tbuckley/cabot-search huggingface dataset:
Abstract PD03-01: EFFECT OF METFORMIN ON APOPTOSIS IN A PRESURGICAL TRIAL IN NON-DIABETIC PATIENTS WITH BREAST CANCER
Authors: M Cazzaniga, A DeCensi, G Pruneri, M Puntoni, A Guerrieri-Gonzaga, P Dell'Orto, OD Gentilini, A Vingiani, G Pagani, A Puccio, B Bonanni
Journal: Cancer Research (2012)

Abstract BACKGROUND: metformin has been associated with antitumor activity in epidemiological and clinical studies. This effect has been related to different mechanisms of actions, including a reduction of the proliferative activity and an increase of apoptosis. We have recently shown that a 4 week pre-surgical treatment with metformin did not affect Ki-67 LI overall but reduced tumor proliferation Ki67 LI in breast cancer (BC) patients with insulin resistance (IR) (HOMA, fasting blood glucose (mmol/L)*insulin (mU/L)/22.5&amp;gt;2.8) or BMI&amp;gt;27 (Bonanni et al. JCO epub May 7, 2012). The objective of the current analysis was to determine whether metformin induced a modulation of apoptosis (TUNEL) overall and by HOMA index. TRIAL DESIGN: After tumor biopsy we randomly allocated 200 non-diabetic women with operable breast cancer to either metformin (850 mg/bid) or placebo for 4 weeks prior to surgery. The primary outcome measure was the difference between arms in Ki-67 after 4 weeks of treatment. Here we analyzed the apoptotic cell nuclei in 88 consecutive core biopsies and their paired surgical samples from the initial 100 randomized subjects. RESULTS: Median TUNEL levels at surgery (Metformin = 10%, IQR, 4–20, Placebo = 8%, IQR, 3–15) were significantly higher as compared with baseline (Metformin = 4%, IQR, 2–7, Placebo = 3%, IQR, 2–6, p &amp;lt; 0.0001), but no difference between arms was noted (p = 0.2, adjusted for age, BMI, TUNEL and Ki67 at baseline). Interestingly, Ki67 and TUNEL levels were highly and positively correlated both at baseline and at surgery (Spearman r=0.51, p &amp;lt; 0.0001). Furthermore, we found a trend to a different metformin effect by the HOMA index (p = 0.1). In the 59 women with HOMA &amp;lt;2.8 there was a higher level of TUNEL at surgery on metformin versus placebo (p = 0.05), while an opposite trend was found in the 28 women with HOMA&amp;gt;2.8 (p = 0.6). CONCLUSIONS: The levels of TUNEL are significantly higher in the surgical specimens compared with baseline biopsy and are directly correlated with those of Ki-67 (TUNEL is high when Ki-67 is high). We found no significant modulation of TUNEL by metformin but a trend to a different effect according to the IR state, with a similar pattern to Ki-67: decrease by metformin in IR women and increase in non-IR women. Our findings confirm the notion that metformin has dual effects on breast cancer according to IR state. As expected, cancer apoptosis and proliferation are directly related. Our results strengthen the importance of placebo control arms in biomarker trials. ACKNOWLEDGEMENTS: 2 Grants by AIRC and Italian Ministry of Health. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD03-01.
Multiple Sclerosis: The Impact of Physical Impairment and Cognitive Dysfunction on Social and Sparetime Activities
Authors: Egon Stenager, Lone Knudsen, Knud Jensen
Journal: Psychotherapy and Psychosomatics (1991)

In a cross-sectional investigation of 116 patients with multiple sclerosis, the social and sparetime activites of the patient were assessed by both patient and his/her family. The assessments were correlated to physical disability which showed that particularly those who were moderately disabled suffered from severe psychosocial strain. The literature shows that the strain becomes even more severe in certain periods of progression of the disease with the result that psychosomatic conditions arise.
Paying the Doctor: Systems of Remuneration and Their Effects
Authors: John O'Rourke
Journal: JAMA (1970)

In the near future, the United States Congress will consider legislation which could drastically change the traditional method of paying for physician services. William Glaser's book,<i>Paying the Doctor</i>, is a descriptive analysis of the principal mechanisms adopted in other countries. The book is welldocumented and can serve as an excellent introduction to the issue. The objective of this book is to demonstrate how various payment mechanisms affect the provision of health services. The author has drawn his information from 16 countries including Sweden, England, Israel, and the Soviet Union. His data have been collected from personal interviews and from publications. The evaluation of these facts is somewhat subjective. However, it is probably more a strength than a weakness since the reader can hardly remain disinterested. The first five chapters of the book contain a discussion of the basic strengths and weaknesses of fee-forservice, salary, and capitation payment systems. The
Clinical characteristics of three patients with UV<sup>S</sup> syndrome, a photosensitive disorder with defective DNA repair
Authors: T. ITOH, M. YAMAIZUMI, M. ICIHASHI, M. HIRO-OKA, T. MATSUI, M. MATSUNO, T. ONO
Journal: British Journal of Dermatology (1996)

Recently, we established a new category of photosensitive disorder termed UVs syndrome. Cells from patients with UVs syndrome have a similar UV sensitivity as xeroderma pigmentosum (XP) cells, but have a normal level of unscheduled DNA synthesis (UDS) unlike XP. UVs syndrome is distinct from Cockayne syndrome (CS) or XP including XP variant (XP-V), as determined by studies of genetic factors using cell fusion, microinjection, and postreplication repair assays. In this study, we identified three Japanese patients with UVs syndrome: an 11-year-old girl, a 17-year-old male, and an 8-year-old boy. The first two patients were siblings, while the third was a case from a different family. All of these patients exhibited acute recurrent sunburn. Common clinical manifestations of these patients were slight erythema and dryness, a number of freckles on sun-exposed areas, and slight telangiectasia only seen on the cheek and nose. Patient 3 showed a lowered minimal erythema dose between 280 and 300 nm. The patients' fibroblasts showed similar characteristics to those in CS, such as UV sensitivity, and a failure of RNA synthesis (RRS) after UV irradiation, despite a normal level of UDS. Thus, UVs syndrome is a new hereditary photosensitive disorder with clinical manifestations similar to a mild form of XP but showing the cellular characteristics of CS.
On the Evolution of Our Knowledge of Congenital Malformations of the Heart
Authors: HELEN B. TAUSSIG
Journal: Circulation (1965)

Jones when he was in charge of the House of the Good Samaritan makes it a genuine pleasure to give the T. Duckett Jones Memorial Lecture.Although a year younger than I, Duckett was 4 years ahead of me in medical school and by the time I graduated he was established at the House of the Good Samaritan.Duckett offered me my first jobas a histologist to the Good Samaritan.Al- though I did not accept the position, we remained warm friends throughout his life.His sister,
SODIUM GLYCOCHOLATE IN DISEASES OF THE LIVER.
Authors: T. W. KEOWN
Journal: JAMA (1902)

The problem in therapeutics has been to discover some drug which would have an alterative effect upon the liver by increasing the excretion of its waste products of metabolism and arrested toxins by the bile, preventing the precipitation of cholesterin and pigments in the gallbladder, thereby preventing the formation of gallstones. <h3>ORGANOTHERAPY.</h3> In recent years organo-therapy has received a great amount of attention owing to the splendid results obtained by the administration of thyroid extract in myxedema and cretinism, and it is strange that more attention has not been paid to the bile acids which are undoubtedly one of the active principles of the liver, apparently utilized for the purpose of dissolving and holding in solution the excretory products of the liver and procuring their elimination by means of the bile into the intestine. Huppert, Rosenberg, Pfaff and Balch, Schaeffer and many other experimenters have proved conclusively that none of
Diseases as Museum Pieces
Authors: G. G. Liddle
Journal: JAMA (1966)

To the Editor:—  Diseases come and diseases go, while life goes on forever. The notorious breakthrough commonly is supposed to result in the elimination of a disease from the roster of those afflicting man, thereby increasing his health, his numbers, and the population problems of the world.  I would like to suggest either a limitation on breaks through, or the establishment of a Disease Preservation Museum for the maintenance of interesting and fascinating conditions. This could be tied to the population explosion, with a community of prisoners and other derelicts from society serving as a reservoir of diseases, even as similar persons are subjected to experiments promising to produce information to improve the health of society. A reasonable incongruity would be created, with suitable pampering of the subjects who have dedicated their lives in this manner.  This proposal came to mind while I was reading of Australia's dedication to preservation
Clinical Significance of Serum Mesothelin in Patients with Mesothelioma and Lung Cancer
Authors: Alfonso Cristaudo, Rudy Foddis, Agnese Vivaldi, Giovanni Guglielmi, Nicola Dipalma, Rosangela Filiberti, Monica Neri, Marcello Ceppi, Michela Paganuzzi, Gian Paolo Ivaldi, Manlio Mencoboni, Pier Aldo Canessa, Nicolino Ambrosino, Antonio Chella, Luciano Mutti, Riccardo Puntoni
Journal: Clinical Cancer Research (2007)

Abstract Purpose: High levels of serum-soluble mesothelin family proteins (SMRP) have been found to be associated with malignant mesothelioma (MM), but not lung cancer (LC). To verify the clinical role of this marker for both these tumors, we tested serum SMRP in the largest population of thoracic cancers ever assembled. Experimental Design: SMRP blood concentrations were measured in 107 patients with MM, 215 patients with LC, 130 patients with benign respiratory diseases (BRD), and 262 controls. Statistical comparison between mean serum SMRP levels in all groups was done and receiver operating characteristic curves were constructed to evaluate the performance of this marker. Results: SMRP levels were significantly higher in patients with MM and LC than in patients with benign respiratory diseases and controls (P &amp;lt; 0.001). The area under the receiver operating characteristic curve for serum SMRP discriminating MM and controls was 0.77 (95% confidence interval, 0.71-0.83), with a best cutoff of 1.00 nmol/L (sensitivity, 68.2%; specificity, 80.5%). In both MM and LC, serum SMRP levels did not differ significantly between early and late stages. High SMRP levels proved to be an independent negative prognostic factor in patients with MM. Conclusions: Our data confirm that serum SMRP is a promising marker for the diagnosis, prognosis, and clinical monitoring of MM. We found that serum SMRP dosage may prove helpful in LC diagnosis as well. These data may also have positive repercussions on secondary preventive medical strategies for workers previously exposed to asbestos.
Anti-HCV antibody titers before and after interferon therapy in 43 patients with chronic non A non B hepatitis: Relationship with response to treatment
Authors: F. Luncl, M. Perrin, D. Valla, J.F. Cadranel, A.Devil echabrolle, P. Grippon, J.M. Huraux, P. Opolon
Journal: Journal of Hepatology (1990)
Surface immunoglobulin on activated human peripheral blood thymus-derived cells.
Authors: T L Whiteside, B S Rabin
Journal: Journal of Clinical Investigation (1976)

Human peripheral blood lymphocytes grown in vitro were stimulated with nonspecific mitogens and in mixed lymphocyte culture. The presence of IgM and thymus (T) surface markers on large and small lymphocytes was investigated by immunofluorescence and correlated with spontaneous rosette formation. All stimulated large lymphocytes formed spontaneous rosettes and all except pokeweed mitogen (PWM)-stimulated large lymphocytes had IgM and T markers. IgG, IgA, and light chain determinants were only detected on PWM-induced large lymphocytes. Thus, surface markers expressed on activated human lymphocytes may differ for different mitogens. IgM was always present on large cells which had the T markers, and it cannot be used to identify a lymphocyte as a bone marrow-derived (B) cell. Due to the overlap of surface markers, the classification into B and thymus-derived (T) cells ought to be restricted to functional phenomena of antibody-production or cell-mediated immunity.
A7.20 Response to Infliximab Therapy can be Predicted using Distinct, Non-Overlapping Gene Panels of Peripheral Blood Gene Expression in Rheumatoid Arthritis and Crohn’s Disease
Authors: Zoltán Szekanecz, Bertalan Meskó, Szilárd Poliska, Andrea Váncsa, Károly Palatka, Zsolt Holló, Gábor Zahuczky, János Podani, Attila Horváth, László Steiner, László Nagy
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Biological therapies targeting tumour necrosis factor α (TNF-α) have been widely used to treat chronic inflammatory disorders including rheumatoid arthritis (RA) and Crohn's disease (CD). As these treatment modalities are rather expensive, there is a need for biomarkers that may predict therapeutic responses. As RA and CD have similar pathogenic background, one may expect to detect overlapping gene panels in predicting the response to the same therapy by the same approach. There have been very few studies using simultaneous pharmacogenomic approach in two diseases. <h3>Methods</h3> In this study, we performed peripheral blood global gene expression profiling followed by Canonical Variates Analysis (CVA) in CD and RA to identify gene sets that can differentiate responders from non-responders for infliximab therapy; and validated the results in an independent cohort by RT-QPCR. <h3>Results</h3> In CD, global gene expression analysis of samples obtained at baseline resulted in a list of 48 probe sets differentiating responders from non-responders. Comparing baseline and week 2 samples resulted in a list of five genes including AQP9, IGKC, MGAM, MMP8 and TNFAIP6 that exert expression changes upon treatment. Similarly, in RA, analysis of baseline samples resulted in a list of 30 probe sets that differentiated responders from non-responders. Expression of 3 genes; AQP9, IGJ and TNFAIP6 showed significant difference between baseline and week 2 samples. Results were validated by RT-QPCR on independent patient cohorts in both diseases. CVA analysis yielded to 15 and 12 genes in RA and CD, respectively, showing the best discriminatory power between responders and non-responders in both diseases, however there was no overlap between these two gene lists. <h3>Conclusions</h3> We provided two pieces of proof of concept evidence showing that 1) peripheral blood gene expression profiles are suitable for determining gene panels with the highest discriminatory power in order to differentiate responders and non-responders in a patient cohort in CD and RA; and 2) distinct, non-overlapping gene panels are required for the prediction of the responder status in CD and RA despite the fact that these conditions have similar pathogenic background. Application of such gene panels could solve unmet needs in the clinical settings by determining specific responses to expensive biological therapies.
Dual Isotope F-18 FDG and Tc-99m RBC Imaging for Lung Cancer
Authors: ROBERT BURT
Journal: Clinical Nuclear Medicine (1998)

Purpose: To produce fluorodeoxyglucose (FDG) images with markers for normal organs and large blood vessels in patients with suspected lung cancer. Methods: Dual isotope SPECT images were made using F-18 FDG- and Tc-99m-labeled autologous red cells. Results: FDG-positive lesions are localized in relation to major structures when they are viewed in a fused rotating three-dimensional display or in cross sections. Conclusions: Tc-99m red cell and FDG fusion imaging provides relative location information for lung tumors.
Symptomatic Response to Antiarrhythmic Drug Therapy Is Modulated by a Common Single Nucleotide Polymorphism in Atrial Fibrillation
Authors: Babar Parvez, Joseph Vaglio, Shane Rowan, Raafia Muhammad, Gayle Kucera, Tanya Stubblefield, Shannon Carter, Dan Roden, Dawood Darbar
Journal: Journal of the American College of Cardiology (2012)
Deficiency of Gelatinase A Suppresses Smooth Muscle Cell Invasion and Development of Experimental Intimal Hyperplasia
Authors: Masafumi Kuzuya, Shigeru Kanda, Takeshi Sasaki, Norika Tamaya-Mori, Xian Wu Cheng, Takeshi Itoh, Shigeyoshi Itohara, Akihisa Iguchi
Journal: Circulation (2003)

Background— Although it has been demonstrated that matrix metalloproteinases (MMPs) play an important role in the arterial remodeling in atherosclerosis and restenosis, it is not clear which MMP is involved in which process. To define the role of MMP-2 in arterial remodeling, we evaluated the influence of the targeted deletion of the MMP-2 gene on vascular remodeling after flow cessation in the murine carotid arteries. Methods and Results— The left common carotid arteries of wild-type and MMP-2–deficient mice were ligated just proximal to their bifurcations, and the animals were then processed for morphological and biochemical studies at specific time points. MMP-2 activity and mRNA levels increased in ligated carotid arteries of wild-type mice on the basis of observation by gelatin zymography and quantitative real-time RT-PCR. There was significantly less intimal hyperplasia in MMP-2–deficient mice at 2 and 4 weeks after ligation than there in wild-type mice. Arterial explants from the aorta of MMP-2–deficient mice showed that smooth muscle cell (SMC) migration was inhibited in comparison with wild-type mice. The chemoattractant-directed invasion through a reconstituted basement membrane barrier was significantly reduced in cultured SMCs derived from MMP-2–deficient mice, although no difference was observed in SMC migration across the filter or in proliferative response between the control and MMP-2–deficient mice. Conclusions— In a mouse carotid artery blood flow cessation model, MMP-2 contributes to intimal hyperplasia mainly through the SMC migration from the media into the intima by degrading and breaching the extracellular matrix proteins surrounding each cell and the internal elastic lamina.
Modification by <i>ALAD</i> of the Association between Blood Lead and Blood Pressure in the U.S. Population: Results from the Third National Health and Nutrition Examination Survey
Authors: Franco Scinicariello, Ajay Yesupriya, Man-huei Chang, Bruce A. Fowler
Journal: Environmental Health Perspectives (2009)

Environmental lead exposure has been found to be associated with an increased risk of hypertension. Individuals vary greatly in susceptibility to lead toxicity, and genetic susceptibility has often been cited as the probable cause for such variation.The main objective is to determine the role of the aminolevulinic acid dehydratase (ALAD) gene, which encodes the main carrier protein of lead in blood, in the association between lead exposure and blood pressure (BP) and hypertension in the U.S. population.We analyzed data from individuals >or= 17 years of age who participated in the Third National Health and Nutrition Examination Survey for whom DNA was available (n = 6,016). Multivariable logistic and linear regressions stratified by race/ethnicity were used to examine whether hypertension and BP were associated with ALAD and blood lead levels (BLL).BLL was associated with systolic BP in non-Hispanic whites and with hypertension and systolic and diastolic BP in non-Hispanic blacks. BLL was not associated with BP outcomes in Mexican Americans. Non-Hispanic white ALAD2 carriers in the highest BLL quartile (3.852.9 microg/dL) had a significantly higher adjusted prevalence odds ratio for hypertension compared with ALAD1 homozygous individuals. We also found a significant interaction between lead concentration and the ALAD2 allele in non-Hispanic whites and non-Hispanic blacks in relation to systolic BP.BLL may be an important risk factor for hypertension and increased systolic and diastolic BP. These associations may be modified by ALAD genotype.
Multifunctional Hybrid Nanocarriers Consisting of Supramolecular Polymers and Quantum Dots for Simultaneous Dual Therapeutics Delivery and Cellular Imaging
Authors: Yun‐Long Wu, Hui Yin, Feng Zhao, Jun Li
Journal: Advanced Healthcare Materials (2012)

A novel multifunctional hybrid nanocarrier consisting of a red fluorescence quantum dot core and a star-shaped cationic β-cyclodextrin polymer shell is demonstrated. Chemotherapeutic drug paclitaxel is supramolecularly preloaded into the nanocarrier, which co-delivers the drug and DNA with an enhanced gene expression, while the quantum dot core allows simultaneous cellular imaging using laser scanning confocal microscopy.
Abstract 2619: Potential advantages of CUDC-101, a multi-targeted HDAC, EGFR and HER2 inhibitor, on preventing drug resistance and tumor metastasis
Authors: Jing Wang, Kader Selmi, Maria Samson, Jeffrey Forrester, Ruzanna Atoyan, Hui Qu, Ling Yin, Da-Gong Wang, Brian Zifcak, Mylissa Borek, Steven DellaRocca, Rudi Bao, Hai-Xiao Zhai, Xiong Cai, Changgeng Qian, Pierre Savagner, Cheng-Jung Lai
Journal: Cancer Research (2011)

Abstract CUDC-101 is a novel small-molecule multi-target anti-cancer agent currently in Phase Ib clinical trial, which targets histone deacetylase (HDAC), epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor2 (HER2). Previously, we reported that CUDC-101 has potent anti-proliferative and pro-apoptotic activities in cultured tumor cells and in vitro xenograft models when compared to other single-target agents. Additionally, we demonstrated that CUDC-101 reduces the levels of phosphorylated and total MET. MET amplification and secondary EGFR mutation are two validated mechanisms responsible for EGFR tyrosine kinase inhibitor (TKI) drug resistance in patients. In an effort to expand on our previous findings, we further substantiate here that cancer cells harboring MET amplification are sensitive to CUDC-101. This result, together with the finding that cancer cells containing the EGFR-T790M mutation are sensitive to CUDC-101, suggests that RTK inhibitor-resistant tumor cells are sensitive to treatment with CUDC-101. Additionally, erlotinib-resistant HCC827 cells, which lost their EGFR dependence, are still sensitive to treatment with CUDC-101. Interestingly, this drug-resistant cell line shows neither secondary EGFR mutation nor c-Met amplification, suggesting that CUDC-101 has the potential to overcome drug resistance through other mechanisms. Because c-Met plays an important role in metastasis, we further investigated the effect of CUDC-101 in regulating cell motility, and demonstrate that CUDC-101 can induce E-cadherin accumulation in MDA-MB-231 cells and inhibit EGF induced epithelial-mesenchymal transition (EMT) in in vitro cultured cell and in vivo animal models. In vitro functional study also shows that CUDC-101 reduces tumor cell migration and invasion. Together, our findings suggest that CUDC-101, an investigational anti-cancer drug, may provide great potential for simultaneously overcoming tumor growth, metastasis, and drug resistance. 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 2619. doi:10.1158/1538-7445.AM2011-2619