tbuckley/cabot-search huggingface dataset:
Cryotherapy for Barrett's esophagus: does the gas really matter?
Authors: J. Dumot, B. Greenwald
Journal: Endoscopy (2011)

Endoscopic spray cryotherapy is a unique advancement in the endoscopist's toolbox. Not long ago, the technology of cryotherapy in spray form was limited to dermatology, where it still enjoys frequent use and efficacy for the elimination of epithelial neoplasia and other unwanted tissue. Non-contact endoscopic ablation modalities include laser, photodynamic therapy (PDT), argon plasma coagulation (APC), and spray cryotherapy. Cryotherapy is distinguished from these other technologies by the use of intensely cold temperatures to disrupt cellular and extracellular functions and to induce apoptosis. Two very different systems are commercially available for endoscopic cryotherapy: liquid nitrogen (CryoSpray Ablation, CSA Medical, Baltimore, Maryland, USA) and carbon dioxide (CO2; Polar Wand, GI Supply, Camp Hill, Pennsylvania, USA). The CO2 system relies on the Joule–Thompson effect, whereby rapid expansion of CO2 freezes the tissue to –78 ° C as it exits the specialized catheter. The liquid nitrogen system delivers actual liquid nitrogen at a temperature of –196 ° C to the target tissue. It is not hard to imagine that the difference of –100 ° C would translate into differences in the technical application, efficacy, and risk profile of each method of endoscopic cryotherapy.
Patient Safety beyond the Hospital
Authors: Tejal K. Gandhi, Thomas H. Lee
Journal: New England Journal of Medicine (2010)

The vast majority of health care is delivered in ambulatory settings, yet we are only just beginning to understand the safety risks that exist outside of hospital walls. There are 900 million visits to physicians' offices in the United States each year, as compared with 35 million hospital discharges,1 and spending on outpatient care is the fastest growing segment of health care spending.2 Yet most patient-safety research and safety-improvement work have been done in inpatient settings; indeed, a search of the Patient Safety Network Web site of the Agency for Healthcare Research and Quality shows that since 2005 only about . . .
Abstract 1789: Preclinical profile of novel and potent c-Met kinase inhibitors
Authors: Swaroop Vakkalanka, Meyyappan Muthuppalaniappan, Babu Govindarajulu, Kanthikiran Varanasi, Sridhar Veeraraghavan, Sumalatha Kuppireddi, Srikant Viswanadha, Nagarathnam Dhanapalan, Prashant Bhavar
Journal: Cancer Research (2012)

Abstract Background: c-Met is a proto-oncogene that encodes the protein Met with intrinsic tyrosine kinase activity. Aberrant Met kinase activity triggers a series of unwarranted phosphorylation events and signalling processes that ultimately lead to the development of cancer. Alteration of the Met kinase signalling cascade represents an attractive approach aimed at blocking invasion and metastasis of cancer cells. Herein, we describe the biological and pharmacokinetic properties of representative molecules from a series of novel and small molecule inhibitors with scope to be further developed as clinical candidates for cancers mediated by dysregulated Met kinase activity. Methods: Met Kinase activity of test compounds was determined using an HTRF® KinEASE assay kit (Cisbio, Bedford, MA) with modifications. Met-dependent anti-proliferative effect was determined in MKN-45 cells. Inhibition of constitutive Met kinase phosphorylation in MKN-45 and NCI-H441 cells was measured in an ELISA assay. Subsequently, effect of the compounds on Akt phosphorylation, a downstream marker in the Met signalling cascade, was determined. Metabolic stability of the compounds was evaluated in microsomes obtained from mouse, rat, dog, monkey, and human. Results: Among the compounds evaluated, RP1269 and RP1316 demonstrated remarkable potency against the purified Met kinase enzyme (20.17 &amp; 40.5 nM) as well as in an MKN-45 cell proliferation assay (18.0 &amp; 2.3 nM). In addition, the compounds caused a significant reduction in constitutive Met kinase phosphorylation in MKN-45 (11.5 &amp; 33.3 nM) and NCI-H441 (2.2 &amp; 4.1 nM) cells. As a consequence, Akt phosphorylation was inhibited at half-maximally in MKN-45 and NCI-H441 cells at &amp;lt;100 nM and &amp;lt;50 nM respectively. Further, the compounds exhibited a favourable ADME profile across the species studied. Conclusions: Our findings demonstrate that RP1269 and RP1316 are potent Met kinase inhibitors with efficacy values comparable to existing Met kinase inhibitors in development. On lines with selective inhibitors, the compounds display anti-proliferative effect only in cells with amplification of the Met kinase gene. The compounds are currently being tested for efficacy and target inhibition in various xenograft models. Clinical candidate shall be nominated by 2012. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1789. doi:1538-7445.AM2012-1789
877 THE EFFICACY AND SAFETY OF TREATING HEPATITIS C IN PATIENTS WITH A DIAGNOSIS OF SCHIZOPHRENIA
Authors: Z. Mustafa, J. Schofield, P.R. Mills, M. Priest, R. Fox, S. Datta, J. Morris, E. Forrest, R. Gillespie, A.J. Stanley, S. Barclay
Journal: Journal of Hepatology (2013)
THU0519 Tissue Factor Over-Expression Identify Patients with Rheumatic Diseases
Authors: N. Maugeri, V. Canti, M. Baldini, P. Rovere-Querini, E. Baldissera, M.G. Sabbadini, A. Manfredi
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Premature coronary heart disease and thromboembolic complications have emerged as a major cause of morbidity and mortality in patients with autoimmune rheumatic diseases. Tissue factor (TF) is a pivotal signal within the coagulation cascade that results in the thrombin generation. In turn thrombin, besides its well-characterized role as an effector of clot formation, is also a potent signal driving the activation of platelets and endothelial cells. An elevated incidence of thromboembolic events has been reported in patients with autoimmune diseases. <h3>Objectives</h3> We analyzed the TF expression on blood cells in patients with autoimmune diseases and matched healthy controls. <h3>Methods</h3> We studied a group of twelve active rheumatic patients comprising 8 females and 4 males, 45 (24-65) years old. Four patients had with reactive arthritis, two with Adult Still9s disease (AOSD), three with ankylosing spondylitis (SA) and three with rheumatoid arthritis (RA). We compared results with 14 healthy donors, sex (8 female and 6 male) and age (median 47, range 27-65 years old) – matched. TF expression was analyzed in platelets, monocytes and neutrophils by flow cytometry in whole blood samples. Results are expressed as mean ± SEM. <h3>Results</h3> A strikingly higher fraction of patients blood cells expressed TF compared to healthy controls. Specifically, platelets expressing TF were the 23.6±2.0 in patients vs. 2.5±0.7% in controls. The monocyte TF expression was 19.2±4.0 in patients vs. 1.9±0.6% in controls and neutrophil TF expression was 22.3±3.3 in patients vs. 2.4±1.1% in controls. All <i>p</i>&lt;0.001. We did not observe any significant association between blood cell TF expression and age, sex, actual diagnosis, disease duration or treatment. <h3>Conclusions</h3> The fraction of TF positive leukocytes and platelets was consistently higher in patients with rheumatic diseases compared with matched controls. This features is shared by patients with diseases with different pathogenesis and clinical features, such as AR, SA and AOSD. This feature could be involved in the increased thromboembolic risk associated to rheumatic conditions. <h3>References</h3> Maugeri N. et al; Srp Arh Celok Lek. 2010. Maugeri N. et al; Autoimmunity 2009. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5071
Cathepsin D and Prognosis in Breast Cancer
Authors: Atul K. Tandon, Gary M. Clark, Gary C. Chamness, John M. Chirgwin, William L. McGuire
Journal: New England Journal of Medicine (1990)

We investigated the possibility that cathepsin D, an estrogen-induced lysosomal protease, might have value as a prognostic factor in breast cancer by studying frozen tissue specimens from 397 patients. We measured the 34-kd mature form of the enzyme by Western blot assay and densitometry. Among 199 patients with node-negative disease, but not among 198 with node-positive disease, high levels of cathepsin D proved to be a significant predictor of reduced disease-free survival (median follow-up, 64 months), either as a continuous variable (log cathepsin D; P = 0.018) or as a dichotomous variable with an optimized cutoff point (P = 0.0001). Results were similar for overall survival (P = 0.009 and 0.0001, respectively). Relating the level of cathepsin D to other prognostic factors in the patients with node-negative disease, we found an association with aneuploidy but none with estrogen or progesterone receptors, tumor size, or the age of the patient. In multivariate analyses, a high level of cathepsin D was the most important independent factor in predicting shorter disease-free and overall survival in patients with node-negative disease. As compared with the risk in women with low levels of cathepsin D, the relative risk of tumor recurrence was 2.6 (95 percent confidence interval, 1.6 to 4.4) and the relative risk of death was 3.9 (95 percent confidence interval, 2.1 to 7.3) among those with high levels of cathepsin D. For disease-free survival, cathepsin D status was predictive of outcome primarily among those with aneuploid tumors; the actuarial five-year recurrence rates of aneuploid tumors were 60 percent among women with high levels of cathepsin D and 29 percent among those with low levels, as compared with 22 percent for all diploid tumors. We conclude that cathepsin D may be an independent predictor of early recurrence and death in node-negative breast cancer.
Having Cancer and Looking Different--A Classroom Experiment With Hair Loss
Authors: J. A. Steele
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Having Cancer and Looking Different—A Classroom Experiment With Hair Loss Get access Julie A. Steele Julie A. Steele Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 8, 17 April 1991, Page 538, https://doi.org/10.1093/jnci/83.8.538 Published: 17 April 1991
FUNCTION OF ECOTROPIC VIRAL INTEGRATION SITE 1 (EVI1) GENE IN MOUSE NEURAL PRECURSOR CELLS AND HUMAN GLIOMA INITIATING CELLS
Authors: H. Takeshima, K. Yokogami, A. Mizuguchi, K. Yamasaki, T. Kawasoe, K. Morishita
Journal: Neuro-Oncology (2014)

BACKGROUND: Ecotropic viral integration site 1 (EVI1) gene encodes a transcription factor, containing ten zinc finger motifs found within two domains of the protein. Abnormal expression of EVI1 is found in 5-10% of patients with acute myeloid leukemia (AML), and is associated with unfavorable outcome. EVI1 maintains the self-renewal capacity of hematopoietic stem cells (HSCs), of cell quiescence and stem cell-like phenotypes in leukemia cells. EVI1 knocked out mice die approximately 10.5 days post-coitus (d.p.c.; E10.5) with defect or hypoplasty in heart, cranial ganglia, peripheral nervous system. It is possible that EVI1 also regulates the fate of neural stem cells (NPCs) and glioma initiating cells (GICs) as well as HSCs. METHODS: We investigated the biological effect of knockdown and overexpression of EVI1 against NPCs and GICs. RESULTS: We found that NPCs from nestin-cre induced EVI1 (-/-) mouse differentiated to neuron and glial cells earlier than wild type NPCs. Notch signals were altered in EVI1 (-/-) NPCs. Knockdown experiment with shEVI1 in GICs showed the monolayerd GICs hard to stick to laminin-coated dish by alteration of integrin signals. Because laminin is a major component of niche of NPCs and GICs, EVI1 has an important role to maintain the stem cell capacity by committing to niche. Moreover overexpression of EVI1 in U87 MG and GICs decreased cell proliferation. CONCLUSIONS: Taken together, EVI1 regulates the cell fate and proliferation of NPCs and GICs. SECONDARY CATEGORY: n/a.
Behavioral Economics and Physician Compensation — Promise and Challenges
Authors: Dhruv Khullar, Dave A. Chokshi, Robert Kocher, Ashok Reddy, Karna Basu, Patrick H. Conway, Rahul Rajkumar
Journal: New England Journal of Medicine (2015)

Interview with Dr. Dhruv Khullar on uses of behavioral economics concepts in modifying physicians' behavior under value-based health care models. (09:26)Download Health care organizations embracing new payment models may find that applying behavioral economics can boost the effect of new incentives. By creating more favorable decision-making environments, we can take advantage of cognitive biases to encourage high-value care.
Endovascular Therapy for Stroke — It's about Time
Authors: Anthony J. Furlan
Journal: New England Journal of Medicine (2015)

Although many stroke centers worldwide have performed endovascular stroke therapy since the results of the Prolyse in Acute Cerebral Thromboembolism (PROACT) II trial were published in 1999,1 lingering uncertainties about efficacy and the selection of patients created an uneasy equipoise. Especially nettlesome was the uncertain benefit of endovascular therapy as compared with intravenous tissue plasminogen activator (t-PA). The controversy over endovascular therapy was heightened in 2013 when the results of the Interventional Management of Stroke (IMS) III,2 Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE),3 and Local versus Systemic Thrombolysis for Acute Ischemic Stroke (SYNTHESIS Expansion)4 clinical . . .
Abstract 1025: Rac1 is a novel binding partner of the anti-apoptotic protein Bcl-2
Authors: Jia Kang, Rathiga Velaithan, Jayshree L. Hirpara, Thomas Loh, Catherine Brenner, Marie-Veronique Clement, Shazib Pervaiz
Journal: Cancer Research (2010)

Abstract We have previously reported that Bcl-2 expression resulted in an increase in intracellular superoxide anion and that a dominant negative mutant of the small GTPase Rac1 sensitized Bcl-2 expressing cells to apoptosis. Here we report that silencing and functional inhibition of Rac1 blocks Bcl-2 mediated increases in intracellular and mitochondrial superoxide levels in tumor cells. We provide evidence that this effect is mediated via specific interaction between the two proteins using co-immunoprecipitation, confocal and electron microscopy, as well as GST-fusion proteins. Analysis of the sub-cellular localization of these proteins revealed increased association of Bcl-2 and mitochondrial Rac1 in Bcl-2 overexpressing cells. This interaction can be blocked in vitro and in vivo by BH3 mimetics such as HA14-I, BH3-I as well as synthetic Bcl-2 BH3 domain peptides. That this interaction is functionally relevant is supported by the ability of the Bcl-2 BH3 peptide to inhibit intracellular superoxide production as well as overcome drug resistance in Bcl-2 overexpressing cells. Lastly, using patient-derived primary tissues, we observed the interaction only in cancerous tissues with marked overexpression of Bcl-2 and not in peripheral blood leukocytes or samples from non-cancerous tissue. These data provide a novel facet in the biology of Bcl-2 with potential implications for targeted anti-cancer drug design. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1025.
Abstract 2442: A precise orthotopic rectal tumor model for evaluating therapeutic response of cancer treatment
Authors: Satoru Kikuchi, Hiroyuki Kishimoto, Hiroshi Tazawa, Yuuri Hashimoto, Futoshi Uno, Masahiko Nishizaki, Shunsuke Kagawa, Yasuo Urata, Robert M. Hoffman, Toshiyoshi Fujiwara
Journal: Cancer Research (2012)

Abstract We have previously reported a “true” orthotopic rectal model in which tumors start forming in the rectal mucosal tissue from which tumors actually arise. The model was generated by intrarectal transplantation of mouse rectal cancer cells stably expressing fluorescent protein, followed by disrupting the epithelial cell layer of the rectal mucosa by soaking with an acetic acid solution. Early stage tumor was detected on the rectal mucosa from as early as 6 days after transplantation, which then became invasive into the submucosal tissue. The tumor incidence on the rectal mucosa was 100%, and it was proved that this rectal tumor model reflects the natural course of rectal cancer accurately. Spontaneous lymph node metastasis and lung metastasis were observed 4 weeks after transplantation in over 90% of mice. In the present study, we will report whether this model is useful for evaluating therapeutic response of surgical local resection of tumor with combination of anticancer drugs such as a telomerase-specific replicating adenovirus designed for cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2442. doi:1538-7445.AM2012-2442
Abstract 2480: High-level activation of the Notch pathway in diffuse intrinsic pontine glioma
Authors: Marianne Hutt, Kah Jing Lim, Katherine Warren, Howard T. Chang, Charles G. Eberhart, Eric H. Raabe
Journal: Cancer Research (2012)

Abstract Diffuse intrinsic pontine glioma (DIPG) is a universally fatal pediatric brain tumor. Due to its critical location within the brainstem, and its characteristic MRI signature, biopsy is rarely performed. Since many patients die at home in hospice care, autopsy specimens have traditionally been rare. Because of this difficulty in obtaining tissue, three institutions (Johns Hopkins, Children's National Medical Center, and the National Institutes of Health - Pediatric Oncology Branch) have formed the Mid-Atlantic DIPG Consortium (MADC), to collect and disseminate rapid-autopsy material from patients with DIPG. Using a fresh tissue specimen obtained from a rapid autopsy and disseminated through the MADC, we have established a human DIPG xenograft and neurosphere cell line, JHH-DIPG1. In vitro, these cells are GFAP positive and express human neural stem cell markers often observed in glioblastoma, including human specific SOX2 and NESTIN. They also show marked invasive properties in vitro as measured by transwell invasion assay. In vivo, JHH-DIPG1 forms tumor xenografts in approximately six months in immunocompromised mice. Tumor cells diffusely infiltrate distant brain structures, recapitulating the invasive phenotype of DIPG. Due to their high level expression of neural stem cell markers, and the well-known roles of the Notch pathway in stem cell biology and aggressive brain tumors, we examined the expression of members of the Notch pathway in DIPG. Notch downstream effectors, specifically Hes1, Hes5 and Hey1, are highly expressed in JHH-DIPG1, at levels equal to or exceeding those observed in neurosphere cell lines derived from adult supratentorial glioblastoma. The JHH-DIPG1 tumor cell line represents one of only a handful of pediatric DIPG cell lines extant, and the high level of Notch pathway activation in these cells suggests that blockade of the Notch pathway using gamma secretase inhibitors and shRNAs against the canonical Notch effector CBF may be efficacious in DIPG. Our laboratory is actively investigating the role of the Notch pathway in DIPG using this and other DIPG cell lines, with the goal of moving Notch inhibition into clinical trials for these currently highly lethal tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2480. doi:1538-7445.AM2012-2480
Abstract 1474: Semaphorin 3A potentiates metastatic disease by binding to endothelial Neuropilin-1 and disrupting vascular barrier function
Authors: Lisette M. Acevedo, Jay Desgrosellier, David A. Cheresh
Journal: Cancer Research (2011)

Abstract We previously showed that Semaphorin 3A (Sema3A), a known inhibitor of axonal sprouting, inhibits VEGF-induced angiogenesis yet induces vascular permeability. In patient samples, immunohistochemical analysis of Sema3A showed that its expression increased with disease progression and metastasis. Similarly, Sema3A expression was higher in cell lines with enhanced metastatic potential. We considered whether Sema3A expression in a variety of highly malignant tumor cells might contribute to their metastatic properties based on Sema3A's capacity to disrupt vascular barrier function. To evaluate this, we stably knocked down Sema3A expression in CT26 (colon) and B16-BL6 (skin) cells and examined their growth and invasive properties both in vitro and in vivo. Loss of Sema3A significantly decreased the incidence of pulmonary lung metastasis. Importantly, Sema3A knockdown did not impair tumor cell adhesion, migration, proliferation, or anchorage-independent growth in vitro; and it had no effect on primary tumor growth and angiogenesis in vivo, suggesting a role for Sema3A in tumor cell extravasation. Furthermore, tamoxifen-inducible conditional knockout of the Sema3A receptor Neuropilin-1 (Nrp1) within the adult endothelium inhibited lung colonization and metastasis but had no effect on primary tumor growth. Similarly, a function blocking antibody against Nrp1 known to inhibit Sema3A-mediated permeability prevented lung colonization. Because Nrp1 is also a co-receptor for VEGF, we reintroduced a mutant of Nrp1 that lacks Sema3A but not VEGF binding capability into our tamoxifen-inducible endothelial-specific Nrp1 knockout mouse. Expression of mutant Nrp1 inhibited experimental metastasis, but not primary tumor growth confirming a specific role for Sema3A-Nrp1 interaction in extravasation. Together these findings define a pathological role for tumor cell secreted Sema3A as a potentiator of tumor cell metastasis and vascular barrier disruption. 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 1474. doi:10.1158/1538-7445.AM2011-1474