tbuckley/cabot-search huggingface dataset:
Incidence and Demographic and Tumor Characteristics of HER2-Positive Invasive Breast Cancer in a Large, Unselected Population, 2000-2006.
Authors: L. Fehrenbacher, L. Habel, A. Capra, A. Anthony, X. Li, C. Quesenberry, R. Fulton
Journal: Cancer Research (2009)

Abstract BACKGROUND: Most HER2 data have been generated from populations of invasive breast cancer (IBC) patients with selected patient and tumor characteristics (clinical trials, referral centers). The average age of women in US adjuvant trastuzumab trials was 49. Pre 2000, clinical trials of adjuvant chemotherapy included 25-40% HER2+ cases. We used an unselected population of women with IBC to estimate the age-specific incidence rates of HER2+ IBC and compare patient and tumor characteristics of HER2+ and HER2- disease.METHODS: Among female members of Kaiser Permanente Northern California (KPNC) 20 years or older (n=1.22 million), we identified all those diagnosed with a new primary IBC in 2000-2006 (n=16,975). During this period, all IBCs were routinely tested for HER2 by KPNC's regional IHC laboratory (center of excellence for HercepTest, CLIA licensed and CAP certified) and those that were IHC 2+ were sent for FISH testing; IHC 3+ or IHC 2+/FISH+ (ratio ≥ 2.0) were considered HER2+. Demographic and tumor characteristics were derived from the KPNC tumor registry. *Complete HER2 testing available for 94% of IBCs.RESULTS: Incidence of HER2+ IBC increased less dramatically with age and peaked 20 years earlier than incidence of all IBC (Table 1). Among those with IBC, the percent that were HER2+ decreased with age. Of all HER2+ IBCs, 69% were ≥50 years old and 42% were ≥60 years old.Incidence of all IBC and incidence of HER2+ diseaseAge GroupPerson-YrsNo. of IBCsIBC rate/100KHER2+ IBCs*%HER2+HER2+IBC rate/100K20-39288153371024.6416424.75.6940-4917402132680154.0049819.728.6250-5915535284354280.2759914.538.5660-699677624280442.2649412.351.0570-796676013318497.002718.740.5980+3666531633445.381429.638.73ALL817729016975207.59216813.626.51 The percent of tumors that were HER2+ increased with stage (local=11%, regional=18%, distant =25%), tumor differentiation (well =2%, moderate =12%, poor=26%, undifferentiated=30%), and generally with size (&amp;lt;0.5cm=17%, 0.5-0.9cm=7%, 1-1.9 cm=10%, 2-4.9 cm=17%, &amp;gt;5 cm=20%). ER- and PR- tumors were more likely to be HER2+ (of all ER- tumors, 29% were HER2+; of all PR- tumors, 25% were HER2+; of all ER+ tumors, 10% were HER2+; of all PR+ tumors, 9% were HER2+). Among all IBC patients, percent of disease that was HER2+ was highest for Asians (20%) and lowest for Caucasians (12%).CONCLUSION: In a large, unselected, population of invasive breast cancer patients, the incidence of HER2+ disease was highest among women aged 60-69 years. Among breast cancer patients, HER2+ disease was highest in Asians. The percent HER2+ was 13.6% for all breast cancer patients in this population based cohort and highest (24.7%) in the 20-39 year age group. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3058.
Morphology of segmented filamentous bacteria and their patterns of contact with the follicle-associated epithelium of the mouse terminal ileum
Authors: Michele Caselli, John Holton, Paola Boldrini, Dino Vaira, Girolamo Calò
Journal: Gut Microbes (2010)

Recent evidence indicates that segmented filamentous bacteria (SFB), "Candidatus Arthromitus", play a unique role in different aspects of the maturation of the immune system, including T cell responses.
NOVEL SINGLE-NUCLEOTIDE POLYMORPHISMS PREDICT THE RISK OF RECURRENCE IN PATIENTS WITH ATRIAL FIBRILLATION UNDERGOING CATHETER ABLATION
Authors: Sanghamitra Mohanty, Prasant Mohanty, Chintan Trivedi, Luigi Di Biase, Pasquale Santangeli, Rong Bai, Carola Gianni, John Burkhardt, G. Gallinghouse, Javier Sanchez, Patrick Hranitzky, Amin Al-Ahmad, Rodney Horton, Andrea Natale
Journal: Journal of the American College of Cardiology (2015)
Modification of tooth development by heat shock protein 60
Authors: Tamas Papp, Angela Polyak, Krisztina Papp, Zoltan Meszar, Roza Zakany, Eva Meszar-Katona, Palne Terdik Tünde, Chang Hwa Ham, Szabolcs Felszeghy
Journal: International Journal of Oral Science (2016)

Although several heat shock proteins have been investigated in relation to tooth development, no available information is available about the spatial and temporal expression pattern of heat shock protein 60 (Hsp 60). To characterize Hsp 60 expression in the structures of the developing tooth germ, we used Western blotting, immunohistochemistry and in situ hybridization. Hsp 60 was present in high amounts in the inner and outer enamel epithelia, enamel knot (EK) and stratum intermedium (SI). Hsp 60 also appeared in odontoblasts beginning in the bell stage. To obtain data on the possible effect of Hsp 60 on isolated lower incisors from mice, we performed in vitro culturing. To investigate the effect of exogenous Hsp 60 on the cell cycle during culturing, we used the 5-bromo-2-deoxyuridine (BrdU) incorporation test on dental cells. Exogenously administered Hsp 60 caused bluntness at the apical part of the 16.5-day-old tooth germs, but it did not influence the proliferation rate of dental cells. We identified the expression of Hsp 60 in the developing tooth germ, which was present in high concentrations in the inner and outer enamel epithelia, EK, SI and odontoblasts. High concentration of exogenous Hsp 60 can cause abnormal morphology of the tooth germ, but it did not influence the proliferation rate of the dental cells. Our results suggest that increased levels of Hsp 60 may cause abnormalities in the morphological development of the tooth germ and support the data on the significance of Hsp during the developmental processes. Increased levels of a protein produced in response to stress cause abnormal tooth development. Similar 'heat shock' proteins, including Hsp 25 and Hsp 27, have previously been implicated in the origin and formation of teeth, but no one had looked at Hsp 60. Tamás Papp from the University of Debrecen, Hungary, and colleagues examined the expression pattern of Hsp 60 in the lower incisors of mice. They found high levels of the protein in tooth germs, in layers inside the enamel organ called the stratum intermedium, ameloblasts and in cells of the outer dental pulp. The authors applied extra amounts of Hsp 60 to the teeth of embryonic mice and observed morphological defects in the precursor cells that eventually form teeth. The findings suggest that Hsp 60 could be involved in dental disease.
EXERCISE RESPONSE OF HFPEF VERSUS HFREF PATIENTS: INSIGHTS ON LEFT ATRIAL FUNCTION AND RIGHT VENTRICULAR TO PULMONARY CIRCULATION COUPLING BY COMBINING CARDIOPULMONARY EXERCISE TESTING WITH STRESS ECHO
Authors: Tadafumi Sugimoto, Francesco Bandera, Greta Generati, Eleonora Alfonzetti, Marta Pellegrino, Vincenzo Tufaro, Marco Guazzi
Journal: Journal of the American College of Cardiology (2016)
Lymphoscintigraphy Revealed Chyloperitoneum After Gastrectomy for Gastric Cancer
Authors: Dae-Weung Kim, Myoung Hyoun Kim, Chang Guhn Kim
Journal: Clinical Nuclear Medicine (2014)

A 74-year-old woman underwent the radical near-total gastrectomy with Billroth II anastomosis and lymph nodes dissection due to the advanced gastric cancer. On the seventh day after gastrectomy, edema on the both legs and abdominal distention were developed. On the lymphoscintigraphy, the abnormal activity in the peritoneal cavity was revealed, and chyloperitoneum was diagnosed, and additional dynamic scans could localize the chyle leakage focus. Localization of chyle leakage focus enabled surgeon to establish the proper operative plan for the injured lymphatics.
Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2
Authors: Dennis J. Slamon, Brian Leyland-Jones, Steven Shak, Hank Fuchs, Virginia Paton, Alex Bajamonde, Thomas Fleming, Wolfgang Eiermann, Janet Wolter, Mark Pegram, Jose Baselga, Larry Norton
Journal: New England Journal of Medicine (2001)

The HER2 gene, which encodes the growth factor receptor HER2, is amplified and HER2 is overexpressed in 25 to 30 percent of breast cancers, increasing the aggressiveness of the tumor.
PTU-122 Autonomic Nervous System Recovery following Oesophageal Intubation is Influenced by Personality Traits &amp; Anxiety
Authors: A D Farmer, S J Coen, M Kano, Q Aziz
Journal: Gut (2013)

<h3>Introduction</h3> Oesophageal intubation activates a complex stress response, mediated in part by the autonomic nervous system (ANS) (1). Measurement of ANS tone at intubation is thus a useful method of assessing the duration of the physiological stress response which may influence any subsequent measurement of oesophageal sensory-motor function. For instance, it is known that both ANS tone and psychological factors such as the personality trait of neuroticism and anxiety levels, influence oesophageal sensitivity to distension (1). However, factors that influence recovery of ANS tone following intubation are incompletely understood. Thus the aim of the study was to evaluate the ANS response to oesophageal intubation and to identify whether personality traits influence its recovery to baseline. <h3>Methods</h3> 50 healthy subjects (25 male, mean age 38.1 years, range 21–59 years) had personality traits, using the validated Big-Five Inventory (BFI), and anxiety levels, using the validated Spielberger State/Trait Anxiety Inventory (STAI). ANS tone was assessed using cardiac vagal tone (CVT) which is a validated measure of brainstem mediated parasympathetic (PNS) efferent tone at baseline (10 minutes) &amp; continuously thereafter in addition to heart rate (HR) and mean arterial blood pressure (MBP) which are mixed measures of PNS and sympathetic tone. Subjects were then intubated with a naso-oesophageal catheter, without the aid of local anaesthetic, and monitored for a further 20 minutes. <h3>Results</h3> All subjects tolerated the study well. The mean BFI neuroticism score (BFI-N) was 2.86 (range 1–5). The mean baseline HR, MBP and CVT was 65 beats per minute (range 48–88), 87 mmHg (range 68–104) and 7.8 (range 2.2–14.1) respectively. As expected, naso-esophageal intubation caused a significant elevation in HR (<i>p</i> &lt; 0.0001) and MBP (<i>p</i> &lt; 0.0001) with associated CVT withdrawal (<i>p</i> = 0.001). The mean recovery time of CVT to baseline was 4.5 minutes (range 1.1 – 14.9). BFI-N, state STAI and trait STAI were positively correlated with recovery time (r = 0.86, <i>p</i> &lt; 0.0001; r = 0.48, <i>p</i> &lt; 0.0001; r = 0.58, <i>p</i> &lt; 0.0001). <h3>Conclusion</h3> Naso-oesophageal intubation results in the withdrawal of PNS tone and an increase in HR and MBP and the speed of recovery to baseline of PNS tone is correlated with neuroticism. Future studies should allow for at least 15 minutes of recovery time after intubation before any physiological assessments are made and consideration should be given to psychological trait measures as these can influence the recovery of stress response to intubation. <h3>Disclosure of Interest</h3> None Declared <h3>Reference</h3> Paine <i>et al.</i> Pain 2011
Increasing expression of connexin 43 in breast cancer cells reduces metastatic potential to bone by down regulation of FAK and Paxillin
Authors: Zhongyong Li, Zhiyi Zhou, Henry J. Donahue
Journal: Cancer Research (2006)

3275  Breast cancer cells commonly metastasize to bone, but the mechanism underlying this osteotropism is not known. Studies from our laboratory suggest that gap junctional intercellular communication (GJIC) and connexin (Cx) expression profile contribute to breast cancer metastatic potential to bone. For instance, breast cancer cells express the gap junction protein Cx32 but not Cx43, whereas normal breast epithelial cells express Cx43, but not Cx32. Furthermore, expressing Cx43 in breast cancer cells reduces their metastatic potential, in vitro and in vivo, and reduces expression of bone related genes, including osteopontin (OPN), osteocalcin (OC) and Cbfa-1, that are upregulated in breast cancer cells. The mechanism by which Cx expression affects metastatic potential is unknown, but may involve the expression of proteins, associated with cancer cell adhesion, invasion and migration, including focal adhesion kinase (FAK), paxillin and CT10 regulator of kinase protein (Crk). To explore this possibility we examined the hypothesis that increasing expression of Cx43 in a breast cancer cell line MDA-MET (MET), reduces cell adhesion, migration, invasion and the expression of protein associated with these processes. Cx43 genes were transfected into MET cells and clones of transfectants (MET/Cx43+) screened by Q-RT-PCR. Four clones of MET/Cx43+, which expressed increased Cx43 mRNA levels, and plasmid control MET/HY were selected for further investigation. MET/Cx43+ mRNA levels increased 240% while Cx26 and OC mRNA levels were decreased 31% and 26%, respectively, relative to control. Cx45, Cx32, OPN and Cbfa-1 mRNA levels did not change significantly. Western blot analysis revealed that protein levels of FAK and paxillin in MET/Cx43+ were decreased 25% and 24%, respectively, relative to control, but there was no change in CrkI or CrkII protein. Quantitative fluorescent dye adhesion assay and Biocoat FluoroBlok Invasion System revealed that MET/Cx43+ adhesion to osteoblastic cells (hFOB 1.19) was reduced 61% and invasiveness was reduced 20%, respectively, relative to control. Cell migration did not change significantly. This study confirms and extends our previous data suggesting that the connexin expression profile and GJIC contribute to the mechanism by which breast cancer cell metastasize to bone. More importantly, these results suggest that Cx43 expression, GJIC, or both, regulate the expression of FAK and paxillin. This in turn regulates the adhesion, migration and invasion of breast cancer cells in vitro. Therefore, increasing expression of Cx43 in breast cancer cells would be expected to decrease their ability to metastasize in vivo.
Abstract 944: Preventive effects of UV radiation and dietary vitamin D on autochthonous murine mammary tumors
Authors: Parastoo Davari, Farzam Gorouhi, Jeffrey E. Green, Ervin H. Epstein
Journal: Cancer Research (2010)

Abstract Epidemiologic studies support an inverse correlation between solar UV radiation and breast cancer incidence and mortality, a matter of some concern in a society being urged to avoid sun exposure. We assessed directly whether UV radiation of skin has any preventive effect on mammary tumor carcinogenesis in the C3(1)SV40 Tag transgenic mouse. Mice fed diets depleted of vitamin D (+ rescue minerals) were treated with 0 [group A] or 350mJ/cm2 UV 3 times a week without [Group B] or with [Group C] topical 7-dehydrocholesterol, the precursor of cutaneous vitamin D3. Control mice were fed an otherwise identical diet but containing normal levels of vitamin D (1,000IU/kg + rescue minerals) [Group D]. We also fed mice a separate diet containing high (20,000IU/kg) [Group E] or normal (1,000IU/kg) [Group F] vitamin D. We examined mice and excised all palpable tumors (“lumpectomies”) every two weeks at ages 16-28 weeks. Blood was collected at the end of the study. Analyses were performed using Krusskal Wallis test, Mann Whitney test, Spearman's test, life table survival analysis, and log rank test. Circulating 25-hydroxyvitamin D3 (25D3) levels in 59 mice, measured in ng/mL [median (interquartile range)] in groups A-F were 3.0(1.0) 34.0(26.3), 26.0(18.0), 28.0(13.0), 121.0(82.5), and 42.0(15.5), respectively (p&amp;lt;0.001). We found no significant correlation among groups between 25D3 levels and tumor number, mean size, or total tumor volume/mouse. Mice fed the vitamin D depleted diet had a tumor burden that was reduced by UV radiation or by addition of dietary vitamin D, and UV-treated mice had a longer tumor free survival than did the D-depleted mice not so treated. By contrast, the high vitamin D diet, despite tripling the circulating 25D3 level, by comparison to the control diet did not influence mammary tumor number or size or tumor free survival. We interpret these data to suggest that although UV can inhibit development of autochthonous murine mammary tumors, the failure of tumor development to correlate strictly with circulating 25OH D3 levels suggests that its effects may be mediated in part by non-obvious pathways and/or that the anti-mammary cancer effects of vitamin D may plateau. 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 944.
A Glucagon-Secreting Alpha-Cell Carcinoma of the Pancreas
Authors: Malcolm H. McGavran, Roger H. Unger, Lillian Recant, Hiram C. Polk, Charles Kilo, Marvin E. Levin
Journal: New England Journal of Medicine (1966)

TUMORS of the islands of Langerhans have been associated with three distinct entities: hyperinsulinism; the nlcerogenie Zollinger – Ellison syndrome; and a syndrome of diarrhea unassociated with gastric hypersecretion. This report documents a fourth type of humoral activity, that of hyperglucagonism, associated with an alpha-cell carcinoma of the pancreatic islets. It is probable that cases of this disorder are at present unrecognized, or classified otherwise. Therefore, the clinical, laboratory and cytologic findings whereby this condition may be identified are set forth.Case ReportA 42-year-old housewife was first seen in February, 1963, because of a bullous and eczematoid dermatitis of . . .
Abstract 3000: MIIP regulates histone H3 phosphorylation at serine 10 and securin degradation during mitosis in colon cancer cells
Authors: Ping Ji, Limei Hu, Wei Zhang
Journal: Cancer Research (2011)

Abstract Chromosome condensation and segregation are highly orchestrated during mitosis. In early mitosis, dramatic structural changes occur to produce metaphase chromosomes, each consisting of a pair of compacted sister chromatids (condensation), At anaphase onset, a signal is produced to disrupt the linkage between sister chromatids (segregation), allowing them to be pulled apart to two daughter cells. Recently, we discovered that the MIIP protein, encoded by the Migration and invasion inhibitory protein gene located on chromosome 1p36, plays a critical role in mitotic transition through negatively regulating APC/CCdc20 activity and stabilizing cyclin B1 in glioma cells. Here we report that MIIP inhibits chromosome condensation and segregation resulting in G2/M arrest and polyploidy cell formation in colon cancer cells. Gain-of-function studies showed that the MIIP expression inhibited colony formation of isogenic HCT116 cells independent of the TP53 and PUMA status. To understand the potential role of MIIP in colon cancer cells, a panel of six colon cancer cell lines (DLD1, SW620, SW480, HCT116, NCI-747 and SW837) was used to elevate MIIP expression by adenovirus expression vector (Ad-MIIP). The G2/M arrest and polyploidy cell formation were observed in all the six cell lines we tested irrespective of the status of microsatellite stability and TP53 mutation. By using double thymidine block strategy, we synchronized HCT116 cells at G1/S boundary and released the cells in fresh medium to enrich the cell population in different stage during the cell cycle. We found that the expression of MIIP is cell cycle dependent and peaks at mitosis. Two major mitotic regulators, cyclin B1 and securin, were induced by MIIP. The cycloheximide (CHX) chase experiments showed that MIIP blocked cyclin B1 and securin degradation, which is consistent with our previous finding that MIIP directly interacted with Cdc20 and inhibited APC/CCdc20 activity. We further found that MIIP inhibited histone H3 phosphorylation at serine 10. Taken together, our studies provide evidence that MIIP plays a critical role in chromosome condensation and segregation in mitosis. Because chromosome 1p36 region is commonly deleted in colon cancer cells, the MIIP gene may represent a novel negative cell cycle regulator that is abnormally altered thus contributing to genomic instability in colon cancer. 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 3000. doi:10.1158/1538-7445.AM2011-3000
Clinical Comparison of End-to-Side and Side-to-Side Portacaval Shunt
Authors: Telfer B. Reynolds, Norah M. Hudson, William P. Mikkelsen, Fred L. Turrill, Allan G. Redeker
Journal: New England Journal of Medicine (1966)

THE portacaval shunt is now widely used in the treatment of portal hypertension in chronic liver disease. Though its effect on longevity remains to be proved it is well established that a portacaval shunt is effective in preventing hemorrhage from esophageal varices. Since Longmire and his colleagues1 showed, in 1958, that a side-to-side portacaval anastomosis was technically feasible, there has been uncertainty whether the side-to-side or the end-to-side procedure was preferable. It has been proposed that the former is superior for the treatment of refractory ascites2 though operative mortality has been high in most of the published reports.3 A good . . .
P580Dose dependent Pitx2 loss of function impairs Zfhx3, Wnt8a and calcium handling; novel links to atrial arrhythmogenesis
Authors: E Lozano-Velasco, F Hernandez-Torres, L Hove-Madsen, J Cinca, A Aranega-Jimenez, D Franco-Jaime
Journal: Cardiovascular Research (2014)

Atrial fibrillation (AF) is the most common cause of arrhythmogenesis in humans yet the genetic cause of AF remains elusive. Recent genome-wide association studies (GWAS) have reported risk variants in four distinct genetic loci (4q25, 1q21, 16q22 and 16q13) which have been associated with AF. Among them, the most significant are 4q25 risk variants, which are located in the vicinity of the PITX2 gene. Given the key developmental role of Pitx2 during cardiogenesis and particularly its role in pulmonary vein deployment, it has been postulated that Pitx2 dysfunction might be the molecular link to AF. Experimental evidences in distinct laboratories, including ours, have demonstrated that Pitx2 loss of function predisposes to atrial arrhythmogenesis. However, the molecular mechanisms driven by Pitx2 in this context remain somehow elusive, proposing either embryonic or mature gene expression defects. In order to get further insights into the molecular mechanisms driven by Pitx2 and their putative relation with novel AF GWAS associated genes, we have generated a new Pitx2 conditional mouse line, by intercrossing Sox2Cre and Pitx2floxed mice. Epiblast deletion of Pitx2 leads to the generation of heterozygous and systemic null Pitx2 null mutants, respectively. As expected, embryonic mortality and cardiac defects were similarly observed in Sox2CrePitx2 null mice as those previously reported for Pitx2 knock-out mice. Molecular analyses of the left atrial appendage in heterozygous Sox2CrePitx2 mice (20-30% reduction in Pitx2 expression) and atrial-specific NppaCrePitx2 null mice (60-70% reduction in Pitx2 expression) demonstrate that AF GWAS associated genes such as Zfhx3, Kcnn3 and Wnt8a are severely impaired while other such as Cav1, Synpo2l or Prrx1 are not. Surprisingly, beta-adrenergic signaling is not altered in these models whereas multiple calcium handling genes such as Serca2a, calsequestrin, phospholamban are severely impaired in atrial-specific NppaCrePitx2 null mice but not in heterozygous Sox2CrePitx2 mice. Functional assessment of calcium handling further underscores these findings. Importantly, neither Zfhx3 nor Wnt8a gain-of-function or loss-of-function experiments impairs Pitx2 expression, suggesting that Pitx2 is upstream of these genes. Furthermore, these data suggest a dose-dependent relation between Pitx2 expression and the susceptibility to display basal or only inducible electrophysiological defects. We are currently studying the hierarchical between Pitx2, AF GWAS associated genes and calcium handling, as well as to putative involvement of post-transcriptional modulators such as microRNAs.