tbuckley/cabot-search huggingface dataset:
All-oral combination of oral vinorelbine (NVBo) and capecitabine (X) in HER2-negative metastatic breast cancer (MBC): latest results of a multicenter, international phase II trial with a median follow-up of 37.7 months.
Authors: N Tubiana-Mathieu, P Bougnoux, D Becquart, A Chan, F Majois, M Espie, M Morand, N Vaissiere, G Villanova, P Conte
Journal: Cancer Research (2009)

Abstract Abstract #6125 Background: Combination chemotherapy regimens are widely considered among the standards in the management of MBC. Oral therapy is an attractive option for many patients. The all-oral regimen of NVBo and X is active with good tolerability in MBC. We report an updated analysis of efficacy and safety from an international phase II study of NVBo plus X.&amp;#x2028; Methods: Main eligibility criteria included: measurable HER2-negative, CT-naive MBC, relapse ≥ 6 months after completing (neo)adjuvant CT, Karnofsky PS ≥ 70%, age ≥ 18 years. Study treatment: 3-weekly cycles of NVBo 80 mg/m2 (after a first cycle at 60) d1 and d8, plus X 1000 (750 if ≥ 65 years) mg/m2 twice-daily d1-14. Treatment was continued until progression or unacceptable toxicity.&amp;#x2028; Results: 55 pts were enrolled and 54 were treated: median age: 58.5 years (41% ≥ 65); prior (neo)adjuvant CT in 63%; type of CT: anthracycline 67%, anthracycline + taxane 18%, CMF 15%; visceral involvement in 78%; &amp;gt; 2 metastatic sites in 46%. Median 7 cycles (range 1-58); median relative dose intensity: NVBo 87%, X 87%; NVBo escalated to the recommended dose of 80 mg/m2 in 91% of pts. G3/4 NCI CTC v2 adverse events: (n=53) neutropenia 49% of pts, (n=54) vomiting 9%, stomatitis 7%, asthenia 7%, febrile neutropenia 6%, infection with G3/4 neutropenia 6%, nausea 4%, diarrhoea 4%, hand-foot syndrome 4%, thrombosis/embolism 4%. Efficacy (n=46 evaluable pts): objective response rate (RECIST) 52% (95% CI [37-67]), CR 2%, PR 50%, SD 28%, PD 20%, disease control (CR+PR+ SD ≥ 6 months) 63% (95% CI [48-77]). Median duration of response was 7.2 months (95% CI [6.0-11.7]). With a median follow-up of 37.7 months, median progression-free survival was 8.4 months (95% CI [5.8-9.7]) and median overall survival was 30.1 months (95% CI [18.2- 40.1]). 21 of the 54 pts treated in the study are still alive.&amp;#x2028; Conclusion: These results show that the all-oral combination of NVBo and X is an effective and well-tolerated first-line poly-chemotherapy regimen for MBC. A retrospective analysis has been made between pts with &amp;lt; or ≥ 65 years (efficacy and safety) and results will be presented during the meeting. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6125.
Abstract 3425: Interleukin-27 inhibits epithelial mesenchymal transition in lung carcinogenesis
Authors: Jay M. Lee, Ling Zhang, Puja Kachroo, Xiaoyan Cui, Saswati Hazra, Tonya C. Walser, John D. Minna, Sherven Sharma, Steven M. Dubinett
Journal: Cancer Research (2011)

Abstract Interleukin-27 (IL-27), the newest member of the IL-6/IL-12 family, is secreted by antigen presenting cells and has anti-tumor activity through its activation of the JAK-STAT pathway. Transcriptional factors STAT1 and STAT3 have been implicated in the balance of tumor suppressor and oncogenic functions. Epithelial mesenchymal transition (EMT) is a process whereby cells undergo changes from a highly polarized epithelial phenotype to a mesenchymal, migratory phenotype, which plays an important role in tumor metastasis. The role of IL-27 in EMT was evaluated in lung carcinogenesis. Human bronchial epithelial cells (HBECs), genetically modified HBEC to over-express Snail and K-ras (HBEC-Snail, HBEC-K-ras), and non-small cell lung cancer (NSCLC) lines (A549, H2122) were treated with IL-27 at multiple time points. Phosphorylation of STAT1 and STAT3 measured by Western Blot demonstrated activation of both pathways in these cell lines treated with IL-27. However, the STAT1 pathway was attenuated in HBEC-K-ras cells exposed to IL-27. Western analysis of markers for epithelial to mesenchymal transition (EMT) (E-cadherin, γ-catenin, N-cadherin, Vimentin, and Snail) showed up-regulation of E-cadherin and γ-catenin, important for the epithelial phenotype, which peaked 8 hours after IL-27 exposure, while markers important for the mesenchymal phenotype (N-cadherin, Vimentin, and Snail) were all down-regulated at similar time points. The addition of a STAT3 inhibitor to IL-27 treatment led to continued down-regulation of Vimentin beyond 8 hours. A wound healing functional assay to study cell migration after IL-27 treatment of cancer cell lines for up to 48 hours, demonstrated overall decrease in cell migration. In summary, IL-27 inhibits epithelial mesenchymal transition in NSCLCs and oncogenically manipulated HBECs through the regulation of STAT1 and STAT3 pathways. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3425. doi:10.1158/1538-7445.AM2011-3425
PWE-192 Efficacy and safety of extensive endomucosal resection for complete Barrett's eradication in early Barrett's neoplasia: a meta-analysis
Authors: R Krishnamoorthy, K R Abrams, K Ragunath, T Thomas
Journal: Gut (2012)

<h3>Introduction</h3> The efficacy of complete Barrett9s eradication by extensive endomucosal resection (E-EMR) of Barrett9s oesophagus with early cancer ranges from 60% to 100% with a post-resection stricture rate of up to 88% in a recent RCT.<sup>1</sup> The primary aim of this meta-analysis was to determine the long-term efficacy and safety of E-EMR for complete Barrett9s eradication in patients with early Barrett9s cancer. <h3>Methods</h3> MEDLINE, EMBASE and PubMed databases were searched using keywords, “Barrett9s oesophagus,” “oesophageal cancer,” “endomucosal resection,” “circumferential endomucosal resection,” Barrett9s high-grade dysplasia and Barrett9s intra-mucosal carcinoma from January 1965 to December 2011. Articles were selected/reviewed and data collected based on pre-defined inclusion criteria, independently by two authors (RK and TT). Meta-analysis using random effects model was done. <h3>Results</h3> Thirteen studies (N=691) were included in the final analysis. (586 males, average age, 65.9 range 65–67). 116 patients in six studies had long-segment Barrett9s. The average Barrett9s length was 3.78 cm (range 2–4.9 cm). Visible lesions were seen in 371/586 (63.3%) patients. At an average of 2 (range 1.5–2.5) EMR sessions, four resections (range 3–8) were done per session Complete Barrett9s eradication was achieved in 71.9% (95% CI 68.1% to 75.4%) and eradication of early Barrett9s cancer in 96% (95% CI 91% to 99%) of patients. At an average follow-up of 20.5 months (range 9–31.6) Barrett9s/dysplasia recurrence was seen in 13% (95% CI 10.7%&gt;15.9%). Total number of resections (p=0.026) and age (p=0.037) were significant confounders for complete Barrett9s eradication. The overall stricture rate was 39% (95% CI 35%&gt;43%). Procedure related perforations occurred in 12/691 (1.3%) and bleeding in 9.9% (95% CI 5.1%&gt;13.5%) of patients. On meta-regression analysis there were no significant confounders for stricture formation. <h3>Conclusion</h3> Complete long-term complete Barrett9s eradication in patients harbouring early cancer is effective in only 71.9% of patients with age and total endoscopic resections being significant confounders. The procedure appears safe but has a stricture rate of 39%. <h3>Competing interests</h3> R Krishnamoorthy: None declared, K Abrams: None declared, K Ragunath Conflict with: Member of the shortlisting panel for the Endoscopy section of the BSG., T Thomas: None declared. <h3>Reference</h3> 1. <b>van Vilsteren FG</b>, Pouw, ER, Seewald S, <i>et al.</i> Stepwise radical endoscopic rsection versus radiofrequency ablation for Barrett9s oesophagus with high-grade dysplasia or early cancer: a multicentre randomised trial. <i>Gut</i> 2011;<b>60</b>:765–73.
Assessment of Radiofrequency Ablation of Lung Metastasis From Colorectal Cancer Using Dual Time-Point PET/CT
Authors: Sergio Lafuente, Pedro Arguis, David Fuster, Ramon Vilana, Francisco Lomeña, Francesca Pons
Journal: Clinical Nuclear Medicine (2011)

A 70-year-old man with operated colorectal cancer relapsed with a solitary lung metastasis. Dual time-point PET/CT performed at 60' (standard images) and after 2 hours (delayed images) showed focal uptake in the lung nodule. A second uptake in the liver dome was also visualized only in the delayed images. Radiofrequency of the lung metastasis was performed by CT-fluoroscopy guide. A PET/CT 1 month after radiofrequency showed significant reduction of activity in the delayed images, and the uptake at 3 months was virtually normal. A fine-needle biopsy of the liver lesion confirmed the final diagnosis of metastasis from adenocarcinoma.
Short Anabolic Peptides for Bone Growth
Authors: Zaid Amso, Jillian Cornish, Margaret A. Brimble
Journal: Medicinal Research Reviews (2016)

Abstract Loss of bone occurs in the age‐related skeletal disorder, osteoporosis, leading to bone fragility and increased incidence of fractures, which are associated with enormous costs and substantial morbidity and mortality. Recent data indicate that osteoporotic fractures are more common than other diseases, which usually attract public attention (e.g., heart attack and breast cancer). The prevention and treatment of this skeletal disorder are therefore of paramount importance. Majority of osteoporosis medications restore skeletal balance by reducing osteoclastic activity, thereby reducing bone resorption. These agents, however, do not regenerate damaged bone tissue, leaving limited options for patients once bone loss has occurred. Recently, attention has turned to bone‐anabolic agents. Such agents have the ability to increase bone mass and strength, potentially reversing structural damage. To date, only one bone‐anabolic drug is available in the market. The discovery of more novel, cost‐effective bone anabolic agents is therefore a priority to treat those suffering from this disabling condition. Short peptides offer an important alternative for the development of novel bone‐anabolic agents given their high target binding specificity, which translates into potent activity with limited side effects. This review summarizes attempts in the identification of bone‐anabolic peptides, and their development for promoting bone growth.
The Relationship between Sales Data for Asthmatic Drugs and Asthma Events
Authors: A. Tanaka, K. Sugiyama, H. Hirata, T. Kakuta, M. Watanabe, M. Tatewaki, A. Takeda, M. Arima, Y. Fukushima, T. Fukuda
Journal: Journal of Allergy and Clinical Immunology (2012)
S136 Mtor Signalling Is An Essential Pathway For Tgf- 1 Induced sma And Collagen Gene Expression
Authors: H. Woodcock, S. Peace, C. Nanthakumar, T. Maher, P. Mercer, R. Chambers
Journal: Thorax (2014)

<h3></h3> Emerging evidence suggests a role for PI3K/mTOR signalling in the pathology of organ fibrosis. The aim of this study was to delineate PI3K/mTOR signalling in response to TGF-β<sub>1 </sub>stimulation of primary human lung fibroblasts (HLFs), and to investigate the role of this pathway in TGF-β<sub>1</sub> mediated myofibroblast differentiation and collagen synthesis. A time-course of SMAD 2/3 and Akt (Ser473) phosphorylation, the major downstream effector of the PI3K/mTOR pathway, was constructed to assess TGF-β<sub>1</sub> induced signalling kinetics in HLFs. TGF-β<sub>1 </sub>(1 ng/ml) induced rapid phosphorylation of SMAD2/3, peaking at 1 h, followed by Akt phosphorylation which peaked 12 h after initial stimulation. Maximal expression of <i>ACTA2</i> and <i>COL1A1</i> was observed 36 h after TGF-β<sub>1</sub> stimulation, correlating with the delayed time-course of Akt phosphorylation. To investigate the role of the PI3K/mTOR pathway in TGF-β<sub>1</sub> induced myofibroblast differentiation and collagen gene expression, HLFs were treated with pharmacological titrations of potent pathway inhibitors. Maximal Akt signalling and expression of <i>ACTA2 </i>and <i>COL1A1</i> were significantly inhibited by a dual PI3K/mTOR inhibitor, while SMAD phosphorylation was unaffected. Treatment with an ATP competitive mTOR inhibitor also resulted in significantly reduced Akt phosphorylation and expression of <i>ACTA2</i> and <i>COL1A1</i>, in response to TGF-β<sub>1</sub>. In contrast, treatment of HLFs with either an allosteric or ATP competitive Akt inhibitor showed no inhibitory effect on TGF-β<sub>1 </sub>induced gene expression. These data suggest PI3 kinase/mTOR signalling is an important component in TGF-β<sub>1</sub> induced αSMA and collagen gene expression and that an mTOR dependent, Akt independent pathway mediates this functional response in primary HLFs.
Abstract 912: Soy isoflavone intake, <i>MDM2</i> gene polymorphism and breast cancer risk among Chinese women in Singapore
Authors: Woon-Puay Koh, Renwei Wang, David Van Den Berg, Jian-Min Yuan, Mimi C. Yu
Journal: Cancer Research (2010)

Abstract Epidemiologic studies among populations that consume moderate to high amount of soy have shown that soy isoflavones may reduce breast cancer risk, and the chemopreventive effects are postulated to be related to the anti-estrogenic properties of soy isoflavones. Recently, experimental studies have revealed that dietary isoflavones may also down-regulate the expression of the MDM2 oncogene, and the inhibition of the expression of the MDM2 oncoprotein has in turn been associated with antitumor activities in breast cancer models. Furthermore, a polymorphism in the promoter region of MDM2 SNP309 (T&amp;gt;G change at nucleotide 309 in the first intron; rs2279744) leads to increased expression of the oncogene and has been associated with earlier onset of breast cancer. We have previously shown that postmenopausal women with a higher than median intake of soy have a reduced risk of breast cancer compared with those with a lower intake. If down-regulation of the MDM2 oncogene is one of the mechanistic pathways for the chemopreventive effects of soy isoflavones in breast cancer, we postulate that the protective effect of soy isoflavones on breast cancer will be stronger in those possessing the high-activity MDM2 genotype. To confirm this hypothesis, we conducted a nested case-control study among 281 incident, postmenopausal breast cancer cases and 462 postmenopausal control subjects within the Singapore Chinese Health Study Cohort. Overall, there was no significant association between MDM2 gene polymorphism and breast cancer risk. Postmenopausal women who had a higher than median intake of soy had a reduced risk of breast cancer [odds ratio (OR), 0.76; 95% confidence interval (CI), 0.56-1.03]. This inverse association was principally noted among women homozygous for the high activity MDM2 allele (GG genotype). There was a statistically significant, roughly 50% reduction in breast cancer risk between above versus below median level of soy consumption in this subgroup of women (OR, 0.52; 95% confidence interval, 0.28-0.98). On the other hand, a much weaker, and statistically nonsignificant association was noted among women possessing the lower-activity MDM2 genotypes (OR, 0.86, 95% CI, 0.59-1.24). Our findings suggest that the ability of soy isoflavones to down-regulate the MDM2 oncoprotein may be one etiologic mechanism through which the intake of soy is associated with breast cancer protection. 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 912.
PWE-056 Cancer is the Leading Cause of Hospital Death in 30 Day Mortality Audit following Endoscopy
Authors: M Kasi, S P Dunlop
Journal: Gut (2013)

<h3>Introduction</h3> Mortality post endoscopy is a quality standard for all endoscopy units. Many of the published 30 day mortality studies relate specifically to those presenting with gastro-intestinal bleeding or following a therapeutic procedure, rather than for any indication or after any endoscopic procedure. <h3>Methods</h3> We reviewed all hospital deaths occurring within 30 days following any endoscopic procedure in 12 months from 1 January 2011 to 31 December 2011, at Derriford Hospital. Data was available from Clinical coding by linking the endoscopy database with the death registry. All patients’ case notes were analysed and data collected including patient demographics, indications for the procedure, type of procedure, immediate post procedure complications and cause of death. <h3>Results</h3> There were 13310 procedures performed (gastroscopy 6224; colonoscopy 4660; flexible sigmoidoscopy 1920; ERCP 348; other procedure 158). 146 patients died within 30 days of their endoscopy (all cause mortality 1.0%). Of these, 118 patients died in hospital (81%) and 28 patients died within the community (19%). 35/118 (30%) of hospital patients died within 7 days of the procedure. Cancer was the leading cause of hospital death, accounting for 35/118 (30%); GI Cancer accounted for 24/35 (69%) and Non GI Cancer 11/35 (31%). Other causes were pneumonia 22/118 (19%); upper GI bleeding 8/118 (7%); vascular complications 16/118 (14%). All deaths from upper GI bleeding occurred within 7 days and 12/16 (75%) deaths from vascular complications occurred after 7 days. 30 day all cause mortality rates for each procedure were: colonoscopy 0.7%; ERCP 2.2%; flexible sigmoidoscopy 0.9%; upper GI endoscopy 2%; others 1.6%. Two patients had perforated distal bowel after having had flexible sigmoidoscopy (procedure related death, 2/13,283; 0.015% or 1.5 in 10,000). There were no other procedure related deaths. Eight patients died on the same day of their procedure due to uncontrolled bleeding (n = 3), acute kidney injury (n = 1), multi-organ failure following ERCP for cholangitis (n = 1), respiratory failure (n = 2) and acute ischaemia of stomach (n = 1). There were no sedation related complications nor use of reversal agents. <h3>Conclusion</h3> Deaths within 30 days following an endoscopic procedure are most likely associated with cancer or pneumonia with procedure related or associated deaths being rare. GI cancers are twice as likely to be associated than non-GI cancers. <h3>Disclosure of Interest</h3> None Declared.
Endoscopic ultrasound-guided gastroenterostomy for palliative drainage of an obstructed hepaticojejunostomy loop
Authors: S. Chatterjee, B. Ibrahim, R. Charnley, J. Scott, M. Nayar
Journal: Endoscopy (2011)

A 63-year-old man was admitted with obstructive jaundice. Computed tomography (CT) scan showed a mass in the head of the pancreas. Endoscopic retrograde cholangiopancreatography (ERCP) revealed a common bile duct stricture, which was stented, and biliary brushings confirmed primary pancreatic adenocarcinoma. As the tumor was unresectable, he underwent a double bypass operation (i. e. hepaticojejunostomy and gastrojejunostomy). The patient presented 2 months later with jaundice (bilirubin 300 mg/dL). CT scan confirmed obstruction and dilatation of the hepaticojejunostomy loop due to tumor invasion ([Fig. 1]).
Abstract B74: A microRNA expression signature of response to EGFR inhibition targets EMT in both lung and pancreatic cell lines
Authors: Justin M. Balko, Virginia L. Coakley, Joel S. Britson, Michael C. Willian, Andrey Frolov, Esther P. Black
Journal: Cancer Research (2009)

Abstract Purpose: The intent of the study described herein is to develop and characterize a microRNA gene expression signature of response to EGFR inhibition portable to solid tumors for which treatment with an EGFR inhibitor is indicated. Experimental Design: Treatment with inhibitors of the epidermal growth factor receptor (EGFR) can result in clinical response in both non-small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC), but only in a minority of unselected patients. Identification of biomarkers that can direct treatment to the responsive population is essential and here we describe generation of a microRNA gene signature of response to EGFR inhibition. Using a Taqman MicroRNA Array of 381 probes, we demonstrate that a 20-gene microRNA signature derived from NSCLC cell lines can predict sensitivity of both lung and pancreatic cancer cell lines to erlotinib, a small molecule inhibitor of EGFR. Overlap of independently generated microRNA expression signatures of NSCLC and pancreatic cell lines produces a fourgene signature. We characterize a target of the reduced signature, ZEB1, in NSCLC and pancreatic cancer cell lines by evaluation of mRNA and protein expression. We evaluated ZEB1 protein and the ZEB1 target, E-cadherin, after transfection of mir-200c into inhibitor-resistant NSCLC cell line, A549. Results: We have identified a 20-gene microRNA signature of response to EGFR inhibition that predicts both inhibitor-sensitive NSCLC and pancreatic cell lines. By overlapping independent signatures of response in NSCLC and pancreatic cancer cell lines, a four gene microRNA signature is identified that targets proteins responsible for epithelial to mesenchymal transition (EMT). Of those proteins, ZEB1 is a transcription factor responsible for repression of E-cadherin expression. Both ZEB1 mRNA and protein expression are down-regulated in erlotinib-sensitive NSCLC in which the microRNA genes 200b, 200c, and 141 are up-regulated. Ectopic expression of mir-200c in inhibitor-resistant lines induces cell death, suggesting that down-regulation of this microRNA is essential for viability in these NSCLC lines. Conclusions: The 20-gene miRNA signature of sensitivity provides a means for defining response that can be generated from FFPE samples of tumor rather than fresh tumor samples. Whereas mRNA is difficult to isolate from FFPE samples due to degradation, microRNA may survive the fixation process. Thus, response to EGFR inhibition in the second- or third-line can be predicted from fixed tumor samples collected early in the treatment of an individual patient, eliminating the need for acquisition of fresh tumor. Further, the microRNA signature identifies the well-studied EMT pathway indicative of EGFR-inhibitor sensitivity and provides biological significance for the members of the signature. Citation Information: Cancer Res 2009;69(23 Suppl):B74.