tbuckley/cabot-search huggingface dataset:
AT-34CONSTRUCTION OF AN INTEGRATED DIAGNOSTIC ALGORITHM CONSISTING OF CONSENSUS HISTOLOGIC AND MOLECULAR PARAMETERS OF TWO EORTC TRIALS ON ANAPLASTIC GLIOMA
Authors: Johan M. Kros, Pim French, Martin J. van den Bent, Thierry Gorlia
Journal: Neuro-Oncology (2014)

BACKGROUND: With the rapid discovery of prognostic and predictive molecular parameters for glioma, the status of histopathology in the diagnostic process should be scrutinized. The present project aimed at the construction of an evidence-based diagnostic algorithm for gliomas. To reach this goal, histological features were scrutinized for their prognostic relevance and acceptable inter-observer variability. In addition, molecular markers should be validated for their prognostic power and possible overlap when simultaneously applied. METHODS: The pathology slides of EORTC trials 26951 and 26882 were scanned for virtual microscopy, an electronic scoring form was created and a panel of six pathologists was formed to independently evaluate the slides. The molecular analysis for IDH1, 1p/19q loss; EGFR amplification; loss of chromosome 10 and 10q, gains of chromosome 7 and hypermethylation of the promoter of MGMT were available for appr. half of cases. The slides were divided in a test (discovery) set (n = 500) and a validation set (n = 300). All follow-up data were available at the EORTC data center in Brussels and the results were statistically tested with the aim to create and validate the diagnostic algorithm. RESULTS: In 66% of cases consensus of overall diagnosis was present. Cox regression analysis of consensus histological features and molecular markers revealed the prognostic significance of the parameters necrosis, cell density, mitotic index, loss 1p/19q and IDH1 mutation. A diagnostic algorithm consisting of relevant (consensus and prognostically significant) histological features and molecular markers was identified by CART analysis and consisted of 2 molecular markers and 1 histological feature. The order of prognostic power was: 1p/19q loss; EGFR amplification; astrocytic morphology, and 4 diagnostic nodes were identified. Validation of the nodes in the validation set yielded 4 significantly different survival curves (Overall Wald test p < 0.0001). CONCLUSION: we succeeded in the creation of a timely combined histologic and molecular diagnostic algorithm.
Abstract 4487: Inverse associations between soluble cytokine receptors and colorectal cancer risk
Authors: Gloria YF Ho, Xiaonan Xue, Lilly S. Zheng, Mary Cushman, Jianfeng Xu, Lesley Tinker, Tao Wang, Sylvia Wassertheil-Smoller, Howard D. Strickler, Marc J. Gunter, Thomas E. Rohan
Journal: Cancer Research (2012)

Abstract Laboratory studies have suggested that soluble receptors of proinflammatory cytokines could be anti-inflammatory by acting as decoy receptors, blocking binding of the cytokines to their membrane receptors, and hence inhibiting cytokine signaling. Thus, relatively high levels of soluble cytokine receptors and receptor antagonists may be protective factors against colorectal cancer, which is an inflammation-associated disease. This case-cohort study nested within the Women's Health Initiative Observational Study of postmenopausal women 50-79 years of age at baseline (1993-1998) examined whether baseline plasma levels of IL-1 receptor antagonist (IL-1Ra) and the soluble receptors of IL-6 (sIL-6R and sgp130), TNF (sTNF-R1 and sTNF-R2), and IL-1 (sIL-1R2) were inversely associated with colorectal cancer risk. Analytes were measured in 433 incident colorectal cancer cases and 823 subcohort members using multiplex assays (Millipore, Billerica, MA). Circulating levels of IL-6, TNF-α, insulin, and estradiol measured previously were also available for data analyses. IL-1Ra and the 5 soluble receptors did not correlate with each other or with their ligands (all correlations r &amp;lt; 0.3), with the exception of sTNFR2, which was moderately correlated with sTNFR1 (r=0.51) and TNF-α (r=0.43). The table below shows the hazard ratios for colorectal cancer risk, when each analyte was entered separately into a Cox regression model adjusting for other colorectal cancer risk factors. Colorectal cancer risk decreased significantly with increasing levels of sIL-6R and sIL-1R2. The ratios of IL-6 or TNF-α to their soluble receptors were not associated with colorectal cancer risk. There were also no significant interactions between pairs of soluble receptors or between soluble receptors and their ligands. Increased circulating levels of sIL-6R and sIL-1R2 may confer protection against colorectal cancer. If our results are confirmed, these soluble receptors can be considered for chemoprevention. 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 4487. doi:1538-7445.AM2012-4487
PWE-169 Dna Methylation and Expression of TNF, IFNG and FOXP3 in Colorectal Cancer
Authors: S Ganapathi, A Beggs, S Hodgson, D Kumar
Journal: Gut (2013)

<h3>Introduction</h3> Colorectal cancer (CRC) progression is associated with suppression of host cell mediated immunity (CMI) and local immune escape mechanisms (1.2). The aim of the study was to assess immune function in terms of the DNA methylation and expression of TNF, IFN- γ and FOXP3 and to identify potential targets for immunotherapy in CRC. <h3>Methods</h3> 60 CRC patients and 15 matched controls were recruited. TaqMan quantitative PCR (qRT-PCR) was performed for relative quantitation of expression of TNF, IFNG, FOXP3 in the PBMC and tumour. Methylation specific PCR was performed to determine the methylation status. MSI status was determined using microsatellite primers BAT25 and BAT26. <h3>Results</h3> TNF expression was suppressed in CRC tumours (median fold change 0.48). IFN- γ was found to be suppressed in the PBMC (median 0.34) of CRC patients. Tumours showed enhanced expression of FOXP3 (median 2.2). Expression of FOXP3 in tumours was significantly higher when the size of the tumour was more than 50mm (p = 0.005). Methylated <i>TNFpromoter</i> and <i>FOXP3cpg</i> correlated significantly with suppression of TNF and FOXP3 respectively. Significant TNF suppression (p = 0.002) was noted in the PBMC of patients with MSI. No correlation was observed between the MSI status and DNA methylation status of our study genes. <h3>Conclusion</h3> Our study identified changes in protein expression which correlated with the methylation status. It demonstrates the influence of DNA methylation on gene expression that could act as a biomarker for future immunotherapy with possible role for demethylating agents. <h3>Disclosure of Interest</h3> None Declared. <h3>References</h3> Heriot AG, Marriott JB, Cookson S, Kumar D, Dalgleish AG. Reduction in cytokine production in colorectal cancer patients: association with stage and reversal by resection.<i> Br J Cancer</i> 2000;<b> 8</b>2(5): 1009–1012. Galizia G, Lieto E, De Vita F, Romano C, Orditura M, Castellano P, Imperatore V, Infusino S, Catalano G, Pignatelli C. Circulating levels of interleukin-10 and interleukin-6 in gastric and colon cancer patients before and after surgery: relationship with radicality and outcome. <i>J Interferon Cytokine Res</i><i></i> 2002; <b>22</b>(4): 473–482.
Accuracy of Diagnostic Coding for Medicare Patients under the Prospective-Payment System
Authors: David C. Hsia, W. Mark Krushat, Ann B. Fagan, Jane A. Tebbutt, Richard P. Kusserow
Journal: New England Journal of Medicine (1988)

Abstract Reimbursement of hospitals by Medicare under the prospective-payment system is based on patients' diagnoses as coded at discharge. During the period October 1984 through March 1985, we studied the accuracy of the coding for diagnosis-related groups (DRGs) in hospitals receiving Medicare reimbursement. We used a two-stage cluster method to sample 7050 medical records from 239 hospitals that were stratified according to size. Using blinded techniques with reliability checks, medical-record specialists reabstracted the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes to assign correct DRGs to discharged patients. The correct DRGs were then compared with those originally assigned by the physician and the hospital administration. The study revealed an error rate of 20.8 percent in DRG coding. Errors were distributed equally between physicians and hospitals. Small hospitals had significantly higher error rates. Previous studies had found that errors occurred randomly, so that half the errors benefited the hospital financially and half penalized the hospital. The present study found that a statistically significant 61.7 percent of coding errors favored the hospital. These errors caused the average hospital's case-mix index — a measure of the complexity of illness of the hospital's patients—to increase by 1.9 percent. As a result, hospitals received higher net reimbursement from Medicare than was supportable by the medical records. We conclude that "creep" does occur in the coding of DRGs, resulting in overpayment to hospitals for patients covered by Medicare. (N Engl J Med 1988; 318: 352–5.)
P110 Quantitative PCR-based detection and quantification of atypical bacteria at baseline and exacerbation of COPD
Authors: D. S. Garcha, S. J. Thurston, A. R. C. Patel, J. J. P. Goldring, T. D. McHugh, G. C. Donaldson, J. A. Wedzicha
Journal: Thorax (2010)

<h3>Introduction</h3> Airway bacterial infections are associated with exacerbations of COPD. The potential role of atypical bacteria as a trigger for exacerbations is not well understood. Atypical bacteria such as <i>Chlamydophila pneumoniae</i> (CP), <i>Legionella pneumophila</i> (LP) and <i>Mycoplasma pneumoniae</i> (MP) are difficult to culture as they are intracellular pathogens. LP can be detected by urinary antigen, and serology can be performed for MP, but these techniques give no indication as to the atypical bacterial load. Quantitative PCR (qPCR) offers an alternative approach to identification and quantification of bacteria in sputum. <h3>Methods</h3> Multiplex qPCR was used to detect and quantify CP, LP and MP in 238 samples prospectively collected from 87 patients in the London COPD Cohort: mean (±SD) age 71.4 (±8.1); predicted FEV<sub>1</sub> 43.4% (±17.5%); male gender 47.9%; current smoker 49.2%. Baseline (n=104), exacerbation (n=95), and follow-up (n=39) samples were tested: Baseline was defined as at least 6-weeks without exacerbation, and exacerbation was defined as 2 consecutive days of two symptoms (Anthonisen criteria), at least one of which is a major symptom (dyspnoea; sputum purulence; sputum volume). Follow-up involved taking samples 2 or 5 weeks post-exacerbation onset. Using a qPCR developed by our clinical diagnostic service, the CP, MP and LP gene targets were RNA-polymerase β-chain; P1 adhesin protein; and MIP respectively. Routine microbiological analysis was also performed on these samples. <h3>Results</h3> No samples were positive for the atypical organisms using culture. With qPCR analysis 6/238 samples (six separate patients) were positive for LP (2.5%), four at baseline and two at exacerbation/follow-up. One baseline sample was positive for MP (0.42%), and no samples were positive for CP. Atypical bacteria were present at 0.83% of exacerbations. Median (IQR) bacterial load was 4.3x10<sup>4</sup> cfu ml<sup>−1</sup> (2.0x10<sup>4</sup>–8.55x10<sup>4</sup>) for LP PCR-positive samples; the MP-positive sample load was 2.64x10<sup>7</sup> cfu ml<sup>−1</sup>. <h3>Conclusion</h3> Quantitative PCR was more sensitive and informative than standard microbiological culture for the detection of atypical bacteria. Atypical bacteria in sputum were detected at very few exacerbations of COPD; moreover, when they were detected by qPCR, the load was low, indicating little or no significance in the aetiology of these events.
Abstract P2-04-01: HER2 Status as Predictor of Mammographic Screening Detection: Comparison of Interval-and Screen-Detected Breast Cancers
Authors: A Musolino, M Michiara, GM Conti, D Boggiani, F Bozzani, M Zatelli, P Sgargi, A. Ardizzoni
Journal: Cancer Research (2010)

Abstract Background: To determine whether markers of poor prognosis are associated with risk of breast cancer diagnosis in the interval between screening examinations, we estimated the effect of the mode of detection on distribution of breast cancer molecular subtypes using population cancer registry data. Material and Methods: Subjects (n = 641) comprised all breast cancers systematically collected by the Cancer Registry of Parma Province and diagnosed in women aged 50-69, from 2004 to 2007. These included 370 screen-detected and 271 symptomatic breast cancers (63 women with interval cancers and 208 who had not attended screening). We used logistic regression to determine whether interval cancers were associated with selected clinical and biologic characteristics. We also estimated the relative risk of cause-specific fatality and disease-free survival (DFS) by each resulting predictive factor (screen-detected compared to either symptomatic or interval cancers). Results: Interval-detected cancers occurred more in younger women and were of more advanced tumor stage than screen-detected cancers. In unconditional logistic regression models adjusted for age and tumor stage, tumors with high histologic grade (odds ratio[OR] = 2.2; 95% CI =1.0-5.4), high proliferation rate (OR =2.7; 95% CI =1.5-4.8), or positive HER2 status (OR =2.6; 95% CI =1.3-5.1) were more likely to surface in the interval between screening examinations. After adjusting for various potential biases, women with screen-detected breast cancer had a substantial survival advantage over those with symptomatic breast cancer. In a multivariate model, positive HER2 status independently predicted poor DFS when the mode of cancer detection was included as covariate in addition to age, histologic grade, proliferation rate, and tumor stage. Conclusions: This is the first population-based cancer registry study demonstrating that HER2-positive tumors account for a substantial proportion of mammographic screening failure to detect breast cancer. Our data indicate that molecular subtype distribution of screen-detected breast cancer differs from that of interval cancers and accounts in part for the better outcome of screen-detected cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-04-01.
Abstract IA23: Harnessing genetic dependencies in cancer therapy
Authors: Alan Ashworth
Journal: Cancer Research (2011)

Abstract Many tumors harbor defects in their ability to maintain genomic integrity. This contributes to the mutational burden and likely fosters pathogenesis. We have been exploring therapeutic strategies to exploit these defects. We have used a synthetic lethal approach to target the defect in DNA repair by homologous recombination in tumors with a BRCA1 or BRCA2 mutation. This strategy using PARP inhibitors is showing considerable promise in the clinic. Here, I will describe the approach as well recent work defining determinants of sensitivity and resistance to PARP inhibitors. The application of the synthetic lethal approach to other cancer types will also be discussed. In addition, we have been using high- and medium-throughput RNAi screens to uncover new therapeutic targets for cancer as well as biomarkers of patients who might respond to specific treatments. In particular, I will discuss the integration of genomic, gene expression, and RNAi data to generate functional maps of cancer cell lines. 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 IA23.
1093 POPULATION PHARMACOKINETIC (PK) ANALYSIS OF RIBAVIRIN (COPEGUS) IN CHRONIC HEPATITIS C (CHC) PATIENTS WITH CHRONIC KIDNEY DISEASE (CKD) LEADS TO CHANGES IN RECOMMENDED DOSING
Authors: B. Brennan, M.O. Magnusson, J.J. Wilkins, P. Martin, K. Nieforth, J. Solsky, C. Wat
Journal: Journal of Hepatology (2012)
Nonmelanoma Skin Cancer Associated with Use of a Tanning Bed
Authors: Laurence R. Lever, Clifford M. Lawrence
Journal: New England Journal of Medicine (1995)

To the Editor: Ultraviolet A radiation used for cosmetic tanning is thought to be capable of inducing nonmelanoma skin cancer.1,2 Premalignant keratoses, but not cancers, have been observed in user...
Activity of cabozantinib (XL184) in metastatic melanoma: Results from a phase II randomized discontinuation trial (RDT).
Authors: Michael S. Gordon, Harriet M. Kluger, Geoffrey Shapiro, Razelle Kurzrock, Gerald Edelman, Thomas A. Samuel, Ali H. Moussa, David A. Ramies, A. Douglas Laird, Frauke Schimmoller, Xiaodong Shen, Adil Daud
Journal: Journal of Clinical Oncology (2012)

8531 Background: MET and VEGF signaling are implicated in angiogenesis, invasion, and metastasis. Cabozantinib (cabo) is an oral, potent inhibitor of MET and VEGFR2. A RDT evaluated activity and safety in 9 tumor types. Here we report on the metastatic melanoma cohort, including the ocular subtype. Methods: Eligible patients (pts) were required to have progressive measurable disease per RECIST. Pts received cabo at 100 mg qd over a 12 wk Lead-in stage. Tumor response (mRECIST) was assessed q6 wks. Treatment ≥ wk 12 was based on response: pts with PR continued open-label cabo, pts with SD were randomized to cabo vs placebo, and pts with PD discontinued. Primary endpoint in the randomized phase was progression free survival (PFS). Results: Enrollment to this cohort is complete (n = 77); all pts are unblinded. Baseline characteristics: median age 66 years; melanoma subtype: cutaneous/mucosal 70% and ocular 30%; known BRAF mutation 32%; LDH ≥ 1.1 x upper limit normal 35%; bone metastases 19%; median prior lines of therapy 1 (range 0-5). Median follow-up was 2.8 months (range 0.3 - 25). 35 pts (45%) completed the open-label Lead-in stage with 25 pts randomized to continue cabo (n=12) or to placebo (n=13). Median PFS from randomization was 5.7 months for cabo vs. 3 months for placebo (HR=0.3, p =0.055). Median PFS from Study Day 1 was 4.4 months. The estimate of PFS at month 6 (PFS6) is 44%. Evidence of objective tumor regression was observed in 39/65 pts (60%) with ≥ 1 post-baseline tumor assessment including 11/23 pts (48%) with ocular melanoma. Two bone scan evaluable pts demonstrated partial resolution of bone lesions at wk 6 accompanied by pain relief. Most common Grade 3/4 AEs were fatigue (14%), HTN (9%), constipation (4%), and diarrhea (3%); one related Grade 5 AE of diverticular perforation and peritonitis reported during Lead-in stage. Conclusions: Cabo demonstrates activity in metastatic melanoma pts, regardless of subtypes or BRAF mutation status, with improvement in PFS relative to placebo, and high rates of PFS6 and objective tumor regression. The safety profile of cabo was comparable to that of other VEGFR TKIs.
An Endocrine Active Insulinoma with Extended Lymphogenic Dissemination
Authors: Richard Bökenkamp, Christianne S J Duchateau, Marcel P M Stokkel
Journal: Clinical Nuclear Medicine (2003)

BÖKENKAMP, RICHARD M.D.; DUCHATEAU, CHRISTIANNE S. J. M.D.; STOKKEL, MARCEL P. M. M.D., PH.D.Author Information
Abstract P4-03-03: Lower Vitamin D Levels Are Highly Prevalent in Women with Breast Cancer
Authors: SP Li, RN Moule, M-L Seah, S Rainbow, R Bhatti, KA Steer, E Windmill, A. Makris
Journal: Cancer Research (2010)

Abstract Purpose: The objectives of this study were to determine the prevalence of vitamin D insufficiency or deficiency as measured by serum 25-hydroxyvitamin D (25-OHD) in women with breast cancer and relate this to age, ethnic group, disease stage, and seasonal variation. Methods: Levels of serum 25-OHD were requested on blood samples collected from 129 female patients with histologically-proven breast cancer (median age 61 years; range, 30-88). Vitamin D deficiency was defined as serum 25-OHD less than 12.5 nmol/L, insufficiency as 12.5 to 50 nmol/L, and sufficient levels as greater than 50 nmol/L. The prevalence of inadequate (insufficient or deficient) vitamin D levels and median 25-OHD values were calculated for the cohort as a whole and analysed according to age, ethnicity (Asian (Indian/Pakistani), White and other), disease stage (early versus metastatic), and seasons. Statistical analysis was performed using non-parametric methods and a significance level set at a two-tailed p-value &amp;lt; 0.05. Results: Overall 52% of women had inadequate levels of 25-OHD (45% deficient, 7% insufficient; median 29 nmol/L). There was no relationship with age. Lower levels were more common in Asian women (n=56) (64%; 16% deficient, 48% insufficient) compared with white women (n=65) (40%; all insufficient) and other (n=8) (62.5%; all insufficient). 25-OHD levels were significantly lower overall in Asian women in comparison with white women (median 36.5 versus 60 nmol/L; p=0.0002). When disease stage was considered, 54% of women with early breast cancer had inadequate 25-OHD levels (n=103) (7% deficient, 47% insufficient) in comparison with 42% of women with metastatic disease (n=26) (8% deficient, 34% insufficient) although overall levels were not significantly different between groups. There was no seasonal variation in 25-OHD levels. Conclusion: The prevalence of insufficient or deficient vitamin D levels as assessed by 25-OHD in women with breast cancer, especially in the Asian population, is high. Our findings suggest that all patients with breast cancer should have routine testing of vitamin D status and if appropriate, offered adequate vitamin D supplementation. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-03-03.
Risk of Hepatobiliary Cancer in Carriers of Salmonella typhi
Authors: A. MELLEMGAARD, K. GAARSLEV
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Risk of Hepatobiliary Cancer in Carriers of Salmonella typhi Get access ANDERS MELLEMGAARD, ANDERS MELLEMGAARD 1Danish Cancer Society, Danish Cancer Registry, Institute of Cancer EpidemiologyLandskronagade 66, DK-2100 Copenhagen, Denmark Search for other works by this author on: Oxford Academic PubMed Google Scholar KNUD GAARSLEV KNUD GAARSLEV 2The Serum InstituteAmagar, Boulevard 80 DK-2300, Copenhagen, Denmark Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 4, 20 April 1988, Page 288, https://doi.org/10.1093/jnci/80.4.288 Published: 20 April 1988