tbuckley/cabot-search huggingface dataset:
Abstract 220: New computerized image analyzing technique for analysis of bone marrow microvessel density in multiple myeloma
Authors: Kong Sun-Young, Nuri Lee, Young Jae Kim, Ji Yeon Sohn, Hyewon Lee, Hyeon-Seok Eom, Kwang Gi Kim
Journal: Cancer Research (2015)

Abstract Background: Angiogenesis is important in proliferation and survival of neoplastic cells in multiple myeloma (MM). Microvessel density (MVD) is a useful angiogenesis marker, which can be detected by anti-CD34 immunohistochemical stain. However, counting the MVD of bone marrow (BM) by light microscopy has a limitation in standardization due to inter-observer differences. Consistent method for MVD assessment has been required to resolve the variation in number. Here we developed the MVD counting method using computerized image analyzer (CIA) and light microscopy. Methods: A total of 21 patients with primary diagnosed with MM were evaluated. MVD was assessed by screening three hot spots of CD34 positive vessels on BM biopsy section (x40 magnification). MVD was measured by three different ways. First, the number of vessels was counted using light microscope at the time of diagnosis by several hematopathologists (MVD-A). Second, the total count of microvessels per 14435.2 μm2 (1388 × 1040μm) of marrow area was measured by a Zeiss microscope using AxioVison LE Image Analyzer with developed image analyzer program (MVD-B). In addition, manual count of captured image by CIA with one observer was examined (MVD-C). Software was developed using Microsoft visual studio (ver. 2010, Microsoft, USA) and VTK (ver. 5.10.0, Kitware, USA) library. Captured image was labeled via pre-processing for image enhancement and seed region growing algorithm to detect the MVD candidates. Using histogram texture analysis, each candidate was determined to MVD. Results: The range of MVD was as followings: MVD-A (range 3-52; mean 16.5; SD 12.8), MVD-B (range 4-38; mean 19.6; SD 10.0), and MVD-C (range 5-34; mean 14.8; SD 7.8).There was a significant correlation between theses angiogenesis parameters. Pearson's correlation coefficient of MVD-A with MVD-B was 0.535 (P = 0.01), MVD-A with MVD-C was 0.581 (P &amp;lt; 0.01), and MVD-B with MVD-C was 0.897 (P &amp;lt; 0.01). Conclusions: We developed the computer aided diagnostic tools to measure MVD more objectively. MVD count using image analyzer was well correlated with manual count and more accurate than MVD count on light microscope. Further studies with continuous upgrades on counting program are now in progress. Finally, we tried to apply this method in practice to predict the prognostic impact on MM patient at the time of diagnosis. Citation Format: Kong Sun-Young, Nuri Lee, Young Jae Kim, Ji Yeon Sohn, Hyewon Lee, Hyeon-Seok Eom, Kwang Gi Kim. New computerized image analyzing technique for analysis of bone marrow microvessel density in multiple myeloma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 220. doi:10.1158/1538-7445.AM2015-220
OP10DEVELOPMENT OF A POTENTIAL PRE-OPERATIVE RISK STRATIFICATION TOOL OF CEREBELLAR MUTISM SYNDROME IN CHILDREN WITH POSTERIOR FOSSA TUMOUR
Authors: R.A. Dineen, S. Avula, T. Chambers, M. Dutta, D. Macarthur, S. Harave, C. Ong, C. Mallucci, R. Kumar, B. Pizer, D. Walker
Journal: Neuro-Oncology (2015)

INTRODUCTION: Previous studies have identified potential clinical and radiological predictors of post-operative cerebellar mutism syndrome (CMS); however, a unifying pre-operative risk stratification model for use during surgical consent is currently lacking.The project aimed to develop a risk stratification tool via: (1) a retrospective analysis of clinical and radiological data at an institution to develop a preliminary model; then (2) validate and modify the model further in a larger cohort.METHOD: Post-operative CMS status was ascertained from clinical notes.Pre-operative MRI scans underwent structured evaluation for a 21 tightly-defined candidate imaging risk markers based on prior literature.The strongest predictors identified from logistic regression were used to test their ability to stratify patient risk.RESULTS: The combined cohort consists of 89 patients from two major treatment centres (age: 2-23yrs, gender28M,61F, MRI pathology estimate 36 medulloblastoma, 40 pilocytic astrocytoma, 12 ependymoma, 1 non-committal, 26 developed post-operative CMS).A risk model combining IV ventricular location and brainstem invasion allowed separation of the cohort into low (9-14%), intermediate (40%) and high-risk (60%).This model will be further validated and modified using a bootstrap modelling approach in May/June 2015.CONCLUSION: A risk stratification model for post-operative CMS was developed, which would indicate increased risk pre-operatively and allow reconsideration of primary intervention.This would limit risk of surgical damage, in particular, where the areas of post operative damage seem to affect the inferior olivary nucleus and associated brainstem tracts.
Abstract 4231: Combination of epigenetic, differentiation and DNA damaging agents induce tumor cell death and stem cell depletion in breast cancer
Authors: Vanessa F. Merino, Nguyen Nguyen, Helen Sadik, Soonweng Cho, Leslie Cope, Xian C. Zhou, Zhe Zhang, Qian Chen, Duojia Pan, David L. Huso, Syed Ali, Christina Adams, Balázs Győrffy, Saraswati Sukumar
Journal: Cancer Research (2015)

Abstract The histone deacetylase inhibitor, entinostat, is a new-generation epigenetic drug, which has recently demonstrated notable clinical efficacy when used in combination with standard therapy. Retinoids induce differentiation in various types of stem cells. However, its delivery to patients is challenging because of its rapid metabolism. Also, epigenetic changes in the retinoic acid receptors often render cancer cells retinoid-resistant. We have shown that a combination of entinostat, all-trans retinoic acid (ATRA) and doxorubicin causes significant regression of xenografts of triple negative breast cancer (TNBC) cells and investigated the mechanism underlying the effectiveness of this combination therapy. Combinations of entinostat, retinoic acid and doxorubicin were optimal in causing tumor regression in triple negative breast cancer xenografts. Gene expression analysis of treated TNBC cells identified genes most effectively reprogrammed by entinostat and doxorubicin (ED) combination therapy. These genes are involved in cell cycle arrest, inflammation and differentiation, which are related to better survival outcome in patients. Entinostat sensitizes the cells to doxorubicin-induced growth arrest, resulting in increased apoptosis and necrosis. Adding ATRA to ED regulated interferon genes and members of the cancer/testis antigens (CTA) and tripartite motif (TRIM) family of proteins and induces inflammation in nude mice. Entinostat/ATRA/dox therapy was most effective to target breast cancer stem cells (BCSC) in limiting dilution assays of growth in mammary fat pads. The epithelium-specific ETS transcription factor-1 (ESE-1 or ELF3), known to regulate cellular proliferation and differentiation mediates the epigenetic differentiation effect. Patient-derived distant metastases responded to entinostat/ATRA/dox therapy in culture. Thus, the combination therapy may have significant effects in decreasing both local and metastatic growth in breast cancer, especially in decreasing recurrence by targeting breast cancer stem cells. Citation Format: Vanessa F. Merino, Nguyen Nguyen, Helen Sadik, Soonweng Cho, Leslie Cope, Xian C. Zhou, Zhe Zhang, Qian Chen, Duojia Pan, David L. Huso, Syed Ali, Christina Adams, Balázs Győrffy, Saraswati Sukumar. Combination of epigenetic, differentiation and DNA damaging agents induce tumor cell death and stem cell depletion in breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4231. doi:10.1158/1538-7445.AM2015-4231
PO26MICRORNA-449A IS IMPORTANT FOR IMPEDING THE GROWTH AND INVASION OF TUMOUR INITIATING CELLS IN EXPERIMENTAL BRAIN TUMOUR MODELS
Authors: Ningning Li, Kastytis Sidlauskas, Sebastian Brandner
Journal: Neuro-Oncology (2015)

INTRODUCTION: Combinations of genetic mutations determine the phenotype of brain tumours. In our model, deletion of Pten/p53 genes in the stem cells of murine subventricular zone (SVZ) gives rise to gliomas, whereas deletion of Rb/p53 generates PNETs. The results confirm that differentiation to glial or neural lineage depends on individual oncogenic signals. Here we aimed at identifying the role of strong post-transcriptional regulators -microRNAs - in determining the malignant characteristics of tumour-initiating cells. METHOD: Stem cells were isolated from the brain of p53lox/lox/Ptenlox/lox, or p53lox/lox/Rblox/lox mice, recombined in vitro by adeno-cre, and grown on laminin surfaces to form monolayers for in vitro assays. The murine tumours were generated by grafting the stem cells to the striatum of nude mice. MicroRNA arrays were performed on solid brain tumours. RESULTS: MicroRNA-449a is upregulated in experimental PNETs (tumours in Rb/p53 mice) and in vitro recombined cells with the same mutations. Downregulation of microRNA-449a in Rb/p53 deficient cells increased invasiveness, proliferation and migration. However, it did not affect self-renewal and response to chemotherapeutic agents. CONCLUSION: Our study demonstrates that microRNA-449a is important in inhibiting growth and invasion of tumour-initiating cells. This is in line with our observation that the primary experimental PNETs are well demarked and non-invasive in comparison to experimental gliomas, suggesting that microRNA-449 may be involved in causing an invasive phenotype. The role of the downstream targets of this microRNA is currently being investigated.
Abstract 568: Fibroblast growth factor receptors 2 is a novel therapeutic target in esophagogastric junction adenocarcinoma
Authors: Ryuma Tokunaga, Yu Imamura, Kenichi Nakamura, Takatsugu Ishimoto, Shiro Iwagami, Junji Kurashige, Daisuke Izumi, Keisuke Kosumi, Takaaki Higashi, Katsunobu Taki, Yukiharu Hiyoshi, Yoshifumi Baba, Yasuo Sakamoto, Yuji Miyamoto, Naoya Yoshida, Saeki Hiroshi, Eiji Oki, Yoshihiko Maehara, Hideo Baba
Journal: Cancer Research (2015)

Abstract Background: The prognosis of esophagogastric junction (EGJ) adenocarcinoma remains poor, though it is increasing worldwide. The fibroblast growth factor receptors (FGFRs) play critical roles in various human cancers, especially FGFR2 amplification has been implicated as a key genetic alteration in EGJ adenocarcinoma. In this study, we confirmed that FGFR2 can be a therapeutic target for EGJ adenocarcinoma. Methods: Utilizing 200 cases with EGJ adenocarcinoma (Siewert types I-III), FGFR2 copy number was assayed by Real-time PCR (using RNaseP as a referent), and FGFR2 expression was detected by immunohistochemistry. We examined whether FGFR2 amplification correlates with FGFR2 expression. The associations between FGFR2 expression and clinicopathological factors, and prognostic impact of FGFR2 expression were examined. We investigated the role of FGFR2 in cell proliferation, invasion, apoptosis and cell cycle, using OACM 5.1C (FGFR2 overexpressing cell line), by siRNA technique targeting FGFR2. Results: FGFR2 amplification was detected in 33 (22%) cases, and FGFR2 expression was observed in 112 (58%) cases. FGFR2 amplification significantly correlated with FGFR2 expression (p = 0.045). FGFR2 expression was significantly associated with tumor depth of invasion, nodal involvement, distant metastasis, lymphatic invasion, and vascular invasion (all, p &amp;lt; 0.001). In survival analysis, tumors harboring FGFR2 expression experienced significantly unfavorable outcome (p = 0.039). We observed that si-FGFR2 significantly suppressed phosphorylation of Akt and Erk, resulting in suppressing cell proliferation and invasion; and inducing apoptosis and cell-cycle arrest (p&amp;lt;0.001). We also confirmed that FGF 7 promoted the proliferation and AZD4547 inhibited the proliferation through RAS-ERK and PI3K-AKT pathways. Conclusion: FGFR2 can be a therapeutic target for EGJ adenocarcinoma. Citation Format: Ryuma Tokunaga, Yu Imamura, Kenichi Nakamura, Takatsugu Ishimoto, Shiro Iwagami, Junji Kurashige, Daisuke Izumi, Keisuke Kosumi,, Takaaki Higashi, Katsunobu Taki, Yukiharu Hiyoshi, Yoshifumi Baba, Yasuo Sakamoto, Yuji Miyamoto, Naoya Yoshida, Saeki Hiroshi, Eiji Oki, Yoshihiko Maehara, Hideo Baba. Fibroblast growth factor receptors 2 is a novel therapeutic target in esophagogastric junction adenocarcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 568. doi:10.1158/1538-7445.AM2015-568
Abstract 4601: Genetic polymorphisms in the vitamin D pathway in relation to lung cancer risk and survival
Authors: Jinyu Kong, Fangxiu Xu, Jinli Qu, Yu Wang, Ming Gao, Herbert Yu, Biyun Qian
Journal: Cancer Research (2015)

Abstract Studies have suggested that vitamin D may have protective effects against cancer development or tumor progression. To search for additional evidence, we investigated the role of genetic polymorphisms involved in the vitamin D pathway in non-small cell lung cancer (NSCLC). We evaluated common genetic polymorphisms associated with the vitamin D pathway in relation to NSCLC in a case-control study of 603 newly diagnosed NSCLC patients and 661 matched healthy controls. Seven single nucleotide polymorphisms (SNPs) were genotyped, the expression of CYP27B1 and CYP24A1 were measured in 153 tumor samples and their associations with genotypes and patient survival were also analyzed. In the case-control comparison, we found SNP rs3782130 (CYP27B1), rs7041 (GC), rs6068816 and rs4809957 (CYP24A1) associated with NSCLC risk. The risk of NSCLC was increased with the number of risk alleles. CYP27B1 and CYP24A1 expression were significantly different between tumor and normal tissues in NSCLC. High CYP27B1 expression was associated with better overall survival, and the expression was different by the rs3782130 genotype. The study suggests that some genetic polymorphisms involved in the vitamin D pathway may associate with NSCLC risk, and one of the polymorphisms (rs3782130) may affect gene expression and patient survival. Note: This abstract was not presented at the meeting. Citation Format: Jinyu Kong, Fangxiu Xu, Jinli Qu, Yu Wang, Ming Gao, Herbert Yu, Biyun Qian. Genetic polymorphisms in the vitamin D pathway in relation to lung cancer risk and survival. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4601. doi:10.1158/1538-7445.AM2015-4601
Cost-effectiveness of cetuximab, bevacizumab, and panitumumab in first-line treatment of metastatic colorectal cancer (mCRC) for patients with <i>KRAS</i> wild-type (wt) tumors in the United Kingdom.
Authors: Y. Samyshkin, N. Hertel, I. Griebsch
Journal: Journal of Clinical Oncology (2011)

e16571 Background: Combinations of chemotherapy (CT) and monoclonal antibodies (mabs) against the vascular endothelial growth factor (bevacizumab [bev]) and the epidermal growth factor receptor (cetuximab [cet] and panitumumab [pan]) have been shown to improve the clinical outcome of patients (pts) with mCRC. Little is known about the economic implications of their use. The aim of this analysis was therefore to evaluate the cost, clinical- and cost-effectiveness of adding the mabs cet, bev or pan to CT in the first-line treatment of mCRC pts with KRAS wt tumors, from the UK NHS perspective. Methods: A semi-Markov model was developed to simulate patient outcomes and costs for first and subsequent lines of treatment including long-term survival after a curative resection of liver metastases. Data for progression-free survival, resection rates and other model parameters were mainly derived from the CRYSTAL, NO16966 and PRIME phase 3 studies. The long-term benefits of surgery were estimated from a consecutive series of 1439 pts. Resource use included drugs, physician visits, scans, hospitalizations and treatment of adverse events. Extensive scenario and univariate sensitivity analyses were undertaken to explore the robustness of the results with regard to various modeling assumptions and parameter uncertainty. Results: In the base case, the estimated mean life expectancy for cet-, bev- and pan-containing regimens was 3.22, 2.31 and 2.39 years (all undiscounted) respectively. The incremental cost-effectiveness ratio (ICER) for cet + FOLFIRI vs. FOLFIRI alone was £30,665 per quality-adjusted life year (QALY) and £17,626 and £15,326 per QALY compared with bev or pan + FOLFOX respectively. The ICER is mainly driven by the number of pts becoming resectable and the acquisition cost for each antibody. Conclusions: This analysis suggests that cet in combination with FOLFIRI is the most effective treatment regimen for pts with KRAS wt tumors. The incremental cost-effectiveness ratios of cet in combination with CT compared with CT alone, and bev- or pan-containing regimens are within the commonly accepted threshold for cost-effectiveness in the UK.
Abstract 2986: Meta-analysis of whole exome sequencing data reveals the mutational spectrum of testicular germ cell tumors
Authors: Kevin Litchfield, Richard S. Houlston, Robert Huddart, Brenda Summersgill, Janet Shipley, Clare Turnbull
Journal: Cancer Research (2015)

Abstract Testicular germ cell tumors (TGCTs) are the most common cancer in young men. Although cure rates for TGCT are generally high, due to the sensitivity of malignant testicular germ cells to platinum-based chemotherapies, this comes at the cost of an increased risk of metabolic syndrome, infertility and secondary cancer. Furthermore, there are limited options for patients who are platinum resistant, a group for whom the long-term survival rate is less than 15%. Improved targeted therapies for TGCT are predicated on a greater understanding of mutational profile of these tumours, including identification of driver mutations and pathways disrupted. We recently published the first large-scale analysis of whole exome sequencing of TGCTs (comprising 42 tumors), which revealed a uniformly low mutation rate; some ∼ten times lower than average rates observed in other adult solid tumors, consistent with the embryological origin of TGCT. Aside from mutations in the previously known driver gene KIT, no additional novel genes with mutation frequency greater than 15% were associated with tumorigenesis. In parallel The Cancer Genome Atlas consortium is sequencing an additional series of TGCTs. Given the apparent absence of high frequency driver genes aside from KIT, several lower frequency oncogenic pathways may exist, requiring identification through larger sample size studies and/or pooled analysis. Here we present meta-analysis across multiple datasets with variant calling re-processed through a consistent bioinformatic pipeline. We systemically searched for novel recurrent mutational events at three levels:- (i) driver genes (combined sample size was empowered to detect recurrent gene mutations of frequency &amp;gt;5% with 89% power), ii) pathway based associations and iii) focal copy number alterations. In addition we assessed for clinicopathological-molecular associations, with particular focus on mutational events distinguishing treatment responsive and resistant tumors. Comprehensive cataloguing of the mutational spectra, through analyses of our data in combination with other initiatives such as TCGA, is leading to increasing insights into this biology of this cancer. Citation Format: Kevin Litchfield, Richard S. Houlston, Robert Huddart, Brenda Summersgill, Janet Shipley, Clare Turnbull. Meta-analysis of whole exome sequencing data reveals the mutational spectrum of testicular germ cell tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2986. doi:10.1158/1538-7445.AM2015-2986
Should Medicare Value-Based Purchasing Take Social Risk into Account?
Authors: Karen E. Joynt, Nancy De Lew, Steven H. Sheingold, Patrick H. Conway, Kate Goodrich, Arnold M. Epstein
Journal: New England Journal of Medicine (2016)

A new report shows that Medicare beneficiaries with social risk factors had worse outcomes than other beneficiaries on many quality measures, and providers that disproportionately served such beneficiaries tended to have worse performance on quality measures.
PWE-008 The East Midlands polypectomy study
Authors: S DIN, K Kerr, A Goddard
Journal: Gut (2010)

<h3>Introduction</h3> The NHS Bowel Cancer Screening Programme was introduced in 2006 for the early detection of cancer and premalignant polyps. This has resulted in a large number of polyps being found on colonoscopy and an opportunity to accumulate good data and risk stratify polypectomy complication rates. The Munich polpypectomy study was a large, prospective, multicentre study of 4000 snare polypectomies in 2257 patients. Complications occurred in 9.7% of patients (6.1% polyps) with 7.0% of these complications being minor and 2.7% major. Polyp size was identified as an important risk factor for major complications, followed by right sided location and number of polyps. However, there is a lack of large systematic prospective studies in the UK of polypectomy complications. <h3>Methods</h3> Data on all polypectomies at two DGHs were collected prospectively over 24 months as part of the normal bowel screening process. Early and late complications were recorded. The service review included patients enrolled onto the screening programme between the ages of 60–69 and who had a polypectomy. Patients were excluded if they were &lt;60 or &gt;70 years old and not had a polypectomy. The primary endpoints of the study were polypectomy complications which were classed as major or minor. The risk factors for complications were analysed for patient demographics, polyp size, distribution and histology. <h3>Result</h3> 1388 patients participated in the bowel screening programme and 780 patients were identified (535 male and 245 female) with a total of 2098 polypectomies. 45% of the patients had left sided polyps, 13.3% right and the remainder of polyps on both sides. 70% of polyps were &lt;5 mm, 19.8% 5–10 mm, 12.7% 10–20 mm and 7.2% &gt;20 mm. The total complication rate was 1.79% (95% CI 0.86 to 2.72) with a polyp complication rate of 0.67% and zero mortality. There were three (0.38%) major complications (95% CI −0.05 to 0.81); 1 left sided perforation requiring surgery, one right sided perforation which was clipped and one major bleed. Left sided polyp location was a risk factor for minor bleeding complications 1.41% (95% CI 0.58–2.24). Cancerous polyps (3/14) and polyp size 5–10 mm carried an increased risk of complications. <h3>Conclusion</h3> The bowel screening programme has added another dimension due to the large volume of polyps being found and polypectomies undertaken. This study has shown that serious complications are rare. Identification of patient and polyp characteristics can be used as a predictor to reduce the incidence of major complications; however, a larger study is needed to clarify this.