tbuckley/cabot-search huggingface dataset:
SAT0595-HPR Low Levels of Pain Impact on Valued Life Activities in Women and Men with Rheumatoid Arthritis
Authors: I. Ahlstrand, M. Björk, I. Thyberg, T. Falkmer
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Disability in RA is more pronounced in women than in men and pain is strongly related to activity limitation and participation. The Valued life activity scale (VLA) is a questionnaire in which patient's first report if the separate activities are valued or not to perform and secondly difficulties to perform these activities. To measure disability with VLA includes the patient's perspective in a unique way compared to traditional disability measurements of daily activities (e.g., HAQ). <h3>Objectives</h3> <i>Objective</i> was to examine difficulties to perform valued life activities and how this is related to pain in women and men with RA. <h3>Methods</h3> Patients aged 18 - 80 year with RA were recruited from the Swedish Rheumatology's Quality Registry (SRQ) at three clinics. The inclusion criteria were : fulfilling 4 of 7 ACR criteria, ages 18 - 80 year, ≥4 years duration and data registered in SRQ at a visit at the clinic during 2011. Totally 1,277 patients were approached and 737 (58%) responded to the study specific questionnaire which measured performance of 33 differentvalued life activities by a Swedish version of VLA and pain by Visual Analogue Scale (VAS). Patients were sub groupedbased on low-pain intensity (VAS&gt;40) and pain high-pain intensity (VAS &lt;40). The relationship between performance of valued life activities and pain were analysed based on gender. <h3>Results</h3> Across the genders, 85% reported at least one valued life activity affected by RA. Significantly more women encountered difficulties in performing cooking, heavy housework, minor repairs, gardening, community mobility, shopping, child care, having others visit, volunteer work, study, sleeping and meeting new people. No valued life activities were identified in which men reported more difficulties than women. Women (73%) reported higher pain intensity (35 mm) than men (31 mm). Regardless of gender, 58% had low pain (VAS &lt;40) while 42% had high pain (VAS ≥40). Almost all 33 difficulty ratings for valued life activities were significantly higher in the high-pain group than in the low-pain group. There were significant correlations (<i>rho</i> ranging from .19 to .68) with respect to difficulty ratings for valued life activities and pain in the low-pain group. In the high-paingroup, however, difficulty ratings forthe 33 valued life activities were not correlated with the degree of pain. <h3>Conclusions</h3> VLA assisted in identifying that low levels of pain were positively correlated with difficulties to perform valued life activities. Women reported more pain and difficulties in performing valued life activities than men. These results draw attention to the importance of addressing valued activities especially among female patients with low levels of pain, since their pain may impact on their activities in daily life that they identify as important. <h3>Disclosure of Interest</h3> None Declared
Abstract 711: Understanding the mechanisms of resistance to BRAF inhibitors in melanoma
Authors: Jessie Villanueva, Clemens Krepler, Adina Vultur, Yuhao Chen, Xu He, Bradley Wubbenhorst, Katherine L. Nathanson, Meenhard Herlyn
Journal: Cancer Research (2011)

Abstract The presence of activating BRAF mutations in approximately 50% of melanomas, the majority of which are BRAFV600E, has prompted the development of selective BRAF inhibitors for targeted therapy. Pre-clinical data using multiple BRAF inhibitors and results from recent clinical trials using PLX4032 validate the effectiveness of this treatment strategy and offers hope to patients suffering from this deadly disease. However, similar to other malignancies, therapy with BRAF inhibitors is effective in only a subset of patients and even if an initial effective response is observed, tumors eventually develop resistance and patients relapse. We recently reported that acquired resistance to BRAF inhibitors can be mediated by non-genetic mechanisms through rewiring of their signaling pathways and this is mediated by a RAF kinase switch and increased PI3K-dependent survival. However, as melanoma is a highly heterogeneous disease, we anticipate that multiple mechanisms can be associated with acquired resistance to BRAF and/or MEK inhibitors. Also, the mechanisms of intrinsic resistance can be different from those underlying acquired resistance. Here we report that melanoma cells which harbor the BRAFV600E mutation and express PTEN have low levels of phospho-AKT and are sensitive to BRAF inhibitors. In contrast, BRAFV600E mutant melanoma cell lines that do not express PTEN have higher levels of phospho-AKT and are less sensitive to BRAF inhibitors. Co-targeting PI3K and mutant BRAF in melanoma cells that lack functional PTEN sensitizes them to the combination strategy. Our studies suggest that the presence or absence of functional PTEN can modulate response to inhibitors of the MAPK pathway and warrant further evaluation of combination strategies to treat melanomas refractory to BRAF inhibitors. 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 711. doi:10.1158/1538-7445.AM2011-711
Commentary: Application of Biomarkers to Risk Assessment
Authors: David W. Gaylor, Fred F. Kadlubar, Frederick A. Beland
Journal: Environmental Health Perspectives (1992)

Due to difficulties in conducting epidemiological studies, most estimates of cancer risk are based on data from animal bioassays. Extrapolation of cancer risk estimates in animals to humans requires an assumption of equal potency across species based on the average daily dose. The purpose of this paper is to examine the ability to predict tumor incidence across species from DNA adduct concentrations resulting from exposure to carcinogens. A 100-fold range of structurally diverse adduct concentrations corresponding to the same tumor incidence raises questions about quantitative predictability across chemical classes and across species. Differences in adduct structure, mutagenic efficiency, adduct repair rates, and cellular proliferation could account for some of the differences. For specific carcinogen-DNA adducts, the steady-state levels associated with a 50% tumor incidence appear to vary over a narrower range. An equal incidence of liver tumors was obtained at equal concentrations of aflatoxin B1-DNA adducts for rats and trout. A 2to 3-fold range of 4-aminobiphenyl-DNA adduct concentrations between mice and dogs appears to be associated with nearly equal bladder tumor incidence, on the basis of limited data. In humans, a 5-fold higher concentration of a 4-aminobiphenyl-DNA adduct in bladders of smokers than of nonsmokers is compatible with the relative risk of bladder cancer due to smoking. DNA adduct concentrations certainly can be used to improve quantification of chemical exposures for epidemiological studies. Although promising, more data are needed to judge the usefulness of DNA adduct concentrations to predict cancer incidence across species.
Specific detection of Helicobactor pylori and non-Helicobactor pylori flora in small-and large-cell primary gastric B-cell non-Hodgkin's lymphoma
Authors: I.A.M. Gisbertz, D.M.A.E. Jonkers, J.W. Arends, F.J. Bot, R.W. Stockbrügger, L.W. Vrints, H.C. Schouten
Journal: Annals of Oncology (1997)
Abstract P1-11-11: Correlation between ER/PgR/Her-2/Ki67 Expression and Response to Neoadjuvant Endocrine Therapy for HR Positive Post-Menopausal Breast Cancer
Authors: T Ouyang, M Ying, L Li, T Wang, Y Xie, A Lu, B. Lin
Journal: Cancer Research (2010)

Abstract Background: Endocrine therapy was standard adjuvant treatment for hormone receptor positive breast cancer. However, there were factors other than receptor status could influence endocrine responsiveness. Neoadjuvant therapy was an excellent platform for predictive factors research, but the standard for evaluating the efficacy of neoadjuvant endocrine therapy was controversy. The aim of this study was to investigate the correlation among the results of different response evaluation system, and the relationships between ER/PgR/Her-2/Ki67 expression and the responses to neoadjuvant endocrine therapy for postmenopausal breast cancer. Methods: Data of consecutive 133 core needle biopsy (CNB) confirmed hormone receptor strongly positive (more than 50% tumor cell stained ER or PgR) postmenopausal breast cancer treated with neoadjuvant endocrine therapy were analysis retrospectively. All pts. were planned to receive endocrine therapy alone as their adjuvant treatment and prescribed Anastrozole 1 mg per day for 16 weeks before surgery. Clinical response were evaluated by using documented ultrasound records,pathological response was evaluated by one senior pathologist with Miller &amp; Payne classification. Cell cycle complete response was defined as post-treatment Ki67 ≥1%. The new slides of pre-treatment and surgical specimens were made for ER/PgR (ER\PR DakoCytomation)/Her-2 (Her-2 Dako HercepTest TM)/Ki67 (Ki67 Ventana) immunohistochemical staining through Benchmark XT Staining Instrument (Ventana Medical Systems. Inc. Arizona. USA) and classified by using image analysis system Ariol (Applied Imaging Inc., San-Jose, California, USA). Results: Clinical response were CR:0.8% PR:33.1% SD:66.1%, pathological response were G5:3% G4+G3:47.4% G2+G1:49.6%, Ki67 change were &amp;lt;1%: 22.8% decrease but &amp;gt;1%:45.1% no decrease: 32.1%. The correlation and consistency among the response evaluated differently were poor [table 1]. The per-treatment ER/PR/Her-2/Ki67 showed low degree of correlation with responses [table 2]. Pre-treatment ER≥90% and PR≥90% and Her-2 coudln't predict better response. The correlation and consistency among response evaluated in different system Conclusion: The correlation and consistency among the results of response to neoadjuvant endocrine therapy evaluated by different system were poor. ER/PgR/Her-2/Ki67 showed low degree of correlation to responses. It's difficult to predict response to Arimidex neoadjuvant endocrine therapy by using ER/PgR/Her-2/Ki67 expression. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-11-11.
Circulating Folate and Vitamin B12 and Risk of Prostate Cancer: A Collaborative Analysis of Individual Participant Data from Six Cohorts Including 6875 Cases and 8104 Controls
Authors: Alison J. Price, Ruth C. Travis, Paul N. Appleby, Demetrius Albanes, Aurelio Barricarte Gurrea, Tone Bjørge, H. Bas Bueno-de-Mesquita, Chu Chen, Jenny Donovan, Randi Gislefoss, Gary Goodman, Marc Gunter, Freddie C. Hamdy, Mattias Johansson, Irena B. King, Tilman Kühn, Satu Männistö, Richard M. Martin, Klaus Meyer, David E. Neal, Marian L. Neuhouser, Ottar Nygård, Par Stattin, Grethe S. Tell, Antonia Trichopoulou, Rosario Tumino, Per Magne Ueland, Arve Ulvik, Stefan de Vogel, Stein Emil Vollset, Stephanie J. Weinstein, Timothy J. Key, Naomi E. Allen
Journal: European Urology (2016)

Folate and vitamin B
Ensuring Equal Access to Specialty Care
Authors: Thomas D. Sequist
Journal: New England Journal of Medicine (2011)

Improving access to specialty care represents an important component of a comprehensive plan to address disparities in health care. At a time when our nation is struggling to rein in health care spending and potential overuse of specialty services,1,2 it is critical to consider the needs of many rural and underserved communities in which access to specialty services is often severely limited. In the Indian Health Service, a federal health system providing care to American Indians and Alaska natives, less than one third of primary care physicians report that they have regular access to specialty care.3 This limited access . . .
Abstract 153: Hypothyroidism and hyperthyroidism in relation to endometrial cancer: A prospective study.
Authors: Angela Kueck, Jae Hee Kang, Richard Stevens, Gary Curhan, Erik Alexander, Bernard Rosner, Immaculata DeVivo, Shelley Tworoger
Journal: Cancer Research (2013)

Abstract Background Thyroid hormones may be involved in tumorigenesis and metastasis in hormone sensitive cancers. Thyroid hormones strongly influence the menstrual cycle, implantation and fertility, suggesting that thyroid hormones also could play a role in the development of endometrial cancer (EC), which is hormone-sensitive. No prospective studies have examined this association. Methods We prospectively evaluated the association between self-reported physician-diagnosed hypothyroidism and hyperthyroidism in the Nurses’ Health Study (NHS) from 1976 - 2010. Reports of thyroid dysfunction were based on self-report on biennial follow-up questionnaires, and have shown high validity when compared to medical records. Incident EC cases were confirmed with medical, pathology and death records. Multivariate rate ratios (RRs) for endometrial cancer were calculated, adjusting for major EC risk factors (i.e., body mass index, smoking, parity, age at last birth, oral contraceptive use, family history, age at menarche, age at menopause, postmenopausal hormone use, type 2 diabetes, and height). Results During 34 years of follow-up in NHS, we documented 917 cases of incident EC. Compared to those without any reported thyroid dysfunction, the multivariable RR for hypothyroidism was 0.99 (95% CI, 0.75-1.30) and the null associations were consistent across categories of time since hypothyroidism diagnosis. The multivariable RR for hyperthyroidism was 1.38 (95% CI 0.79 - 2.41). An association was observed with longer time since hyperthyroidism diagnosis (median time since hyperthyroidism diagnosis was 6 years in NHS); the RR for EC associated with 6+ years since hyperthyroidism diagnosis was 2.08 (95% CI, 1.02, 4.23). Conclusions Overall self-reported hypothyroidism and hyperthyroidism were not associated with risk of EC; however, longer time since hyperthyroidism diagnosis may be associated with an increased risk of EC. Due to the overall small number of cases with hyperthyroidism, on-going analyses will incorporate results from the Nurses’ Health Study II to increase power for these analyses. Citation Format: Angela Kueck, Jae Hee Kang, Richard Stevens, Gary Curhan, Erik Alexander, Bernard Rosner, Immaculata DeVivo, Shelley Tworoger. Hypothyroidism and hyperthyroidism in relation to endometrial cancer: A prospective study. [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 153. doi:10.1158/1538-7445.AM2013-153
Abstract 4822: Nonsense mediated decay defines deleterious TP53 mutations and tumor aggressiveness in ovarian cancer
Authors: Ahmed A. Ahmed, Robert C. Bast, David Bowtell, Juliet Goldsmith
Journal: Cancer Research (2011)

Abstract Genetic mutations leading to premature termination of protein translation, nonsense mutations, result in aberrant precursor mRNA processing and subsequent UPF1-dependent exosomal degradation of mRNA. The significance of this surveillance mechanism in controlling the expression of key mutated tumor suppressor genes in cancer in vivo has remained unclear. We have recently shown that TP53 mutations are almost invariably present in high-grade serous ovarian cancers (Ahmed at al., Journal of Pathology, 2010;221:49) and that about one third of such mutations are nonsense. We have now tested the hypothesis that nonsense mutations induce nonsense mediated decay resulting in TP53 mRNA depletion. We analyzed microarray expression profiling data from 136 epithelial ovarian cancers with known TP53 mutation status and found a strikingly statistically significant underexpression of TP53 mRNA transcript in cancers with truncating mutations (p&amp;lt;0.0001) compared to other types of mutations. This effect allowed the identification of a class of TP53-non-expressing serous epithelial cancers that comprised all TP53 truncating mutations. We next conducted a systematic analysis of 18 publically available expression profiling ovarian cancer studies published at the Gene Expression Omnibus database. We validated the results by showing that cancers that had nonsense mutations had a significantly lower TP53 expression irrespective of stage. Importantly, this systematic analysis of multiple independent data set established that lack of TP53 expression was, almost exclusively, a feature of high grade serous cancers and invasion as opposed to low grade disease or tumors of low malignant potential (p&amp;lt;0.0001 and p=0.002, respectively). Expression profiling analysis revealed that cancers with truncating mutations had a distinct gene expression signature compared to those with missense mutations. This signature was enriched for genes that regulated angiogenesis such as CSPG4 and metabolism. Surprisingly, however, the magnitude of expression differences was not high. Based on these results, we propose a model for the biogenesis of a subset of high-grade serous ovarian cancers that is defined by nonsense mediated decay of nonsense TP53 mutations. 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 4822. doi:10.1158/1538-7445.AM2011-4822
Abstract 597: The combination of valproic acid and fludarabine treatment induces a synergistic apoptotic response in chronic lymphocytic leukemia (CLL) patients involving the lysosomal protease cathepsin B.
Authors: Ju Yoon Yoon, David Szwajcer, Ganchimeg Ishdorj, Pat Benjaminson, Rajat Kumar, James B. Johnston, Spencer B. Gibson
Journal: Cancer Research (2013)

Abstract Chronic Lymphocytic Leukaemia (CLL) is the most common hematological malignancy in the western world. Fludarabine, a nucleoside analogue, is commonly used in combinational treatments for CLL. However, patients commonly develop resistance to fludarabine based therapies. Valproic Acid (VPA), an inhibitor of histone deacetylases (HDACs), showed synergistic apoptotic responses when combined with fludarabine in human leukemic cells and primary CLL cells. The mechanism for this synergistic apoptotic response is unknown. We found that fludarabine and VPA treatment increased activates caspases-8, -9, -3, and caspase-2 and a decreased in expression of anti-apoptotic proteins Mcl-1 and XIAP. Treatment with fludarabine alone or in combination with VPA led to the loss of lysosome integrity suggesting a leakage of the lysosomal content into the cytosol in response to these drugs. Chemical inhibition of a specific lysosomal protease, cathepsin B, using CA074-Me was sufficient to stabilize Mcl-1 and XIAP while reducing caspase activation and apoptosis. Addition of purified cathepsin B to leukemic cell lysates led to the reduction in protein levels of Mcl-1, XIAP and pro-caspase-2, thus suggesting that the re-localization of cathepsin B into the cytosol is sufficient to degrade these proteins. VPA treatment increased cathepsin B levels in both leukemic cell lines and primary CLL cells. VPA also increased cathepsin B activity. In addition, six relapsed CLL patients who had received at least one prior therapy with fludarabine were treated with VPA alone or in combination with fludarabine. No responses were seen after 28 days using VPA alone but in five patients who continued on VPA with fludarabine, three patients showed reduced lymphocyte count after receiving at most five cycles of the combination therapy. When the CLL cells from VPA-treated CLL patients were examined, VPA administration induced increased levels of histone-3 acetylation and cathepsin B expression in vivo. Thus, VPA and fludarabine synergistic apoptotic response is mediated by cathepsin B activation leading to a decrease in anti-apoptotic proteins in CLL cells and likely contributes to the clinical response observed in relapsed, fludarabine-refractory CLL patients. Citation Format: Ju Yoon Yoon, David Szwajcer, Ganchimeg Ishdorj, Pat Benjaminson, Rajat Kumar, James B. Johnston, Spencer B. Gibson. The combination of valproic acid and fludarabine treatment induces a synergistic apoptotic response in chronic lymphocytic leukemia (CLL) patients involving the lysosomal protease cathepsin B. [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 597. doi:10.1158/1538-7445.AM2013-597
Abstract 2666: Relationship between chromatin structure and sensitivity to molecularly-targeted radiation therapy
Authors: Samantha Y.A Terry, Katherine A. Vallis
Journal: Cancer Research (2011)

Abstract The open structure of euchromatin renders it more susceptible to DNA damage by ionising radiation (IR) compared to compact heterochromatin. The goal was to investigate whether chromatin accessibility also affects the toxicity of Auger electron-emitting radiopharmaceuticals. SAHA is a histone deacetylase inhibitor that results in chromatin remodelling to an open structure and is used to treat cutaneous T-cell lymphoma. Epidermal growth factor receptor (EGFR)-overexpressing MDA-MB-468 and MDA-MB-231/H2N breast cancer cells were treated with SAHA and irradiated (137Cs source, 1Gy/min, 0.5Gy) or incubated with 111Indium-DTPA-hEGF (111In-EGF) for one hour. Cells were stained for γH2AX, a marker of DNA double-strand breaks, 30min after γ-irradiation or after exposure to 111In-EGF. Nuclear uptake of 111In following SAHA was evaluated in cellular fractionation experiments. Total cellular H2AX protein expression after SAHA treatment was analysed by western blot. Cells treated with SAHA and consequently irradiated (up to 6Gy) or incubated with 111In-EGF (24h), were plated and incubated for 7-10 days in clonogenic survival experiments. Cells were exposed to calyculin A (50nM) or NaCl (0.5M), which result in chromatin condensation, irradiated (1Gy) or incubated with 111In-EGF (1h) and stained for γH2AX as before. In both MDA-MB-468 and MDA-MB-231/H2N cells, SAHA resulted in an increase in the number of γH2AX foci (16 and 14 per cell respectively) compared to IR alone (12 and 11 foci/cell respectively). SAHA plus 111In-EGF also increased DNA damage (22 and 12 foci/cell respectively) compared to 111In-EGF alone (15 and 7 foci/cell respectively). SAHA did not alter the extent of nuclear uptake of 111In in either cell line (0.4-0.6% of total administered), nor did it alter total cellular H2AX protein expression. Preliminary clonogenic data suggest that SAHA decreases cell survival after either irradiation or incubation with 111In-EGF in both cell lines. MDA-MB-468 cells treated with calyculin A accumulated less damage after γ-irradiation (11 foci/cell) compared to IR alone (20 foci/cell). Treatment of both cell lines with NaCl before irradiation (11 and 9 foci/cell) also protected against DNA damage compared to IR alone (19 and 16 foci/cell). Preliminary data suggests that cells treated with NaCl prior to incubation with 111In-EGF also acquired less DNA damage. Chromatin density modification alters radiosensitivity and DNA damage after γ-irradiation. The results of this study indicate that this is also the case for Auger electron-emitting molecularly-targeted radiation therapeutic agents. 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 2666. doi:10.1158/1538-7445.AM2011-2666