tbuckley/cabot-search huggingface dataset:
P4-17-10: Insights into Mechanisms Involved in the Accumulation of Nanovectors within the Breast Cancer Brain Metastasis.
Authors: K Yokoi, L Xuewu, JF Alexander, IJ Fidler, F Mauro, G Biana
Journal: Cancer Research (2011)

Abstract Systemic chemotherapy for brain metastasis of breast cancer (BMBC) is considered to be inefficient. It is widely accepted in the literature that blood-brain-barrier (BBB) is responsible for clinical failures with the conventional chemotherapy. We hypothesized that nanovectors, therapeutic carriers with submicron dimensions, can be delivered to the brain tissue through a different pathway than molecular therapeutics. The objective of this study was to examine the accumulation of various intravenously injected nanovectors into the brain metastasis of breast and other cancers loci and to explore possible mechanisms involved. Both human (MDAMB231) and mouse (4T1) breast cancer brain metastasis were evaluated. We also tested lung (3LL) and colon (CT26) originated cancers. Orthotopic brain tumors were produced either by intracarotid injection or stereotactic brain injection of cancer cells. When the animals became moribund, they were injected intravenously with one of the following nanovectors including fluorescently labeled PEGylated (100nm) and non-PEGylated (100nm, 250nm, 500nm) liposomes, disc-shape silicon particles (600, 1000nm in diameter). The accumulation of the nanovectors was compared to an unencapsulated fluorescent molecule. The accumulation of the nanovectors in the brain tumor tissue was evaluated through live animal imaging (IVIS) and immunohistochemical analysis. Immunohistochemical staining of endothelial cells and basal membrane markers was performed to determine the integrity of the tumor associated vasculature and the co-localization of the fluorescent nanovectors/molecules with tumor associated vasculature. Interestingly, we have found that brain metastasis of different tumors (originated form breast, lung and colon cancers) possess dissimilar accumulation profiles for intravenously administered nanovectors. For example when comparing various tumor origins, 4T1 breast cancer originated brain tumors enabled the highest accumulation of the nanovectors as compared to CT26 and 3LL. On the other hand, free molecule accumulated into the 4T1 brain metastasis model to a much lower extend than in nanovector. Finally, the observed brain distribution of nanovectors corresponded well with impairment in vascular endothelium and basal membrane integrity shown in immunohistochemical analysis. The results of our study point toward a possibility to treat specific patients with impaired BBB function with nanovector encapsulated chemotherapeutics based on the fact that their transport, accumulation and retention in the brain tissue are governed by different biological mechanisms, such as Enhanced Permeation and Retention (EPR) effect. These studies indicate that it is possible to cross the blood brain barrier, thus giving hope to patients with brain metastasis. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-17-10.
Medical Education in China in the Postcultural Revolution Era
Authors: Chi-Pang Wen, Charles W. Hays
Journal: New England Journal of Medicine (1975)

The Cultural Revolution has had an important impact on Chinese medical education. The Chinese system is engaged in a vigorous program to solve health-manpower needs in the rural areas by emphasizing de-professionalization, mass orientation and accountability to the community. Among the notable changes within the medical schools are the following: an admission process favoring the recruitment of peasants, factory workers, and the military; a three-year program with heavy emphasis on practicing in rural communities; widespread integration of the traditional Chinese and Western systems of medical practice; and manual labor and political seminars, which compose more than 25 per cent of the required curriculum. These innovations have been greatly facilitated by a strong national commitment and supportive political system. The fact that less than 10 per cent of doctors in China today are graduates of college-level medical education indicates the importance of other entry possibilities.
P32 Does Disease Severity Affect Patient Activation Scores in COPD?: Abstract P32 Table 1
Authors: NJ Roberts, IS Patel, L Kidd, M Lawrence, J Booth
Journal: Thorax (2012)

<h3>Background</h3> As part of the NHS Plan patients are encouraged to manage their own health. Healthcare professionals have a responsibility to ensure that patients have the right tools and education to self-manage their conditions. Hibbard <i>et al</i> have developed a patient activation measure (PAM) which measures the extent to which individuals have the attributes and skills to manage their condition. The PAM determines how “activated” an individual is and can highlight what help an individual needs to improve self-management skills. For example, Level 2 indicates when patients lack confidence/knowledge to take action, whereas Level 3 is where individuals start to take action. <h3>Methods</h3> 18 patients attending consultations or pulmonary rehabilitation(PR) during a one-week period in June 2012 were recruited to participate in this observational study. <h3>Results</h3> We recruited 18 COPD patients [8 Females, 10Males, Mean age 68 yrs ±8], eleven with moderate COPD, 5 had severe COPD and 2 had very severe COPD. The group had a mean percent predicted FEV1 of 53% and a mean MRC Score of 3±0.8. Five were current smokers and 12 were ex-smokers. In total there had been 10 respiratory admissions and 45 exacerbations in the last 12 months. The group mean PAM score was 66.9±21, and the mean level of activation was 2.89±1.13. Those who had more hospitalisations in the last 12 months had a lower PAM score (Pearsons correlation= –0.456, p=0.066). There was no correlation between COPD stratification and PAM Score (Pearsons correlation= –0.343, p=0.164). Sub-analysis (Table 1) showed 6 patients who had not received PR [mean age 66±5.6, mean MRC Score 2.62±0.48], 8 who were currently doing PR [mean age 71±11, mean MRC Score 3±0.75] and 4 who were post-PR [mean age 67.3±3.6, mean MRC Score 3.38±1.10]. <h3>Conclusions</h3> Pilot results show that there was no correlation between COPD severity and PAM Scores. Differences in PAM scores were found between those in current PR, as well as those with more hospitalisations. Further work is needed to evaluate the PAM as a tool for multiple points in an individual’s journey such as at diagnosis, after a first or repeat admission and as part of PR programmes.
Effects of Regular Exercise on Blood Pressure and Left Ventricular Hypertrophy in African-American Men with Severe Hypertension
Authors: Peter F. Kokkinos, Puneet Narayan, John A. Colleran, Andreas Pittaras, Aldo Notargiacomo, Domenic Reda, Vasilios Papademetriou
Journal: New England Journal of Medicine (1995)

The prevalence of hypertension and its cardiovascular complications is higher in African Americans than in whites. Interventions to control blood pressure in this population are particularly important. Regular exercise lowers blood pressure in patients with mild-to-moderate hypertension, but its effects in patients with severe hypertension have not been studied. We examined the effects of moderately intense exercise on blood pressure and left ventricular hypertrophy in African-American men with severe hypertension.
Postgastrectomy protein-losing cytomegalovirus jejunitis in an immunocompromised patient
Authors: Philip Roelandt, Helene Poels, Ester Meeus, Eric Van Cutsem, Hans Prenen
Journal: Endoscopy (2014)

A 59-year-old man was admitted because of nausea and fatigue. He had been diagnosed with gastric adenocarcinoma 7 months earlier, and because of gastric outlet obstruction had undergone total gastrectomy with esophagojejunostomy and omentectomy (pT3N3bM0R1). Postoperatively, platinum-based chemotherapy was initiated, followed by radiochemotherapy (5-fluorouracil + 45 Gy) approximately 2 weeks before admission.
Multifocal Coronary Thromboembolism from a Left Ventricular Thrombus
Authors: Gregory M. Lanza, Brett J. Berman, Megumi Taniuchi
Journal: New England Journal of Medicine (1999)

To the Editor: Acute myocardial infarction due to coronary thromboembolism from a left ventricular thrombus has been suspected in patients with dilated or aneurysmal left ventricles, but it has rarely been documented. In previous reports of acute myocardial infarction in the presence of widely patent coronary arteries, the infarction was attributed to thromboembolism1,2 or coronary spasm.3 In another report, coronary-artery thrombosis that was identified by angiography was suggested to have been caused by thromboembolism from an unidentified left ventricular clot.4 We describe a young patient with dilated cardiomyopathy and acute myocardial infarction who underwent emergency coronary catheterization; the procedure . . .
Abstract 5242: Obtaining a transcriptomic profile of a single prostate cancer cell
Authors: Colm Morrissey, Ilsa Coleman, Shu Chen, Roger Coleman, Roman Gulati, Bryce Lakely, Lisha G. Brown, Martin Kinnunen, Eva Corey, Ruth Etzioni, Paul H. Lange, Peter S. Nelson, Robert L. Vessella
Journal: Cancer Research (2011)

Abstract There have been considerable advances in the detection, isolation and characterization of circulating tumor cells (CTC) and disseminated tumor cells (DTC) in prostate cancer (PCa) patients. However, the ability to interrogate these cells is restricted by the small number detected and isolated (typically &amp;lt;10), and current technologies available to characterize individual cells. We set out to determine the limit of commercially available technologies to obtain a transcriptomic profile of a single PCa cell. To do this we isolated clonally selected Aphidicolin synchronized C4-2B PCa cells. Ten sets of C4-2B cells were isolated individually or in pools of 5 or 10 cells. All thirty samples were amplified using WT-Ovation™ One-Direct (NuGEN), hybridized on a 44K Whole Human Gene Expression Microarray (Agilent Technologies) normalized for batch effects, and normalized within and between arrays. The amplified material was also assessed by realtime-PCR. Using a high stringency cut off (mean signal intensity of 300) on the oligonucleotide arrays 22,365 probes were Cy3 positive for 10 cells, 19,393 for 5 cells and 15,441 for 1 cell. Furthermore, using the same high stringency cut off, the sensitivity and specificity between 1 and 10 cells was 0.640 and 0.946 respectively, and between 1 and 5 cells was 0.713 and 0.932, demonstrating a very low false positive rate. Ten-thousand randomly selected pairs of commonly expressed genes had a Pearson correlation coefficient of 0.862 and 0.908 for 1 vs. 10 cells and 1 vs. 5 cells respectively, indicating that the vast majority of detected probes maintained consistent relative abundance. The cycle threshold values for single cell samples by realtime-PCR were well within the detectable range for abundant transcripts (e.g. AR and KLK3). However, other transcripts (e.g. FKBP5 and TMPRSS2) were not detected in the single cell samples and had limited detection in 5 cell samples when compared to 10 cell samples. These data suggest that currently commercially available technologies allow for the detection of a limited but significant number of genes from a single PCa cell. We are using the methodology described herein, to determine the heterogeneity of single DTC isolated from the bone marrow of patients with PCa. 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 5242. doi:10.1158/1538-7445.AM2011-5242
AB0374 End-organ damage in a cohort of filipino patients with systemic lupus erythematosus at two tertiary hospitals
Authors: J. P. C. Consignado, C. Macapagal, S. V. Navarra
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives: Objective</h3> The study aims to describe the prevalence of end-organ damage in a cohort of systemic lupus erythematosus (SLE) patients at two tertiary hospitals and determine any association of SLE manifestations, medications and end-organ damage. <h3>Methods: Design</h3> Data of adult (≥18 years old) patients seen at the lupus clinics of two tertiary hospitals (University of Santo Tomas, St. Luke's Medical Center) from January to June 2012 was assessed using the Systemic Lupus International Collaborating Clinics/SLE Damage Index (SLICC/SDI). Medical records were reviewed for SLE characteristics, American College of Rheumatology (ACR) presenting manifestations of SLE, cumulative steroid dose, and immunosuppressive agents. T test, Fisher's Exact test, univariate and multivariate analysis were utilized for data analysis. <b>Results: Results.</b> 187 SLE patients (177, 94.7% females), with mean age at diagnosis at 29±10.75 years and mean disease duration of 9±6.7 years were included in the study. 108 (57.7%) had at least 1 end-organ damage. Common end-organ damage were steroid-induced cataract, proteinuria, and stroke in 25 (23%), 22 (20%), and 14 (13%) patients respectively. Damage occurred at an average of 6.6 years after diagnosis. Development of subsequent end-organ damage occurred at an average of 3 years after the preceding damage. Presenting manifestations at SLE diagnosis of proteinuria (<i>p=0.024</i>), anemia (<i>p=0.028</i>), and thrombocytopenia (<i>p=0.049</i>) and immunosuppressive treatment with cyclophosphamide <i>(p=0.046)</i> and cumulative prednisone dose of more than 10 grams <i>(p=0.043)</i> were significantly associated with damage. <b>Conclusions: Conclusion.</b> In this cohort of SLE patients, majority were found to have at least one end-organ damage, most commonly steroid-induced cataract, proteinuria, and stroke. Presenting manifestations of proteinuria, anemia, and thrombocytopenia were significantly associated with damage, reflecting a high disease activity that required increased doses of glucocorticoids. Of the therapies, cylophosphamide and a cumulative prednisone dose ≥ 10 grams were significantly associated with development of end-organ damage. <h3>Disclosure of Interest</h3> None Declared
Abstract 1961: PKCΔ mediates glycodelin-induced differentiation of breast cancer cells
Authors: Laura C. Hautala, Riitta Koistinen, Hannu Koistinen
Journal: Cancer Research (2011)

Abstract Glycodelin is a secreted lipocalin family glycoprotein, expressed mainly in differentiated epithelia in reproductive tissues. The expression of glycodelin in breast and endometrial cancer cells induces cell differentiation. We have found that transfection of glycodelin cDNA into MCF-7 breast cancer cells changes cellular morphology and gene expression towards less malignant direction. In pre-clinical xenograft mouse model glycodelin-producing cells formed significantly smaller tumors with lower proliferation rate than control cells. This is in keeping with the association of glycodelin with well-differentiated and less proliferative tumors in sporadic breast cancer patients. The aim of the present study is to elucidate the mechanism(s) mediating glycodelin-induced differentiation of breast cancer cells. The gene expression changes between glycodelin-producing and control cells were compared using a cDNA micro array. The cells were grown on Matrigel with and without protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA), PKCΔ inhibitor Rottlerin and various other kinase inhibitors. PKCΔ was also down-regulated with RNAi. The levels of PKCΔ were measured using Western Blotting. The gene expression changes induced by glycodelin were enriched in several pathways, including mitogen-activated protein kinase (MAPK) -pathway. Among various studied proteins of MAPK-pathway, we found that phosphorylated PKCΔ was down-regulated in glycodelin-producing cells. Further studies with activators and inhibitors indicated that addition of PKC activator PMA to cell culture medium induced dramatic morphological changes and increased motility of the control cells, while glycodelin-producing cells were unresponsive. The effect of PMA was abolished by Rottlerin, an inhibitor of PKCΔ, as well as by using siRNA for PKCΔ. These results suggest that the glycodelin-induced differentiation of breast cancer cells is mediated by PKCΔ, which in other studies has been proposed to be a potential target for cancer treatment. 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 1961. doi:10.1158/1538-7445.AM2011-1961
Abstract 459: Activation of macrophages by IL-4 and other cytokines: priming for protumoral functions
Authors: Hao-Wei Wang, Vasilena Gocheva, Johanna A. Joyce
Journal: Cancer Research (2011)

Abstract While macrophages are a fundamental constituent of the host immune system, tumor-associated macrophages (TAMs) have been shown to fuel tumorigenesis, although there remain many critical open questions regarding how TAMs acquire their tumor-promoting functions and how they actually facilitate tumor growth and progression. Previously, we have shown that TAM-supplied cysteine cathepsin proteases play critical roles in several steps of carcinogenesis including cell proliferation, angiogenesis and invasion. We have also identified interleukin-4 (IL-4) as a key tumor-derived factor which induces high cathepsin activity in TAMs. Here we set out to investigate the mechanisms underlying the induction of cathepsin activity in TAMs by IL-4, and to identify other factors that act in concert with IL-4 to trigger this activity switch. Using a cell-based model, we have demonstrated that IL-4 upregulates the transcription of several cathepsins in bone marrow-derived macrophages (BMDMs) through a STAT6-dependent mechanism. In addition, by using an activity-based probe for cathepsin proteases, we have also shown that IL-4 can induce the secretion of active cathepsins from BMDMs. Moreover, several other cytokines that are expressed in the tumor microenvironment can act redundantly or synergistically with IL-4 to induce cathepsin expression and secretion. In sum, our data indicate that complex cytokine signaling pathways in the tumor microenvironment are capable of shaping the tumor-promoting phenotypes of TAMs in part through the induction of cathepsin activity. 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 459. doi:10.1158/1538-7445.AM2011-459
Eosinophil And Interleukin-5 In Urine Of Patients With Systemic Lupus Erythematosus
Authors: V.S.F. Sales, M.J.P. Vilar, L.K.P. Arruda, L.B.F.C. Souza, A.L.S.B. Faria, S.D.V. Medeiros, T.N.S. Brito
Journal: Journal of Allergy and Clinical Immunology (2012)
SAT0071 Dependence of rheumatoid arthritis disease aggressivity and activity on the presence of parvovirus B19 infection markers
Authors: O. Bratslavska, A. Kadisa, S. Kozireva, E. Pavlova, N. Kakurina, A. Lejnieks, M. Murovska
Journal: Annals of the Rheumatic Diseases (2013)

Summary: We describe a rare case of multiple dural arteriovenous shunts (DAVSs) in a 5-year-old boy. MR imaging performed at 1 year of age showed only a dilated anterior part of the superior sagittal sinus; however, angiography at 5 years of age revealed an infantile-type DAVS there and two other DAVSs of the adult type. The pathophysiological evolution of DAVSs in children and their treatment strategies are discussed.
Abstract 419: Periostin activates integrin alpha5/beta1 through AKT-dependent pathway in invasion of cholangiocarcinoma
Authors: Chanitra Thuwajit, Kusumawadee Utispan, Jumaporn Sonongbua, Peti Thuwajit
Journal: Cancer Research (2011)

Abstract Cholangiocarcinoma (CCA), a cancer arising from bile duct epithelial cells, is a serious health problem in Thai people. It is a progressive tumor with high metastatic potency. Recently, our group has found that periostin, an extracellular matrix protein, mainly produced from stromal activated fibroblasts of CCA has strong impact to induce cancer cell invasion. This work aims to investigate specific integrins which are utilized by periostin to drive invasion of CCA cells. The activated intracellular signal transduction pathway is also explored. Seven Thai patients-derived CCA cell lines were investigated their integrin expression patterns by real time PCR. The results indicated high level of integrin alpha6 in almost all cell lines. In addition, integrin alpha5 was also detected in not only CCA cell lines but also in immortalized non-tumorigenic biliary epithelial cell. For beta subunit integrin, the result revealed high expression levels of integrins beta1 and beta4 in CCA and non-tumorigenic cells. These results implied high level of integrins alpha5/beta1 and alpha6/beta4 in CCA cells. Flow cytometry and immunocytochemistry analysis confirmed intact molecules of these 2 integrin receptors on the membrane of M213 CCA cell line. Cell adhesion on periostin-coated surface was significantly decreased after integrin alpha5/beta1, but not alpha6/beta4, was blocked with the corresponding neutralizing antibodies. This result indicated that CCA cells preferred to use integrin alpha5/beta1 to bind with periostin. Moreover, cells treated with a neutralizing antibody against integrin alpha5/beta1 showed attenuated effect of periostin-induced invasion as similar to cells exposed to siRNA against integrin alpha5. Furthermore, we found that integrin alpha5-knocked down cells had decreased level of intracellular pAKT compared to negative control cells after activation with periostin. Taken these results together, it is likely to say that periostin activates CCA invasion through integrin alpha5/beta1 and AKT-dependent signal transduction pathway. This study suggests fibroblast-derived periostin, the stromal cell-derived substance, in promotion of CCA progression. Importantly, the obtained data highlight the potential of using the mechanism underlying stroma-driven cancer progression as an alternative target in the treatment of CCA patients. 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 419. doi:10.1158/1538-7445.AM2011-419
Antimetastatic Activity of Atu027, a Liposomal Sirna Formulation, Targeting Protein Kinase N3: Final Results of a Phase I Study
Authors: D. Strumberg, B. Schultheis, A. Santel, F. Gebhardt, W. Meyer-Sabellek, O. Keil, K. Giese, J. Kaufmann
Journal: Annals of Oncology (2013)