tbuckley/cabot-search huggingface dataset:
ORFV: A Novel Oncolytic and Immune Stimulating Parapoxvirus Therapeutic
Authors: Julia L Rintoul, Chantal G Lemay, Lee-Hwa Tai, Marianne M Stanford, Theresa J Falls, Christiano T de Souza, Byram W Bridle, Manijeh Daneshmand, Pamela S Ohashi, Yonghong Wan, Brian D Lichty, Andrew A Mercer, Rebecca C Auer, Harold L Atkins, John C Bell
Journal: Molecular Therapy (2012)

Replicating viruses for the treatment of cancer have a number of advantages over traditional therapeutic modalities. They are highly targeted, self-amplifying, and have the added potential to act as both gene-therapy delivery vehicles and oncolytic agents. Parapoxvirus ovis or Orf virus (ORFV) is the prototypic species of the Parapoxvirus genus, causing a benign disease in its natural ungulate host. ORFV possesses a number of unique properties that make it an ideal viral backbone for the development of a cancer therapeutic: it is safe in humans, has the ability to cause repeat infections even in the presence of antibody, and it induces a potent T(h)-1-dominated immune response. Here, we show that live replicating ORFV induces an antitumor immune response in multiple syngeneic mouse models of cancer that is mediated largely by the potent activation of both cytokine-secreting, and tumoricidal natural killer (NK) cells. We have also highlighted the clinical potential of the virus by demonstration of human cancer cell oncolysis including efficacy in an A549 xenograft model of cancer.
Papillary muscle rupture following myocardial infarction: Successful treatment by resection of akinetic left ventricular area, mitral valve replacement, and aorta to coronary artery bypass graft
Authors: D. A. Mary, B. C. Pakrashi, M. I. Ionescu
Journal: Thorax (1973)

A patient is reported in whom rupture of the posterior papillary muscle of the left ventricle occurred following myocardial infarction. The intractable pulmonary oedema that followed responded to the combined surgical approach of mitral valve replacement, resection of the akinetic area of the left ventricular wall, and saphenous vein aortocoronary bypass. This combination of surgical procedures has not been reported to date, and was considered to have preserved adequate left ventricular performance.
A New Role for P-Selectin in Shear-Induced Platelet Aggregation
Authors: Michael Merten, Thomas Chow, J. David Hellums, Perumal Thiagarajan
Journal: Circulation (2000)

P-selectin, expressed on platelets on activation, mediates rolling of platelets on endothelial cells, but its role in shear-induced platelet aggregation is not known.Platelets were exposed to either a single pulse (30 seconds) or 3 pulses (10 seconds) of high shear stress (150 to 200 dynes/cm(2)) each followed by low shear stress (10 dynes/cm(2)) for 4.5 minutes or 90 seconds, respectively, at 37 degrees C to resemble more closely in vivo conditions such as those in stenotic arteries. Under these conditions, platelet aggregation was significantly increased compared with low or high shear stress alone. Monoclonal anti-P-selectin antibodies inhibited shear-induced platelet aggregation, especially when induced by the combination of high and low shear stress, by approximately 70% and had an additive effect on the inhibition by abciximab (anti-glycoprotein (GP) IIb/IIIa antibody). However, anti-P-selectin antibody inhibited shear-induced platelet aggregation only at 37 degrees C, not at 22 degrees C, whereas abciximab inhibited shear-induced platelet aggregation at both 22 degrees C and 37 degrees C. This differential effect of anti-P-selectin antibody is explained by the finding that shear-induced P-selectin expression on platelets was observed mainly at 37 degrees C.These results indicate that pulsatile shear stress, which resembles flow conditions in stenotic arteries, induces significantly more platelet aggregation at 37 degrees C than monophasic shear stress. Under these conditions, we show a novel role for P-selectin in platelet aggregation distinct from that of GP IIb/IIIa, which may be of importance in the initiation of thrombosis associated with atherosclerotic lesions.
Generation and Homing of iPSC-Derived Hematopoietic Cells In Vivo
Authors: Bin-Kuan Chou, Zhaohui Ye, Linzhao Cheng
Journal: Molecular Therapy (2013)

Extensive investigations by dozens of laboratories around the world over the past decade have failed to develop a reproducible and reliable way to differentiate human pluripotent stem cells such as embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) into hematopoietic stem cells (HSCs) that are functional both in vivo and in vitro. However, in this issue of Molecular Therapy, Suzuki et al. describe the use of iPSC-derived teratomas as in vivo bioreactors mimicking early embryos for the generation of engraftable HSC-like cells.
Sagopilone (ZK-EPO, ZK 219477) for recurrent glioblastoma. A phase II multicenter trial by the European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumor Group
Authors: R. Stupp, A. Tosoni, J.E.C. Bromberg, P. Hau, M. Campone, J. Gijtenbeek, M. Frenay, L. Breimer, H. Wiesinger, A. Allgeier, M.J. van den Bent, U. Bogdahn, W. van der Graaf, H.J. Yun, T. Gorlia, D. Lacombe, A.A. Brandes
Journal: Annals of Oncology (2011)

BackgroundSagopilone (ZK 219477), a lipophylic and synthetic analog of epothilone B, that crosses the blood–brain barrier has demonstrated preclinical activity in glioma models.Patients and methodsPatients with first recurrence/progression of glioblastoma were eligible for this early phase II and pharmacokinetic study exploring single-agent sagopilone (16 mg/m2 over 3 h every 21 days). Primary end point was a composite of either tumor response or being alive and progression free at 6 months. Overall survival, toxicity and safety and pharmacokinetics were secondary end points.ResultsThirty-eight (evaluable 37) patients were included. Treatment was well tolerated, and neuropathy occurred in 46% patients [mild (grade 1) : 32%]. No objective responses were seen. The progression-free survival (PFS) rate at 6 months was 6.7% [95% confidence interval (CI) 1.3–18.7], the median PFS was just over 6 weeks, and the median overall survival was 7.6 months (95% CI 5.3–12.3), with a 1-year survival rate of 31.6% (95% CI 17.7–46.4). Maximum plasma concentrations were reached at the end of the 3-h infusion, with rapid declines within 30 min after termination.ConclusionsNo evidence of relevant clinical antitumor activity against recurrent glioblastoma could be detected. Sagopilone was well tolerated, and moderate-to-severe peripheral neuropathy was observed in despite prolonged administration.
Pathological Response and Circulating Tumor Cell Count Identifies Treated HER2+ Inflammatory Breast Cancer Patients with Excellent Prognosis: BEVERLY-2 Survival Data
Authors: Jean-Yves Pierga, Thierry Petit, Christelle Lévy, Jean-Marc Ferrero, Mario Campone, Joseph Gligorov, Florence Lerebours, Henri Roché, Thomas Bachelot, Emmanuelle Charafe-Jauffret, Jacques Bonneterre, Juana Hernandez, François-Clément Bidard, Patrice Viens
Journal: Clinical Cancer Research (2014)

The BEVERLY-2 single-arm phase II trial assessed the efficacy and safety of combining neoadjuvant chemotherapy with bevacizumab and trastuzumab for the treatment of HER2-positive inflammatory breast cancer (IBC). Here, we report the results of a preplanned survival analysis at 3 years of follow-up, along with the association between outcome and circulating biomarkers and pathologic complete response (pCR).Patients received fluorouracil, epirubicin, cyclophosphamide, and bevacizumab (cycles 1-4) and docetaxel, trastuzumab, and bevacizumab (cycles 5-8) before surgery, followed by trastuzumab and bevacizumab for 30 weeks after surgery. Circulating tumor cell (CTC) and endothelial cell (CEC) counts were assessed at baseline, cycle 5, preoperative, postoperative, and at 1 year.Fifty-two patients were included. The 3-year disease-free survival (DFS) rate was 68% and overall survival (OS) rate was 90%. pCR (centrally reviewed) was strongly associated with 3-year DFS [80% and 53% in patients with/without pCR, respectively (P = 0.03)]. CTC detection also independently predicted 3-year DFS [81% vs. 43% for patients with <1 vs. ≥1 CTC/7.5 mL at baseline (P = 0.01)]. Patients with no CTCs detected at baseline and with pCR had a high 3-year DFS (95%). CEC changes during treatment had no prognostic value.Our study suggests that the prognosis of IBC relies on more than the achievement of pCR and highlights the role of early hematogenous tumor dissemination as assessed by CTCs. Combining these two prognostic factors isolates a subgroup of IBC with excellent survival when treated with bevacizumab- and trastuzumab-containing regimens.
Attenuation of acid induced oesophagitis in VR-1 deficient mice
Authors: K Fujino
Journal: Gut (2005)

<b>Background and aims:</b> Activation of the vanilloid receptor subtype 1 (VR-1) results in release of proinflammatory peptides which initiate an inflammatory cascade known as neurogenic inflammation. We investigated its role in an acute model of surgically induced oesophagitis. <b>Methods:</b> Oesophagitis was induced by pyloric ligation in wild-type and VR-1 deficient mice. A subset of animals were administered the VR-1 antagonist capsazepine, famotidine, or omeprazole one hour before surgery. Five hours after surgery, myeloperoxidase activity (MPO), histological damage scores, intragastric pH, and immunocytochemical analysis of substance P (SP) receptor endocytosis were determined. <b>Results:</b> Oesophagitis induced knockout mice exhibited significantly lower levels of MPO activity, histological damage scores, and SP receptor endocytosis than wild-type mice. Inflammatory parameters were significantly reduced by acid inhibition and capsazepine in wild-type mice. <b>Conclusions:</b> We conclude that acute acid induced oesophagitis is reduced in animals lacking VR-1. This suggests that acid induced oesophagitis may act through VR-1 and that inhibition of the receptor may reduce inflammation.
Suppressor of cytokine signalling 1 in lymphocytes regulates the development of intestinal inflammation in mice
Authors: K Inagaki-Ohara
Journal: Gut (2005)

<b>Background and aims:</b> Imbalance between pro- and anti-inflammatory cytokines produced by intestinal T cells induces inflammatory bowel diseases (IBD). However, the importance of regulation of cytokine signalling in IBD has not been fully clarified. We have demonstrated that suppressor of cytokine signalling 1 (SOCS1) is expressed in inflamed tissues in an experimental colitis model. In the present study, we investigated the role of SOCS1 in colitis models to clarify the mechanism of IBD development. <b>Methods:</b> Intestinal T cells in transgenic mice expressing high levels of SOCS1 in lymphocytes (SOCS1Tg mice) were characterised by flow cytometric analysis and cytokine production from intestinal T cells was determined by ELISA. 2,4,6-Trinitrobenzene sulphonic acid (TNBS) induced colitis was induced in SOCS1Tg mice and severity was compared with control littermates by measurement of survival rates. Intracellular signalling was assessed by western blotting analysis. <b>Results:</b> SOCS1Tg mice developed colitis spontaneously with age. Young SOCS1Tg mice less than 15 weeks of age, before the onset of colitis, were susceptible to TNBS induced colitis. Intestinal T cells of SOCS1Tg mice showed increased interferon γ and tumour necrosis factor α production and decreased transforming growth factor β production. Expression of cytotoxic T lymphocyte associated antigen 4 (CTLA-4), a negative regulator of T cell activation, in SOCS1Tg mice was severely impaired at the protein level although mRNA levels of CTLA-4 in SOCS1Tg mice were comparable with those in control mice. <b>Conclusions:</b> Our data suggest that SOCS1 plays an important role in the regulation of colitis by controlling intestinal T cell activation mediated through CTLA-4 expression.
Scaling Up Diabetes Prevention in Victoria, Australia: Policy Development, Implementation, and Evaluation
Authors: James A. Dunbar, Abirami Jayawardena, Greg Johnson, Karen Roger, Amy Timoshanko, Vincent L. Versace, Jane Shill, Benjamin Philpot, Erkki Vartiainen, Tiina Laatikainen, James D. Best, Edward D. Janus
Journal: Diabetes Care (2013)

OBJECTIVE The Australian lifestyle intervention program Life! is only the second reported, large-scale diabetes prevention program. This article describes the genesis and the successful establishment of Life! and its key outcomes for participants and implementation. RESEARCH DESIGN AND METHODS Life!, a behavior-change intervention, comprises six group sessions over 8 months. The Victorian Department of Health funded Diabetes Australia–Victoria to implement the program. Experience of the Greater Green Triangle diabetes prevention implementation trial was used for intervention design, workforce development, training, and infrastructure. Clinical and anthropometric data from participants, used for program evaluation, were recorded on a central database. RESULTS Life! has a statewide workforce of 302 trained facilitators within 137 organizations. Over 29,000 Victorians showed interest in Life!, and 15,000 individuals have been referred to the program. In total, 8,412 participants commenced a Life! program between October 2007 and June 2011, and 37% of the original participants completed the 8-month program. Participants completing sessions 1 to 5 lost an average of 1.4 kg weight (P &amp;lt; 0.001) and waist circumference of 2.5 cm (P &amp;lt; 0.001). Those completing six sessions lost an average of 2.4 kg weight (P &amp;lt; 0.001) and waist circumference of 3.8 cm (P &amp;lt; 0.001). The weight loss of 2.4 kg represents 2.7% of participants’ starting body weight. CONCLUSIONS The impact of Life! is attributable to applying available evidence for the system’s design of the intervention and collaboration between policy makers, implementers, and evaluators using the principles of continuous quality improvement to support successful, large-scale recruitment and implementation.
MYCN amplification predicts poor outcome for patients with supratentorial primitive neuroectodermal tumors of the central nervous system
Authors: Marco Gessi, André O. von Bueren, Andras Treszl, Anja zur Mühlen, Wolfgang Hartmann, Monika Warmuth-Metz, Stefan Rutkowski, Torsten Pietsch
Journal: Neuro-Oncology (2014)

Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are a rare group of neoplasms occurring in the CNS that includes supratentorial CNS-PNETs, medulloepitheliomas, and ependymoblastomas. While ependymoblastomas frequently carry chromosome 19q13.41 amplification and show aggressive clinical behavior, the biological mechanisms and molecular alterations contributing to the pathogenesis of supratentorial CNS-PNETs remain poorly understood. Moreover, genetic alterations suitable for molecular risk stratification are undefined to date. In order to identify possible molecular markers, we performed multiplex ligation-dependent probe amplification (MLPA) and molecular inversion probe (MIP) analysis on DNA samples of 25 supratentorial CNS-PNETs (median age, 5.35 years; range, 2.41–17.28 years). Tumors with ependymoblastic rosettes (ependymoblastoma/ETANTR) and LIN28A positivity were excluded. MLPA and MIP analysis revealed large losses of genomic material of chromosomes 3, 4, 5, and 13, while frequent gains affected chromosomes 1, 17, 19, 20, and 22. High copy number gains (amplifications) were found in particular at chromosomes 2p24.3 (MYCN, n = 6 cases) and 4q12 (n = 2 cases). Patients with tumors harboring 2p gain or MYCN amplification showed unfavorable overall survival (P = .003 and P = .001, respectively).These markers were independent of the presence of metastases, which was indeed a clinical factor associated with poor overall survival (P = .01) in this series. In the era of the personalized neuro-oncology, the identification of these molecular prognostic markers associated with patient outcome may represent a significant step towards improved patient stratification and risk-adapted therapeutic strategies for patients suffering from supratentorial CNS-PNETs.
SERUM CHANGES FOLLOWING THYROPARATHYROIDECTOMY
Authors: William Petersen, James W. Jobling, A. A. Eggstein
Journal: The Journal of Experimental Medicine (1916)

1. In thyroparathyroidectomized dogs the onset of tetany bears no constant relation to the ferment-antiferment balance of the serum. 2. The serum lipase titer remains at a low level throughout. 3. A progressive increase in non-coagulable nitrogen and proteoses is observed in the serum following the removal of the glands. 4. The amino nitrogen of the serum is usually increased at the time when tetany is most marked.
Visuomotor Performance in <i>KCNJ11</i>-Related Neonatal Diabetes Is Impaired in Children With DEND-Associated Mutations and May Be Improved by Early Treatment With Sulfonylureas
Authors: Reshma P. Shah, Karen Spruyt, Brigette C. Kragie, Siri Atma W. Greeley, Michael E. Msall
Journal: Diabetes Care (2012)

To assess performance on an age-standardized neuromotor coordination task among sulfonylurea-treated KCNJ11-related neonatal diabetic patients.
Glutathione Peroxidase 3, Deleted or Methylated in Prostate Cancer, Suppresses Prostate Cancer Growth and Metastasis
Authors: Yan P. Yu, Guoying Yu, George Tseng, Kathleen Cieply, Joel Nelson, Marie Defrances, Reza Zarnegar, George Michalopoulos, Jian-Hua Luo
Journal: Cancer Research (2007)

Abstract Glutathione peroxidase 3 is a selenium-dependent enzyme playing a critical role in detoxifying reactive oxidative species and maintaining the genetic integrity of mammalian cells. In this report, we found that the expression of glutathione peroxidase 3 (GPx3) was widely inactivated in prostate cancers. Complete inactivation of GPx3 correlates with a poor clinical outcome. Deletions (hemizygous and homozygous) of GPx3 gene are frequent in prostate cancer samples, occurring in 39% of the samples studied. The rate of methylation of the GPx3 exon 1 region in prostate cancer samples reaches 90%. Overexpression of GPx3 in prostate cancer cell lines induced the suppression of colony formation and anchorage-independent growth of PC3, LNCaP, and Du145 cells. PC3 cells overexpressing GPx3 reduced invasiveness in Matrigel transmigration analysis by an average of 2.7-fold. Xenografted PC3 cells expressing GPx3 showed reduction in tumor volume by 4.8-fold, elimination of metastasis (0/16 versus 7/16), and reduction of animal death (3/16 versus 16/16). The tumor suppressor activity of GPx3 seems to relate to its ability to suppress the expression of c-met. The present findings suggest that GPx3 is a novel tumor suppressor gene. [Cancer Res 2007;67(17):8043–50]
From Kanner to DSM-5: Autism as an Evolving Diagnostic Concept
Authors: Fred R. Volkmar, James C. McPartland
Journal: Annual Review of Clinical Psychology (2013)

Seven decades have elapsed since Leo Kanner described the syndrome he termed early infantile autism. Over this time, and particularly over the past two decades, noteworthy changes have occurred in how the condition is conceptualized. Here we provide an overview of these changes, beginning with a brief discussion of the significance of classification in general before discussing Kanner's original paper and subsequent changes. We touch on relevant issues, such as comorbidity, dimensional aspects of diagnosis and screening, and the complex issue of diagnosis relative to eligibility for services. Approaches to diagnosis have tended to swing from emphasizing overarching groups (lumping) to focusing on potentially distinct subgroups (splitting). Autism raises particular problems given the broad range of syndrome expression over age and developmental level. The most recent revision of the American Psychiatric Association's diagnostic taxonomy marks a significant departure from its predecessor and has been the focus of much debate. It remains unclear which of the currently existing categorical approaches will ultimately be most widely applied. We hope to convey a sense of areas in which consensus has been achieved and areas of continued controversy.
Cancer Treatment and Age: Patient Perspectives
Authors: P. A. Newcomb, P. P. Carbone
Journal: JNCI Journal of the National Cancer Institute (1993)

Despite some evidence that age does not meaningfully influence the efficacy or toxicity of cancer treatment, older patients tend to receive less comprehensive cancer therapies.We conducted a population-based study to evaluate the selection of cancer treatment among the elderly.Between September 1 and November 30, 1990, we interviewed by telephone a sample of 628 female Wisconsin residents recently diagnosed with breast (507) or colorectal (121) cancer. The women, aged 20-74 at the time of diagnosis, were identified through Wisconsin's statewide tumor registry. The approximately 30-minute long telephone interview, part of a larger study of cancer etiology, included questions on treatment history, physician specialty, and reasons for the selection of specific therapies. Analyses compared the proportion of subjects with various treatment characteristics according to age (< 65 and > or = 65 years). In evaluating the effect of age on selected therapies, we adjusted summary proportions for stage of disease using the indirect method. The Mantel-Haenszel chi square statistic was used to evaluate statistical significance of the differences in proportions.After adjusting for stage of disease at diagnosis, substantial variation was observed in cancer treatment according to age for both breast and colorectal cancer. Older women (> or = 65 years) with breast cancer were less likely than younger women (< 65 years) to have received conservative surgery, radiation, and adjuvant therapy. Older women were, in fact, more likely than younger women to accept mastectomy (P = .03). Consultation with a medical or radiation oncologist was less common among older than younger patients (57% versus 73%). Older women were also less likely to have alternative therapies presented to them (19% versus 31%). While older patients were less likely to have been offered adjuvant treatments, like chemotherapy (P < .01), they were also more likely than younger women to reject these treatments when offered (P = .01). These differences were observed in both breast and colorectal cancer patients. Regardless of age, the most common reasons for not selecting treatments were physicians' recommendations and the desire for more comprehensive treatment. Concern about side effects, however, was more frequently reported by older women (P = .07).Patients' ages influence the choice of treatment. Physicians offer older women with cancer different treatments from those offered to younger women and are less likely to recommend specialist consultation. Physicians' advice and description of toxicity may influence patients' selection of treatment. However, older patients' concerns about the consequences of cancer treatment may also influence treatment choice.
Episomal amplification of NUP214-ABL1 fusion gene in B-cell acute lymphoblastic leukemia
Authors: Toby Eyre, Claire J. Schwab, Ross Kinstrie, Ann Keen McGuire, Jen Strefford, Andrew Peniket, Adam Mead, Tim Littlewood, Tessa L. Holyoake, Mhairi Copland, Anthony V. Moorman, Christine J. Harrison, Paresh Vyas
Journal: Blood (2012)
Larger and Stronger Expression of Tregs Gut Homing Receptors with Epicutaneous Than with Sublingual or Oral Immunotherapy
Authors: Vincent Dioszeghy, Lucie Mondoulet, Sophie Wavrin, Benjamin Pelletier, Camille Plaquet, Emilie Puteaux, Mélanie Ligouis, Véronique Dhelft, Christophe Dupont, Pierre Henri Benhamou
Journal: Journal of Allergy and Clinical Immunology (2015)