tbuckley/cabot-search huggingface dataset:
Abstract 4617: High expression of snail is associated with EZH2 expression and lymph node metastasis in large neuroendocrine lung cancer
Authors: Yueh-Fu Fang, Min-Chia Lee
Journal: Cancer Research (2018)

Abstract Background Large neuroendocrine lung cancer was less than adenocarcinoma or squamous cell carcinoma of lung. EZH2 expression was high in small cell lung cancer with component of neuroendocrine. There was no study of EZH2 in large neuroendocrine lung cancer. We planned to identify the expression of EZH2 and EMT markers and the clinical outcome in large neuroendocrine lung cancer. Methods and Patient There were 25 resectable large neuroendocrine lung cancer patients in our hospital before 2014. Twenty-two patients' tissue was done for EZH2 and EMT markers. The EZH2-GSK3 and EMT signaling were performed in H1299 and H460 cancer cell lines. EZH2 inhibitor, Akt inhibitor and protease inhibitor was used to validate the cell signaling from EZH2 to EMT markers. Results There were 10 patients had high EZH2 and snail and 10 patients had low EZH2 and snail. The correlation between EZH2 and snail was very high. Snail expression showed high prevalence of lymph node metastasis but no EZH2. The overall survival and progression free survival showed no definite in EZH2 and other insomnia. The recurrence was also not significant difference. The cellular study showed the same result. Conclusion Over expression of snail showed high correlation with EZH2 and was a predictable marker. Citation Format: Yueh-Fu Fang, Min-Chia Lee. High expression of snail is associated with EZH2 expression and lymph node metastasis in large neuroendocrine lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4617.
Abstract 2350: Efficient survival multifactor dimensionality reduction method for genome-wide association study
Authors: Jiang Gui, Xuemei Ji, Christopher I. Amos
Journal: Cancer Research (2018)

Abstract The problem of identifying associations between SNPs and case-control outcome has been studied extensively and a number of new techniques have been developed. Little progress has been made, however in the analysis of SNP effect in relation to censored survival data. We present an extension of the two class multifactor dimensionality reduction (MDR) algorithm that enables detection and characterization of epistatic SNP-SNP interactions in the context of survival outcome. The proposed an Efficient Survival MDR (ES-MDR) method handles censored data by modifying MDR's constructive induction algorithm to use logrank Test. We applied ES-MDR to genetic data of over 470,000 SNPs from the OncoArray Consortium. We use onset age of lung cancer and case-control (n=27,312) status as the survival outcome and divided data into training and testing sets. We also adjust for subject's age, gender and smoking status. From training set, we identified strong association from SNPs in BRCA1 and IL17RC genes with lung cancer onset age. This result is validated in the testing set. Citation Format: Jiang Gui, Xuemei Ji, Christopher I. Amos. Efficient survival multifactor dimensionality reduction method for genome-wide association study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2350.
Abstract 2166: Dasatinib displays antitumor efficacy in an orthotopic xenograft mouse model of histiocytic sarcoma
Authors: Marilia Takada, Lauren Smyth, Vilma Yuzbasiyan-Gurkan
Journal: Cancer Research (2018)

Abstract Histiocytic sarcoma (HS) is an orphan hematological malignancy with an incidence of less than 1% of all non-Hodgkin's lymphoma, affecting both children and adults. It is a highly metastatic disease, and can affect any organ in the body including spleen, lungs, bone marrow, liver and lymph nodes. It is associated with a poor prognosis as treatment options are scarce and responses are short lived. Dogs spontaneously develop a similar form of HS with an appreciable frequency, and therefore present a unique translational model to investigate better treatments. Preliminary data from in vitro studies identified dasatinib, a multi tyrosine kinase inhibitor, as a highly potent drug against HS cell lines derived from tumors in dogs, but non-toxic to normal normal tissue surrogate fibroblasts. The current study was undertaken to evaluate if the efficacy of dasatinib could be re-capitulated in an in vivo orthotopic xenograft model of HS. The mouse model was generated in NOD-SCID mice by surgical injection of HS cells, transfected with a luciferase reporter construct, into their spleen. Tumor growth was monitored using In Vivo Imaging System. Mice were treated with 30 mg/kg of dasatinib intraperitoneally once a day or vehicle control, with five mice in each group. Dasatinib treated mice had a significantly decreased tumor growth rate in comparison to untreated mice. Most importantly, treatment with dasatinib significantly increased their survival time. All mice from the vehicle control group reached humane endpoints for euthanasia by day 27, while treated mice were clinically stable at day 53, with the difference in survival being highly significant (p&amp;lt;0.0001). In conclusion, here we report the first orthotopic xenograft mouse model of HS, that offers the possibility to test therapeutic response to novel agents, such as dasatinib. Our findings indicate that dasatinib is a promising treatment option for HS, and provide a rational for the initiation of clinical trials. Citation Format: Marilia Takada, Lauren Smyth, Vilma Yuzbasiyan-Gurkan. Dasatinib displays antitumor efficacy in an orthotopic xenograft mouse model of histiocytic sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2166.
Orthostatic Hypotension as a Prodromal Marker of α-Synucleinopathies—Reply
Authors: Rodolfo Savica, Bradley F. Boeve, Michelle M. Mielke
Journal: JAMA Neurology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Genome-Wide Analysis of the Zebrafish ETS Family Identifies Three Genes Required for Hemangioblast Differentiation or Angiogenesis
Authors: FengLiu, RogerPatient
Journal: Circulation Research (2008)

ETS domain transcription factors have been linked to hematopoiesis, vasculogenesis, and angiogenesis. However, their biological functions and the mechanisms of action, remain incompletely understood. Here, we have performed a systematic analysis of zebrafish ETS domain genes and identified 31 in the genome. Detailed gene expression profiling revealed that 12 of them are expressed in blood and endothelial precursors during embryonic development. Combined with a phylogenetic tree assay, this suggests that some of the coexpressed genes may have redundant or additive functions in these cells. Loss-of-function analysis of 3 of them, erg, fli1, and etsrp, demonstrated that erg and fli1 act cooperatively and are required for angiogenesis possibly via direct regulation of an endothelial cell junction molecule, VE-cadherin, whereas etsrp is essential for primitive myeloid/endothelial progenitors (hemangioblasts) in zebrafish. Taken together, these results provide a global view of the ETS genes in the zebrafish gen...
Specific Cardiomyopathy Caused by Multisystemic Lipid Storage in Jordan’s Anomaly
Authors: YuichiOshima, HisaoHirota, HiroyukiNagai, MasahiroIzumi, YoshikazuNakaoka, TomoakiOsugi, YasushiFujio, HitoneTateyama, MasanoriKikui, KeikoYamauchi-Takihara, IchiroKawase
Journal: Circulation (2002)
Abstract 2735: Cancer immunotherapy with agonistic anti-4-1BB scFv producing and secreting <i>Bifidobacterium</i> in syngeneic mouse model
Authors: Tomio Matsumura, Koichiro Shioya, Yasuyoshi Kanari, Yuko Shimatani, Shiro Kataoka, Shun'ichiro Taniguchi, Takaaki Nakamura
Journal: Cancer Research (2018)

Abstract Agonistic antibodies against immune checkpoint molecules, such as 4-1BB, reportedly demonstrate antitumor effects at the early clinical phase, whereas immune-related adverse events hamper further development. A single chain variable fragment (scFv), which is expected to have better penetration into tissues, is clinically being investigated, however, poor distribution into tumor tissues due to rapid clearance is a serious issue. In order to improve drug delivery and decrease adverse events, we have developed in situ Delivery and Production System (i-DPS) by genetically engineering a non-pathogenic anaerobic Bifidobacterium. We previously reported that the modified Bifidobacteria localized and proliferated only in the hypoxic area of the tumor engrafted in the mouse post i.v. injection, thus producing anti-tumor molecules persistently and selectively at the tumor site (AACR2010). Here we present i-DPS with agonistic anti-murine 4-1BB scFv. We created a recombinant Bifidobacterium producing and secreting anti-murine 4-1BB scFv. The anti-murine 4-1BB scFv increased IFN-γ production by 171% over the control group (PBS(-)) in the mouse splenocytes activated by ant-CD3 antibody in vitro. Anti-tumor effects of Bifidobacteria producing the anti-murine 4-1BB scFv were demonstrated in the syngeneic model of CT-26 in Balb/c mouse (61.7% tumor growth inhibition (TGI) at 1×109 cfu/mouse, i.v. on day 14). We further evaluated the anti-tumor effects of i-DPS for anti-murine 4-1BB scFv (1×109 cfu/mouse, i.v.) in combination with PD-1 antibody (i.p.), and confirmed that the combination therapy significantly suppressed the tumor growth on day 21 (TGI: combination, 60.7%; anti-murine 4-1BB scFv, 38.8%; anti-mPD-1 mAb, 8.9%). In conclusion, i-DPS for anti-4-1BB scFv will provide a new promising modality for the immune-therapy targeting hypoxic solid tumors. Citation Format: Tomio Matsumura, Koichiro Shioya, Yasuyoshi Kanari, Yuko Shimatani, Shiro Kataoka, Shun'ichiro Taniguchi, Takaaki Nakamura. Cancer immunotherapy with agonistic anti-4-1BB scFv producing and secreting Bifidobacterium in syngeneic mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2735.
Abstract 2863: Dissecting the structural basis for inhibitors of RNA-binding proteins
Authors: Lan Lan, Minli Xing, Xiaoqing Wu, Philip Gao, Justin T. Douglas, Yu Zhan, Gulhumay Gardashova, Jiajun Liu, Robert P. Hanzlik, Jeffrey Aubé, Kristi L. Neufeld, Berl R. Oakley, Roberto N. De Guzman, Liang Xu
Journal: Cancer Research (2018)

Abstract RNA-binding proteins (RBPs) are key regulators of cellular functions, especially in post-transcriptional regulations. Dysregulation of RBPs is implicated in many diseases including cancer. One of the RBPs that is overexpressed in a variety of human cancer is Musashi-2 (MSI2). Elevated MSI2 expression is associated with ectopic oncogenic pathways, including but not limited to NUMB/Notch, PTEN/mTOR, TGF-β/SMAD3, making MSI2 a promising therapeutic target for cancer. In the case of NUMB, MSI2 binds to and negatively regulates translation of NUMB, a negative regulator of Notch signaling. Protein structure is critical for drug discovery and structure-based rational design. However, so far there is no structure available for MSI2 protein. Recently, using nuclear magnetic resonance (NMR) we solved the first solution structure of MSI2 RNA-recognition Motif 1 (MSI2-RRM1) that forms the major long narrow RNA-binding pocket. Using a fluorescence polarization (FP) chemical libraries screening, we identified several groups of hit compounds that disrupt the binding of MSI2-NUMB RNA potently. These compounds induced apoptosis, inhibited cancer cell proliferation, invasion and metastasis in multiple tumor models tested in vitro and in vivo. They also interfered with cancer stem cell functions with reduced tumorsphere formation. Several lead compounds showed promising efficacy in animal tumor models of human breast, prostate and colon cancer. To investigate the specificity of the compounds towards other RBPs, the compounds were tested in biophysical binding assays such as FP, time resolved Fluorescence Resonance Energy Transfer assay (TR-FRET), NMR spectroscopy and cell-based assays. We compared the affinity of these MSI2 inhibitors towards other RBPs such as MSI1 and HuR. Using docking and molecular dynamics simulation, we analyzed the structure-activity relationship of these inhibitors towards different RBP targets. This work adds significant information to the structure of MSI2-RRM1 and the structural basis for designing more potent and specific inhibitors of RBPs. Citation Format: Lan Lan, Minli Xing, Xiaoqing Wu, Philip Gao, Justin T. Douglas, Yu Zhan, Gulhumay Gardashova, Jiajun Liu, Robert P. Hanzlik, Jeffrey Aubé, Kristi L. Neufeld, Berl R. Oakley, Roberto N. De Guzman, Liang Xu. Dissecting the structural basis for inhibitors of RNA-binding proteins [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2863.
Induction of NAD(P)H Oxidase by Oxidized Low-Density Lipoprotein in Human Endothelial Cells
Authors: UweRueckschloss, JanGalle, JuergenHoltz, Hans-ReinhardZerkowski, HenningMorawietz
Journal: Circulation (2001)

Background Elevated oxidative stress and superoxide anion formation in vascular cells could promote conversion of LDL to atherogenic oxidized LDL (oxLDL), contributing to endothelial dysfunction and atherosclerosis. As a major source of vascular superoxide anion formation, an endothelial NAD(P)H oxidase, similar to the leukocyte enzyme, has been identified. Methods and Results To elucidate functional differences between NAD(P)H oxidases of endothelial cells and leukocytes, DNA sequences of endothelial NAD(P)H oxidase subunits were determined. Gp91phox cDNA sequence showed no difference between the 2 cell types. Endothelial p67phox cDNA sequence revealed 2 known polymorphisms, which do not affect NAD(P)H oxidase function. Next, we analyzed relative mRNA expression of NAD(P)H subunits in human umbilical vein endothelial cells (HUVECs) and leukocytes using a common cRNA standard in competitive reverse transcription–polymerase chain reaction. NAD(P)H oxidase subunits p22phox and p47phox are expressed at a sim...
Abstract 1886: A novel inhibitor of eIF4F protein translation complex sensitizes DLBCL cells to BCL-2 targeted therapy
Authors: Lee-or Herzog, Nancy Nguyen, Honyin Chiu, Sharmila Mallya, Ze'ev A. Ronai, David A. Fruman
Journal: Cancer Research (2018)

Abstract The purpose of this project is to investigate the feasibility of using small molecules targeting cap-dependent translation to sensitize B cell lymphoma cells to killing by BCL-2 inhibitors (venetoclax/ ABT-199). We hypothesized that diffuse large B-cell lymphoma (DLBCL) cell survival requires cap-dependent translation, which is facilitated by eukaryotic translation initiation factor 4E (eIF4E)-eIF4G interaction and is promoted by mTOR complex 1 (mTORC1). We used the compound SBI-756, a novel inhibitor targeting the scaffolding protein eIF4G (1). SBI-756 is more potent and selective than previously reported compounds targeting the eIF4E cap-binding protein, or compounds targeting eIF4A helicase. By treating DLBCL cells (germinal center B-cell subtype) with SBI-756 (sub μM concentrations), we discovered profound synergistic induction of apoptosis when combined with venetoclax. Cell viability was reduced even more compared to mTOR kinase inhibitor (TOR-KI) treatment combination. Moreover, SBI-756 was found to reduce the viability (IC50 = 653nM) of VAL lymphoma cells lacking 4E-BP1, while VAL were insensitive to TOR-KI treatment. By using Proximity Ligation Assay (PLA) we showed that SBI-756 treatment prevents eIF4E-eIF4G association in intact lymphoma cells. Dual luciferase assays validated this and indicated a dose-dependent reduction in cap-dependent translation following SBI-756 treatment. Also, Western blot analyses confirmed that SBI-756 treatment did not change mTOR substrates' phosphorylation, indicating that the SBI-756 effect is specific to preventing the eIF4E-eIF4G interaction. Furthermore, SBI-756 treatment reduced polysome formation with a corresponding increase in abundance of monosomes. Lastly, induced expression of 4E-BP1 mutant, which irreversibly binds eIF4E, sensitized DLBCL cells to venetoclax treatment to a similar extent as TOR-KI treatment. Ongoing studies will investigate: (1) The molecular mechanism by which translation inhibition by SBI-756 synergizes with venetoclax to prime DLBCL cells toward apoptosis, and (2) pharmacokinetic and pharmacodynamic effects of venetoclax and SBI-756 treatment on DLBCL progression in vivo. Hence, this project highlights a novel combination for treatment of aggressive lymphomas, and establishes its efficacy using preclinical models. Reference: 1. Feng Y., et al. SBI-0640756 attenuates the growth of clinically unresponsive melanomas by disrupting the eIF4F translation initiation complex. Cancer Res 2015;75(24):OF1-8. Citation Format: Lee-or Herzog, Nancy Nguyen, Honyin Chiu, Sharmila Mallya, Ze'ev A. Ronai, David A. Fruman. A novel inhibitor of eIF4F protein translation complex sensitizes DLBCL cells to BCL-2 targeted therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1886.
The Spatial QRS and T Vector in 178 Normal Middle-Aged Men
Authors: Ernstsimonson, Ancelkeys
Journal: Circulation (1954)

From the means and standard deviations of the coordinates of the spatial QRS and T vectors in 178 normal middle-aged men, preliminary normal range limits were calculated for the total group, three positional subgroups, and three relative body weight groups. The superiority of spatial vector analysis over analysis of the scalar electrocardiogram made it possible for the first time to investigate meaningful correlations between electrocardiographic variables, such as the relationship between the magnitude of QRS and T vectors. The relationship between fundamental constitutional variables and spatial vectors was also investigated as background necessary for the diagnostic use of spatial vectors.
Only half of patients store methadone in safe place
Authors: L. Calman, E. Finch, B. Powis, J. Strang
Journal: BMJ (1996)

EDITOR,—The value of oral methadone maintenance programmes in opiate dependence has now been established,1 but supplies of methadone given to patients to take home pose risks of overdose to adults and children who inadvertently drink the linctus.2 3 Altogether 36% of prescriptions for methadone are reportedly dispensed in weekly instalments,4 yet no information is available on the adequacy of the storage of take home supplies. We report on the domestic …
Abstract 1363: Regulation of BRCA1 by SIRT2
Authors: Elizabeth Minten, Hui Zhang, Chunyang Li, PamelaSara Head, David Yu
Journal: Cancer Research (2018)

Abstract In our everyday lives, we are constantly being exposed to DNA damaging agents, both from internal and external sources. The most deleterious type of DNA damage a cell can suffer is the DNA double-stranded break (DSB). Breast Cancer 1 (BRCA1) is a protein necessary for the proper repair of resultant DNA DSBs through the homologous recombination (HR) pathway. Defects in BRCA1 have been linked to different types of cancer in both men and women, including breast, ovarian, and pancreatic cancer. However, the regulation of BRCA1 is not yet well understood, and in many cases, how defects in this pathway lead to an increased risk of developing cancer is also unknown, making preventative care and treatment of resulting cancers more difficult. Our lab has discovered that SIRT2, a histone deacetylase and putative human tumor suppressor, plays a crucial role in the DNA damage response (DDR) and repair of DNA DSBs. We have shown that depletion of SIRT2 impairs HR and increases cell sensitivity to IR in a deacetylase-dependent manner. A mass spectrometry analysis showed SIRT2 interacts with a number of proteins involved in DDR, including BRCA1. We validated the interaction between SIRT2 and BRCA1 and also found SIRT2 deacetylates BRCA1 both in vitro and in cells. Depletion of SIRT2 and subsequent deacetylation of BRCA1 decreases BRCA1 protein levels in cells and thus impairs HR. Our results show SIRT2 is a novel regulator of BRCA1 and is critical for the repair of DNA DSBs through HR. These findings provide insight into how dysregulation of SIRT2 or BRCA1 can result in genomic instability and lead to the development of cancer. Citation Format: Elizabeth Minten, Hui Zhang, Chunyang Li, PamelaSara Head, David Yu. Regulation of BRCA1 by SIRT2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1363.