tbuckley/cabot-search huggingface dataset:
PTH-004 Colorectal cancer incidence and trend among UK South Asians: a 20-year study: Abstract PTH-004
Authors: S Hebbar, W J Fuggle, A M Veitch
Journal: Gut (2010)

<h3>Introduction</h3> The incidence of colorectal cancer is lower in South Asians compared to the British white population. There have been very few large studies looking into the incidence of colorectal cancer in UK South Asians. Wolverhampton has a population of 236 585 (13.6% South Asians) and we aimed to determine the incidence and trend of colorectal cancer in the South Asian subgroup over a 20-year period. <h3>Methods</h3> All patients of South Asian origin and cases of colonic and rectal tumours from 1989 to 2008 were identified from the Histopathology department database. Age sex standardised incidences were calculated using 1991 and 2001 census data. <h3>Results</h3> The median age-sex standardised incidence of colonic cancer from 1989 to 2008 was 3.09/100 000/year in South Asians compared to 45.11/100 000/year in non-South Asians (77.79% white population) (p&lt;0.0001). For rectal cancers, the median age-sex standardised incidence in South Asians was 0/100 000/year compared to 28.70/100 000/year in non-South Asians (p&lt;0.0001). In non-South Asians, there was trend towards an increased colonic cancer (p=0.03), but not in South Asians. Rectal cancer incidence is increasing in South Asians (p=0.0004), but there is no increased trend in non-South Asians. <h3>Conclusion</h3> There is significantly reduced incidence of colonic and rectal cancers in UK South Asians compared to non-South Asians (majority being white Caucasians). However, a trend towards increasing rectal cancer in South Asians and increasing colonic cancer in non-South Asians has been noted.
Routinely collected data may usefully supplement randomised controlled data on treatment effects for mortality
Authors: David Pérol, Mathieu Robain, Suzette Delaloge, Christian Cailliot
Journal: BMJ (2016)

Hemkens and colleagues investigated the effects of treatment on mortality in routinely collected data and subsequent randomised trials.1 They found that observational studies with routinely collected data substantially overestimated the effects of treatment, despite the use of propensity scores to address confounding bias.

This overestimation might, however, be partially due to the selection of studies. In randomised controlled trials, a pitfall is choosing a control that reflects the realities of medical care, and a major …
Abstract 1703: A 3D tissue culture-based utra-high content screening platform that uses phenotypic profiling of cancer tissues to identify selective inhibitors of receptor tyrosine kinases
Authors: Leo S. Price, Tijmen Booij, Maarten Klop
Journal: Cancer Research (2015)

Abstract 3D tissue cultures provide a more physiologically relevant context for the screening of compounds, compared to 2D cell cultures. Cells cultured in 3D hydrogels also show complex phenotypes, increasing the scope for phenotypic profiling. Here we describe a high-content screening platform that uses human micro-tissues cultured in 3D in standard 384 well assay plates to study the activity of biologically active molecules. Image analysis tools were developed to process 3D image data to measure 854 phenotype-derived parameters. Multiparametric analysis was used to evaluate the effect of compounds on tissue morphology. We applied this screening platform to measure the activity and selectivity of inhibitors of the c-Met and EGF receptor (EGFR) tyrosine kinases in 3D cultured prostate carcinoma cells. c-Met and EGFR activity was quantified based on the invasive phenotypic profiles induced by their respective ligands, HGF and EGF, which were added in parallel assays. c-Met and EGFR inhibitors generally showed the expected inhibitory profile equivalent to that obtained in the absence of cognate ligand. However, one phase-III c-Met inhibitor, displayed an unexpected phenotypic profile characterised by potent inhibition of tumour cell invasion and off-target effects consistent with a previously reported polypharmacology of this compound. The screening method was applied to a novel collection of 70 bi-specific compounds designed to target both c-Met and EGFR. Compounds were identified that induced phenotypic profiles indicative of selective inhibition of either c-Met, EGFR or both targets. In conclusion, this poster describes a fully scalable high-content screening platform that uses phenotypic profiling to evaluate receptor tyrosine kinase inhibitor selectivity and activity in a physiologically relevant setting. Citation Format: Leo S. Price, Tijmen Booij, Maarten Klop. A 3D tissue culture-based utra-high content screening platform that uses phenotypic profiling of cancer tissues to identify selective inhibitors of receptor tyrosine kinases. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1703. doi:10.1158/1538-7445.AM2015-1703
Establishment of Carrier Detection and Prenatal Diagnosis Service for Hemophilia in a Developing Country: Experience From International Hemophilia Training Center-Bangkok.
Authors: Ampaiwan Chuansumrit, Nongnuch Sirachainan, Pantep Angchaisuksiri, Werasak Sasanakul, Pakawan Wongwerawattanakoon, Praguywan Kadegasem, Patama Promsonthi, Hathaiwut Lamthean
Journal: Blood (2012)
Stabilization of Myelodysplastic Syndromes (MDS) Following Hypomethylating Agent (HMAs) Failure Using the Immune Checkpoint Inhibitor Ipilimumab: A Phase I Trial
Authors: Amer M. Zeidan, Joshua F. Zeidner, Amy Duffield, Hanna A. Knaus, Anna Ferguson, Katherine Sheldon, Amy E. DeZern, Ivana Gojo, Steven D. Gore, Howard Streicher, Leo Luznik, B. Douglas Smith
Journal: Blood (2015)
Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma: The ORCHARRD Study
Authors: Gustaaf W. van Imhoff, Andrew McMillan, Matthew J. Matasar, John Radford, Kirit M. Ardeshna, Kazimierz Kuliczkowski, WonSeog Kim, Xiaonan Hong, Jette Soenderskov Goerloev, Andrew Davies, María Dolores Caballero Barrigón, Michinori Ogura, Sirpa Leppä, Michael Fennessy, Qiming Liao, Bronno van der Holt, Steen Lisby, Anton Hagenbeek
Journal: Journal of Clinical Oncology (2017)

Purpose We compared the efficacy of ofatumumab (O) versus rituximab (R) in combination with cisplatin, cytarabine, and dexamethasone (DHAP) salvage treatment, followed by autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Patients and Methods Patients with CD20+ DLBCL age ≥ 18 years who had experienced their first relapse or who were refractory to first-line R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)-like treatment were randomly assigned between three cycles of R-DHAP or O-DHAP. Either O 1,000 mg or R 375 mg/m2 was administered for a total of four infusions (days 1 and 8 of cycle 1; day 1 of cycles 2 and 3 of DHAP). Patients who experienced a response after two cycles of treatment received the third cycle, followed by high-dose therapy and ASCT. Primary end point was progression-free survival (PFS), with failure to achieve a response after cycle 2 included as an event. Results Between March 2010 and December 2013, 447 patients were randomly assigned. Median age was 57 years (range, 18 to 83 years); 17% were age ≥ 65 years; 63% had stage III and IV disease; 71% did not achieve complete response (CR) or experience response for < 1 year on first-line R-CHOP. Response rate for O-DHAP was 38% (CR, 15%) versus 42% (CR, 22%) for R-DHAP. ASCT on protocol was completed by 74 patients (33%) in the O arm and 83 patients (37%) in the R arm. PFS, event-free survival, and overall survival were not significantly different between O-DHAP versus R-DHAP: PFS at 2 years was 24% versus 26% (hazard ratio [HR], 1.12; 95% CI, 0.89 to 1.42; P = .33); event-free survival at 2 years was 16% versus 18% (HR, 1.10; P = .35); and overall survival at 2 years was 41% versus 38% (HR, 0.90; P = .38). Positron emission tomography negativity before ASCT was highly predictive for superior outcome. Conclusion No difference in efficacy was found between O-DHAP and R-DHAP as salvage treatment of relapsed or refractory DLBCL.
Abstract 3711: The decrease in global cancer mortality
Authors: Paolo Boffetta
Journal: Cancer Research (2015)

Abstract Background: A decrease in cancer mortality has been reported in the United States, Europe and other developed regions of the world during the last two decades. Whether similar trends apply to less-developed countries - and globally - is unclear. Methods: We aimed to describe the global patterns of cancer mortality by conducting a systematic analysis of the WHO mortality database for countries for which high- or intermediate-quality data on death certifications are available for a period of at least 10 years (typically 2003-2012). We included 60 countries in the analysis, and calculated age-specific and age-adjusted mortality rates. Results: A decrease in overall cancer mortality of approximately 1% per year was present in both developed and less-developed regions, and in both genders. For cancers of the esophagus, stomach, larynx and thyroid, the average decrease in global mortality rate was greater than 2% per year. Individual cancers which showed an increase in mortality rates on a global scale are limited to pancreas and brain (both genders), lung (women), melanoma and kidney (men) and endometrium. Conclusions: Reasons for the decrease in cancer mortality in less-developed countries may include decrease in cancer incidence, shift in the stage distribution, shift in the proportional contribution of individual cancers, and improved therapy. The increase in the number of cancer deaths, globally and in less-developed countries, is primarily driven by changes in the demographic structure of the population, but the risk of the individual of dying from cancer appears to decrease in all countries with reliable data. Cancers with increasing mortality rates should be given priority for research. Citation Format: Paolo Boffetta. The decrease in global cancer mortality. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3711. doi:10.1158/1538-7445.AM2015-3711
A Novel Method Using Extracted Human Neutrophil Antigens From HNA Gene-Transfected Cell Lines for Detection of Antibodies Against Human Neutrophil Antigens
Authors: Rie Onodera, Kazuhiro Nakamura, Kikuyo Taniguchi, Emi Kurita, Asako Hiraoka, Kaduta Yasui, Nobuki Matsuyama, Fumiya Hirayama, Masao Kobayashi
Journal: Blood (2012)
Cost-effectiveness of intraoperative radiation therapy for breast conservation.
Authors: M. Alvarado, E. Ozanne, A. Mohan, L. Esserman
Journal: Journal of Clinical Oncology (2011)

6081 Background: Results from the TARGIT trial at 4 years median follow-up for women >50 yrs with node negative tumors show equivalent outcomes in local recurrence, however, it has been argued that long-term follow-up is required before adoption. Modeling can inform this decision by evaluating the tradeoffs between costs, adverse outcomes, and quality of life. Methods: Using a Markov model, a cost-utility analysis compared lumpectomy with Intraoperative Radiation Therapy (IORT) versus standard External Beam Radiation Therapy (EBRT). Local recurrence rates (LRR) were based on results from the TARGIT trial. For the base case, LRR for EBRT was assumed to progress linearly to an expected 2.4% at 10 years. LRR for IORT was set to 5.5%, resulting in a more than 3-fold increase from the observed, published 4-year rate. Utilities were derived from the literature. Baseline utility for no disease after RT was set to .92 for IORT and EBRT. Medicare CPT codes were used for direct costs and non-medical costs were ascertained. Quality adjusted life years (QALY), costs, and the incremental cost-effectiveness ratio (ICER) were calculated over 10 years. Results: In the baseline analysis, IORT is less costly than EBRT, but less effective in terms of QALYs. The use of EBRT led to an increase in .011 QALYS (<5 days) but an incremental increase in $2840, resulting in an ICER of more than $250,000 per QALY. For the ICER to decrease to $81,000/QALY the observed LRR for IORT must increase 8.8 fold from the 4-year rate. Sensitivity analyses demonstrated the ICER to be affected most by the costs of radiation treatment, LRR, and utility measures for post-lumpectomy IORT and EBRT. If the utility for IORT were increased by .002 (out of 1.000), IORT becomes cost-saving, offering greater QALY’s for less cost. Conclusions: The ICER for EBRT is much higher than the accepted willingness-to-pay threshold of $75,000 on the conservative assumption that the utility for no disease after RT is equal for both IORT and EBRT, and that LRR for IORT would more than triple at 10 years. Only a minute improvement in utility for IORT—which is likely since it is a single dose given at time of surgery and avoids multiple visits for EBRT—makes the IORT treatment less expensive and more effective.
Intermediate-Risk Acute Lymphoblastic Leukemia (ALL) Patients with and without Relapse Differentially Depend on Survival Signals From Microenvironment
Authors: Peter Rhein, Rita Mitlohner, Renate Kirschner-Schwabe, Christian Hagemeier, Gunnar Cario, Martin Stanulla, Martin Schrappe, Iduna Fichtner, Richard Ratei, Wolf-Dieter Ludwig, Leonid Karawajew
Journal: Blood (2011)
Abstract POSTER-BIOL-1335: Threonyl-tRNA synthetase overexpression correlates with angiogenesis and progression of human ovarian cancer
Authors: Theresa L. Wellman, Midori Eckenstein, Cheung Wong, Mercedes Rincon, Takamaru Ashikaga, Sharon L. Mount, Christopher S. Francklyn, Karen M. Lounsbury
Journal: Clinical Cancer Research (2015)

Abstract Ovarian tumors create a dynamic microenvironment that promotes angiogenesis and reduces immune responses. There is growing evidence that tRNA synthetases have a role in cell signaling separate from their function in protein synthesis. Our research has revealed that threonyl-tRNA synthetase (TARS) has an extracellular angiogenic activity. Exploration of protein and mRNA databases further showed a connection between TARS expression and ovarian cancer. The objective of this study was to test the hypothesis that TARS is secreted by ovarian cancer cells and that its expression in clinical samples correlates with angiogenic markers and ovarian cancer progression. TARS secretion by SKOV3 human ovarian cancer cells was induced by hypoxia or tumor necrosis factor-α (TNF-α) as detected by ELISA and Western blot of culture media (p&amp;lt;0.001). For the clinical study, TARS, vascular endothelial growth factor (VEGF) and PECAM were assessed by immunohistochemistry in serial sections of paraffin embedded ovarian tissues from 70 patients diagnosed with epithelial ovarian cancer and 12 control patients. Serum samples from 31 tissue-matched patients were analyzed by ELISA for TARS, CA125, and tumor necrosis factor-α (TNF-α). There was a strong association between the tumor expression of TARS and advancing stage of epithelial ovarian cancer (p&amp;lt;0.001). TARS expression and localization were also correlated with VEGF (p&amp;lt;0.001). A significant proportion of samples included heavy TARS staining of infiltrating leukocytes which also correlated with stage (p=0.017). Patient serum TARS was related to tumor TARS and angiogenic markers, but did not achieve significance with respect to stage. Multivariate Cox proportional hazard models revealed a surprising inverse relationship between TARS expression and mortality risk in late stage disease (p=0.062). Together these results show that TARS is secreted in response to cell stress and that its expression is increased in epithelial ovarian cancer according to stage and angiogenic progression. These findings and the association of TARS with disease survival provide clinical validation that TARS is associated with angiogenesis in ovarian cancer. These results encourage further study of TARS as a regulator of the tumor microenvironment and possible target for diagnosis and/or treatment in ovarian cancer. Citation Format: Theresa L. Wellman, Midori Eckenstein, Cheung Wong, Mercedes Rincon, Takamaru Ashikaga, Sharon L. Mount, Christopher S. Francklyn, Karen M. Lounsbury. Threonyl-tRNA synthetase overexpression correlates with angiogenesis and progression of human ovarian cancer [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-BIOL-1335.
Gotta catch’em all! Pokémon GO and physical activity among young adults: difference in differences study
Authors: Katherine B Howe, Christian Suharlim, Peter Ueda, Daniel Howe, Ichiro Kawachi, Eric B Rimm
Journal: BMJ (2016)

To estimate the effect of playing Pokémon GO on the number of steps taken daily up to six weeks after installation of the game. Cohort study using online survey data. Survey participants of Amazon Mechanical Turk (n=1182) residing in the United States, aged 18 to 35 years and using iPhone 6 series smartphones. Number of daily steps taken each of the four weeks before and six weeks after installation of Pokémon GO, automatically recorded in the "Health" application of the iPhone 6 series smartphones and reported by the participants. A difference in difference regression model was used to estimate the change in daily steps in players of Pokémon GO compared with non-players. 560 (47.4%) of the survey participants reported playing Pokémon GO and walked on average 4256 steps (SD 2697) each day in the four weeks before installation of the game. The difference in difference analysis showed that the daily average steps for Pokémon GO players during the first week of installation increased by 955 additional steps (95% confidence interval 697 to 1213), and then this increase gradually attenuated over the subsequent five weeks. By the sixth week after installation, the number of daily steps had gone back to pre-installation levels. No significant effect modification of Pokémon GO was found by sex, age, race group, bodyweight status, urbanity, or walkability of the area of residence. Pokémon GO was associated with an increase in the daily number of steps after installation of the game. The association was, however, moderate and no longer observed after six weeks.
JAK2V617F Mutation Selectively Exerts the STAT3 Pathway for Enhancing a Neutrophil Activation Marker.
Authors: Seido Oku, Katsuto Takenaka, Kotaro Shide, Takashi Kumano, Kikushige Yoshikane, Takuro Kuriyama, Shingo Urata, Chika Iwamoto, Takuji Yamauchi, Haruko Shimoda, Toshihiro Miyamoto, Kazuya Shimoda, Koichi Akashi
Journal: Blood (2009)
Abstract 13426: Suppression of Epsin Expression Rescues Diabetes Triggered Impaired Lymphatic Function by Limiting VEGFR3 Degradation
Authors: Hong Chen
Journal: Circulation (2016)

Rationale: Impaired lymphatic circulation causes lymphedema and contributes to pathological conditions, such as diabetes. VEGF-C/VEGFR3 signaling is a crucial regulator of lymphatic development; however, whether manipulation in signaling improves lymphatic circulation under pathological conditions is unclear. Objective: We recently uncovered that loss of epsins in lymphatic endothelial cells (LECs) caused heightened VEGFR3 signaling and delayed lymphatic formation during development. Herein, we investigated whether elevated VEGFR3 signaling caused by epsin loss is critical for pathological lymphatic circulation in adult mice. Methods and Results: Using innovative near-infrared lymphatic imaging, and tail lymphedema models, we demonstrated that epsin loss accelerated recovery from diabetic secondary lymphedema. High-glucose-induced oxidative stress results in reduced VEGFR3 signaling, impaired lymphangiogenesis and delayed recovery from diabetic secondary lymphedema. The dual luciferase reporter assay system and ChIP assay showed in STZ-induced diabetic mice drove Src- and AP-1- mediated upregulation of epsin expression. Epsin deletion in primary LECs caused heightened VEGFR3 signaling and promoted in vitro lymphangiogenesis by preventing VEGFR3 downregulation. Mechanistically, we showed that by protecting cell surface VEGFR3 from degradation, lack of epsin rescued high-glucose-induced VEGFR3 loss, defective lymphangiogenesis in vitro , and ameliorated STZ-induced diabetic secondary lymphedema in vivo . Conclusions: Epsins essentially regulate lymphatic circulation through the modulation of VEGFR3 signaling. In STZ- induced diabetic mice, Src induces epsin expression via transcription factor AP-1. Epsin depletion ameliorated diabetic secondary lymphedema under hyperglycemic condition by protecting VEGFR3 from oxidative stress-induced degradation. Our findings highlight the therapeutic potential for targeted inhibition of epsins within the lymphatic endothelium as a treatment for secondary lymphedema caused by uncontrolled diabetes. Key Words: Epsin, VEGFR3, Lymphatics, Secondary Lymphedema, Diabetes
Phase III Evaluation of Once-Daily, Oral Therapy with ICL670 (Exjade®) Versus Deferoxamine in Patients with β-Thalassemia and Transfusional Hemosiderosis.
Authors: Maria Cappellini, Mohamed Bejaoui, Silverio Perrotta, Leyla Agaoglu, Antonios Kattamis, Patricia Giardina, Gritta Janka-Schaub, Herbert Opitz, Catherine Ressayre-Djaffer, Daniele Alberti
Journal: Blood (2004)
Phase I Trial of High-Dose Clofarabine and Busulfan as a Myeloablative Regimen Prior to Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Relapsed or Refractory Acute Leukemia.
Authors: Sherif Farag, Lisa L Wood, Jennifer E. Schwartz, Shivani Srivastava, Robert P. Nelson, Michael Robertson, Rafat Abonour, Hamid Sayar, Larry D. Cripe
Journal: Blood (2009)
MRI helps diagnose fetal brain abnormality after 20 week scan, study finds
Authors: Susan Mayor
Journal: BMJ (2016)

Carrying out a magnetic resonance imaging (MRI) scan helps to diagnose fetal brain abnormalities more accurately in women whose 20 week pregnancy ultrasound scan has shown a potential problem, a prospective study has found.1

The study included 570 women aged over 16 whose ultrasound scan at around 20 weeks of pregnancy suggested a brain abnormality in their developing fetus. This is relatively common, occurring in around three in 1000 pregnancies.

The women in the study had an in utero MRI scan within 14 …