tbuckley/cabot-search huggingface dataset:
SAT0338 Adaptation and Validation of the Osteoarthritis Knee and Hip Quality of Life (Oakhqol) Questionnaire in Turkish Population.
Authors: M. T. Duruöz, E. Duruöz, Ü. Uçar, E. Topçu
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To adapt and validate the OAKHQOL for using in osteoarthritis patients of Turkish population. <h3>Methods</h3> The cross-cultural adaptation of OAKHQOL according to guideline used forward and backward translations from French to Turkish, with an emphasis on expert committee informed decision making. Patients with knee and hip osteoarthritis were recruited into the study. Systemic inflammatory rheumatic diseases were in exclusion criteria. Internal consistency of OAKHQOL subgroups were assessed. Face and content validity were assessed via cognitive debriefing interviews with OA patients. The OAKHQOL subgroups were correlated with SF36, Lequesnes index, Nothingam Health Profile (NHP), WOMAC and VASpain to evaluate construct validity. Spearman correlation coefficient managed to compare qualitative parameters. p&lt;0.05 was significant. <h3>Results</h3> Eighty two patients (63 female) with aged 56,31 (SD:11,12) years were recruited. Sixtynine patients had osteoarthritis at knees, 11 had at hips and 2 patients had both. The Body Mass Index (BMI) was 27,19 (SD:3,90) and the disease duration was 4,77 years (range: 0,5 – 30). The internal consistency of OAKHQOL subgroups (1 to5) were 0,80; 0,51; 0,87; 0,77 and 0,31. The mean scores of subgroups were 47,19 (SD: 19,77); 42,46 (SD: 34,58); 56,47 (SD: 22,96); 59,92 (24,89) and 49,75 (34,32). According to expert and patient desicions the Turkish version of OAKHQOL had good face and content vaidity. The physical activity, pain and mental health subgroups of OAKHQOL had significant correlation with all subgroups of SF36. The social support and social activities subgroups had not significant correlation with SF36 scores. Lequesnes index had good correlation only with physical activity (p=0,001) and pain (p&lt;0,0001) subgroups of OAKHQOL. The total score of WOMAC had significant correlation with the physical activity (p=0,001), pain (p=0,001) and mental health (p=0,001) subgroups of OAKHQOL. Physical activity and pain subgroups of NHP had significant correlation only with the physical activity, pain and mental health subgroups of OAKHQOL. There was not any significant correlation with social support and social activities subgroups of OAKHQOL with other quality of life scales. <h3>Conclusions</h3> The psychometric properties of Turkish version of OAKHQOL show that it is useful scale to assess the quality of life of patients with knee and hip osteoarthritis in our population. <h3>Disclosure of Interest</h3> None Declared
1199 FINDINGS FROM CLINICAL VIROLOGY STUDIES ON ACH-3102 ARE CONSISTENT WITH PRECLINICAL OBSERVATIONS ON ITS IMPROVED POTENCY AGAINST GENOTYPE-1a HCV AND RESISTANT VARIANTS
Authors: G. Yang, D. Patel, Y. Zhao, J. Fabrycki, W. Yang, S. Podos, H. Robison, L. Robarge, H. Kocinsky, M. Deshpande, M. Huang
Journal: Journal of Hepatology (2013)
S145 The impact of cigarette smoke extract on inflammatory responses and toll-like receptor-4 expression in healthy nasal epithelial cells
Authors: D. Comer, J. S. Elborn, V. Brown, C. McDowell, M. Ennis
Journal: Thorax (2010)

Although cigarette smoke extract (CSE) is widely used in respiratory research, the methods used in its preparation are diverse and there is no consensus as to whether cigarette smoke extract (CSE) induces a pro-inflammatory or an immunosuppressive response in epithelial cells.1 Although the adverse effect that cigarette smoke has on the lower airway has been extensively studied, the responses of the nasal epithelium are not well described. Our aims were to study the effects of a non-cytotoxic CSE exposure on LPS-induced innate immune responses from primary nasal epithelial cells (PNECs), to assess the constitutive gene expression and the localisation of TLR-4 in PNECs by RT-PCR and flow cytometry, and finally to analyse the modulation of TLR-4 expression after stimulation PNECs by LPS±CSE pre-treatment. CSE was prepared by combusting 1 or 2 12 mg tar Marlboro cigarettes through 25 ml of media. Submerged PNEC cultures were treated with CSE (or vehicle) followed by stimulation with LPS. Supernatants were assessed for IL-8 and IL-6 and the expression and localisation of TLR-4 was established. Cell viability was not affected except after 24 h incubation with 5% CSE made from two cigarettes, or using single cigarette along with a 24 h stimulation with 20–25 μg/ml LPS. A brief incubation with CSE (4 h) significantly inhibited LPS-induced cytokine release. In contrast, a more prolonged incubation with CSE (24 h) heightened LPS-induced cytokine release. Incubation with CSE (4 h and 24 h) had no significant impact on expression of TLR4 mRNA. A brief incubation with CSE (4 h) resulted in a lower percentage of surface and intracellular TLR4. A prolonged incubation with CSE (24 h) did not affect surface or intracellular TLR4. CSE exposure for 4 h suppresses the inflammatory response in PNECs to stimulation with LPS whereas 24 h CSE exposure was pro-inflammatory. A reduced surface TLR-4 may account for the immunosuppressive effects, but unaltered surface and intracellular TLR-4 after 24 h CSE treatment suggests that alternative pathways may be responsible for the pro-inflammatory effects.
Three Agencies To Cooperate in Largest Agricultural Study
Authors: N. Volkers
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Three Agencies To Cooperate in Largest Agricultural Study Get access Nancy Volkers Nancy Volkers Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 3, 3 February 1993, Pages 178–179, https://doi.org/10.1093/jnci/85.3.178 Published: 03 February 1993
Abstract 3630: Non-enrichment based method for analysis of androgen receptor expression in circulating tumor cells (CTCs) in patients with metastatic castrate resistant prostate cancer
Authors: Mitchell E. Gross, Daniel C. Lazar, Edward H. Cho, Madelyn Luttgen, Maria L. Uson, Peter Kuhn, Melissa L. Torrey
Journal: Cancer Research (2012)

Abstract Background: We have established a fluid phase biopsy approach that identifies CTCs which preserves cytologic features in high-definition (HD) for diagnostic pathology without using immune or surface receptor-based enrichment. HD-CTCs identified with this approach can be used for enumeration and molecular characterization. Methods: Blood was collected from metastatic prostate cancer patients and normal donors in Cyto-Chex® tubes (Streck, Omaha, NE) as part of IRB approved protocols at each site. Following erythrocyte lysis, 3 million nucleated cells were deposited on a glass slide. Samples were incubated with a pan-cytokeratin (CK), CD45, and androgen receptor (AR) antibodies and counter-stained with DAPI. LNCaP cells were spiked into normal blood. Images were obtained with a fluorescent scanning microscope and analyzed with a computer algorithm. Candidate HD-CTCs were subsequently verified by expert readers. Slides were re-imaged for quantitative analysis using at a fixed exposure and gain. Results: A total of 227 CTCs from ten patients were compared to 20 LNCaP cells. The median (range) HD-CTCs in this cohort was: 9 (1-62) cells/ml. The mean ± standard deviation measurements in HD-CTCs were observed: CK intensity 60.4±154; total cell area 89.0 ± 53.8 μm2; nuclear area 61.1 ± 36.0 μm2. LNCaP cells spiked into normal blood gave the following values: CK intensity 1166+/−306; total cell area 143 ± 48.1 μm2; nuclear area 63.1 ± 18.6 μm2. CTCs were additionally classified as either AR positive (AR+) or AR negative (AR-). 37 of the 227 (16.3%) HD-CTCs were AR+. The average CK intensity was significantly higher in AR+ versus AR- cells at 174.23 and 39.86, respectively (p&amp;lt;0.001). The AR expression intensity in AR+ HD-CTCs and LNCaP cells was comparable at 979.4 and 902.2, respectively (p=0.824). Conclusions: We find a positive association between AR and CK expression on a per cell basis. Further, we find AR is expressed at comparable levels in CTCs from patients and human prostate cancer cells in culture. The HD-CTC based approach may be used for enumeration and molecular interrogation of CTCs in patients with prostate 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 3630. doi:1538-7445.AM2012-3630
Phase I and II Study of Induction Chemotherapy With Methotrexate, Rituximab, and Temozolomide, Followed By Whole-Brain Radiotherapy and Postirradiation Temozolomide for Primary CNS Lymphoma: NRG Oncology RTOG 0227
Authors: Jon Glass, Minhee Won, Christopher J. Schultz, Daniel Brat, Nancy L. Bartlett, John H. Suh, Maria Werner-Wasik, Barbara Jean Fisher, Marcia K. Liepman, Mark Augspurger, Felix Bokstein, Joseph A. Bovi, Matthew C. Solhjem, Minesh P. Mehta
Journal: Journal of Clinical Oncology (2016)

This study investigated the treatment of primary CNS lymphoma with methotrexate, temozolomide (TMZ), and rituximab, followed by hyperfractionated whole-brain radiotherapy (hWBRT) and subsequent TMZ. The primary phase I end point was the maximum tolerated dose of TMZ. The primary phase II end point was the 2-year overall survival (OS) rate. Secondary end points were preirradiation response rates, progression-free survival (PFS), neurologic toxicities, and quality of life.The phase I study increased TMZ doses from 100 to 150 to 200 mg/m(2). Patients were treated with rituximab 375 mg/m(2) 3 days before cycle 1; methotrexate 3.5 g/m(2) with leucovorin on weeks 1, 3, 5, 7, and 9; TMZ daily for 5 days on weeks 4 and 8; hWBRT 1.2 Gy twice-daily on weeks 11 to 13 (36 Gy); and TMZ 200 mg/m(2) daily for 5 days every 28 days on weeks 14 to 50.Thirteen patients (one ineligible) were enrolled in phase I of the study. The maximum tolerated dose of TMZ was 100 mg/m(2). Dose-limiting toxicities were hepatic and renal. In phase II, 53 patients were treated. Median follow-up for living eligible patients was 3.6 years, and 2-year OS and PFS were 80.8% and 63.6%, respectively. Compared with historical controls from RTOG-9310, 2-year OS and PFS were significantly improved (P = .006 and .030, respectively). In phase II, the objective response rate was 85.7%. Among patients, 66% (35 of 53) had grade 3 and 4 toxicities before hWBRT, and 45% (24 of 53) of patients experienced grade 3 and 4 toxicities attributable to post-hWBRT chemotherapy. Cognitive function and quality of life improved or stabilized after hWBRT.This regimen is safe, with the best 2-year OS and PFS achieved in any Radiation Therapy Oncology Group primary CNS lymphoma trial. Randomized trials that incorporate this regimen are needed to determine its efficacy compared with other strategies.
Abstract 4363: Inhibitory efficacy of curcumin ± stem cell specific RNAi on the growth of tumorospheres in vitro: Assay development and mechanisms of action
Authors: Carla Kantara, Shubhashish Sarkar, Rafal Swiercz, Robert Ullrich, Pomila Singh
Journal: Cancer Research (2011)

Abstract Colorectal cancer (CRC) is the third most common cancer and leading cause of cancer related deaths in the Unites States. Several therapies are currently being used to treat the disease but recurrence remains a challenge. It is believed that cancer stem cells (CSCs) may be resistant to currently used radiation and chemotherapeutic treatments, and may thus be the likely cause of relapse. It is postulated that CSCs may arise from normal adult stem cells and, therefore, preventing aberrant proliferation of stem/progenitor cells and/or targeting CSCs may improve treatment outcomes. However, to-date, there are no assays for examining response of ‘stem cells’ in vitro. Therefore one of our goals was to isolate stem cells from colorectal cancers, and establish stem/progenitor cell bioassays to examine inhibitory efficacy of chemo preventive agents and stem cell specific siRNA. In recent years, several putative stem/progenitor cell markers have been identified, including DCAMKL-1, CD44 and LGR5. Curcumin is being used in clinical trials for treating CRCs. For our studies we chose to isolate CSCs using the above indicated stem cell markers, each of which expresses an extracellular domain. We successfully isolated stem cell populations enriched in the indicated markers, and established tumorospheres from a colon cancer cell line (HCT-116); these growths are selective for stem cells, and can therefore be used in bioassays for examining inhibitory efficacy of drugs on stem cells in vitro. We examined the inhibitory efficacy of curcumin±DCAMKL-1 siRNA against growth of HCT-116 tumorospheres. Spheres were fixed and stained for DCAMKL-1, CD44, and LGR5, and examined by fluorescence confocal microscopy. The effect on growth signaling pathways was quantified by Western Blot analysis. Our results reveal that both DCAMKL-1 siRNA and curcumin exert inhibitory effects on growth of HCT-116 tumorospheres, and reduce relative expression levels of NFκBp65 and β-catenin in tumorospheres. Importantly, DCAMKL-1 siRNA potentiated inhibitory potency of Curcumin. In conclusion, we have successfully established in vitro methods for examining proliferative/inhibitory efficacy of various molecules on the biology and response of cancer stem cells, which can be expected to impact cancer treatment strategies. This work is supported by NIH grants CA97959 and CA114264 to PS and NASA grants NNX09AM08G and NNJ04HD83G to RU. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4363. doi:10.1158/1538-7445.AM2011-4363
Abstract 775: Sequential common gamma-chain cytokines facilitate differentiation of tumor-reactive T cells that are resistant to MDSC and can induce rejection of breast tumors
Authors: Kyle K. Payne, Maciej Kmieciak, Debasmita Basu, Viswanathan Ramakrishnan, Harry D. Bear, Masoud H. Manjili
Journal: Cancer Research (2011)

Abstract Adoptive T cell immunotherapy (AIT) utilizing ex vivo expanded HER-2/neu-specific T cells is a promising modality in the treatment of patients with breast carcinoma. Previously, our group has described the ability of tumor-sensitized T cells activated ex vivo with bryostatin 1 and ionomycin (B/I) and subsequently expanded with common γ-chain receptor family cytokines IL-2 and IL-7/IL-15 cultured in an alternating manner to induce primary breast tumor regression in FVBN202 transgenic mice. These results, however, required the combination of AIT with in vivo depletion of myeloid-derived suppressor cells (MDSCs) as the presence of these cells abrogated the anti-tumor efficacy of neu-specific lymphocytes. Presently, we report the implementation of a novel ex vivo expansion protocol, in which IL-2 and IL-7/IL-15 are cultured in a sequential manner post B/I with tumor-specific activated cells and support expansion of tumor reactive CD44+CD62L− effector T cells (TE) and CD44+CD62L+ central memory T cells (TCM). We show that tumor-specific cells activated in this manner induce rejection of primary breast tumor and provide long-term protection against the tumor, even in the presence of MDSC. Of particular interest, tumor-reactive CD4+ and CD8+ lymphocytes expanded with this method conferred resistance to the suppressive effects of MDSCs in vitro. Additionally, we demonstrate that innate immune cells are essential in eliciting tumor rejection. Flow cytometric analysis indicates Natural Killer (NK) and Natural Killer T-cell (NKT) as well as the Interferon-γ Producing Killer Dendritic Cell (IKDC) populations significantly increase following ex vivo expansion with sequential common γ-chain cytokines. Depletion of innate immune cells in adoptively transferred cells resulted in the failure of AIT to reject tumor. Together, our data suggest that sequential common γ-chain cytokines can support differentiation of tumor-reactive T cells which are resistant to MDSC, as well as innate immune cells which may be essential in supporting the anti-tumor efficacy of T cells. These results potentially provide a new paradigm in therapeutic AIT of breast carcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 775. doi:10.1158/1538-7445.AM2011-775
Abstract P1-17-02: Outcome after Locoregional Recurrence in Patients with Inflammatory Breast Cancer
Authors: HJ Patel, J Li, AM Gonzalez-Angulo, E Strom, GH Perkins, W Tereffe, T-K Yu, K Hoffman, BD Smith, A Lucci, V Valero, TA Buchholz, W. Woodward
Journal: Cancer Research (2010)

Abstract Purpose: High rates of locoregional recurrence (LRR) have been reported in spite of comprehensive tri-modality therapy for patients with inflammatory breast cancer (IBC). The aim of this study was to examine the prognosis of patients who have experienced LRR after treated primary IBC. Methods: We retrospectively reviewed information for 124 IBC patients who experienced a LRR seen in our institution from 1990-2008. 63 patients had simultaneous distant disease (DM) +/−3 months of LRR (simLRR), 5 patients had LRR &amp;gt; 3 months subsequent to DM, while 56 patients had isolated LRR &amp;gt;3 months prior to DM (isLRR). Overall survival (OS) was calculated from date of recurrence using the Kaplan-Meier method. Results: Median time to LRR from diagnosis was 13 months (interquartile range 8-21 months). Median survival after LRR was 15 months. 2-yr OS was 46%. Regarding the primary tumors, 23% were estrogen receptor positive (ER+), 33% were HER2-neu positive (H2N+), 81% had lymph vascular space invasion (LVSI), and 83% were grade 3. Comparing isLRR and simLRR cohorts, median survival was 18 months vs. 10 months and 2 yr-OS was 66% vs. 28%, respectively. ER+ and H2N+ primary status predicted for longer 2 yr OS among patients with simLRR but not among isLRR patients. (simLRR, ER+ 57% vs. ER-19% p = 0.02, H2N+ 45% vs. H2N-17% p = 0.01; IsLRR ER+ vs. ER-92% vs. 55% p = 0.15, H2N+ 86% vs. H2N-57% p = 0.11). LVSI was not prognostic in either group and Grade 3 primary trended towards worse outcome among isLRR cohort only, Grade 2 83% vs. Grade 3 64% P = 0.08. Molecular subtyping using ER and H2N status to group tumors demonstrates basal subtype in the primary tumor compared to H2N, luminal B and luminal A is associated with significantly worse 2 yr OS after isLRR (43% vs. 88%, 82%, and 83%, P = 0.04) and simLRR (13% vs. 34%, 80%, 32% P = 0.005) respectively. Conclusions: Forty-five% of LRR occurred as isolated first events. LRRs generally occur within 2 years after primary IBC treatment and are associated with poor outcomes even as first events. Basal subtype predicts for worse overall survival regardless of distant disease. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-17-02.
Abstract 3801: p53 acetylation by green tea polyphenols leads to upregulation of GSTP1 activity
Authors: Vijay S. Thakur, Karishma Gupta, Sanjay Gupta
Journal: Cancer Research (2010)

Abstract Epigenetic modifications including DNA methylation and post-translational changes in histone proteins cause alteration in gene regulation. Expression of glutathione-S-transferase Pi (GSTP1), an enzyme of phase II cellular metabolism involved in detoxification of carcinogens and other cellular functions found to be silenced in 80-90% prostate cancers due to hypermethylation of its promoter. We have recently demonstrated that green tea polyphenols (GTPs) cause re-expression of GSTP1 in human prostate cancer LNCaP cells [Int J Cancer. 2009; PMID: 19856314]. However, the mechanism of GSTP1 re-expression is not fully elucidated. Similar to GSTP1 gene, p53 tumor suppressor is also involved in a number of important cellular events including cell cycle, DNA repair, and apoptosis which is reported to be mutated or has defective signaling in most human cancers including prostate cancer. Human GSTP1 gene has a p53-binding motif located in intron 4 and is highly homologous to consensus p53-binding motifs in other p53-responsive genes having the ability to transcriptionally activate GSTP1. Whether p53 participates in GTP-mediated re-expression of GSTP1 is unknown. In the present study we attempted to elucidate the role of tumor suppressor p53 in GSTP1 re-expression after treatment with GTPs. Human prostate cancer LNCaP cells which possess epigenetic signatures of GSTP1 silencing and functional p53 were treated with physiologically achievable doses of GTPs (5μg/mL) or its major constituent epigallocatechin-3-gallate (20μM) up to 7 days. Exposure of LNCaP cells to green tea polyphenols caused acetylation of p53 at its C-terminal amino acid positions K373 and K382, other than K305, which correlated with increased GSTP1 expression. Discontinuation of treatment with GTPs resulted in the loss of p53 acetylation with progressive decrease in GSTP1 expression in these cells. Furthermore, GSTP1 levels were significantly reduced after GTP treatment in cells with the knockdown of p53 expression achieved using shRNA in lentiviral vector. Taken together, our results demonstrate that expression of GSTP1, in part, could be enhanced through p53 acetylation after treatment with green tea polyphenols and thus protect the cells from undergoing epigenetic alterations which may contribute to prostate tumorigenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3801.
Radio: Living with Pain
Authors: I. McClure
Journal: BMJ (2001)

BBC Radio 4, Wednesdays at 9 pm, 15 to 29 August

After a hard day's slog, many doctors' idea of pain might be to sit and listen to a half hour radio programme about pain itself. However, if you haven't yet tuned in to this rewarding series, you might just be missing out.

For a start, it will probably tell you a lot of things you don't already know. In the space of just 30 minutes, the first of the three programmes treated us to a dazzling medley of the physiology of pain, the representation of pain in art through the …