tbuckley/cabot-search huggingface dataset:
Abstract PD09-05: Impact of Body Mass Index (BMI) on the Efficacy of Endocrine Therapy in Postmenopausal Breast Cancer Patients — An Analysis of the ABCSG 6 and 6a Trial
Authors: G Pfeiler, H Stöger, C Singer, M Seifert, R Jakesz, P Dubsky, H Samonigg, R Greil, C Menzel, D Heck, M. Gnant
Journal: Cancer Research (2010)

Abstract Background: Recently, we have demonstrated that BMI significantly impacts on the efficacy of anastrozole but not tamoxifen (TAM) in premenopausal breast cancer patients. As aromatase inhibitors (AIs) are a mainstay in the treatment of endocrine responsive postmenopausal breast cancer patients, it is of certain interest, if this influence of BMI on endocrine therapy is also true for the postmenopausal situation. Methods: For analysis of the ABCSG 6 and 6a trial, patients were classified as normal weight (BMI 18.5-24.9 kg/m2) or as overweight (BMI ≥25kg/m) according to WHO criteria. The underweight population was excluded from the analyses. We retrospectively analysed the ABCSG 6 trial, which examined the efficacy of TAM versus TAM + aminoglutethimide (first generation AI) in endocrine responsive postmenopausal breast cancer patients. All patients have been censored after 60 months since the majority of patients without events have been re-randomized into trial ABCSG 6a after 5 years. Further, we retrospectively analysed the ABCSG 6a trial, which examined 3 additional years of anastrozole versus no further treatment after 5 years of endocrine treatment. Results: 1,566 patients (311 events/214 deaths) and 477 patients (108 events/64 deaths) were included in the analyses of the ABCSG-6 trial and the ABCSG-6a trial, respectively. About two thirds of all patients in both trials were overweight and one third was normal weight. Analysing the ABCSG 6 trial, no difference in disease free survival (DFS) and overall survival (OS) between normal weight and overweight patients treated with TAM versus TAM + aminoglutethimide could be observed. Analysing the ABCSG-6a trial, normal weight patients treated with anastrozole showed a remarkable and significant reduced risk in DFS and OS compared to control (HR 0.464, 95%CI 0.242 0.842 p=0.02 and HR 0.372, 95%CI 0.16 0.863, p=0.02). In contrast, in overweight patients anastrozole compared to control did not improve DFS and OS (HR 0.991, 95%CI 0.611 1.608, p=0.97 and HR 0.871, 95%CI 0.456 1.662, p=0.67). Conclusion: BMI impacts on the efficacy of anastrozole but not tamoxifen in postmenopausal breast cancer patients. It seems that overweight patients in contrast to normal weight patients do not benefit from additional 3 years of anastrozole after 5 years of endocrine therapy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD09-05.
AB0403 Dose Optimization of Biological Therapies in Rheumatoid Arthritis in Clinical Practice: Table 1.
Authors: M. Arredondo, L. Sala, I. Cañamares, E. Ramírez-Herráiz, I. González-Άlvaro, J.P. Lόpez-Bote, A. Morell, R. García-Vicuña, J.M. Alvaro-Gracia
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Biological therapies (BT) have resulted in a remarkable improvement in the treatment of rheumatoid arthritis (RA). One of the limiting factors for its use is cost. For this reason, the development of optimization strategies is becoming increasingly frequent. <h3>Objectives</h3> To analyze the optimization of BT in RA in daily clinical practice. <h3>Methods</h3> We conducted an observational cross-sectional study including all patients with RA under BT (except anakinra and rituximab) in a tertiary referral hospital. Data from the first three months of 2013 were analyzed and extrapolated to one year. The analyzed parameters included: dose, administration intervals and cost. In addition, in order to have an estimate of the tendency of this practice, data from the first three months of 2011 were taken for comparison. Patients were considered as down-titrated/optimized when the quarterly dose of BT was ≤83% of the approved dose. Effectiveness was measured by DAS28. Statistical comparison of both periods was performed by T-test. <h3>Results</h3> 265 patients were studied in 2013. Percentage of down-titrated patients, total mean dose and mean dose in the titrated group are displayed in Table. Our data showed an average decrease of 16.10% in total mean dose of BT. This represented an additional 5% reduction in total mean dose compared to 2011. Data ranged from 0 to 25.80% with the different BT. This reduction in quarterly dose was not associated to loss of efficacy as measured by average DAS 28 between 2011 and 2013 [DAS 28 =2.94 (2.05-3.84) vs 2.88 (1.80-3.96) (p=0.742)]. <h3>Conclusions</h3> Optimization of BT in RA is increasingly frequent in clinical practice. This strategy contributes to cost containment in this and other conditions. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4952
RIVAROXABAN COMPARED TO LOW MOLECULAR WEIGHT HEPARIN IN TREATMENT OF MALIGNANCY ASSOCIATED VENOUS THROMBOEMBOLISM
Authors: Robert D. McBane, Benjamin Simmons, Rayya Saadiq, Waldemar Wysokinski, Dalene Bott-Kitslaar, Charles Lenz, Paul Daniels, Kevin Cohoon, Aneel Ashrani, Charles Loprinzi
Journal: Journal of the American College of Cardiology (2016)
Abstract 1750: Clinically relevant paclitaxel concentrations cause chromosome missegregation rather than mitotic arrest.
Authors: Lauren M. Zasadil, Mark Burkard, Beth A. Weaver
Journal: Cancer Research (2013)

Abstract Paclitaxel is a chemotherapeutic, microtubule-stabilizing drug used to treat a variety of cancers, including those of the breast. In the neoadjuvant setting, paclitaxel effects tumor shrinkage in up to half of patients. Identification of a biomarker to predict response to paclitaxel would reduce side effects and improve patient outcomes. It has long been known that micromolar concentrations of paclitaxel cause cells in culture to arrest in mitosis, which can lead to cell death. However, the concentration range found within patient tumors remains unclear, both because it has not been directly measured and because paclitaxel accumulates intracellularly up to 1000 fold. In a pilot clinical trial, we are directly measuring the intratumoral drug concentration in breast tumors following neoadjuvant paclitaxel treatment. Our preliminary data support the hypothesis that treatment of cultured cells with a low nanomolar concentration more accurately models the intratumoral drug levels in breast cancer patients. Unlike treatment with micromolar concentrations, treatment with low nanomolar paclitaxel does not cause a significant mitotic arrest. Rather, cells treated with low nanomolar paclitaxel frequently proceed through mitosis with multipolar mitotic spindles, resulting in chromosome missegregation and the production of two or more daughter cells. This alternative mechanism of action may explain why tumors treated with paclitaxel fail to show an increase in mitotic index. Previous studies have shown that low rates of chromosome missegregation are well tolerated, but high rates of chromosome missegregation cause cell death due to loss of both copies of one or more essential chromosomes. Therefore, the fidelity of chromosome segregation may be of use as a predictor of response to paclitaxel. In chromosomally stable breast cancer cells, exposure to paclitaxel for two days is sufficient to induce aneuploidy, and within three days there is an increase in cell death. However, a subset of cells are able to survive in low nM paclitaxel for over one week, and survival is higher than in cells which exhibit chromosomal instability (CIN), and have a preexisting rate of chromosome missegregation during division. In patients, chromosomal stability is of potential use as a predictive biomarker to select patients most likely to respond to paclitaxel treatment. Citation Format: Lauren M. Zasadil, Mark Burkard, Beth A. Weaver. Clinically relevant paclitaxel concentrations cause chromosome missegregation rather than mitotic arrest. [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 1750. doi:10.1158/1538-7445.AM2013-1750
Correction of Phenylketonuria after Liver Transplantation in a Child with Cirrhosis
Authors: Pietro Vajro, Pietro Strisciuglio, Didier Houssin, Gilbert Huault, Jocelyne Laurent, Fernando Alvarez, Olivier Bernard
Journal: New England Journal of Medicine (1993)

To the Editor: Liver transplantation has been performed in a few children with inborn errors of metabolism that do not cause liver failure but may be responsible for severe disease of extrahepatic ...
Hugh Michael Norman
Authors: W. Norman
Journal: BMJ (2013)

Hugh Michael Norman (“Mike”) found his training interrupted after his first year, when he caught polio while walking in the Pyrenees. He took a year to recover, and, with the help of a Morris Minor gifted by a favourite aunt, he was able to return to his studies on crutches initially and then a stick that stayed with him the rest of his life.

Initially interested …
Elevated Blood Cyanide Concentrations in Victims of Smoke Inhalation
Authors: Frédéric J. Baud, Patrick Barriot, Véronique Toffis, Bruno Riou, Eric Vicaut, Yves Lecarpentier, Raymond Bourdon, Alain Astier, Chantal Bismuth
Journal: New England Journal of Medicine (1991)

The nature of the toxic gases that cause death from smoke inhalation is not known. In addition to carbon monoxide, hydrogen cyanide may be responsible, but its role is uncertain, because blood cyanide concentrations are often measured only long after exposure.We measured cyanide concentrations in blood samples obtained at the scene of residential fires from 109 fire victims before they received any treatment. We compared the results with those in 114 persons with drug intoxication (40 subjects), carbon monoxide intoxication (29 subjects), or trauma (45 subjects). The metabolic effect of smoke inhalation was assessed by measuring plasma lactate at the time of admission to the hospital in 39 patients who did not have severe burns.The mean (+/-SD) blood cyanide concentrations in the 66 surviving fire victims (21.6 +/- 36.4 mumol per liter, P less than 0.001) and the 43 victims who died (116.4 +/- 89.6 mumol per liter, P less than 0.001) were significantly higher than those in the 114 control subjects (5.0 +/- 5.5 mumol per liter). Among the 43 victims who died, the blood cyanide concentrations were above 40 mumol per liter in 32 (74 percent), and above 100 mumol per liter in 20 of these (46 percent). There was a significant correlation between blood cyanide and carbon monoxide concentrations in the fire victims (P less than 0.001). Plasma lactate concentrations at the time of hospital admission correlated more closely with blood cyanide concentrations than with blood carbon monoxide concentrations. Plasma lactate concentrations above 10 mmol per liter were a sensitive indicator of cyanide intoxication, as defined by the presence of a blood cyanide concentration above 40 mumol per liter.Residential fires may cause cyanide poisoning. At the time of a patient's hospital admission, an elevated plasma lactate concentration is a useful indicator of cyanide toxicity in fire victims who do not have severe burns.
AB1178 Comparison of the prevalence of proxy- or self-reported side effects of methotrexate administered orally, subcutaneously or intramuscularly in children with juvenile idiopathic arthritis:
Authors: M. Bertamino, A. Consolaro, S. Magni-Manzoni, G. Bracciolini, V. Muratore, T. Daniela, A. Martini, A. Ravelli
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Methotrexate (MTX) is the disease-modifying medication of first-choice for the treatment of juvenile idiopathic arthritis (JIA). Although serious adverse effects are rare, MTX intolerance, particularly gastrointestinal discomfort, is frequently observed. However, it is unclear whether the prevalence of adverse events varies across different routes of administration. <h3>Objectives</h3> To compare the rate of parent proxy-reported or child self-reported side effects of MTX administered orally, subcutaneously or intramuscularly. <h3>Methods</h3> The parents of children with JIA who were seen at our center from March 2007 and September 2011 and were receiving MTX therapy were asked to complete the proxy-report version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR), which includes a checklist of medication side effects. The self-report version of the same questionnaire was also completed by children, if aged more than 7-8 years. The JAMAR lists 18 side effects and offers the possibility to record up to 2 side effects not included in the list. MTX therapy was started in all patients, irrespective of the route of administration, at 15 mg/m<sup>2</sup>/week. All patents were given folate supplementation with folinic acid. <h3>Results</h3> The JAMAR was completed by 337 parents in 1007 visits and by 183 children in 419 visits. The frequency of parent proxy-reported side effects by route of administration is shown in the Table. <h3>Conclusions</h3> The frequency of nausea and vomiting was greater in children receiving MTX parenterally than in those on oral MTX. Children taking MTX orally had more frequently stomach pain/burning or sleep disturbances than those on parenteral MTX. <h3>Disclosure of Interest</h3> None Declared
Abstract 3174: A real-time qPCR approach to detect fusions between the KIF5B and RET genes in non-small cell lung cancer.
Authors: Katherine Bell, Dana Gaffney, Gabriela Martinez, Suso Platero, Jayaprakash Karkera
Journal: Cancer Research (2013)

Abstract Lung cancer is the leading cause of death in cancer worldwide. There are two major forms of lung cancer, including small cell lung cancer (SCLC) which accounts for approximately 20% of all lung cancers and non-small cell lung cancer (NSCLC) which accounts for approximately 80% of lung cancers. Around 25% of these lung cancer patients are never smokers and these cancers tend to be the result of single somatic mutation events. Several somatic events have been reported in NSCLC, including mutations in EGFR and KRAS along with an EML4-ALK fusion gene, however more than 40% of these cancers are the result of unknown genetic events. Recently several papers have reported a novel fusion gene resulting from a 10.6 Mb inversion on chromosome 10 which leads to a fusion between the KIF5B and RET genes. The RET gene is a well-known tyrosine-kinase proto-oncogene which has been linked to papillary thyroid carcinomas and its expression is generally very low in lung. RET tyrosine kinase stimulates autophosphorylation of the tyrosine kinase unit which activates several pathways including STAT3, RAS/ERK, MAPK, PI3K/AKT and SRC. In the KIF5B-RET fusion KIF5B retains its coiled-coil domain necessary for homodimerization and the RET retains its kinase function leading to aberrant activation of several kinase pathways. Several fusion genes between the exons of KIF5B and RET have been previously reported including KIF5B15:RET12, KIF5B16:RET12, KIF5B22:RET12, KIF5B23:RET12, KIF5B15:RET11, KIF5B24:RET8 and KIF5B24:RET11. In this study we developed a TaqMan qRT-PCR-based approach to evaluate the expression of these seven (7) KIF5B-RET fusion transcripts in 64 NSCLC fresh frozen biopsies, ranging from stage I to stage III, including 25 adenocarcinoma and 37 squamous cell carcinoma samples, respectively. Our findings confirm the presence of the fusion between KIF5B15 (exon 15) and RET12 (exon 12) at a frequency of 1.56% in all subtypes. The clinicopathological background of the KIF5B/RET fusion-positive patient agrees with previously reported trends for this fusion event consisting of a caucasian female, non smoker, with adenocarcinoma subtype. Although this percentage is relatively small, it still represents around 12,000 individuals worldwide that express this fusion transcript, presenting a promising biomarker for targeted therapeutics in the treatment of NSCLC disease. Citation Format: Katherine Bell, Dana Gaffney, Gabriela Martinez, Suso Platero, Jayaprakash Karkera. A real-time qPCR approach to detect fusions between the KIF5B and RET genes in non-small cell lung cancer. [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 3174. doi:10.1158/1538-7445.AM2013-3174
NASA and NIH Sign Research Agreement
Authors: T. Reynolds
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article NASA and NIH Sign Research Agreement Get access Tom Reynolds Tom Reynolds Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 16, 19 August 1992, Page 1229, https://doi.org/10.1093/jnci/84.16.1229 Published: 19 August 1992
THU0600 Rheumatologists’ Lack of Understanding and Discounting for Patients with Fibromyalgia and Rheumatoid Arthritis
Authors: M. B. Kool, A. C. Venhuizen, H. van Middendorp, J. W. G. Jacobs, J. W. Bijlsma, R. Geenen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Abstract</h3> Montreal has been the epicentre of the COVID-19 pandemic in Canada with the highest number of deaths in the country. The cumulative numbers of cases and deaths, as of July 25th, 2021, recorded in the 33 areas of Montreal are modelled through a bivariate hierarchical Bayesian model using Poisson distributions. The Poisson means are decomposed in the log scale as the sums of fixed effects and latent effects. The areal median age, the educational level, and the number of beds in long-term care homes are included in the fixed effects. To explore the correlation between cases and deaths inside each area and across areas, three bivariate models are considered for the latent effects, namely an independent one, a conditional autoregressive model, and one that allows for both spatially structured and unstructured sources of variability. As the inclusion of spatial effects change some of the fixed effects, we extend the Spatial+ approach to a Bayesian areal set up to investigate the presence of spatial confounding. Results show that the cumulative totals of cases and deaths are negatively correlated inside and across the boroughs of Montreal. The covariates are not associated in a similar manner for the cases and deaths due to COVID-19. The educational level and the median age seem spatially confounded for the cases and deaths across the boroughs of Montreal.
Abstract 2258: Targeting MACC1: In vivo imaging of distant metastases reduction by MACC1-shRNA in human colon cancer xenografts
Authors: Ulrike S. Stein, Ulrike Sack, Dennis Kobelt, Inken Kelch, Iduna Fichtner, Wolfgang Walther, Peter M. Schlag
Journal: Cancer Research (2010)

Abstract We identified the previously undescribed gene MACC1 by a genome-wide search for differentially expressed genes in human colon cancer tissues, metastases and normal tissues. MACC1 plays an important role for metastasis prediction, in particular for early-stage patients. Based on MACC1 mRNA expression in not (yet) metastasized primary colon cancers of stages I, II and III, our negative and positive prediction of the development of metachronous distant metastases was correct to 80% and 74%, respectively. The 5-year-survival for subjects suffering from colon cancer was 80% for MACC1 low expressors, but 15% for individuals with high MACC1 expression in their primary tumors. Moreover, we found MACC1 to act as an inducer of migration, invasion and proliferation in cell culture, and of distant metastases in several xenograft models. MACC1 transcriptionally regulates the receptor tyrosine kinase Met, that activates the HGF/Met signaling pathway resulting in enhanced cell motility, invasion and metastasis. Here we report the reduction of metastasis by using shRNA targeting the metastasis-inducer MACC1 in vivo. MACC1 high expressing human colon cancer cells were transfected with MACC1-shRNA, Met-shRNA, or control-shRNA harboring plasmids, together with luciferase-containing constructs. Cell clones were intrasplenically transplanted into mice. Tumor growth and metastases formation was demonstrated by in vivo imaging. Signals in MACC1-shRNA/luc mice and in Met-shRNA/luc mice originated exclusively from spleen tumors, not from liver metastases, as demonstrated with the isolated organs by luminescence. By contrast, signals in control-shRNA/luc mice originated from spleen tumors and liver metastases. These findings were confirmed by brightfield images, demonstrating reduced tumor growth and metastases development in MACC1-shRNA/luc and Met-shRNA/luc mice compared to control-shRNA/luc mice. In summary, knock down of MACC1 by MACC1-shRNA led to reduction of tumor growth and metastasis in mice, making MACC1-shRNA a useful tool for metastasis intervention of colon cancer. 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 2258.
1,25(OH)2D3 modulates gene expression involved in cytokine production, proliferation, survival and migration of TH17 cells from patients with rheumatoid arthritis
Authors: Wendy Dankers, Jan Piet van Hamburg, Patrick S Asmawidjaja, Nadine Davelaar, K Wen, Adriana M C Mus, Edgar M Colin, Johannes P T M van Leeuwen, Johanna M W Hazes, Erik Lubberts
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Vitamin D has suppressive effects on autoimmune diseases, such as rheumatoid arthritis (RA). Within these diseases, T-helper-17 (Th17) cells have been implicated to play a crucial role in the development and progression of chronic inflammation. Recently, the authors have found that the active vitamin D compound, 1,25(OH)<sub>2</sub>D<sub>3</sub>, has direct suppressive effects on both human and mouse Th17 cytokine expression and activity. Using gene-expression profiling, the authors aim to identify molecular targets of 1,25(OH)<sub>2</sub>D<sub>3</sub> signaling underlying this suppressive action of 1,25(OH)<sub>2</sub>D<sub>3</sub> in Th17 cells. <h3>Materials and methods</h3> Primary Th17 cells were sorted from peripheral blood of treatment naïve patients with early RA and cultured with or without 1,25(OH)<sub>2</sub>D<sub>3</sub>. From these cultures gene-expression profiles were generated. Expression of genes of interest was confirmed by Q-PCR and/or specific ELISA. <h3>Results</h3> In the presence of 1,25(OH)<sub>2</sub>D<sub>3</sub>, protein expression of Th17 associated cytokines IL-17A and IL-22 was inhibited, while in contrast the anti-inflammatory cytokine IL-10 was induced. These findings were supported by the gene-expression profiles from these cultures. Furthermore, 1,25(OH)<sub>2</sub>D<sub>3</sub> inhibited transcription of the cytokine receptors IL-23R and IL-7R, which are involved in Th17 survival and proliferation. Chemokines CCL20 and CXCL10 were down-regulated and chemokine receptors CCR2, CXCR6, CXCR3 and CCR10 were up-regulated. Importantly, Rorγt, which is critically involved in Th17 differentiation and function and the cell-size regulator and oncogene, c-Myc were down-regulated by 1,25(OH)<sub>2</sub>D<sub>3</sub>. <h3>Conclusions</h3> From these findings, the authors concluded that 1,25(OH)<sub>2</sub>D<sub>3</sub> modulates the expression of genes involved in cytokine production, proliferation, survival and migration of Th17 cells. These data indicate that 1,25(OH)<sub>2</sub>D<sub>3</sub> not only suppresses Th17 cell activity but also regulates migration of these cells to sites of tissue inflammation in RA.