tbuckley/cabot-search huggingface dataset:
New strategies against drug resistance to herpes simplex virus
Authors: Yu-Chen Jiang, Hui Feng, Yu-Chun Lin, Xiu-Rong Guo
Journal: International Journal of Oral Science (2016)

Herpes simplex virus (HSV), a member of the Herpesviridae family, is a significant human pathogen that results in mucocutaneous lesions in the oral cavity or genital infections. Acyclovir (ACV) and related nucleoside analogues can successfully treat HSV infections, but the emergence of drug resistance to ACV has created a barrier for the treatment of HSV infections, especially in immunocompromised patients. There is an urgent need to explore new and effective tactics to circumvent drug resistance to HSV. This review summarises the current strategies in the development of new targets (the DNA helicase/primase (H/P) complex), new types of molecules (nature products) and new antiviral mechanisms (lethal mutagenesis of Janus-type nucleosides) to fight the drug resistance of HSV. So-called "Janus" drugs with two molecular "faces" may help address the pressing need for new treatments for herpes simplex virus (HSV). The emergence of resistance to common antiviral drugs such as acyclovir is an increasing problem, especially for patients with weakened immune systems. A team led by Yu-Chen Jiang at Sichuan University, and Hui Feng, Central South University, Changsha, review key strategies for new ways to halt the multiplication of HSV. One of the most promising involves drugs that, like acyclovir, mimic the molecular components of DNA and therefore interfere with the manufacture of viral DNA. Two key DNA components are purines and pyrimidines. The Janus drug molecules have one side that mimics purines while the other side mimics pyrimidines, allowing a double-hit against virus multiplication.
AB0829-HPR Influence of ra patient personality for more aggressive therapies
Authors: L. Leon, M. Redondo, L. Abasolo, A. Garcia-Vadillo, I. Gonzalez-Alvaro, L. Arrieti, P. Macarron, M. A. Perez-Nieto, J. A. Jover
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Actually, patients with rheumatoid arthritis (RA) play a more active role in relation to his illness, and the choice of treatment. The patient's personality can be an important part in this process. Few studies associate medical characteristics of the patient with prognosis and treatment. However, for the evaluation of RA using self-administered questionnaires (eg HAQ) or the patient's own assessment (DAS28), which are being influenced by patient characteristics such as personality. <h3>Objectives</h3> To evaluate the influence of personality factors in the type of treatment that patients receive. <h3>Methods</h3> Multicenter study of a cohort of patients with RA, with a crossover design. We selected patients diagnosed RA of recent onset in two hospitals, with a maximum follow-up of 18 months. All patients who consented completed a form that included general sociodemographic variables, the Eysenck Personality Questionnaire (EPQ-A), Locus of Control Health-related questionnaire (MHLC), and Beliefs and Self-statements about Pain questionnaire (PRCS / PRSS). Also collected measures of disease activity (DAS28 and CRP in the first year after diagnosis). Aggressive treatment was considered to have received more than two DMARDs, or Biological, during follow up. A descriptive analysis of the variables associated with more aggressive treatment and a logistic regression analysis to determine personality variables associated with treatment, adjusting for sociodemographic and clinical characteristics were performed. <h3>Results</h3> A total of 176 RA patients were included in the study. 80% of the sample was women. The mean age was 55.7 ± 13.2 years. The 48.8% of the sample received aggressive treatment. The 50.89% of patients had high scores on extraversion, and 28.7% scored high in neuroticism. We do not found significant differences in age and sex related to aggressive treatment. We performed a multivariate logistic regression analysis, finding that the personality trait of neuroticism is the only predictor of receiving more aggressive treatment (p = 0.01, OR = 0.34). <h3>Conclusions</h3> Patients with high scores on neuroticism are more worried, anxious and / or depressed, affecting their assessment of the disease and may influence the increased demand for therapeutic resources. <h3>Disclosure of Interest</h3> None Declared
AB0682 A Rare Adverse Effect of Isotretinoin Treatment: Sacroiliitis: Table 1.
Authors: N.S. Yaşar Bilge, T. Kaşifoğlu, C. Korkmaz
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Isotretinoin,13-cis-retinoic asid, is used for treatment of severe nodular, cystic acne. Dry skin, hyperlipidemia, hepatotoxicity, arthralgia, myalgia, skeletal hyperosteosis and calcification of tendons are well known side effects (1). Sacroiliitis due to isotretinoin usage is a rare adverse effect. <h3>Objectives</h3> The aim of this study was to underline an uncommon side effect of isotretinoin treatment. <h3>Methods</h3> Five cases with sacroiliitis related with isotretinoin usage is reported. Hospital files of the patients were retrospectively evaluated and clinical and laboratory characteristics were recorded. <h3>Results</h3> Clinical and laboratory features of patients are summerised in Table 1. <h3>Conclusions</h3> Isotretinoin is a widely used drug for treatment of acne vulgaris. Apart from other well-known side effects, sacroiliitis is a rare adverse effect of isotretinoin. The mechanisms underlying the induction of sacroiliitis by isotretinoin are not currently known. Isotretinoin may stimulate matrix metallopretinase-2 activity and consequent membrane degradation in joints or detergent-like properties of isotretinoin may cause joints to be more susceptible to degenerative processes (2). All of the patients were HLA B27 negative, acute phase response reactants were within normal limits except one, they all received indomethacin treatment and achieved partial response. After interrupting isotretinoin therapy all symptoms of the patients completely resolved. In young patients receiving isotretinoin who have back pain without typical signs of spondyloartropathy, isotretinoin must be considered as aetiological factor. Patients may be re-evaluated for resolution of sacroiliitis with radiologic imaging.after interrupting isotretinoin administration <h3>References</h3> Brelsford M, Beute TC. Preventing and managing the side effects of isotretinoin. Semin Cutan Med Surg. 2008;27(3):197-206. Levinson M, Gibson A, Stephenson G. Sacroiliitis secondary to isotretinoin. Australas J Dermatol. 2012;53(4):298-300 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4705
THU0150 Large differences in affordability and availability of synthetic dmards across 46 european countries:
Authors: P. Putrik, S. Ramiro, M. Pavlova, T. Kvien, T. Uhlig, A. Boonen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In the drug treatment for RA patients, EULAR recommends to initiate synthetic DMARDs immediately after diagnosis. However, it is questionable whether these treatments are equally available and affordable across European countries. If recommended care implies higher economic burden, recommendations might be poorly adhered to, contributing to health disparities[1]. <h3>Objectives</h3> To explore the availability and affordability of synthetic DMARDs for treatment of RA across Europe. <h3>Methods</h3> Availability and prices of synthetic DMARDs (MTX, LEFL, SSZ, HDX/Chloroq and PRED), as well as amount of co-payments, were collected by a questionnaire sent to a representative rheumatologist in 48 countries of the European region. Data on RA health status (DAS28, HAQ, TJC, SJC, ESR) were retrieved from the literature (Quest RA)[1]. Data on socio-economic welfare (gross domestic product (GDP), health expenditure, median income and minimum wage) were retrieved from web-based sources. To ensure comparability, national prices were converted into international dollars ($) to adjust for the countries' purchasing power parity (PPP).An affordability index (ratio between co-payments and minimum wage) was calculated. Prices and co-payments were correlated with indicators of welfare and RA health status using Spearman correlations. <h3>Results</h3> Forty-six countries (response rate 96%) provided data. Of the 5 drugs surveyed, MTX and SSZ were available in all the countries, and only Uzbekistan had less than 4 drugs available. Average annual prices of available DMARDs ranged from €100 to 498 (price ratio 4.98). After adjusting the prices for PPP, they ranged from int.$230 to int.$1812 (price ratio 7.9). In 7 countries (Armenia, Georgia, Kazakhstan, Russia, Tajikistan, Ukraine, Uzbekistan), no public reimbursement schemes were available. In 38 countries some form of personal contribution existed. The cost of 30 days treatment with available DMARDs, expressed as the number of calendar days a person receiving the minimum salary would have to work to cover this cost assuming no reimbursement, ranged from 0.30 (Luxemburg) to 5.47 (Bulgaria). Negative associations were found between the prices (adjusted to PPP) and the affordability index with welfare indicators. Prices and affordability index were also positively correlated with RA disease activity (table). <h3>Conclusions</h3> Treatment with synthetic DMARDs is less affordable in lower income European countries. In countries where co-payments exist, there is an additional disadvantage for persons with low income. The data suggest that lower availability and affordability result in poorer RA health status. <h3>References</h3> Sokka T et al. Ann Rheum Dis 2009;68,1666-72 <h3>Disclosure of Interest</h3> None Declared
An Ultrashort 1-Day Protocol of Tc-99m Tetrofosmin
Authors: N Hattori, N Tamaki, I Masuda, Y Taniguchi, H Kitano, T Kudoh, M Inubushi, E Tadamura, Y Magata, K Nakao, J Konishi
Journal: Clinical Nuclear Medicine (1999)

Purpose: This study describes a new 1-day protocol with Tc-99m tetrofosmin that requires only 100 minutes to obtain both stress and resting cardiac images by using a double-injection and subtraction method. Methods: This procedure was performed in 48 consecutive patients. Rest-rest double injections were performed in eight patients (five men, three women; mean age, 69 ± 9.8 years) to evaluate count and image reproducibility (subprotocol A), and stress-rest and additional resting perfusion images (true rest) were done on a different day in 11 patients (five men, six women; mean age, 63 ± 5.9 years) to confirm the validity of the new protocol (subprotocol B). Results: Image quality scores of the resting image were excellent (35 of 48, or 72.9%), good (7 of 48, or 14.6%), fair (3 of 48, or 6.3%), and poor (3 of 48, or 6.3%). The scintigraphic findings with the new protocol corresponded closely with those of angiography in 26 of 34 cases (76.5%), with a tendency for underestimation (in 5 of 34 cases, or 14.7%) rather than overestimation (in 3 of 34 cases, or 8.8%). In subprotocol A, count reproducibility between the two resting images was excellent (r = 0.95; P < 0.0001); and in subprotocol B, the early-rest images were concordant visually and quantitatively with the true rest images (r = 0.89, P < 0.0001). Conclusion: Although there are some limitations, this protocol can be used as a routine stress-rest protocol.
REAL-WORLD COMPARISON OF INPATIENT BLEEDING RISK, BLEEDING-RELATED HOSPITALIZATION RATES AND COSTS AMONG NON-VALVULAR ATRIAL FIBRILLATION PATIENTS ON APIXABAN, DABIGATRAN, RIVAROXABAN: COHORTS COMPRISING NEW INITIATORS AND/OR SWITCHERS FROM WARFARIN
Authors: Ping Tepper, Jack Mardekian, Cristina Masseria, Ruslan Horblyuk, Shital Kamble, Melissa Hamilton, Younos Abdulsattar, William Petkun, Gregory Y.H. Lip
Journal: Journal of the American College of Cardiology (2016)
Abstract 3237: Combination therapy of paclitaxel and EW-7197, a novel ALK5 inhibitor prolonged the life span of breast tumor bearing mice.
Authors: Sol J. Kim, Jee Y. Son, Min J. Kim, Sang A. Park, Seon J. Lee, So Y. Park, Seung W. Kim, Dae-Kee Kim, Jeong S. Nam, Yhun Y. Sheen
Journal: Cancer Research (2013)

Abstract TGF-β has multifunctional effects on carcinogenesis. In the early stage tumor, TGF-β acts as a tumor suppressor but in later stage of tumor, TGF-β promotes tumor invasiveness and metastasis. TGF-βRI kinase has been the target of anti-metastatic drugs, so we have synthesized new ALK5 inhibitor (EW-7197) and investigated anti-metastatic effects of EW-7197. The treatment of the EW-7197 also inhibited the luciferase activity in the lung of 4T1-Luc cell-orthotopic implanted mouse compared to that of untreated animal. The levels of MMP2 and MMP9 were decreased in the lung and breast tumor of the EW-7197 treated mice. To determine the inhibitory effect of EW-7197 on TGF-β1-induced transcriptional activation, we performed luciferase reporter gene assay in breast cancer cells. EW-7197 effectively blocked TGF-β1-induced luciferase activity in the cells in a dose-dependent manner. TGFß signaling, the phosphorylation of smad2/3 was decreased by EW-7197. TGFß-stimulated mesenchymal markers of epithelial mesenchymal transition (EMT) were inhibited by ALK5 inhibitor concomitant treatment. And also, EW-7197 showed higher inhibition on cell motility and cell invasion based on wound healing assay or invasion assay. Further, we investigated combination effect of EW-7197 and paclitaxel. To investigate anti-metastatic effect we did experiment on BALB/c-nu/nu MB231-luc cells xenografted mice by treating EW-7197 and paclitaxel. Both EW-7197 alone group and EW-7197 and paclitaxel combination group showed inhibition of metastasis and the expression of lung metastatic markers were inhibited. We experiment on BALB/c-nu/nu MB231 cells xenografted mice for survival analysis. EW-7197 and paclitaxel combination therapy lengthen the life span of mice. In summary, EW-7197 could be effective therapeutic choice for breast cancer metastasis. Also EW-7197 and paclitaxel combination therapy could be more effective than paclitaxel alone therapy for anti-metastatic effect and survival. Citation Format: Sol J. Kim, Jee Y. Son, Min J. Kim, Sang A. Park, Seon J. Lee, So Y. Park, Seung W. Kim, Dae-Kee Kim, Jeong S. Nam, Yhun Y. Sheen. Combination therapy of paclitaxel and EW-7197, a novel ALK5 inhibitor prolonged the life span of breast tumor bearing mice. [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 3237. doi:10.1158/1538-7445.AM2013-3237
Bleeding Meckel's Diverticulum Presenting as Focal Extravasation on Pertechnetate Scintigraphy
Authors: KARAN LOTFI, ELIZABETH OATES
Journal: Clinical Nuclear Medicine (1996)

The evaluation of gastrointestinal hemorrhage may include a Meckel's scan, particularly in children. Typically, a Meckel's diverticulum shows discrete, focal uptake in the right lower abdomen. The authors describe an adult whose bleeding Meckel's diverticulum manifested as brisk, intermittent intraluminal tracer extravasation.
Abstract LB-107: Mitochondrial DNA mutations are diagnostic markers of renal oncocytomas.
Authors: Martin Lang, Cathy D. Vocke, Maria J. Merino, Laura S. Schmidt, Marston W. Linehan
Journal: Cancer Research (2013)

Abstract Oncocytomas are mostly benign tumors of epithelial origin, characterized by dense accumulation of defective mitochondria. To date, no nuclear gene has been found to be responsible for these tumors, but a correlation of the oncocytic phenotype with the occurrence of disruptive mitochondrial DNA (mtDNA) mutations, mostly affecting genes encoding for proteins of Complex I of the respiratory chain (NADH dehydrogenase), has been shown in sporadic oncocytomas of different organs, including renal oncocytomas (RO). Kidney cancer is made up of a number of tumors that present with a different histology and clinical course. They are caused by different genes, and therefore therapy needs to be adapted for each type of renal tumor. Imaging techniques are usually not sufficient to distinguish between benign and malignant forms of renal cell cancer (RCC). In addition, it is difficult to differentiate benign ROs from malignant forms of RCCs in samples from biopsies, because they share ultrastructural appearances, including abnormal mitochondria with altered cristae. Therefore, a reliable diagnostic tool would be invaluable to guide clinicians in the management of patients with RCC of unclear phenotype. In our current work we tested whether mtDNA mutations can be used as diagnostic tools to distinguish between benign ROs and more aggressive forms of RCC. We sequenced the entire mtDNA in 36 samples that included sporadic, bilateral and multifocal as well as familial ROs and 30 non-oncocytic RCCs of different histologies. Moreover, the mitochondrial copy number was determined in all samples by real-time PCR. Furthermore, we sequenced the mtDNA from biopsies and compared it to the mtDNA sequence of the resected tumor. We found a strong correlation between the presence of disruptive mtDNA mutations affecting complex I genes and the oncocytic phenotype in renal tumors. Additionally, oncocytomas showed significantly higher mtDNA copy number when compared to other RCCs. We also show that the mtDNA sequences from the biopsies correspond to the sequence of the tumor itself and are predictive of the phenotype. Hence, we propose that sequencing of the mitochondrial genome, supported by the analysis of the mtDNA copy number, may be used as a diagnostic tool to distinguish between benign and aggressive forms of RCCs to guide physicians in choosing the appropriate treatment for patients. Citation Format: Martin Lang, Cathy D. Vocke, Maria J. Merino, Laura S. Schmidt, Marston W. Linehan. Mitochondrial DNA mutations are diagnostic markers of renal oncocytomas. [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 LB-107. doi:10.1158/1538-7445.AM2013-LB-107
Abstract 4228: Aryl hydrocarbon receptor nuclear translocator is associated with cisplatin resistance in cancer cells
Authors: Ben-Kuen Chen, Sriram Kalpana, Wen-Chang Chang
Journal: Cancer Research (2012)

Abstract The (ARNT) belongs to the basic-helix-loop-helix (bHLH) transcription factors containing Per-Arnt-Sim (PAS) domain. In addition to forming heterodimers with many other bHLH-PAS proteins, including the aryl hydrocarbon receptor (AhR) and hypoxia-inducible factor 1α, ARNT can also form homodimers. Our previous study had shown that ARNT is a new factor involved in EGF regulated COX-2 gene expression under normoxia involving tumorigenesis in cervical cancer tissues. Resistence to cisplatin is often observed in cervical cancer therapy. Here we showed that ARNT expression is critical for cisplatin resistance. Specifically, we showed that in HeLa cervical cancer lines, cisplatin decreased ARNT expression level. Over-expression of ARNT rendered HeLa cells resistant to cisplatin. In addition, inhibition of ARNT by small interfering RNA silencing increased cisplatin induced cell death by activation of caspase 3 and sensitized drug resistant cells to cisplatin. Using ARNT deficient and ARNT fully expressed cell lines showed that induction of apoptosis by cisplatin correlates with ARNT. Importantly down regulation of ARNT decreased drug efflux pump protein MDR1 expression, suggesting that MDR1 gene expression depends on ARNT activity. In conclusion, ARNT mediates the efflux of cisplatin and has a functional role in cervical cancer cell sensitivity to cisplatin. In a xenograft analysis of SCID mice, cisplatin also efficiently inhibited ARNT-deficient tumor formation. These results suggest that targeting ARNT could overcome cisplatin resistance in human cervical cancer. 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 4228. doi:1538-7445.AM2012-4228
Biosafety and Ethics Issues Under Review For Human Gene Splice Test
Authors: P. A. Newman
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Biosafety and Ethics Issues Under Review For Human Gene Splice Test Get access Patricia A. Newman Patricia A. Newman Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 12, 17 August 1988, Page 895, https://doi.org/10.1093/jnci/80.12.895 Published: 17 August 1988
BIOLOGICALLY-BASED THERAPEUTICS FOR THE TREATMENT OF DIFFUSE INTRINSIC PONTINE GLIOMAS
Authors: N. Gupta, R. Hashizume, N. Andor, Z. Zhang, C. Petritsch, S. Mueller, C. D. James
Journal: Neuro-Oncology (2014)

BACKGROUND: Diffuse intrinsic pontine gliomas (DIPGs) in children carry a dismal prognosis despite the use of aggressive multi-modality treatment. Recent results have identified a somatic mutation in the H3F3A gene, resulting in replacement of lysine 27 by methionine in its encoded histone H3.3 protein (H3.3-K27M), which occurs primarily in DIPGs. The K27M mutation results in both increased and decreased gene expression. This specific mutation is an attractive therapeutic target for the treatment of DIPGs. METHODS: Using cell lines and tissues from two pediatric DIPGs and one pediatric GBM tumor obtained from surgical biopsies, H3.3-K27M mutation status was determined by direct sequencing. Histone H3.3 lysine 27 (H3K27) methylation status was evaluated by western blotting with antibodies specific for mono-, di-, and trimethylated H3K27. A selective inhibitor of the H3K27 demethylase JMJD3, GSK-J4, was used to examine cell proliferation and survival. GSK-J4 was found to inhibit JMJD3-induced H3K27 demethylation, resulting in an increase of H3K27 methylation. RESULTS: The H3.3-K27M mutation was identified in the two DIPG cell lines, but not in the pediatric GBM cells, nor in other adult glioma cells. H3.3-K27M mutant DIPG cells showed rapid growth in vitro, with a doubling time of approximately 30 hrs. In contrast, a pediatric GBM cell line with wild-type H3.3 grew much more slowly, with a doubling time of 72 hrs. H3.3-K27M mutant DIPG cells showed elevated H3K27 methylation in comparison to H3.3 wild-type glioma cells. GSK-J4 induced a marked dose-dependent inhibition of growth in H3.3-K27M mutant DIPG cells while H3.3 wild-type glioma cells showed no response to GSK-J4. GSK-J4 appears to have a potent and specific effect on tumor cells with the K27M mutation. CONCLUSIONS: Altered histone H3.3 K27 methylation is associated with rapid tumor cell growth in vitro, and is associated withn increased tumor cell sensitivity to GSK-J4. SECONDARY CATEGORY: Tumor Biology.