tbuckley/cabot-search huggingface dataset:
OC-048 Does the performance of faecal calprotectin testing in primary care differentiate patients with inflammatory bowel disease?: Abstract OC-048 Table 1
Authors: S Conroy, M Hale, S Cross, K Swallow, R Sidhu, R Sargur, A Lobo
Journal: Gut (2015)

<h3>Introduction</h3> Measurement of faecal calprotectin (FC) may identify those harbouring inflammatory bowel disease (IBD). Use of the test is supported by NICE guidance (DG11) but evidence of its performance, in “real-life”, in patients presenting to primary care, is limited. <h3>Aim</h3> To assess the yield of IBD from FC testing in primary care. <h3>Method</h3> FC testing (Immunodiagnostics Phical Calprotectin ELISA) was made available to clinicians in October 2013. The results of all FC assays from 1.10.13 to 28.2.14 were reviewed retrospectively with results of GI investigations. <h3>Results</h3> Of FC measurements undertaken in 526 patients, 26 could not be identified on the local patient administration system, 57 were initiated in secondary care, 23 had known IBD and outcomes were not available for 22 patients with a raised FC (median 90 μg/g); range 54–995). These were excluded. 398 patients had FC requested in primary care (158 male; median age 42; range 6–91). FC was “positive” (&gt;50 μg/g) in 132/398 (33.2%; median age 44 (range 6–91); median FC 128.5 μg/g (51–1770). 122/132 with positive FC underwent further investigation; 94 (77%) had lower GI endoscopy: IBD (7), colorectal cancer (2), adenoma (8), nil significant (77). 87/94 had lower GI endoscopy for a false positive FC (no IBD). 49/266 FC-negative patients also underwent lower GI endoscopy (median age 47; range 19–76) finding IBD (2), diverticulitis (1), adenomas (2), nil significant (43). 3/266 FC negative patients had IBD. IBD was diagnosed in 11/398 (2.3%; 4 ulcerative colitis (UC), 3 Crohn’s disease (CD), 2 collagenous colitis, 2 lymphocytic colitis (Table 1)). 8/11 were FC positive (range 67–1170); 3 were FC negative. At a 50 μg/g threshold, sensitivity for detecting IBD was 72.7%, specificity 68%, positive predictive value (PPV) 6.1%, negative predictive value 98.9%. <h3>Conclusion</h3> FC testing in primary care has lower sensitivity and specificity than in secondary care and poor PPV for detecting IBD. False positive FC is associated with more lower GI investigation than previously estimated. This experience differs from data used to inform NICE DG11. Strategies to target use to those with higher pre-test probability of IBD are needed. <h3>Disclosure of interest</h3> S. Conroy: None Declared, M. Hale: None Declared, S. Cross: None Declared, K. Swallow: None Declared, R. Sidhu: None Declared, R. Sargur: None Declared, A. Lobo Consultant for: Takeda UK and Vifor Pharma.
Abstract 4016: c-MET associated with osteogenesis in multiple myeloma patients by induction of MMP9 expression by HGF in BMSCs
Authors: Hyejoo Park, Jeong In Oh, Kwang-Sung Ahn, Youngil Koh, Sung-Soo Yoon
Journal: Cancer Research (2015)

Abstract HGF-mediated c-MET signaling plays a critical key in the progression of multiple myeloma. That signaling is associated with cell proliferation, drug resistance and osteoblast. In addition dynamic interplay between MM cell and bone marrow stromal cell regulates that signaling activation. The expression level of HGF in bone marrow plasma of MM patients is higher when compared to case control. However, the role of HGF-mediated c-Met was obscure in the progression of MM. In this study, we elucidate the role of c-Met signaling in osteogenesis in MM using co-culture system. In our previous data, we found that the expression levels of HGF in bone marrow serum of multiple myeloma patients was correlated with the expression levels of OPN and RUNX2. Also, those expression levels were associated with bone lesion. It suggested that HGF might be one of regulators in the progression of osteogenesis. However, mechanisms by HGF-mediated c-MET activation modulate the expression of matrix metalloproteinases still remain unknown. In our study, we found that Our data show that PI3K inhibitor effectively inhibited the MMP9 mRNA expression in both OPN alone treatment and co-treatment with OPN and HGF in BMSCs. Induction of OPN and RUNX2 by HGF in MM cells could be one of the major factors for the progression of MM through interaction of MM cells and BMSCs. We suggested that induction of OPN/MMP9 strongly associated with osteoclast. For further analysis, we performed co-culture system which MM cells were grown with BMSCs obtained from MM patients’ bone marrow specimen in order to verify the role of HGF mediated c-MET activation in the progression of MM patient's osteogenesis. To explore the detail mechanisms of HGF-mediated osteogenesis, various inhibitors was used and the expression levels of a set of genes was examined using real-time PCR. Subsequently, HGF-mediated c-MET activation was regulated the expression of OPN/MMP-9 via co-effects of PIK3 activation and activation of wnt signaling pathway in BMSCs from bone marrow of MM patients. In conclusion, cross-talk between PI3K/AKT pathway and wnt singaling pathway could be one of the major factors for the progression of MM through interaction of MM cells and BMSCs. Citation Format: Hyejoo Park, Jeong In Oh, Kwang-Sung Ahn, Youngil Koh, Sung-Soo Yoon. c-MET associated with osteogenesis in multiple myeloma patients by induction of MMP9 expression by HGF in BMSCs. [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 4016. doi:10.1158/1538-7445.AM2015-4016
Molecular Biological Mechanisms of Cyclosporine a, Tetrandrine and Their Combination on the Reversion of Multidrug Resistance in Leukemia Cell Line
Authors: Bao-An Chen, Jing-jing Guo, Jian Cheng, Feng Gao, Wen-lin Xu, Hui-lin Shen, Jia-hua Ding, Chong Gao, Yun-Yu Sun, Jun Wang, Gang Zhao, Hui-hui Song, Wen Bao, Xin-chen Sun, Hong-yan Cheng, Yu-xia Deng, Guo-hong Li, Li-jie Liu, Wen-ji Chen, Jue-qiong Wang, Peng Yuan, Xiao-ping Pei, Ning-na Chen, Xue-mei Wang
Journal: Blood (2008)
“Getting to go” for FDA Approvals for the Treatment of Hematologic Versus Solid Tumor Malignancies: A Report from the Research on Adverse Drug Events and Reports (RADAR) Project
Authors: Elizabeth A Richey, Veena Shankaran, Steven Hirschfeld, Steven M Trifilio, June McKoy, Kenneth R Carson, Beatrice J Edwards, Thanh Ha Luu, Narissa Nonzee, A. Oliver Sartor, Charles L. Bennett
Journal: Blood (2008)
Abstract 4334: Elevated lactic acid is a negative prognostic factor in metastatic lung cancer
Authors: Panagiotis J. Vlachostergios, Nirav Parikh, Katerina Oikonomou, Eugene Gibilaro, George Apergis
Journal: Cancer Research (2015)

Abstract Introduction: Hyperlactatemia with or without type B lactic acidosis is a rare complication of malignancy, previously observed most often in hematological malignancies. Underlying pathophysiology involves reduced lactic acid metabolism from metastatic liver dysfunction as well as overproduction of lactic acid from aberrant glycolytic metabolism of tumors. Clinical data to evaluate the potential value of arterial or venous lactic acid (LA) level assessment as a predictor of overall survival (OS) or/and response to treatment are lacking. The aim of this study was to assess the prognostic value of LA in patients with metastatic lung cancer. Methods: Patients diagnosed with stage IV non-small cell lung cancer (NSCLC) or extensive stage small cell lung cancer (SCLC) from 2012 to present, were included in this single center, retrospective study. Patients with sepsis or acute exacerbation of heart failure were excluded from the study. Arterial and venous LA level, bicarbonate, anion gap, urine ketones, serum LDH were recorded for each patient and their associations with demographic and clinical data and OS were analyzed with the Chi-square test, Kaplan-Meier's actuarial method (log-tank test) and Cox proportional hazard model. Results: 85 patients (43 males, mean age 73.1, range 45-96 years) were studied. The maximal levels of arterial or venous LA were significantly associated with presence of ≥2 metastatic sites (p = 0.001), ICU admission or transfer (p = 0.016), intubation (p = 0.029), elevated serum anion gap (p&amp;lt;0.001) and LDH levels (p&amp;lt;0.001). No significant associations emerged between LA level and gender, age, smoking status, histology, tumor size or grade, previous lung resection, location of metastases, COPD, previous metformin use, ketonuria, and previous or ongoing palliative chemotherapy. Hyperlactatemia (p&amp;lt;0.001), histologic subtype (p = 0.019), ICU admission or transfer (p = 0.014), intubation (p = 0.026), number of metastatic sites (p = 0.01), AG (p&amp;lt;0.01) and LDH (p&amp;lt;0.001) were univariately associated with OS. LDH was the only independent prognostic factor [OR = 0.162 (95% CI: 0038-0.687), p = 0.014]. Conclusion: Our results suggest that elevated LA is a predictor of poor OS in metastatic lung cancer patients, irrespective of chemotherapy. Here lie implications for targeting tumor-derived LA production via manipulation of glycolytic enzymes or lactate transporters, with use of LA as a surrogate marker of response. Citation Format: Panagiotis J. Vlachostergios, Nirav Parikh, Katerina Oikonomou, Eugene Gibilaro, George Apergis. Elevated lactic acid is a negative prognostic factor in metastatic lung 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 4334. doi:10.1158/1538-7445.AM2015-4334
Endoscopy International Open – recently published
Journal: Endoscopy (2020)

Comment on: Preliminary report on the safety and utility of a novel automated mechanical endoscopic tissue resection tool for endoscopic necrosectomy: a case seriesEndosc Int Open 2020; 08(03): E274-E280DOI: 10.1055/a-1079-5015 Comment on: EUS-guided 22-gauge fine needle biopsy versus single-incision with needle knife for the diagnosis of upper gastrointestinal subepithelial lesions: a randomized controlled trialEndosc Int Open 2020; 08(03): E266-E273DOI: 10.1055/a-1075-1900 Comment on: Irregularly branched microvessels as visualized by magnifying endoscopy: a reliable marker for predicting deep submucosal invasion of superficial esophageal squamous cell carcinomaEndosc Int Open 2020; 08(03): E234-E240DOI: 10.1055/a-1072-4676
Autologous Stem Cell Transplantation in Patients with Autonomic Neuropathy Due to AL Amyloidosis
Authors: David Dingli, Shaji K. Kumar, Francis K. Buadi, Angela Dispenzieri, Suzanne R. Hayman, Martha Q. Lacy, Dennis A. Gastineau, Mark R. Litzow, Morie A. Gertz
Journal: Blood (2008)
Pediatric Myelodysplastic Syndromes and Allogeneic Hematopoietic Progenitor Cell Transplantation (HPCT): A Single Center Perspective.
Authors: Jeffrey R. Andolina, Morris Kletzel, David Jacobsohn, William T. Tse, Jennifer Schneiderman, Reggie Duerst, Irene Helenowski, Sonali Chaudhury
Journal: Blood (2009)
PTH-023 Impact of capsule endoscopy in the clinical management and outcome of patients with obscure gastrointestinal bleeding: a 5-year experience
Authors: V Mitra, A Naqvi, A Soloman, K Kapur
Journal: Gut (2010)

<h3>Introduction</h3> Obscure gastrointestinal bleed (OGB) occurs in 5% of patients who present with gastrointestinal haemorrhage.1 In 2008, the British Society of Gastroenterology (BSG) published guidelines stating patients who present with obscure gastrointestinal bleeding with a negative gastroscopy and colonoscopy should undergo capsule endoscopy (CE).2 <h3>Methods</h3> A retrospective review of all patients presenting with OGB who underwent CE between 2005 and August 2009 was performed. Data were collected on patient demographics, indications, diagnosis and further management following CE. We evaluated the impact of CE in the management and outcome of patients with OGB in our hospital. <h3>Results</h3> 161 patients, with a mean age of 61 years, were referred for CE for investigation of OGB of which 18.7% (n=30) patients had overt bleeding (OB) and 81% (n=131) had iron deficiency anaemia (IDA). 117 (72.5%) were females. Angiodysplasia was the most common finding in 27.5% of patients (n=44). Other findings included GAVE (3.7%), Crohn9s (1.8%), duodenitis/jejunoileitis (3.7%), NSAID induced ulcers (3.7%), coeliac (0.6%), HHT (1.8%), unexplained ulcers (1.8%), phlebectasia (1.2%), lymphangiectasia (1.2%) and gastritis (3%) while CE was normal in 49% (n=79). The diagnostic yield was 63% and 44% in the OB and IDA groups, respectively (odds ratio 2.17). CE resulted in a change of management in 33% (n=53) of patients of which 46 (89.7%) had a positive outcome. In the OB group, 8 (27.5%) patients were diagnosed with active bleeding of which 1 underwent surgery, 1 had their NSAID stopped and 6 underwent argon plasma coagulation (APC) to treat angiodysplastic lesions. In the remaining 22 patients in the OB group, 8 (27.5%) were initiated on new medications (PPI/Iron), 6 (20%) underwent repeat endoscopic tests and 8 were reassured and discharged. In the IDA group, 7 (5.5%) patients had evidence of active bleeding and had APC to the angiodysplastic lesions. In the remaining 124 patients in the IDA group, 10 (7.6%) were started on new medications, 3 (2.5%) and 1 (0.5%) patient were diagnosed with Crohn9s and Coeliac disease, respectively, and started on appropriate treatment, 2 (1.5%) had their NSAIDs stopped and 1 (0.5%) underwent repeat endoscopic investigation. The remaining 100 (69 normal, 31 with non-bleeding abnormalities) were reassured and advised to continue iron tablets. <h3>Conclusion</h3> The high diagnostic yield of CE in OGB influences clinical management leading to improved outcomes. CE led to a change in management in 33% of patients while reassurance with a concrete management plan was obtained in the rest. More patients (73.3%) underwent a change in management plan in the OB group compared to the IDA though the numbers in the OB group were comparatively small (OR 8.8).
Abstract POSTER-TECH-1122: Mass spectrometric imaging of ovarian cancer mouse model tissue: searching for high-grade serous carcinoma biomarkers
Authors: Martin R. L. Paine, Rachel V. Bennett, Jaeyeon Kim, M. Cameron Sullards, Martin M. Matzuk, Facundo M. Fernández
Journal: Clinical Cancer Research (2015)

Abstract High-grade serous carcinoma (HGSC) is the most common and deadliest ovarian cancer responsible for 90% of all ovarian cancer deaths. Studying the origin and early progression of this deadly cancer is critical in identifying biomarkers for early detection of the disease. Unfortunately, in the case of HGSC, it is virtually impossible to obtain early-stage human HGSC tissue samples because there is no diagnostic method capable of detecting early forms of HGSC. The recent breakthrough of an animal model (Dicer-Pten double-knockout mice) provides an invaluable opportunity to finally investigate the early tumor microenvironment. The model exhibits remarkable similarities to human HGSC, allowing greater insight into the biochemistry associated with nascent neoplastic changes within ovarian and fallopian tube tissues. An important aspect of determining potential biomarkers is to correlate any detected chemical changes with observed histological changes. To visualize the spatial distribution of chemical changes, tissue-based mass spectrometric imaging (MSI) can be employed as an unbiased way of visualizing the changes of proteins, metabolites, or both in cancer tissues. MSI is particularly useful for identifying molecules uniquely elevated or lowered in early tumor tissues, in which cell-type specific changes are expected to occur due to intratumoral microenvironment heterogeneity. In this study, two complementary MSI techniques – matrix-assisted laser desorption ionization (MALDI) and desorption electrospray ionization (DESI) mass spectrometry – are applied to thin tissue sections of Dicer-Pten mutant mouse ovaries and fallopian tubes. Several sulfatide lipids d18:1/C16:0, d18:1/C24:1 and d18:1/C24:0 have been implicated as potential biomarkers in human ovarian cancer. These metabolites, among others, are being included in a thorough MSI experiment to visualize molecular changes in multiple cell types in the microenvironment during early tumor progression. In addition to providing information about the early molecular changes taking place, the knowledge gained from this study will also help understand which specific cell types in the fallopian tube are more prone to early tumorigenesis. (Grant support: Marsha Rivkin Ovarian Cancer Challenge Grant) Citation Format: Martin R. L. Paine, Rachel V. Bennett, Jaeyeon Kim, M. Cameron Sullards, Martin M. Matzuk, Facundo M. Fernández. Mass spectrometric imaging of ovarian cancer mouse model tissue: searching for high-grade serous carcinoma biomarkers [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-TECH-1122.
Abstract LB-263: Effects of black raspberry diet on the metabolomic profile of C57BL/6J mouse tissues
Authors: Chad W. Skaer, Pan Pan, Matthew Young, Hsin Tzu Wang, Kiyoko Oshima, Yi-Wen Huang, Gary D. Stoner, John Lechner, Li-Shu Wang
Journal: Cancer Research (2015)

Abstract In our previous work, a diet containing 5% freeze-dried black raspberries (BRB) was shown to significantly inhibit colorectal cancer in ApcMin mice. Studies in recent years have shown that metabolomics may help to elucidate the anti-cancer effects of dietary factors. Initially, therefore, we evaluated the effects of black raspberries on the metabolomic profiles of C57BL/6J mice, the mouse strain from which ApcMin mice were derived. In this study, we report the effects of the BRB diet on the metabolomic profiles from C57BL/6J mice. After 8 weeks on a 5% BRB or control AIN-76A diet, feces, liver, and colon mucosa tissues from 9 BRB-fed mice and 7 control-diet fed mice were collected and profiled using mass spectrometry. A total of 424 named metabolites were observed in the liver, feces, and colon mucosa, with 115 metabolites whose levels were significantly different between BRB and control-diet mice (P&amp;lt;0.05). Of these 115 differentiated metabolites, 41 were altered in the colon mucosa, and 38 and 44 metabolites were different in the feces and liver, respectively. Almost all of the changed metabolites in the colon mucosa (36 of 41) were downregulated by the BRB diet, whereas in the feces and liver the majority were upregulated (58 of 82). Included in the upregulated metabolites were lipids and amino acids in the feces and liver tissue. Benzoate derivatives, the product of gut bacteria metabolism of BRB polyphenols, were also up in all tissues. Among the downregulated metabolites were lipids in the colon mucosa and lysolipids in the liver. The decreased levels of lipid metabolites, particularly fatty acids, in the colon mucosa of mice indicates that antagonizing fatty acid synthesis is a potential mechanism by which the BRB diet is altering energy utilization in the colon mucosa of mice. Citation Format: Chad W. Skaer, Pan Pan, Matthew Young, Hsin Tzu Wang, Kiyoko Oshima, Yi-Wen Huang, Gary D. Stoner, John Lechner, Li-Shu Wang. Effects of black raspberry diet on the metabolomic profile of C57BL/6J mouse tissues. [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 LB-263. doi:10.1158/1538-7445.AM2015-LB-263
Abstract 1366: Mdm2 antagonist RG7388 does not interfere with tumor angiogenesis <i>in vitro</i> and <i>in vivo</i>
Authors: Christian Lehmann, Thomas Friess, Erica Lorenzon, Frank Herting, Markus Dangl
Journal: Cancer Research (2015)

Abstract MDM2 interacts with the transcription factor p53 via its N-terminal domain and is the most prominent and best described natural inhibitor of the p53 tumor suppressor pathway. Apart from this very well investigated function, MDM2 has been reported to be involved in angiogenesis via various mechanisms. Published data indicate that MDM2 interacts directly with and activates HIF1a but can also display HIF1a independent effects such as VEGF mRNA stabilization or regulation of ERK1/2 signaling. Taken together, these reports suggest that MDM2 antagonists might have the potential to inhibit tumor-angiogenesis or age-related macular degeneration. In order to test the potential anti-angiogenic activity of interfering with MDM2-p53 binding, we utilized the highly selective, clinical stage MDM2 antagonist RG7388. First, it was tested if RG7388 influences the induction of response to hypoxic conditions using a HRE-reporter cell line, followed by analyzing the interference of RG7388 with human endothelial cell tubule formation. The in-vitro results showed no statistically significant inhibition of HIF1a facilitated GFP reporter activation nor any effect on HUVEC tubule formation, viability or proliferation. In a mouse cornea pocket assay in-vivo, systemic administration of a MDM2 antagonist did not prevent VEGF-A or FGF-2 induced vessel formation. Finally, RG7388 and vehicle treated SJSA xenograft tumors were explanted and analyzed in detail for changes in vessel architecture. No effects on microvascular density or vessel structure were observed. Taken together, these data indicate that RG7388, a highly selective MDM2 antagonist that binds to the p53-binding pocket of MDM2 and prevents interaction of MDM2 with p53, is not suitable for anti-angiogenic treatment. One possible explanation for the lack of anti-angiogenic activity is the increased potency/specificity of RG7388 resulting in higher selectivity and fewer off target effects compared to Nutlin-3a. Citation Format: Christian Lehmann, Thomas Friess, Erica Lorenzon, Frank Herting, Markus Dangl. Mdm2 antagonist RG7388 does not interfere with tumor angiogenesis in vitro and in vivo. [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 1366. doi:10.1158/1538-7445.AM2015-1366