tbuckley/cabot-search huggingface dataset:
Abstract 3760: EGFL6 is a tumor vascular regulator of ovarian CSC asymmetric division and a novel therapeutic target.
Authors: Ronald J. Buckanovich, Shoumei Bai, Ning Deng, Patrick Ingram, Euisik Yoon
Journal: Cancer Research (2013)

Abstract Cancer stem cells (CSC) are closely associated with tumor vasculature in the CSC niche. Tumor vascular cells are known to provide critical growth, differentiation, and survival cues for CSC. Unfortunately little is known about the specific factors produced by vascular cells. EGFL6 is a factor specifically secreted by ovarian tumor vascular cells. EGFL6 is reported to regulate the differentiation of normal stem cells. We examined the impact of EGFL6 on ovarian cancer cell growth. We found that EGFL6 significantly promoted ovarian cancer cell growth in vitro. Ovarian cancer cell proliferation was associated with a decrease in the percentage of ALDH+ ovarian CSC. Using a novel single cell microfluidic culture system we found that EGFL6 acts specifically on ALDH+ CSC to promote proliferation via asymmetric division. We used a in vivo novel model of human tumor vasculature to express EGFL6 in vivo and demonstrate that EGFL6 significantly promotes ovarian tumor growth. Finally we generated an EGFL6 blocking antibody and found that anti-EGFL6 antibodies could restrict tumor growth and delay disease recurrences. Thus EGFL6 is an import vascular regulator of ovarian CSC and EGL6 blocking antibodies represent a potentially important ovarian CSC targeting therapeutic. Citation Format: Ronald J. Buckanovich, Shoumei Bai, Ning Deng, Patrick Ingram, Euisik Yoon. EGFL6 is a tumor vascular regulator of ovarian CSC asymmetric division and a novel therapeutic target. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3760. doi:10.1158/1538-7445.AM2013-3760
Abstract 4273: C-kit expression promotes prostate cancer cell migration and invasion through Brca2 downregulation
Authors: Xiaoning Zhe, Marcelo Quintanihla Azevedo, Michael L. Cher, Hyeong-Reh C. Kim, R. Daniel Bonfil
Journal: Cancer Research (2012)

Abstract In many human cancers, expression or activity of the receptor tyrosine kinase (RTK) c-kit is often associated with increased malignancy. In prostate cancer (PCa), we reported an association between expression of c-kit and clinical progression, with the highest expression seen in castrate-resistant metastatic bone specimens. We also found de novo c-kit expression in experimental intraosseous tumors formed by otherwise c-kit negative PCa cells. However, the biological consequences of c-kit expression and activation in PCa cells remain unknown. Here, we show that c-kit overexpression in PC3 and C4-2B PCa cells significantly enhances their migratory and invasive ability in vitro. Consistent with this result, we found that expression and activation of c-kit in PCa cells decreased the expression of E-cadherin and increased the expression of vimentin, suggesting an epithelial mesenchymal transition-like phenomenon. Furthermore, activation by c-kit ligand in PC3 and C4-2B cells transfected with c-kit lead to phosphorylation of Akt. This contributes to the enhanced invasiveness of c-kit-expressing PCa cells, as demonstrated by an inhibitory effect by PI3K/Akt inhibitors LY294002 and Wortmannin. In an attempt to identify genes differentially expressed in c-kit-expressing and -non-expressing PCa cells, we used a microarray containing 84 genes, representing growth factor receptors, transcription factors, cell cycle, and DNA repair genes. The analysis of the array demonstrated a consistent down-regulation of Brca2 in both c-kit-expressing PC3 and C4-2B cells, further validated by qRT-PCR and immunoblotting. Re-introduction of Brca2 into c-kit-expressing PCa cells suppressed c-kit-enhanced invasiveness to levels similar to those shown by c-kit-non-expressing cells, and led to reduced phosphorylation of Akt. Our results provide evidence that c-kit expression in PCa cells, an event which is induced upon interaction with the bone microenvironment, promotes tumor migration and invasion through an Akt-dependent mechanism regulated by Brca2 down-regulation. The identification of this novel signaling axis and its importance in PCa migration and invasion reveal potential therapeutic targets for regulating the expansion of PCa metastatic lesions in bone. 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 4273. doi:1538-7445.AM2012-4273
PWE-063 Colonoscopy In The Over Nineties: How Useful And Safe Is It?
Authors: SK Butt, A Chitembwe, K Besherdas
Journal: Gut (2014)

<h3>Introduction</h3> Colonoscopy is accepted as the gold standard imaging modality of the colon for investigation of colonic symptoms including altered bowel habit, anaemia, rectal bleeding and for the detection of colorectal cancer. The incidence of pathological findings within the colon in particular colorectal cancer increases with age, and the detection of these cancers comprise a major role of colonoscopy in the elderly population. However, colonoscopy in the elderly may be more difficult, as elderly patients are more likely than younger patients to have poor bowel preparations. Furthermore, complications of colonoscopy, in particular cardiovascular, maybe higher in this age group. To date no data exist in colonoscopies performed in those over 90 years of age. <h3>Methods</h3> The aim of the study was to assess the diagnostic yield and safety of colonoscopy in the very elderly patients over 90 years of age. A single centre, retrospective analysis of patients over 90 years of age in a district general hospital from north London was performed. The patients were identified using the Unisoft Endoscopy reporting software over a period between June 2006 to March 2013. Data obtained during the study period was scrutinised for indication, sedation administered, quality of bowel prep, findings of procedure, and complications. <h3>Results</h3> During the study period, 66 colonoscopies were performed out of a total 666 endoscopic procedures in patients over 90. The indications for colonoscopy included : abnormal CT scan 5/66, altered bowel habit in 17/66, anaemia 24/66, rectal bleeding 15/66, colonic obstruction 3/66, previous polyp/colon cancer 4/66, abdominal mass 1/66. 18/66 patients had poor bowel prep. Findings included normal in 18/66, colo-rectal cancer in 13/66 patients, colonic polyps in 5/66, ischaemic colitis 1/66, angiodysplasia 2/66, diverticulosis in 31/66. Sedation administered varied from none in 4/66, to midazolam 5 mg + pethidine 50 mg in 2/66. There were no complications from the colonoscopy in 66 patients within the study. <h3>Conclusion</h3> The data from this study demonstrates that colonoscopies can be performed safely in patients over 90 years of age with no increase in procedure related mortality. Despite poor bowel preparation encountered in 28%, the diagnostic yield of pathology in patients over 90 having colonoscopy was very high with an abnormality in 48/66 (72% in this study). Colonoscopy in the very elderly is very safe and worthwhile and clinicians should not be reluctant in referring those over 90 years of age for colonoscopic examination. <h3>Disclosure of Interest</h3> None Declared.
Reducing the Time From Initial Call to First Appointment: The Impact of Patient Access Redesign and a Nurse Navigation Program
Authors: Lori J. Goldstein, Bonnie J. Miller, Nancy Nicotera, Delinda Pendleton
Journal: Journal of the National Comprehensive Cancer Network (2014)

Fox Chase Cancer Center (FCCC) participated in the NCCN Opportunities for Improvement project with the purpose of optimizing the quality of care delivered at FCCC to patients with breast cancer based on the ASCO and NCCN Guidelines. Historically, FCCC's performance has demonstrated a high level of concordance, based on findings from the NCCN Oncology Outcomes Database project benchmarking data in breast cancer. Access to the NCCN Breast Cancer Timing in Continuation and Transition of Care (TiCToC) Measures data analysis (performed by NCCN) provided an opportunity to further identify specific opportunities related to care along the continuum. The initial goal of the project was to continue participation in the NCCN Oncology Outcomes Database for Breast Cancer, with the overall objective of sustaining high concordance. FCCC's recent data were compared with historical data and benchmarked against those from other participating NCCN Member Institutions.
BOOK REVIEWS: Review 2
Authors: J. V. SIMONE
Journal: JNCI Journal of the National Cancer Institute (1989)

BOOK REVIEWS: Review 2 Get access Principles and Practice of Pediatric Oncology. Philip A. Pizzo, David G. PoplackPhiladelphia: J. B. Lippincott Company, 1989, 1150 pp. $125. JOSEPH V. SIMONE JOSEPH V. SIMONE St. Jude Children's Research Hospital332 N. Lauderdale P.O. Box 318 Memphis, TN 38101-0318 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 11, 7 June 1989, Pages 876–877, https://doi.org/10.1093/jnci/81.11.876-a Published: 07 June 1989
Palonosetron (PALO) plus aprepitant (APREP) and dexamethasone (DEX) for the prevention of chemotherapy-induced nausea and vomiting (CINV) after emetogenic chemotherapy (CT)
Authors: T. Grote, J. Hajdenberg, A. Cartmell, S. Ferguson, A. Ginkel, S. Gallagher, V. Charu
Journal: Journal of Clinical Oncology (2004)

8262 Background: PALO is the only 5-HT3 receptor antagonist (RA) approved by the FDA for prevention of acute & delayed CINV after moderately emetogenic CT. Aprepitant is a NK1 RA approved for prevention of acute & delayed CINV after highly emetogenic CT when used with a 5-HT3 RA & DEX. We now report the first study combining these novel antiemetics in patients (pts) receiving a wide variety of moderately to moderate-highly emetogenic chemotherapy. Methods: This multicenter, phase II, open-label study assessed the efficacy & safety of a single IV dose of PALO 0.25 mg on Day 1 of CT, along with 3 daily oral doses of APREP (125 mg on Day 1; 80 mg on Days 2–3) plus DEX (12 mg on Day 1; 8 mg on Days 2–3). Eligible pts were naïve or non-naïve to CT. Efficacy assessments included complete response (CR: no emetic episodes [EE] and no rescue medication) and no EE during the acute (0–24 hr), delayed (24–120 hr), and overall (0–120 hr) intervals post-CT. Adverse events were collected to assess safety. Results: Intent-to-treat assessments of the first 39 of the planned 50 pts are reported. Most pts were women with breast cancer; 39% were chemo-naïve. The most common CT regimens were doxorubicin+cyclophosphamide and paclitaxel+carboplatin. CR; no emetic episodes and no rescue medication. The most common adverse events included diarrhea, fatigue, and constipation, consistent with product labeling for PALO and/or APREP. Conclusions: Preliminary results indicate that PALO, APREP, and DEX may be safely combined and may improve the overall prevention of CINV. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MGI Pharma MGI Pharma MGI Pharma MGI Pharma MGI Pharma
P18 Idiopathic pulmonary fibrosis survival has not improved in the 21st century; analysis of CPRD gold primary care data
Authors: Tm Maher, H Strongman, R Boggon, I Kausar
Journal: Thorax (2013)

<h3>Introduction and Objectives</h3> Idiopathic pulmonary fibrosis (IPF) is a progressive and invariably fatal disease. Historical cohort studies have reported a median survival of 2.8–3.2 years<sup>1</sup>. The UK has seen a number of important developments for IPF patients in the last year which it is hoped will translate to improved outcomes for individuals with this devastating disease. These include: the licensing and approval by NICE of the first anti fibrotic therapy, pirfenidone; specialist commissioning of ILD services; and publication of NICE IPF guidelines. If the impact of these important developments is to be measured it is vital that current IPF disease burden is understood. <h3>Methods</h3> The incidence and mortality of IPF-Clinical Syndrome, using broad and narrow disease definitions, was assessed via the Clinical Practice Research Datalink (CPRD) GOLD dataset. <h3>Results</h3> The incidence of broadly defined IPF-CS between 2000–2012 was 8.65 (95% CI 8.40–8.90) per 100,000 person years and significantly increased over time (incidence rate ratio adjusted by gender, region and age category = 1.02, p for linear trend &lt;0.0001). Kaplan-Meier survival estimates show no significant survival difference by year of diagnosis (log rank test for equality of survivor functions, p = 0.17) with a median survival of 3.0 years (95% CI 2.8–3.1). There was no significant survival difference for broad and narrow definitions (log rank test for equality of survivor functions, p = 0.06) validating the definition of IPF-CS. <h3>Conclusions</h3> In keeping with previous data the incidence of IPF-CS continues to rise and the survival time from diagnosis remains unchanged. The mortality burden of IPF-CS is therefore increasing. The results of this study provide an important benchmark against which the effects of changes in the management and delivery of care for individuals with IPF can be measured. <h3>References</h3> Navaratnam V, Fleming KM, West J, Smith CJ, Jenkins RG, Fogarty A, Hubbard RB. The rising incidence of idiopathic pulmonary fibrosis in the U. K. <i>Thorax</i>. 2011;66:462–7.
Abstract 5161: Role of glutamine in cancer growth, invasion and progression: Therapeutic modulation of glutamine pathway
Authors: Lifeng Yang, Deepak Nagrath
Journal: Cancer Research (2012)

Abstract Glutamine, an alternative carbon source to glucose, has recently been shown to be important for the cancer cell survival, growth and progression. The link between glycolysis, glutaminolysis and fatty acid oxidation is not known. Thus, there is a strong motivation to study metabolic alternations caused by glutamine and uncover links between various fuel sources for highly and less invasive cancer cells. Here, we postulate that glutamine will increase glutamine uptake through up-regulating ASCT2 expression, while decreasing the glucose uptake by down-regulating GLUT1 expression for aggressive cancer cells. However, for non-aggressive cancer cells, glutamine will have no effect on glutamine and glucose uptake. Our findings indicate that NAD+/NADH ratio regulates the glutamine's direct effect on the lactate production irrespective of the bioenergetic substrate requirement for different kinds of cancer cells. Our findings using quantification of metabolites pertaining to central carbon and nitrogen metabolism provided clues as to which pathways relevant to glycolysis, the pentose phosphate pathway, the TCA and urea cycles, lipid cycle, and amino acid and nucleotide metabolisms, may be altered by glutamine in cancer cells, resulting in identification of dominant factors which control cancer metabolism. Through this study, we clearly demonstrate the exact of glutamine's effect on cancer metabolism. Our results set the stage for the development of glutaminolysis inhibitors based therapeutics for reprogramming of cancer metabolism. We believe that development of our oncosecretomics based metabolic strategy provides an unprecedented opportunity for the development of nutritional supplementation that can deregulate the adaptations and alterations induced by various nutrients in cancer metabolism. 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 5161. doi:1538-7445.AM2012-5161
Abstract 3297: CD90/Thy-1-positive cells in the peripheral blood of tumor patients co-express CD44
Authors: Kathleen Wagner, Alexander Berndt, Andreas Hochhaus, Joachim H. Clement
Journal: Cancer Research (2010)

Abstract Aims: Interactions between epithelial tumor cells and the surrounding milieu are an essential regulatory component of tumor development. Especially the contribution of the crosstalk between epithelial tumor cells and tumor-associated fibroblasts (TAFs) on tumor progression and metastasis formation is of emerging interest. Therefore, we ask whether circulating TAFs could be detected in the peripheral blood of tumor patients and how they could be further characterized. Methods: CD90/Thy-1 is a putative marker of TAFs. A fluorescence-scanning-cytometer (scanR) was used to detect and quantify vital CD90-positive cells in blood samples from individual tumor patients (e.g. breast, bladder, kidney). For further analysis CD90-positive cells were separated from leukocyte fractions pooled from different tumor patients using an immunomagnetic cell separation technology (ROBOSEP®). The CD90-positive fraction was subsequently analyzed by immunofluorescence and immunohistochemistry. We focused on the expression of other stroma markers like FAP-alpha and cell surface proteins like CD44 which are involved in metastasis formation. Results: In cell culture experiments we established CD90 as a highly specific marker for fibroblasts. The amount of CD90 positive cells in whole blood samples varied from 0 up to 54,000 cells/ml and changed over time. The CD90-positive cells were enriched immunomagnetically from the leukocyte fraction pooled from tumor patients. By immunofluorescence we approved the cell vitality and verified that the separated cells do not belong to the sub-population of CD34-positive blood stem cells. Blood samples from more than 300 patients with solid tumors were tested for the presence of CD90-positive cells. Immunofluorescence double staining of the separated cells showed the co-expression of CD90 and CD44, which participates in a wide variety of cellular functions like hematopoiesis and tumor metastasis formation. Further immunohistochemical analysis demonstrated the expression of CD29 which is involved in metastasis formation and CD105 a marker for activated fibroblasts in a subset of the CD90-positive cell fraction. Conclusions: We could show that CD90-positive cells circulate in the peripheral blood of tumor patients. The additional expression of other stroma and tumor associated proteins on the cells could argue for their involvement in aspects of tumor progression. Ongoing studies should evaluate their suitability as prognostic factor. 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 3297.
CT, MR Imaging, and Radionuclide Imaging in a Patient With Hepatic Involvement in Primary Amyloidosis
Authors: HITOYA OHTA, HIROYUKI KOKURYU, TAKAYO OTA, NAOMI TOMONO, TATSUO SHIMIZU, MASAYUKI SHINTAKU, TOMOO KOMIBUCHI
Journal: Clinical Nuclear Medicine (1997)

The authors present CT, MR, and radionuclide images of a patient with hepatic involvement of primary amyloidosis. Hepatomegaly with heterogeneous tracer distribution was seen on Tc-99m phytate and Tc-99m GSA scintigraphy. Abnormal tracer accumulation in the liver was recognized on Tc-99m PYP and Tc-99m (V) DMSA scintigraphy. Scintigraphy seemed to be more useful than CT or MR in the evaluation of hepatic involvement of primary amyloidosis.
Pure transgastric NOTES in an adnexal procedure: the first human case report
Authors: B.-R. Liu, X.-C. Kong, G.-X. Cui, X.-Y. Zhang, J.-T. Song, Y. Kuang, L.-J. Kong, Y. Si
Journal: Endoscopy (2013)

Natural orifice transluminal endoscopic surgery (NOTES) is an innovative procedure that represents a further evolution of minimally invasive surgery. To date, there are few cases reported in the literature that have been performed using pure NOTES [1] [2] [3]. Recently, Lee et al. [4] described pure transvaginal NOTES in adnexal procedures using modern laparoscopic rigid instruments. To the best of our knowledge, however, transgastric NOTES for adnexal disease has not previously been reported in humans. Herein, we report on a pure transgastric NOTES procedure performed for adnexal disease in a young woman.
A6.18 Novel compound cytokine release inhibitory drug 3 (CRID3) inhibits the NLRP3 inflammasome in rheumatoid arthritis
Authors: T McGarry, RC Coll, AAB Robertson, MA Cooper, LA O’Neill, DJ Veale, U Fearon
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background/Objectives</h3> The NLRP3 inflammasome is a multi-protein complex activated in response to environmental pathogens. These pathogens activate toll-like receptors, initiating a cascade leading to the activation of this inflammasome which results in caspase-1-dependant cleavage of pro-IL-1β and IL-18 to their active and mature form. Recent studies have implicated the NLRP3 inflamamsome is the pathogenesis of Rheumatoid Arthritis. This study demonstrates the effect of novel inhibitory compound CRID3 in the RA joint. <h3>Methods</h3> To assess if the NLRP3 inflammasome is active in RA, the expression of inflammasome components NLRP3, IL-1β, IL-18 and Caspase-1 were measured in Rheumatoid Arthritis (RA) and Osteoarthritis (OA) <i>ex vivo</i> synovial tissue biopsies by RT-PCR, ELISA and immunohistochemistry. RA synovial explant cultures <i>ex vivo</i> were cultured under basal conditions or in the presence of CRID3 (100 nM), a novel compound which is thought to act on or closely to NLRP3. Expression of NLRP3, IL-1β, IL-18 and Caspase-1 in synovial explant cultures were analysed by Taqman PCR, ELISA and Western blotting. Furthermore, the effect of CRID3 on spontaneous secretion of pro-inflammatory and pro-angiogenic mediators (IL-6, IL-8, TNFα, VEGF, Tie-2, bFGF, MMP-3, IL-10) from RA explants was determined by ELISA or MSD multiplex assay. <h3>Results</h3> Transcripts of inflammasome components pro-IL-1β, pro-IL-18 and NLRP3 were significantly higher in RA versus OA synovial biopsies (all p &lt; 0.05). In addition, Caspase-1 is highly expressed in RA synovial tissue compared to healthy control synovium, localised to the lining and sub-lining layers. Incubation of <i>ex vivo</i> RA synovial explants with CRID3 decreased NLRP3 transcripts, pro-IL1β and pro-IL-18, which was mirrored by a decrease in spontaneous secretion of active IL-1β and IL-18 (all p &lt; 0.05). CRID3 also inhibited Caspase-1 expression in RA explant cultures. Pro-inflammatory cytokines IL-6 and IL-8 were also significantly inhibited following incubation with CRID3 (p &lt; 0.05). In contrast, CRID3 had no effect on other pro-inflammatory/angiogenic mediators – TNFα, MMP-3, VEGF, Tie-2, bFGF and IL-10. <h3>Conclusion</h3> CRID3, thought to interact with the NLRP3 inflammasome, inhibits NLRP3 inflammasome components IL-1β, IL-18 and Caspase-1, in addition to other pro-inflammatory cytokines in the joint, but is independent of TNFα. This is the first study to demonstrate the effects of CRID3 in RA patient tissue and may represent a novel therapeutic strategy.