tbuckley/cabot-search huggingface dataset:
Mitotic Activity Index Identifies Both Over- and Undertreated Lymph Node Negative Breast Cancer Patients &amp;lt; 55 Year According to the Norwegian Treatment Guidelines.
Authors: T. Hoel Lende, T. Hoel Lende, T. Hoel Lende, E. Gudlaugsson, E. Gudlaugsson, E. Janssen, F. Voorhorst, P. Van Diest, H. Søiland, J. Baak, J. Baak, J. Baak
Journal: Cancer Research (2009)

Abstract Background: It is a challenge to avoid under- and overtreatment of breast cancer patients in the adjuvant setting. Patients who have not received adjuvant systemic treatment and with a known outcome demonstrate the natural course of the disease after surgery. Such patients may be re-evaluated in specific guidelines like the Norwegian Breast Cancer Group (NBCG) based on the St. Gallen criteria. NBCG classify the patients in a low-risk group which should not receive systemic treatment, and a high-risk group which should be offered such therapy. New factors may be evaluated in these two strata, possibly discriminating groups of under- or overtreated patients. The aim of this study was to explore if the previous established marker of proliferation, the mitotic activity index (MAI), could give any additional information.Patients and methods: The study comprised 516 lymph node negative patients &amp;lt; 55 years from the Dutch prospective Multicenter Morphometric Mammary Carcinoma Project (MMMCP; 1987-1989)1. No adjuvant systemic treatment was given after surgery to these patients. The guidelines from NBCG-2005 were used to classify the patients in “NBCG low-risk” group (n=100) defined as pT1/Grade 1, all ages and pT1a-b/Grade 2-3, &amp;gt;35 years, all hormone receptor positive. The rest of the patients (n=416) was grouped as “NBCG high-risk”. Breast Cancer Specific Survival (BCSS) was estimated by the Kaplan-Meier method. MAI was analyzed after a standardized protocol in the invasive front of the tumor. The previous established thresholds of MAI with low (&amp;lt;3), intermediate (3-9) and high (≥10) proliferation were used in the calculations.Results: In the “NBCG low-risk” group 10 % of the patients had MAI ≥10. These had a 14-years BCSS of 50 % (HR=15.47, 95 % CI=3.61-66.30) and may be regarded as undertreated patients. Patients with MAI &amp;lt;3 and 3-9 had a BCSS of 95 % and 83 % respectively. In the “NBCG high-risk”group 24 % of the patients with MAI&amp;lt;3 had a 14-years BCSS of 92 % indicating overtreatment. Furthermore, patients with MAI 3-9 and ≥10 had a BCSS of 74 % and 63 % (p-trend &amp;lt;0.0001).Discussion: MAI represents the “converging mitotic drive” from all cellular signal pathways in the peripheral growing zone of the tumor, where also micro-environmental factors are known to influence proliferation of cancer cells. This may explain why MAI gives original information strong enough to identify subgroups breast cancer patients who would not get optimal adjuvant treatment. A disadvantage of this study is that the HER-2 status in this MMMCP material is not known. National prospective studies are needed to verify our results.1 Baak, JPA et al: Pathol Res Pract 185:664-70,1989. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3182.
The Impact and Evolution of Medicare Part D
Authors: Julie M. Donohue
Journal: New England Journal of Medicine (2014)

Interview with Prof. Julie Donohue on the policy lessons from Medicare’s drug benefit. (12:44)Download Criticisms during the implementation of Medicare Part D are echoed in those being voiced about the Affordable Care Act. Yet Part D successfully expanded drug benefits to millions of beneficiaries and improved access to medications, at lower-than-expected cost.
PWE-050 Development Of A Performance Management Framework For Bsw Colonoscopists
Authors: N Hawkes, H Heard, S Dolwani
Journal: Gut (2014)

<h3>Introduction</h3> The Bowel Screening Wales (BSW) programme has completed 12,000 colonoscopies since 2008. All Screening Colonoscopists are assessed, approved and quality assured by BSW. Colonoscopy is an invasive procedure with inherent risks. Complication rates in the BSW programme have occurred at expected levels but investigation has highlighted potentially preventable causes. We have developed a Performance Management Framework (PMF) to support colonoscopists where lesion assessment or therapeutic decision-making was associated with a pattern of adverse outcomes. <h3>Methods</h3> A researcher (NH) conducted semi-structured interviews with BSW colonoscopists following active diary collection on BSW lists (Jan–Feb 2013). Narrative data was examined related to documented or recalled near-miss episodes or complications and evaluated alongside existing published case-control or cohort studies and BSW root-cause analysis data to inform the development of the PMF. The main criteria used in its development were; fairness, transparency, consistency of application, practicality and alignment to existing BSW QA frameworks (centralised data, feedback, QA visits and training). A draft PMF was presented to BSW Lead Colonoscopists in November 2013. <h3>Results</h3> The framework comprises the following steps: 1) Identification of issues; 2) Investigation; 3) Observation; 4) Training. Issues may be identified from performance data, reported near-miss episodes, self- or peer-reported complications or from patient complaints. Investigations review all documentation, endoscopic images, pathology and radiology depending on the nature of incident. Trained QA assessors and mentors are required to provide detailed observation of performance in the context of colonoscopist's usual working environment, using validated DOPS methodology (incorporating discussion around decision-making). The final step involves the colonoscopist agreeing a tailored training plan based on feedback from BSW QA advisors, assessors and mentors. This states 1) the nature of the concerns identified; 2) specific goals to be achieved; 3) timetabling and 4) tools to be employed to measure progress. Where there is serious concern for participant safety the BSW Colonoscopy Panel may consider suspension pending appropriate investigation and training. The outcome of training will be reviewed by this Panel to determine ongoing suitability to perform as a screening colonoscopist. <h3>Conclusion</h3> A pragmatic Performance Management Framework for BSW Colonoscopists has been developed. It seeks to provide a safe and supportive environment for both patients and colonoscopists respectively undergoing and performing complex therapeutic interventions, aiming to provide early identification of problems through central data analysis and specific, targeted training interventions where required. <h3>Disclosure of Interest</h3> None Declared.
Impact of Primary Site Surgical Resection on Survival in Stage IV Breast Cancer.
Authors: S. Ahn, W. Han, J. Min, J. Bae, E. Ko, J. Yu, D. Noh
Journal: Cancer Research (2009)

Abstract Background: Currently, primary treatments for stage IV breast cancer are radiation and systemic therapy which include chemotherapy, endocrine therapy and targeted therapy. Surgical resection of primary tumor is usually done for tumor-related complications. A recent review suggested that surgery may improve long-term survival in stageIV breast cancer patients. We evaluated the impact of primary site surgical resection on survival in such patients.Material and Methods: We reviewed the records of stage IV breast cancer patients treated at Seoul National University Hospital between 1992 and 2008. Clinical and tumor characteristics, systemic and local treatments were compared for the surgically versus nonsurgically treated patients.Results: Of 199 patients identified, 111(55.8%) recevied surgical excision of their primary tumor and 88(44.2%) did not. The mean survival of surgically treated patients was 67 months versus 52 months for patients those who did not(p=0.0276). In multivariate analysis, after adjustment for ER status, visceral metastasis, number of metastatic sites and herceptin treatment, surgery remained an independent factor associated with improved survival(HR 0.547[95%CI 0.359-0.971] p=0.001).Discussion: Surgical resection of the primary tumor in stage IV breast cancer patient was independently associated with improved survival, even after adjustment for other factors associated with survival. Randomized prospective trials are needed to validate these findings. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3117.
Abstract 1465: Prognostic significance of stem cell and EMT phenotype in Circulating Tumor Cells.
Authors: Areti D. Strati, Vasilis Georgoulias, Evi Lianidou
Journal: Cancer Research (2013)

Abstract Background: Circulating tumor cells (CTCs) are associated with prognosis and can be used as a liquid biopsy for repeated follow up examinations. The subpopulation of CTCs that successfully establish distant metastases share EMT and stemness features. These cells have been found to be associated with resistance to anti-cancer therapies and treatment failure. Patients and methods: Peripheral blood (20 mL in EDTA) was obtained and after density gradient centrifugation, immunomagnetic Ber-EP4 coated capture beads were used to enrich for epithelial cells from 102 patients with early breast cancer and 23 patients with verified metastasis. Messenger RNA was isolated from enriched epithelial cells using oligo (dT)25 coated magnetic beads. After cDNA synthesis the expression of CK-19, MAGE-A3, HER-2, PBGD and CD24, CD44, ALDH1, HPRT was tested, using two different quadruplex RT-qPCR assays. Moreover we performed RT-qPCR for the expression of TWIST1, hMammaglobin and hTERT α+β+. Results: The presence of circulating tumor cells was evaluated using CK-19, MAGE-A3, HER-2, hTERT α+β+, and mammaglobin gene transcripts. In 102 operable breast cancer patients 31 patients (30.4%) were found positive for the presence of CTCs. CTC biomarkers were significantly correlated with lymph nodes (P=0.032). In the CTC+ group, 10 patients (32.3%) were positive for TWIST1 and 16 (51.6%) were positive for CD44+/CD24-/low and ALDH1+ cell phenotype. We found a significant correlation between HER2 negative tumors with TWIST1 expression (P=0.027) and Stem Cell phenotype (P=0.012). The detection of both EMT and Stem Cell characteristics was associated with shorter disease-free survival (P=0.024). In the CTC positive group of patients with verified metastasis (39.1%) 1 patient (11.1%) was positive for TWIST1 and 4 (44.4%) were positive for CD44+/CD24-/low and ALDH1+ cell phenotype. The detection of CK19+, Stem Cell and Stem Cell and/or EMT phenotype was associated with shorter overall-free survival (P=0.036, P=0.001 and P=0.002). Discussion: CTCs in breast cancer patients share both stem cell and/or EMT phenotype. The detection and molecular characterization of CTCs with an EMT or stem cell-like characteristics could be a powerful diagnostic tool for the determination of prognosis and designing new therapeutic drugs for the elimination of minimal residual disease. Citation Format: Areti D. Strati, Vasilis Georgoulias, Evi Lianidou. Prognostic significance of stem cell and EMT phenotype in Circulating Tumor Cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1465. doi:10.1158/1538-7445.AM2013-1465
Severe Hypothyroidism Caused by Type 3 Iodothyronine Deiodinase in Infantile Hemangiomas
Authors: Stephen A. Huang, Helen M. Tu, John W. Harney, Maria Venihaki, Atul J. Butte, Harry P.W. Kozakewich, Steven J. Fishman, P. Reed Larsen
Journal: New England Journal of Medicine (2000)

Hemangiomas are the most common tumors of infancy, with a prevalence of 5 to 10 percent among one-year-olds. They are characterized by rapid growth in the first year of life, followed by involution and gradual regression by adolescence.1,2 We recently treated a three-month-old infant with massive hepatic hemangiomas and primary hypothyroidism who needed very high doses of thyroid hormone to restore euthyroidism and normal thyrotropin secretion. This finding suggested that the rate of degradation of thyroid hormone was accelerated. We subsequently identified high levels of type 3 iodothyronine deiodinase activity in the hemangioma tissue. This selenoenzyme, normally present in . . .
Phosphoproteomic study of breast cancer: high-throughput SH2 screening.
Authors: K Machida, KP Claffey, CM Thompson, D Shin, BJ Mayer
Journal: Cancer Research (2009)

Abstract Abstract #2031 Background: Protein tyrosine phosphorylation plays an important role in breast cancer cells. Tyrosine kinases such as Src and HER-2 have been shown to be overexpressed in invasive breast cancer tissues, and thus are used as prognostic markers and therapeutic targets. However, substrate proteins for tyrosine kinases in breast cancer tissues have not been extensively studied due to technical difficulties including low sensitivity and large sample requirement. Recently we established a high-throughput method using Src homology 2 (SH2) domain probes, termed SH2 profiling, to profile proteomes based on interaction between SH2 domains and tyrosine-phosphorylated proteins. In this study we aimed to optimize the assay for breast cancer tissues and evaluate SH2 profiling based classification. Material and Methods: Protein lysates from 10 breast cancer patient tissues as well as cancer cell lines were prepared and spotted in multiple duplicates on a nitrocellulose membrane. The blocked membrane was incubated with HRP-labeled GST-SH2 domain probes using a 96 well chamber apparatus. Bound probes were detected by chemiluminescence and signals were quantified using densitometry. Quantitative SH2 binding profiles of breast cancer samples were compared using a hierarchical clustering program. Results and discussion: 1. Although signal-to-noise ratio of breast cancer tissues was relatively low compared to cell lines, possibly due to non-cancerous material in clinical samples, specific signal was detectable using as little as 100 micrograms of sample protein for the entire assay. 2. Unsupervised clustering analysis based on SH2 binding patterns correctly separated HER-2 positive from HER-2 negative tumors, indicating the diagnostic potential of this method. Further validation studies with more samples are needed. 3. Although phosphoproteomics has not yet been adopted in the clinic because of issues related to sample requirements, reproducibility, and sensitivity, this pilot study strongly suggests that clinical applications of phosphoproteomics are feasible. This study is supported by the Breast Cancer Alliance. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2031.
Abstract 274: PGC-1α over-expression is related to increased cell proliferation and tumorigenesis
Authors: Joo-In Park, Sung-Won Shin, Eun-Seon Park, Seong-Hoon Yun, Seon-A Lee, Jin-Sook Jeong, Jong-Young Kwak
Journal: Cancer Research (2011)

Abstract Peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) is a coactivator interacting with multiple transcription factors and regulates several metabolic processes. Recent studies have focused on the role of several coactivators in cancer. Especially, a role of PGC-1α in cancer has been controversial. Some studies show that the expression level of PGC-1α decreased in certain cancer tissues and PGC-1α over-expression induces apoptosis in ovarian cancer cells. On the contrary, it has been found that PGC-1α promotes cell growth in prostate cancer cells, suggesting that PGC-1α may be involved in the pathogenesis of cancer. However, the molecular mechanism for it has not been clarified. Thus, the role of PGC-1α in the cell proliferation and tumorigenesis was evaluated using human embryonic kidney HEK293 cells that stably over-expressed PGC-1α. Forced expression of PGC-1α in HEK293 cells resulted in increased cell proliferation and anchorage-independent growth in soft agar. In addition, HEK293 cells that highly expressed PGC-1α enhanced tumor formation when these cells are subcutaneously injected into the bilateral flanks of immunodeficient Balb/c mice. To find out the molecular targets for increased proliferation and tumorigenesis by PGC-1α, GeneFishing DEG screening system was employed. As a result, one up-regulated gene (acyl-CoA binding protein; ACBP) was identified. Up-regulated ACBP expression was confirmed by Western blot and immunofluorescence microscopy. The expression of ACBP was decreased by PGC-1α siRNA transfection. These data suggest that the expression of ACBP may be related to the expression of PGC-1α. In addition, down-regulation of ACBP and PGC-1α by siRNA transfections resulted in the decreased cell proliferation. Taken together, these findings suggest that PGC-1α may promote cell proliferation and tumorigenesis. Thus, PGC-1α can be a good candidate for a molecular therapeutic target for cancers. However, the detailed molecular mechanisms for up-regulation of ACBP by PGC-1α are remained unresolved. Thus, further studies on the clarification of molecular interactions of ACBP and PGC-1α are needed. This study was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) through the Medical Research Center for Cancer Molecular Therapy at Dong-A University (R13-2002-044-05002-0). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 274. doi:10.1158/1538-7445.AM2011-274
Abstract PR1: Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis
Authors: Mvriam Labelle, Shahinoor Begum, Richard O. Hynes
Journal: Cancer Research (2011)

Abstract Interactions of cancer cells with the primary tumor microenvironment are important determinants of cancer progression towards metastasis but it is unknown whether additional prometastatic signals are provided during the intravascular transit to the site of metastasis. Here, we have tested whether platelets present in the bloodstream can provide a signaling platform for cancer cells outside of the primary tumor and influence the metastatic potential of tumor cells. We show that platelet-tumor cell interactions are sufficient to prime tumor cells for subsequent metastasis. Platelet-derived TGFß and direct platelet-tumor cell contacts synergistically activate the TGFß/Smad and NF-κB pathways in cancer cells, resulting in their transition to an invasive mesenchymal-like phenotype and enhanced metastasis in vivo. Inhibition of NF-κB signaling in cancer cells or ablation of TGFß1 expression solely in platelets protects against lung metastasis in vivo. Thus, our study establishes platelets as a major and critical source of TGFß bioavailable to cancer cells in the circulation, and reveals that the metastatic potential of tumor cells continues to evolve outside the primary tumor site, in response to tumor-host interactions in the bloodstream. Platelet-tumor cell interactions and the signaling pathways that they trigger are therefore crucial determinants of cancer metastasis and potential targets for anti-metastatic therapies. This abstract is also presented as Poster A9. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr PR1.
Metastatic Pure Papillary Thyroid Carcinoma Presenting as a Toxic Hot Nodule
Authors: ROBERT L. CIRILLO, RODNEY V. POZDERAC, DONNA A. CANIANO, JAMES M. FALKO
Journal: Clinical Nuclear Medicine (1998)

In the majority of cases, carcinoma of the thyroid presents as a cold nodule by radioiodine and Tc-99m sodium pertechnetate scintigraphy. Whereas the presence of a hot nodule usually implies a benign entity, it does not provide complete assurance against thyroid malignancy. Presented is a rare case of metastatic pure papillary thyroid carcinoma appearing as a hot nodule on Tc-99m sodium pertechnetate and I-123 sodium iodide scintigraphy. The implications of such a case, its management, and review of the pertinent literature are discussed.
Accelerated chemotherapy with high-dose epirubicin and cyclophosphamide plus r-met-HUG-CSF in locally advanced and metastatic breast cancer
Authors: A.F. Scinto, V. Ferraresi, N. Campioni, R. Tonachella, L. Piarulli, I. Sacchi, D. Giannarelli, F. Cognetti
Journal: Annals of Oncology (1995)
Cadaver-Kidney Transplant Failures at One Month
Authors: E.A. Clark, P.I. Terasaki, G. Opelz, M.R. Mickey
Journal: New England Journal of Medicine (1974)

Three major factors contributing to early one-day and one-month failure rates were determined in a series of 1899 cadaver-kidney transplantations in over 100 transplant centers in the United States and Canada. The first was that one-month failure rates were greater among 1206 kidneys preserved by continuous perfusion (30 per cent) than among 479 kidneys preserved without perfusion (20 per cent) (p < 0.0001). The one-year survival rate for machine-preserved kidneys was 40 ± 2 per cent as compared to 62 ± 4 per cent for cold-stored kidneys (p < 0.0001). Secondly, a significant association of nonfunction with increasing levels of cytotoxins was found at one day and at one month. In the highly presensitized group 49 per cent of 65 grafts failed in one month. Finally, as expected, warm ischemia time was also progressively detrimental to one-month function. (N Engl J Med 291:1099–1102, 1974)
LEFT ATRIAL APPENDAGE MORPHOLOGY AND STROKE RISK IN PATIENTS WITH ATRIAL FIBRILLATION: A META-ANALYSIS
Authors: Florentino Lupercio, Juan Carlos Diaz, Pedro Villablanca Spinetto, David Briceno, Jorge Romero, Susana Gonzalez, Carola Maraboto, Andrew Krumerman, Mario Garcia, Andrea Natale, Luigi Di Biase
Journal: Journal of the American College of Cardiology (2016)
Phthalates in food on the Belgian market: occurrence and possible contamination pathways
Authors: Mirja Van Holderbeke, Lieve Geerts, Tine Fierens, Kelly Servaes, Guido Vanermen, Isabelle Sioen
Journal: Environmental Health Perspectives (2011)

Background and Aims: Phthalates are used in many industrial and consumer products. High-molecular-weight phthalates are primarily used as plasticizers to soften PVC products, while low-molecular-weight phthalates are widely used as solvents to hold colour and scent in products. Phthalates have been detected in food and also measured in humans.
This study investigated phthalates in food products on the Belgian market in order to explore possible contamination pathways. 
Methods: 650 Representative samples of widely consumed foods were purchased in Belgian shops.  The levels of eight phthalates were determined and product specific properties were stored in a database. This database was used to explore the contamination pathways by identifying relations between sample properties (e.g. fat content, pH and packaging) and measured phthalate concentrations.    
Results: The results of the measurement campaign show a wide variety of phthalate concentrations in the food samples. Concentrations are higher in high-fat food products like butter, oil and cheese compared to low-fat food products, like vegetables and juices. Higher phthalate concentrations were also detected in some cardboard packed food, probably due to migration from inks and glues. Aluminium inner package seems to be a good barrier for migration. A wide range of phthalate levels in bread was found and further research is necessary.   
Conclusions: A wide variety in phthalate concentration was found. The fat content of the food product, the composition of the food as well as the composition and properties of the packaging material have been identified as possible contamination causing conditions. In a next phase of this study, we will use these data to quantify the dietary intake of phthalates for the Belgian population.