tbuckley/cabot-search huggingface dataset:
Study comparing the concordance between PET/CT and bone scan in detecting skeletal metastasis in breast cancer patients.
Authors: D. Landau, S. M. Constantino, S. Maddipatla, Z. J. Zhang, M. Hart, N. C. Shah, S. Baidas
Journal: Journal of Clinical Oncology (2011)

e11122 Background: Bone metastasis is the most common site of metastases from breast cancer. Bone scan using technetium-99m is widely used for the detection of bony metastasis in patients with breast cancer but specificity is lowered by benign processes and sensitivity is lessened by poor detection of osteolytic metastasis. Positron emission tomography (PET) using 2-[18F] - fluoro-2-deoxy-D-glucose is a useful tool for the detection of metastatic disease in patients with breast cancer. It is unclear whether one or both modalities should be used to detect bone metastasis. Methods: Within our institution, we reviewed PET/CT scans and bone scans from 97 female patients with breast cancer whose scans were within a 4 -week period between June 2007 and March 2010 (109 studies of each, PET scan and bone scan). Data was divided into three sites: spine, pelvis+ribs, extremities. All scans were reviewed by 2 independent expert nuclear medicine physicians. Utilizing bone scan as the standard, McNemar’s test was performed to examine the marginal homogeneity of diagnoses for each of the three locations. The sensitivity, specificity, and accuracy of PET scan as opposed to bone scan were compared. Results: See table. Conclusions: There is no statistical difference between PET/CT scan compared with bone scan when bone scan is utilized as the standard test for detection of skeletal metastasis. In addition, using bone scan as a standard, PET scan has higher sensitivity (lower false-positive rates) in detecting spine metastasis, higher specificity (lower false-negative rates), and accuracy in detecting extremity metastasis. Spine Pelvis/Rib Extremity Overall PET +/bone scan + 35 31 10 76 PET +/bone scan - 8 8 8 24 PET -/bone scan + 7 9 6 22 PET -/bone scan - 59 61 85 205 Sensitivity 83.3% 77.5% 62.5% 77.6% Specificity 88.1% 87.1% 91.4% 89.5% Accuracy 86.2% 84.4% 87.2% 85.9% p value 1.000 1.000 0.791 0.883
Improved Clinical Outcome of Adult Patients with Ph+ ALL After a Combined Imatinib-Chemotherapy Induction/Consolidation Program Followed by Allogeneic Hematopoietic Stem Cell Transplantation: Results From a Prospective Study of the Northern Italy Leukemia Group
Authors: Alessandro Rambaldi, Orietta Spinelli, Elena Oldani, Anna Grassi, Giuseppe Rossi, Enrico Maria Pogliani, Eros Di Bona, Emanuele Angelucci, Irene Cavattoni, Giorgio Lambertenghi-Deliliers, Francesco Mannelli, Alessandro Levis, Fabio Ciceri, Daniele Mattei, Erika Borlenghi, Elisabetta Terruzzi, Claudio Borghero, Claudio Romani, Manuela Tosi, Adelaide Bussini, Tamara Intermesoli, Renato Bassan
Journal: Blood (2010)
Incidental Detection of Retiform Hemangioendothelioma by 68Ga DOTATOC PET/CT
Authors: Manuela Vadrucci, Andrea Vandoni, Laura Gilardi
Journal: Clinical Nuclear Medicine (2016)

A 52-year-old man underwent Ga DOTATOC PET/CT scan for postsurgical staging of a neuroendocrine tumor of the lung. The PET images showed a single focus of increased activity in a soft tissue nodule located posteriorly to a cervical vertebra. Surgical removal of the lesion led to the histological diagnosis of retiform hemangioendothelioma.
Final Results of Open-Label Treatment with Eltrombopag During ENABLE 1: A Study of Eltrombopag As An Adjunct for Antiviral Treatment of Hepatitis C Virus Associated with Thrombocytopenia
Authors: Geoffrey Dusheiko, Nezam H Afdhal, Edoardo Giannini, Pei-Jer Chen, Kwang-Hyub Han, Yasser Mostafa Kamel, Andres Brainsky, James Geib, Sandra Y. Vasey, Rita Patwardhan, Fiona Campbell, Dickens Theodore
Journal: Blood (2011)
Impact of Additional Cytogenetic Abnormalities and Variant t(9;22) at Diagnosis on Prognosis of Childhood Chronic Myelogenous Leukemia : The Experience of the International Registry for CML in Children and Adolescents (I-CML-Ped Study)
Authors: Frédéric Millot, Joelle Guilhot, Meinolf Suttorp, Pietr Sedlacek, Eveline S.J.M. de Bont, Chi Kong Li, Krzysztof Kalwak, Birgitte Lausen, Culic Srdjana, Marie-Francoise Dresse, Andrea Biondi, André Baruchel, Françoise Brizard
Journal: Blood (2014)
376. Correction of Metabolic Abnormalities in Murine Glycogen Storage Disease Type Ib by Gene Therapy
Authors: Young Mok Lee, Joonhyun Kwon, David A. Weinstein, Janice Y. Chou
Journal: Molecular Therapy (2015)

Glycogen storage disease type Ib (GSD-Ib) is an autosomal recessive disorder caused by deficiencies in a glucose-6-phosphate (G6P) transporter (G6PT) that transloacates G6P from the cytoplasm into the lumen of the endoplasmic reticulum where it is hydrolyzed to glucose and phosphate by the glucose-6-phosphatase-α (G6Pase-α or G6PC) enzyme. The functional coupling of G6PT and G6Pase-α maintains interprandial blood glucose homeostasis. GSD-Ib patients manifest impaired glucose homeostasis characterized by fasting hypoglycemia, hepatomegaly, nephromegaly, hyperlipidemia, hyperuricemia, lactic acidemia, and growth retardation. The current dietary therapies enable patients to maintain normoglycemia but the underlying pathological processes remain uncorrected and long-term complications, including hepatocellular adenoma (HCA), are common. In this study, we examined the efficacy of liver G6PT delivery mediated by two human G6PT-expressing recombinant adeno-associated virus (AAV) pseudotype 2/8 (rAAV8) vectors. One is a single-stranded vector containing a 2864-bp of the human G6PC promoter/enhancer (rAAV8-GPE-G6PT) and the other is a double-stranded vector containing the minimal human G6PT promoter/enhancer (rAAV8-miGT-G6PT). GSD-Ib mice were infused with either vector neonatally, then at age 4 weeks, and metabolic profiles of the infused animals were monitored at age 12 weeks. We show that the rAAV8-GPE-G6PT vector directed significantly higher levels of hepatic G6PT expression, achieved greater reduction in hepatomegaly, and led to a better toleration of fasting in GSD-Ib mice than the rAAV8-miGT-G6PT vector. Our results suggest that the rAAV8-GPE-G6PT vector is an efficacious vector in correcting metabolic abnormalities in murine GSD-Ib.
Racial Disparities in Cell of Origin Among DLBCL Patients.
Authors: Christopher R. Flowers, Loretta Nastoupil, Uma Borate, Pareen J Shenoy, Will Donnellan, Nassoma King, Kevin Bumpers, Mary Jo Lechowicz, Leon Bernal-Mizrachi, Rajni Sinha, Elizabeth Chastain, Kevin E Fisher, James M. Foran, Vishnu Reddy, David L Jaye
Journal: Blood (2012)
Abstract 8984: A New Therapeutic Modality for Ischemia-Reperfusion Injury: Nanoparticle-Mediated Delivery of Pitavastatin into Reperfused Myocardium Reduces Myocardial Ischemia/Reperfusion Injury in Rats
Authors: Kazuhiro Nagaoka, Tetsuya Matoba, Kaku Nakano, Kenji Sunagawa, Kensuke Egashira
Journal: Circulation (2011)

Background: In ST-elevation acute myocardial infarction (STEMI), early reperfusion is the most effective therapeutic strategy. Reperfusion, however, induces ischemia-reperfusion (I/R) injury that can paradoxically cancel the beneficial impacts of reperfusion. Pretreatment with statins at high doses before the occurrence of ischemia is known to reduce I/R injury by activating reperfusion injury salvage kinase (RISK) pathway, whereas treatment with statins at the time of reperfusion is reported to elicit no therapeutic effects. Nanoparticle (NP)-mediated drug delivery system may be promising for targeting reperfused myocardium where vascular permeability is enhanced. Hence we tested the hypothesis that NP-mediated site-specific delivery of pitavastatin into ischemic myocardium ameliorates I/R injury through activation of RISK pathway. Methods and Results: In the rodent model of 30-min myocardial ischemia and subsequent reperfusion, we intravenously (IV) injected NP containing 0.1 mg FITC or 0.1 mg FITC solution at the time of reperfusion. Three hours after reperfusion, we found, in the NP group, significant FITC fluorescence in viable cardiomyocytes within the area at risk (Figure A, B), while did not find in the FITC solution group (Figure B). IV treatment of pitavastatin-NP containing 1.0 mg/kg pitavastatin, but not pitavastatin solution (1.0, 10 mg/kg), reduced infarct size 24-hours after reperfusion (Figure C). Pitavastatin-NP activated RISK pathway such as Akt signals (enhanced phosphorylation at Thr 308) in the reperfused myocardium. Pretreatment of wortmannin, a PI3K inhibitor, blunted the therapeutic effects of pitavastatin-NP (Figure C). Conclusions: NP-mediated delivery of pitavastatin into ischemic myocardium at the time of reperfusion reduced myocardial infarct size by activating RISK pathway in rodent I/R model. This study may provide an innovative medical approach that complement current reperfusion therapy for STEMI.
76. Guide Adoptively Transferred T Cells Migrating Into and Killing Tumors With an HSV-2 Based Oncolytic Virus
Authors: Xinping Fu, Armando Rivera, Lihua Tao, Xiaoliu Zhang
Journal: Molecular Therapy (2015)

Adoptive T-cell therapy has shown promises for cancer treatment. However, for treating solid tumors, there is a need for improving the ability of the adoptively transferred T cells to home into and expand in tumors. We explored the possibility of using our developed oncolytic virus FusOn-H2, derived from HSV-2, to induce high levels of local chemo-attractants for the improvement of migration of adoptively transferred T cells and tumor inhibition. In a xenograft animal model, mice bearing PancO2-H7-OVA tumors received an intratumoral injection of FusOn-H2 (1X107 pfu), followed by an intravenous injection of OT-1 cells, which contain a T cell receptor specific to OVA antigen. For imaging and tracing T cell homing to and expanding in the tumor, OT-1 cells were transduced with retroviruses carrying luciferase gene. Our data showed that intratumoral administration of this virus could indeed induce high levels of local chemokine release which were specific attractants for T cells migration, like CXCL9 and CXCL10, and other inflammatory chemokines such as CCL2, CCL3, CCL4 and CXCL1. This chemokine profile really improved the migration of the adoptively transferred T cells to the treated tumor, with a 14-fold increase of T cell tracking in the tumor compared to mock-treatment, based on the luciferase activity in tumors. Moreover, once attracted to the tumor site by the virus, T cells could persist and expand in the tumor for a month without diminishing, significantly longer and more than in mock-treated tumor. These virus induced high chemokines and improved homing of T-cell to the tumor also led to a significantly enhanced therapeutic effect, with a profound inhibition on the tumor growth and even 40% tumor eradication. Our data suggest that HSV-2 based virotherapy combined with adoptive T-cell therapy can potentiate their therapeutic effect against solid tumors that are otherwise difficult to be managed with either treatment alone.
Abstract 1194: O-GlcNAcylation regulates breast cancer lipid metabolism via sterol regulatory element binding protein 1
Authors: Valerie L. Sodi, Zachary Bacigalupa, Christina Ferrer, Mauricio Reginato
Journal: Cancer Research (2015)

Abstract The Warburg hypothesis states that cancer cells display altered metabolic features to support their rapid growth and biosynthetic demands including increased glycolytic flux to synthesize necessary building blocks required by growing cells. Increased glucose uptake feeds not only glycolysis but other glucose dependent pathways as well, such as the Hexosamine Biosynthetic Pathway (HBP). HBP diverts fructose-6-phosphate from glycolysis to produce UDP-GlcNAc, the amino sugar donor to O-GlcNAc Transferase (OGT). Analagous to phosphorylation, O-GlcNAcylation can alter protein function and stability and itself is altered in several disease states. Our lab has demonstrated that OGT and O-GlcNAcylation are elevated in breast cancer and that expression of this enzyme is critical for various cancer phenotypes such as avoidance of ER stress and apoptosis, supporting invasion and metastasis and more recently promotion of Warburg effect. Here we demonstrate that OGT and O-GlcNAc are important for lipid metabolism in cancer cells through regulation of transcription factor SREBP-1 and its targets. Metabolic profiling revealed that OGT depletion in MDA-MB-231 cells decreased various lipids metabolites measured, including long-chain fatty acids, lysolipids and essential fatty acids. OGT suppression results in a decrease in SREBP-1 protein and mRNA and reduction of its transcriptional targets, enzymes involved in lipid synthesis, in both breast cancer cells and highly lipogenic normal tissue, the mammary fat pad. Over-expression of SREBP-1 blocks apoptosis induced by OGT suppression in 2D and 3D culture. Overall, we show that OGT and O-GlcNAc play a role in yet another process critical to cancer cell survival, lipid metabolism. Citation Format: Valerie L. Sodi, Zachary Bacigalupa, Christina Ferrer, Mauricio Reginato. O-GlcNAcylation regulates breast cancer lipid metabolism via sterol regulatory element binding protein 1. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1194. doi:10.1158/1538-7445.AM2015-1194
SOX2-related micrornas, miR-145 and miR-367, as prognostic markers of time to recurrence (TTR) in surgically resected non-small cell lung cancer (NSCLC) patients (p).
Authors: A. Navarro, M. Campayo, N. Vinolas, V. Ciria, T. Diaz, R. M. Marrades, L. Molins, J. Ramirez, M. Monzo
Journal: Journal of Clinical Oncology (2011)

10583
Abstract 2580: Screening of a mixture-based synthetic combinatorial library identifies small molecules that inhibit the ability of GTP to displace mant-GDP from mutant G12D KRas
Authors: Perry C. Kennedy, Marc C. Guilanotti, Travis LsVoi, Said M. Sebti
Journal: Cancer Research (2015)

Abstract Although mutant KRas significantly contributes to human oncogenesis and patient tumor resistance to therapy, there are no anticancer drugs directly targeting mt KRas available in clinic. A major effort in our laboratory is to identify novel compounds that bind mt KRas and inhibit potently and selectively KRas-driven malignant transformation. To this end, we have used a mixture-based synthetic combinatorial library (scaffold ranking library) containing over 6 million compounds in a mant-GDP assay to identify chemical scaffolds that inhibit the ability of GTP to displace mant-GDP from mt G12D KRas. Subsequent screening of the positional scanning libraries derived from the hit mixtures led to several individual compound hits with the most potent inhibiting the ability of GTP to displace mant-GDP from mt G12D KRas with IC50 of 61 μM. Current studies are focused on physical characterization of the hits to mt KRas and cellular activities of these hits in mt KRas-dependent and -independent human cancer cell lines. Citation Format: Perry C. Kennedy, Marc C. Guilanotti, Travis LsVoi, Said M. Sebti. Screening of a mixture-based synthetic combinatorial library identifies small molecules that inhibit the ability of GTP to displace mant-GDP from mutant G12D KRas. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2580. doi:10.1158/1538-7445.AM2015-2580
435. Skin Delivery of a RSV Vaccine with Surface Electroporation Provides Full Protection from Lower Respiratory Disease in the Cotton Rat
Authors: Trevor Smith, Katherine Schultheis, Jay McCoy, Niranjan Sardesai, Kate Broderick
Journal: Molecular Therapy (2016)

Respiratory syncytial virus (RSV) is a massive medical burden in infants and children worldwide, and an effective and safe RSV vaccine remains an unmet need. Here we report a novel vaccination strategy to deliver a pDNA vaccine encoding RSV-F using a surface electroporation device (SEP) to target epidermal cells in clinically relevant experimental models. We demonstrate the ability of this strategy to target epidermal Langerhans cells, and elicit robust cellular and humoral immune responses. In the cotton rat challenge model we demonstrate complete resistance to pulmonary infection after delivering a single low dose of vaccine. In contrast to the formalin-inactivated RSV (FI-RSV) vaccine there was no enhanced lung inflammation upon virus challenge after pDNA vaccination. In summary the data presented outlines the pre-clinical development of a highly efficacious, tolerable and safe non-replicating vaccine strategy against RSV.
In localized prostate cancer, active monitoring, prostatectomy, and radiotherapy did not differ for 10-y cancer deaths
Authors: Philipp Dahm, Timothy Wilt
Journal: Annals of Internal Medicine (2016)

Source Citation Hamdy FC, Donovan JL, Lane JA, et al; ProtecT Study Group. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med. 2016;375:1415-24. 27626136
Platelet Microparticle Generation Assay: a Valuable and Simpler Alternative to 14C-SRA for Type-II HIT Diagnosis.
Authors: François Mullier, Nicolas Bailly, Yvan Cornet, Severine Robert, Jean-Claude Osselaer, Christian Chatelain, Ismail Elalamy, Jean-Michel Dogné, Bernard Chatelain
Journal: Blood (2010)
Abstract 3756: Identification of prognostic gene signatures of glioblastoma: a study based on TCGA data analysis
Authors: Yong-Wan Kim
Journal: Cancer Research (2015)

Abstract The Cancer Genome Atlas (TCGA) project is a large-scale effort with the goal of identifying novel molecular aberrations in glioblastoma (GBM). Here, we describe an in-depth analysis of gene expression data and copy number aberration (CNA) data to classify GBMs into prognostic groups to determine correlates of subtypes that may be biologically significant. To identify predictive survival models, we searched TCGA in 173 patients and identified 42 probe sets that could be used to divide the tumor samples into 3 groups and showed a significantly improved overall survival. Kaplan-Meier plots showed that the median survival of group 3 was markedly longer (127 weeks) than that of groups 1 and 2 (47 and 52 weeks, respectively). We then validated the 42 probe sets to stratify the patients according to survival in other public GBM gene expression datasets (eg, GSE4290 dataset). An overall analysis of the gene expression and copy number aberration using a multivariate Cox regression model showed that the 42 probe sets had a significant prognostic value independent of other variables. By integrating multidimensional genomic data from TCGA, we identified a specific survival model in a new prognostic group of GBM and suggest that molecular stratification of patients with GBM into homogeneous subgroups may provide opportunities for the development of new treatment modalities. [This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (NRF-2013R1A1A2063115) and the MSIP (Ministry of Science, ICT and Future Planning), Korea, under the “IT Consilience Creative Program” (NIPA-2014-H0201-14-1002) supervised by the NIPA (National IT Industry Promotion Agency)] Citation Format: Yong-Wan Kim. Identification of prognostic gene signatures of glioblastoma: a study based on TCGA data analysis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3756. doi:10.1158/1538-7445.AM2015-3756
More than meets the eye
Authors: Usha B Blessin, Andreas Fischer, Thomas Schneider, Verena Moos, Tobias Müller, Karsten H Weylandt, Uwe Pleyer
Journal: Gut (2016)

A 74-year-old woman was admitted to the ophthalmology department with progressive vision loss, vitreous clouding and suspected endogenous endophthalmitis. Bilateral eye problems had started several weeks before and grew worse under oral prednisolon therapy. After admission, progressive vitreous haze was diagnosed (figure 1A). A diagnostic vitrectomy was performed for microbiological testing.



Figure 1 
Assessment of the left eye before vitrectomy. Preretinal ‘white material’ was visible on ophthalmoscopy within the vitreous cavity (A). Endoscopic view into the second part of the duodenum (B) and the terminal ileum (C), showing ragged erythematous mucosa and lymphangiectasia.



The patient was also presented with watery diarrhoea that had started 6 months ago. Bowel movements were independent of food ingestion and occurred also during the night; furthermore, the patient reported weight loss of 6–7 kg, epigastric pain, latent nausea and deterioration …
Pyruvate dehydrogenase kinase 4 deficiency attenuates cisplatin-induced acute kidney injury
Authors: Chang Joo Oh, Chae-Myeong Ha, Young-Keun Choi, Sungmi Park, Mi Sun Choe, Nam Ho Jeoung, Yang Hoon Huh, Hyo-Jeong Kim, Hee-Seok Kweon, Ji-min Lee, Sun Joo Lee, Jae-Han Jeon, Robert A. Harris, Keun-Gyu Park, In-Kyu Lee
Journal: Kidney International (2016)
PWE-013 Assessment of rapid on site evaluation for cytology of solid pancreatic masses evaluated by endoscopic ultrasound fine-needle aspiration: impact on a new team's learning curve
Authors: R McCrudden, D Collins, J McCutcheon, B Foria
Journal: Gut (2010)

<h3>Introduction</h3> Rapid on site evaluation (ROSE) of cytology from endoscopic ultrasound fine-needle aspiration (EUS-FNA) is uncommon in the UK. The impact of ROSE in the learning curve of a new EUS-FNA service is largely unknown. Documenting the yield of malignancy in solid pancreatic lesions may provide a benchmark for performance of EUS-FNA. <h3>Aim</h3> We report the initial findings of ROSE and its impact on the first 36 consecutive cases of solid pancreatic mass lesions (SPML). <h3>Methods</h3> We prospectively collected data on the first 70 patients referred for an EUS-FNA incorporating a single endosonographer competent in radial EUS, a single cytotechnologist (ROSE) and two pathologists. <h3>Result</h3> The average age was 62.9 with a M/F ratio of 42:28. SPML accounted for 36/70 (51.4%). No samples were deemed inadequate. Cytology confirmed adenocarcinoma in 30/36 (83.3%). Of the remaining six, follow-up data (cytology, subsequent surgery, oncology, clinical follow-up) confirmed two cases consistent with chronic pancreatitis; one suspicious for malignancy (subsequent CT revealed lung metastases), while EUS criteria suggested malignancy in the remaining three cases cytology was non-diagnostic. One patient elected for a Whipples which showed pT3N1 pancreatic cancer, one remains under current surveillance follow-up, one died of metastatic tumour presumed pancreatic in origin. ROSE suggested malignancy in 34/36 (94%) cases. There was good agreement therefore between on site evaluation and final cytology reporting. <h3>Conclusion</h3> EUS FNA gave a high yield in the diagnosis of adenocarcinoma in solid pancreatic tumours in 30/34 (88%) one further case was suspicious for malignancy. ROSE had an immediate impact on determination of necrotic centres within tumour masses, immediate feedback on tissue acquisition and blood contaminating specimens thus guiding decisions re suction vs no suction, limiting the number of passes when material was deemed adequate thus optimising the procedure time, and guiding the evolving technique of FNA passes within a tumour mass. No case returned for a second EUS FNA. In a new FNA service ROSE contributed to the accuracy of staging, the learning curve of the team and enabled decision making to take place on the day of the procedure.