tbuckley/cabot-search huggingface dataset:
Proteomic discovery and verification of biomarkers for colorectal cancer
Authors: Graham Robertson, Lucy Jankova, Xiaomin Song, Matthew McKay, Charles Chan, Pierre Chapuis, Les Bokey, Mark Baker, Stephen Clarke, Mark Molloy
Journal: Clinical Cancer Research (2007)

B30  Colorectal cancer (CRC) is a leading cause of cancer death in the Western world. Identification of diagnostic, prognostic, predictive and monitoring biomarkers will improve outcomes for CRC patients, especially in regard to individual patients response to chemotherapy and susceptibility to develop cachexia. The aim of our study is to discover candidate CRC tissue biomarkers with prognostic value for patient outcome using quantitative mass spectrometry based analysis techniques.  In the project’s “discovery” phase we utilised iTRAQ mass spectrometry to profile 16 CRC patients at various disease stages (Australian Clinico-Pathological stages A3 to D2), comparing carcinoma tissue to normal gut mucosa of the same patient. In addition, iTRAQ was used to make inter-tumour comparisons from the individual patients. iTRAQ routinely enabled quantification of 600 proteins simultaneously in 4 samples per run with up to 1100 proteins quantified in the best experiments. We identified several proteins that were consistently upregulated in CRC tumour tissue including S100 family proteins, various annexins, alpha-defensin 3 and lactate dehydrogenase amongst others. Conversely, consistently down-regulated proteins included liver fatty acid binding protein, selenium binding protein, galectins 3 and 4 and carbonic anhydrase. Interestingly, from a prognostic perspective, many proteins showed varying expression levels that did not appear to correlate with disease stage, and we hypothesize that these may be useful biomarkers to consider with patient outcome in a larger cohort. We are currently developing multiple reaction monitoring (MRM) assays to enable more efficient screening of these tumour samples. The MRM verification assays will assist in selecting robust biomarker candidates to move forward for immunohistochemistry validation using tissue microarrays of large CRC patient cohorts. IHC results will then be correlated with patient outcome statistics to evaluate the utility of the candidate prognostic biomarkers.
Abstract 19190: National Community Chain-of-Survival Initiatives Are Associated With Improved Bystander Cardiopulmonary Resuscitation Rates and Survival for Cardiac Arrests in Taiwan
Authors: Hao-Yang Lin, Wen-Chu Chiang, Ming-Ju Hsieh, Patrick C Ko, Jen-Tang Sun, Shih-Chiang Hung, Chan-Wei Kuo, Yu-Ting Chung, Chih-Hao Lin, Shih-Sheng Chang, Matthew H Ma
Journal: Circulation (2016)

Introduction: Out-of-hospital cardiac arrests (OHCA) remain a medical and public challenges in the communities. Since 2012, several national policy and implementation initiatives, including compres...
PTX1 up-regulates interferon-β in prostate cancer cell line PC-3.
Authors: Simon C. M. Kwok, Xianhong Liu, Patricia Mangel, Ierachmiel Daskal
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5002 

PTX1 is a gene identified by subtractive hybridization on the basis that it is expressed in normal prostate and not in prostatic carcinoma. It is unrelated to the pituitary homeobox protein (Ptx1 or Pitx1) that regulates pituitary hormone gene expression, and its function is currently unknown. Recently, it was found to be identical to Erv41, an endoplasmic reticulum (ER) resident protein involved in protein trafficking between ER and Golgi. Our earlier study showed that ectopic expression of PTX1 in prostate cancer cell line, PC-3, induced cellular senescence. To study its mechanism of action, we transfected PC-3 cells with PTX1 expression construct and determined the genes that were up-regulated by PTX1 using gene expression profiling, reverse transcriptase-PCR, and promoter-luciferase reporter assay. Gene expression microarray analyses showed that interferon-β (IFN-β) and a number of IFN-inducible proteins, among other proteins, were up-regulated by PTX1 expression. Up-regulation of IFN-β by PTX1 was confirmed by RT-PCR and a PTX1 responsive element upstream from the IFN-β gene was identified by promoter-luciferase reporter assay. These results suggest that PTX1 may induce cellular senescence in PC-3 cells via the IFN-β pathway. However, ectopic expression of IFN-β in PC-3 cells did not induce senescence. Since PTX1-induced senescence in PC-3 cells cannot be explained by up-regulation of IFN-β alone, other PTX1-induced protein(s) may also be involved in this process.
Recommendations for Childhood Cancer Screening and Surveillance in DNA Repair Disorders
Authors: Michael F. Walsh, Vivian Y. Chang, Wendy K. Kohlmann, Hamish S. Scott, Christopher Cunniff, Franck Bourdeaut, Jan J. Molenaar, Christopher C. Porter, John T. Sandlund, Sharon E. Plon, Lisa L. Wang, Sharon A. Savage
Journal: Clinical Cancer Research (2017)

Abstract DNA repair syndromes are heterogeneous disorders caused by pathogenic variants in genes encoding proteins key in DNA replication and/or the cellular response to DNA damage. The majority of these syndromes are inherited in an autosomal-recessive manner, but autosomal-dominant and X-linked recessive disorders also exist. The clinical features of patients with DNA repair syndromes are highly varied and dependent on the underlying genetic cause. Notably, all patients have elevated risks of syndrome-associated cancers, and many of these cancers present in childhood. Although it is clear that the risk of cancer is increased, there are limited data defining the true incidence of cancer and almost no evidence-based approaches to cancer surveillance in patients with DNA repair disorders. This article is the product of the October 2016 AACR Childhood Cancer Predisposition Workshop, which brought together experts from around the world to discuss and develop cancer surveillance guidelines for children with cancer-prone disorders. Herein, we focus on the more common of the rare DNA repair disorders: ataxia telangiectasia, Bloom syndrome, Fanconi anemia, dyskeratosis congenita, Nijmegen breakage syndrome, Rothmund–Thomson syndrome, and Xeroderma pigmentosum. Dedicated syndrome registries and a combination of basic science and clinical research have led to important insights into the underlying biology of these disorders. Given the rarity of these disorders, it is recommended that centralized centers of excellence be involved directly or through consultation in caring for patients with heritable DNA repair syndromes. Clin Cancer Res; 23(11); e23–e31. ©2017 AACR. See all articles in the online-only CCR Pediatric Oncology Series.
PTU-197 Diagnosis of gastro-esophageal reflux disease (GERD) and prediction of treatment response to proton pump inhibitors (PPI) by prolonged wireless ph monitoring: a prospective assessment: Abstract PTU-197 Figure 1
Authors: M Fox, R Sweis, E Tucker, J Wright, K Knowles, A Anggiansah, T Wong, D Menne
Journal: Gut (2012)

<h3>Introduction</h3> Increasing duration of pH studies improves consistency of GERD diagnosis but clinical utility of the method is not established. Aim: (1) to identify measurements from prolonged pH studies that discriminate healthy volunteers (HVs) and GERD patients (2) to compare prediction of PPI response from prolonged and standard measurement. <h3>Methods</h3> HVs and patients with reflux symptoms entered a prospective trial. Quality of life (RAND-36) and symptom severity (Eraflux) was assessed on and off PPI and after 2 weeks ×2/day PPI. Endoscopy recorded mucosal disease. Wireless pH system (Bravo®, Given Imaging) measured acid reflux and symptoms up to 4 days. Receiver Operating Curve (ROC) assessed prediction of PPI response. For each prediction 80% of patients were randomly selected as training set, remaining 20% constituted test set. This was repeated 200 times producing average ROC with SEs. Area under Curve (AUC) quantified quality of prediction. <h3>Results</h3> Complete data were available from 25/33 HVs (18F, age 20–56) and 70/108 patients (31F, age 18–77), &gt;320 days in total. Oesophagitis was present in 9 HVs (32%: Grade A) and 26 patients (33%: Grade A=19, B=2, C-D=5). Acid exposure time was elevated (AET &gt;5.6%) in 3 (12%) HVs and 35 (50%) patients. Eraflux off-PPI was &gt;25 (consistent with GERD) in 60/63 patients and fell by mean 7 (95% CI 5 to 10) on PPI, 46% reported positive response (&gt;3 fall). Diagnosis: Endoscopy, AET and reflux-symptom association analysis (Symptom Index (SI)) did not discriminate health/disease; but reflux-associated symptoms/day (nRS/Day) covered different ranges for HV and patients. Logistic regression with bootstrap validation identified that ≥3 RS/day corresponded to ∼50% probability that participant was a patient. PPI response: Clinical parameters and AET did not predict outcome. SI (9.2 vs 30.2, p=0.0023) and nRS/Day (1 vs 2.6, p=0.012) were higher in responders. RAND-36 scores for poor physical role and pain were higher in non-responders (p∼0.1). SI ROC had an AUC of 0.73 (CI 0.51 to 0.92). SI &gt;25 was the optimal cut-off for identifying PPI responders (Abstract PTU-197 figure 1). Prediction quality from 24 h studies was lower (AUC 0.69) and CIs for all parameters were wider with lower CI. <h3>Conclusion</h3> Diagnostic consistency for all parameters increases with study duration. A simple count of nRS/Day best discriminates HVs from patients on pH studies. SI &gt;25 provides single best prediction of PPI response; but quality of predictions was modest in this population with low PPI response. <h3>Competing interests</h3> None declared.
Abstract 21: Diabetic Ketoacidosis Compromises Cardiac Mitochondrial Quality Control in Humans
Authors: Satoru Kobayashi, M.G.F. Gilliland, William H Hoffman, Alice O’Connor, Qiangrong Liang
Journal: Circulation Research (2015)

Mitochondrial injury plays a key role in the pathogenesis of diabetic cardiomyopathy, a risk factor for heart failure in diabetic populations. Dysfunctional mitochondria are eliminated through several coordinated mitochondrial quality control mechanisms including the autophagy-lysosome degradation pathway, a process termed mitophagy. Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of type 1 diabetes. We have shown that adolescents and young adults with uncomplicated DKA mount a robust systemic inflammatory response which is associated with diastolic cardiac abnormality. However, it remains unknown if cardiac abnormality in patients with DKA is correlated with altered mitochondrial quality control processes. In the present study, using immunofluorescent labeling and confocal microscopic imaging, we examined a series of proteins involved in autophagy, mitophagy and mitochondrial dynamics in paraffin-embedded autopsy heart tissues from young people without or with fatal DKA. We found that the expression levels of beclin 1, microtubule-associated protein light chain 3 (LC3) and lysosome-associated membrane protein (LAMP) 1/2 are not changed, but that of p62 is increased in the heart of DKA patients, suggesting a decreased autophagy. Also, the expression levels and localization of Pink1, parkin and Rab9, three potential regulators of mitophagy, are markedly changed, indicating an altered mitophagy in the DKA heart. In addition, mitochondrial fusion and fission proteins (Mitofusin 2, Opa1, Drp1 and Fis1) are all altered to varying degrees in the DKA heart, which is accompanied by increased mitochondrial fragmentation, oxidative injury and apoptosis (TUNEL positive cells). Together, these findings demonstrate that the mitochondrial quality control mechanisms are not operating normally in the heart of patients with DKA. Therefore, therapeutic strategies that aim to improve the efficiency of the mitochondrial quality control may have the potential to reduce diabetic cardiac injury and heart failure in young type 1 diabetic patients.
Loss of transcriptional activation of the potassium channel Kir5.1 by HNF1β drives autosomal dominant tubulointerstitial kidney disease
Authors: Andreas Kompatscher, Jeroen H.F. de Baaij, Karam Aboudehen, Anke P.W.M. Hoefnagels, Peter Igarashi, René J.M. Bindels, Gertjan J.C. Veenstra, Joost G.J. Hoenderop
Journal: Kidney International (2017)
Pain, sleep disturbance, and fatigue symptom cluster in patients suffering from chronic chemotherapy-induced neuropathic pain (CINP).
Authors: Jennifer S. Gewandter, Charles E Heckler, Katie Devine, Supriya Gupta Mohile, Oxana Palesh, Joseph Roscoe, Gary R. Morrow, Martin Joseph Bury, Andrew Jacobs
Journal: Journal of Clinical Oncology (2012)

9113 Background: Various symptom cluster combinations of pain, fatigue, sleep disturbance (SD), and depression have been identified in cancer patients. The presence of symptom clusters has not been assessed in patients with persistent CINP. This exploratory analysis aimed to determine which symptoms statistically clustered with pain in cancer survivors with CINP. Methods: The University of Rochester Cancer Center Community Clinical Oncology Program recruited 461 patients with CINP &gt; 4 (on a 0-10 scale) who had completed chemotherapy (median 7 months ago) for a pain intervention trial. At baseline, groups of highly associated symptoms that included pain were identified empirically using factor and cluster analyses of the 11 symptoms in the University of Rochester Symptom Inventory plus the Hospital Anxiety and Depression Scale (HADS) scores. To investigate if associated symptoms track together over time, multiple linear regression (MLR) analysis was performed using changes in symptom severity between baseline and week 6, controlling for gender, age, education, race, and marital status. Results: Subjects were 88% white and 71% female, and on average 61 years old. Mean (standard deviation) baseline pain, fatigue, and SD were 5.7 (2.8), 5.0 (2.7), and 4.2 (3.1), respectively; 26% of subjects had borderline or abnormal HADS scores. Factor analysis identified 3 factors that accounted for 88% of the variance. One factor included pain, fatigue, SD, but not HADS, and accounted for 37% of the variance. Variable clustering also identified pain, SD, and fatigue as 1 symptom cluster. Changes in severity of SD and fatigue (p &lt; 0.0001), but not HADS, were associated with changes in pain (adjusted R 2 = 0.168) in MLR analysis. Conclusions: Pain, fatigue, and SD were identified as a symptom cluster by factor and cluster analyses, and were found to track together over time by MLR. Since these data suggest that pain is associated with sleep quality and fatigue in patients with persistent CINP, targeting one of these symptoms may lead to reductions in the others. Future research should investigate interventions that target pain, fatigue, and SD concurrently in cancer survivors suffering from CINP.
Cardiac outcomes of raltitrexed in the treatment of colorectal cancer patients with 5-fluorouracil (5-FU) cardiotoxicity.
Authors: Aryan Firouzbakht, Daniel John Renouf, Leo Chen, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2013)

e14607 Background: Both 5-FU and raltitrexed are thymidylate synthase inhibitors, but the latter has a toxicity profile that is distinct from 5-FU. Therefore, it is commonly used as an alternative to 5-FU in the treatment of colorectal cancer patients who have a history of cardiac problems or prior 5-FU cardiotoxicity. To date, the population-based risk of cardiac effects from raltitrexed is uncertain. Our aim was to characterize the patterns of treatment and outcomes of patients receiving raltitrexed-based chemotherapy. Methods: We conducted a retrospective study of all patients diagnosed with colorectal cancer from 1988 to 2012, evaluated at 1 of 5 regional cancer centers in British Columbia, Canada and treated with raltitrexed at any point during their disease. At the institutions in our province, raltitrexed use is limited to those in whom 5-FU is contraindicated. Using chi-squared tests and logistic regression analyses, we evaluated the associations between use of raltitrexed and various cardiovascular events, such as angina, myocardial infarction, hypertension and arrhythmias, as well as other toxicity outcomes, including nausea, vomiting and diarrhea. Results: A total of 186 patients were included: median age was 63 years (IQR 55-70), 97 (52%) were men, and 21 (11%) experienced at least one cardiovascular outcome. Only 4 (2%) patients had a documented cardiac history prior to receipt of any systemic therapy. Among the 21 cases of cardiovascular events, 10 reported angina, 1 suffered a myocardial infarction, 6 had hypertension, and 6 experienced arrhythmias. A significant number of patients also presented with other general toxicities: 25 (13%) reported fever, 11 (6%) suffered mucositis, 75 (40%) had nausea, and 51 (27%) experienced diarrhea. On regression analyses, patients with a previous history of coronary artery disease had a higher risk of cardiovascular events than those without (50 vs 11%, p=0.01). Exposure to 5-FU before raltitrexed did not increase cardiovascular outcomes (p=0.81). Conclusions: Raltitrexed is associated with a low risk of cardiovascular events, but its use should be monitored closely in those with prior coronary artery disease.
Cancer Screening Recommendations for Individuals with Li-Fraumeni Syndrome
Authors: Christian P. Kratz, Maria Isabel Achatz, Laurence Brugières, Thierry Frebourg, Judy E. Garber, Mary-Louise C. Greer, Jordan R. Hansford, Katherine A. Janeway, Wendy K. Kohlmann, Rose McGee, Charles G. Mullighan, Kenan Onel, Kristian W. Pajtler, Stefan M. Pfister, Sharon A. Savage, Joshua D. Schiffman, Katherine A. Schneider, Louise C. Strong, D. Gareth R. Evans, Jonathan D. Wasserman, Anita Villani, David Malkin
Journal: Clinical Cancer Research (2017)

Abstract Li-Fraumeni syndrome (LFS) is an autosomal dominantly inherited condition caused by germline mutations of the TP53 tumor suppressor gene encoding p53, a transcription factor triggered as a protective cellular mechanism against different stressors. Loss of p53 function renders affected individuals highly susceptible to a broad range of solid and hematologic cancers. It has recently become evident that children and adults with LFS benefit from intensive surveillance aimed at early tumor detection. In October 2016, the American Association for Cancer Research held a meeting of international LFS experts to evaluate the current knowledge on LFS and propose consensus surveillance recommendations. Herein, we briefly summarize clinical and genetic aspects of this aggressive cancer predisposition syndrome. In addition, the expert panel concludes that there are sufficient existing data to recommend that all patients with LFS be offered cancer surveillance as soon as the clinical or molecular LFS diagnosis is established. Specifically, the panel recommends adoption of a modified version of the “Toronto protocol” that includes a combination of physical exams, blood tests, and imaging. The panel also recommends that further research be promoted to explore the feasibility and effectiveness of these risk-adapted surveillance and cancer prevention strategies while addressing the psychosocial needs of individuals and families with LFS. Clin Cancer Res; 23(11); e38–e45. ©2017 AACR. See all articles in the online-only CCR Pediatric Oncology Series.
The upper airway in pregnancy and pre-eclampsia
Authors: B Izci, Renata Riha, Sarah Martin, M Vennelle, WA Liston, K Dundas, Andrew Calder, Neil Douglas
Journal: Thorax (2002)

Snoring is common in pregnancy, and snoring pregnant women have increased rates of pre-eclampsia. Patients with pre-eclampsia show upper airway narrowing during sleep. The present study aimed to compare upper airway dimensions in pregnant and nonpregnant women and in patients with pre-eclampsia. A total of 50 women in the third trimester of pregnancy and 37 women with pre-eclampsia were recruited consecutively from the antenatal service and matched with 50 nonpregnant women. Upper airway dimensions were measured using acoustic reflection. Comparisons were made by analysis of variance and Student-Newman-Keuls tests. Snoring was reported by 14% of nonpregnant women, 28% of pregnant women, and 75% of pre-eclamptic women (p   0.3). The study showed that women with pre-eclampsia have upper airway narrowing in both upright and supine postures. These changes could contribute to the upper airway resistance episodes during sleep in patients with pre-eclampsia, which may further increase their blood pressure.
Lymphomatoid papulosis associated with chronic lymphocytic leukaemia/small lymphocytic lymphoma: three cases
Authors: H. Adamski, S. Ingen‐Housz‐Oro, L. Machet, A.C. Carriou, C. Ram‐Wolff, N. Ortonne, F. Le Gall, A. Durlach, J. Dupuis, C. Dauriac, A. Dupuy, F. Grange, M. Bagot
Journal: British Journal of Dermatology (2017)

Lymphomatoid papulosis (LyP) is considered as an indolent CD30+ lymphoproliferative cutaneous disorder. 1,2 Nevertheless, 10%–20% up to 50% of patients with LyP have coexistent lymphoma. 1, 3–7 The most frequently associated malignancies are mycosis fungoides, primary cutaneous anaplastic large cell lymphoma, or Hodgkin's disease. There are only seven reported cases of an association between LyP and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). 5, 7-9 Herein, we report and analyze three new cases.

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A novel endpoint for exacerbations in asthma to accelerate clinical development: a post-hoc analysis of randomised controlled trials
Authors: Anne L Fuhlbrigge, Thomas Bengtsson, Stefan Peterson, Alexandra Jauhiainen, Göran Eriksson, Carla A Da Silva, Anthony Johnson, Tariq Sethi, Nicholas Locantore, Ruth Tal-Singer, Malin Fagerås
Journal: The Lancet Respiratory Medicine (2017)
Lysosomal Degradation Is Required for Sustained Phagocytosis of Bacteria by Macrophages
Authors: Ching-On Wong, Steven Gregory, Hongxiang Hu, Yufang Chao, Victoria E. Sepúlveda, Yuchun He, David Li-Kroeger, William E. Goldman, Hugo J. Bellen, Kartik Venkatachalam
Journal: Cell Host & Microbe (2017)
Revisiting the diet-heart hypothesis: critical appraisal of the Minnesota Coronary Experiment
Authors: Tumas Beinortas, Kamal R Mahtani, David Nunan
Journal: BMJ (2017)

Several articles have concluded that associations between high cholesterol and premature death are lacking and advocate revision of current guidance advising low consumption (<10%) of saturated fat.123 Ramsden and colleagues recovered 45 year old data from the Minnesota Coronary Experiment, a randomised controlled trial conducted in state psychiatric hospitals and nursing homes in Minnesota, USA, and reassessed the effect of a diet rich in linoleic acid on serum cholesterol and mortality.3 The authors found that the diet lowered total cholesterol but did not reduce the risk of premature mortality and might even have increased it.

To change current consensus, however, these claims should be based on valid and reliable evidence. We performed a critical appraisal of the Minnesota Coronary Experiment using the methods and data provided in three publicly available descriptions of this trial: two peer reviewed papers (by Ramsden and colleagues3 and Frantz et al4) and a thesis by Broste,5 on which the primary data in the analysis by Ramsden and colleagues were based.

We used the Cochrane risk of bias tool to assess the internal validity of data from the original experiment (table 1⇓).6

View this table:

Table 1 
Cochrane risk of bias table



We …