstract Loss of Pten expression and mutational inactivation of p53 are frequent molecular events in liver cancer associated with advanced disease stage and poor prognosis. The tumor suppressor PTEN is a phosphoinositide phosphatase that antagonizes the class IA PI3K-engaged oncogenic signaling by dephosphorylating PtdIns(3,4,5)P(3); however, the specific roles of class IA PI3K isoforms, p110a and p110b, have not been assessed in genetically engineered mouse models of liver cancer with Pten inactivation. Furthermore, effective treatment strategies for Pten and p53 deficient liver malignancy remain to be defined. In this study, we showed that combined deletion of Pten and p53 in liver led to rapid development of hepatocellular carcinoma and cholangiocellular carcinoma, the two most common types of liver cancer, with complete penetrance. While a single ablation of p110a or p110b markedly reduced the tumor burden, inactivation of both p110a and p110b completely blocked the liver tumorigenesis. Although liver tumors driven by inactivation of Pten and p53 showed a good response to GDC-0941, a pan-PI3K inhibitor, the combined treatment with both GDC-0941 and Rad001, an mTOR inhibitor or single-agent BEZ235, a dual pan-PI3K and mTOR inhibitor, led to marked tumor regression. These studies suggest that Pten and p53 cooperate to constrain the PI3K/mTOR pathway activation and inhibitors targeting both PI3K and mTOR may effectively treat Pten and p53 deficient liver cancers. Citation Format: Pixu Liu, Hailing Cheng, Lynn Symonds, Erbo Xu, Sauveur-Michel Maira, Emmanuelle di Tomaso, Thomas Roberts, Jean Zhao. The Pten and p53 tumor suppressors cooperate to constrain the PI3K/mTOR pathway activation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2713. doi:10.1158/1538-7445.AM2013-2713
Textbook of Radiopharmacy: Theory and Practice
Authors: James A. Ponto
Journal: Clinical Nuclear Medicine (2000)

University of Iowa Hospitals and Clinics, and College of Pharmacy Iowa City, Iowa CLINICAL NUCLEAR MEDICINE publishes in each issue a section of references to articles of interest to its readers taken from the world medical literature. Articles below were selected from listings received through May 11, 2000. Slavic and Oriental language articles have English summaries unless marked with an asterisk after language abbreviation.
CS-29 * A KINOME-WIDE RNAi-SCREEN IN DROSOPHILA GLIA AND HUMAN GBM CELLS REVEALS THAT Stk17A DRIVES NEOPLASTIC GLIAL CELL PROLIFERATION AND INVASION
Authors: R. Read, J. Marquez, C. Mosley
Journal: Neuro-Oncology (2014)

Glioblastomas (GBM), the most common primary malignant brain tumors, are highly proliferative and diffusely invasive, and are incurable with current therapies. Genetic and molecular analyses reveal that GBMs frequently harbor mutations that activate the EGFR receptor tyrosine kinase (EGFR) and Pi-3 kinase (PI3K) signaling pathway, and the ability of these mutations to drive gliomagenesis has been verified in mouse models. Yet, current data indicate that EGFR and PI3K signaling cooperates with as yet unknown factors to drive invasive pathology and therapeutic resistance in GBM. To uncover such factors, we used a multidisciplinary approach and performed as series of genetic screen in both Drosophila melanogaster and mammalian GBM model systems, and sought to isolate novel genes that augment EGFR- and PI3K- dependent neoplasia. Results in Drosophila and GBM cell culture systems indicate that Stk17A, a cytoplasmic serine-threonine kinase, is required for GBM invasion and cell proliferation, and that Stk17A loss sensitizes GBM cells to chemotherapy. In GBMs and in lower grade gliomas, Stk17A is subject to copy-gain and/or amplification and becomes overexpressed, and Stk17A overexpression is significantly associated with poor prognosis in patients. Stk17A copy-gain and overexpression are also significantly associated with mutation of EGFR and PI3K pathway components. Our Drosophila data show that overexpression activates Stk17A signaling, which cooperates with oncogenic EGFR mutations to stimulate increased glial cell proliferation and invasion. Our Drosophila data also suggest that Stk17A function is not required for normal glial development. Together, these data indicate that Stk17A drives gliomagenesis, and that Stk17A may serve as a tumor-cell specific therapeutic target for GBM and other gliomas. Therefore, we are examining the molecular function of Stk17A in GBM in order to determine how Stk17A contributes to tumor pathology.
Epistemic normativity from the reasoner's viewpoint
Authors: Joëlle Proust
Journal: Behavioral and Brain Sciences (2011)

Abstract Elqayam &amp; Evans (E&amp;E) are focused on the normative judgments used by theorists to characterize subjects' performances (e.g. in terms of logic or probability theory). They ignore the fact, however, that subjects themselves have an independent ability to evaluate their own reasoning performance, and that this ability plays a major role in controlling their first-order reasoning tasks.
Abstract 5506: HPV genotyping of 15,307 Brazilian patients using a microarray based platform.
Authors: Monica M. Stiepcich, Ismael D. Silva, Bruno Scarpellini
Journal: Cancer Research (2012)

Abstract Introduction: Human papillomavirus (HPV) is the leading cause of cervical cancer and genital lesions in women and men, representing an important global health problem. There are still few data about the prevalence and HPV co-infection in Brazilian patients. Objective: This study aims to describe type specific distribution and co-infection of HPV in patients of a private health clinic using HPV DNA testing. Material and Methods: From April 2010 to October 2011, 15,307 consecutive patients of a private health institution in Sao Paulo, Brazil, were tested using a DNA-array assay, which detects simultaneously 24 HPV types - 19 high risk (HR) and 5 low risk (LR) types (PapilloCheck®). Results: HPV infection was detected in 39% of 13,770 female and 65% of 1,537 male samples. The most common HR-HPV types in women were HPV16, 51, 53, 68, 56 (7.3; 7.2; 7.1; 7.1 and 6.7%) followed by types 39, 66, 52, 31 and 58 (4.7 to 3.9%), which accounted for approximately 56.2% of all detected HPV types. LR-HPV 42 (8.5%) and 44/45 (8.2%) were the most frequent LR types. In males, HR-HPV 16, 51, 56, 68, 53, 39 and 66 (7.8; 7.3; 5.3; 4.6; 4.4 and 4.2%) accounted for 38,7% of all types; HPV 6 (12,8%) and 42 (8%) were the most frequent LR types. HPV 18 accounted for only 1,8% and 2,3% of HPV DNA-positive women and men. Co-infection was observed in 16.3% of female and 36.4% of male samples. 7.1% of women and 22.8% of men showed co-infection with three or more types of HPV. Overall, 59.8% of women and 44% of men had only HR type-infections. 17,6% of women and 23,7% of men had only LR-HPV infections. Co-infection with HR and LR-HPV was observed in 22,6% of female and 32,3% of male samples. Conclusion: Our findings show a high HPV infection prevalence and a high proportion of co-infections in our population. These data can be useful to plan in a more efficient way screening programs and application of prophylactic HPV vaccines in Brazil. 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 5506. doi:1538-7445.AM2012-5506
Mechanism of Seizures Associated with Breath-Holding Spells
Authors: Ehor W. Gauk, Langford Kidd, John Stobo Prichard
Journal: New England Journal of Medicine (1963)

NICHOLAS Culpeper (1616–1654),1 the arch herbalist of the seventeenth century, probably wrote the earliest word on breath-holding spells:There is a disease ... in Children from Anger or Grief, when the Spirits are much stirred and run from the Heart to the Diaphragms forceably, and hinder or stop the Breath ... but when the passion ceaseth, this Symptom ceaseth.It has long been common knowledge to parents that certain young children when angered or startled will briefly stop breathing. Ordinarily, such episodes are of little or no consequence. Particularly troublesome are the few children who extend this behavior to the . . .
PTH-069 Nurse Telephone Triaged Straight To Test Colonoscopy
Authors: A Thapar, S Rodney, D Haboubi, J Wilson, C Bhan, M Walshe, J Haddow, A Oshowo, H Mukhtar
Journal: Gut (2014)

<h3>Introduction</h3> In 2011 patients referred with suspected colorectal cancer at our institution waited a median of 36 days (IQR28–46) for a treatment plan. This resulted in 61% of colorectal cancerstaking over 31 days to reach a decision to treat. We aimed to reduce the time spent in the diagnostic phase, which was perceived to be the main hold up in the fast track pathway. <h3>Methods</h3> A quality improvement approach was employed to change the new pathway from the existing clinic-first service to a straight-to-test service. The new nurse-led telephone triage service confirmed symptoms and assessed fitness for colonoscopy, with higher-risk patients defaulting to flexible sigmoidoscopy or clinic. Results for the first year of the new service are presented. <h3>Results</h3> 438 patients were referred between 1/10/2012 and 1/10/2013. 222 (50%) went straight to colonoscopy and 136 (31%) to flexible sigmoidoscopy, 46 (11%) went to clinic, 32(7%) patients did not attend and data was missing for 2(1%) patients. Final diagnoses are shown in the attached figure. Colorectal cancer was found in 14/358 patients (4%). Median time from receipt of referral to first endoscopy was 13 days (IQR 11–20), with 128/348 patients (29%) waiting more than 14 days. Median time to decision to treat colorectal cancer was 25 days (IQR 20–34) in straight to test patients, a significant reduction compared to 2010–2011 (p = 0.01), with 5/14 (36%) waiting more than 31 days. Median time to first oncological treatment was 40 days (IQR 28–44), with 1/14 (7%) waiting more than 62 days. 41/66 (62%) of patients with a normal colonoscopy were discharged directly from endoscopy back to their GP. <h3>Conclusion</h3> The new straight to test service was applicable to the majority of new colorectal fast track patients and a high patient uptake was observed. Colorectal cancer was in fact uncommon, which is being fed back to those referring into the system. Physical colorectal clinic appointments were saved in four-fifths of new patients and in two-thirds of those with a normal colonoscopy, which could be allocated to newly diagnosed cancers, or those requiring treatment for benign conditions. The straight to endoscopy service resulted in an average reduction of 11 days in making a treatment plan for new colorectal cancers. This contributed towards a low rate of breaches of the 62 day treatment target. However one-third of new cancer patients still waited over a month for a decision to treat, highlighting the extra time required for ancillary investigations and MDT discussion. These can be addressed by triggering staging investigations and MDT discussion at the time of endoscopy. <h3>Disclosure of Interest</h3> None Declared.
NO EVIDENCE TO SUPPORT THE EXISTENCE OF A SMOKER’S PARADOX IN ACUTE ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION MANAGED BY PRIMARY PERCUTANEOUS CORONARY INTERVENTION
Authors: Lloyd Steele, Amelia Lloyd, James Fotheringham, Ayyaz Sultan, Javaid Iqbal, Ever Grech
Journal: Journal of the American College of Cardiology (2015)
Abstract 4967: Array-based genomic resequencing of acute myeloid leukemia
Authors: Yoshihiro Yamashita, Toshihide Ueno, Manabu Soda, Hiroyuki Mano
Journal: Cancer Research (2011)

Abstract Somatic mutations within cancer-related genes play a central role in the pathogenesis of many human malignancies, as clearly demonstrated for the cases with mutated RAS and EGFR. Although a new generation of sequencing technologies is now available, whole-genome resequencing of many samples remains a demanding task. DNA microarray-based sequencing is suitable for analysis of multiple samples. However, currently available platforms are limited in the number of nucleotides that each array is able to probe. To overcome such limitations, we have now developed extra-large DNA arrays (“wafers”) for resequencing the human genome, in a collaborative study with Perlegen Sciences, Inc. With its capacity to assay ∼9 Mbp, we could place, on the array, oligonucleotides to interrogate sequence alterations at protein-coding exons and exon-intron boundaries for 5648 human genes that are possibly involved in malignant transformation mechanism. To identify transforming mutations in acute myeloid leukemia (AML), hybridization of genomic DNA from CD34-positive blasts of AML (n = 19) or myeloproliferative disorder (MPD) (n = 1) to the arrays revealed a total of 9148 nonsynonymous nucleotide changes on 3403 independent genes in this cohort (Phase I). To discriminate somatic changes from germ-line polymorphisms, we developed a second array for a direct analysis of the 9148 nucleotide changes, which was hybridized with genomic DNA from the leukemic blasts as well as with that from CD4-positive T cell fractions (paired controls) from the same cohort (Phase II). Analysis of CD4-positive fractions revealed that most of these nucleotide changes in Phase I were also present in the paired control genome, leaving only 11 somatic, nonsynonymous mutations among 11 genes. One of these somatic changes results in a Met-to-Ile substitution at amino-acid position 511 of Janus kinase 3 (JAK3), and the JAK3(M511I) protein exhibited transforming potential both in vitro and in vivo. Further screening for JAK3 mutations showed novel and known transforming changes in 9 out of 286 cases with leukemia. Our experiments also showed a somatic change responsible for the Arg-to-His substitution at amino-acid position 882 of DNA methyltransferase 3A, which results in a loss of &amp;gt;50% of the catalytic activity. Our data have thus revealed a unique profile of gene mutations in human leukemias. Given that only a small number of sequence alterations were proved to be “somatic” after Phase II selection, it would be important to use appropriate paired control samples in the search for somatic mutations in the cancer genome. 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 4967. doi:10.1158/1538-7445.AM2011-4967
Improve the diagnosis of biliary cancers by fluorescent in situ hybridization in brush samples
Authors: Wu Xi, Zeng Xuan, Yang Aiming, Yao Fang, Guo Tao, Lu Xinghua
Journal: Endoscopy (2011)

Aim: We investigated the diagnostic value of Fluorescent in situ hybridization (FISH) (UroVysion kit) for the bile duct carcinoma in brush samples, comparing to the clinical methods such as ERC and IDUS.
Abstract 5481: Mitochondrial DNA copy number and lung cancer risk among Chinese female non-smokers
Authors: Lina Mu, Matthew Bonner, Alyssa Irla, Jiahe Jin, James Olson, Corie Ellison, Zuo-feng Zhang
Journal: Cancer Research (2012)

Abstract Objectives It has been speculated that mitochondrial DNA copy number is involved in carcinogenesis of several cancers. The purpose of this pilot study was to explore the role of mitochondrial DNA copy number in the development of lung cancer among Chinese female non-smoker. Methods A subset of lung cancer cases (N=95) and healthy controls (N=96) were randomly selected from an original lung cancer case-control study conducted in Taiyuan City, China. mtDNA content was determined with Quantitative Real-time Polymerase Chain Reaction (qRT-PCR). Cases and controls were blindly assayed consecutively. Each sample was done in triplicate. Unconditional logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals after adjusting for age, education level and annual personal income. Spearman correlation coefficient was applied to determine correlation between mtDNA copy number and age or indoor air pollution index. Results Lung cancer cases had a significantly lower median mtDNA copy number of 4.5 as opposed to 7.2 in the controls (p&amp;lt;0.0001). There was an inverse relationship seen between mtDNA copy number and risk of lung cancer. Risk of lung cancer decreased in a dose-response manner with mtDNA copy number (Ptrend=0.0409) in the crude analysis. Those women in the highest quartile of mtDNA have a seventy percent lower risk of lung cancer as opposed to those women in the lowest quartile (aOR=0.3, 95%CI: 0.1-0.7). A significant negative correlation was observed between mtDNA copy number and indoor air pollution index which was developed based on individual's exposure to passive smoking, solid fuel use for heating and cooking, frequency of opening windows and exhaust hood use in the kitchen (p=0.0026). There was not a significant correlation between mtDNA copy number and age (p=0.6672), however a significant inverse relationship seen between mtDNA copy number and risk of lung cancer in those women over the age of 57.1. Conclusion Although the exploratory study showed that mtDNA copy number was negatively associated with indoor air pollution exposure and risk of lung cancer, the small sample size of the study and random selection of the subset from original study has limited the power and generalization of pilot study. Further large sample size studies are needed to verify the findings. 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 5481. doi:1538-7445.AM2012-5481
P55 HCV quasispecies analysis of patients with genotype 3 HCV who relapse suggest two different mechanisms of relapse
Authors: J. Waters, D. Shoeb, G. R. Foster
Journal: Gut (2011)

<h3>Introduction</h3> Patients persistently infected with genotype 3 HCV are more likely to have a sustained viral response (SVR) to interferon and ribavirin therapy than patients infected with genotype 1. However many patients with advanced fibrosis infected with genotype 3 HCV relapse following therapy. The mechanisms underlying relapse are not known. <h3>Aim</h3> To examine the speed of relapse and compare quasispecies prior to and immediately following relapse. <h3>Method</h3> 30 chronically infected patients with advanced fibrosis (fibrosis score &gt;F3/6) were treated for 24–48 weeks with Peg IFN α 2a and ribavirin. Plasma samples were taken pre-treatment, during treatment and weekly post treatment. The HCV quasispecies in the pre-treatment sample and the first HCV-RNA positive post-treatment samples of the relapsed patients were assessed. <h3>Results</h3> All of the patients responded with loss of virus on treatment. 18 had a sustained viral response and 12 patients relapsed post-treatment. All of the patients that relapsed did so within 4–6 weeks of treatment cessation. HCV-RNA was extracted from the pre- and post samples of relapsed patients. 10–15 clones from both samples were successfully prepared and sequenced over the E2 region, including the HVR1, 2 and 3 regions and the PKR-eIF2α region in five patients. Construction of phylogenetic trees showed that in two patients the quasispecies that emerged post-treatment were similar to those seen pre-treatment but in three patients a dramatic shift in populations occurred. <h3>Conclusion</h3> Relapse post therapy is very rapid and two distinct patterns of relapse were seen. These data suggest that there may be different mechanisms of relapse following treatment withdrawal in patients with genotype 3 HCV.