tbuckley/cabot-search huggingface dataset:
Effect of Resistive Loading on Variational Activity of Breathing
Authors: THOMAS BRACK, AMAL JUBRAN, MARTIN J. TOBIN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

To examine the effect of resistive loading on variational activity of breathing, we studied 18 healthy subjects breathing at rest and with inspiratory resistive loads of 3 and 6 cm H2O/L/s, applied randomly for 1 h each. Compared with resting breathing, a resistive load of 3 cm H2O/L/s decreased the total variational activity of expiratory time (Te) and minute ventilation (V˙ i), whereas a load of 6 cm H2O/L/s increased the total variational activity of inspiratory time (Ti). Compared with the load of 3 cm H2O/L/s, the load of 6 cm H2O/L/s increased total variational activity of tidal volume (Vt), Ti, Te, and V˙ i. Partitioning of the total variational activity revealed that these alterations were due to changes in the random uncorrelated fraction. Compared with rest, both the resistive loads of 3 and 6 cm H2O/L/s increased the number of breath lags displaying significant serial correlations ("short-term memory") of Ti. Compared with rest, the load of 3 cm H2O/L/s increased the autocorrelation coefficient at a lag of one breath for Vt and the load of 6 cm H2O/L/s increased the correlated fraction of variational activity of Vt. Thus, three measures of correlated behavior—autocorrelation coefficient at a lag of 1 breath, "short-term memory," and the correlated fraction of total variational activity— increased with loading. In conclusion, resistive loading changed total variational activity according to the size of the load: the random fraction decreased with the smaller load but increased with the larger load; in contrast, correlated behavior increased with both loads. The different behaviors of random and correlated variability with loading may reflect different physiologic influences on respiratory control.
P4-19-04: Evaluation of Histopathological Parameters in Male Breast Cancer Reveals Differences Compared with Female Breast Cancer.
Authors: C Nilsson, I Johansson, C Ahlin, S Thorstenson, L Bergkvist, R-M Amin, M Holmqvist, I Hedenfalk, M-L Fjällskog
Journal: Cancer Research (2011)

Abstract Purpose: To characterize male breast cancer (MBC) by evaluating established histopathological parameters and their prognostic value. Methods: 197 male patients with invasive breast cancer and available paraffin-embedded tumor tissue were retrospectively assessed. Patient files were reviewed for clinicopathological data. Tumors were re-evaluated for histologic grading on conventional sections. Immunohistochemical (IHC) stainings for estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), silver-enhanced in situ hybridization (SISH), Ki-67, CK5/6 and epidermal growth factor receptor (EGFR) were performed on tissue micro arrays. Data on vital status and cause of death were retrieved from the Cause of Death Registry. Cox proportional regression models were used for uni- and multivariate analyses. Results: ER and PgR positivity was demonstrated in 93 and 78 % of patients, respectively. Nottingham histologic grade III was seen in 41% and HER2 positivity in 11% of all patients. Defining molecular phenotypes using IHC markers revealed luminal (ER+ and/or PgR+, and HER2−) in 83%, luminal/HER2+ (ER+ and/or PgR+, and HER2+) in 11%, basal-like (ER-,PgR-,HER2−,EGFR+ and/or CK5/6 +) in 1%, but no cases of HER2-like or unclassified. Node-positivity (HR 4.6; 95% CI 1.9−11.4), tumor size &amp;gt; 20 mm (HR 2.3; 95% CI 1.1−5.0) and ER-negativity (HR 5.2; 95% CI 1.9−14.2) were significant risk factors for breast cancer death. Grade, HER2 status, Ki-67, or age did not demonstrate independent prognostic information. No difference in breast cancer deaths was demonstrated between luminal and luminal/HER2. Conclusion: Male breast cancer tumors seem to be of grade III more often than female breast cancer, whereas HER2 expression appears equally common. In our study, the most important predictors for breast cancer death in male breast cancer were lymph nodes, tumor size and ER status. The most common molecular phenotype was luminal. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-19-04.
OC-011 Beware the Caecum: Colonoscopic Adverse Events in the English NHS Bowel Cancer Screening Programme
Authors: M D Rutter, C Nickerson, J Patnick, C J Rees, R G Blanks
Journal: Gut (2013)

<h3>Introduction</h3> The NHS bowel cancer screening programme (BCSP) commenced in 2006 and is one of the world’s largest organised screening programmes. Minimising adverse events (AEs) is an essential part of the programme. This study examines colonoscopic AEs and asociated risk factors. <h3>Methods</h3> The study examined the AEs of bleeding, post-procedure pain and perforation on all colonoscopies conducted between Aug 2006 and Jan 2012 within the BCSP. Crude AE rates were reported and logistic regression used to examine the risk of an AE against various explanatory variables, including age, gender, polyp size, morphology, location and therapy device. Detailed analysis was conducted on the subset of single polypectomy procedures. <h3>Results</h3> Data are from 130,831 colonoscopies including 167,208 polypectomies. There were 30,896 single polypectomy procedures. Caecal polyp location (but not the rest of the proximal colon) and increasing polyp size were the two most important factors predicting risk of bleeding, bleeding requiring transfusion, post-procedure pain and perforation. After adjustment for polyp size the RR for bleeding requiring transfusion for caecal diathermy snare polypectomy was 13.5 (95%CI 4.5–40.6) relative to the distal colon. After adjustment for polyp size the RR for perforation occurring during caecal non-pedunculated polypectomy was 7.7 (95%CI 1.3–46.1) relative to the distal colon. The predicted risk of bleeding requiring transfusion for a 50mm caecal polypectomy was as high as 1 in 22. Further analysis applying estimated risks from the single polyp analysis to multiple polypectomies showed that the absolute risk was not additive. <h3>Conclusion</h3> This national study is the largest to focus on polyp-specific risk factors. Uniquely, we have been able to focus on colonoscopies where only one polypectomy was performed, allowing a detailed examination of risk to be undertaken where the characteristics of the polyp causing the AE can be clearly established. We have confirmed that the greatest risk factor for an AE is the size of the polyp. Perhaps more importantly however, for the first time we have demonstrated a substantially and significantly increased risk for both bleeding requiring transfusion and perforation from caecal polyps (but not in other sites in the proximal colon) for a given polyp size, when compared to the distal colon. Endoscopists should take particular care in resecting caecal polyps. Additional polypectomies, adjusted for polyp size and location, carry a much lesser risk and therefore confirm that performing multiple polypectomies during the same procedure maximises benefit whilst incurring a lesser level of harm per polyp resected. <h3>Disclosure of Interest</h3> None Declared
Abstract C58: Heterotetramers of ERBB2 and ERBB3 generate qualitatively distinct signals from heterodimers and provide most of the neuregulin-induced phosphorylation of ERBB2
Authors: Qian Zhang, Eisun Park, Kian Kani, Ralf Landgraf
Journal: Cancer Research (2011)

Abstract The efficient tyrosine phosphorylation of the orphan ERBB2 (HER2) receptor in heterodimer with the kinase-impaired ERBB3 presents a highly potent source of mitogenic signal. However, it is also a conceptual challenge to our established model of dimer-based signal generation through transphosphorylation. Proposed and mutually not exclusive models for ERBB2 phosphorylation in complex with ERBB3 include autophosphorylation in cis after complex formation and allosteric activation of its kinase domain by ERBB3 in trans, phosphorylation of ERBB2 in trans by the low but detectable kinase activity of ERBB3, or phosphorylation of ERBB2 in proxy. Proxy activation refers to phosphorylation between ERBB2 receptors of activated heterodimers in higher order complexes. We previously reported that the ligand-induced activation and growth stimulation through ERBB2/ERBB3 can be efficiently inhibited by an aptamer directed against the extracellular portion of ERBB3. Studies of the exact mode of inhibition now reveal that the aptamer neither acts by interfering with ligand binding nor by suppressing heterodimer formation. Combined biochemical studies and homology models identified the binding site of the aptamer and suggest that it interferes with the transition from activated heterodimers to heterotetramers. This inhibits the proxy activation of ERBB2 and associated MAPK activation while heterodimerization, the phosphorylation of ERBB3, and downstream activation of AKT are largely insensitive to inhibition. The fact that ERBB2 appears to receive most of its tyrosine phosphorylation through a proxy mechanism is consistent with reports of a prevalence of tetramers in the context of EGFR activation. Furthermore, our study demonstrates for the first time that mechanistically definable and dissectible higher order ERBB complexes contribute to signaling in a manner that is qualitatively distinct from the signal that emanates from isolated dimers. This forces us to fundamentally reinterpret approaches to therapeutic intervention that are at present conceptually centered around modulating the formation of dimers but often generate experimental and clinical outcomes that do not readily reconcile with dimer-based models. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C58.
Abstract 838A: Characterization of sphingosine kinase isoenzyme selective inhibitors
Authors: Peng Gao, Yan Zhuang, Charles D. Smith
Journal: Cancer Research (2010)

Abstract Sphingosine kinases (SphKs) play key roles in cell proliferation, migration and inflammation by catalyzing the formation of sphingosine-1-phosphate (S1P). However, the two isoenzymes, SphK1 and SphK2, play only partially overlapping roles in tumor epithelial cells. Our genetic approach (siRNA) revealed that SphK2 knockdown cells had more effects on decreasing cell proliferation and migration than SphK1 knockdown. A novel non-radioactive HPLC method based on florescence was developed to measure the activities of SphK. It revealed the increased SphK1 activity induced by SphK2 knockdown could not rescue the cells from apoptosis. In order to confirm the results from the genetic approach, we developed pharmacological approaches that used SphK isoenzymes selective inhibitors to dissect the functions of SphK isoenzymes. After the structure optimization of the lead compounds identified by high throughput screening, two compounds were identified as SphK inhibitors: 3-(4-Chlorophenyl)adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amide hydrochloride salt - termed ABC294640 and 3-(4-Chlorophenyl)adamantane-1-carboxylic acid [2-(3,4-dihydroxyphenyl)ethyl]amide - termed ABC294735. The inhibition specificities of these compounds were characterized. ABC294640 is a SphK2 selective inhibitor (IC50 60μM), while ABC294735 (IC50SphK1 6μM, IC50SphK2 10μM) and SKI-II (IC50SphK1 2μM, IC50SphK2 1μM) are dual inhibitors in the presence of 10μM sphingosine as substrate. Lineweaver-Burk plots using the data from recombinant SphK1/2 active enzymes and kinase assay kit revealed ABC294640, ABC294735 and SKI-II were SphK competitive inhibitors. A possibly SphK1-selective inhibitor has also been identified by high-throughput screening and is currently being characterized. 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 838A.
Abstract 129: miR-345 is a novel tumor suppressor microRNA in pancreatic cancer
Authors: Sanjeev K. Srivastava, Seema Singh, Arun Bhardwaj, William E. Grizzle, Ajay P. Singh
Journal: Cancer Research (2011)

Abstract Pancreatic cancer is a highly lethal malignancy due to late diagnosis, rapid progression and lack of effective therapies for treatment. In majority of cases, the disease is diagnosed at a stage when it is locally advanced or has already metastasized to distant organs. In that scenario, chemotherapy is considered as an option, but the effects are usually modest due to chemo-resistance. Hence, there is an urgent need to identify novel diagnostic/therapeutic targets for effective management of this malignancy. MicroRNAs (miRNAs) have received significant attention as a new class of non-coding-RNAs engaged in the regulation of gene expression. It is now evident that miRNAs exhibit differential expression in cancer and play important roles in the disease processes. According to recently published studies, a number of miRNAs are differentially expressed in pancreatic cancer, including miR-345, which is among the top aberrantly-expressed genes exhibiting significant downregulation. miR-345 has remained an understudied miRNA with no report on its functional role in pancreatic cancer. Here, we show that miR-345 is differentially-expressed in pancreatic cancer cell lines with relatively more downregulated expression in poorly-differentiated cancer cells. Ectopic overexpression of miR-345 in two poorly-differentiated pancreatic cancer cell lines, Panc1 and MiaPaCa, diminished their growth, clonogenicity, motility and invasion, and enhanced cell-cell interaction. miR-345-overexpressing cells had distinguishable morphological differences and an increased expression of epithelial (E-cadherin) and loss of mesenchymal markers (N-cadherin, vimentin, twist, slug and snail) as compared to the control cells. Furthermore, our data showed that miR-345-overexpressing pancreatic cancer cells were more sensitive to gemcitabine-cytotoxicity as compared to the control cells. Altogether, our findings demonstrate novel tumor suppressive roles of miR-345 in pancreatic cancer and indicate that miR-345 downregulation may be one of the mechanisms underlying the chemo-resistance of pancreatic 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 129. doi:10.1158/1538-7445.AM2011-129
Protective Effect of Inhaled Furosemide on Allergen-Induced Early and Late Asthmatic Reactions
Authors: Sebastiano Bianco, Maria G. Pieroni, Rosa M. Refini, Luigia Rottoli, Piersante Sestini
Journal: New England Journal of Medicine (1989)

The movement of ions and water across the membranes of bronchial cells is part of the control of the bronchial obstructive response to physical stimuli. In a double-blind, randomized, crossover study, we compared the effect of an aerosol of the loop diuretic furosemide with that of a placebo on the early (within 60 minutes) and late (4 to 12 hours) asthmatic responses to a specific inhaled allergen. We studied 11 subjects with mild allergic asthma, who had both early and late asthmatic responses to a specific inhaled allergen in a preliminary challenge. After placebo administration, the maximal changes (mean +/- SE) from base line in the forced expiratory volume in one second (FEV1) and specific airway resistance were, respectively, a decrease of 35 +/- 4 percent and an increase of 288 +/- 56 percent between 0 and 60 minutes after inhalation of the allergen (early response) and a decrease of 35 +/- 5 percent and an increase of 301 +/- 40 percent between 4 and 12 hours (late response). After furosemide administration (4 ml; 10 mg per milliliter), the early response to inhaled allergen was markedly attenuated in all the subjects, and the late response in all but one. The maximal changes in the FEV1 and specific airway resistance were, respectively, a decrease of 11 +/- 2 percent and an increase of 61 +/- 2 percent between 0 and 60 minutes and a decrease of 20 +/- 4 percent and an increase of 178 +/- 25 percent between 4 and 12 hours (P less than 0.05 for all comparisons). No significant differences were seen in the bronchoconstrictor response to inhaled methacholine after furosemide or placebo administration. We conclude that a furosemide-sensitive mechanism in the airways is involved in the pathogenesis of the reactions of patients with allergic asthma. Whether inhaled furosemide might be useful in the treatment of allergic asthma is uncertain and will require further study.
Dual Pathologic Findings on Heat-Denatured Tc-99m Erythrocyte Scintigraphy with Computed Tomographic Correlation
Authors: GABRIELLE A. CEHIC, DYLAN BARTHOLOMEUSZ
Journal: Clinical Nuclear Medicine (2003)

CEHIC, GABRIELLE A. M.B., B.S., F.R.A.C.P.; BARTHOLOMEUSZ, DYLAN M.B., B.S., M.D., F.R.A.C.P. Author Information
Management of Anticoagulation before and after Elective Surgery
Authors: Clive Kearon, Jack Hirsh
Journal: New England Journal of Medicine (1997)

The most common indications for warfarin therapy are atrial fibrillation, the presence of a mechanical heart valve, and venous thromboembolism.1,2 Treatment with warfarin presents a problem if patients with these indications need surgery, because the interruption of anticoagulant therapy increases the risk of thromboembolism. After warfarin therapy is discontinued, it takes several days for its antithrombotic effect to recede, and when it is resumed, several days are needed to reestablish therapeutic anticoagulation.There is no consensus on the appropriate perioperative management of anticoagulation for patients who have been receiving long-term warfarin therapy. Rational decisions about the treatment of such . . .
Senate Holds Hearing on 1992 Cancer Budget
Authors: D. A. Tisevich
Journal: JNCI Journal of the National Cancer Institute (1991)

Senate Holds Hearing on 1992 Cancer Budget 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 8, 17 April 1991, Page 537, https://doi.org/10.1093/jnci/83.8.537-a Published: 17 April 1991
Abstract 345: Prostaglandin receptors differentially regulate prostate cancer growth: A novel treatment target
Authors: Hosea F. Huang, Ping Shu, Thomas F. Murphy, Sherita King, Chris Wright, Mark L. Jordan
Journal: Cancer Research (2010)

Abstract INTRODUCTION AND OBJECTIVE: Prostaglandin E2 (PGE2) acts through a series of distinct prostanoid receptors, EPR 1-4. Since PGE2 is implicated in prostate cancer (CaP) tumorigenesis and metastasis, we hypothesized that EP receptor expression may influence CaP growth. METHODS: 27 consecutive radical prostatectomy specimens were assessed by immunohistochemistry (IHC) for EPR expression and compared with normal human prostate epithelium (NP) from the same specimen as control. As a corollary, the expression of EP receptors in both normal (PrEC, PWR1E and PZ-HPV7) and CaP cells (LNCaP, PC3 and CA-HPV10) were assessed by RT-PCR and Western blot. The functional significance of EPR was assessed by growth of malignant and benign cell lines in vitro after siRNA EPR knockdown. All studies were approved by the local institutional review board (IRB) and all in vitro experiments performed a minimum of 3 times. RESULTS: EP1, EP2, EP3 and EP4 receptors were detected by IHC in all NP clinical specimens. Compared with NP, EP4 and EP2 were over-expressed in 74% (20/27) and 63% (17/27) of CaP specimens, respectively; in contrast, EP3 expression was reduced in 93% (25/27) clinical samples (Figure). EP1 showed no specific differential expression pattern. Western blot showed increased EP4 but reduced EP3 in CaP lines (CA-HPV10, LNCaP and PC3) compared with NP lines; EP2 and EP4 knockdown significantly suppressed whereas EP3 knockdown stimulated in vitro growth of CA-HPV10 vs PZ-HPV7 cells. Expression of Runx 2 and MMP9, (known to contribute to CaP metastatic potential) was also reduced after EP2 and EP4 knockdown in CaP cells. CONCLUSION: We observed EP4 and EP2 over-expression and reduced EP3 expression in 27 consecutive resected CaP specimens and in 6 representative cell lines. These observations were corroborated by the effects of EP4, EP2 and EP3 knockdown on tumor cell growth in vitro. These data suggest that EP receptor subtypes may regulate CaP growth which may represent a novel therapeutic approach. 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 345.
1164 HEMOGLOBINE DECLINE DURING PEGINTERFERON ALFA-2B/RIBAVIRIN TREATMENT IN REAL-LIFE IS ASSOCIATED WITH FAVORABLE SVR RATES IN DIFFICULT-TO-TREAT PATIENTS WITH HCV GENOTYPE 1 INFECTION
Authors: G. Teuber, S. Mauss, D. Hüppe, E. Zehnter, M.P. Manns, T. Dahhan, U. Meyer, T. Witthöft, B. Möller, N. Dikopoulos, J. Brack, B. Stade, M. Bilzer
Journal: Journal of Hepatology (2012)