tbuckley/cabot-search huggingface dataset:
P237 Lung function decline is associated with serum periostin level but not fractional exhaled nitric oxide or blood eosinophils in severe asthma
Authors: AH Mansur, V Mitchell, J Sullivan, K O’Shea, L White
Journal: Thorax (2016)

<h3>Background</h3> In the airways, periostin encoded by the POSTN gene is up-regulated by IL13-IL4-TGF-β axis. It is produced by structural cells such as epithelial cells and fibroblasts and inflammatory cells such as eosinophils and macrophages. Consequently it has been linked to airways remodelling, mucus production and subepithelial fibrosis. However, an association between periostin and lung function impairment in severe asthma has not been confirmed. <h3>Methods</h3> Unselected patients attending severe asthma centre were clinically characterised using systematic protocol and undergone lung functions, serum periostin, fraction exhaled nitric oxide (FeNO) and peripheral blood eosinophils (PBE) measurement. Correlation analysis and one way analysis of variance were undertaken to explore the relationships. <h3>Results</h3> 127 patients consented to the study (mean age 45.5 yrs [range 17–70], 88 [69%] females), 72/103 (69%) were atopic. The mean FEV1 was 2 L, mean%predicted FEV1 68.1, and mean FEV1/FVC ratio was 71.3. The mean inhaled daily corticosteroids dose was 1.65mg/day and 56.3% were on maintenance oral corticosteroids. Periostin measurement was available in 78 patients who had a mean level of 49.5 ng/L (SD ± 18.1). Using 50 ng/L as a cut-off point, 30/78 (36%) patients had high periostin and 48/78 (62%) had low periostin. The mean FEV1 in the periostin high group was 1.69 L Compared to 2.15 L in the low group (p = 0.018) (see Figure). We also observed significant correlation between serum periostin and% predicted FEV1 (r = 0.36, p = 0.0017). In contrast the association analysis between FeNO and PBE with FEV1 were both non-significant (p = 0.8 and p = 0.35 respectively). <h3>Conclusion</h3> Raised serum periostin is associated with low lung function in this cohort of severe asthma but not FeNO or BPE. Further research is required to confirm this relation and explore the role of periostin as predictor of decline in lung function and airway remodelling.
APP Gene Involves in the Regulation of Cell Apoptosis in AML1-ETO-Positive Leukemia Via SCF/c-Kit Signaling Pathway
Authors: Guopan Yu, Ling Jiang, Changxin Yin, Zhixiang Wang, Hongsheng Zhou, Xuejie Jiang, Qifa Liu, Fanyi Meng
Journal: Blood (2015)
MA07.03 Alectinib (ALC) versus Crizotinib (CRZ) in ALK-Positive Non-Small Cell Lung Cancer (ALK+ NSCLC): Primary Results from Phase III Study (J-ALEX)
Authors: Young Kim, Toyoaki Hida, Hiroshi Nokihara, Masashi Kondo, Koichi Azuma, Takashi Seto, Yuichi Takiguchi, Makoto Nishio, Hiroshige Yoshioka, Fumio Imamura, Katsuyuki Hotta, Satoshi Watanabe, Koichi Goto, Kazuhiko Nakagawa, Tetsuya Mitsudomi, Nobuyuki Yamamoto, Hiroshi Kuriki, Ryoichi Asabe, Tomohiro Tanaka, Tomohide Tamura
Journal: Journal of Thoracic Oncology (2017)
P2.03b-022 Outcome in Molecularly Defined NSCLC within the NOWEL Network: The Influence of Sequential 2nd and 3rd Generation TKI in EGFR mt+ and ALK+ pts
Authors: Julia Roeper, Maria Netchaeva, Anne Lueers, Ursula Stropiep, Cora Hallas, Markus Tiemann, Nicole Neemann, Lukas Heukamp, Markus Falk, Gunther Wiest, Claas Wesseler, Dieter Ukena, Sandra Sackmann, Frank Griesinger
Journal: Journal of Thoracic Oncology (2017)
MA07.07 Ceritinib in ROS1-Rearranged Non-Small-Cell Lung Cancer: An Update of Korean Nationwide Phase II Study
Authors: Byoung Chul Cho, Sun Min Lim, Hye Ryun Kim, Jong-Seok Lee, Ki-Hyeong Lee, Yun-Gyoo Lee, Young Joo Min, Eun Kyung Cho, Seung-Sook Lee, Hyo Sup Shim, Jin-Haeng Chung, Yoon-La Choi, Myung-Ju Ahn
Journal: Journal of Thoracic Oncology (2017)
Homeostatic Reconstitution of CD4+ Regulatory and Conventional T Cell Subsets in Adult Patients after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Authors: Ana Cristina Alho, Kim T Haesook, Carol G Reynolds, Marie J Chammas, Sean McDonough, Suzan Lazo-Kallanian, John Daley, Sarah Nikiforow, Corey S Cutler, John Koreth, Vincent T Ho, Philippe Armand, Robert J. Soiffer, Joseph H Antin, Jerome Ritz
Journal: Blood (2014)
Correlates of contralateral prophylactic mastectomy in a population-based sample.
Authors: S. T. Hawley, R. Jagsi, M. Morrow, S. J. Katz
Journal: Journal of Clinical Oncology (2011)

6010 Background: Little is known about correlates of contralateral prophylactic mastectomy (CPM) in diverse, population-based samples of breast cancer patients. Methods: We surveyed 2,245 women newly diagnosed with breast cancer and reported to the Detroit and Los Angeles SEER registries from 6/05-2/07 and merged these data to SEER. Patients were surveyed again approximately 4 years after diagnosis (expected n=1520). We report on a preliminary sample of 707 patients. The primary outcome was choice of surgery for curative intent: CPM vs. unilateral mastectomy (UM) or BCS. Independent variables were having a 1st degree family history of breast cancer, receipt of genetic testing, worry about recurrence, and clinical factors (age and tumor stage). Multinomial logistic regression was used to evaluate factors associated with CPM vs. BCS and UM. Results: 61 patients (8.8%) had CPM, 34.8% UM and 56.4% BCS. Of the 707 respondents, 27% had a 1st degree family history of breast cancer, 18% had a genetic test (10% of which were positive), and 78% reported being very worried about recurrence when making their treatment decision. Of those who had CPM, most did not have a family history (53%) or a genetic test (90%). Having a 1st degree family history and receipt of genetic testing were significantly associated with choice of CPM vs. either BCS or UM. Worry about recurrence was also associated with choice of CPM over other surgical options. These factors were not associated with choice of UM vs. BCS (Table). Conclusions: Most women who had CPM did so in the absence of factors known to increase contralateral cancer risk. This finding suggests that some women may be getting CPM with low net clinical benefit. Further investigation is needed to determine whether patients who choose CPM in the absence of substantial clinical benefit are well informed of their actual risk of a new primary cancer. ORs and 95% CIs CPM vs. BCS CPM vs. UM UM vs. BCS 1st-degree family history 2.14 (1.14-4.06) 2.61 (1.33-5.09) 0.82 (0.55-1.23) Genetic test receipt 6.18 (3.02-12.67) 6.95 (3.24-14.92) 0.88 (0.54-1.47) Worry about recurrence 3.40 (1.26-9.16) 2.97 (1.07-8.19) 1.14 (0.76-1.73) Controlled for age and stage.
p38MAPK Inhibitor LSN2322600 Modulates the Bone Marrow Microenvironment and Inhibits Osteoclastogenesis in Multiple Myeloma.
Authors: Kenji Ishitsuka, Teru Hideshima, Paola Neri, Sonia Vallet, Norihiko Shiraishi, Noopur Raje, Zhenxin Shen, Tanyel Kiziltepe, Enrique M. Ocio, Klaus Podar, Dharminder Chauhan, Nikhil Munshi, Robert M. Campbell, Alfonso De Dios, Chuan Shih, James J. Starling, Kazuo Tamura, Kenneth C. Anderson
Journal: Blood (2006)
P2.03a-011 Population Pharmacokinetic/Pharmacodynamic Monitoring of Pemetrexed to Predict Survival in Patients with Advanced NSCLC
Authors: Sabine Visser, Stijn Koolen, Marcel Stoop, Theo Luider, Ron Mathijssen, Bruno Stricker, Joachim Aerts
Journal: Journal of Thoracic Oncology (2017)
P3.03-019 Molecular Characterization of Malignant Pleural Mesothelioma (MPM) by next Generation Sequencing
Authors: Susana Cedres, Am Martinez De Castro, Nuria Pardo, Alejandro Navarro, Alex Martinez, Fabiola Amair, Fabricio Racca, Eulalia Scheenaard, Sergi Recasens, Iris De La Fuente, Andrea Retter, Marta Vilaro, Ana Vivancos, Enriqueta Felip
Journal: Journal of Thoracic Oncology (2017)
M16 Construct validity of the needs assessment tool progressive diseases for interstitial lung disease (NAT: PD-ILD) patients
Authors: C Reigada, C Fairhurst, J Yorke, J Ross, J Boland, S Hart, D Currow, G Grande, S Bajwah, A Wells, U Macleod, M Bland, M Johnson
Journal: Thorax (2016)

<h3>Background</h3> People with ILD, currently have less access to SPC and there is no validated needs assessment tool (NAT). We adapted the NAT:PD-cancer for use in ILD and conducted psychometric testing. <h3>Aim</h3> To test the construct validity of NAT:PD-ILD. <h3>Methods</h3> ILD clinicians in four hospitals were trained to use the NAT:PD-ILD. After a consultation, the clinician completed the NAT:PD-ILD, patients completed the St. George’s Respiratory Questionnaire (SGRQ-I) and carers completed the Carer Strain Index (CSI) and Carer Support Needs Assessment Tool (CSNAT). Kendall’s Tau-b correlation coefficient (and associated p-value) was calculated to determine the correlation between the NAT: PD-ILD items relating to patient wellbeing, and a total score for a subset of SGRQ-I questions identified <i>a priori</i> as measuring similar constructs. The prevalence and bias adjusted kappa (PABAK), Cohen’s kappa and percentage of agreement were used to assess whether responses were similar between the NAT: PD-ILD items relating to the ability and wellbeing of the carer and appropriate CSI and CSNAT items which were considered to measure similar concerns/support needs. <h3>Results</h3> A total of 68 patients were recruited. The average age of participating patients was 66 years (range 34 to 87) and 62% were male. Forty-five (66%) patients had a carer of whom 27 completed the CSI (mean 4.4, SD 3.0, median 4, range 0–11) and 29 completed at least one item of the CSNAT. Items 2, 3, 5 and 6 of the NAT: PD-ILD statistically significantly positively correlated with their comparator SGRQ-I scores (ρ range 0.24 to 0.36, p &lt; 0.05). PABAK values comparing the NAT: PD-ILD items with appropriate CSI and CSNAT items show most items have PABAK positive values (range from 0.04 to 0.57, with a minimum of 52% agreement). However, NAT:PD-ILD items 11 and 13 have negative PABAK values (Inter-personal relationships and Grief topics – Psychosocial Dimension). <h3>Conclusion</h3> The NAT: PD-ILD has adequate construct validity for most domains. However, agreement is poor for physical symptoms and spiritual concerns. This may indicate that clinicians identify concerns with symptoms less well unless they are severe.
A liver‐specific long noncoding RNA with a role in cell viability is elevated in human nonalcoholic steatohepatitis
Authors: Biljana Atanasovska, Sander S. Rensen, Marijke R. van der Sijde, Glenn Marsman, Vinod Kumar, Iris Jonkers, Sebo Withoff, Ronit Shiri‐Sverdlov, Jan Willem M. Greve, Klaas Nico Faber, Han Moshage, Cisca Wijmenga, Bart van de Sluis, Marten H. Hofker, Jingyuan Fu
Journal: Hepatology (2017)

Hepatocyte apoptosis in nonalcoholic steatohepatitis (NASH) can lead to fibrosis and cirrhosis, which permanently damage the liver. Understanding the regulation of hepatocyte apoptosis is therefore important to identify therapeutic targets that may prevent the progression of NASH to fibrosis. Recently, increasing evidence has shown that long noncoding (lnc) RNAs are involved in various biological processes and that their dysregulation underlies a number of complex human diseases. By performing gene expression profiling of 4,383 lncRNAs in 82 liver samples from individuals with NASH (n = 48), simple steatosis but no NASH (n = 11), and healthy controls (n = 23), we discovered a liver-specific lncRNA (RP11-484N16.1) on chromosome 18 that showed significantly elevated expression in the liver tissue of NASH patients. This lncRNA, which we named lnc18q22.2 based on its chromosomal location, correlated with NASH grade (r = 0.51, P = 8.11 × 10-7 ), lobular inflammation (r = 0.49, P = 2.35 × 10-6 ), and nonalcoholic fatty liver disease activity score (r = 0.48, P = 4.69 × 10-6 ). The association of lnc18q22.2 to liver steatosis and steatohepatitis was replicated in 44 independent liver biopsies (r = 0.47, P = 0.0013). We provided a genetic structure of lnc18q22.2 showing an extended exon 2 in liver. Knockdown of lnc18q22.2 in four different hepatocyte cell lines resulted in severe phenotypes ranging from reduced cell growth to lethality. This observation was consistent with pathway analyses of genes coexpressed with lnc18q22.2 in human liver or affected by lnc18q22.2 knockdown.We identified an lncRNA that can play an important regulatory role in liver function and provide new insights into the regulation of hepatocyte viability in NASH. (Hepatology 2017;66:794-808).
Effect of Fish Oil Supplementation and Aspirin Use on Arteriovenous Fistula Failure in Patients Requiring Hemodialysis
Authors: Ashley B. Irish, Andrea K. Viecelli, Carmel M. Hawley, Lai-Seong Hooi, Elaine M. Pascoe, Peta-Anne Paul-Brent, Sunil V. Badve, Trevor A. Mori, Alan Cass, Peter G. Kerr, David Voss, Loke-Meng Ong, Kevan R. Polkinghorne
Journal: JAMA Internal Medicine (2017)

Vascular access dysfunction is a leading cause of morbidity and mortality in patients requiring hemodialysis. Arteriovenous fistulae are preferred over synthetic grafts and central venous catheters due to superior long-term outcomes and lower health care costs, but increasing their use is limited by early thrombosis and maturation failure. ω-3 Polyunsaturated fatty acids (fish oils) have pleiotropic effects on vascular biology and inflammation and aspirin impairs platelet aggregation, which may reduce access failure.To determine whether fish oil supplementation (primary objective) or aspirin use (secondary objective) is effective in reducing arteriovenous fistula failure.The Omega-3 Fatty Acids (Fish Oils) and Aspirin in Vascular Access Outcomes in Renal Disease (FAVOURED) study was a randomized, double-blind, controlled clinical trial that recruited participants with stage 4 or 5 chronic kidney disease from 2008 to 2014 at 35 dialysis centers in Australia, Malaysia, New Zealand, and the United Kingdom. Participants were observed for 12 months after arteriovenous fistula creation.Participants were randomly allocated to receive fish oil (4 g/d) or matching placebo. A subset (n = 406) was also randomized to receive aspirin (100 mg/d) or matching placebo. Treatment started 1 day prior to surgery and continued for 12 weeks.The primary outcome was fistula failure, a composite of fistula thrombosis and/or abandonment and/or cannulation failure, at 12 months. Secondary outcomes included the individual components of the primary outcome.Of 1415 eligible participants, 567 were randomized (359 [63%] male, 298 [53%] white, 264 [47%] with diabetes; mean [SD] age, 54.8 [14.3] y). The same proportion of fistula failures occurred in the fish oil and placebo arms (128 of 270 [47%] vs 125 of 266 [47%]; relative risk [RR] adjusted for aspirin use, 1.03; 95% CI, 0.86-1.23; P = .78). Fish oil did not reduce fistula thrombosis (60 [22%] vs 61 [23%]; RR, 0.98; 95% CI, 0.72-1.34; P = .90), abandonment (51 [19%] vs 58 [22%]; RR, 0.87; 95% CI, 0.62-1.22; P = .43), or cannulation failure (108 [40%] vs 104 [39%]; RR, 1.03; 95% CI, 0.83-1.26; P = .81). The risk of fistula failure was similar between the aspirin and placebo arms (87 of 194 [45%] vs 83 of 194 [43%]; RR, 1.05; 95% CI, 0.84-1.31; P = .68).Neither fish oil supplementation nor aspirin use reduced failure of new arteriovenous fistulae within 12 months of surgery.anzctr.org.au Identifier: CTRN12607000569404.
The Role of Bortezomib-Containing Regimens in Improving Response in Patients with Waldenstrom Macroglobulinemia
Authors: Ranjit Banwait, Edie Weller, Nitin Ropur, Claudia E. Paba-Prada, Lina Benajiba, Meghan Bagshaw, Steven P Treon, Irene M. Ghobrial
Journal: Blood (2011)
P1.06-027 Retrospective Study of Treatment for Postoperative Local Recurrence of Lung Cancer
Authors: Kenjiro Tsuruoka, Keiji Miyoshi, Ninso Matsunaga, Takahiko Nakamura, Shuhei Yoshida, Yousuke Tamura, Masafumi Imanishi, Soichiro Ikeda, Yasuhito Fujisaka, Isao Goto
Journal: Journal of Thoracic Oncology (2017)
S112 Long-term safety and efficacy of ivacaftor in paediatric patients aged 2–5 years with cystic fibrosis and a CFTR gating mutation
Authors: JC Davies, S Robertson, J Cooke, M Higgins, M Rosenfeld
Journal: Thorax (2016)

<h3>Background and objectives</h3> The 24-week open-label Phase 3 KIWI study demonstrated that the pharmacokinetics and safety of ivacaftor in patients aged 2–5 years with cystic fibrosis and a <i>CFTR</i> gating mutation are similar to those seen in older patients.¹ We report the final results from KLIMB, the long-term open-label extension of KIWI. <h3>Methods</h3> Patients who completed KIWI Part B enrolled in KLIMB and received ivacaftor for an additional 84 weeks. Patients aged 2–5 years received weight-based dosing (50 mg q12h for weight &lt; 14 kg; 75 mg q12 h for ≥14 kg); patients who turned 6 received 150 mg q12h. The primary endpoint was safety. Secondary endpoints included change from baseline (at the start of KIWI) in sweat chloride, weight, and body mass index (BMI). Exploratory endpoints included faecal elastase-1 (FE-1) and immunoreactive trypsinogen (IRT) levels. <h3>Results</h3> Of 34 patients in KIWI Part B, 33 enrolled in KLIMB (mean age at KLIMB baseline, 3.7 years). Five patients discontinued study drug (1 for elevated alanine transaminase/aspartate transaminase [ALT/AST] levels, 2 switched to commercial ivacaftor, 2 for noncompliance). The most common adverse event (AE) of any grade was cough (73%). Eleven patients had serious AEs; 2 were considered related to ivacaftor (elevated ALT/AST levels). Ten patients had elevated ALT/AST levels &gt; 3 × upper limit of normal (ULN). Of these, 4 had elevated ALT/AST levels &gt; 8 × ULN in KIWI; ivacaftor was maintained or resumed in all patients except 1 who discontinued. Significant improvements in sweat chloride, FE-1 and IRT levels, and BMI <i>z </i>scores were observed at week 84 (Table 1). <h3>Conclusion</h3> Ivacaftor demonstrated a stable safety profile during an extended 84-week follow-up period in patients with cystic fibrosis aged 2–5 years with a <i>CFTR</i> gating mutation. Reported AEs were consistent with the known safety profile; the incidence of elevated ALT/AST levels per 24-week period was consistent with that observed in KIWI. The improvements seen in KIWI in sweat chloride, BMI <i>z</i> score, and measures of pancreatic function were maintained at the end of KLIMB. Sponsored by Vertex Pharmaceuticals Incorporated Please refer to page A270 for declarations of interest in relation to abstract S112.
P1.06-006 Treatment beyond Progression in Patients with Advanced Squamous NSCLC Participating in the Expanded Access Programme (EAP)
Authors: Frederico Cappuzzo, Angelo Delmonte, Serena Capici, Lucio Crinò, Antonio Fabio Logroscino, Paolo Sandri, Lorenzo Livi, Fabiana Vitiello, Diego Signorelli, Luana Calabrò, Daniele Turci, Silvia Quadrini, Paola Antonelli, Sabrina Giusti, Francesco Di Costanzo, Francesca Rastelli, Paolo Marchetti, Giovanna Finocchiaro, Enrico Cortesi, Andrea Ardizzoni
Journal: Journal of Thoracic Oncology (2017)
Detection of LMO2 in Normal Human Tissues and Haematopoietic and Non-Haematopoietic Tumours by a Newly Developed Rabbit Monoclonal Antibody.
Authors: Claudio Agostinelli, Jennifer C Paterson, Rajeev Gupta, Simona Righi, Federica Sandri, Pier Paolo Piccaluga, Francesco Bacci, Elena Sabattini, Stefano A. Pileri, Teresa Marafioti
Journal: Blood (2009)
SOCS3 Promoter Methylation Is Not Involved in Primitive Myelofibrosis Megakaryocytic Spontaneous Growth
Authors: Ronan Chaligné, Carole Tonetti, Rodolphe Besancenot, Jean-Jacques Kiladjian, Gerard Socie, Dominique Bordessoule, William Vainchenker, Stéphane Giraudier
Journal: Blood (2008)
P250 Real flight spo2 compares with hypoxic challenge testing in adults with cystic fibrosis
Authors: R Peat, J Furlong, E Spencer, D Russell, M Ledson, MJ Walshaw
Journal: Thorax (2016)

<h3>Introduction</h3> Limited data are available comparing air travel with the hypoxic challenge test (HCT) in adults with cystic fibrosis (CF). The aim of this study was to assess the predictive capability the HCT to in-flight hypoxaemia in adult passengers with CF. <h3>Methods</h3> Fifteen subjects (three male) volunteered for this study. Lung function measurements (FEV1) were performed pre and post flight. Oxygen saturation measured by pulse oximetry (SpO2) and symptoms were recorded in-flight on both outward and inward flights. The HCT was performed post flight and the in-flight oxygenation response was compared to the HCT and lung function results. <h3>Results</h3> All subjects flew without the use of oxygen, and no adverse events were recorded in-flight. Air travel caused significant desaturation (p &lt; 0.001) (mean pre flight SpO<sub>2</sub> 95+−1%; mean in-flight SpO<sub>2</sub> 90 ± 3%). The HCT caused mean desaturation (p ≤ 0.001) that was comparable to that of air travel (90 ± 3%). The pre flight FEV1 and in-flight SpO<sub>2</sub> showed weak correlation (r = 0.41 p = 0.125). The HCT SpO<sub>2</sub> showed strong correlation with in-flight SpO<sub>2</sub> (r = 0.74 p &lt; 0.001). The HCT showed the strongest correlation with the lower SpO<sub>2</sub> value measured from both outward and inward flights (r = 0.92 p &lt; 0.001). <h3>Conclusions</h3> Significant in-flight desaturation can be expected in passengers with CF. The HCT results compare favourably with air travel data and may be considered the best widely available laboratory test to predict in-flight hypoxaemia in adults with CF.
OA05.05 Randomized Phase 2 Study: Alisertib (MLN8237) or Placebo + Paclitaxel as Second-Line Therapy for Small-Cell Lung Cancer (SCLC)
Authors: Taofeek Owonikoko, Kristiaan Nackaerts, Tibor Csoszi, Gyula Ostoros, Christina Baik, Claudio Dansky Ullmann, Erin Zagadailov, Emily Sheldon-Waniga, Dirk Huebner, E Jane Leonard, David Spigel
Journal: Journal of Thoracic Oncology (2017)
Antitumor effect of tyrosine kinase inhibitor, AMN107, in hepatocellular carcinoma
Authors: Eric Lh Lui, Yuqing Liu, Ronnie Tp Poon, Sheung Tat Fan
Journal: Cancer Research (2007)

3244   Hepatocellular Carcinoma (HCC) is one of the most common malignancies and is responsible for more than one million deaths worldwide. In Hong Kong, it is the second leading cause of cancer death. Surgical resection or liver transplantation is the treatment of choice when HCC is diagnosed at an early stage. However, around 70% of patients are inoperable because of advanced tumor growth or severe underlying cirrhosis. Targeted therapy could be one of the main options for HCC patients.  AMN107 is a novel and potent inhibitor of the protein tyrosine kinase activities of Bcr-Abl, c-kit and PDGFR. In the previous studies, the antitumor activity of AMN107 was attributed mainly to the treatment of chronic myeloid leukemia by targeting Bcr-Abl, and a direct antitumor effect in solid tumor was rarely reported. In this study, we investigated direct effect of AMN107 in nude mice bearing human HCC xenograft. Tumor tissues from a HCC nude mice established by human HCC cell lines were implanted orthotopically in the liver of nude mice. The in vitro effect of AMN107 on proliferation and apoptosis of human HCC cell lines was studied by MTT assay, flow cytometry and Western blot. Our results demonstrated that AMN107 oral administration to mice at 50mg/kg/day resulted in a significant reduction in tumor growth of HCC xenografts in nude mice. AMN107 inhibited tumor cell proliferation in a dose-dependent manner and also induced tumor cells to undergo apoptosis in vitro. Furthermore, AMN107 downregulated bcl-xL expression in HCC cells. In addition, it is also found that PDGF could induced phosphorylation of ERK in HCC cell lines. The simulated effect by PDGF could be blocked by AMN107. In conclusion, this study demonstrated that AMN107 is potent inhibitors of tumor growth in HCC. The inhibition of tumor volumne by AMN107 may through direct effects on inhibition of tumor cell proliferation, induction of tumor cell apoptosis and blocking bcl-xL expression. AMN107 also inhibited the PDGF induced activation of ERK. Our data suggest that AMN107 may provide an effective therapy for human HCC.
MA12.02 MMP12 and LMO7, Two Key Players on opposite Sides of Early Lung Squamous Cell Carcinoma Development
Authors: Angela Barrett, Sofia Lourenco, Krishna Kolluri, Bernadette Carroll, Mary Falzon, Elaine Borg, Jeremy George, Sam Janes, Vitor Teixeira
Journal: Journal of Thoracic Oncology (2017)