tbuckley/cabot-search huggingface dataset:
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Authors: Jenny Yeuk‐Ki Cheng, Yee‐Kit Tse, Grace Lai‐Hung Wong
Journal: Hepatology (2016)

Potential conflict of interest: Dr. Wong consults for and is on the speakers' bureau for Otsuka and Gilead. She consults for Abbott and AbbVie. She is on the speakers' bureau for Bristol‐Myers Squibb, Roche, Echosens, and Furui. We thank Drs. Erfan, Saeid, and their colleagues for their interest in our work. As for the worry that the results of our study1 were biased by multicollinearity among metabolic syndrome components, we have now checked for collinearity for the associations between those components and various clinical outcomes, namely, hepatic events, cardiovascular events, and death in univariate and multivariate analysis, respectively. We assessed the variance inflation factor (VIF) of our variables, which quantifies the severity of multicollinearity. The results reveal that all variables included in our models are of low VIF (i.e., below 2). Therefore, we believe that our study is not biased by the multicollinearity among metabolic components. Concerning the issue of the dose‐response or nonlinear association between each component of metabolic syndrome with cardiovascular events and death, it would be less of a concern in our study. This is because all the components of metabolic syndrome were analyzed as binary categorical covariates, according to the modified National Cholesterol Education Program Adult Treatment Panel III criteria,2 in the multivariable analysis. On the other hand, we acknowledge that our use of a single measurement may dilute the relationship between metabolic syndrome components and the studied outcomes. We may try to involve serial measurements instead of single baseline measurements for our future studies.
605. Cerebrospinal Fluid for Delivery of AAV Gene Therapy in GM1 Gangliosidosis
Authors: Amanda L. Gross, Heather Gray-Edwards, Bryan Murdock, Amanda Taylor, Brandon Brunson, Ashley N. Randle, Lorelei Stocia, Sophia Todessa, Jaclyn Lata, Miguel Sena-Esteves, Douglas R. Martin
Journal: Molecular Therapy (2016)

GM1 gangliosidosis, a hereditary lysosomal storage disease caused by a deficiency of lysosomal β-galactosidase, is characterized by rapidly progressing and fatal neurologic disease. The most common form of GM1 affects children and is fatal by approximately 4 years of age. Currently, there is no effective treatment for GM1 gangliosidosis beyond palliative or supportive care. There are several naturally occurring models of GM1 gangliosidosis, including a well-characterized feline model that closely reproduces human disease progression and facilitates testing of experimental therapies for clinical application. Adeno-associated viral (AAV) therapy has proven effective in GM1 cats, with a greater than 6 fold increase in lifespan after thalamic and deep cerebellar nuclei injections. Prior to initiation of human clinical trials, CSF delivery was evaluated to circumvent the risk of cerebellar parenchymal injection and to improve cortical biodistribution. AAVrh10 was delivered at a total dose of 1e12 vector genomes/kg body weight via 3 routes: cisterna magna (CM), bilateral intracerebroventricular (ICV), or lumbar cistern (LC). Cats were followed for 4 weeks post injection, after which biodistribution of enzyme and vector were assessed. After LC injection, enzyme was limited to the spinal cord, where it reached a maximum of 0.7 fold normal. As expected, the highest vector concentration was limited to the lumbar spinal cord. This indicates limited cranial flow of vector from the lumbar cistern of injected cats, minimizing the efficacy of lumbar delivery. Delivery by the CM led to 0.4 fold - 1.5 fold normal levels of enzyme activity in the spinal cord and up to 2.1 fold the cerebellum and thalamic regions. Following CM injection, vector distributed well to the caudal region of the cerebrum, all of the cerebellum, and throughout the spinal cord. Enzyme activity after ICV injections showed increases from 0.2 fold - 0.8 fold normal in the spinal cord and 0.1 fold - 0.5 fold in the brain. ICV injections led to vector distribution throughout the cerebrum as well as the spinal cord. CSF delivery via cisterna magna, ICV, or lumbar injection is substantially less invasive than cerebellar injection. Based on the results presented here, CM or ICV injection may prove beneficial in clinical trials. Additionally, combining cisterna magna and ICV injection of vector could further enhance therapeutic effect.
An Animal Model Suitable for Predicting In Vivo Behavior of Platelets in Humans: A Tool for New Product Development.
Authors: Morris A. Blajchman, Junzhi Li, Myron Kulczycky, Zofia Woskowska, Henry Pieters, Jan Roodt, Philip Badenhorst, Robert Crookes, Anthon Heyns, Raymond Goodrich
Journal: Blood (2004)
Achievement of CR and nCR Before and After First High-Dose Therapy Followed by Autologous Stem Cell Transplantation Is a Major Marker for Long-Term Survival in Multiple Myeloma Patients.
Authors: Hartmut Goldschmidt, Gerlinde Egerer, Ute Hegenbart, Markus Munder, Thomas Hielscher, Christiane Heiβ, Uta Bertsch, Jens Hillengaβ, Jana Schlenzka, Marc-Steffen Raab, Dirk Hose, Michael Hundemer, Kai Neben, Anthony D. Ho
Journal: Blood (2009)
Increased M2 Macrophages in Multiple Myeloma Patients with Progressive Disease and Down-Regulated Polarization with the JAK2 Inhibitor Ruxolitinib
Authors: Haiming Chen, Eric Sanchez, Mingjie Li, Cathy Wang, Abby Gillespie, Anna Shvartsur, Suzie Vardanyan, Nika M Harutyunyan, Gigi Garzio, George Tang, Benjamin Bonavida, James R. Berenson
Journal: Blood (2014)
Abstract 1205: Identification of a novel adjuvant therapeutic agent for obesity related pancreatic cancer
Authors: Adriana Harbuzariu, Robin C. Garrison, Danielle S. Daley-Brown, Derrick J. Beech, Frederick D. Cason, Tia L. Harmon, Lily Yang, Ruben R. Gonzalez-Perez
Journal: Cancer Research (2015)

Abstract PURPOSE: Pancreatic cancer (PC) is an aggressive disease that develops in a symptom-free manner and is usually advanced at the time of diagnosis; the overall 5 year survival rate is less than 5%. Obesity is pandemic in the US and strongly linked to higher incidence of many cancer types. Obese people are 20% more likely to develop PC. We hypothesize that high level of leptin shown by obese PC patients could increase tumor progression and drug resistance. METHODS: A panel of PC cell lines (Panc-1, BxPC-3 and MiaPaCa-2) was challenged with leptin, a specific leptin inhibitor coupled with nanoparticles (IONP-LPrA2) and various chemotherapeutic agents (Gemcitabine, Cisplatin, Paclitaxel and Sunitinib). Cell viability, proliferation and the expression levels of molecular markers were analyzed. Further, we investigated the ability of PC cells to form tumorspheres when treated with leptin and IONP-LPrA2. The number of colonies was counted and pancreatic cancer stem cells (PCSC) markers (ALDH1, CD44, CD24, ESA) and OB-R expression was assessed. PCSC markers were determined in PC tissue arrays. RESULTS: PCSC markers were expressed in obese PC patients. Leptin induced S phase progression, overexpression of Notch and PCSC markers and increased stemness and tumorigenesis of PC cells. In addition, leptin impaired the efficacy of chemotherapeutic agents on PC cells and derived tumorspheres. The inhibition of leptin signaling via IONP-LPrA2 abrogated PC growth, reduced PCSC markers expression and enhanced chemotherapeutic action by inducing apoptosis. Our data suggests that leptin signaling is essential for PC cells proliferation and survival and reduces chemotherapeutic effects. These findings are of great importance for obese PC patients which show the highest level of leptin, poor prognosis and chemotherapy outcome. LPrA2 has no toxicity and it has been shown that it does not affect health status, appetite, body weight or energy balance in mice. IONP-LPrA2 could be a novel adjuvant for PC treatment, especially for obese PC patients. Acknowledgements: this work was supported by NIH/NCI 5SC1CA138658-05 and the DOD Breast Cancer Idea Award (W81XWH13-1-0382) to RRGP; NIH/2G12RR003034-26 and U54 MSM/UAB Cancer Center Partnership. This research was also supported by facilities and support services at Morehouse School of Medicine (NIH 1C06 RR18386). Citation Format: Adriana Harbuzariu, Robin C. Garrison, Danielle S. Daley-Brown, Derrick J. Beech, Frederick D. Cason, Tia L. Harmon, Lily Yang, Ruben R. Gonzalez-Perez. Identification of a novel adjuvant therapeutic agent for obesity related pancreatic cancer. [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 1205. doi:10.1158/1538-7445.AM2015-1205
Abstract 4058: Hypoxia-induced soluble CD137 in malignant cells blocks CD137L-costimulation as an immune escape mechanism
Authors: Sara Labiano, Asís Palazón, José I. Quetglas, Elixabet Bolaños, Arantza Azpilicueta, Aizea Morales-Kastresana, Alfonso Rodriguez, Maria Rodriguez-Ruiz, Alfonso Gurpide, M Angela Aznar, Maria Jure-Kunkel, Ignacio Melero
Journal: Cancer Research (2015)

Abstract Hypoxia is a common feature in solid tumors that has been implicated in immune-evasion. In this study, we show that exposure of mouse and human tumor cell lines to hypoxic conditions (1% O2) promotes CD137 transcription. Previous studies from our group have shown that hypoxia up-regulates the co-stimulatory receptor CD137 on activated T lymphocytes and on vascular endothelial cells. However, our results show that the CD137 transcript upregulated under hypoxia in tumor cell lines is predominantly an alternatively spliced form that encodes for a soluble variant, which lacks the transmembrane domain. Accordingly, soluble CD137 (sCD137) is detectable by ELISA in the supernatant of hypoxia-exposed cell lines and in the serum of tumor-bearing mice. sCD137, as secreted by tumor cells, is able to bind to CD137-Ligand (CD137L). Our studies on primed T lymphocytes in co-culture with stable transfectants for CD137L demonstrate that tumor-secreted sCD137 prevents co-stimulation of T lymphocytes. Such an effect results from preventing the interaction of CD137L with the transmembrane forms of CD137 expressed on T lymphocytes undergoing activation. This mechanism is interpreted as a molecular strategy deployed by tumors to repress lymphocyte co-stimulation via CD137/CD137L. Citation Format: Sara Labiano, Asís Palazón, José I. Quetglas, Elixabet Bolaños, Arantza Azpilicueta, Aizea Morales-Kastresana, Alfonso Rodriguez, Maria Rodriguez-Ruiz, Alfonso Gurpide, M Angela Aznar, Maria Jure-Kunkel, Ignacio Melero. Hypoxia-induced soluble CD137 in malignant cells blocks CD137L-costimulation as an immune escape mechanism. [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 4058. doi:10.1158/1538-7445.AM2015-4058
VISLISI trial, a prospective clinical study allowing identification of a new metalloprotease and putative virulence factor from Staphylococcus lugdunensis
Authors: X. Argemi, G. Prévost, P. Riegel, D. Keller, N. Meyer, M. Baldeyrou, N. Douiri, N. Lefebvre, K. Meghit, C. Ronde Oustau, D. Christmann, S. Cianférani, J.M. Strub, Y. Hansmann
Journal: Clinical Microbiology and Infection (2016)
Epigenetic Suppression of the CTNNA1 Gene, Encoding the α-Catenin Protein, which Is Located in the 5q31 Critical Deleted Region in Malignant Myeloid Disorders with del(5q).
Authors: Ting Xi Liu, Michael Becker, Karl Hsu, Jaroslav Jelinek, Min Deng, Clara Bloomfield, Jean-Pierre Issa, Michael F. Clarke, A. Thomas Look
Journal: Blood (2004)
350. Kidney-Directed Gene Therapy for Murine Glycogen Storage Disease Type IA
Authors: Youngmok Lee, Seongho Bae, Celine J. Rocca, Stephanie Cherqui, David A. Weinstein, Janice Y. Chou
Journal: Molecular Therapy (2016)

Glycogen storage disease type Ia (GSD-Ia, MIM232200) is an autosomal recessive disorder caused by deficiencies in glucose-6-phosphatase-α (G6Pase-α or G6PC) that is expressed primarily in the liver and kidney. GSD-Ia patients manifest impaired glucose homeostasis and a long-term complication of renal disease and there is no existing therapy to address this complication. We have previously shown that systemic administration of rAAV8-G6PC, a rAAV8 vector expressing human G6Pase-α directed by the human G6PC promoter/enhancer, delivers the G6Pase-α transgene to the liver of G6Pase-α-deficient (G6pc-/-) mice and corrects hepatic G6Pase-α deficiency. However, the rAAV8-G6PC vector transduces the kidney poorly and the treated G6pc-/- mice continued manifest renal dysfunction. In this study, we used the rAAV9-G6PC vector in a kidney-targeted gene delivery to improve renal function. The G6pc-/- die early even with glucose therapy. To overcome this, we performed a two-step kidney-directed gene delivery, first neonatally via the temporal vein with rAAV8-G6PC to sustain the survival of the mice, then at 12 weeks of age via retrograde renal vein injection with rAAV9-G6PC. Metabolic profiles and renal function were examined over a 52-week study. The rAAV-treated G6pc-/- mice exhibited normal fasting glucose profiles and could sustain a 24 hour of fast. Moreover, the treated G6pc-/- mice displayed normalized blood urea nitrogen concentrations, indicative of improved renal function. Our results strongly suggest that kidney-directed gene delivery with the rAAV9-G6PC vectors offers a promising and efficacious treatment for renal disease in GSD-Ia.
Abstract 4932: Development of a highly sensitive library prep method for identifying pathogenic variants from FFPE tumor samples
Authors: Amanda G. Young, Charles Lin
Journal: Cancer Research (2015)

Abstract The application of genomics in cancer has led to an improved understanding of the disease. To date, 125 known driver genes have been discovered*. These genes and their pathways have become the focus of small-molecule drug development. While the number of available targeted therapies is limited, an estimated 800 oncology drugs are in development*, many of which target specific mutations. Single-analyte companion diagnostics exist for the approved therapies, and more might be developed as new therapeutics become available, but the need to assay each variant individually can be ineffective.. An additional, well-known challenge is the degradation and damage caused to DNA in formalin-fixed, paraffin-embedded (FFPE) samples. For these reasons, Illumina is developing a novel method for simultaneous detection of multiple somatic variants from FFPE specimens. This method leverages a multiplexed PCR approach with amplicons designed to a 15-gene panel that can detect somatic variants in 14 genes, and copy number changes in 3 genes. In our experiments, this multiplexed PCR assay has been demonstrated to be highly sensitive, yielding results from as little as 20 ng of DNA extracted from FFPE tissue, even if the DNA is highly damaged and degraded. Somatic variants can be detected down to 5% allele fraction, and gene amplifications can be detected for ≥ 2.2-fold change in copy number. This method, incorporating newly designed software, will be deployed as part of the Illumina Universal Oncology Test System on the MiSeqDx™ (under development), analyzing the sequencing results, and generating reports of mutations and copy number changes in cancer samples. Citation Format: Amanda G. Young, Charles Lin. Development of a highly sensitive library prep method for identifying pathogenic variants from FFPE tumor samples. [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 4932. doi:10.1158/1538-7445.AM2015-4932
Acute Myeloid Leukemia with Translocation t(8;16) Demonstrates Specific Cytomorphological, Cytogenetic, and Gene Expression Characteristics and Can Clearly Be Discriminated from Other AML with Balanced Translocations.
Authors: Torsten Haferlach, Helmut Loeffler, Alexander Kohlmann, Martin Dugas, Wolfgang Hiddemann, Wolfgang Kern, Susanne Schnittger, Claudia Schoch
Journal: Blood (2004)
<i>Sequenom v. Ariosa</i> — The Death of a Genetic Testing Patent
Authors: Robert Cook-Deegan, Subhashini Chandrasekharan
Journal: New England Journal of Medicine (2016)

In June, the U.S. Supreme Court declined to uphold a patent on “a method for detecting paternally inherited nucleic acid of fetal origin” in maternal serum or plasma. Clarification of patent eligibility will now have to wait for a case with narrower patent claims.
Cystatin-C Is a Sensitive Marker of Renal Impairment with an Independent Predictive Value for Survival in Multiple Myeloma; Reduction Post Bortezomib Monotherapy.
Authors: Evangelos Terpos, Eirini Katodritou, Evangelos Tsiftsakis, Efstathios Kastritis, Anastasia Pouli, Dimitrios Christoulas, Evridiki Michali, Evgenia Verrou, Anastasia Banti, Konstantinos Tsionos, Meletios A. Dimopoulos, Konstantinos Zervas
Journal: Blood (2007)
Abstract 3067: Expression of miR-301a regulates metastasis and act as a lethal marker for prostate cancer
Authors: Trinath P. Das, Suman Suman, Arokya Ms PapuJohn, Akhila Ankhem, Sandhya R. Rao, Jamie C. Messer, Houda Alatassi, Murali M. Ankhem, Chendil Damodaran
Journal: Cancer Research (2015)

Abstract Prostate Specific Antigen (PSA) screening contributes as a biomarker for diagnosis of prostate cancer; however, PSA screening has been considered an over diagnosis in some cases. This has lead to the identification of novel invasive markers which could eventually differentiate patients with lethal prostate cancer from those with indolent disease. Emerging evidences suggest that a small set of microRNAs (miRNA) are linked to prostate cancer pathogenesis leading to castration resistant prostate cancer (CRPC). In our studies of genome wide miRNA profiling, we have found that miR-301a is highly expressed in prostate cancer (CaP) cell lines as compared to normal prostate epithelial cells. While analyzing CaP samples, we found higher expression of miR-301a at specific stages. Interestingly, the miR-301a induction varies from 10 to 250 fold in aggressive tumors which clearly correlate with metastases. To confirm these findings, we utilized metastatic lesions from transgenic mice model of Trans Adenocarcinoma of Mouse Prostate (TRAMP) tissues, where higher levels of miR301a expression were observed in prostate tumors in comparison with normal prostate. Further, micro dissecting the tumors (metastasis) from lung showed ∼15 fold induction of miR301a expression compared to the normal lung components. Silencing specifically miR-301a resulted in the inhibition of proliferation, colony forming abilities, invasion, and migration and cell adhesion properties in CaP cell lines. Our molecular studies also suggest that miR-301 regulates Rho GTPases family proteins and transcriptionally activates Epithelial-Mesenchymal-Transition (EMT) markers like slug and β-catenin. Our ongoing studies may not only reveal whether miR-301 regulates Rho-associated kinases (ROCK) but also the potential role of EMT in CaP. Furthermore, we intend to perform a case control study by screening an additional 100 CaP cases besides indolent controls. As mentioned earlier, besides revealing the functional role in CaP pathogenesis, results from these findings will also suggest whether miR-301 expression distinguishes lethal CaP from indolent disease. Citation Format: Trinath P. Das, Suman Suman, Arokya Ms PapuJohn, Akhila Ankhem, Sandhya R. Rao, Jamie C. Messer, Houda Alatassi, Murali M. Ankhem, Chendil Damodaran. Expression of miR-301a regulates metastasis and act as a lethal marker for prostate cancer. [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 3067. doi:10.1158/1538-7445.AM2015-3067
The Wee1 Inhibitor, MK-1775, Sensitizes Leukemic Cells to Different Antineoplastic Drugs Interfering with DNA Damage Response Pathway
Authors: Andrea Ghelli Luserna Di Rora, Ilaria Iacobucci, Neil Beeharry, Simona Soverini, Cristina Papayannidis, Giovanni Martinelli, Timothy J Yen
Journal: Blood (2015)
Long-Term Outcome After CRT in the Presence of Mechanical Dyssynchrony Seen With Chronic RV Pacing or Intrinsic LBBB
Authors: Ivan Stankovic, Christian Prinz, Agnieszka Ciarka, Ana Maria Daraban, Yujing Mo, Marit Aarones, Mariola Szulik, Stefan Winter, Aleksandar N. Neskovic, Tomasz Kukulski, Svend Aakhus, Rik Willems, Wolfgang Fehske, Martin Penicka, Lothar Faber, Jens-Uwe Voigt
Journal: JACC. Cardiovascular imaging (2016)
Abstract 3026: Gastric cancer associated variant of DNA polymerase Beta (Leu22Pro) induce genomic instability and cellular transformation
Authors: Dawit Kidane, Jenna Rozacky, Joann B. Sweasy
Journal: Cancer Research (2015)

Abstract DNA polymerase beta (Pol β) is a key enzyme for the protection of oxidative DNA lesions via its role in base excision repair (BER). Approximately 1/3 of tumors studied to date express Pol β variant proteins, and several tumors overexpress Pol β. Pol β possesses DNA polymerase and dRP lyase activities, both of which are known to be important for efficient BER. The dRP lyase activity resides within the 8kDa amino terminal domain of pol β, is responsible for removal of the 5′ phosphate group and the polymerase domain at subsequent steps fills the gaps. Previously, we demonstrated that gastric cancer-associated variant of pol β (Leu22Pro (L22P)) lacks dRP lyase function in-vitro. Here, we have employed DNA fiber labeling to quantify, for the first time, the extent to which the normal function of dRP lyase of DNA polymerase beta is critical to maintain global replication fork rates in normal gastric epithelial cells. We report that replication fork rates in L22P expressing cells are on average half of those observed with wild-type cells. In addition, we show that L22P variant promotes replication dependent double strand breaks that may likely responsible for chromosomal aberrations. These data may implicate normal function of dRP lyase is critical to stabilize replication fork stall and prevent replication fork collapse to DNA double strand breaks. Citation Format: Dawit Kidane, Jenna Rozacky, Joann B. Sweasy. Gastric cancer associated variant of DNA polymerase Beta (Leu22Pro) induce genomic instability and cellular transformation. [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 3026. doi:10.1158/1538-7445.AM2015-3026
Prevalence of atopic dermatitis in infants by domestic water hardness and season of birth: Cohort study
Authors: Kristiane A. Engebretsen, Peter Bager, Jan Wohlfahrt, Lone Skov, Claus Zachariae, Anne-Marie Nybo Andersen, Mads Melbye, Jacob P. Thyssen
Journal: Journal of Allergy and Clinical Immunology (2016)
Evaluating a Value-Driven Outcomes Program—Reply
Authors: Vivian S. Lee, Kensaku Kawamoto, Rachel Hess
Journal: JAMA (2016)

In Reply Dr Weeks describes 2 limitations in our analyses of 3 value improvement projects: the lack of concurrent control groups as in a randomized clinical trial and the lack of covariate or risk adjustment. We agree with these critiques, as noted in our article.
Aberrantly Hypermethylated Genes in Adult T-Cell Leukemia Cells: The Implications in the Leukemogenesis.
Authors: Jun-ichirou Yasunaga, Yuko Taniguchi, Kisato Nosaka, Yorifumi Satou, Mlka Yoshida, Ken Takai, Tatsunori Sakai, Hiroaki Mitsuya, Masao Matsuoka
Journal: Blood (2004)
Direct Interaction of G-CSF-Stimulated-Neutrophils and HUVECs Are Necessary for Production of IL-8 in Endothelial Cells.
Authors: Yasuhiro Okamoto, Tsutomu Watanabe, Toshihiro Onishi, Hiroyoshi Watanabe, Yuni Yamaki, Yuichi Kodama, Takuro Nishikawa, Takayuki Tanabe, Yuichi Shinkoda, Yoshifumi Kawano
Journal: Blood (2007)