tbuckley/cabot-search huggingface dataset:
Tumor Marker Usage and Medical Care Costs Among Older Early-Stage Breast Cancer Survivors
Authors: Scott D. Ramsey, N. Lynn Henry, Julie R. Gralow, Dana K. Mirick, William Barlow, Ruth Etzioni, David Mummy, Rahber Thariani, David L. Veenstra
Journal: Journal of Clinical Oncology (2014)

Although American Society of Clinical Oncology guidelines discourage the use of tumor marker assessment for routine surveillance in nonmetastatic breast cancer, their use in practice is uncertain. Our objective was to determine use of tumor marker tests such as carcinoembryonic antigen and CA 15-3/CA 27.29 and associated Medicare costs in early-stage breast cancer survivors.By using Surveillance, Epidemiology, and End Results-Medicare records for patients diagnosed with early-stage breast cancer between 2001 and 2007, tumor marker usage within 2 years after diagnosis was identified by billing codes. Logistic regression models were used to identify clinical and demographic factors associated with use of tumor markers. To determine impact on costs of care, we used multivariable regression, controlling for other factors known to influence total medical costs.We identified 39,650 eligible patients. Of these, 16,653 (42%) received at least one tumor marker assessment, averaging 5.7 tests over 2 years, with rates of use per person increasing over time. Factors significantly associated with use included age at diagnosis, diagnosis year, stage at diagnosis, race/ethnicity, geographic region, and urban/rural status. Rates of advanced imaging, but not biopsies, were significantly higher in the assessment group. Medical costs for patients who received at least one test were approximately 29% greater than costs for those who did not, adjusting for other factors.Breast cancer tumor markers are frequently used among women with early-stage disease and are associated with an increase in both diagnostic procedures and total cost of care. A better understanding of factors driving the use of and the potential benefits and harms of surveillance-based tumor marker testing is needed.
Epigenetic silencing of MAL, a putative tumor suppressor gene, can contribute to human epithelium cell carcinoma
Authors: Wei Cao, Zhi-yuan Zhang, Qin Xu, Qiang Sun, Ming Yan, Jun Zhang, Ping Zhang, Ze-guang Han, Wan-tao Chen
Journal: Molecular Cancer (2010)

Abstract Background To identify new and useful candidate biomarkers in head and neck squamous cell carcinoma (HNSCC), we performed a genome-wide survey and found that Myelin and lymphocyte-associated protein (MAL) was a gene that was markedly down-regulated in HNSCC. Hence, we investigated the mechanism of MAL silencing and the effects of MAL on the proliferation, invasion, and apoptotic potential in HNSCC. Results MAL was significantly down-regulated in 91.7% of HNSCC specimens at the mRNA level as compared with adjacent normal tissues ( P = 0.0004). Moreover, the relative transcript levels of the MAL gene were remarkably decreased by five-fold in nine HNSCC cell lines as compared with normal head and neck epithelium cells. MAL gene expression was restored in 44%, 67%, and 89% in HNSCC cell lines treated with TSA, 5-Aza-dC, and TSA plus 5-Aza-dC, respectively. Furthermore, bisulfate-treated DNA sequencing demonstrated that the two CpG islands (that is, M 1 and M 2 ) located in MAL promoter region were completely methylated in the HNSCC cell lines (CpG methylated ratio was more than 90%), and only one CpG island (that is, M 1 ) was partially methylated in HNSCC tissues (CpG methylated ratio between 20% and 90%). A significant reduction in cell proliferation and a change in the cell cycle profile were also observed in MAL transfectants. Matrigel assay demonstrated that the invasiveness of HNSCC cells significantly decreased. A significant increase in the population of apoptotic cells was observed in MAL transfected cells. The exogenous expression of the MAL gene suppressed malignant phenotypes, while the cell death induced by MAL gene transfer was a result of apoptosis as demonstrated by the induction of cleavage of the poly (that is, ADP-ribose) polymerase. Additionally, tumor growth was suppressed in cells expressing MAL as compared with cells not expressing MAL . Conclusion Our data suggest that the epigenetic inactivation of MAL , as a candidate tumor suppressor gene, can contribute to human epithelial cell carcinoma and may be served as a biomarker in HNSCC.
Activation of proteolysis by calpains and structural changes in human paroxysmal and persistent atrial fibrillation
Authors: B Brundel
Journal: Cardiovascular Research (2002)

Objective: Atrial fibrillation (AF) is accompanied by electrical, structural and ion-channel protein remodeling. We tested if proteolysis by calpain and proteasome is activated during AF, and studied the relation with the remodeling processes. Methods: Right atrial appendages were obtained from patients with paroxysmal (n=7) or persistent (n=10) lone AF and compared to controls (n=10) in sinus rhythm undergoing coronary artery bypass grafting (CABG). Proteolysis was measured using Suc-Leu-Leu-Val-Tyr-7-amino-4-methyl-coumarin. Protein expression of calpain I and II was assessed by Western-blot and calpain I localization by immunohistochemistry. Structural changes were quantified by counting atrial myocytes with contraction bands or hibernation. Results: Calpain activity was significantly increased in paroxysmal AF (2-fold, P<0.001) and persistent AF (3-fold, P<0.001), mainly due to calpain I activation. Increased calpain I protein expression was found in AF with Western blot and immunohistochemistry. Myocytes from all AF groups showed increased contraction bands, whereas hibernation was only found in persistent AF. Calpain activity correlated with L-type Ca2+ channel and Kv1.5 protein amounts (r=−0.80, P<0.001 and r=−0.72, P<0.001, respectively), degree of structural changes (r=0.90, P<0.001), shortening of atrial effective refractory period (AERP) (basic cycle length 500 ms, r=−0.60, P<0.001) and AERP rate adaptation (r=−0.80, P<0.001). Conclusions: Calpain activity is induced during AF and correlates with parameters of ion-channel protein, structural and electrical remodeling. The results suggest that calpain activation represents an important mechanism linking calcium overload to cellular adaptation mechanisms in human AF.
Is the pleural fluid transudate or exudate? A revisit of the diagnostic criteria
Authors: J Joseph, P Badrinath, G S Basran, S A Sahn
Journal: Thorax (2001)

<h3>BACKGROUND</h3> Pleural effusions are classified into transudates and exudates based on criteria developed in the 1970s. However, their accuracy has not been evaluated. We compared the performance of the pleural fluid absolute lactic dehydrogenase level (FLDH), fluid to serum ratio of LDH (LDHR), and fluid to serum ratio of total protein (TPR). TPR has been used instead of the absolute value of fluid protein based on the observation that fluid protein is influenced by changes in the serum protein concentration. However, the rationale for using LDHR remains unexplored. <h3>METHODS</h3> Of 212 consecutive patients with pleural effusions, four with multiple causes and eight with an uncertain diagnosis were excluded. ROC curves were generated using sensitivity and 1–specificity values for TPR, FLDH, and LDHR and positive likelihood ratios (LR +ve) were computed using the optimum cut off values. The correlation between pleural fluid and serum concentrations of total protein and LDH was also estimated. <h3>RESULTS</h3> Of 200 effusions studied, 156 were exudates and 44 were transudates. The optimum cut off levels were: FLDH 163 IU/l, TPR 0.5, LDHR 0.6, and the FLDH-TPR combination 163 and 0.4, respectively. The area under the curve (AUC) with 95% confidence interval (CI) was: 0.89 (0.86 to 0.96) for FLDH, 0.86 (0.80 to 0.91) for TPR, 0.82 (0.77 to 0.89) for LDHR, and 0.90 (0.86 to 95) for FLDH-TPR. A significant correlation was observed between serum and pleural fluid protein levels in transudates and exudates (<i>r</i>=0.5 and 0.6, respectively), but the correlation between serum and pleural fluid LDH levels was insignificant. <h3>CONCLUSION</h3> FLDH is the most accurate marker for the diagnostic separation of transudates and exudates and LDHR has no role in this process. Combining TPR with FLDH appears to improve the diagnostic accuracy slightly.
Prevention of <i>N</i>-Methyl-<i>N</i>-Nitrosourea–Induced Breast Cancer by α-Fetoprotein (AFP)–Derived Peptide, a Peptide Derived from the Active Site of AFP
Authors: Rahul R. Parikh, Neil Gildener-Leapman, Amithi Narendran, Hung-Yun Lin, Nicole Lemanski, James A. Bennett, Herbert I. Jacobson, Thomas T. Andersen
Journal: Clinical Cancer Research (2005)

Abstract Purpose: α-Fetoprotein (AFP) is a protein of pregnancy associated with a decrease in lifetime risk of breast cancer in parous women. A synthetic, cyclic nonapeptide has been developed that mimics the antioncogenic active site of AFP. To test the hypothesis that the AFP-derived peptide (AFPep) can prevent breast cancer, the N-methyl-N-nitrosourea–induced breast cancer model was used in rats. Experimental Design: AFPep was given daily by injection beginning 10 days after N-methyl-N-nitrosourea treatment and continued for 23 days (a time designed to mimic pregnancy) or for other times to assess efficacy as a function of drug duration. Tumor incidence, multiplicity, and latency were noted as end points. At necropsy, pathology analysis of tumors and major organs were obtained. Results: AFPep prevented cancer in a dose-dependent fashion. Significantly longer mean tumor-free days (P &amp;lt; 0.02), lower tumor incidence (P = 0.004), and lower tumor multiplicity were observed for AFPep-treated groups. No evidence of host toxicity as measured by body weight, cage activity, fur texture, and organ weights (liver, uterus, heart, kidney, and spleen) were found in animals treated with AFPep. Mechanistic studies using transplantable human breast cancer xenografts showed that the peptide interfered with estrogen-dependent breast cancer growth inhibited the phosphorylation of the estrogen receptor and activated phosphorylation of p53. Conclusions: AFPep is a well-tolerated, mechanistically novel, chemopreventive agent in models of breast cancer and warrants further development for the prevention and treatment of this disease in humans.
An antibody precipitating urease and its possible relation to gastric ulcer
Authors: F. S. Freisinger
Journal: Gut (1963)

An antibody precipitating urease was found in 171 out of 180 human sera. Data obtained on limited material (50 cases) suggest that the anti-urease titre is appreciably higher in the serum of patients suffering from gastric ulcer. This is a pointer towards a possible antigen-antibody mechanism in the genesis of chronic gastric ulceration.
The contribution of endothelial nitric oxide synthase to early ischaemic preconditioning: the lowering of the preconditioning threshold. An investigation in eNOS knockout mice
Authors: R Bell
Journal: Cardiovascular Research (2001)

Nitric oxide (NO) is implicated in triggering and mediating delayed preconditioning. However, the role of NO and endothelial nitric oxide synthase (eNOS) in early ischaemic preconditioning is controversial. To investigate the role of eNOS in this paradigm further, the response of hearts isolated from either eNOS knockout (KO) or eNOS wild type (WT) mice to various ischaemic-preconditioning stimuli were studied. To determine whether eNOS is pivotal to early ischaemic preconditioning, hearts from both groups were subjected to a robust ischaemic-preconditioning stimulus consisting of four cycles of 5 min ischaemia and reperfusion (4PC) prior to an injurious ischaemia/reperfusion insult. Both WT and KO animals demonstrated significant attenuation of infarct size from 34.91±2.14 to 21.32±2.53% and from 30.92±1.87 to 22.60±2.98%, respectively. Whilst eNOS/NO appears not to be pivotal to early ischaemic preconditioning, NO can nonetheless mediate protection in both WT and KO hearts, as the NO donor, S-nitroso N-acetyl penicillamine (2 μM), was seen to mimic preconditioning protection. Therefore, it appears that the targets for NO mediated protection exist in both WT and KO hearts. Reducing the number of preconditioning cycles from four to three to two continued to result in significant attenuation of infarct size in WT hearts (26.30±2.86 and 26.70±1.95%). However, early ischaemic preconditioning failed in the KO hearts with any preconditioning stimulus less robust than the four cycle protocol used in the initial experiments (3PC 32.51±3.04%, 2PC 28.64±2.55%). Therefore, whilst eNOS is not essential for robust early ischaemic preconditioning, NO can be shown to be cardioprotective in its own right, and, moreover, eNOS and thus nitric oxide synthesis may contribute to early ischaemic preconditioning by lowering the ischaemic threshold for protection.
The Pharmacology of Ryanodine and Related Compounds
Authors: John L. Sutko, Judith A. Airey, William Welch, Luc Ruest
Journal: Pharmacological Reviews (1997)

The goal of this review has been to describe the current state of the pharmacology of ryanodine and related compounds relative to the vertebrate RyRs. Resolution of questions concerning the molecular properties of RyR channel function and the contributions made by the RyR isoforms to cellular signaling in a variety of tissues will require the production of new pharmacological agents directed against these proteins. Novel naturally occurring ryanodine congeners have been identified, and significant advances have been made in developing chemical approaches that permit the structure of ryanodine to be derivatized in selective ways. Moreover, several of these changes have yielded compounds that differ in their binding affinities and in their abilities to modify the properties of the RyR channels. These advances give substance to the possibility of designing the required pharmacological agents based on rational design changes of the structure ryanodine.
Association of Antigen-Processing Machinery and HLA Antigen Phenotype of Melanoma Cells with Survival in American Joint Committee on Cancer Stage III and IV Melanoma Patients
Authors: Andrea Anichini, Roberta Mortarini, Daisuke Nonaka, Alessandra Molla, Claudia Vegetti, Elisabetta Montaldi, Xinhui Wang, Soldano Ferrone
Journal: Cancer Research (2006)

Because changes in the expression level of antigen-processing machinery (APM) components and HLA class I and II antigens in melanoma cells are expected to affect their interactions with the immune system of the host, we assessed the clinical relevance of quantitative variations in the expression of these molecules in melanoma lesions. Short-term (<10 in vitro passages) melanoma cell lines isolated from 85 American Joint Committee on Cancer (AJCC) stage III and IV patients were stained with APM component and HLA class I antigen-specific and HLA class II antigen-specific monoclonal antibodies and analyzed by flow cytometry. The phenotype of all tumors was characterized by intertumor and intratumor heterogeneity in the expression of all the markers and by significant correlations in the level of expression of markers belonging to the HLA class I antigen-processing and presentation pathway. Hierarchical clustering of the mean fluorescence intensity data defined two main clusters of tumors. The corresponding groups of patients differed significantly in the overall survival but not in other relevant clinical variables, including AJCC stage and therapy received after surgery. Cox regression analysis showed that beta2-microglobulin and HLA class II antigen expression were significantly associated with patients' survival. This evidence was corroborated by the immunohistochemical analysis for HLA class II antigen expression of melanoma lesions from an unrelated group of 52 AJCC stage III and IV patients. These results suggest that quantitative variations in APM component and HLA expression in melanoma lesions from AJCC stage III and IV patients may have an effect on the clinical course of the disease.
Ectopic ATP Synthase Blockade Suppresses Lung Adenocarcinoma Growth by Activating the Unfolded Protein Response
Authors: Hsin-Yi Chang, Hsuan-Cheng Huang, Tsui-Chin Huang, Pan-Chyr Yang, Yi-Ching Wang, Hsueh-Fen Juan
Journal: Cancer Research (2012)

Ectopic expression of the mitochondrial F(1)F(0)-ATP synthase on the plasma membrane has been reported to occur in cancer, but whether it exerts a functional role in this setting remains unclear. Here we show that ectopic ATP synthase and the electron transfer chain exist on the plasma membrane in a punctuated distribution of lung adenocarcinoma cells, where it is critical to support cancer cell proliferation. Applying ATP synthase inhibitor citreoviridin induced cell cycle arrest and inhibited proliferation and anchorage-independent growth of lung cancer cells. Analysis of protein expression profiles after citreoviridin treatment suggested this compound induced the unfolded protein response (UPR) associated with phosphorylation the translation initiation factor 2α (eIF2α), triggering cell growth inhibition. Citreoviridin-enhanced eIF2α phosphorylation could be reversed by siRNA-mediated attenuation of the UPR kinase PKR-like endoplasmic reticulum kinase (PERK) combined with treatment with the antioxidant N-acetylcysteine, establishing that reactive oxygen species (ROS) boost UPR after citreoviridin treatment. Thus, a coordinate elevation of UPR and ROS initiates a positive feedback loop that convergently blocks cell proliferation. Our findings define a molecular function for ectopic ATP synthase at the plasma membrane in lung cancer cells and they prompt further study of its inhibition as a potential therapeutic approach.
Innate Immunity and Angiogenesis
Authors: Stefan Frantz, Karen A. Vincent, Olivier Feron, Ralph A. Kelly
Journal: Circulation Research (2005)

Activation of an innate immune response is among the first lines of defense after tissue injury. Restoring blood flow to the site of injured tissue is often a necessary prerequisite for mounting an initial immune response to pathogens and for subsequent initiation of a successful repair of wounded tissue. The multiple links among pathogen recognition and suppression, increased angiogenesis, and tissue repair are the topics of this review, which examines of the roles of antimicrobial peptides, mammalian toll-like receptors (TLRs), inflammatory cytokines, and putative “danger” signals, among other signaling pathways, in triggering, sustaining, and then terminating an angiogenic response.
Selective binding of somatostatin-14 and somatostatin-28 to islet cells revealed by quantitative electron microscopic autoradiography.
Authors: M Amherdt, Y C Patel, L Orci
Journal: Journal of Clinical Investigation (1987)

Quantitative electron microscopic autoradiography was used for comparing the binding of labeled somatostatin-14 (S-14) and somatostatin-28 (S-28 section) to islet cells. Monolayer cultures of rat islet cells were incubated with [125I-Tyr11]S-14 (S-14 section) or [125I-Leu8, D-Trp22, Tyr25]S-28 (S-28 section) in the presence or absence of excess unlabeled peptides. Autoradiographic grains (ARG) associated with individual islet cells were identified and expressed as the mean number per B, A, and D cells. Specific ARG associated with S-14 were found over B and A cells. S-28 section-related specific ARG were concentrated over B, A, as well as D cells. The highest density of S-14 section labeling occurred over A cells, which under conditions of maximum labeling (37 degrees C for 60 min) contained five times as many ARG as did B cells. By contrast, under the same incubation conditions, the labeling density with S-28 section was maximal over B cells, which contained four and five times as many grains as A and D cells, respectively. These observations show preferential association of S-14 section with the A cell and S-28 section with the B cel provide strong evidence for the existence of separate binding sites for S-14 section and S-28 section on A and B cells, respectively, which presumably mediate the previously reported glucagon selective inhibitory effect of S-14 and the insulin-selective action of S-28.
Clinical Manifestations of Liver Dysfunction in Patients With Anorexia Nervosa
Authors: Kyoko Tomita, Hiroaki Haga, Tomohiro Katsumi, Chikako Sato, Kazuo Okumoto, Yuko Nishise, Hisayoshi Watanabe, Takafumi Saito, Yoshiyuki Ueno
Journal: Clinical Gastroenterology and Hepatology (2013)
PharmGKB Submission Update: V. PMT Submissions of Genetic Variation in SLC22 Family Transporters
Authors: Yan Shu, Thomas J. Urban, Maya K. Leabman, Tomoe Fujita, Andrew R. Erdman, Leah L. Lagpacan, Chaline Brown, Richard A. Castro, Conrad C. Huang, Doug Stryke, Michiko Kawamoto, Susan J. Johns, Travis R. Taylor, Wendy Chan, Melanie De La Cruz, Elaine J. Carlson, Thomas E. Ferrin, Claire M. Brett, Esteban G. Burchard, Ira Herskowitz, Deanna L. Kroetz, Kathleen M. Giacomini
Journal: Pharmacological Reviews (2006)

Category: genotype Project: Pharmacogenetics of Membrane Transporters [Table 1][1] provides HUGO Gene Nomenclature Committee (HGNC) symbols, PharmGKB submission URLs, submission dates, and release dates. [Table 2][2] provides HGNC symbols, HGNC names, synonyms, GenBank accession numbers, and locus
Hand osteoarthritis and MRI: development and first validation step of the proposed Oslo Hand Osteoarthritis MRI score
Authors: Ida K Haugen, Siri Lillegraven, Barbara Slatkowsky-Christensen, Espen A Haavardsholm, Sølve Sesseng, Tore K Kvien, Désirée van der Heijde, Pernille Bøyesen
Journal: Annals of the Rheumatic Diseases (2011)

Objectives MRI scoring systems for hand osteoarthritis (HOA) are currently not available. The present work proposes the Oslo HOA MRI (OHOA-MRI) score and examines the intrareader and inter-reader reliability. Methods Relevant HOA features were included in the initial version of the OHOA-MRI score after literature review and informal group discussions. After a training session and two calibration exercises (with three readers), features with low reliability and/or low prevalence were excluded, and feature definitions/gradings were improved. In the reliability exercise 3 readers independently evaluated MRI scans of distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints in 10 patients with HOA according to the final proposed score. The reading was repeated after 1 week. Intraclass correlation coefficients (ICCs), percentage exact agreement/percentage close agreement (PEA/PCA) and smallest detectable difference were calculated. Results The final proposed OHOA-MRI score includes assessment of synovitis, flexor tenosynovitis, erosions, osteophytes (OPs), joint space narrowing (JSN) and bone marrow lesions (BMLs) on a 0–3 scale, and absence/presence of cysts, malalignment (frontal/sagittal plane), collateral ligaments (CLs) and BMLs at CL insertion sites. Inter-reader reliability was very good for synovitis, erosions, OPs, JSN, malalignment (frontal) and BMLs (ICCs ≥0.83, PCA ≥89%), and good for flexor tenosynovitis (ICC 0.64, PCA 80%) and CL presence (ICC 0.79, PEA 63%). Cysts, malalignment (sagittal) and BMLs at CL insertion sites showed high PEA (≥85%), but poor to moderate ICCs (0.00–0.59). Intrareader reliability was similar. The reliability was generally highest in PIP joints. Conclusions The proposed OHOA-MRI score could reliably assess HOA features. However, further validation is needed.