tbuckley/cabot-search huggingface dataset:
Abstract 1097: Transient mechanical stimulation can enhance cancer cell invasion.
Authors: Snehal Orzakar, Karen A. Beningo
Journal: Cancer Research (2013)

Abstract Formation of secondary tumors by metastasis is a leading cause of death in cancer patients. During metastasis cells separate from the primary tumor, invade the stroma, travel through blood and lymph and colonize tissues distant from the primary mass. Several biochemical factors have been identified which are able to drive this metastatic cascade. However information of the role of mechanical factors in cancer metastasis has primarily focused on the effect of compliance, overshadowing other mechanical factors that might facilitate the metastatic progression. For example, contractile cells produce short term stress on extracellular matrix fibers during extensive remodeling of the stroma, such variable and transient force would easily propagate through the fibers providing communication between cells. To simulate this type of stress, we developed an in vitro invasion assay where cancer cells are subjected to tugging or pulling forces, similar in randomness and magnitudes to those produced by contractile cells in the tumor microenvironment, without interference of any secreted factors that could be provided by the stromal cells. We discovered a significant difference in the extent of invasion by cancer cells that were mechanically stimulated in this manner verses non- stimulated cell culture environments. This response requires the presence of fibronectin in the extracellular matrix. The objective of our current study is to understand the mechanotransduction pathway leading to enhanced invasion. We speculated that in response to mechanical forces in the stroma, tumor cells will show an altered expression of genes involved in mechanosensing. We performed expression profiling of several genes related to cell migration, adhesion and tumor metastasis by real-time PCR analysis. Given a 24 hour assay period, six genes were confirmed to be differentially expressed between mechanically stimulated and non-stimulated conditions. Of particular interest was the down-regulation of a fibronectin specific integrin subunit in response to the mechanical stimulation that enhanced invasion. Over-expression of this gene resulted in a significant decrease in enhanced invasion, supporting its role in sensing the mechanical stimulus. We speculate that mechanical stimulation during cancer cell invasion results in integrin cross-talk leading to the downregulation of specific integrins, while enriching others within the invadopodia. Citation Format: Snehal Orzakar, Karen A. Beningo. Transient mechanical stimulation can enhance cancer cell invasion. [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 1097. doi:10.1158/1538-7445.AM2013-1097
PTU-269 Lack of engagement in surgical quality improvement research is associated with poorer quality of care
Authors: BE Byrne, P Aylin, A Bottle, OD Faiz, A Darzi, CA Vincent
Journal: Gut (2015)

<h3>Introduction</h3> Existing research suggests consultants who engage in national specialty-specific audits have better outcomes than those who do not. This study used public data to assess for differences between units that did or did not participate in a recent interview study. <h3>Method</h3> Risk-adjusted length of stay after elective colonic surgery was determined for all English National Health Service hospitals between January 2011 and December 2012. Units with high or low outlying length of stay were selected for interview. Public data was collected for selected units, covering a range of structures, processes and outcomes, including: number of medical staff per bed; rate of incident reporting per 100 hospital admissions; healthcare acquired infection rates; and patient and staff surveys. Participant and non-participant groups were compared using the independent samples Mann-Whitney U test. <h3>Results</h3> Fewer long length of stay units participated in interviews (10/10 units with short versus 5/12 units with long length of stay, <i>p = </i>0.005). Of 56 items compared between participants and non-participants, 9 were significantly different at <i>p &lt; </i>0.10. In each case, the difference suggested superior performance among participating hospitals, which had: lower rates of Clostridium difficile infections; lower rates of cancellation of elective operations; fewer staff reporting work-related stress; and higher patient survey ratings of doctors and nurses. <h3>Conclusion</h3> Failure to engage in quality improvement research may be a marker of poor performance. Future research should explore this lack of engagement, and identify strategies for overcoming barriers to participation. Organisations with poor performance may stand to benefit the most from quality improvement research. <h3>Disclosure of interest</h3> None Declared.
Multimodal endoscopic therapy for multifocal intraepithelial neoplasia and superficial esophageal squamous cell carcinoma - a case series
Authors: V. Becker, M. Bajbouj, R. Schmid, A. Meining
Journal: Endoscopy (2011)

Local endoscopic procedures are increasingly used and accepted treatments for unifocal superficial esophageal squamous cell carcinoma (SESCC). In multifocal SESCC, esophagectomy with or without chemoradiotherapy is often regarded as standard therapy. However, a combination of local endoscopic resection and new techniques such as radiofrequency ablation may play an increasing role in the treatment of selected patients with multifocal SESCC. The aim of this series was to evaluate the feasibility of a multimodal endoscopic approach. We report a case series of six consecutive patients from a European tertiary center who underwent endoscopic treatment for multifocal SESCC. The treatment comprised endoscopic mucosal resection using the cap technique or endoscopic submucosal dissection, in combination with radiofrequency ablation. The main outcome measure was complete tumor eradication after therapy and during the follow-up period. Using such an approach, complete eradication of cancer was achieved in all patients during follow-up. No major adverse events occurred. In conclusion, in selected patients with multifocal or residual SESCC, local resection techniques in combination with radiofrequency ablation may be safe and potentially curative alternative treatments.
Abstract 3877: ABT-737 synergizes with bortezomib to induce apoptosis: Activation of Bid, Bak, and Bax in the apoptotic response in malignant human glioma cells
Authors: Esther P. Jane, Daniel Premkumar, Joseph DiDomenico, Naomi Agostino, Natalie Vukmer, Ian Pollack
Journal: Cancer Research (2012)

Abstract Glioblastomas are invasive tumors with poor prognosis despite current therapies. ABT-737 has monotherapeutic toxicity against leukemia, lymphoma and other malignancies, and we and others have noted some antiglioma activity, although insufficient to warrant use as monotherapy. We have recently demonstrated that proteasome inhibitors, such as bortezomib, dramatically sensitized highly resistant glioma cells to apoptosis induction, suggesting that proteasomal inhibition may be a promising combination strategy for glioma therapeutics. In this study, we examined whether bortezomib could enhance response to ABT-737 inhibition in glioma cells. Although primary cells from glioblastoma multiforme (GBM) patients and established glioma cell lines did not show significant induction of apoptosis with ABT-737 treatment alone, the combination of ABT-737 plus bortezomib, significantly enhanced apoptosis. The enhanced efficacy was due to proapoptotic mitochondrial injury and increased generation of reactive oxygen species. Our results also revealed that combination of bortezomib/ABT-73 enhanced apoptosis by increasing Bid cleavage, Noxa upregulation, Bak, Bax activation, and cytochrome c release. Further downregulation of Mcl-1 using shRNA enhanced cell killing by the bortezomib/ABT-737 combination. The significantly enhanced antitumor activity that results from the combination of bortezomib and ABT-737 offers promise as a novel treatment for glioma patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3877. doi:1538-7445.AM2012-3877
Which are the interactions between baseline body mass index (BMI), toxicity of chemotherapy (CT), and efficacy of adjuvant treatments? 9-year follow-up results of French Adjuvant Study Group (FASG) trials
Authors: L. Gladieff, P. Fumoleau, P. Kerbrat, J. Bonneterre, F. Mayer, M. Namer, A. Monnier, M.-J. Goudier, E. Luporsi, H. Roche
Journal: Journal of Clinical Oncology (2004)

550 Objective: The aim of our analysis was to determine the role of BMI on toxicities of adjuvant CT, and if the efficacy of adjuvant treatments was modified by an abnormal BMI (abBMI). Methods: Among the 8 FASG trials, 3,144 patients (pts) were assessable: 1,618 received adjuvant CT alone, 890 CT plus tamoxifen (Tam), 441 hormonotherapy alone, and 195 no systemic treatment. In 2,508 pts receiving CT, it was FEC regimens (epirubicin [E] 50,75, or 100 mg/m2) in 68%, and other E-based CT in the others. The median follow-up was 9 years. BMI = weight (kg)/[size (m)]2: abBMI value was defined as > 27 (WHO classification). We compared pts characteristics and toxicities according to BMI. Then, disease-free (DFS) and overall survival (OS) were computed in a multivariate model according to adjuvant treatment. Results: Median BMI was 24 kg/m2 with 810 (26%) pts > 27. AbBMI was significantly more frequent in menopausal pts, if tumor size > 2 cm, N > 3, and progesterone receptors positive (PR+). Mean E cumulative dose delivered was higher in abBMI pts (342 v 326 mg/m2, P = .009). AbBMI pts had less grade 3–4 neutropenia (11.2% v 14.7%, P = .001), and more left ventricular dysfunction (1.8% v 0.9%, P = .03). In pts receiving E > 450 mg/m2, abBMI pts had less alopecia (P = .03) and more asthenia (P = .01). The 9-year DFS and OS were significantly worse in abBMI pts (54.7% v 59.8, P = .01; 62.3%v 68.3%, P = .0003, respectively). The multivariate analysis showed that abBMI had no prognostic value for relapse in pts receiving Tam alone or no systemic treatment, but was an independent prognostic factor of relapse in pts receiving CT combined or no with Tam (P = .02, and P = .002, respectively). Conclusion: AbBMI pts had less acute toxicity of CT, but developed more delayed cardiac toxicity irrespective of dose. The efficacy of hormonal treatment was not modified by BMI. It seems that an abBMI decreased the effect of CT whereas these pts received higher E dose. Probably, CT drugs have a modified distribution profile in these pts and these findings questioned about the dose calculation in mg/m2 when BMI is upper normal value. No significant financial relationships to disclose.
Why the BMJ needs your data
Authors: R. Smith
Journal: BMJ (1997)

The most useful information for doctors is valid, relevant, and easy to access.1 Unfortunately none of the information that is drowning them at the moment scores highly on these criteria.2 One way to increase the relevance of material to readers is to know much more about them and their needs. Medical publishers may then—through electronic means or modern printing methods—be able to send them information that is more relevant. That is one reason why modern organisations need good information on their members, subscribers, or customers, and that is the main reason why the BMJ has been gathering information on doctors. Unfortunately an ill informed piece of journalism in GP magazine, a British tabloid for doctors, has caused misplaced disquiet about the activities …
TRENDS IN BLEEDING RELATED COMPLICATIONS IN PATIENTS WITH ATRIAL FIBRILLATION UNDERGOING CORONARY INTERVENTION FOR ACUTE MYOCARDIAL INFARCTION
Authors: Nileshkumar Patel, Dhaval Pau, Nish Patel, Nilay Patel, Abhishek Deshmukh, Carlos Alfonso, Mauricio Cohen, Deepak Bhatt
Journal: Journal of the American College of Cardiology (2016)
P122 IMPAIRED HCV-SPECIFIC CTL REACTIVITY DUE TO APOPTOSIS INDUCTION DURING CHRONIC INFECTION IS NOT RESTORED BY IL-7 TREATMENT
Authors: E. Moreno-Cubero, S. García-Garzón, J. Miquel, E. Sanz-de-Villalobos, A. Lázaro, A. González-Praetorious, C. Perna, J.R. Larrubia
Journal: Journal of Hepatology (2014)
On the "Principles of the Heart" and the Psychiatric Insights of Zen
Authors: Ilza Veith
Journal: New England Journal of Medicine (1971)

Abstract Two basic tenets of Zen Buddhism emphasize the importance of life in and with nature, and immersion of the individual in the family, the group and the community. A Japanese physician, Shomei Morita, has used these elements of Zen conduct to construct a form of psychotherapy. The Morita regimen discourages egocentric analysis, and every effort is made to have the patient immerse himself in nature and society. This approach to psychotherapy has no parallel in any Western psychiatric system.
O8.03 * LOW GRADE DIFFUSE ASTROCYTOMA - PROGNOSTIC FACTORS TO ANAPLASTIC TRANSFORMATION
Authors: C. Izquierdo, C. Majos, M. Simo, A. Lucas, M. Macia, G. Plans, M. Gil, R. Velasco, J. Bruna
Journal: Neuro-Oncology (2014)

INTRODUCTION: Low grade gliomas (LGG) comprise nearly 20% of all central nervous system (CNS) glial tumors. LGG are characterized by their infiltrative growth and frequent tumor recurrence with malignant progression. They have a heterogeneous clinical behavior being histological, first line resection, velocity of diameter tumor expansion during pretherapeutic period,tumor volume, contrast enhancement and patients' characteritics the only described factors for identifying patients at risk of progression. The identification and validation of new imaging prognostic factors would help to minimize potential treatment-related side effects in LGG. OBJECTIVE: The aim of our study was to analyze the impact of clinical (gender, age, first symptom), histological (gemistocytic) and neuroimaging (tumor growth ratio at 6 months- GR6m) factors on malignant progression in a cohort of diffuse low grade astrocytomas. We conducted serial volumetric analysis using Flair sequences. The time to malignant progression (TMP) was defined as time between histological diagnose and first MRI showing contrast enhancement or histology proven progression. RESULTS: Patients' mean age was 42.5 ± 14.6 years with a male:female ratio of 1.7:1. Median Pignatti index (PI) was 2 (1-4). The median TMP was of 4.76 (0.33-11.8) years. Nearly half (48.2%) of the patients showed a malignant progression. This group had a higher GR6m (49% versus 3%, p = 0.032). A cut-point of GR6m < 2% obtained by ROC analysis showed a sensitivity and specificity of 92.3% and 71% (p = 0.001). In the multivariate analysis the GR6m < 2% (HR: 5.23, 95% CI (1.4-19.61), P = 0.014), gemistocytic component (HR 8, 95% CI (1.6-39.3), p = 0.01) and a PI of 3-4 (HR : 6.94, 95% CI (1.64-29.4), p = 0.008) were identified as independent predictors of TMP. CONCLUSIONS: GR6m resulted as independent prognostic factor of TMP. In addition, our study confirmed PI and gemystocitic histology as prognostic factors on TMP.It is important to define new prognostic factors to anaplastic transformation due to individualized treatment in patients.
Exposure Classification and Temporal Variability in Urinary Bisphenol A Concentrations among Couples in Utah—The HOPE Study
Authors: Kyley J. Cox, Christina A. Porucznik, David J. Anderson, Eric M. Brozek, Kathryn M. Szczotka, Nicole M. Bailey, Diana G. Wilkins, Joseph B. Stanford
Journal: Environmental Health Perspectives (2015)

Bisphenol A (BPA) is an endocrine disruptor and potential reproductive toxicant, but results of epidemiologic studies have been mixed and have been criticized for inadequate exposure assessment that often relies on a single measurement.Our goal was to describe the distribution of BPA concentrations in serial urinary specimens, assess temporal variability, and provide estimates of exposure classification when randomly selected samples are used to predict average exposure.We collected and analyzed 2,614 urine specimens from 83 Utah couples beginning in 2012. Female participants collected daily first-morning urine specimens during one to two menstrual cycles and male partners collected specimens during the woman's fertile window for each cycle. We measured urinary BPA concentrations and calculated geometric means (GM) for each cycle, characterized the distribution of observed values and temporal variability using intraclass correlation coefficients, and performed surrogate category analyses to determine how well repeat samples could classify exposure.The GM urine BPA concentration was 2.78 ng/mL among males and 2.44 ng/mL among females. BPA had a high degree of variability among both males (ICC = 0.18; 95% CI: 0.11, 0.26) and females (ICC = 0.11; 95% CI: 0.08, 0.16). Based on our more stringent surrogate category analysis, to reach proportions ≥ 0.80 for sensitivity, specificity, and positive predictive value (PPV) among females, 6 and 10 repeat samples for the high and low tertiles, respectively, were required. For the medium tertile, specificity reached 0.87 with 10 repeat samples, but even with 11 samples, sensitivity and PPV did not exceed 0.36. Five repeat samples, among males, yielded sensitivity and PPV values ≥ 0.75 for the high and low tertiles, but, similar to females, classification for the medium tertile was less accurate.Repeated urinary specimens are required to characterize typical BPA exposure.Cox KJ, Porucznik CA, Anderson DJ, Brozek EM, Szczotka KM, Bailey NM, Wilkins DG, Stanford JB. 2016. Exposure classification and temporal variability in urinary bisphenol A concentrations among couples in Utah-the HOPE study. Environ Health Perspect 124:498-506; http://dx.doi.org/10.1289/ehp.1509752.
Mutations in the A3 domain of Von Willebrand factor inducing combined qualitative and quantitative defects in the protein
Authors: Paulette Legendre, Ana-Maria Navarrete, Julie Rayes, Caterina Casari, Pierre Boisseau, Catherine Ternisien, Claudine Caron, Edith Fressinaud, Jenny Goudemand, Agnès Veyradier, Cécile V. Denis, Peter J. Lenting, Olivier D. Christophe
Journal: Blood (2013)
1324 QUANTIFICATION OF LIVER FAT USING NON-CONTRAST CT: COMPARISON OF LIVER/SPLEEN RATIO (CTLS), LIVER-SPLEEN DIFFERENCE (CTL − T) WITH LIVER FAT PERCENTAGE (CTLFP)
Authors: A.F. Jon, A.N. Khan, A.R. Cheema, A. Karellas, Z. Malik, F. Khosa, F.K. Welty, M.E. Clouse
Journal: Journal of Hepatology (2013)
Long-Term Influence of Inhaled Corticosteroids on Bone Metabolism and Density
Authors: LOUIS-PHILIPPE BOULET, JOANNE MILOT, LOUISE GAGNON, PATRICE E. POUBELLE, JACQUES BROWN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Long-term effects of high doses of inhaled corticosteroids (ICS) on bone density and metabolism are still uncertain. Fifty-one patients (37 male, 14 female) using beclomethasone or budesonide at a daily dose > 800 μ g/d (high-dose group [Group HD] mean: 983 μ g/d [prescribed dose × estimated compliance]) or no or < 500 μ g/d (control group [Group C] mean: 309 μ g/d) for more than 5 yr were enrolled in this study. Each had, 3 yr ago and at this last evaluation, a clinical evaluation and measurements of expiratory flows and of bone density and bone metabolism markers. Lumbar spine bone density (last visit) was similar in the two groups with respective values of 0.94 ± 0.03 (HD) and 0.96 ± 0.03 g/cm2 (C) (p > 0.05). T and Z scores were − 1.21 ± 0.19 and − 0.70 ± 0.18 (HD), − 0.95 ± 0.25 and − 0.47 ± 0.21 (C) respectively (p > 0.05). A correlation was found between the decrease in bone density and the mean daily dose of corticosteroid in Group HD although these changes were quite small, mean bone density being unchanged over the 3-yr period. Serum and urinary parameters were similar in the two groups. Furthermore, neither initial bone density nor any of the biological parameters could predict changes in bone density over a period of 3 yr. In conclusion, bone density was similar in both study groups and not significantly different over a 3-yr period. Neither initial bone density nor biological markers of bone metabolism helped to predict changes in bone mass.
1097 HYPERMETHYLATION OF THE microRNA LET-7A-3 GENE REPRESSES THE PRIMARY AND MATURE LET-7A-3 WITH AN INVERSE CORRELATION TO IGF-II mRNA IN HCV-INDUCED HEPATOCELLULAR CARCINOMA
Authors: A. Waly, H.M. El Tayebi, K.A. Hosny, G. Esmat, A.I. Abdelaziz
Journal: Journal of Hepatology (2013)
Disease stabilization with pembrolizumab for metastatic acral melanoma in the setting of autoimmune bullous pemphigoid
Authors: Kristen M. Beck, Joanna Dong, Larisa J. Geskin, Vincent P. Beltrani, Richard G. Phelps, Richard D. Carvajal, Gary Schwartz, Yvonne M. Saenger, Robyn D. Gartrell
Journal: Journal for ImmunoTherapy of Cancer (2016)

To date, patients with pre-existing autoimmune conditions have been excluded from immunotherapy trials out of concern for severe autoimmune exacerbations.We describe the first case of a patient with metastatic cKIT mutated acral melanoma, brain metastasis, and pre-existing severe autoimmune bullous pemphigoid (BP) with stable and asymptomatic disease 10 months after treatment with pembrolizumab. The patient experienced severe BP exacerbation after therapy with ipilimumab requiring systemic immune suppression, but nonetheless pembrolizumab was administered on further disease progression.This case suggests that pembrolizumab may confer more benefit than risk even in patients with known severe autoimmune conditions who require intermittent systemic immunosuppression.
Abstract 4530: A novel blood-based method for evaluating KRAS in circulating microvesicles from colorectal cancer patients
Authors: Kimberly Yeatts, Meredith Millis, Shannon Smith, Janet Duncan, Brittany Moran, Gerri Ortiz, Tanya Little, Amber Conrad, David B. Spetzler, Traci Pawlowksi
Journal: Cancer Research (2012)

Abstract Circulating microvesicles (cMV) are lipid-encapsulated bodies that are secreted from various tissues and can be detected in a number of body fluids, including plasma. Once collected from plasma, they can be exploited diagnostically for their protein and RNA signatures. Mutations in KRAS are diagnostically important for predicting response to chemotherapy and prognosis. A blood-based method of assessing KRAS mutation status would be helpful for patients with colorectal cancer (CRC). Traditional methods of KRAS detection examine the genomic DNA sequence. We developed a method to sequence exon 3 from KRAS using Pyrosequencing. The limit of detection for the assay was 0.78 ng/uL of mutant cDNA for both Pyrosequencing and Sanger sequencing. To further enhance mutation detection, we sorted cMV from CRC patients by first capturing cMV with a CRC associated membrane protein and then sorting for CD63 and CD24 positive events. A Taqman gene expression assay was not sensitive enough to detect KRAS in the sorted samples. However, Pyrosequencing was sufficient to identify mutant and wild-type sequences in patient plasma samples. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4530. doi:1538-7445.AM2012-4530