tbuckley/cabot-search huggingface dataset:
Rupture of a suspected pancreatic lymphoepithelial cyst causing chemical peritonitis after endoscopic ultrasound guided-fine needle aspiration
Authors: Hiroyuki Matsubayashi, Shinya Sugimoto, Yoshihiro Kishida, Yasuyuki Tanaka, Kenichiro Imai, Naomi Kakushima, Keiko Sasaki, Hanako Kurai, Teichi Sugiura, Hiroyuki Ono
Journal: Endoscopy (2014)

Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) is considered a safe technique not only for solid lesions but also for cystic lesions of the pancreas [1].
Abstract B26: A requirement for p63 function in squamous cell carcinoma <i>in vivo:</i> Can the pathway be targeted for therapy?
Authors: Matthew R. Ramsey, Catherine Wilson, William C. Faquin, Alea A. Mills, Leif W. Ellisen
Journal: Clinical Cancer Research (2010)

Abstract Squamous cell carcinoma (SCC) is a common form of human cancer that can arise in various epithelial tissues such as the lungs, skin, and head and neck region. Morbidity and mortality rates for SCC are high compared to many other cancers, and relatively little progress has been made in treatment due to a lack of molecular understanding of the disease. The p53-related protein p63 is essential for the formation of various epithelial tissues, such as the skin, and has many reported roles including suppression of apoptosis, maintenance of stem cell regenerative potential, regulation of differentiation, and maintenance of cellular adhesion. In SCC, p63 is overexpressed and has found to be the target of genomic amplification suggesting an important role in this disease. Previous in vitro studies have shown that p63 is required for survival of SCC cells in culture, however, cell lines lack the complex microenvironment found in human cancer, and thus the in vivo relevance of these results is unclear. To determine the role of p63 in vivo, we have generated a murine model of SCC, which faithfully recapitulates many of the molecular and pathological features of human SCC including invasion and metastasis. To test the role of p63 in tumor maintenance we crossed this model to a conditional p63-null allele (p63flox) and a tamoxifen-inducible Cre transgene, K14-CreER. We have found that genetic excision of both copies of p63 in established SCC tumors results in rapid and dramatic regression of tumors. In addition, even loss of a single copy of the p63 gene results in a reduced rate of growth, suggesting that SCC tumors are exquisitely sensitive to levels of p63 protein. These results support the idea that the p63 pathway is critical for the survival of SCC tumors in vivo, and targeting this pathway in SCC may result in more effective therapy for this highly refractory tumor type. Citation Information: Clin Cancer Res 2010;16(14 Suppl):B26.
P9 Epidemiological survey suggests lung cancer is less common in patients with hereditary haemorrhagic telangiectasia compared to controls
Authors: AE Hosman, HL Devlin, BM Silva, AH Elphick, CL Shovlin
Journal: Thorax (2013)

<h3>Background</h3> Over 41,000 people are diagnosed with lung cancer annually in the UK with only 8% of men, and 9% of women surviving at least 5 years after diagnosis. Antibodies against the endothelial cell protein endoglin are proving promising in early clinical trials [1]. Many individuals with hereditary haemorrhagic telangiectasia (HHT) have inherited endoglin mutations. This autosomal dominant trait affects approximately 1 in 5,000 people, causing multi-systemic vascular lesions. We hypothesised that lung cancer rates may differ in individuals with HHT. <h3>Methods</h3> To provide sufficient power to compare lung cancer rates in HHT patients and controls, we developed a questionnaire capturing data on multiple relatives per respondent, powered to detect differences in lung cancer rates. Blinded to cancer responses, reports of HHT-specific features allowed assignment of participants and relatives as HHT-subject, unknown, or control. Logistic and quadratic regression were used to calculate crude and age-adjusted odds ratios. <h3>Results</h3> By data download on 30.6.2012, 1,307 participants (including 1,012 HHT-subjects, 142 controls) completed the questionnaire. Ages (medians 55/53ys), gender (65/65% female) and general demographics were similar. The number of current/former smokers did not differ significantly between HHT and control groups (p = 0.38), but the HHT arm reported significantly greater pack year smoking histories than the controls (Mann Whitney p = 0.01). Combining data of participants and relatives resulted in a control-arm of 2,817 (52% female), and HHT-arm of 2,166 (58% female). Median ages were77ys [IQR 65–82] and 66ys [IQR 53–77] respectively. Rates of 15 cancers predominantly recognised as primary cancers in the control group generally matched the age standardised frequency of the general population. The ratio of observed/expected incidence was significantly higher for cancers at common sites of metastatic spread (lung, liver and brain). As expected cancer rates increased with age (p &lt; 0.0001, all cancers). In both crude and age-adjusted regression, lung cancers were significantly less frequent in the HHT arm compared to controls (age-adjusted odds ratio 0.48 [0.30, 0.70], p = 0.0012). <h3>Conclusions</h3> Individuals with HHT may be protected against primary and/or metastatic lung cancer. This does not appear to be due to reduced smoking habit. <h3>References</h3> Bernabeu and Shovlin, Thomson Reuters Pharma (21 December 2011) [Online].
Pharmacological Characterization of TASP0412098, A Selective CRTH2 (Chemoattractant Receptor-Homologous Molecule Expressed on Th2 Cells) Antagonist
Authors: M. Kawanishi, K. Watanabe, Y. Asakura, A. Oka, T. Naruse, R. Nishikawa, T. Takayama, T. Koami, D. Wakasugi, M. Kawamura, A. Takaoka, S. Tokita
Journal: Journal of Allergy and Clinical Immunology (2012)
Abstract 1534: Bioassay-guided identification of novel P-glycoprotein inhibitors from traditional Chinese medicines
Authors: Ranadheer Ravula, Jeffrey Wang, Ying Huang
Journal: Cancer Research (2010)

Abstract Multi-drug resistance (MDR) is an obstacle for therapeutic success of anticancer agents. Overexpression of P-glycoprotein (P-gp), encoded by ABCB1 gene, plays a key role in conferring MDR via active efflux of anticancer drugs from cells. Previous efforts with several generations of P-gp inhibitors had not been successful in modulating clinical MDR. Recently, an increasing number of cancer patients are using complementary and alternative medicines, in particular, traditional Chinese medicines (TCMs), in combination with conventional anticancer agents. The purpose of this study is to examine the effects of TCM extracts on modulating P-gp function. We initiated our study from four single herbal products (Glycyrrhiza uralensis, Hibiscus syriacus, Tripterygium wilfordii, and Cephalotaxus sinensis) and one formula of herbal mixture (Si-Wu-Tang), using a bio-assay guided fractionation method. Crude extracts were firstly prepared with ethanol. The most active extracts identified were further extracted with hexane, chloroform, acetone and ethanol sequentially to obtain fractions of increasing polarity. The MDR modulating effects of the crude extracts and individual fractions were evaluated based on their capability to enhance daunorubicin (DNR) accumulation in P-gp over-expressing human leukemia cell line K562/DOX. The intracellular fluorescence intensity in the presence or absence of test drugs or known P-gp inhibitor cyclosporine A (10 µM) was measured by flow cytometer. The crude extracts were also tested for cytotoxicity against K562/DOX cells by the MTS cell proliferation assay. This study revealed that among the five TCMs, the crude extracts of Tripterygium wilfordii demonstrated a dose-dependent effect on increasing the DNR accumulation, indicating the presence of novel P-gp inhibitor(s). Upon further separation, the chloroform fractions of this herb showed the highest P-gp inhibitory activity. However, known compounds present in this herb, celastrol, triptolide and myristic acid did not show effects on DNR accumulation. Most of the plant extracts tested were able to inhibit the growth of K562/DOX cells with Cephalotaxus sinensis being the most effective, consistent with literature reports that this herb contains highly cytotoxic compound homoharringtonine and congeners. The potency of P-gp inhibition for the five TCMs was not correlated with their cytotoxicity. In conclusion, our results demonstrated that the chloroform fractions of Tripterygium wilfordii contain unknown components for P-gp inhibition. Our current efforts are focused on isolation and identification of active compounds from it. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1534.
The introduction of numerical methods to assess the effects of medical interventions during the 18th century: a brief history
Authors: Ulrich Tröhler
Journal: Journal of the Royal Society of Medicine (2011)

Although numerical approaches were used by John Graunt to analyse patterns of mortality in 17th-century London,1 it was not until the early 18th century that numbers began to be used to assess the effects of medical interventions.2–7 This development occurred chiefly, but not exclusively, in Britain.8–27 In 1731, for example, Francis Clifton published a book entitled Tabular observations recommended as the plainest and surest way of practising and improving physick,28 followed by a work entitled The state of physick, ancient and modern, briefly considered: with a plan for the improvement of it.29 Clifton pointed out that, instead of assessing the worth of therapies by whether they accorded with theories, physicians needed to base their judgements about the effects of treatments on a sufficient number of their own (or otherwise testified) observations, organized in tables.30

Clifton was followed later in the 18th century by others emphasizing similar principles: for example, William Hillary's Inquiry into the means of improving medical knowledge;31 Thomas Percival's commentary on the ‘dogmatist’ and the ‘empiricist’ physician in his Essays medical and experimental;32 John Gregory's Observations on the duties and offices of a physician;33 James Sims’ Discourse on the best method of prosecuting medical enquiries;34 a section in John Aikin's Thoughts on hospitals;35 Thomas Kirkland's Inseparability of the different branches of medicine;36 an anonymous author's contribution to Medical Observations and Inquiries;37 Gilbert Blane's Observations on the diseases incident to seamen;38 and George Fordyce's An attempt to improve the evidence of medicine,39 which was published in the Transactions of a Society for the Improvement of Medical and Chirurgical Knowledge.

Of course, there is a difference between calls for numerical methods to be applied and actually applying them. However, the principles enunciated by Clifton and others were applied widely in civilian practice in Britain, as well as in the British armed forces.
Racial disparities in magazine coverage of mammography.
Authors: GA Petrak
Journal: Cancer Research (2009)

Abstract Abstract #5100 Background: African-American (AA) women are diagnosed with breast cancer later, at a higher stage disease, and have a higher mortality than European-American (EA) women. AA women have a lower rate of mammography screening and this lower rate may account, in part, for AA women's more severe disease at diagnosis and higher mortality. One possible reason for this racial disparity in mammography screening may be that AA women receive a different message than EA women from mass circulation magazines about mammography.&amp;#x2028; Material and Methods: A computer-aided content analysis was performed of AA and EA women's magazines with a circulation of greater than one million that contained at least 1,000 words across all the mammography-related articles or sections of articles that were published between January 1, 2002 and December 31, 2007. The words that shared similar meanings were grouped into seven categories: (1) religiosity, (2) activity, (3) positive and (4) negative emotions, (5) medical terms, (6) risk factors, (7) race portrayed, by which is meant when race was noted in articles as African American/Black or European American/White. The frequencies of each word were counted across all articles by type of magazine, i.e., predominately AA readers and EA readers. The Pearson product-moment method was used to calculate correlations, the Student's t-test was used for correlated samples to compare the means of the continuous variables, and McNemar's test was used to assess the difference between two correlated proportions. Significance was set at the 0.05 level.&amp;#x2028; Results: The magazines that met the study criteria were the African-American magazines Ebony and Essence and the European-American magazines Good Housekeeping, Marie Claire, Redbook, and Vogue. The six magazines yielded the following total number of words per magazine that focused on mammography: (a) Ebony: 17,221 words, (b) Essence: 20,257 words, (c) Good Housekeeping: 12,998 words, (d) Marie Claire: 7,654 words, (e) Redbook: 29,201 words, and (f) Vogue: 11,482 words. The word categories were compared in terms of their relative word frequencies, AA and EA.&amp;#x2028; &amp;#x2028; Discussion: There were clear differences in the mammography messages presented in the AA and the EA magazines. The AA magazines contained more references to religiosity, activity, positive and negative emotions, and risk. It was striking that racial references to African Americans were ubiquitous in the African-American magazines, whereas, racial references to either African Americans or European Americans were almost completely absent from the European-American magazines. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5100.
P3-11-04: A Randomized Phase II Biomarker Study of Atorvastatin in Premenopausal Women at Increased Risk for Breast Cancer.
Authors: ME Wood, F Kingsley, JA Ellerton, JN Atkins, SS Grubs, HB Muss, JE Garber
Journal: Cancer Research (2011)

Abstract Statins have been shown in epidemiological and laboratory studies to have breast cancer risk reduction properties. We evaluated the effect of atorvastatin on breast mammographic density (MD) and other breast cancer biomarkers in a small randomized placebo controlled trial. Methods: Premenopausal women at increased risk for breast cancer (due to family history, BRCA positivity, prior biopsy history or history of chemoradiotherapy for Hodgkins disease) enrolled after signing informed consent and received either 40 mg of atorvastatin or placebo daily for 1 year. Biomarker assessment was performed prior to initiation and prior to completion of study medication. MD was determined using both Breast Imaging Reporting and Data System (BI-RADS) and the Visual Analogue Scale (VAS). Results: 63 women were enrolled between 7/05 - 8/10 in this multi-institutional trial. 44 have completed study medication and 3 remain on study. 25% have withdrawn; 17% of them for toxicity/side effects. Of those completing the study; mean age was 47 (range 35–50), 96% Caucasian, mean BMI 26.8. 66% had a strong family history (2% were BRCA+), 27.7% had ADH/LCIS. We present analysis of MD in the first 37 women completing study drug. The two treatment groups were well balance for age, BMI, risk factors and baseline density. Mean density by VAS was 31.6% at study entry and 32.4% at end of treatment. There was no different in change in density over time between atorvastatin and placebo using either BIRAD or VAS; controlling for BMI did not change results. Futility analysis demonstrates low probability of a significant difference between treatment groups and the study was closed. Conclusions: In this multi-institutional randomized prospective clinical trial of premenopausal women at increased risk for breast cancer we have failed to demonstrate a significant effect of atorvastatin on mammographic density. There are several possible reasons for this relating to: the study population, method of density determination and/or biomarker analyzed. While the primary aim of this study (MD) was not met we have shown that biomarker studies can be done in a multi-institutional setting. Further biomarker evaluation may prove informative. Funding: This study is sponsored by grants from Breast Cancer Research Foundation and Cancer and Leukemia Group B to M. Wood. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-11-04.
A Functional Role for CERT in Cancer Drug Induced Autophagy and Prognosis in Her2 Positive Breast Cancer.
Authors: A. Lee, P. East, B. Nicke, N. Jones, J. Downward, P. Gorman, R. Roylance, N. Murphy, A. Hanby, C. Swanton, C. Swanton
Journal: Cancer Research (2009)

Abstract CERT was recently identified in a functional genomic siRNA screen for regulators of multi-drug sensitivity. CERT encodes a ceramide transporter which shuttles the pro-apoptotic lipid ceramide from the endoplasmic reticulum to the golgi. Silencing CERT, promoted sensitivity to paclitaxel, doxorubicin, cisplatin and 5-FU in breast, colon and non-small cell lung cancer cell lines. Further analysis of CERT expression in 18 NCI-60 cancer cell lines together with drug sensitivity data for over 5000 drugs within the NCI database, revealed that elevated CERT expression is associated with multi-drug resistance to diverse cancer cytotoxics. CERT mRNA was significantly elevated in HER2 positive breast cancer cell lines. Consistent with these data, in a primary breast cancer tissue microarray cohort of 356 primary breast cancers with outcome data, CERT protein expression was significantly greater in Her2 positive disease (p&amp;lt;0.0001). Survival analysis indicates that increased CERT expression correlates with significantly poorer long-term survival across the whole cohort and in Her2 positive patients.In order to explore the downstream molecular targets of CERT activity, we used the Affymetrix GeneChip Exon Array to detect gene expression changes following siRNA mediated CERT silencing. Genes that were differentially expressed following CERT silencing were identified and validated by real-time PCR. Significant representation of genes involved in the autophagy pathway were identified. One of these genes, LAMP2, a protein involved in autophagosome-lysosome fusion, is up-regulated following CERT silencing. LAMP2 silencing promotes paclitaxel resistance when depleted from cancer cells. Consistent with a role for CERT silencing in mediating an autophagy response following drug exposure, CERT depletion together with Paclitaxel treatment induces alterations in the autophagy response marker-LC3 similar to those seen in starvation-induced autophagy and an increase in lysosomal activity as visualised by microscopy. These data indicate a role for autophagy in regulating cytotoxic drug response in cancer.The pharmacological targeting of CERT, a poor prognostic marker in breast cancer, may be a rational approach to enhance drug response and patient outcome. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1137.
London's health services need radical change, says NHS England
Authors: J. Wise
Journal: BMJ (2013)

London’s hospital system is at breaking point, and demand for healthcare will outstrip funding in seven years unless there is a fundamental change in the way services are delivered, NHS England’s regional medical director for London, has warned.

Andy Mitchell gave the warning at the launch of a report, London: A Call to Action , which argues that health inequalities and an ageing population mean that the existing model of NHS healthcare is unsustainable in the capital.1

The report is the London version of the national call to action launched by NHS England’s chief executive, David Nicholson, in July.2 NHS England said that the analysis would be useful to stimulate debate about the challenges facing healthcare in London. Discussions will be led by London’s clinical commissioning groups, working with health and wellbeing boards.

Anne Rainsberry, NHS England’s regional director for London, said that there was likely …
Abstract 2010: A Network Phenotyping Strategy (NPS) for HCC identifies distinct coherent survival groupings from observed clinical traits
Authors: Petr Pancoska, Brian I. Carr, Robert A. Branch
Journal: Cancer Research (2010)

Abstract Background: HCC is a complex disease with tumor growth replacing adjacent liver. Our initial hypothesis was that tumor traits and loss of liver function are independent processes. We examined this, seeking evidence of coherent discrete structure with respect to survival. Methods: NPS was used to analyze 970 patients with biopsy-proven, non-surgical HCC, all followed prospectively until death. We assumed stochasticity with respect to timing of diagnosis and ambiguity of each variable with respect to survival and used a combination of k-partite graph-based analysis with statistical processing of pairwise dependencies of clinical data ordered by survival, each characterized by the mean of clinical parameters of the 100 patients with the closest survival, for 678 survivals. Results: NPS clearly identified heterogeneity, with 3 distinctive phenotypes based on coherence of multiple variables. Each had different survival ranges with trends of collinear relationships between bilirubin, AFP, alkaline phosphatase, SGOT and GGTP. In patients &amp;gt;70 years, the larger the tumor the higher the biochemical values, with the trends decreasing with longer survival. Above 80 years, bilirubin and AFP were normal, with long survival, 330-1250 days. There were 2 groups of younger patients (&amp;lt;55 years). One, with 30-45 days survival, had a similar profile to the older group. In the other, with 90-330 days survival, the profile was for multiple small tumors to trend with biochemical values. A striking finding was the close correlation in trends for AFP against bilirubin, alkaline phosphatase, GGTP or SGOT values, suggesting that liver damage parameters and tumor parameters were not independent factors, but might be inter-twined, especially in older patients. Conclusions: This NPS analysis does not support the hypothesis that tumor growth and cirrhotic damage are independent, but are intertwined processes. Furthermore, we have evidence based on coherence between variables that the growth rates for unifocal tumors of equivalent size are faster in the young than in the elderly. NPS provides useful insights to design future genomic studies to compare different phenotypes and understand the different pathophysiological processes involved. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2010.