tbuckley/cabot-search huggingface dataset:
Predictors of care for early-stage breast cancer in Appalachia.
Authors: Gretchen Genevieve Kimmick, Fabian Camacho, Teresa Kern, Steven Fleming, Jason Liao, Stephen Matthews, Wenke Hwang, Heath B. Mackley, Joseph Lipscomb, Pamela Short, John Moran, Nengliang Yao, Roger T. Anderson
Journal: Journal of Clinical Oncology (2013)

6558 Background: We studied care for early-stage breast cancer in Appalachia, a region with health infrastructure, socioeconomic (SES) and geographic disparities. Methods: Cases of stage I-III breast cancer diagnosed 2006-2008 were identified from cancer registries of KY, NC, OH, and PA and linked to Medicare data. Guideline concordance was studied in eligible groups, as follows: endocrine therapy for hormone receptor positive cancer (n=1429); and radiation (RT) use after breast conserving surgery (BCS) divided into two groups - age 70 years and older with ER/PR+, &lt;2 cm, node negative tumors where it may have been acceptable to forgo RT (OptRT, n=1108) and all other cases (IndRT, n=1422). Multivariate (MV) and univariate analyses were performed. Covariates included age, state, Appalachian Regional Commission (ARC) economic status, Commission of Cancer (CoC) status, state, access to care, number of beds, surgery facility ownership, volume, and chemotherapy/radiation offered, provider graduation year and volume, Charlson comorbidity, diagnosis year, Medicaid/Medicare dual status, histology, tumor size, tumor sequence, positive lymph nodes, ER/PR status, stage, herceptin use, and BCS/mastectomy indicator. Results: Mean age was 74 years and 97% were white. Guideline-concordance was 76% for endocrine therapy, 83% for IndRT, and 77% for OptRT. Younger age predicted higher concordance in all groups. Endocrine therapy use was lower in NC vs PA (OR 0.60; 95% CI 0.41-0.88) and greater for cases whose provider graduated in years 1984-1988, vs. 1989+ (1.55; 1.06-2.29). In IndRT, provider volume in the 3 rd quartile vs. highest quartile predicted increased radiation use (2.36; 1.46-3.81). In OptRT, less receipt of radiation was predicted by residence in NC vs. PA (0.26; 0.18-0.48), and competitive ARC class vs. transitional (0.60; 0.36-0.99). Conclusions: Within Appalachia, there are SES and provider characteristics that are associated with use of guideline concordant care.
The role of tissue factor and the coagulation system in the function of tumor initiating (stem) cells
Authors: Chloe Milsom, Joanne Yu, Brian Meehan, Nathalie Magnus, Linda May, Mark Anderson, Nigel Mackman, Janusz Rak
Journal: Cancer Research (2008)

5852  Oncogenic events affect tumor initiating cancer stem cells (CSCs), but also play a significant role in tumor-host interrelationships, including cancer-related Trousseau syndrome, angiogenesis and metastasis. It is of note that some of the latter events are attributed to the procoagulant cell membrane receptor known as tissue factor (TF), or thromboplastin. TF binds the clotting factor VIIa and thereby activates the coagulation cascade. At the same time TF also triggers intracellular signalling, gene expression and alters cellular behaviour. Collectively, this raises the question as to the possible relationship between CSCs and TF in cancer.  Our studies show that cancer cells frequently upregulate TF downstream of several different oncogenic events. In A431 squamous cell carcinoma cells driven by the amplification of the epidermal growth factor receptor (EGFR) TF levels are controlled by this genetic lesion. This is evident from the fact that in this context EGFR inhibitors downregulate TF expression and procoagulant activity and also suppress tumor growth and angiogenesis in vivo. At the same time in the subset of A431 cells, which express high levels of CD133 (a marker of CSCs) we observed several fold greater TF activity than in the corresponding CD133-negative tumor cell population. It is of interest whether high and sometimes heterogenous TF expression can also be linked to the CSC subset in other cell lines and tumors. Notably, in some of these instances tumor growth/take can be inhibited by the administration of TF inhibitors.  Host TF also plays a role in tumor growth. Thus, while TF expressing cancer cells readily form tumors in mice hypomorphic for this receptor, cells rendered TF-deficient fail to grow in such recipients. We postulate that activation of the coagulation system and TF signaling, may deliver growth-promoting stimuli (e.g. fibrin, thrombin, platelets) to dormant CSCs and thereby facilitate tumor take, growth, angiogenesis and metastasis.  In summary, TF may be expressed by CSCs and provide them with the capacity to generate provisional (coagulation-related) cancer stem cell niche due to stimulating influences of coagulation proteases, growth factors and the fibrin matrix. Alternatively, these CSC growth/survival-promoting activities may be associated with the intercellular TF transfer, as cargo of microvesicles, or are delivered in a paracrine manner i.e. by various 9activated9 elements of the tumor stroma (blood vessels, inflammatory cells and mesenchymal cells). Thus, targeting TF may diminish the potential of CSCs to initiate tumor growth, metastasis or recurrence.
Validation of citrate and derivatives in expressed prostatic secretions to predict prostate cancer: High-resolution 1H-NMR study
Authors: Natalie J. Serkova, Eduard J. Gamito, Richard H. Jones, Colin O'Donnell, E. David Crawford
Journal: Cancer Research (2006)

651  Reliable markers for early detection of prostatic cancer which sensitivity/ specificity will be higher than those of PSA (prostatic specific antigen) are desirable. High concentrations of citrate have been reported in vivo in the healthy prostate gland. Quantitative proton nuclear magnetic resonance spectroscopy (1H-NMR) along with a novel statistical method were utilized to analyze and validate endogenous metabolites in expressed prostatic secretions (EPS) from men with prostate cancer (PCa) and from healthy controls. Flash frozen EPS samples from 66 men (40 with PCa and 26 controls) were analyzed by high-resolution 1H-NMR spectroscopy using a Bruker 500 MHz DRX NMR spectrometer with a 1-mm microprobe. The total number of scans per fully relaxed 1H-NMR spectrum was n=40 with water suppression. Absolute concentrations of endogenous metabolites (citrate, spermine, myo-inositol, lactate, alanine, phosphocholine, glutamate, acetate, hydroxybutyrate) were quantified using trimethylsilyl-propionic acid as an external standard reference. Stepwise multivariable logistic regression (LR) was used to model the risk of PCa based upon the levels of the measured metabolites. The average age of the EPS donors was 54.7 ± 9.8 years. The median Gleason score for the men with PCa was 6 (range 5-9). The Wilcoxon rank sum test indicated that citrate, spermine, inositol, citrate/spermine, and citrate/lactate were all significant predictors of PCa (p
Overexpression of BRCA1-IRIS protein in familial ovarian cancers with no <i>BRCA1</i> or <i>BRCA2</i> germline mutation
Authors: R. Boustany, P. Pautier, A. Rey, S. Delaloge, A. Chompret, B. Bressac-De Paillerets, W. M. ElShamy, D. M. Livingston, J. Feunteun, A. Spatz
Journal: Journal of Clinical Oncology (2007)

5513 Background: Germline mutations of the BRCA1 and BRCA2 genes account for the majority of hereditary breast-ovarian carcinomas. Nevertheless, in some patients with family history of ovarian cancers, neither point mutations nor genomic alterations are identified. Recently, IRIS gene, an open reading frame that extended from codon 1 of BRCA1 to a termination point in intron 11, has been identified. The encoded protein has been reported to play a role in controlling the replication origins firing (ROF) pathway. The study presented here aims at characterizing whether ROF-related proteins are differentially expressed among familial ovarian cancers associated with a germline BRCA1 or 2 mutation, familial ovarian cancers with wild-type BRCA1/2 genes, and sporadic ovarian cancers. Methods: Tumor samples from 72 patients with ovarian cancer and screened for BRCA1 and BRCA2 mutation because of family history of breast/ovarian cancer were collected. These cases were matched with 134 sporadic ovarian cancers (controls) according to age, year of diagnosis, tumor stage, histological subtype, and grade. The cases distributed among 26 BRCA1-linked (BRCA1*) tumors, 9 BRCA2-linked (BRCA2*) tumors and 37 with no identified mutation (BRCA1 wt /BRCA2 wt ). Tissue micro-arrays were prepared from the paraffin blocks. P53, MCM3, MCM4, Geminin, PTTG and BRCA1-IRIS immuno-expression were scored with no information on the sample group as follows: the final score was the product of the positive cells percentage by the staining intensity, the final result being used as a continuous variable. Differences between cases and controls were tested by a Wilcoxon test for paired samples. Results: IRIS expression was significantly higher in familial cancers than in controls (P=0.002). When BRCA1/2 genes status was taken into account, differences remained significant when BRCA1 wt /BRCA2 wt tumors (P=0.04), but not when BRCA1* tumors were compared with controls. However, the latter showed significant higher expression of Geminin than controls (P=0.04). Conclusions: BRCA-1 IRIS protein is overaccumulated in ovarian cancers developed by patients with family history. Our results suggest IRIS may play a role in the development of ovarian cancers and could be related with an ovarian susceptibility. No significant financial relationships to disclose.
Methylation-specific MLPA (MS-MLPA): Detection of CpG methylation and copy number changes of up to 40 sequences in one simple reaction
Authors: Chise Matsushita, Seisho Takeuchi, Yang Yang, Masahide Matsushita, Jacques J. M. Van Dongen, Tomasz Szczepański, Claus R. Bartram, Norihide Yoshino, H. Phillip Koeffler, Hirokuni Taguchi
Journal: Cancer Research (2005)

873  Copy number changes and CpG methylation of various genes are hallmarks of tumor development but are not yet widely used in diagnostic settings. The recently developed MLPA method has increased the possibilities for multiplex detection of copy number changes in a routine laboratory. Here we describe a novel robust method: the Methylation-Specific Multiplex Ligation-dependent Probe Amplification (MS-MLPA) which can detect changes in both CpG methylation as well as copy number of up to 40 chromosomal sequences in one simple reaction. In MS-MLPA, the probes are designed similar to ordinary MLPA probes except that the sequences detected by these probes contain a recognition sequence for a methylation-sensitive endonuclease such as HpaII or HhaI. After hybridization of the probes with their targets, the genomic DNA-probe hybrid complexes are simultaneously ligated and digested. Only probes that recognize methylated DNA sequences will generate a signal. In contrast, if the sequences are unmethylated a probe signal will not be detected. Digestion of the genomic DNA-probe complex, rather than double stranded genomic DNA, allowed the use of DNA derived from formalin treated paraffin-embedded tissue samples, enabling retrospective studies. To validate this novel method, we used MS-MLPA to detect aberrant methylation in DNA samples of patients with Prader-Willy syndrome (PWS), Angelman syndrome (AS) or acute myeloid leukemia (AML).
Foot care in epidermolysis bullosa: evidence‐based guideline
Authors: M.T. Khan, M. O'Sullivan, B. Faitli, J.E. Mellerio, R. Fawkes, M. Wood, L.D. Hubbard, A.G. Harris, L. Iacobaccio, T. Vlahovic, L. James, L. Brains, M. Fitzpatrick, K. Mayre‐Chilton
Journal: British Journal of Dermatology (2019)

This guideline was designed to provide service providers and users with an evidence-based set of current best practice guidelines for people and their families and carers, living with epidermolysis bullosa (EB). A systematic literature review relating to the podiatric care of patients with EB was undertaken. Search terms were used, for which the most recent articles relating to podiatric treatment were identified from as early as 1979 to the present day, across seven electronic search engines: MEDLINE, Wiley Online Library, Google Scholar, Athens, ResearchGate, Net and PubFacts.com. The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used. The first guideline draft was analysed and discussed by clinical experts, methodologists and patients and their representatives at four panel meetings. The resulting document went through an external review process by a panel of experts, other healthcare professionals, patient representatives and lay reviewers. The final document will be piloted in three different centres in the U.K. and Australia. Following an EB community international survey the outcomes indicated six main areas that the community indicated as a priority to foot management. These include blistering and wound management, exploring the most suitable footwear and hosiery for EB, management of dystrophic nails, hyperkeratosis (callus), maintaining mobility and fusion of toes (pseudosyndactyly). The evidence here is limited but several interventions currently practised by podiatrists show positive outcomes.
Abstract 9180: HMG-CoA Reductase Inhibitor Stabilizes Mast Cells and Attenuates Atrial Fibrillation in Stressed Hearts
Authors: Masanori Fujimoto, Hiroshi Akazawa, Toshio Nagai, Yoshio Kobayashi, Haruaki Nakaya, Issei Komuro
Journal: Circulation (2011)

Atrial fibrillation (AF) is a common arrhythmia, which increases the risk of stroke and heart failure. We previously reported that mast cells play a pathogenic role in atrial fibrosis and AF inducibility in transverse aortic constriction (TAC)-operated mice. On the other hand, it has been reported that treatment with HMG-CoA reductase inhibitors significantly decreased the incidence of postoperative AF after cardiac surgery. To explore the potential use of HMG-CoA reductase inhibitors in the upstream therapy for AF, we investigated whether pitavastatin could stabilize mast cells and thereby prevent the occurrence of AF in TAC-operated mice. Pressure overload induced interstitial fibrosis in atrium, and electrical stimulation on atrium evoked AF under Langendorff perfusion. However, treatment with pitavastatin (3 mg/kg/day) remarkably attenuated both atrial fibrosis and AF inducibility in pressure-overloaded mice. In addition, pressure overload induced mast cell degranulation and macrophage infilatration in atrium, which was associated with increased mRNA levels of MCP-1, IL-6, IFN-γ, TNF-α and PDGF-A. Notably, activation of mast cells and macrophages, as well as up-regulations of these inflammatory cytokines and growth factors, in atrium of TAC-operated mice was almost completely inhibited by pitavastatin treatment. Endothelin-1, known as potent mast cell activator, is up-regulated in atrium after TAC operation, and ET-1-induced degranulation in mouse peritoneal cavity-derived mast cells was significantly inhibited by treatment with pitavastatin (5 μM). These results suggest that pitavastatin suppresses mast cell activation both in vitro and in vivo, and thereby alleviates atrial fibrosis and AF inducibility through inhibition of cytokine production and macrophage infiltration in atrium of pressure-overloaded mice.
Myocardial infarction triggers cardioprotective antigen-specific T helper cell responses
Authors: Max Rieckmann, Murilo Delgobo, Chiara Gaal, Lotte Büchner, Philipp Steinau, Dan Reshef, Cristina Gil-Cruz, Ellis N. ter Horst, Malte Kircher, Theresa Reiter, Katrin G. Heinze, Hans W.M. Niessen, Paul A.J. Krijnen, Anja M. van der Laan, Jan J. Piek, Charlotte Koch, Hans-Jürgen Wester, Constantin Lapa, Wolfgang R. Bauer, Burkhard Ludewig, Nir Friedman, Stefan Frantz, Ulrich Hofmann, Gustavo Campos Ramos
Journal: Journal of Clinical Investigation (2019)

T cell autoreactivity is a hallmark of autoimmune diseases but can also benefit self-maintenance and foster tissue repair. Herein, we investigated whether heart-specific T cells exert salutary or detrimental effects in the context of myocardial infarction (MI), the leading cause of death worldwide. After screening more than 150 class-II-restricted epitopes, we found that myosin heavy chain alpha (MYHCA) was a dominant cardiac antigen triggering post-MI CD4+ T cell activation in mice. Transferred MYHCA614-629-specific CD4+ T (TCR-M) cells selectively accumulated in the myocardium and mediastinal lymph nodes (med-LN) of infarcted mice, acquired a Treg phenotype with a distinct pro-healing gene expression profile, and mediated cardioprotection. Myocardial Treg cells were also detected in autopsies from patients who suffered a MI. Noninvasive PET/CT imaging using a CXCR4 radioligand revealed enlarged med-LNs with increased cellularity in MI-patients. Notably, the med-LN alterations observed in MI patients correlated with the infarct size and cardiac function. Taken together, the results obtained in our study provide evidence showing that MI-context induces pro-healing T cell autoimmunity in mice and confirms the existence of an analogous heart/med-LN/T cell axis in MI patients.
Mass spectrometry-based proteomic techniques to identify cerebrospinal fluid biomarkers for diagnosing suspected central nervous system infections. A systematic review
Authors: Tehmina Bharucha, Bevin Gangadharan, Abhinav Kumar, Xavier de Lamballerie, Paul N. Newton, Markus Winterberg, Audrey Dubot-Pérès, Nicole Zitzmann
Journal: Journal of Infection (2019)

Central nervous system (CNS) infections account for considerable death and disability every year. An urgent research priority is scaling up diagnostic capacity, and introduction of point-of-care tests. We set out to assess current evidence for the application of mass spectrometry (MS) peptide sequencing in identification of diagnostic biomarkers for CNS infections.We performed a systematic review (PROSPEROCRD42018104257) using PRISMA guidelines on use of MS to identify cerebrospinal fluid (CSF) biomarkers for diagnosing CNS infections. We searched PubMed, Embase, Web of Science, and Cochrane for articles published from 1 January 2000 to 1 February 2019, and contacted experts. Inclusion criteria involved primary research except case reports, on the diagnosis of infectious diseases except HIV, applying MS to human CSF samples, and English language.4,620 papers were identified, of which 11 were included, largely confined to pre-clinical biomarker discovery, and eight (73%) published in the last five years. 6 studies performed further work termed verification or validation. In 2 of these studies, it was possible to extract data on sensitivity and specificity of the biomarkers detected by ELISA, ranging from 89-94% and 58-92% respectively.The findings demonstrate feasibility and potential of the methods in a variety of infectious diseases, but emphasise the need for strong interdisciplinary collaborations to ensure appropriate study design and biomarker validation.
The prevalance of chronic autoimmune urtiker and angioedema among lung and breast carcinoma cases
Authors: D. Yalcin, A. Kargi, B. Savas, A. Bisgin, M. Ozdogan, S. Coskun, E. Terzioglu
Journal: Journal of Clinical Oncology (2009)

e20707 Background: Although the risk of allergy and atopy in cancer patients has been studied in various prospective studies previously, no significant association was found between leukemia, breast, colorectal, lung cancers and allergic disorders or atopy. Our purpose in this study was to investigate the prevalance of chronic urticeria and angioedema in breast and lung carcinoma of adults in Mediterrianean Coast of Turkey, Antalya. Methods: 86 breast and 62 lung carcinoma patients that had diagnosed and underwent chemotherapy in Akdeniz University Oncology Clinic were studied. Blood eosinophil, total IgE, ANA, C3, C4, hepatitis markers and autologous skin test were examined in the cases with probable chronic autoimmune urticeria, angioedema. The data were statistically assessed with SPSS version 13.00. Results: Overall 148 patients were included. Median age was 62.4±14.6 years, 60.1% of the patients were women (47.2% of which is not working). 55.6% of the patients are living in apartments. In general, 5.4% (8 case) of the investigated population were diagnosed as autoimmun urticeria; Seven of the 8 of these were breast carcinoma cases (7 out of 86 breast Ca). In contrast, only one of them was lung carcinoma (1 out of 62 lung Ca). Total IgE level was 122 ± 21.4. None of the cases with positive autologous skin test has ANA positivity. Similarly, these cases were also HBV and HCV seronegative. Accompanying angioedema was present 3 cases (with no drug or food history). One case has a hashimato tiroiditis who underwent LT4 replacement. Another patient with autoimmun urticeria has allergical asthma together with 5 cases of allergical rhinitis and conjunctivitis. Conclusions: In this study the frequency of autoimmune urticeria is much higher in breast carcinoma cases compared to patients with lung carcinoma. Further researchs are needed to verify these results and to determine why such association exist. No significant financial relationships to disclose.
Abstract #3101: PRL-2 knockdown inhibits tumor cell migration and invasion
Authors: Yan Wang, John Lazo
Journal: Cancer Research (2009)

The Phosphatase of Regenerating Liver (PRL) family, consisting of PRL-1, PRL-2, and PRL-3, is a group of prenylated phosphatases being considered as potential biomarkers and therapeutic targets in cancer. Individual PRLs are over-expressed in a variety of cancer cell lines and tissues, and the over-expression of PRLs is associated with tumorigenesis and metastasis. Several recent studies have shown that ectopic expression of PRL-1 or PRL-3 can influence cell proliferation, migration and invasion. Knockdown of endogenous PRL-1 or PRL-3 can abrogate cell motility and metastasis in mouse models. However, little is known about the biological functions of PRL-2. In this study, we evaluated the role of PRL-2 in cell migration, invasion and metastatic processes in human cancer cells. PRL-2 was over-expressed in four lung cancer cells, including A549, when compared with normal lung cells. We transfected A549 lung cancer cells with four short hairpin RNAs for PRL-2 and selected single colonies with significantly suppressed PRL-2. The down-regulation of PRL-2 resulted in about 40% inhibition on cell migration and invasion. We also used short interference RNAs for transient PRL-2 knockdown to study the signaling pathway(s) for PRL-2 mediated cell migration and invasion. We found decreased p130cas and vinculin expression, and increased tyrosine phosphorylation of Focal adhesion kinase (FAK) and ezrin in the PRL-2 knockdown cells. Previous data indicated that the PRL-1 knockdown inhibited tumor invasion by decreasing c-Src levels in A549 cells. However, our current data suggested that PRL-2 knockdown may inhibit tumor cell migration and invasion through a Src-independent p130cas signaling pathway. Thus, PRL-1 and PRL-2 appear to be functionally similar, but not redundant.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3101.