tbuckley/cabot-search huggingface dataset:
THE RÔLE OF THE RETICULO-ENDOTHELIAL SYSTEM IN IMMUNITY
Authors: C. W. Jungeblut, J. A. Berlot
Journal: The Journal of Experimental Medicine (1926)

1. Intravenous injections of India ink into guinea pigs caused a decided drop in the complement titer which set in as early as 15 minutes after the injection, but did not reach its maximum for 3 hours. This drop was followed by a return to normal within the first 24 hours following the injection. 2. India ink mixed in vitro with guinea pig serum adsorbs the complement almost immediately to its full extent. 3. By means of reduction tests (methylene blue and nitroanthraquinone) it was shown that the respiration of the cells of the liver and spleen of guinea pigs was markedly impaired for the first 8 hours, following an intravenous injection of ink. Evidences of a return to normal functional vitality, however, became apparent by the end of the 1st day after the injection.
Aetiology of pleural plaques
Authors: V. Rous, J. Studeny
Journal: Thorax (1970)

Pleural plaques were found in 644 (6·6%) of 9,760 photofluorograms taken in 1965 in a region of Pelhřimov district; the incidence was highest in the age group 66-70 years. The advanced age of those affected may be explained by the greater frequency of the causative agent in the past. The disorder was known in Pelhřimov district as early as 1930; it was then thought to be posttuberculous. The past history of the cases was uninformative; as a rule, the only common previous disease was pleurisy with effusion, occurring in 9·7%. The general condition of those affected was excellent; only 8% were aware of the fact that pleural lesions were present. The disorder was found mainly in farmers, familial incidence was common, and if two generations of one family suffered from the condition, the older generation was affected in 100%. Pleural plaques consist morphologically of limited areas of hyalinized collagenous connective tissue with calcium salt deposits. Tubercle bacilli could not be cultivated from the lesions. Mineralological analysis showed no evidence of silicates in the pleural plaques and a normal content in the lungs. The aetiological factor responsible for the development of pleural plaques in Pelhřimov district is not known, but asbestos cannot be implicated. The unknown noxious agent is carried to the pleura by the lymph and blood stream. Pleural plaques are an endemic disorder. The traditional view that lesions are post-tuberculous appears, in the region submitted to this study, to be a possible explanation.
Time trend in treatment-related deaths of patients with advanced non-small-cell lung cancer enrolled into phase III trials of systemic treatment
Authors: Y. Fujiwara, K. Hotta, M. Di Maio, K. Kiura, N. Takigawa, M. Tabata, M. Tanimoto
Journal: Annals of Oncology (2010)

Despite recent improvements in supportive care, treatment-related death (TRD) remains a serious problem for lung cancer patients undergoing systemic chemotherapy. However, few studies have formally assessed possible changes in the TRD rate over the past two decades.We searched phase III trials to address the role of systemic treatment of advanced non-small-cell lung cancer (NSCLC). Time trend was assessed using linear regression analysis.The overall incidence of TRD was calculated from 119 trials including 263 chemotherapy arms (46 477 patients), with information about the causes of deaths available for 197 arms (75%, 30 147 patients). Cisplatin-based regimens were the most frequently investigated. The crude TRD rate in the overall cohort of 119 trials was 1.26% and has been notably consistent over the investigated time (P = 0.762). The most common cause of death was febrile neutropenia, with no significant change in its incidence over the years (P = 0.139). In contrast, deaths due to renal toxicity decreased significantly (P = 0.042), whereas deaths due to pulmonary disorder increased significantly (P = 0.007). Among the pharmacological agents investigated, docetaxel (Taxotere) and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were associated with relatively high rates of deaths from pulmonary disorders, but EGFR-TKIs were not associated with death from any other cause.Despite of potential confounders in our results, the overall TRD rate has remained low, but not negligible, in phase III trials for advanced NSCLC, over the past two decades. Notably, the incidence and pattern of TRD stratified by cause have changed considerably.
A Robust Assay for Alternative Lengthening of Telomeres in Tumors Shows the Significance of Alternative Lengthening of Telomeres in Sarcomas and Astrocytomas
Authors: Jeremy D. Henson, Jonathan A. Hannay, Stanley W. McCarthy, Janice A. Royds, Thomas R. Yeager, Robert A. Robinson, Stephen B. Wharton, David A. Jellinek, Susan M. Arbuckle, Jinyoung Yoo, Bruce G. Robinson, Diana L. Learoyd, Paul D. Stalley, S. Fiona Bonar, Dihua Yu, Raphael E. Pollock, Roger R. Reddel
Journal: Clinical Cancer Research (2005)

Telomeres of tumor cells may be maintained by telomerase or by alternative lengthening of telomeres (ALT). The standard ALT assay requires Southern analysis of high molecular weight genomic DNA. We aimed to establish and validate an ALT assay suitable for archived paraffin-embedded tumors and to use it to examine the prevalence and clinical significance of ALT in various types of tumors that are often telomerase negative.To assay for ALT, we detected ALT-associated promyelocytic leukemia (PML) bodies (APBs) by combined PML immunofluorescence and telomere fluorescence in situ hybridization. APBs are PML nuclear domains containing telomeric DNA and are a known hallmark of ALT in cell lines. The APB assay concurred with the standard ALT assay in 62 of 62 tumors and showed that 35% of 101 soft tissue sarcomas (STS), 47% of 58 osteosarcomas (especially younger patients), 34% of 50 astrocytomas, and 0% of 17 papillary thyroid carcinomas were ALT positive (ALT+). The prevalence of ALT varied greatly among different STS subtypes: malignant fibrous histiocytomas, 77%; leiomyosarcomas, 62%; liposarcomas, 33%; synovial sarcomas, 9%; and rhabdomyosarcomas, 6%. ALT correlated with survival in glioblastoma multiforme and occurred more often in lower-grade astrocytomas, but ALT+ and ALT- sarcomas were equally aggressive in terms of grade and clinical outcome.The APB assay for ALT is suitable for paraffin-embedded tumors. It showed that a substantial proportion of STS, osteosarcomas, and astrocytomas, but not papillary thyroid carcinomas use ALT. APB positivity correlated strongly with survival of patients with astrocytomas.
ERG and FLI1 binding sites demarcate targets for aberrant epigenetic regulation by AML1-ETO in acute myeloid leukemia
Authors: Joost H. A. Martens, Amit Mandoli, Femke Simmer, Bart-Jan Wierenga, Sadia Saeed, Abhishek A. Singh, Lucia Altucci, Edo Vellenga, Hendrik G. Stunnenberg
Journal: Blood (2012)
Preserving Prostaglandin E2 Level Prevents Rejection of Implanted Allogeneic Mesenchymal Stem Cells and Restores Postinfarction Ventricular Function
Authors: Sanjiv Dhingra, Peng Li, Xi-Ping Huang, Jian Guo, Jun Wu, Anton Mihic, Shu-Hong Li, Wang-Fu Zang, Daniel Shen, Richard D. Weisel, Pawan K. Singal, Ren-Ke Li
Journal: Circulation (2013)

Background— Allogeneic mesenchymal stem cells (MSCs) were immunoprivileged early after cardiac implantation and improved heart function in preclinical and clinical studies. However, long-term preclinical studies demonstrated that allogeneic MSCs lost their immunoprivilege and were rejected in the injured myocardium, resulting in recurrent ventricular dysfunction. This study identifies some of the mechanisms responsible for the immune switch in MSCs and suggests a new treatment to maintain immunoprivilege and preserve heart function. Methods and Results— Rat MSC immunoprivilege was mediated by prostaglandin E2 (PGE2)–induced secretion of 2 critical chemokines, CCL12 and CCL5. These chemokines stimulated the chemoattraction of T cells toward MSCs, suppressed cytotoxic T-cell proliferation, and induced the production of T regulatory cells. MSCs treated with 5-azacytidine for 24 hours differentiated into myogenic cells after 2 weeks, which was associated with decreased PGE2 and chemokine production and the loss of immunoprivilege. Treatment of differentiated MSCs with PGE2 restored chemokine levels and preserved MSC immunoprivilege. In a rat myocardial infarction model, allogeneic MSCs (3×10 6 cells/rat) were injected into the infarct region with or without a biodegradable hydrogel that slowly released PGE2. Five weeks later, the transplanted MSCs expressed myogenic lineage markers and were rejected in the control group, but in the PGE2-treated group, the transplanted cells survived and heart function improved. Conclusions— Allogeneic MSCs maintained immunoprivilege by PGE2-induced secretion of chemokines CCL12 and CCL5. Differentiation of MSCs decreased PGE2 levels, and immunoprivilege was lost. Maintaining PGE2 levels preserved immunoprivilege after differentiation, prevented rejection of implanted MSCs, and restored cardiac function.
New Strategies in Peripheral T-Cell Lymphoma: Understanding Tumor Biology and Developing Novel Therapies
Authors: Kieron Dunleavy, Richard L. Piekarz, Jasmine Zain, John E. Janik, Wyndham H. Wilson, Owen A. O'Connor, Susan E. Bates
Journal: Clinical Cancer Research (2010)

Peripheral T-cell lymphomas (PTCL) constitute a group of heterogeneous diseases that are uncommon, representing, in Western countries, only approximately 10% of all non-Hodgkin lymphomas. They are typically associated with a poor prognosis compared with their B-cell counterparts and are much less well understood with respect to tumor biology, owing to their rarity and biologic heterogeneity, and to the fact that characteristic cytogenetic abnormalities are few compared with B-cell lymphomas. Although the outcome for patients with anaplastic large cell lymphoma (ALCL), particularly anaplastic lymphoma kinase (ALK)-positive ALCL, is good, other types of PTCLs are associated with a poor prognosis, even with aggressive anthracycline-based chemotherapy. In this respect, there is a need for new approaches in these diseases, and this review focuses on and explores recent experience with novel therapies in PTCL.
Scale to Predict Survival After Surgery for Recurrent Glioblastoma Multiforme
Authors: John K. Park, Tiffany Hodges, Leopold Arko, Michael Shen, Donna Dello Iacono, Adrian McNabb, Nancy Olsen Bailey, Teri Nguyen Kreisl, Fabio M. Iwamoto, Joohee Sul, Sungyoung Auh, Grace E. Park, Howard A. Fine, Peter McL. Black
Journal: Journal of Clinical Oncology (2010)

Despite initial treatment with surgical resection, radiotherapy, and chemotherapy, glioblastoma multiforme (GBM) virtually always recurs. Surgery is sometimes recommended to treat recurrence. In this study, we sought to devise a preoperative scale that predicts survival after surgery for recurrent glioblastoma multiforme.The preoperative clinical and radiographic data of 34 patients who underwent re-operation of recurrent GBM tumors were analyzed using Kaplan-Meier survival analysis and Cox proportional hazards regression modeling. The factors associated with decreased postoperative survival (P < .05) were used to devise a prognostic scale which was validated with a separate cohort of 109 patients.The factors associated with poor postoperative survival were: tumor involvement of prespecified eloquent/critical brain regions (P = .021), Karnofsky performance status (KPS) < or = 80 (P = .030), and tumor volume > or = 50 cm(3) (P = .048). An additive scale (range, 0 to 3 points) comprised of these three variables distinguishes patients with good (0 points), intermediate (1 to 2 points), and poor (3 points) postoperative survival (median survival, 10.8, 4.5, and 1.0 months, respectively; P < .001). The scale identified three statistically distinct groups within the validation cohort as well (median survival, 9.2, 6.3, and 1.9 months, respectively; P < .001).We devised and validated a preoperative scale that identifies patients likely to have poor, intermediate, and good relative outcomes after surgical resection of a recurrent GBM tumor. Application of this simple scale may be useful in counseling patients regarding their treatment options and in designing clinical trials.
<i>PIK3CA</i> Mutation Is Associated with a Favorable Prognosis among Patients with Curatively Resected Esophageal Squamous Cell Carcinoma
Authors: Hironobu Shigaki, Yoshifumi Baba, Masayuki Watanabe, Asuka Murata, Takatsugu Ishimoto, Masaaki Iwatsuki, Shiro Iwagami, Katsuhiko Nosho, Hideo Baba
Journal: Clinical Cancer Research (2013)

PIK3CA encodes the catalytic subunit of PI3K, p110α. Mutant PIK3CA stimulates the AKT pathway and promotes cancer cell proliferation. PIK3CA mutations have been associated with poor prognosis in patients with colorectal or lung cancer. In contrast, the relationship between PIK3CA mutations and favorable prognoses has been shown in breast cancer. However, the influence of PIK3CA mutations on the prognosis of patients with esophageal squamous cell carcinoma (ESCC) remains unclear.Using a nonbiased database of 219 curatively resected ESCCs and eight esophageal cancer cell lines, we evaluated PIK3CA mutational status by pyrosequencing. The expression of p53 and phosphorylated AKT (i.e., AKT activation) was evaluated by immunohistochemistry.PIK3CA mutations in exon 9 and/or 20 were detected in 46 cases (21%). No ESCC cell line harbored PIK3CA mutations. PIK3CA mutations were significantly associated with phosphorylated AKT expression, but not with p53 expression, sex, age at surgery, tobacco use, alcohol use, or histologic grade. Compared with wild-type PIK3CA cases, patients with PIK3CA mutations in exons 9 and/or 20 experienced significantly better disease-free survival [log-rank P = 0.0089; univariate HR: 0.37, 95% confidence interval (CI): 0.15-0.75, P = 0.0042; multivariate HR: 0.34, 95% CI: 0.10-0.86, P = 0.021] and overall survival (log-rank P = 0.012; univariate HR: 0.38, 95% CI: 0.16-0.78, P = 0.0060; multivariate HR: 0.35, 95% CI: 0.10-0.90, P = 0.028).PIK3CA mutations in ESCC are associated with longer survival, suggesting its role as a prognostic biomarker. Future studies are needed to confirm this association and to elucidate the exact mechanisms by which PIK3CA mutations affect tumor behavior.
Starvation and hypothyroidism exert an overlapping influence on rat hepatic messenger RNA activity profiles.
Authors: F E Carr, S Seelig, C N Mariash, H L Schwartz, J H Oppenheimer
Journal: Journal of Clinical Investigation (1983)

To assess the effect of starvation and to explore the potential interrelationship of starvation and thyroid status at the pretranslational level, we have analyzed by two-dimensional gel electrophoresis, the hepatic translational products of starved and fed euthyroid and hypothyroid rats. 5 d of starvation resulted in a statistically significant change in 27 of 240 products visualized, whereas hypothyroidism caused a change in 20, both in comparison with the fed euthyroid state. Of considerable interest was that 68% of all changing messenger (m)RNA sequences were common to the hypothyroid and starved groups and showed the same directional shift. Further, both starvation and hypothyroidism yielded comparable decreases in total hepatic cytoplasmic RNA content. Although it has been well established that the level of circulating triiodothyronine (T3) and the level of hepatic nuclear receptors fall in starvation, this reduction cannot account for the observed decrease of total hepatic RNA nor for all of the alterations in the concentrations of specific mRNA sequences. Thus, administration of T3 to starved animals in a dose designed to occupy all nuclear T3 receptors fails to prevent the fall in total RNA and the majority of starvation-induced changes in the level of mRNA sequences. Moreover, starvation of athyreotic animals results in a further decrease in total RNA and in a further change in the level of individual mRNA species. We conclude, therefore, that although the reduced levels of circulating T3 and the nuclear T3 receptors can contribute to the observed results of starvation, the starvation-induced changes are not exclusively mediated by this factor. The striking overlap in the genomic response between hypothyroid and starved animals raises the possibility that those biochemical mechanisms regulated at a pretranslational level by T3 are either not helpful or injurious to the starving animal. The reduction in circulating T3 and nuclear receptor sites together with T3-independent mechanisms initiated in the starved animal may constitute redundant processes designed to conserve energy and substrate in the nutritionally deprived organism.
Mining for coexpression across hundreds of datasets using novel rank aggregation and visualization methods
Authors: Priit Adler, Raivo Kolde, Meelis Kull, Aleksandr Tkachenko, Hedi Peterson, Jüri Reimand, Jaak Vilo
Journal: Genome biology (2009)

We present a web resource MEM (Multi-Experiment Matrix) for gene expression similarity searches across many datasets. MEM features large collections of microarray datasets and utilizes rank aggregation to merge information from different datasets into a single global ordering with simultaneous statistical significance estimation. Unique features of MEM include automatic detection, characterization and visualization of datasets that includes the strongest coexpression patterns. MEM is freely available at http://biit.cs.ut.ee/mem/ .
AMP-Activated Protein Kinase Regulates Endothelial Cell Angiotensin-Converting Enzyme Expression via p53 and the Post-Transcriptional Regulation of microRNA-143/145
Authors: Karin Kohlstedt, Caroline Trouvain, Thomas Boettger, Lei Shi, Beate Fisslthaler, Ingrid Fleming
Journal: Circulation Research (2013)

High-angiotensin-converting enzyme (ACE)-levels are associated with cardiovascular disease, but little is known about the regulation of its expression.To assess the molecular mechanisms regulating endothelial ACE expression focusing on the role of the AMP-activated protein kinase (AMPK) and miR-143/145.Shear stress decreased ACE expression in cultured endothelial cells, an effect prevented by downregulating AMPKα2 but not AMPKα1. AMPKα2(-/-) mice expressed higher ACE levels than wild-type littermates resulting in impaired hindlimb vasodilatation to the ACE substrate, bradykinin. The latter response was also evident in animals lacking the AMPKα2 subunit only in endothelial cells. In cultured endothelial cells, miR-143/145 levels were increased by shear stress in an AMPKα2-dependent manner, and miR-143/145 overexpression decreased ACE expression. The effect of shear stress was unrelated to an increase in miR-143/145 promoter activity and transcription but could be attributed to post-transcriptional regulation of precursor-miR-143/145 by AMPKα2. The AMPK substrate, p53, can enhance the post-transcriptional processing of several microRNAs, including miR-143/145. We found that shear stress elicited the AMPKα2-dependent phosphorylation of p53 (on Ser15), and that p53 downregulation prevented the shear stress-induced decrease in ACE expression. Streptozotocin-induced diabetes mellitus in mice was studied as a pathophysiological model of altered AMPK activity. Diabetes mellitus increased tissue phosphorylation of the AMPK substrates, p53 and acetyl-coenzyme A carboxylase, changes that correlated with increased miR-143/145 levels and decreased ACE expression.AMPKα2 suppresses endothelial ACE expression via the phosphorylation of p53 and upregulation of miR-143/145. Post-transcriptional regulation of miR-143/145 may contribute to the vascular complications associated with diabetes mellitus.
Blood Pressure and the Risk of Cardiovascular Disease
Authors: Stephen MacMahon
Journal: New England Journal of Medicine (2000)

The level of blood pressure has long been recognized as a determinant of the risks for several common cardiovascular diseases, including coronary heart disease, cerebrovascular disease, and heart failure. Throughout the 20th century, most attention has focused on the risks of these diseases (and the possibility of their reversal) among persons considered to have hypertension. However, there are several important reasons to question the appropriateness of continuing to focus attention primarily on hypertension and its treatment, as opposed to the broader concept of blood-pressure–related disease and its prevention. Some of these reasons are illustrated in the report by van den . . .
Early stages of osteoarthritis: the search for sensitive predictors
Authors: F A Wollheim
Journal: Annals of the Rheumatic Diseases (2003)

Risk factors, standard radiography, and biomarkers can be used to detect pre-OA

Osteoarthritis (OA) is perhaps the most common disabling joint affection in developed countries, and consequently a large burden to their health systems.1 Furthermore, it is a growing global problem due to increasing life expectancy as well as obesity and smoking, all identified as risk factors for developing knee OA and knee pain.2,3 Efforts to identify early stages of knee OA are gaining importance because of its prevalence and morbidity and the possible emergence of preventive or modifying interventions. However, radiographic delineation of OA at its onset is not a trivial problem as highlighted by the careful study of Mazzuca et al in this issue of the journal.4 In essence the paper shows that radiographically normal is not identical to anatomically normal. Thus the designation of the unilateral nature of knee OA in the Chingford study is not strictly correct.15 Nevertheless, the Chingford approach to studying early phases of progression and searching for methods to retard or stop this progression is useful and should be pursued.

“The Chingford approach to studying knee OA is not strictly correct but, nevertheless useful” 

Recent work has provided new insight into the formation of cartilage and bone during embryonic development. This highly regulated process has bearing on the pathogenesis of OA. Collagen IIA, a splice variant of mature collagen type II, is formed in chondrogenesis.5 It is absent in adult healthy cartilage but can again be found in OA.6 This observation opens ways to search for biochemical signs of early OA which may be of clinical or scientific use. The problem that …
Building a Rapid Learning Health Care System for Oncology: The Regulatory Framework of CancerLinQ
Authors: Richard L. Schilsky, Dina L. Michels, Amy H. Kearbey, Peter Paul Yu, Clifford A. Hudis
Journal: Journal of Clinical Oncology (2014)

Today is a time of unprecedented opportunity and challenge in health care generally and cancer care in particular. An explosion of scientific knowledge, the rapid introduction of new drugs and technologies, and the unprecedented escalation in the cost of health care challenge physicians to quickly assimilate new information and appropriately deploy new advances while also delivering efficient and high-quality care to a rapidly growing and aging patient population. At the same time, big data, with its potential to drive rapid understanding and innovation, promises to transform the health care industry, as it has many others already. CancerLinQ is an initiative of the American Society of Clinical Oncology (ASCO) and its Institute for Quality, developed to build on these opportunities and address these challenges by collecting information from the electronic health records of large numbers of patients with cancer. CancerLinQ is, first and foremost, a quality measurement and reporting system through which oncologists can harness the depth and power of their patients' clinical records and other data to improve the care they deliver. The development and deployment of CancerLinQ raises many important questions about the use of big data in health care. This article focuses on the US federal regulatory pathway by which CancerLinQ will accept patient records and the approach of ASCO toward stewardship of the information.