tbuckley/cabot-search huggingface dataset:
Abstract 4113: Discovery and optimization of potent SDF1α antagonist peptides.
Authors: Julia A. Coronella, Yanwen Fu, Kimberly Johnson, Jingping Zhong, Lioudmila Campbell, Gang Chen, Dorian Willhite, Joselyn Del Rosario, Abhijit Bhat, Gary Woodnutt, Nancy Levin
Journal: Cancer Research (2013)

Abstract The SDF1α / CXCR4 axis contributes to cancer metastasis, proliferation, angiogenesis and resistance to standard of care drugs. Here we describe novel phage display derived peptide SDF1α antagonists. Phage displayed peptides were optimized through a multistep process that resulted in a 400-fold improvement in activity, from 6.4 uM IC50 inhibition of SDF1α -driven Calcium flux to 16 nM IC50. First, peptides were affinity matured via panning of focused phage libraries. Peptides exhibiting enhanced potency were bioconjugated to the CovX antibody scaffold IgG (CVX-2000), generating bivalent CovX-Bodies with 5-fold improved potency in SDF1α driven Calcium flux assays. N and C-terminal extension of the peptide and introduction of unnatural amino acids produced an additional 11-fold improvement in activity to 16 nM. Constructs with optimal pharmacokinetic stability were identified, and demonstrated single agent tumor inhibition in a Ramos B cell lymphoma xenograft model. Citation Format: Julia A. Coronella, Yanwen Fu, Kimberly Johnson, Jingping Zhong, Lioudmila Campbell, Gang Chen, Dorian Willhite, Joselyn Del Rosario, Abhijit Bhat, Gary Woodnutt, Nancy Levin. Discovery and optimization of potent SDF1α antagonist peptides. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4113. doi:10.1158/1538-7445.AM2013-4113
Inter- and intra-criteria reproducibility of RECIST ver 1.1 and modified EASL (European Association for the Study of the Liver) tumor response criteria to transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC): From the dataset of JIVROSG (Japan Interventional Radiology in Oncology Study Group) 0401
Authors: Y. Sato, H. Watanabe, M. Sone, H. Onaya, N. Sakamoto, K. Osuga, M. Takahashi, S. Yamamoto, Y. Arai
Journal: Journal of Clinical Oncology (2009)

e15501 Background: In spite of systemic response evaluation criteria, RECIST is widely used for evaluating the tumor response (TR) in local therapy. As a result, there are double standard criteria (RECIST ver 1.1 and modified EASL) in the evaluation for TR of HCC treated by TACE. Tumor size is evaluated by measurement of the entire lesion including necrotic part in RECIST ver 1.1 (EJC 2009;45:228), whereas the only contrast-enhanced part on radiological images is measured when the modified EASL are used (JNCI 2008;100:698). Both criteria adopt the unidimensional measurement. Methods: This is a study of the radiological findings of patients who underwent TACE for multiple HCCs in the JIVORSG 0401 study. The subjects were 65 lesions in 21 patients treated by pan- hepatic TACE using cisplatin and gelatin particles without mixing iodized-oil. Five radiologists measured independently each lesion twice, therefore 130 measurements were performed per radiologist according to the 2 criteria (RECIST ver 1.1 and modified EASL). To compare the inter- and intra- criteria reproducibility of TR for each lesion, CR rate, response rate, proportion of agreement, and the kappa statistics for response categories were calculated. Results: Results are shown in the table. CR rate and response rate obtained using the modified EASL were higher than those obtained using RECIST ver 1.1. The inter-criteria reproducibility between RECIST ver 1.1 and modified EASL were poor. The intra-criteria reproducibility of RECIST ver 1.1 indicated substantial agreement, while that of modified EASL indicated almost perfect agreement. Conclusions: For a precise interpretation of the tumor response in clinical trials of TACE for HCCs, appropriate attention must be paid to the criteria employed for the evaluation. [Table: see text] No significant financial relationships to disclose.
Cladribine combined with cyclophosphamide and mitoxantrone as front-line therapy in chronic lymphocytic leukemia
Authors: T Robak, JZ Błoński, M Kasznicki, J Góra-Tybor, J Dwilewicz-Trojaczek, P Boguradzki, L Konopka, B Ceglarek, J Sułek, K Kuliczkowski, D Wołowiec, B Stella-Hołowiecka, AB Skotnicki, W Nowak, B Moskwa-Sroka, A Dmoszyńska, M Calbecka
Journal: Leukemia (2001)
P70 Talc slurry pleurodesis: does mixing talc with 50% dextrose rather than normal saline increase success rate?
Authors: A. Khanna, C. Mackinlay, A. Kerry
Journal: Thorax (2010)

<h3>Introduction</h3> Symptomatic malignant pleural effusions can be managed effectively with talc pleurodesis. Various studies document the success rate for talc pleurodesis around 80%. In these studies, talc was mixed with normal saline to make the slurry prior to pleurodesis. We audited the success rate for pleurodesis in our hospital using slurry made by mixing talc with normal saline and slurry made by mixing talc with 50% dextrose to see if changing the ‘solvent’ made any difference to the success of the procedure. The hypothesis that 50% dextrose, being ‘stickier’ than normal saline, will achieve a better success rate was thus tested. <h3>Method</h3> In group 1, 28 patients underwent pleurodesis using slurry obtained by mixing talc with normal saline. The findings were presented to BTS in 2008. Subsequently we re-audited our practice with group 2, in which 18 patients were pleurodesied using slurry obtained by mixing talc with 50% dextrose. <h3>Results</h3> Procedure success was defined as absence of fluid reaccmulation requiring intervention at 3 months post pleurodesis. The success rate for the first group was 34% while the success rate for the second group was 76%. The second group underwent more rigorous protocol ensuring drain clamping for 1-h post procedure and use of suction in 100% compared to 80% and 87.5% in the first group. However, subgroup analysis of the first group did not reveal a statistically significant difference in success rate for these variables. Use of NSAID analgesia for 28% patients in group 1 compared to none in group 2 could have influenced the results significantly. Lastly, better patient selection and operator bias might have resulted in better success rate in the second group as recommendations from first audit were implemented in second cycle. Overall best success rate of 76% was inferior to that reported in previous studies due to more liberal patient selection. <h3>Conclusions</h3> Use of 50% dextrose rather than normal saline to mix talc for talc slurry with strict patient selection and a rigorous pleurodesis protocol as recommended by BTS guidelines can result in better success rate. This is possibly because of the resulting stickier inert slurry. However, research with a randomised control trial is required to assess this question further.
Abstract 4950: Discovery of the pro-apoptotic genes induced by tumor suppressor p53
Authors: Nurmaa DASHZEVEG, Naoe TAIRA, Yoshio MIKI, Kiyotsugu YOSHIDA
Journal: Cancer Research (2012)

Abstract The tumor suppressor p53 regulates apoptosis in response to DNA damage. Promoter selectivity of p53 depends mainly on its phosphorylation. Notably, the phosphorylation at serine-46 (Ser46) of p53 is indispensable to promote pro-apoptotic genes. However, little is known about the pro-apoptotic genes induced by Ser46 phosphorylation of p53. In our study, we aimed to investigate pro-apoptotic genes induced by p53 using microarray analysis and ChIP sequencing assay. Although microarray analysis became common tool in molecular biology, novelty of our research is combining microarray analysis with ChIP sequencing assay to discover direct target of p53 in Ser46 specific manner. Analyze of microarray showed specific up-regulation of 2723 genes in wild type p53 (wt-p53). Alternatively, 1338 genes were interacted directly with only wt-p53 but not with mutant p53 (Ser46 is substituted with alanine, p53S46A) in ChIP sequencing assay. The comparison of two assays, microarray analysis and ChIP sequencing assay, investigated thirty genes in relation with Ser46 phosphorylation of tumor suppressor p53. Those thirty genes were clarified by real time RT-PCR and the genes strongly elicited were chosen further study. The research will be continued with more clarification and apoptotic function of candidate genes in response to DNA damage will be investigated. We hope that the discovery of pro-apoptotic genes induced by p53 will convey the important role in cancer research and therapy. Acknowledgement: This project is partly supported by Global Center of Excellence (GCOE) program at TMDU. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4950. doi:1538-7445.AM2012-4950
Self-Induced Water Intoxication without Predisposing Illness
Authors: Hans Langgård, William O. Smith
Journal: New England Journal of Medicine (1962)

THE term "water intoxication" was first applied by Rowntree1 to the symptoms of increased neuroexcitability, delirium, convulsions and coma due to sudden lowering of the ratio of solutes to water in the body fluids induced by excessive intake of water. Subsequently, several authors2 3 4 5 6 7 8 9 10 reported various cases of water intoxication in patients on parenteral fluid therapy and in patients with various predisposing illnesses. It is generally believed that water intoxication does not occur in healthy people by the voluntary ingestion of water. Barahal11 reported 1 case in a schizophrenic but otherwise healthy patient who drank large quantities of water and then . . .
Transduction of Feline Hematopoietic Cells by Oncoretroviral Vectors Pseudotyped with the Subgroup A Feline Leukemia Virus (FeLV-A)
Authors: Neil C. Josephson, Kathleen M. Sabo, Janis L. Abkowitz
Journal: Molecular Therapy (2000)

The domestic cat is an outbred species with many identified analogues of human genetic diseases. Therefore, it has the potential to serve as a large animal model for evaluating the feasibility of hematopoietic stem cell gene therapy. This study compared gene transfer rates into feline hematopoietic progenitors by oncoretroviral vectors pseudotyped with the subgroup A feline leukemia virus (FeLV-A), the gibbon ape leukemia virus (GALV), and the murine amphotropic virus. Gene transfer rates were superior with the FeLV-A pseudotypes, which were then tested for their ability to transduce a cat hematopoietic repopulating cell. At more than 1 year posttransplantation, persistent marking was seen in both lymphoid and myeloid lineages of a myeloablated domestic cat that had received autologous marrow cells transduced with an FeLV-A pseudotyped vector. The domestic cat is an outbred species with many identified analogues of human genetic diseases. Therefore, it has the potential to serve as a large animal model for evaluating the feasibility of hematopoietic stem cell gene therapy. This study compared gene transfer rates into feline hematopoietic progenitors by oncoretroviral vectors pseudotyped with the subgroup A feline leukemia virus (FeLV-A), the gibbon ape leukemia virus (GALV), and the murine amphotropic virus. Gene transfer rates were superior with the FeLV-A pseudotypes, which were then tested for their ability to transduce a cat hematopoietic repopulating cell. At more than 1 year posttransplantation, persistent marking was seen in both lymphoid and myeloid lineages of a myeloablated domestic cat that had received autologous marrow cells transduced with an FeLV-A pseudotyped vector.
SP0071 Is the Risk of Cancer after anti TNF Exposal Nule? Data from Worldwide Databases
Authors: J.J. Gomez-Reino
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Rheumatoid arthritis (RA) patients have an increased tumor risk compared with the general population. TNF antagonists do not increase the overall cancer risk in adults with rheumatoid arthritis. At least five recent meta-analyses including clinical trials and data from registries have failed to show an increased risk of malignancy in RA patients treated with TNF antagonists. In contrast, a previous meta-analysis showed a 3-fold increase in the rate of malignancies compared with placebo. This latter study did not adjust for exposure time despite a larger number of dropouts in the placebo group during the randomized controlled phase. After correction for follow-up time, the increased risk could not be demonstrated. Further analysis of other reports shows that type of inhibitor and duration of treatment do not changed the overall risk. Also, there is no increase in specific cancers. The increased risk of relapse or second primary cancers in patients treated with TNF antagonists is disputed. In clinical trials, patients with a malignancy before the trial are commonly excluded. In reports, no conclusive information was found The risk of lymphoma is also higher in RA patients than in the general population. One risk factor associated with lymphoma in RA patients is high inflammatory activity. These patients are more likely to be treated with TNF antagonists and would be at an increased risk of lymphoma. In a large RA study of patients with an exposure of 89,710 person-years, the OR for lymphoma in patients treated with TNF antagonists compared with non-exposed patients was 1.0 (95% CI 0.6-1.8). In another study, RA patients treated with TNF antagonists were at increased risk of lymphoma compared with the general population. After adjustment for age, sex, and disease duration, the risk of lymphoma in patients treated with TNF antagonists was not higher than RA patients non-exposed to with TNF antagonists. In summary, the risk of lung tumor and lymphoma is increased in RA patients compared to the general population, but treatment with TNF antagonists does not increase further this risk <h3>Disclosure of Interest</h3> J. Gomez-Reino Grant/Research support from: Pfizer, MSD, Roche, Consultant for: Abbott, BMS, Pfizer, MSD, Roche, UCB, Conflict with: Abbott, BMS, Pfizer, MSD, Roche, UCB <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6210
Thymic Hypoplasia and Thyroid Dysfunction
Authors: Richard Hong, Richard Gatti, John C. Rathbun, Robert A. Good
Journal: New England Journal of Medicine (1970)

Thymic hypoplasia and associated hypothyroidism in a child seemed to represent an embryologic fault involving the derivatives of the second and third pharyngeal pouches. The immunologic deficiency affected primarily the cellular system and was associated with an underdeveloped, undifferentiated thymus. Humoral immunity was generally not affected. Normal parathyroid glands were present. The thyroid gland was hypoplastic and fibrotic. The case provides another example of the relative independence of the humoral antibody system from the thymus. However, the presence of antibodies to thyroglobulin, detected by hemagglutination, also suggested autoimmunity as a possible cause of the thyroid disorder. The unusual age at onset for thyroiditis or autoimmune thyroid disease may be related to the developmental abnormality of thymus and the consequently disturbed immunologic balance.
LESIONES TIROIDEAS INCIDENTALES EN PACIENTES SOMETIDOS A ECOENDOSCOPIA. RESULTADOS PRELIMINARES
Authors: A Ginés, C Gutiérrez, J Albrecht-Bonomo, G Fernández-Esparrach, O Sendino, H Córdova, A Rodriguez-D'jesus, H Uchima, B González, J Llach
Journal: Endoscopy (2013)

Introducción: El tiroides es fácilmente visible por ecoendoscopia (USE) desde el esófago cervical. No existe ningún estudio que haya evaluado la incidencia de lesiones tiroideas en pacientes sometidos a USE por cualquier indicación. Objetivo: evaluar prospectivamente la incidencia de lesiones tiroideas en los pacientes sometidos a USE. Material y Método: Desde Julio de 2011 a Julio de 2012, se practicó USE a 473 pacientes. Todos fueron explorados bajo sedación profunda con el ecoendoscopio radial (Olympus GF UE 160) y aquellos a quienes se indicó punción, se practicó con el ecoendoscopio lineal Olympus GF UCT140, ambos acoplados a una consola Aloka Alpha-5. Tras realizar la exploración indicada en cada caso, al retirar el ecoendoscopio se exploraron sistemáticamente los dos lóbulos tiroideos. Resultados: Se hallaron lesiones en el tiroides en 10 pacientes (2%), todas ellas mujeres, con edad media de 58,7 + 18 años (34 – 84 a). Las indicaciones para la USE fueron: lesiones quísticas del páncreas (n = 4), neoplasia gástrica (n = 1), de páncreas (n = 1), de vía biliar (n = 1), tumoración subepitelial gástrica (n = 1), linfoma gástrico (n = 1), y tumor neuroendocrino pancreático (n = 1). Las lesiones tiroideas halladas fueron: lesión quística única (n = 4), lesiones quísticas múltiples (n = 3), nódulo sólido (n = 2) o combinación de quiste y nódulo (n = 1). En 3 pacientes la existencia de dichas lesiones se comprobó por otras técnicas de imagen: TC (n = 1) o ecografia tiroidea (n = 2). En estos dos últimos casos se practicó PAAF que mostró un bocio nodular y un carcinoma papilar de tiroides respectivamente. Conclusiones: Es posible detectar lesiones tiroideas incidentales por USE, que en algún caso corresponden a patología significativa de dicha glándula. Comentario: Dada la facilidad y rapidez con que puede explorarse el tiroides al retirar el ecoendoscopio y la no despreciable incidencia de lesiones en este órgano, sería aconsejable su revisión ssitemática en pacientes explorados por cualquier motivo.
A5.15 How Micrornas Control Plasma Cells
Authors: Julia Schmid, Martina Porstner, Andreas Brandl, Edith Roth, Thomas Winkler, Michael Bösl, Andreas Radbruch, Jürgen Wittmann, Hans-Martin Jäck
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> Our long-term goal is to understand how one class of interfering non-coding RNAs, the so-called micro-RNAs (miRNAs), regulates and fine-tunes the differentiation of mature B cells into effector cells, i.e., memory B cells and antibody-secreting plasma cells. miRNAs control the expression of specific target genes at the post-transcriptional level by binding to target sequences e.g., in the 3’-untranslated region of mRNAs, which, depending on the degree of the binding, results either in a block of translation or an accelerated degradation of the respective target mRNA. Lineage-specific deletion of the miRNA-processing DICER protein as well as of individual miRNAs revealed the importance of miRNA pathway in early steps of central B cell maturation. However, the mechanisms by which miRNA-dependent circuits control the antigen-induced phase of B cell activation of mature naive B cells and their subsequent differentiation into effector cells remain largely elusive. <h3>Methods</h3> To change this situation we established a transgenic knock-in mouse line with a floxed allele of DGCR8, an essential subunit of the nuclear miRNA processing complex. B cell-specific deletion of DGCR8 resulted in a complete maturation block at the pro-B stage, indicating that miRNA processing is essential for central B cell maturation. We have also established a culture system that allows us to delete a floxed DGCR8 gene in freshly isolated B cells using retrovirally transduced Cre. Using this system, we found that the miRNA pathway is required for mitogen-induced in vitro proliferation of mature B cells. <h3>Results</h3> We have also obtained genome-wide miRNA expression profiles of all major mouse B cell subsets, including long-lived plasma cells, and found a profound upregulation of one miRNA in plasma cells. Ectopic expression of this plasma cell signature-miRNA in primary mouse B cells accelerated the differentiation into antibody-secreting plasmablast, as indicated by upregulation of CD138 and enhanced IgM secretion. We also verified several targets of this miRNA, e.g., Bach2 and MiTF, that are part of the transcriptional circuit that controls germinal centre reactions and plasma cell differentiation. <h3>Conclusions</h3> These studies will provide new molecular insights into regulatory circuits that control the production of antibodies and could potentially lead to new avenues for diagnosing or treating diseases associated with aberrant plasma cell development, e.g., primary antibody deficiencies, plasma cell malignancies, and autoimmune disorders.
Abstract 3893: Inhalational temozolomide–a new mode of treating malignant gliomas
Authors: Thomas C. Chen, Heeyon Cho, Weijun Wang, Florence M. Hofman
Journal: Cancer Research (2012)

Abstract Temozolomide (TMZ) is the standard of care chemotherapy for treatment of malignant gliomas; it is currently delivered orally or intravenously. Perillyl alcohol is a monoterpene which has been used to treat patients with malignant gliomas via an intranasal delivery system. Recently, we have constructed a new chemical entity (NCE) by conjugating temozolomide to perillyl alcohol via a carbamate bond. This new compound has been named TMZ-POH (NEO212). This new compound has been tested in-vitro in a number of assays. Its mechanism of action does not appear to be MGMT mediated, as addition of O6-benzylguanine has no effect on its cytotoxicity in glioma cells regardless of their MGMT status. On the other hand, TMZ-POH appears to induce endoplasmic reticulum stress (ERS) in malignant glioma cells, as demonstrated by an increase in glucose-regulated protein 78 (GRP78) and the apoptotic protein CHOP expression. MTT assays demonstrate that TMZ-POH is effective in both temozolomide sensitive and resistant U251, U87, LN229 malignant glioma cell lines. IC50 for colony formation assays (CFA) was determined for U251 temozolomide sensitive and resistant cells to be 18 uM and not achieved (0-60 uM). TMZ-POH, on the other hand, had IC50 of 10 uM and 30 uM respectively for TMZ sensitive and resistant U251 glioma cells. MTT assays using glioblastoma cancer stem cells (CSC) demonstrated that TMZ-POH induced IC50 cytotoxicity at 200 uM, compared to no cytotoxicity in the TMZ treated CSC. Moreover, TMZ-POH demonstrated no toxicity on normal astrocytes. Treatment of glioma cells with TMZ alone, POH alone, TMZ dissolved in POH, and TMZ-POH demonstrated that TMZ-POH was two orders of magnitude more cytotoxic than TMZ dissolved in POH. These data lead us to conclude that TMZ-POH is a NCE which may be evaluated for potential intranasal drug delivery to treat patients with malignant gliomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3893. doi:1538-7445.AM2012-3893
David Arthur Conn
Authors: Alan G Conn, I Graeme Conn
Journal: BMJ (2016)

David Arthur Conn was the son of a general practitioner and a teacher. At the age of 8 he developed exertional chest pain, and his father, Ian (see obituary: http://www.bmj.com/content/336/7646/727.1), diagnosed aortic stenosis. Cardiac catheterisation in Glasgow revealed a complex aortic root hypoplasia. At the National Heart Hospital, under the care of Jane Sommerville and Donald Ross, David underwent aortoplasty and later, an aortic homograft. A second homograft was required in his late teens when the first graft calcified.

With remarkable strength of character, David turned a childhood of …