tbuckley/cabot-search huggingface dataset:
Recruitment of stromal cells into tumour microenvironment promote the metastatic spread of breast cancer
Authors: Billy Samuel Hill, Annachiara Sarnella, Giuliana D’Avino, Antonella Zannetti
Journal: Seminars in Cancer Biology (2019)

Currently, metastasis remains the primary cause of death of patients with breast cancer despite the important advances in the treatment of this disease. In the complex tumour microenvironment network, several malignant and non-malignant cell types as well as components of extracellular matrix cooperate in promoting the metastatic spread of breast carcinoma. Many components of the stromal compartment are recruited from distant sites to the tumour including mesenchymal stem cells, endothelial cells, macrophages and other immune cells whereas other cells such as fibroblasts are already present in both primary and secondary lesions. When these cells come into contact with cancer cells they are "educated" and acquire a pro-tumoural phenotype, which support all the steps of the metastatic cascade. In this Review, we highlight the role played by each stromal component in guiding cancer cells in their venture towards colonizing metastatic sites.
Living wills: GPs should do more to support patients, says charity
Authors: Gareth Iacobucci
Journal: BMJ (2019)

GPs should do more to help patients plan for their care and treatment because of a lack of awareness about advance decisions, says a report from the charity Compassion in Dying.1

Advance decisions are documents that allow people to state in what circumstances they would want to refuse future treatment if they become seriously ill and cannot make or convey such decisions. Formerly known as “living wills,” advance decisions gained legal status in 2005.

Despite their statutory status, however, the report found that some GPs had “significant gaps” in knowledge about advance decisions and how they …
The contribution of epigenetic and genetic changes to predict gastrointestinal stromal tumors (GIST) behavior
Authors: E. Braggio, D. P. Guimaraes, C. E. Bacchi, L. F. Lopes, I. A. Small, M. Valadão, M. J. Portella, S. Romano, I. R. Zalcberg, C. G. Ferreira
Journal: Journal of Clinical Oncology (2006)

9542 Background: To search for markers for better prognostic evaluation in patients (pts) with GIST was our goal. Loss of E-cadherin expression and/or function by hypermethylation has been correlated with increase in the invasive potential of human tumors. Recently, loss of p16INK4a expression was considered as an independent prognostic factor in pts with GIST. Methods: We investigated the methylation (MT) status for p16Ink4a and E-cadherin by the MT -specific PCR, c-KIT mutation by SSCP-sequencing, p16INK4a and cKIT expressions and KI-67 index by IHC, in 81 pts with completely ressected GIST between Jan 1990 and April 2003. Clinical data and follow-up information were obtained from medical records.A cutoff at 20% and 5% positivity was used for p16INK4a and KI-67, respectively. Univariate analysis of disease-free survival (DFS) and overall survival (OS) were performed by Kaplan Meier method with the log-rank test. Results: Median age was 55 (9–78); Male/female 42/58%; primary tumor sites were stomach (46.9%), small bowell (37.0%), colorectal (8.6%) and peritoneal (6.2%). Median tumor size was 8cm (1.2–35.0). The median follow-up was 24 months. Pts were stratified into low- (24.7%), intermediate- (37.0%) and high- (38.3%) risk pts based on tumor size and mitotic index. There was a significant correlation between risk classification and disease free survival (DFS) (p=0.023) and overall survival (OS) (p=0.010). The p16Ink4a and E-cadherin MT were observed in 19.4% and 63.3% pts, respectively. We observed loss of p16INK4a expression in 64.9% of GISTs. Overall, 78.4% had KIT mutation in exon 11 or 9. There was non-significant correlations between epigenetic alterations, cKIT mutation, p16INK4a expression, KI-67 index and survival. By analysing the three groups separately we found a significant correlation between E-cadherin MT with DFS (p&lt;0.047) only in the intermediate risk group. Conclusion: Our results suggest that E-cadherin MT may be a helpful prognostic factor particularly in the intermediate risk group of GISTs. In contrast with previous results from the literature p16INK4a alterations had no prognostic impact in our samples. No significant financial relationships to disclose.
Clinical study of thyroid cancer among a pediatric population born after Chernobyl (first report)
Authors: M. B. Gorobeiko, O. S. Larin, S. M. Cherenko
Journal: Journal of Clinical Oncology (2007)

6069 Background: To evaluate the clinical and patologic results of surgical treatment of children born after Chernobyl and to compare these findings with well-known data of the group of patients who were children at the time of Chernobyl. To compare the clinical and pathologic features of thyroid cancer of children born after the Chernobyl versus those born prior to 1986. Methods: Comparison of clinical and pathologic result of surgical treatment of 141 patients born after Chernobyl (Group 1) and 589 patients (Group 2) aged 0–18 at the time of the disaster (1986) among the single institution clinical cohort within years 1995–2005. Results: In Group 1 there were 31 cancers (22%) vs. 243 (41%) in Group 2 (p&lt;0.05 between Group 1 and Group 2). The rate of extrathyroid invasion was 69% vs. 36% (p&lt;0.05 between Group 1 and Group 2). In Group 1, 17/21(80%) patients with extrathyroid invasion were found to have regional neck metastases (8 unilateral, 9 bilateral).The mean age in this subgroup was 13.4 ± 2.11 years but in the “benign subgroup” of Group 1 the mean age is 16.2 ± 0.77 years.In Group 2, 49/88 (55%) patients with extrathyroid invasion only had regional metastases. The mean age in this subgroup is 31.1 ± 4.7 years (p&lt;0.05 between Group 1 and Group 2). We found cancer multifocality in 1 patient (3%, Group 1) vs. 55 (23%, Group 2).There were 19 cases (13.5%) of atypical adenomas in Group 1 vs. 46 (8%) in Group 2 (p&lt;0.05 between Group 1 and Group 2). Histological types: solid follicular variant of papillary carcinoma (typical for radiation-induced children carcinomas with short latency) was found in 3 cases in Group 1 (9.5%) vs. 76 (31%) in the Group 2 (p&lt;0.05 between Group 1 and Group 2). There was only one case of follicular thyroid cancer in Group 1 (3%) vs. 9% in Group 2. We did not find any relationship of cases of cancer in Group 1 to the Chernobyl-polluted area (only 3 patients − 10% from the nearest to Chernobyl regions) vs. 192 patients (80%) in Group 2 (p&lt;0.05 between Group 1 and Group 2). Among patients with tumors of uncertain malignant potential 9 patients (6%) were from Chernobyl-polluted area vs.72% in Group 2 (p&lt;0.05 between Group 1 and Group 2). Conclusions: Our data demonstrates higher likelihood of aggressive well-differentiated thyroid cancer among a pediatric population independently from Chernobyl irradiation and connected with another etiological factors of genesis of tumor.The solid-follicular variant of papillary cancer and multifocality are typical for radiation-induced carcinoma in children. No significant financial relationships to disclose.
ZEB1 promotes inflammation and progression towards inflammation-driven carcinoma through repression of the DNA repair glycosylase MPG in epithelial cells
Authors: Oriol de Barrios, Lidia Sanchez-Moral, Marlies Cortés, Chiara Ninfali, Nuria Profitós-Pelejà, MC Martínez-Campanario, Laura Siles, Rosa del Campo, María Jesús Fernández-Aceñero, Douglas S Darling, Antoni Castells, Joan Maurel, Azucena Salas, Douglas C Dean, Antonio Postigo
Journal: Gut (2019)

Chronic inflammation is a risk factor in colorectal cancer (CRC) and reactive oxygen species (ROS) released by the inflamed stroma elicit DNA damage in epithelial cells. We sought to identify new drivers of ulcerative colitis (UC) and inflammatory CRC.The study uses samples from patients with UC, mouse models of colitis and CRC and mice deficient for the epithelial-to-mesenchymal transition factor ZEB1 and the DNA repair glycosylase N-methyl-purine glycosylase (MPG). Samples were analysed by immunostaining, qRT-PCR, chromatin immunoprecipitation assays, microbiota next-generation sequencing and ROS determination.ZEB1 was induced in the colonic epithelium of UC and of mouse models of colitis. Compared with wild-type counterparts, Zeb1-deficient mice were partially protected from experimental colitis and, in a model of inflammatory CRC, they developed fewer tumours and exhibited lower levels of DNA damage (8-oxo-dG) and higher expression of MPG. Knockdown of ZEB1 in CRC cells inhibited 8-oxo-dG induction by oxidative stress (H2O2) and inflammatory cytokines (interleukin (IL)1β). ZEB1 bound directly to the MPG promoter whose expression inhibited. This molecular mechanism was validated at the genetic level and the crossing of Zeb1-deficient and Mpg-deficient mice reverted the reduced inflammation and tumourigenesis in the former. ZEB1 expression in CRC cells induced ROS and IL1β production by macrophages that, in turn, lowered MPG in CRC cells thus amplifying a positive loop between both cells to promote DNA damage and inhibit DNA repair.ZEB1 promotes colitis and inflammatory CRC through the inhibition of MPG in epithelial cells, thus offering new therapeutic strategies to modulate inflammation and inflammatory cancer.
P120 and E-cadherin: Double-edged swords in tumor metastasis
Authors: Jan-Hendrik Venhuizen, Femke J.C. Jacobs, Paul N. Span, Mirjam M. Zegers
Journal: Seminars in Cancer Biology (2019)

Cell-cell adhesion by adherens junctions controls proliferation and cell polarization and is crucial to maintain epithelial architecture and homeostasis. Downregulation of two of the main components of adherens junctions, E-cadherin and p120, is an often recurring hallmark of carcinomas, causing loss of polarity and increased proliferation, survival and invasion of epithelial cells. On the other hand, tumor-promoting effects of both E-cadherin and p120 have been reported, substantiated by sustained, or even elevated expression of these molecules in many cancers. In this review, we will discuss how expression regulation by EMT, E-cadherin cleavage or p120 isoform expression can contribute to either tumor-supressing or tumor-promoting processes. Furthermore, we will focus on the contradictory functions of E-cadherin and p120 in the different phases of tumor progression, from carcinoma in situ up to the formation of distant metastasis. Finally, we will discuss the possibilities and challenges when using either protein as a biomarker.
Reply to Puxeddu <i>et al.</i>: CD71<sup>−</sup> Alveolar Macrophages in Idiopathic Pulmonary Fibrosis: A Look beyond the Borders of the Disease
Authors: Adam Byrne
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

As discussed by Allden and coworkers in their article, among other hypotheses, CD71 2 AMs could be an expression of a subpopulation of immature monocytes recruited into the alveolar space from the bloodstream during active inflammation/tissue injury, as was previously shown in a preclinical animal model of lung fibrosis (6).We believe that the lack of specificity about the presence of CD71 2 AMs in IPF that we show in this brief report supports the latter interpretation.Furthermore, the reported association between the proportion of CD71 2 cells and the clinical course of patients with IPF may reflect the ongoing fibrotic process that characterizes the rapidly progressive form of the disease and may also characterize other, non-IPF ILDs that in some cases display an accelerated pathological/clinical evolution.Although further studies on large populations of patients with ILD will be needed to confirm these preliminary observations, we believe that the study by Allden and coworkers is very promising and reinforces the role of BAL as a potential source of fundamental information in the field of translational medicine in respiratory diseases.
Making Open Science Work for Science and Society
Authors: Kevin C. Elliott, David B. Resnik
Journal: Environmental Health Perspectives (2019)

The open science movement is transforming scientific practice with the goal of enhancing the transparency, productivity, and reproducibility of research. Nevertheless, transparency is a complex concept, and efforts to promote some forms of transparency may do relatively little to advance other important forms of transparency.Drawing from the literature in history, philosophy, and sociology of science, we aim to distinguish between different forms of scientific transparency. Our goal is to identify strategies for achieving forms of transparency that are relevant not only to scientists but also to decision makers and members of the public.We draw a distinction between "scientifically relevant transparency" and "socially relevant transparency." Most of the prominent strategies associated with the open science movement (e.g., making data publicly available and registering studies) are designed primarily to promote scientifically relevant transparency. To achieve socially relevant transparency, which is particularly important in fields like environmental health, further steps are needed to provide scientific information in ways that are relevant to decision makers and members of the public.Promoting socially relevant transparency will require a range of activities by many different individuals and institutions. We propose an array of strategies that can be pursued by scientists and other scholars, journals, universities, funders, government agencies, and members of the public. https://doi.org/10.1289/EHP4808.
Abstract 403: COX-2 expression on circulating tumor cells in nasopharyngeal carcinoma predicts a worse survival: A prospective analysis
Authors: Yongjiang Li, Xiaoqi Xie, Feng Wang
Journal: Cancer Research (2019)

Abstract COX-2 expression on circulating tumor cells in nasopharyngeal carcinoma predicts a worse survival: A prospective analysis Yong-Jiang Li1, Xiao-Qi Xie2, Feng Wang1* 1Department of Oncology, West China Hospital, Sichuan University, Chengdu, PR China 2Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, PR China *Corresponding author Short title: COX-2 Expression on CTCs in NPC patients Abstract Background and purpose: The prognostic significance of circulating tumor cells (CTCs) in head and neck cancer is still under debate, as only a few studies have been reported and limited conclusions are reached. Besides, CTCs count alone was utilized as an indicator in the previous researches. As a form of ‘liquid biopsy’, the further identification of genetic or phenotypic biomarkers on CTCs could possibly provide further clinical significance. Materials and methods: The prospective study enrolled 131 patients with nasopharyngeal carcinoma (NPC). CTCs were isolated at baseline and at the end of concurrent chemoradiotherapy, and cyclooxygenase-2 (COX-2) expression status of CTCs was detected by RNA-in situ hybridization (ISH) method. Results were correlated with patient’s clinicopathological parameters and treatment outcomes. Univariate and multivariate survival analysis were performed to determine the prognostic significance. Results: COX-2 expression was found in 87/131 (66.4%) patients at baseline and 53/115 (46.1%) patients at the end of concurrent chemoradiotherapy. Patients with post-therapeutic COX-2 expression had significantly poorer treatment response (P=0.011) and higher risk of tumor relapse (P=0.026) and metastasis (P=0.007). Besides, multivariate analysis revealed that post-therapeutic COX-2 expression on CTCs remained an independent prognostic indicator for poorer progression-free survival (HR 2.17, P=0.019) and overall survival (HR 2.41, P=0.024). Conclusion: The study demonstrated that post-therapeutic COX-2 expression on CTCs was a novel and promising prognostic indicator for NPC patients. Future studies are needed to validate our findings and further clarify the value of integrating the indicator with current clinical strategies in improving survival of NPC patients. Note: This abstract was not presented at the meeting. Citation Format: Yongjiang Li, Xiaoqi Xie, Feng Wang. COX-2 expression on circulating tumor cells in nasopharyngeal carcinoma predicts a worse survival: A prospective analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 403.
Adjuvant endocrine treatment in premenopausal patients with breast cancer: Clinical practice in an Italian cancer center.
Authors: Elena Collovà, Sandro Barni, Antonio Frassoldati, Domenico Amoroso
Journal: Journal of Clinical Oncology (2013)

e11550 Background: Overall results from past and recent trials favor ovarian ablation, with luteinizing hormone-releasing hormone (LHRHa) analogues alone or in combination with the anti-estrogen tamoxifen (TAM), rather than with chemotherapy. The aim of this survey was to obtain more informations about the clinical practice of adjuvant endocrine therapy. Methods: 11 items electronic questionnaire was submitted to italian oncologists and 611 filled questionnaires were collected. The results were examined globally and according to sex, age, working institution and geographical origin of the oncologists. Results: 97.7% of patients less than 40 years needing only hormonal therapy would receive both TAM and LHRHa; 2.3% TAM or LHRHa alone. 93.6% of patients over 40 years would receive the combination with TAM or LHRHa When LHRHa would be added to TAM the treatment length would be: 5 years in 60% and 44%, 3 years in 20.8% and 26.4%, 2 years in 19.2% and 29.6%, in patients aged under and over 40 respectively. At least one risk factors like positive nodes, high ki-67, G3, vascular invasion, HER2 3+, influence neither the therapeutic options nor the length of LHRHa use. In patients under 40 with chemotherapy induced amenorrhea, the oncologists would prescribe: TAM in 22.4%, TAM and LHRHa in 68,1% (LHRHa for 5 years in 55.3%, for 3 years in 22.1%, for 2 years in 22.6%), aromatase inhibitor (AI) +/- LHRHa in 6.6%, LHRHa alone in 2.9%. A greater number of patients would be treated with AI among women aged over 40 (11%). The reasons to add LHRHa toTAM and the length of treatment would be: in higher efficacy of the combination: 45.5%; patient’s age: 30.1%; risk of recurrence: 20.8%; and, side effect: 3.6%. Conclusions: A high concordance between the Italian Oncologist attitude and the European Guidelines is confirmed by this large survey. However, a wide preference for a TAM/LHRHa combination is reported, as well as a significant preference for LHRHa and AI combination in women under 40 years with chemotherapy induced amenorrhoea.
Impact of concurrent indolent lymphoma on the clinical outcome of newly diagnosed diffuse large B-cell lymphoma
Authors: Yucai Wang, Brian K. Link, Thomas E. Witzig, Matthew J. Maurer, Cristine Allmer, Rebecca L. King, Andrew L. Feldman, Thomas M. Habermann, Stephen M. Ansell, Susan L. Slager, James R. Cerhan, Grzegorz S. Nowakowski
Journal: Blood (2019)
Lifestyle Counseling and Long-term Clinical Outcomes in Patients With Diabetes
Authors: Huabing Zhang, Saveli I. Goldberg, Naoshi Hosomura, Maria Shubina, Donald C. Simonson, Marcia A. Testa, Alexander Turchin
Journal: Diabetes Care (2019)

To investigate the relationship between lifestyle counseling in primary care settings and clinical outcomes in patients with diabetes.We retrospectively studied hyperglycemic adults with diabetes treated at primary care practices between 2000 and 2014. We analyzed the relationship between frequency of lifestyle counseling (identified using natural language processing of electronic notes) and a composite outcome of death and cardiovascular events during subsequent follow-up.Among patients with monthly counseling or more, 10-year cumulative incidence of the primary outcome was 33.0% compared with 38.1% for less than monthly counseling (P = 0.0005). In multivariable analysis, higher frequency of lifestyle counseling was associated with lower incidence of the primary outcome (hazard ratio 0.88 [95% CI 0.82-0.94]; P < 0.001).More frequent lifestyle counseling was associated with a lower incidence of cardiovascular events and death among patients with diabetes.
B-Cell Prolymphocytic Leukemia, a Rare Lymphoproliferative Disorder: Analysis of 35 Cases, a Study on Behalf of the French Innovative Leukemia Organization (FILO)
Authors: Caroline Algrin, Elise Chapiro, Justine Saviellis, Anne Quinquenel, Anne-Sophie Michallet, David Ghez, Pierre Feugier, Annie Brion, Cecile Tomowiak, Luc-Matthieu Fornecker, Remy Gressin, Laurent Sutton, Karim Maloum, Catherine Settegrana, Lucile Baseggio, Quentin Vincent, Florence Nguyen-Khac, Véronique Leblond
Journal: Blood (2017)
Association of Residents' Neural Signatures With Stress Resilience During Surgery
Authors: Hemel Narendra Modi, Harsimrat Singh, Francesca Fiorentino, Felipe Orihuela-Espina, Thanos Athanasiou, Guang-Zhong Yang, Ara Darzi, Daniel Richard Leff
Journal: JAMA Surgery (2019)

Intraoperative stressors may compound cognitive load, prompting performance decline and threatening patient safety. However, not all surgeons cope equally well with stress, and the disparity between performance stability and decline under high cognitive demand may be characterized by differences in activation within brain areas associated with attention and concentration such as the prefrontal cortex (PFC).To compare PFC activation between surgeons demonstrating stable performance under temporal stress with those exhibiting stress-related performance decline.Cohort study conducted from July 2015 to September 2016 at the Imperial College Healthcare National Health Service Trust, England. One hundred two surgical residents (postgraduate year 1 and greater) were invited to participate, of which 33 agreed to partake.Participants performed a laparoscopic suturing task under 2 conditions: self-paced (SP; without time-per-knot restrictions), and time pressure (TP; 2-minute per knot time restriction).A composite deterioration score was computed based on between-condition differences in task performance metrics (task progression score [arbitrary units], error score [millimeters], leak volume [milliliters], and knot tensile strength [newtons]). Based on the composite score, quartiles were computed reflecting performance stability (quartile 1 [Q1]) and decline (quartile 4 [Q4]). Changes in PFC oxygenated hemoglobin concentration (HbO2) measured at 24 different locations using functional near-infrared spectroscopy were compared between Q1 and Q4. Secondary outcomes included subjective workload (Surgical Task Load Index) and heart rate.Of the 33 participants, the median age was 33 years, the range was 29 to 56 years, and 27 were men (82%). The Q1 residents demonstrated task-induced increases in HbO2 across the bilateral ventrolateral PFC (VLPFC) and right dorsolateral PFC in the SP condition and in the VLPFC in the TP condition. In contrast, Q4 residents demonstrated decreases in HbO2 in both conditions. The magnitude of PFC activation (change in HbO2) was significantly greater in Q1 than Q4 across the bilateral VLPFC during both SP (mean [SD] left VLPFC: Q1, 0.44 [1.30] μM; Q4, -0.21 [2.05] μM; P < .001; right VLPFC: Q1, 0.46 [1.12] μM; Q4, -0.15 [2.14] μM; P < .001) and TP (mean [SD] left VLPFC: Q1, 0.44 [1.36] μM; Q4, -0.03 [1.83] μM; P = .001; right VLPFC: Q1, 0.49 [1.70] μM; Q4, -0.32 [2.00] μM; P < .001) conditions. There were no significant between-group differences in Surgical Task Load Index or heart rate in either condition.Performance stability within TP is associated with sustained prefrontal activation indicative of preserved attention and concentration, whereas performance decline is associated with prefrontal deactivation that may represent task disengagement.