tbuckley/cabot-search huggingface dataset:
Tumor associated macrophages enhance the establishment and growth of prostate cancer bone metastasis
Authors: Sun Jin Kim, Erik Busby, Jang Seong Kim, Marva Kaya, Junqin He, Fahao Zhang, Dominic Fan, Isaiah Fidler
Journal: Cancer Research (2007)

2458    Objectives:  The progressive growth of androgen-independent metastases is a major cause of death from prostate cancer. The expression of interleukin-6 (IL-6) by tumor cells correlates with tumor cell proliferation and angiogenesis. Since prostate cancer bone metastases are infiltrated by tumor-associated macrophages (TAM) that can produce tumor necrosis factor (TNF-α) which up-regulates expression of IL-6, we determined whether TAM can facilitate the establishment and growth of human prostate cancer bone metastasis in nude mice.     Materials and Methods:  Human prostate cancer, PC-3MM2 cells were transfected with IL-6 small inhibitory RNA (SiRNA) in a Lenti virus or control virus (mock transfected). The level of IL-6 produced by tumor cells and cells treated with IL-1 or TNF-α was determined by ELISA. In the first set of  in vivo  experiments, parental, SiRNA or mock transfected cells (2x10 5 )were injected into the tibia of male nude mice. Four weeks later, the mice were killed and necropsied. Tumor incidence and size, and incidence of lymph node metastasis were recorded. Bone structure was examined by digital radiography. The number of infiltrating tumor-associated macrophages (TAM) was determined by immunohistochemical staining for F4/80. In the second set of  in vivo  experiments, we depleted macrophages in recipient mice by serial intraperitoneal injections of clodronate-liposomes prior to the injection of PC-3MM2 parental, SiRNA and mock transfected cells into the tibia of nude mice. The mice were killed four weeks later and the data were recorded as described above.   Results:  Parental and mock transfected PC-3MM2 cells secreted IL-6. Exogenous TNF-α, but not IL-1, increased the production of IL-6 (p   Conclusion:  The results suggest that IL-6 secreted by prostate cancer cells is chemotactic to TAM and TNF-α produced by TAM can up-regulate the production of IL-6 by tumor cells. Since the increased level of IL-6 contributes to tumor cell proliferation and angiogenesis, the data recommend that TAM and IL-6 may be attractive targets for therapy of prostate cancer bone metastasis.
Network Analysis of Lung Transcriptomics Reveals a Distinct B-Cell Signature in Emphysema
Authors: Rosa Faner, Tamara Cruz, Teresa Casserras, Alejandra López-Giraldo, Guillaume Noell, Ignacio Coca, Ruth Tal-Singer, Bruce Miller, Roberto Rodriguez-Roisin, Avrum Spira, Susana G. Kalko, Alvar Agustí
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by chronic airflow limitation caused by a combination of airways disease (bronchiolitis) and parenchymal destruction (emphysema), whose relative proportion varies from patient to patient.Objectives: To explore and contrast the molecular pathogenesis of emphysema and bronchiolitis in COPD.Methods: We used network analysis of lung transcriptomics (Affymetrix arrays) in 70 former smokers with COPD to compare differential expression and gene coexpression in bronchiolitis and emphysema.Measurements and Main Results: We observed that in emphysema (but not in bronchiolitis) (1) up-regulated genes were enriched in ontologies related to B-cell homing and activation; (2) the immune coexpression network had a central core of B cell–related genes; (3) B-cell recruitment and immunoglobulin transcription genes (CXCL13, CCL19, and POU2AF1) correlated with emphysema severity; (4) there were lymphoid follicles (CD20+IgM+) with active B cells (phosphorylated nuclear factor-κB p65+), proliferation markers (Ki-67+), and class-switched B cells (IgG+); and (5) both TNFRSF17 mRNA and B cell–activating factor protein were up-regulated. These findings were by and large reproduced in a group of patients with incipient emphysema and when patients with emphysema were matched for the severity of airflow limitation of those with bronchiolitis.Conclusions: Our study identifies enrichment in B cell–related genes in patients with COPD with emphysema that is absent in bronchiolitis. These observations contribute to a better understanding of COPD pathobiology and may open new therapeutic opportunities for patients with COPD.
Does sputum, biochemical and radiological markers of infection correlate with antibiotic prescribing in acute exacerbations of COPD?
Authors: Jamie Talbot, Rebecca Dickinson, Joanne Thompson, Karen Thompson, Jaymin Morjaria
Journal: European Respiratory Journal (2014)

Background  Acute exacerbations of COPD (AECOPD) may be due to bacterial or viral infection or exposure to irritants. Anecdotally we have observed antibiotic prescribing with no evidence of bacterial infection. We aimed to compare clinical and biochemical admission characteristics with antibiotic prescribing during AECOPD.  Methods  We reviewed two months of AECOPD admissions to our tertiary hospital collecting data on sputum volume and purulence, total white cell count (WCC), C-reactive protein (CRP), CXR changes and antibiotic prescribing.  Results  117 (74%) of all admission case notes were reviewed (mean age 72.5 yr; 58M, 59F). 89 (76%) patients received antibiotics for their exacerbation. Table 1 summarises antibiotic prescribing related to inflammatory markers and change in sputum and CXR.  Appropriate antibiotic prescribing (100%) was given to all patients with raised WCC and CRP with consolidation, and raised WCC and CRP with sputum change. However 68% of patients with normal WCC and CRP received antibiotics.  Conclusion  Patients with infective symptoms and raised biomarkers are being appropriately treated. However there are patients who receive antibiotics with no evidence of bacterial infection with subsequent unnecessary medications and antibiotic resistance.
Comparing outcome of radiofrequency ablation in Barrett’s with high grade dysplasia and intramucosal carcinoma: a prospective multicenter UK registry
Authors: Rehan Haidry, Gideon Lipman, Matthew Banks, Mohammed Butt, Vinay Sehgal, David Graham, Jason Dunn, Abhinav Gupta, Rami Sweis, Haroon Miah, Danielle Morris, Howard Smart, Pradeep Bhandari, Robert Willert, Grant Fullarton, Jonathon Morris, Massimo Di Pietro, Charles Gordon, Ian Penman, High Barr, Praful Patel, Philip Boger, Neil Kapoor, Brinder Mahon, Jonathon Hoare, Ravi Narayanasamy, Dermot O’Toole, Edward Cheong, Natalie Direkze, Yeng Ang, Andrew Veitch, Anjan Dhar, David Nyalender, Krish Ragunath, Anthony Leahy, Mark Fullard, Manuel Rodriguez-Justo, Marco Novelli, Laurence Lovat
Journal: Endoscopy (2015)

<b>Background and study aim:</b> Mucosal neoplasia arising in Barrett's esophagus can be successfully treated with endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA). The aim of the study was to compare clinical outcomes of patients with high grade dysplasia (HGD) or intramucosal cancer (IMC) at baseline from the United Kingdom RFA registry. <b>Patients and methods:</b> Prior to RFA, visible lesions and nodularity were removed entirely by EMR. Thereafter, patients underwent RFA every 3 months until all visible Barrett's mucosa was ablated or cancer developed (end points). Biopsies were taken at 12 months or when end points were reached. <b>Results:</b> A total of 515 patients, 384 with HGD and 131 with IMC, completed treatment. Prior to RFA, EMR was performed for visible lesions more frequently in the IMC cohort than in HGD patients (77 % vs. 47 %; <i>P</i> < 0.0001). The 12-month complete response for dysplasia and intestinal metaplasia were almost identical in the two cohorts (HGD 88 % and 76 %, respectively; IMC 87 % and 75 %, respectively; <i>P</i> = 0.7). Progression to invasive cancer was not significantly different at 12 months (HGD 1.8 %, IMC 3.8 %; <i>P</i> = 0.19). A trend towards slightly worse medium-term durability may be emerging in IMC patients (<i>P</i> = 0.08). In IMC, EMR followed by RFA was definitely associated with superior durability compared with RFA alone (<i>P</i> = 0.01). <b>Conclusion:</b> The Registry reports on endoscopic therapy for Barrett's neoplasia, representing real-life outcomes. Patients with IMC were more likely to have visible lesions requiring initial EMR than those with HGD, and may carry a higher risk of cancer progression in the medium term. The data consolidate the approach to ensuring that these patients undergo thorough endoscopic work-up, including EMR prior to RFA when necessary.
Abstract MP25: Is Surgical Menopause Associated With Future Cardiovascular Risk Factors Independent Of Antecedent Levels? The Cardia Study
Authors: Duke Appiah, Pamela J Schreiner, Julie K Bower, Barbara Sternfeld, Cora E Lewis, Melissa F Wellons
Journal: Circulation (2014)

Objective: The aim of this study was to compare changes in selected CVD risk factors prior to and after natural or surgical (hysterectomy with or without bilateral oophorectomy) menopause. Methods: Data were obtained from women aged 18 to 30 years at baseline without hysterectomy enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study and followed for 25 years. Piecewise linear mixed effects models were used to examine changes in waist circumference (WC) and HDL-cholesterol (HDL-c) from baseline to index visit (first visit after the date of natural or surgical menopause) and after index visit to the end of observation. Results: During follow up, 639 women reached natural menopause (NM), 304 reported hysterectomy with one or both ovaries conserved (HO) and 153 reported hysterectomy with bilateral oophorectomy (HBO). Baseline mean values of WC were 73.9, 76.4, 75.9 cm, p=0.005 for NM, HO, and HBO respectively while those for HDL-c were 57.6, 54.6, 54.2 mg/dL, p=0.001. After adjustment for race, education, field center, traditional CVD risk factors, lipid-lowering medication, age at and time since menopause, the mean values of WC at the index visit were 88.8, 92.4, 92.0 cm, p=0.001 for NM, HO, and HBO respectively while those for HDL-c were 61.5, 57.0, 57.8 mg/dL, p=0.006. Compared to women with natural menopause, surgically menopausal women (regardless of ovarian status) had higher annual rate of change for WC (0.74 vs. 0.63 cm, p=0.002) as well as lower rate of change for HDL-c (0.15 vs. 0.30 mg/dL, p=0.001) from baseline to index visit. No statistically significant differences in the annual rate of change after index visit to the end of follow up were observed between these two groups for either WC or HDL-c. Conclusion: While surgical menopause is commonly believed to worsen CVD risk, in this population-based sample, we found that women who undergo hysterectomy with or without bilateral oophorectomy had more adverse values for central adiposity and lipids at baseline compared to women with natural menopause. However, antecedent risk factor levels were strongly associated with postmenopausal levels in all women.
Phase III study of maintenance gemcitabine (G) and best supportive care (BSC) versus BSC, following standard combination therapy with gemcitabine-carboplatin (G-Cb) for patients with advanced non-small cell lung cancer (NSCLC).
Authors: C. P. Belani, D. M. Waterhouse, H. Ghazal, S. S. Ramalingam, R. Bordoni, R. Greenberg, R. M. Levine, J. M. Waples, Y. Jiang, G. Reznikoff
Journal: Journal of Clinical Oncology (2010)

7506 Background: The use of single agent cytotoxic or targeted agent as maintenance following combination therapyrepresents a useful strategy to improve patient outcomes in advanced stage NSCLC. An earlier study with gemcitabine as maintenance therapy demonstrated improved time to progression (TTP) compared to BSC (6.6 mos. vs 5.0 mos., p < 0.001) (Brodowicz et al, Lung Cancer, 2006; 52:155-163). Based on this, we conducted a randomized phase III study to compare G + BSC versus BSC as maintenance therapy for patients with advanced NSCLC. Methods: Patients with stage IIIB (wet)/IV NSCLC were initially treated with gemcitabine (1,000 mg/m2 on day 1 and 8) and carboplatin (AUC = 5 mg/mL.min on d 1) every 3 weeks for 4 cycles. Subsequently, patients with CR/PR or SD were randomized 1:1 to receive maintenance G (1,000 mg/m2 on d 1 and 8), every 3 weeks with BSC or BSC alone until disease progression. The primary endpoint was the comparison of overall survivalbetween the two arms and the secondary endpoint was progression free survival (PFS). Results: 519 patients were enrolled (median age-67 years, stage IV disease- 86%, ECOG performance status 0/1-75%). With G-Cb, the RR was 28% (CR-1.2%, PR-26.8%), and 37% had SD. Following 4 cycles of G-Cb, 255 non- progressors were randomized to receive G + BSC (n = 128) or BSC (n = 127). The median PFS was 3.9 m (95% CI:3.3, 5.6) for G + BSC and 3.8 m (95% CI: 2.6, 5.5) for BSC. Median survival was 8.0 m (95% CI: 6.0, 10.2) for G+ BSC and 9.3 m (95% CI: 7.7, 12.7) for BSC. The differences in survival between the two arms were not statistically significant (HR = 0.97 [95% CI: 0.72, 1.30], p = 0.84). Maintenance therapy was tolerated well despite a higher incidence of grade 3/4 toxicity (anemia 9.4% vs. 2.4%; neutropenia 13.3% vs. 1.6%; thrombocytopenia 9.4% vs. 1.4%; and fatigue 3.9% vs. 1.6%). Conclusions: The use of gemcitabine as maintenance therapy failed to improve survival following G-Cb in patients with advanced NSCLC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly
Expression of steroids and HER2-neu receptors in breast tumors associated with BRCA1 gene mutations
Authors: N. A. Zarubina, V. D. Petrova, T. V. Sinkina, S. A. Terekhova, A. F. Lazarev, U. A. Boyarskikh, E. V. Pechkovsky, O. V. Mishukova, M. L. Filipenko
Journal: Journal of Clinical Oncology (2009)

e22223 Background: Hereditary breast carcinomas that are attributable to BRCA1 mutations have their own morphological and immunohistochemical characteristics. This study was aimed to analyze the level of expression of steroids (estrogen and progesterone) and HER2-neu receptors in BRCA1 associated breast cancer. Methods: DNA patterns from 264 patients with hereditary breast cancers (breast cancer diagnosed at the age under 40; bilateral breast cancer; combination of breast and ovarian cancers; 2 and more breast cancers in blood relatives). All the patients were residents of the Altai Territory. BRCA1 gene mutations were registered in 34 patients (12.9%): 5382insC gene mutation - in 28 patients; 300A/C - in 2 patients; 4153del - in 3 patients; 185del - in 1 patient. The frequency of the BRCA1 5382insC allele mutation was 7.3; 300A/C - 0.52; 4153del - 0.26; 185del - 0.83. Immunohistochemical characteristics of BRCA1-associated breast tumors tissue from these patients were investigated. Results: 32 BRCA1-associated breast carcinomas were estrogen receptor- negative; 1 - week positive (H-score 50–100); 1 - moderate positive (H- score 100–200). 33 BRCA1-associated breast carcinomas were progesterone receptor- negative; 1 - positive (H-score 200 and more). HER2-negative were 31 BRCA1-associated breast carcinomas; 2 were week positive (HER2-neu +); 1 - was moderate positive (HER2-neu ++). Conclusion: BRCA1-associated beast carcinomas have been found to be more frequently estrogen receptor-, progesterone receptor-, and HER2- negative. These data show that hereditary breast cancer associated with BRCA1 gene mutations poses poor prognosis. No significant financial relationships to disclose.
Tumor infiltrating lymphocytes (TIL) to predict response to neoadjuvant chemotherapy in breast cancer: A systemic review and meta-analysis.
Authors: Yan Mao, Qing Qu, Yuzi Zhang, Junjun Liu, Kunwei Shen
Journal: Journal of Clinical Oncology (2014)

138 Background: Whether tumor-infiltrating lymphocytes (TILs) predict response to neoadjuvant chemotherapy (NAC) remains elusive. Methods: A systematic review and meta-analysis was undertook to establish the relationship between TIL and pathological complete response (pCR) rate in NAC of breast cancer. A PubMed and Web of Science literature search was designed. Studies were included, in which the predictive significance of intratumoral and/or stromal TIL, and/or CD3+, CD4+, CD8+, and FOXP3+ lymphocytes were determined . Pooled ORs and publication bias was evaluated by STATA software. Results: A total of 13 published studies (including 3,555 patients) were eligible. In pooled analysis, higher number of TIL in pre-treatment biopsy was correlated with higher pCR rate of neoadjuvant chemotherapy, and odds ratio (OR) was 3.82 (95% confidence interval (CI), 3.10-4.70), no matter tested in intratumor (OR=3.32, 95% CI: 2.52-4.37), in stroma (OR=4.15,95% CI: 2.94-5.86), or in combined sites (OR=8.98, 95% CI: 3.79,21.30). Moreover, TIL predicts higher pCR rate in triple negative (OR=5.03,95% CI: 2.31-10.97) and HER2+ (OR=5.54,95% CI: 1.39-22.12) patients, but not in hormonal receptor (HR) +/HER2- patients (OR=2.57, 95% CI: 0.20-33.24). For TIL subsets, CD8+ T-lymphocytes predict better pathological response to NAC no matter in pre- (OR=3.36,95%CI: 1.15-9.85) or post-NAC (OR=4.71,95%CI: 1.29-17.27) tissue, while FOXP3+ T-lymphocytes have similar predictive roles only when tested after NAC (OR=4.26, 95%CI: 1.83-9.92).With limited study, the predictive role of CD3+ and CD4+T-lymphoctes were unclear, more perspective studies were needed in future to establish the relationship. Conclusions: High level of TIL in pre-treatment biopsy could be a good marker indicates better pathological response to NAC in triple-negative and HER2+ breast cancer patients. Different subsets have different predictive roles in the pCR rate to NAC. However, significant heterogeneity and an insufficient number of studies underscore the need for further prospective studies on subsets of T lymphocytes and different subtypes of breast cancer to increase the robustness of the analyses.
Tattooing and piercing – the need for guidelines in EU
Authors: N Noah
Journal: Eurosurveillance (2006)

As in Amsterdam [1], the impetus for UK guidelines for hygienic tattooing came from an outbreak of hepatitis B caused in 1978 by a tattooist. The outbreak resulted in 30 primary and three secondary cases [2]. Guidelines for hygienic tattooing followed soon after, and were taken up, fairly enthusiastically on the whole, by the tattooists. These were expanded in 1982 to include acupuncture, ear-piercing and hair electrolysis. Laws to control the hygiene of these practitioners were introduced at the same time {Local Government Miscellaneous Provisions Act 1982 [amended 2003] and the Greater London Council [General Powers] Act 1982}. Body piercing was hardly heard of at the time: although it was undoubtedly and somewhat furtively practised, it was not as popular or as open as it is now. Guidelines for beauty therapy, hygienic hairdressing and micropigmentation followed.
Two Cases of Small Cell Lung Cancer Transformation from EGFR Mutant Adenocarcinoma During AZD9291 Treatment
Authors: Jun Soo Ham, Seokhwi Kim, Hee Kyung Kim, Seonggyu Byeon, Jong-Mu Sun, Se-hoon Lee, Jin Seok Ahn, Keunchil Park, Yoon-La Choi, Joungho Han, Woongyang Park, Myung-Ju Ahn
Journal: Journal of Thoracic Oncology (2016)
Resuscitation
Authors: S. Leaves, P. Donnelly, C. Lester, D. Assar, A. Sharma
Journal: BMJ (1998)

Editor—In reply to the request by the Resuscitation Council UK1 to report experiences regarding the recovery position of the 1997 International Liaison Committee On Resuscitation (ILCOR 97),2 research carried out by a team in Cardiff has shown a number of important issues that need to be addressed. 

A comparison between the positions of the European Resuscitation Council 1992 (ERC 92)3 and ILCOR 97, in which 86 members of the community participated, has shown a marked preference for the ERC 92 recovery position. A self administered questionnaire was developed to elicit quantitative and qualitative information from adults attending emergency life support courses taught by Heartstart Cardiff and the Vale Instructors. The questionnaire used a Likert scale and gave open and closed questions. 

Two questions asked for the rescuer’s opinion when comparing the techniques of the ERC 92 and ILCOR 97 recovery positions. The rescuer’s opinion was recorded using a Likert scale of “easy” to “difficult.” A closed question then asked which technique the rescuer would use if he or she had a free choice. Three open questions then asked the trainee and the “casualty” for comments on the near side arm position, the turn, and the final resting position. 

The table shows that trainees in the role of the rescuer were more likely to report that the 1992 position was very easy and trainees in the role of the casualty were more likely to report positively on the near side arm position, the turning process, and the final position (all P<0.001). 

The following are examples typical of qualitative comments made by trainees: “This hurts!! it felt like my arm was breaking.” (ILCOR 97) “I definitely prefer ERC 92, ILCOR 97 was damn painful.” “I strongly recommend my lifeguard team not to use ILCOR 97 as it is uncomfortable for the casualty.” 

In view of these results from community resuscitation training we feel that a return to the original ERC 92 recovery position should be considered. Ambulance response times to emergency calls in the United Kingdom mean that a casualty need rarely be kept in the recovery position for more than 10 minutes, so ease of training and avoidance of discomfort for trainees need to be balanced against minimising the risk to the casualty over this short time span.4
Autologous Stem Cell Transplantation Improves Survival For High Risk Cardiac Amyloidosis
Authors: Piyanuch Kongtim, Muzaffar H. Qazilbash, Jatin J. Shah, Robert Z. Orlowski, Amir Hamdi, Nina Shah, Qaiser Bashir, Michael Wang, Richard E Champlin, Simrit Parmar
Journal: Blood (2013)
Abstract 11099: Transcriptome Profiling of Surgical Myectomy Tissue from Patients with Hypertrophic Cardiomyopathy Reveals Marked Overexpression of ACE2
Authors: Virginia B Hebl, J. M Bos, Ann L Oberg, Zhifu Sun, Joseph J Maleszewski, Ozgur Ogut, Kalkidan Bishu, Cristobal G dos Remedios, Steve Ommen, Hartzell V Schaff, Joseph A Dearani, Frank V Brozovich, Michael J Ackerman
Journal: Circulation (2012)

Introduction. Hypertrophic cardiomyopathy (HCM) is one of the leading causes of sudden cardiac death in the young, and the underlying molecular mechanisms are poorly understood. Herein, we aimed to...
Meeting Report Europhosphatase 2015: Phosphatases as Drug Targets in Cancer
Authors: Elmer Hoekstra, Maikel P. Peppelenbosch, Gwenny M. Fuhler
Journal: Cancer Research (2016)

Phosphatases are key regulators of cellular signaling and as such play an important role in nearly all cellular processes governing diseases, including cancer. However, due to their highly conserved structure and highly charged and reactive catalytic site, they have been regarded as "undruggable." Fortunately, during the recent Europhosphatase meeting (Turku, Finland), it became clear that phosphatases can no longer be ignored as potential targets in cancer therapy. As reactivation of tumor-suppressor phosphatases or direct inhibition of phosphatases acting as oncogenes is becoming available, this class of enzymes can now be considered as feasible drug targets. Cancer Res; 76(2); 193-6. ©2016 AACR.