tbuckley/cabot-search huggingface dataset:
Abstract 3172: CCL9 induction in myeloid cells of the premetastatic niche enhances tumor cell survival and metastatic colonization
Authors: Hannah HY Yan, Yanli Pang, Kent Hunter, Chand Khanna, Li Yang
Journal: Cancer Research (2015)

Abstract Tumor cell survival in the hostile distant organ is a rate-limiting step in cancer metastasis. Bone marrow-derived myeloid cells can form a premetastatic niche and provide a tumor-promoting microenvironment. However, it is unclear whether these myeloid cells in the premetastatic site have any direct effect on tumor cell survival. Here we report that chemokine CCL9 was highly induced in Gr-1+CD11b+ immature myeloid cells and in premetastatic lung of mice bearing 4T1 mammary tumor and B16 melanoma. Knockdown of CCL9 in myeloid cells decreased tumor cell survival and metastasis. The expression level of CCL23, the human orthologue for CCL9, in peripheral blood mononuclear cells correlated with progression and survival of cancer patients. Our studies identify CCL9 as a key pro-survival factor for cancer cells in the premetastatic organ. Interestingly, the expression of CCL9 in myeloid cells is regulated by TGF-β signaling as overexpression of CCL9 in myeloid cells lacking TGF-β signaling rescued the tumor metastasis defect observed in mice with myeloid-specific deletion of TGF-β signaling. These data together with our previous report of a fundamental role of myeloid TGF-β signaling in host compromised immune surveillance (Cancer Discovery 2013); demonstrate that myeloid-specific TGF-β signaling constitutes an essential component of the metastasis-promoting puzzle of TGF-β. This finding is different from TGF-β signaling in fibroblasts and a variety of epithelial cells, as well as T cells in which the TGF-β signaling functions as a tumor suppressor. This new understanding of TGF-β at the interface of tumor and host may provide insight into how TGF-β switches from a tumor suppressor to a tumor promoter, a long-standing challenge in cancer biology field. Our study demonstrates that CCL9 could serve as a good candidate for anti-metastasis treatment by targeting the rate-limiting step of cancer cell survival. Additionally, targeting CCL9 may avoid the adverse effects of TGF-β-targeted therapy. Citation Format: Hannah HY Yan, Yanli Pang, Kent Hunter, Chand Khanna, Li Yang. CCL9 induction in myeloid cells of the premetastatic niche enhances tumor cell survival and metastatic colonization. [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 3172. doi:10.1158/1538-7445.AM2015-3172
Clinical Significance of Risk Stratification Based on Disease Risk Index and Hematopoietic Cell Transplantation-Comorbidity Index
Authors: Takayuki Sato, Shinichi Ochi, Takashi Nagayama, Shogo Nabe, Kazuya Sakai, Hiroyuki Muranushi, Yusuke Okamoto, Hiroyuki Sugiura, Kazuya Okada, Aki Sato, Takeshi Maeda, Tatsuhito Onishi, Yasunori Ueda
Journal: Blood (2014)
Sequence-Specific Conversion of βA- to βS-Globin by Small Fragment Homologous Replacement In Hematopoietic Stem/Progenitor Cells.
Authors: Alireza Abdolmohammadi, Rosalie Maurisse, Babek Bedayat, David DeSemir, Damian Laber, Dieter C. Gruenert
Journal: Blood (2010)
ARRY-797, a Potent and Selective Inhibitor of p38 Map Kinase, Inhibits LPS-Induced IL-6 and In Vivo Growth of RPMI-8226 Human Multiple Myeloma Cells.
Authors: Dale Wright, Shannon L. Winski, Deborah Anderson, Patrice Lee, Mark Munson, James Winkler
Journal: Blood (2006)
Abstract 4653: Modulation of mTOR and p53 signaling using rapamycin plus CP-31398 inhibits growth and progression of urothelial carcinoma in-vivo
Authors: Venkateshwar Madka, Altaf Mohammed, Qian Li, Yuting Zhang, Laura Biddick, Jagan M.R. Patlolla, Stanley Lightfoot, Xue-Ru Wu, Vernon Steele, Levy Kopelovich, Chinthalapally V. Rao
Journal: Cancer Research (2015)

Abstract Bladder cancer is the second most common genitourinary cancer worldwide. Despite multidisciplinary treatment advances, muscle-invasive bladder cancer continues to have high mortality. Since dysregulation of p53 and mTOR signaling in urothelium is associated with tumor initiation, growth and invasiveness, we investigated whether up-regulation of TP53 plus inhibition of mTOR additively or synergistically inhibits tumor growth and progression in vivo. Transgenic UPII-SV40T male mice (n = 15/group) were generated, genotyped and fed control or experimental diets containing the mTOR inhibitor rapamycin (8 or 16 ppm) and/or the p53 stabilizing agent CP31398 (150 ppm) starting at 6 weeks of age. After 34 weeks, control diet fed transgenic mice developed urothelium-specific high-grade, invasive transitional cell carcinoma (TCC) with significant increase in bladder weights (140.2 ± 9.8 mg; p&amp;lt;0.0001) compared with wild type (27.3 ± 0.8 mg). Rapamycin (8 or 16 ppm) reduced tumor weight by ∼ 67% or 77% and CP31398 decreased it by &amp;gt;70%. The combination of CP31398 with 8 ppm rapamycin decreased tumor weight by ∼83% (16.47 ± 5.4 mg; p&amp;lt;0.0001). Rapamycin (8 or 16 ppm) suppressed tumor invasion by 53% (p&amp;lt;0.005) or 66% (p&amp;lt;0.0005). CP-31398 alone failed to inhibit tumor invasion; however its combination with low-dose rapamycin inhibited tumor invasion &amp;gt;71% (p&amp;lt;0.0001). Molecular analysis of tumors via real-time PCR, IHC and western blotting showed synergistic inhibition by the drug combination of tumor growth and invasion with suppression of mTOR signaling (mTOR, pmTOR, raptor, rictor, Akt, pAkt); induction of p53 expression; and decreased expression of proliferation (PCNA), cell cycle regulators (cyclin D1, cyclin A), pro-survival molecules (Hif1a, Vegf) and androgen receptor. The combination of CP-31398 and rapamycin appears to be a promising approach for preventing urothelial TCC invasion. (Supported in part by NCI-CN53300) Note: This abstract was not presented at the meeting. Citation Format: Venkateshwar Madka, Altaf Mohammed, Qian Li, Yuting Zhang, Laura Biddick, Jagan M.R. Patlolla, Stanley Lightfoot, Xue-Ru Wu, Vernon Steele, Levy Kopelovich, Chinthalapally V. Rao. Modulation of mTOR and p53 signaling using rapamycin plus CP-31398 inhibits growth and progression of urothelial carcinoma 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 4653. doi:10.1158/1538-7445.AM2015-4653
Labile Plasma Iron (LPI) Is a Clinical Indicator of Overt Iron Overload in Patients with Lower-Risk Myelodysplastic Syndromes (MDS) from the European Leukemianet MDS Registry
Authors: Louise De Swart, Chloé Reiniers, Tim Bagguley, David Bowen, Jaroslav Cermak, Eva Hellström-Lindberg, Aurelia Tatic, Argiris Symeonidis, Gerwin Huls, Panagiotis Panagiotidis, Hege Garelius, Dominic Culligan, Marta Krejci, Corine van Marrewijk, Jackie Droste, Alexandra Smith, Dorine W. Swinkels, Theo de Witte
Journal: Blood (2015)
Tissue expression of osteopontin (OPN) and mesothelin (MES) in malignant pleural mesothelioma (MPM). An immunohistochemical study of 70 consecutive cases
Authors: P. Betta, R. Libener, S. Orecchia, M. Salvio, E. Arnolfo, G. Bottero, M. Botta, E. Piccolini, M. Pavesi
Journal: Journal of Clinical Oncology (2009)

e22102 Background: There is still no single test that can reliably identify malignant mesothelial cells. Recently soluble MES and OPN have been proposed as novel serum markers for MPM but a definitive consensus on their use in routine is still lacking. This study aims at 1. analysing the essential pathological features of a series of consecutive MPMs from a single institution and 2. assessing the tumour tissue expression of OPN and MES and speculating about the potential biological role of these molecules in MPM. Methods: All MPMs diagnosed between 1999 and 2008 were retrieved from the archives of the Pathology Unit of Alessandria Hospital. All the diagnoses had been made on the basis of conventional light microscopy features supplemented by a mucin stain (periodic acid-Schiff with and without diastase treatment) and a panel of immunostains (carcinoembryonic antigen, CD15/LeuM1, BerEP4, calretinin and cytokeratin 5). Immunostaining for OPN (polyclonal antibody) and MES (monoclonal antibody, clone 5B2) was performed using the labelled streptavidin-biotin method, and the staining intensity and extent were assessed. Results: The study group consisted of 50 males and 20 females with a mean age at diagnosis of 78.4 years (range 47–92). Histopathology was epithelial, mixed, and sarcomatous in 52, 12, and 6 patients respectively. OPN positivity (percentage of positive tumour cells &gt;10%) was observed in 67 MPMs (96%) mostly in a granular cytoplasmic pattern and with an intensity ranging from weak (25%) to moderate (31%) and strong (44%). MES positivity (percentage of positive tumour cells &gt;10%) was recorded in 60 MPMs (86%), of which 36% exhibited a weak, 36% a moderate and 28% a strong immunostaining in a membrane pattern. MES was positive in 100% of epithelial MPMs, in 67% of mixed and in 0% of sarcomatous. Positivity was restricted to the epithelial component in mixed MPMs. Conclusions: The high expression of OPN in MPM, irrespective of the histotype, seems to point to a role of this molecule as a marker of malignant transformation of mesothelial cells, while the restriction of positive staining for MES to the epithelial phenotype supports a role of MES as a marker of epithelial differentiation in MPM. No significant financial relationships to disclose.
The Impact of Activated Akt Expression On Clinical Outcome in Diffuse Large B-Cell Lymphoma: A Clinicopathological Study of 99 Cases.
Authors: Jung Yong Hong, Moon Ki Choi, Young Saing Kim, Chi Hoon Maeng, Su Jin Lee, Won Jin Chang, Silvia Park, Seok Jin Kim, Jun Ho Jang, Kihyun Kim, Chul Won Jung, Young Hyeh Ko, Won Seog Kim
Journal: Blood (2012)
Abstract 4323: ALK overexpression is associated with activation of PI3K/AKT signaling pathway in PTC
Authors: Rong Bu, Sarita Prabhakaran, Shaham Beg, Zeenath Jehan, Abdul K. Siraj, Maqbool Ahmed, Azhar Hussain, Saif A. Alsobhi, Fouad Al-Dayel, Shahab Uddin, Khawla S. Al-Kuraya
Journal: Cancer Research (2015)

Abstract Aberrant activation of anaplastic lymphoma kinase (ALK) gene caused by mutation, rearrangement or overexpression plays a fundamental role in tumorigenesis in several tumors and represents an important therapeutic target. Currently, only limited data is available on thyroid cancer with respect to the genetic alteration of ALK. Therefore we investigate the ALK overexpression and amplification, and its correlation with various clinicopathological features and molecular biomarkers in a large cohort of 1040 Middle Eastern PTC. In our study, ALK protein expression was determined by immunohistochemistry. ALK gene amplification and rearrangement were analyzed by in situ hybridization (FISH). We also correlated the data with clinicopathological characteristics and other molecular markers. Our data showed that ALK is overexpressed in 136 of the 997 (13.6%) PTC samples. ALK amplification and rearrangement were not observed by FISH. ALK overexpression was significantly associated with surgical margin, but had no effect on the survival of PTC patients. Interestingly, ALK overexpression was found to be significantly correlated with the higher expression of pAKT and PIK3CA in PTC samples, suggesting that ALK overexpression is associated with activation of PI3K/AKT signaling pathway in PTC. In addition, ALK overexpression is also correlated with overexpression of anti-apopototic marker XIAP and BCL-XL and cell cycle regulatory marker SKP2. Altogether, our results suggest that ALK overexpression presents in a small subset of samples and is not associated with survival in PTC. However ALK overexpression is significantly correlated with PI3K/AKT signaling pathway and might provide a potential therapeutic target for PTC patients with ALK overexpression. Citation Format: Rong Bu, Sarita Prabhakaran, Shaham Beg, Zeenath Jehan, Abdul K. Siraj, Maqbool Ahmed, Azhar Hussain, Saif A. Alsobhi, Fouad Al-Dayel, Shahab Uddin, Khawla S. Al-Kuraya. ALK overexpression is associated with activation of PI3K/AKT signaling pathway in PTC. [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 4323. doi:10.1158/1538-7445.AM2015-4323
68Ga-DOTATATE PET/CT in Primary Hepatic Neuroendocrine Tumor
Authors: Arun Kumar Reddy Gorla, Rajender Kumar Basher, Lileshwar Kaman, Amanjit Bal, Anish Bhattacharya, Bhagwant Rai Mittal
Journal: Clinical Nuclear Medicine (2016)

Primary neuroendocrine tumors of the liver are a diagnostic challenge. We present a rare case of primary hepatic neuroendocrine tumor in which Ga-DOTATATE PET/CT imaging played an important role in the diagnosis and follow-up.
Effect of a Primary Care–Based Psychological Intervention on Symptoms of Common Mental Disorders in Zimbabwe
Authors: Dixon Chibanda, Helen A. Weiss, Ruth Verhey, Victoria Simms, Ronald Munjoma, Simbarashe Rusakaniko, Alfred Chingono, Epiphania Munetsi, Tarisai Bere, Ethel Manda, Melanie Abas, Ricardo Araya
Journal: JAMA (2016)

<h3>Importance</h3> Depression and anxiety are common mental disorders globally but are rarely recognized or treated in low-income settings. Task-shifting of mental health care to lay health workers (LHWs) might decrease the treatment gap. <h3>Objective</h3> To evaluate the effectiveness of a culturally adapted psychological intervention for common mental disorders delivered by LHWs in primary care. <h3>Design, Setting, and Participants</h3> Cluster randomized clinical trial with 6 months' follow-up conducted from September 1, 2014, to May 25, 2015, in Harare, Zimbabwe. Twenty-four clinics were randomized 1:1 to the intervention or enhanced usual care (control). Participants were clinic attenders 18 years or older who screened positive for common mental disorders on the locally validated Shona Symptom Questionnaire (SSQ-14). <h3>Interventions</h3> The Friendship Bench intervention comprised 6 sessions of individual problem-solving therapy delivered by trained, supervised LHWs plus an optional 6-session peer support program. The control group received standard care plus information, education, and support on common mental disorders. <h3>Main Outcomes and Measures</h3> Primary outcome was common mental disorder measured at 6 months as a continuous variable via the SSQ-14 score, with a range of 0 (best) to 14 and a cutpoint of 9. The secondary outcome was depression symptoms measured as a binary variable via the 9-item Patient Health Questionnaire, with a range of 0 (best) to 27 and a cutpoint of 11. Outcomes were analyzed by modified intention-to-treat. <h3>Results</h3> Among 573 randomized patients (286 in the intervention group and 287 in the control group), 495 (86.4%) were women, median age was 33 years (interquartile range, 27-41 years), 238 (41.7%) were human immunodeficiency virus positive, and 521 (90.9%) completed follow-up at 6 months. Intervention group participants had fewer symptoms than control group participants on the SSQ-14 (3.81; 95% CI, 3.28 to 4.34 vs 8.90; 95% CI, 8.33 to 9.47; adjusted mean difference, −4.86; 95% CI, −5.63 to −4.10;<i>P</i> &lt; .001; adjusted risk ratio [ARR], 0.21; 95% CI, 0.15 to 0.29;<i>P</i> &lt; .001). Intervention group participants also had lower risk of symptoms of depression (13.7% vs 49.9%; ARR, 0.28; 95% CI, 0.22 to 0.34;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> Among individuals screening positive for common mental disorders in Zimbabwe, LHW-administered, primary care–based problem-solving therapy with education and support compared with standard care plus education and support resulted in improved symptoms at 6 months. Scaled-up primary care integration of this intervention should be evaluated. <h3>Trial Registration</h3> pactr.org Identifier:PACTR201410000876178
379. Delivery of Human Clotting Factors By Expression from B lymphocytes Genetically Engineered Using the Sleeping Beauty Transposon System
Authors: Kendra A. Hyland, Eric Herbig, Mei Xu, Rian de Laat, Erik R. Olson, Matt Scholz, R. Scott McIvor
Journal: Molecular Therapy (2015)

Hemophilia A and hemophilia B are X-linked, genetic disorders that are caused by defective or deficient coagulation factor VIII and IX, respectively, resulting in the inability to form blood clots and sustained bleeding after trauma or injury. Recombinant clotting factor protein is currently used to treat hemophilia at a high cost per patient. As a therapeutic approach for hemophilia, gene transfer has the potential to provide more consistent levels of circulating clotting factor over an extended period of time for more cost-effective treatment. Moreover, only modest levels of FVIII or FIX expression (2%-5% of normal) can improve clinical outcomes. We are using the Sleeping Beauty (SB) transposon system to engineer autologous human B cells for secretion of clotting factors as a cellular therapy for hemophilia. An in vitro system for expansion and differentiation of memory B cells into plasma cells has been developed. Plasma cells are suitable for sustained delivery of FVIII or FIX, since they secrete high levels of protein and may survive for years in vivo. For human FIX expression, we assembled an SB transposon with the human FIX coding sequence (codon-optimized with R338L mutation for enhanced potency) regulated by the CAGS promoter. Elevated levels of hFIX in cultures of B lymphoblastoid cells required co-electroporation of the hFIX transposon along with an SB transposase encoding plasmid, demonstrating the role of transposition in achieving extended hFIX expression. There have been remarkable advances recently in the treatment of hemophilia B by systemic AAV8-hFIX administration, but similar treatment of hemophilia A presents a significant challenge due to the size of the FVIII-encoding sequence and the complexity of the protein. We previously demonstrated B-domain deleted hFVIII expression and correction of clotting dysfunction in FVIII deficient mice by hydrodynamic delivery using the SB transposon system (Ohlfest et al, Blood 105: 2691, 2005). Current studies are focused on identifying conditions for effective hFVIII transposon delivery and long term expression in primary human B cells after Sleeping Beauty-mediated transposition. Results from these studies will be applicable to the development of a clinical protocol for treatment of human hemophilia by infusion of B cells genetically engineered using the Sleeping Beauty transposon system.
Abstract 5456: FGF9 gene amplification can induce resistance to anti-EGFR therapy in colorectal cancer
Authors: Takuro Mizukami, Yosuke Togashi, Eri Banno, Masato Terashima, Marco A de velasco, Kazuko Sakai, Yoshihiko Fujita, Shuta Tomida, Takako Eguchi Nakajima, Narikazu Boku, Kazuto Nishio
Journal: Cancer Research (2015)

Abstract The prognosis of advanced colorectal cancer (CRC) remains dismal. Fibroblast growth factor (FGF) signals are potent mitogens, morphogens, and inducers of angiogenesis. Abnormal expression of FGF9 has been observed in several malignancies and might result in uncontrolled cell proliferation and carcinogenesis. However, limited information is available regarding the role of FGF9 in CRC. In this study, amplification of FGF9 gene was observed in 14/146 (9.6%) CRC specimens, using a TaqMan copy number assay. FGF9-overexpressed CRC cell lines were created, and FGF9-overexpression induced the resistance to anti-epidermal growth factor receptor (EGFR) therapy (cetuximab or lapatinib) via the FGF receptor (FGFR) signal, which was cancelled by BGJ398, a pan-FGFR inhibitor. In vivo, FGF9-overexpressed xenograft tumors were resistant to cetuximab monotherapy and the combination with BGJ398 overcame the resistance. Considering these results, FGF9 gene amplification may play an important role in the resistance to anti-EGFR therapy in CRC and the combination with an anti-FGFR inhibitor could overcome this resistance. Citation Format: Takuro Mizukami, Yosuke Togashi, Eri Banno, Masato Terashima, Marco A de velasco, Kazuko Sakai, Yoshihiko Fujita, Shuta Tomida, Takako Eguchi Nakajima, Narikazu Boku, Kazuto Nishio. FGF9 gene amplification can induce resistance to anti-EGFR therapy in colorectal 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 5456. doi:10.1158/1538-7445.AM2015-5456
Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease
Authors: Sun-Gou Ji, Brian D Juran, Sören Mucha, Trine Folseraas, Luke Jostins, Espen Melum, Natsuhiko Kumasaka, Elizabeth J Atkinson, Erik M Schlicht, Jimmy Z Liu, Tejas Shah, Javier Gutierrez-Achury, Kirsten M Boberg, Annika Bergquist, Severine Vermeire, Bertus Eksteen, Peter R Durie, Martti Farkkila, Tobias Müller, Christoph Schramm, Martina Sterneck, Tobias J Weismüller, Daniel N Gotthardt, David Ellinghaus, Felix Braun, Andreas Teufel, Mattias Laudes, Wolfgang Lieb, Gunnar Jacobs, Ulrich Beuers, Rinse K Weersma, Cisca Wijmenga, Hanns-Ulrich Marschall, Piotr Milkiewicz, Albert Pares, Kimmo Kontula, Olivier Chazouillères, Pietro Invernizzi, Elizabeth Goode, Kelly Spiess, Carmel Moore, Jennifer Sambrook, Willem H Ouwehand, David J Roberts, John Danesh, Annarosa Floreani, Aliya F Gulamhusein, John E Eaton, Stefan Schreiber, Catalina Coltescu, Christopher L Bowlus, Velimir A Luketic, Joseph A Odin, Kapil B Chopra, Kris V Kowdley, Naga Chalasani, Michael P Manns, Brijesh Srivastava, George Mells, Richard N Sandford, Graeme Alexander, Daniel J Gaffney, Roger W Chapman, Gideon M Hirschfield, Mariza de Andrade, Simon M Rushbrook, Andre Franke, Tom H Karlsen, Konstantinos N Lazaridis, Carl A Anderson
Journal: Nature Genetics (2016)
Abstract 162: Overexpression of long noncoding RNA FTX was associated with colorectal cancer progression
Authors: Takeshi Iwaya, Kei Sato, Kohei Kume, Satoshi Nishizuka, Go Wakabayashi, Koshi Mimori
Journal: Cancer Research (2015)

Abstract Increasing evidence suggests Long noncoding RNAs (lncRNAs) have crucial roles in cancer biology. Using public microarray database, we evaluated the association between the expression status of lncRNAs and colorectal cancer (CRC) prognosis. Among the candidate lncRNAs showed significant higher expression in CRC patients with poor prognosis, we focused on FTX on chromosome X. We validated FTX expression status in 128 primary tumor samples and corresponding normal tissues from CRC patients through quantitative real-time PCR (qRT-PCR) analysis. Primary tumor tissues exhibited higher FTX expression compared to corresponding normal tissues (p = 0.0008). In terms of overall survival, patients in the FTX high expression group (n = 74) had a significantly poorer prognosis than those in the FTX low expression group (n = 74). Multivaliate analysis of overall survival revealed that the level of FTX expression was a prognostic predictor. FTX knockdown inhibited tumor cell proliferation in CRC cell line, HT29. Our results indicate that overexpression of FTX may affect CRC progression. Citation Format: Takeshi Iwaya, Kei Sato, Kohei Kume, Satoshi Nishizuka, Go Wakabayashi, Koshi Mimori. Overexpression of long noncoding RNA FTX was associated with colorectal cancer progression. [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 162. doi:10.1158/1538-7445.AM2015-162