tbuckley/cabot-search huggingface dataset:
Abstract 1018: Inhibition of BET bromodomain targets genetically diverse glioblastoma.
Authors: Jialiang Wang, Zhixiang Cheng
Journal: Cancer Research (2013)

Abstract Epigenetic regulations have been increasingly recognized as an integral part of tumor biology and attractive therapeutic targets. The bromodomain and extra-terminal domain (BET) proteins specifically recognize acetylated lysine residues on histone tails. BET bromodomain inhibition with a first-in-class inhibitor JQ1 reduces expression of a broad spectrum of growth promoting and antiapoptotic genes, including c-Myc, resulting in suppression of several hematopoietic cancers and NUT midline carcinoma. We and other groups have previously reported the critical role of c-Myc in glioblastoma stem cells. Here, we demonstrated broad antineoplastic effects of JQ1 both in ex vivo cultures and orthotopic models using a panel of glioblastoma tumors carrying different genetic lesions. JQ1 induced marked cell cycle arrest and apoptosis in association with p21WIP1/CIP1 induction and hTERT, Bcl-2 and Bcl-xL reduction. Consistent with previous studies, JQ1 decreased c-Myc expression in glioblastoma. However, exogenous c-Myc did not significantly protect glioblastoma from JQ1, unlike the observations in hematopoietic cancers. Cells genetically engineered for Akt hyperactivation or p53/Rb inactivation did not compromise JQ1 efficacy, suggesting that these signaling pathways commonly altered in glioblastoma may not confer resistance to JQ1. Taken together, our results suggest potentially broad therapeutic utility of BET bromodomain inhibition for treating genetically diverse glioblastoma tumors. Citation Format: Jialiang Wang, Zhixiang Cheng. Inhibition of BET bromodomain targets genetically diverse glioblastoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1018. doi:10.1158/1538-7445.AM2013-1018
Those who faced turbulence and launched the era of flow dynamic concepts for cardiac investigation
Authors: C Veyrat
Journal: Cardiovascular Research (2001)

This paper puts emphasis on pioneers who developed cardiac flow dynamics concepts during the second half of the 20th century at a period where pressure measurements were the rule. Thinking flow instead of pressure dynamics corresponded to in-depth conceptual changes: whereas blood pressure generally has a single positive sign and a similar pattern at all points of a cardiac chamber or a vessel, flow fluctuates around the zero line and its pattern changes within a given cardiac chamber or vessel level. These specific changes and fluctuations were the exciting tools needed to renew our pathophysiological insights, just in time with the take off of Doppler ultrasound making noninvasive investigation of fluid dynamics easily available. Each decade was marked by a specific historical contribution to evolving concepts. Instead of a merely phenomenological approach to flow dynamics, pioneers assigned a value of paradigms to basic flow patterns. They generated a system of heuristical hypotheses which turned out to underlay a modernistic understanding of flow dynamics in normal and diseased hearts. So far, flow investigation had definitely gained acceptance completing pressure data at the middle of the 1980s, widely opening a breakthrough for future pathophysiological insights.
Ursodeoxycholic Acid Treatment of Refractory Chronic Graft-versus-Host Disease of the Liver
Authors: Ronald H. Fried, Carol S. Murakami, Lloyd D. Fisher, Richard A. Willson, Keith M. Sullivan, George B. McDonald
Journal: Annals of Internal Medicine (1992)

Objective: To determine the safety and efficacy of ursodeoxycholic acid treatment in patients with chronic graft-versus-host disease (GVHD) of the liver. Design: Open-label study in which each patient served as his or her own control. Setting: Private practice and a university bone marrow transplant center. Patients: Twelve patients with refractory chronic GVHD of the liver were studied after allogeneic bone marrow transplantation. Interventions: After baseline data collection, patients were given ursodeoxycholic acid (UDCA, 10 to 15 mg/kg body weight per day) for 6 weeks. After discontinuation of the drug, patients were followed for an additional 6 weeks. Doses of immunosuppressive drugs were unchanged for these 12 weeks. Measurements: Signs, symptoms, Karnofsky performance scores, hematocrit, total leukocyte count, absolute neutrophil count, platelet count, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, gamma-glutamyltransferase (GGT), total serum bilirubin, prothrombin time, serum creatinine, and blood urea nitrogen were assessed. Results: Serum tests of cholestatic liver injury measured at 2, 4, and 6 weeks showed improvement compared with baseline. At 6 weeks, the percent decrease from baseline in total serum bilirubin was 33% (P < 0.005); in alkaline phosphatase the decrease was 32% (P < 0.038); and in AST the decrease was 37% (P < 0.007). After discontinuation of UDCA therapy, 11 patients were followed for 6 additional weeks. All showed significant worsening in liver function test results. Symptom scores were unchanged throughout the study. One patient with pruritus improved while receiving therapy with UDCA. No adverse effects were observed. Conclusion: Therapy with UDCA was safe, well-tolerated, and efficacious in the short-term treatment of refractory chronic GVHD of the liver. Further investigation is needed to evaluate the long-term effects of UDCA therapy.
Absence of Ischemia in Telangiectasias of Chronic Radiation Proctopathy
Authors: S. Friedland, D. Benaron, P. Maxim, I. Parachikov, R. Soetikno
Journal: Endoscopy (2006)

Background and Study Aims: It has been postulated that chronic radiation proctopathy, clinically manifested by hematochezia and by the appearance of multiple telangiectasias, is caused by ischemia. This theory is based on reports that appeared in the 1980s which described obliterative endarteritis in patients with chronic radiation-induced ulcers. However, bleeding from radiation proctopathy is typically successfully treated endoscopically by widespread tissue coagulation, and the complications that would be expected to occur if the tissue was ischemic, such as poor wound healing, generally do not arise. We therefore hypothesized that the ischemia theory is incorrect and that rectal capillary oxygen saturation is normal in patients with telangiectasias of chronic radiation proctopathy. Patients and Methods: We developed a visible-light spectroscopy device that measures mucosal capillary hemoglobin oxygen saturation during endoscopy (having reported its operating characteristics previously). We prospectively studied 20 patients who had typical findings of multiple rectal telangiectasias, 1 - 20 years after undergoing external-beam irradiation for prostate or rectal carcinoma. We measured and compared the mucosal capillary oxygen saturations in the affected areas of the distal rectum and in endoscopically normal areas in the rectosigmoid colon. Results: Mucosal oxygenation was normal in all 20 patients in affected areas (64 % - 80 %) and in unaffected areas (63 % - 75 %). The mean mucosal hemoglobin oxygen saturation was actually slightly higher in the affected areas of the rectum than in the uninvolved rectosigmoid colon (73 % vs. 69 %, P < 0.01). Conclusions: The common form of chronic radiation proctopathy, characterized by multiple telangiectasias without ulcers or strictures, is not associated with ongoing mucosal ischemia. This finding may explain why endoscopic treatment of this disorder, in which large areas of the mucosa are coagulated with argon plasma or other treatment modalities that cause widespread ulceration, does not typically result in complications from poor wound healing.
Prognostic Value of Enzymes in Myocardial Infarction
Authors: Eugene L. Coodley
Journal: JAMA (1973)

In a series of 125 consecutive patients, enzyme determinations were performed at daily intervals for the first four days following acute myocardial infarction in order to assess the usefulness of enzymes in assessing prognosis. A direct relationship between amplitude of enzyme rise and early mortality was found; levels six times normal were associated with a hospital mortality of 56% (14 of 25). The incidence of arrhythmias was also correlated with enzyme activity, with 81.8% (102 of 125) of ventricular arrhythmias occurring in the group whose enzyme levels exceeded four times normal. In patients who developed congestive heart failure, the initial enzyme levels were four to five times normal. Cardiogenic shock was present in 10.4% (13 of 125) of patients and was not seen in any patient who did not have an enzyme rise at least five times normal.
Virologic and Serologic Studies on Human Products of Conception after Maternal Rubella
Authors: Charles A. Alford, Franklin A. Neva, Thomas H. Weller, Louise S. Kanich, Linda M. Giraldi
Journal: New England Journal of Medicine (1964)

ALTHOUGH the teratogenic potential of rubella virus was established by Gregg1 in 1941 the pathogenesis of fetal damage associated with maternal rubella, of necessity, has remained ill defined. The recent development of procedures for the propagation of rubella virus in the laboratory2 , 3 permits virologic and serologic investigation of congenital rubella infections. Already, rubella virus has been recovered from an aborted human fetus.4 Furthermore, it is established that congenital infection with rubella virus does not result in a state of immunologic tolerance5 , 6; such an infection may induce a persistent antibody response that may permit a retrospective serologic diagnosis in the . . .
CD1a and langerin: acting as more than Langerhans cell markers
Authors: Norikatsu Mizumoto, Akira Takashima
Journal: Journal of Clinical Investigation (2004)

Langerhans cells (LCs) represent a unique DC subset populating the outermost body surface, i.e., the epidermis. Although CD1a and langerin (CD207) are used as specific markers to distinguish LCs from other DC subsets, their immunological functions have remained mostly unknown. A new paper (see the related article beginning on page 701) demonstrates that LCs utilize these markers to induce cellular immune responses to Mycobacterium leprae: CD1a mediates the presentation of nonpeptide antigens to T cells, while langerin facilitates uptake of microbial fragments and perhaps their delivery to a specialized subcellular compartment.
A Preliminary Report of Penile Transplantation: Part 2
Authors: Weilie Hu, Jun Lu, Lichao Zhang, Wen Wu, Haibo Nie, Yunsong Zhu, Zhixiong Deng, Yongbing Zhao, Wen Sheng, Qiyou Chao, Xiaofu Qiu, Jinghua Yang, Ying Bai
Journal: European Urology (2006)
Deaths from Childhood Cancer in Sibs
Authors: Robert W. Miller
Journal: New England Journal of Medicine (1968)

To clarify the extent to which childhood cancer aggregates in sibships, the death certificates for all (21,659) children under 15 years of age who died of cancer in the United States, 1960–64, were studied. The list was alphabetized according to the child's last name, and sibs were identified primarily by matching of the mothers' maiden names. The results revealed five pairs of like-sex twins with leukemia, all under six years of age. The occurrence of leukemia in five pairs of sibs other than twins did not exceed normal expectation. There were six pairs of sibs with brain tumors, well above the expected value of 0.4. The occurrence of brain tumor in one sib and cancer of bone or muscle in another (five families) may also be excessive. In five other sib pairs with cancer, no neoplasm was overrepresented, but in three the primary site was the same in both children.
Effect of intravenous diazepam on human lower oesophageal sphincter pressure under controlled double blind crossover conditions.
Authors: T R Weihrauch, C F Forster, H Kohler, K Ewe, J Krieglstein
Journal: Gut (1979)

The effect of diazepam on the lower oesophageal sphincter (LOS) pressure is controversial. Therefore, a double-blind crossover study was performed on 18 healthy volunteers to determine the sphincter response to intravenous diazepam--70, 140, 280 microgram/kg, which correspond to a total dose of 5, 10, and 20 mg. respectively. After the 5 and 10 mg dose no signficant effect on LOS pressure could be observed when compared with placebo. After the 20 mg dose a significant rise in pressures (deltaPLOS) was recorded for 40 minutes with a maximum deltaPLOS of + 16.2 +/- 6.6 (mean +/- SEM) mmHg after 50 minutes (P less than 0.01) (46 +/- 1.3% increase above the basal pressure). It is concluded that diazepam does not affect lower oesophageal sphincter competence and therefore does not increase the risk of regurgitation and pulmonary aspiration in premedicated patients.
Risk Factors of Developing Proliferative Retinopathy in Type 1 Diabetic Patients
Authors: Harry Dorchy, Catherine Claes, Claire Verougstraete
Journal: Diabetes Care (2002)

In the July issue of Diabetes Care , we read with interest the study by Zangh et al. (1). They revisited material from the Diabetes Control and Complications Trial database in order to search for potential prognostic factors of developing retinopathy in patients with extreme (either good or poor) metabolic control, but who were free of the complication at baseline. The development and progression of retinopathy was defined by a three-step change or more, according to the Early Treatment Retinopathy Study protocol, on stereoscopic color fundus photographs. Their conclusion was that other than duration of diabetes and metabolic control, BMI had a significant predictive value. We found a similar influence of BMI in our population of …
THE PROBLEMS OF SERUM-THERAPY.
Authors: JOSEPH McFARLAND
Journal: JAMA (1902)

With the advance of our knowledge of immune serums the evidence becomes more and more convincing that they operate chemically to produce their effects. So long as we conceived that their introduction into an animal was succeeded by a general vital reaction by means of which the cells received some kind of invigoration or rejuvenation, the conditions under which the serums operated were so occult that it seemed impossible to attain positive information about them. The recognition of the chemical nature of the reaction, and the discovery that the laws governing it are not unlike laws governing other reactions with which we are familiar, together with the discovery that the toxin-antitoxin reaction is but one of a large series of vital reactions, has opened the way to new applications of serums in practice, and has suggested entirely new lines of research. It will be remembered by those who are familiar
Response to Letter Regarding Article, “Hemodynamic Effects of Long-Term Cardiac Resynchronization Therapy: Analysis by Pressure-Volume Loops”
Authors: Paul Steendijk, Sven A. Tulner, Jeroen J. Bax, Pranobe V. Oemrawsingh, Gabe B. Bleeker, Lieselot van Erven, Harriette F. Verwey, Ernst E. van der Wall, Martin J. Schalij, Hein Putter
Journal: Circulation (2006)
Does apoptosis have a role in neurodegeneration?
Authors: R. M Gibson
Journal: BMJ (2001)

Cells within the central nervous system die during both acute and chronic neurodegenerative disorders. Since the morphological and biochemical features of apoptosis were first described, neuroscientists have been asking whether this cell death is due to apoptosis and whether elucidating the mechanisms of apoptosis can provide new treatment strategies for intractable diseases such as stroke, Alzheimer's disease, and Huntington's disease.

Much debate has ensued. Firstly, cell death in the central nervous system may not fit perfectly with our current classification of apoptosis and necrosis, which was defined using peripheral cells. Some of the methods used may not distinguish conclusively between apoptosis and necrosis. For example, transferase-mediated dUTP nick end labelling (TUNEL), a staining method that detects the broken ends of DNA within cells, is used to provide evidence of apoptosis. However, …
Outcome measures should be relevant.
Authors: R. H. Harwood, P. H. Gompertz, S. Ebrahim
Journal: BMJ (1992)

Sen's editorial,' may well be due to tuberculosis; rates there now are comparable with those in the United Kingdom during part of the last century.Tuberculosis is, to a great extent, a disease of social deprivation, and thus Sen's point is valid.For some reason, however, young females have a higher mortality from tuberculosis than their male peers; this phenomenon is not yet understood and may account for at least some of Sen's missing women.
Abstract 518: Identification of differentially expressed microRNAs in human hepatocellular adenoma associated with type I glycogen storage disease: a potential utility as biomarkers
Authors: Ling-Hui Li, Li-Ya Chiu, Priya S. Kishnani, Tzu-Po Chuang, Cheng-Yang Tang, Cheng-Yuan Liu, Deeksha Bali, Dwight Koeberl, Stephanie Austin, Keri Boyette, David A. Weinstein, Elaine Murphy, Adam Yao, Yuan-Tsong Chen
Journal: Cancer Research (2014)

Abstract Background: It is known that malignant transformation to hepatocellular carcinoma (HCC) occurs at a higher frequency in hepatocellular adenoma (HCA) from type I glycogen storage disease (GSD I) compared to HCA from other etiologies. In this study, we aimed to identify differentially expressed miRNAs in GSD Ia HCA as candidates that could serve as putative biomarkers for detection of GSD Ia HCA and/or risk assessment of malignant transformation. Methods: Utilizing massively parallel sequencing, the miRNA profiling was performed for paired adenomas and normal liver tissues from seven GSD Ia patients. Differentially expressed miRNAs were validated in liver tumor tissues, HCC cell lines and serum using quantitative RT-PCR. Results: miR-34a, miR-34a*, miR-224, miR-224*, miR-424, miR-452 and miR-455-5p were found to be commonly deregulated in GSD Ia HCA, general population HCA, and HCC cell lines at compatible levels. In comparison with GSD Ia HCA, the upregulation of miR-130b and downregulation of miR-199a-5p, miR-199b-5p, and miR-214 were more significant in HCC cell lines. Furthermore, serum level of miR-130b in GSD Ia patients with HCA was moderately higher than that in either GSD Ia patients without HCA or healthy individuals. Conclusion: We make the first observation of the distinct miRNA deregulation in HCA associated with GSD Ia. We also provide evidence that miR-130b could serve as a circulating biomarker for detection of GSD Ia HCA. This work provides prominent candidate miRNAs worth evaluating as biomarkers for monitoring the development and progress of liver tumors in GSD Ia patients in the future. Citation Format: Ling-Hui Li, Li-Ya Chiu, Priya S. Kishnani, Tzu-Po Chuang, Cheng-Yang Tang, Cheng-Yuan Liu, Deeksha Bali, Dwight Koeberl, Stephanie Austin, Keri Boyette, David A. Weinstein, Elaine Murphy, Adam Yao, Yuan-Tsong Chen. Identification of differentially expressed microRNAs in human hepatocellular adenoma associated with type I glycogen storage disease: a potential utility as biomarkers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 518. doi:10.1158/1538-7445.AM2014-518
Glutathione <i>S</i>-Transferase π1 Promotes Tumorigenicity in HCT116 Human Colon Cancer Cells
Authors: Duyen T. Dang, Fang Chen, Manu Kohli, Carlo Rago, Jordan M. Cummins, Long H. Dang
Journal: Cancer Research (2005)

GSTP1 is a member of the glutathione S-transferase enzyme superfamily, which catalyzes the conjugation of electrophiles with glutathione in the process of detoxification. GSTP1 is widely overexpressed in colorectal cancer, from aberrant crypt foci to advanced carcinomas. Increased expression of GSTP1 is associated with multidrug resistance and a worse clinical prognosis. However, GSTP1-null mice have an increased risk of tumor formation. Thus, the biological function of GSTP1 in colorectal cancer biology remains speculative. In an effort to gain further insights into the role of GSTP1 in tumorigenesis, we disrupted the GSTP1 gene in HCT116 human colorectal cancer cells using targeted homologous recombination. We find that loss of GSTP1 resulted in impaired clonogenic survival and proliferation. Specifically, under growth-limiting conditions, (a) GSTP1 protected HCT116 cells from oxidative stress and associated apoptosis and (b) promoted mitogen-activated protein kinase-extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase-mediated G1-S cell cycle progression. In vivo, GSTP1 was critical for engraftment and growth of HCT116 tumor xenografts. These studies directly show that GSTP1 promotes clonogenic survival and proliferation in HCT116 human colon cancer cells.
Autoimmune enteropathy and colitis: is there a generalised autoimmune gut disorder?
Authors: S M Hill, P J Milla, G F Bottazzo, R Mirakian
Journal: Gut (1991)

Children with protracted diarrhoea, circulating enterocyte autoantibodies, and an enteropathy showing features of inappropriate HLA molecule expression on the jejunal crypt epithelium, often present with persistent blood and mucus in their stools. Eight children with autoimmune enteropathy were investigated for the presence of associated colonic disease. Six children with protracted diarrhoea, no circulating autoantibodies, and an enteropathy (in five of them) undergoing colonoscopy were used as control subjects. In all eight patients, but not in the control subjects, there was macroscopic and microscopic evidence of an accompanying colitis of variable severity, thus indicating that a more generalised intestinal disorder was present, which might affect the whole intestine. Aberrant expression of DR molecules on the colonic surface and crypt epithelium was also detected. Autoimmunity may play a role in the colitis.
Endobronchial eosinophils preferentially stimulate T helper cell type 2 responses
Authors: H.‐Z. Shi, C.‐Q. Xiao, C.‐Q. Li, X.‐Y. Mo, Q.‐L. Yang, J. Leng, Y.‐Q. Chen
Journal: Allergy (2004)

Background: Antigen‐loaded eosinophils instilled intratracheally into mice were capable of migrating into local lymph nodes and localize to the T cell‐rich paracortical zones where they stimulated antigen‐specific proliferation of CD4 + T cells. The aim of the present study was to evaluate whether eosinophils within the tracheobronchial lumen can stimulate Th2 cell expansion by presenting antigen both in vitro and in vivo . Methods: Airway eosinophils were recovered from ovalbumin‐sensitized and ‐challenged BALB/c mice, these eosinophils were then co‐cultured with sensitized CD4 + cells in the absence or presence of anti‐CD80 or/and ‐CD86 monoclonal antibodies. Airway eosinophils were instilled into the trachea of sensitized mice. At 3 days thereafter, the draining paratracheal lymph nodes were removed and teased into cell suspensions for culture. Cell‐free culture supernatants were collected for detection of cytokines. Results: Our data showed that airway eosinophils functioned as CD80‐ and CD86‐dependent antigen‐presenting cells (APCs) to stimulate sensitized CD4 + lymphocytes to produce interleukin (IL)‐4, IL‐5, and IL‐13, but not interferon (IFN)‐ γ in in vitro assay. When instilled intratracheally in sensitized recipient mice, airway eosinophils migrated into draining paratracheal lymph nodes primed Th2 cells in vivo for IL‐4, IL‐5, and IL‐13, but not IFN‐ γ , production during the in vitro culture that was also CD80‐ and CD86‐dependent. Conclusion: Eosinophils within the lumina of airways could process inhaled antigen function in vitro and in vivo as APCs to promote expansion of Th2 cells. This investigation highlights the potential of eosinophils to not only act as terminal effector cells but also to actively modulate immune responses by amplifying Th2 cell responses.