tbuckley/cabot-search huggingface dataset:
Quantitative proteomics identification of phosphoglycerate mutase 1 as a novel therapeutic target in hepatocellular carcinoma
Authors: Fenglian Ren, Hong Wu, Yunlong Lei, Haiyuan Zhang, Rui Liu, Yong Zhao, Xiancheng Chen, Dequan Zeng, Aiping Tong, Lijuan Chen, Yuquan Wei, Canhua Huang
Journal: Molecular Cancer (2010)

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with poor prognosis due to resistance to conventional chemotherapy and limited efficacy of radiotherapy. There is an urgent need to develop novel biomarkers for early diagnosis, as well as to identify new drug targets for therapeutic interventions.54 paired HCC samples and 21 normal liver tissues were obtained from West China Hospital of Sichuan University. Informed consent was obtained from all the patients or their relatives prior to analysis, and the project was approved by the Institutional Ethics Committee of Sichuan University. Stable Isotope Labeling with Amino Acids in Cell Culture (SILAC)-based proteomics was employed to profile the differentially expressed proteins between a HepG2 human hepatoma cell line and an immortal hepatic cell line L02. Validation of PGAM1 expression was performed by semi-quantitative RT-PCR, immunoblot and immunohistochemistry using clinical samples. shRNA expressing plasmids specifically targeting PGAM1 were designed and constructed by GenePharma Corporation (Shanghai, China), and were utilized to silence expression of PGAM1 in vitro and in vivo. Cell proliferation was measured by a combination of colony formation assay and Ki67 staining. Apoptosis was examined by flow cytometry and TUNEL assay.A total of 63 dysregulated proteins were identified, including 51 up-regulated proteins, and 12 down-regulated proteins (over 2-fold, p < 0.01). Phosphoglycerate mutase 1 (PGAM1) was found markedly upregulated. Clinico-pathological analysis indicated that overexpression of PGAM1 was associated with 66.7% HCC, and strongly correlated with poor differentiation and decreased survival rates (p < 0.01). shRNAs-mediated repression of PGAM1 expression resulted in significant inhibition in liver cancer cell growth both in vitro and in vivo.Our studies suggested that PGAM1 plays an important role in hepatocarcinogenesis, and should be a potential diagnostic biomarker, as well as an attractive therapeutic target for hepatocellular carcinoma.
Spontaneous Remission of Nephrotic Syndrome in Idiopathic Membranous Nephropathy
Authors: Natalia Polanco, Elena Gutiérrez, Adelardo Covarsí, Francisco Ariza, Agustín Carreño, Ana Vigil, José Baltar, Gema Fernández-Fresnedo, Carmen Martín, Salvador Pons, Dolores Lorenzo, Carmen Bernis, Pilar Arrizabalaga, Gema Fernández-Juárez, Vicente Barrio, Milagros Sierra, Ines Castellanos, Mario Espinosa, Francisco Rivera, Aniana Oliet, Francisco Fernández-Vega, Manuel Praga
Journal: Journal of the American Society of Nephrology (2010)

Spontaneous remission is a well known characteristic of idiopathic membranous nephropathy, but contemporary studies describing predictors of remission and long-term outcomes are lacking. We conducted a retrospective, multicenter cohort study of 328 patients with nephrotic syndrome resulting from idiopathic membranous nephropathy that initially received conservative therapy. Spontaneous remission occurred in 104 (32%) patients: proteinuria progressively declined after diagnosis until remission of disease at 14.7 +/- 11.4 months. Although spontaneous remission was more frequent with lower levels of baseline proteinuria, it also frequently occurred in patients with massive proteinuria: 26% among those with baseline proteinuria 8 to 12 g/24 h and 22% among those with proteinuria >12 g/24 h. Baseline serum creatinine and proteinuria, treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists, and a >50% decline of proteinuria from baseline during the first year of follow-up were significant independent predictors for spontaneous remission. Only six patients (5.7%) experienced a relapse of nephrotic syndrome. The incidence of death and ESRD were significantly lower among patients with spontaneous remission. In conclusion, spontaneous remission is common among patients with nephrotic syndrome resulting from membranous nephropathy and carries a favorable long-term outcome with a low incidence of relapse. A decrease in proteinuria >50% from baseline during the first year predicts spontaneous remission.
Non-Hodgkin's Lymphomas
Authors: Andrew D. Zelenetz, Ranjana H. Advani, John C. Byrd, Myron S. Czuczman, Lloyd E. Damon, Madeleine Duvic, Luis Fayad, Andres Forero, Martha J. Glenn, Jon P. Gockerman, Leo I. Gordon, Nancy Lee Harris, Richard T. Hoppe, Steven M. Horwitz, Mark S. Kaminski, Youn H. Kim, Ann S. LaCasce, Auyporn Nademanee, Elise A. Olsen, Pierluigi Porcu, Oliver Press, Leonard Prosnitz, Mitchell R. Smith, Eduardo M. Sotomayor, Julie Marie Vose, Joachim Yahalom, Furhan Yunus
Journal: Journal of the National Comprehensive Cancer Network (2011)

Part 1 Lymphomagenesis: Lymphocyte differentiation Adult T-cell leukaemia/Lymphoma - a model of retrovirus-induced lymphomagenesis Burkitt's lymphoma and Epstein-Barr virus-associated lymphoid malignancies - models for lymphomagenesis T(14 18) translocation. Part 2 Methods: Histological and immunohistochemical methods Genotype. Part 3 Nodal Non-Hodgkin's Lymphomas: The normal lymph node - structure and function Histological classification Staging of NHLs Analytical study of the different subtypes of NHLs - clinical, histological and immunohistochemical aspects NHLs in childhood NHLs associated with HIV infection. Part 4 Extra-Nodal Non-Hodgkin's lymphomas: Malignant lymphomas of mucosa-associated lymphoid tissues Primary gastrointestinal NHLs Pathology of gastro-intestinal NHLs Cutaneous lymphomas NHLs of the Mediastinum NHLs of the lung Bone marrow involvement Blood involvement in chronic (mature) B & T lymphoproliferative syndromes Liver involvement Spleen involvement Extra-cranial head-and-neck NHLs Central nervous system involvement NHLs of bone Urogenital localizations. Part 5 Treatment of Non-Hodgkin's Lymphomas: Methodology and problems in the comparison of results Treatment of lowgrade NHLs The role of radiation therapy Treatment of aggressive lymphomas (intermediate and highgrade) Intensive chemoradiotherapy and bone-marrow transplantation Salvage therapy after failure Treatment of NHLs in childhood.
Screening for Cervical Cancer Precursors With p16/Ki-67 Dual-Stained Cytology: Results of the PALMS Study
Authors: Hans Ikenberg, Christine Bergeron, Dietmar Schmidt, Henrik Griesser, Francisco Alameda, Claudio Angeloni, Johannes Bogers, Roger Dachez, Karin Denton, Jalil Hariri, Thomas Keller, Magnus von Knebel Doeberitz, Heinrich H. Neumann, Luis M. Puig-Tintore, Mario Sideri, Susanne Rehm, Ruediger Ridder
Journal: JNCI Journal of the National Cancer Institute (2013)

Pap cytology is known to be more specific but less sensitive than testing for human papillomavirus (HPV) for the detection of high-grade cervical intraepithelial neoplasia (CIN2+). We assessed whether p16/Ki-67 dual-stained cytology, a biomarker combination indicative of transforming HPV infections, can provide high sensitivity for CIN2+ in screening while maintaining high specificity. Results were compared with Pap cytology and HPV testing.A total of 27,349 women 18 years or older attending routine cervical cancer screening were prospectively enrolled in five European countries. Pap cytology, p16/Ki-67 immunostaining, and HPV testing were performed on all women. Positive test results triggered colposcopy referral, except for women younger than 30 years with only positive HPV test results. Presence of CIN2+ on adjudicated histology was used as the reference standard. Two-sided bias-corrected McNemar P values were determined.The p16/Ki-67 dual-stained cytology positivity rates were comparable with the prevalence of abnormal Pap cytology results and less than 50% of the positivity rates observed for HPV testing. In women of all ages, dual-stained cytology was more sensitive than Pap cytology (86.7% vs 68.5%; P < .001) for detecting CIN2+, with comparable specificity (95.2% vs 95.4%; P = .15). The relative performance of the tests was similar in both groups of women: younger than age 30 and 30 years or older. HPV testing in women 30 years or older was more sensitive than dual-stained cytology (93.3% vs 84.7%; P = .03) but less specific (93.0% vs 96.2%; P < .001).The p16/Ki-67 dual-stained cytology combines superior sensitivity and noninferior specificity over Pap cytology for detecting CIN2+. It suggests a potential role of dual-stained cytology in screening, especially in younger women where HPV testing has its limitations.
The Emerging “Hallmarks” of Metabolic Reprogramming and Immune Evasion: Distinct or Linked?
Authors: Irina Kareva, Philip Hahnfeldt
Journal: Cancer Research (2013)

The role of the immune system in tumor elimination has been shown to be increasingly ambiguous, as many tumors not only escape recognition by the adaptive immune response but also even prime the immune cells to promote tumor growth. This effect is achieved through a number of mechanisms, which include both direct interference with the cells of the adaptive immune response and indirect immunosuppression achieved through modification of the tumor microenvironment. We propose that through upregulation of glycolysis and the consequent lowering of pH in the tumor microenvironment, tumors can take advantage of a pH control system, already exploited by specific immune cell subpopulations, to gain control of the immune system and suppress both cytotoxic and antigen-presenting cells. This is accomplished through the direct competition of tumor cells with actively proliferating glycolytic immune cells for glucose and indirectly through the creation by the tumor of a microenvironment that interferes with maturation and activation of antigen-presenting cells and naïve cytotoxic T cells. Immunosuppressive properties of an acidic microenvironment in the vicinity of the tumor can thus provide additional benefits for upregulation of glycolysis by tumor cells, suggesting that the two emerging "hallmarks of cancer," altered glucose metabolism and immune suppression, are in fact fundamentally linked.
Homozygous HOXA1 mutations disrupt human brainstem, inner ear, cardiovascular and cognitive development
Authors: Max A Tischfield, Thomas M Bosley, Mustafa A M Salih, Ibrahim A Alorainy, Emin C Sener, Michael J Nester, Darren T Oystreck, Wai-Man Chan, Caroline Andrews, Robert P Erickson, Elizabeth C Engle
Journal: Nature Genetics (2005)
Role of spiral volumetric computed tomographic scanning in the assessment of patients with clinical suspicion of pulmonary embolism and an abnormal ventilation/perfusion lung scan.
Authors: A. B. van Rossum, F. E. Treurniet, G. J. Kieft, S. J. Smith, R. Schepers-Bok
Journal: Thorax (1996)

A study was carried out to evaluate the potential place of spiral volumetric computed tomography (SVCT) in the diagnostic strategy for pulmonary embolism.In a prospective study 249 patients with clinical suspicion of pulmonary embolism were evaluated with various imaging techniques. In all patients a ventilation/perfusion (V/Q) scan was performed. Seventy seven patients with an abnormal V/Q scan underwent SVCT. Pulmonary angiography was then performed in all 42 patients with a non-diagnostic V/Q scan and in three patients with a high probability V/Q scan without emboli on the SVCT scan. Patients with an abnormal perfusion scan also underwent ultrasonography of the legs for the detection of deep vein thrombosis.One hundred and seventy two patients (69%) had a normal V/Q scan. Forty two patients (17%) had a non-diagnostic V/Q scan, and in five of these patients pulmonary emboli were found both by SVCT and pulmonary angiography. In one patient, although SVCT showed no emboli, the angiogram was positive for pulmonary embolism. In one of the 42 patients the SVCT scan showed an embolus which was not confirmed by pulmonary angiography. The other 35 patients showed no sign of emboli. Thirty five patients (14%) had a high probability V/Q scan, and in 32 patients emboli were seen on SVCT images. Two patients had both a negative SVCT scan and a negative pulmonary angiogram. In one who had an inconclusive SVCT scan pulmonary angiography was positive. The sensitivity for pulmonary embolism was 95% and the specificity 97%; the positive and negative predicted values of SVCT were 97% and 97%, respectively.SVCT is a relatively noninvasive test for pulmonary embolism which is both sensitive and specific and which may serve as an alternative to ventilation scintigraphy and possibly to pulmonary angiography in the diagnostic strategy for pulmonary embolism.
Integrin β2 (CD18)-Mediated Cell Proliferation of HEL Cells on a Hematopoietic-Supportive Bone Marrow Stromal Cell Line, HESS-5 Cells
Authors: Takashi Tsuji, Iwao Waga, Katsunari Tezuka, Masafumi Kamada, Kimio Yatsunami, Hisashi Kodama
Journal: Blood (1998)
Epicardial adipose tissue and atrial fibrillation
Authors: S. N. Hatem, P. Sanders
Journal: Cardiovascular Research (2014)

Atrial fibrillation (AF) is the most frequent cardiac arrhythmia in clinical practice. AF is often associated with profound functional and structural alterations of the atrial myocardium that compose its substrate. Recently, a relationship between the thickness of epicardial adipose tissue (EAT) and the incidence and severity of AF has been reported. Adipose tissue is a biologically active organ regulating the metabolism of neighbouring organs. It is also a major source of cytokines. In the heart, EAT is contiguous with the myocardium without fascia boundaries resulting in paracrine effects through the release of adipokines. Indeed, Activin A, which is produced in abundance by EAT during heart failure or diabetes, shows a marked fibrotic effect on the atrial myocardium. The infiltration of adipocytes into the atrial myocardium could also disorganize the depolarization wave front favouring micro re-entry circuits and local conduction block. Finally, EAT contains progenitor cells in abundance and therefore could be a source of myofibroblasts producing extracellular matrix. The study on the role played by adipose tissue in the pathogenesis of AF is just starting and is highly likely to uncover new biomarkers and therapeutic targets for AF.
Selective expression of S100A7 in lung squamous cell carcinomas and large cell carcinomas but not in adenocarcinomas and small cell carcinomas
Authors: H Zhang, Q Zhao, Y Chen, Y Wang, S Gao, Y Mao, M Li, A Peng, D He, X Xiao
Journal: Thorax (2008)

S100A7 is a secreted protein and its overexpression has been previously associated with carcinogenesis of certain cancers. This study was undertaken to investigate the possibility that overexpression of S100A7 protein might be detected in the sera of patients with lung cancer.RNA and protein levels of S100A7 were examined in 60 pairs of frozen lung cancer tissues by RT-PCR and western blot. The specific expression of this protein and its cellular distribution were investigated in 145 paraffin embedded lung cancer samples, six benign lung disease and 21 normal lung tissues by immunohistochemistry. The S100A7 protein level was further analysed in serum from 112 patients with lung cancer, 20 with benign lung diseases and 31 healthy individuals by ELISA.Specific expression of both S100A7 mRNA and protein was found in squamous cell carcinomas, adenosquamous carcinomas and large cell lung carcinomas, whereas neither was detected in adenocarcinomas or paired non-cancerous lung tissues. Further immunohistochemical analysis identified positive staining of S100A7 only in squamous cell carcinomas and large cell lung carcinomas, but not in other subtypes of lung cancer and normal lung tissues. Weak expression was also found in the inflammatory cells of benign lung diseases. Our most important finding is that elevated S100A7 protein could be detected in the sera of patients with squamous cell carcinomas.S100A7 was only expressed in squamous cell carcinomas and large cell lung carcinomas and an increase in the level of S100A7 protein in serum may serve as a potential marker for lung cancer diagnosis.
Role of pulmonary infection in the development of chronic lung disease of prematurity
Authors: M.L. Beeton, N.C. Maxwell, P.L. Davies, D. Nuttall, E. McGreal, M. Chakraborty, O.B. Spiller, S. Kotecha
Journal: European Respiratory Journal (2010)

We studied the role of ante- and post-natal infection in the development of chronic lung disease (CLD) of prematurity. 192 newborn infants (61 term and 131 pre-term of <34 weeks gestation: 88 with respiratory distress syndrome, 35 developed CLD and eight died) were recruited. 16S ribosomal RNA (rRNA) genes were identified by PCR of DNA isolated from 840 gastric and lung fluid samples. Ureaplasma spp. were also cultured. Presence of 16S rRNA genes (OR 1.6, 95% CI 1.2-2.2) and Ureaplasma spp. (OR 3.6, 95% CI 1.7-7.7) was significantly associated with the development of CLD. This association remained if the 16S rRNA genes and Ureaplasma spp. were first identified within the first 3 days of life (OR 2.4 (95% CI 1.4-4.1) and 3.8 (95% CI 1.4-10.0), respectively) or if first identified after 3 days of age (OR 1.7 (95% CI 1.1-2.8) and OR 5.1 (95% CI 1.3-19.8), respectively). Peak lung fluid interleukin (IL)-6 and IL-8 were significantly associated with presence of microbes (p<0.0001 and p=0.0001, respectively) and development of CLD (p=0.003 and 0.001, respectively). Both early and late microbial presence in neonatal lung fluid samples was significantly associated with the development of CLD suggesting that both ante- and post-natal infection play a role in the development of CLD.
Funding Oncology Clinical Trials: Are Cooperative Group Trials Sustainable?
Authors: Hsien-Yeang Seow, Patrick Whelan, Mark N. Levine, Kathryn Cowan, Barbara Lysakowski, Brenda Kowaleski, Anne Snider, Rebecca Y. Xu, Andrew Arnold
Journal: Journal of Clinical Oncology (2012)

Many oncology clinical trials departments (CTDs) are in serious fiscal deficit and their sustainability is in jeopardy. This study investigates whether the payment models used to fund industry versus cooperative group trials contribute to the fiscal deficit of a CTD.We examined the lifetime costs of all cooperative group and industry trials activated in the CTD of a cancer center between 2007 and 2011. A trial's lifetime is defined as being from the date the first patient was accrued until the last patient's actual or projected final follow-up visit. For each trial, we calculated the lifetime monthly net income, which was defined as monthly revenue minus monthly costs. Data sources included study protocols, trial budgets, and accrual data.Of the 97 trials analyzed, 64 (66%) were cooperative group trials. The pattern of lifetime net income for cooperative group trials has a positive peak during patient accrual followed by a negative trough during follow-up. In contrast, the pattern for industry trials resembled an "l" shape. The patterns reflect the differing payment models: upfront lump-sum payments (cooperative group) versus milestone payments (industry).The negative trough in the lifetime net income of a cooperative group trial occurs because follow-up costs are typically not funded or are underfunded. CTDs accrue more patients in new trials to offset that deficit. The CTD uses revenue from accrual to existing trials to cross-subsidize past trials in follow-up. As the number of patients on follow-up increases, the fiscal deficit grows larger each year, perpetuating the cycle.
Association of Glomerular Filtration Rate With Outcomes of Acute Stroke in Type 2 Diabetic Patients: Results From the China National Stroke Registry
Authors: Yang Luo, Xianwei Wang, Yilong Wang, Chunxue Wang, Haichen Wang, David Wang, Liping Liu, Qian Jia, Gaifen Liu, Xingquan Zhao, Yongjun Wang
Journal: Diabetes Care (2013)

OBJECTIVE We aim to explore whether a link exists between different levels of estimated glomerular filtration rate (eGFR) and poor outcomes of acute stroke in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Between 2007 and 2009, 6,261 patients with cerebrovascular events and diabetes were included in the final analysis from the China National Stroke Registry (CNSR) and substudy of CNSR (Abnormal Glucose Regulation in Patients with Acute Stroke Across China [ACROSS]).The period of follow-up was 1 year after stroke onset. eGFR was calculated with the Chinese modification of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. The association between eGFR and poor stroke outcomes, including all-cause death, recurrent stroke, combined end point (stroke or death), and stroke disability, was evaluated by multivariate analysis with the adjustment for demographic and clinical features. RESULTS Of 4,836 patients with stroke, low eGFR (&amp;lt;45 mL/min/1.73 m2) occurred in 268 (5.5%) and high eGFR (≥120 mL/min/1.73 m2) in 387 (8.0%). The median value for eGFR in all patients was 92.6 mL/min/1.73 m2. Low eGFR was independently associated with risks of all clinical outcomes in stroke/transient ischemic attack patients or patients with ischemic events, but not in patients with hemorrhagic stroke. Additionally, high eGFR was positively associated with an increased risk of adverse outcomes in all stroke subtypes, including hemorrhagic stroke. CONCLUSIONS Low and high eGFRs (&amp;lt;45 or ≥120 mL/min/1.73 m2, respectively) are independent predictors of all-cause mortality and other poor outcomes after acute stroke in patients with type 2 diabetes.
Coating Solid Lipid Nanoparticles with Hyaluronic Acid Enhances Antitumor Activity against Melanoma Stem-like Cells
Authors: Hongxin Shen, Sanjun Shi, Zhirong Zhang, Tao Gong, Xun Sun
Journal: Theranostics (2015)

Successful anticancer chemotherapy requires targeting tumors efficiently and further potential to eliminate cancer stem cell (CSC) subpopulations. Since CD44 is present on many types of CSCs, and it binds specially to hyaluronic acid (HA), we tested whether coating solid lipid nanoparticles with hyaluronan (HA-SLNs)would allow targeted delivery of paclitaxel (PTX) to CD44-overexpressing B16F10 melanoma cells. First, we developed a model system based on melanoma stem-like cells for experiments in vitro and in mouse xenografts, and we showed that cells expressing high levels of CD44 (CD44(+)) displayed a strong CSC phenotype while cells expressing low levels of CD44 (CD44(-)) did not. This phenotype included sphere and colony formation, higher proportion of side population cells, expression of CSC-related markers (ALDH, CD133, Oct-4) and tumorigenicity in vivo. Next we showed that administering PTX-loaded HA-SLNs led to efficient intracellular delivery of PTX and induced substantial apoptosis in CD44(+) cells in vitro. In the B16F10-CD44(+) lung metastasis model, PTX-loaded HA-SLNs targeted the tumor-bearing lung tissues well and subsequently exhibited significant antitumor effects with a relative low dose of PTX, which provided significant survival benefit without evidence of adverse events. These findings suggest that the HA-SLNs targeting system shows promise for enhancing cancer therapy.