tbuckley/cabot-search huggingface dataset:
Receptor selective retinoids promote monocyte (Mo) differentiation to mature dentritic cells (DC) in peripheral blood of cancer patients
Authors: R. Porta, M. M. Dikov, J. M. Amann, D. P. Carbone
Journal: Journal of Clinical Oncology (2004)

2527 Background: Abnormal differentiation of DC and impaired antigen-presenting function in cancer patients is an important mechanism of tumor escape from immune surveillance. In the current study, we have investigated whether retinoids can induce Mo differentiation into DC and used receptor-selective ligands to characterize the retinoid receptors involved. Methods: We isolate CD14+Mo from the peripheral blood of cancer patients or normal donors using immunomagnetic separation techniques (MACS system). Cells were then cultured for 4 to 6 days in the presence of 30ng/ml GM-CSF with or without receptor-selective retinoids ( Ligand Pharmaceuticals, Inc.) or pan-specific 9-cis-trans-retinoic acid as control. Cell phenotype and number were assessed by flow cytometry. Results: At a concentration of 1 μM, RARα and RARβ/γ-specific compounds effectively promoted differentiation of Mo into DC as characterized by expression of DR, CD86, CD1c and CD83 cell surface markers, with 18%–53% of cells acquiring these markers. RXR-selective compounds were minimum effective, inducing expression in only 0.7%–13% of cells. Conclusions: These data indicate that Mo can be differentiated into DC by retinoid treatment and specifically those selective for RAR. No significant financial relationships to disclose.
Complete Remission after Autologous Stem Cell Transplantation Does Not Impact Relapse or Survival in African Americans with Multiple Myeloma.
Authors: Yasser Khaled, Muneer H. Abidi, Koji Kato, Nalini Janakiraman, Amr Hanbali, John E. Levine, James Ferrara, Shin Mineishi
Journal: Blood (2007)
Inhaled Fine Particles Induce Alveolar Macrophage Death and Interleukin-1α Release to Promote Inducible Bronchus-Associated Lymphoid Tissue Formation
Authors: Etsushi Kuroda, Koji Ozasa, Burcu Temizoz, Keiichi Ohata, Christine X. Koo, Tomohiro Kanuma, Takato Kusakabe, Shingo Kobari, Masanori Horie, Yasuo Morimoto, Saeko Nakajima, Kenji Kabashima, Steven F. Ziegler, Yoichiro Iwakura, Wataru Ise, Tomohiro Kurosaki, Takahiro Nagatake, Jun Kunisawa, Naoki Takemura, Satoshi Uematsu, Masayuki Hayashi, Taiki Aoshi, Kouji Kobiyama, Cevayir Coban, Ken J. Ishii
Journal: Immunity (2016)
Preliminary cytogenetic and pharmacogenomic analysis of muscle-invasive transitional-cell carcinoma (TCC) of the bladder in patients (pts) enrolled in the Italian National Research Council (CNR) phase III randomized trial comparing adjuvant cisplatin-gemcitabine (PG) vs observation (OBS) after radical cystectomy
Authors: C. F. Pollera, N. Merendino, A. M. Cianciulli, M. Gallucci, E. M. Ruggeri, D. Giannarelli, A. Felici, F. Nelli, F. Boccardo, F. Cognetti
Journal: Journal of Clinical Oncology (2005)

4589 Background: We evaluted a panel of genetic alterations and molecular factors predictive for response to PG in TCC samples and tumor-adjacent normal transitional-cell epithelium (TCE) to define their value as markers of genetic instability and tumor progression, as well as adjunctive prognostic predictors in a subset of pts enrolled in the ongoing CNR adjuvant study (NCI-V02–1715). Methods: Both fresh and paraffin-embedded samples of TTC were collected from 38 pts with the following characteristics: median age: 64 years (53–74), M/F 11/89%, stage: pT2G3 24%, pT3–4a 76%, pN1–2 39%; G ≤2/3–4 8/92%; study arm PG/OBS: 45/55%. Overall, 36 and 20 samples for TCC and TCE, respectively were available for cytogenetic analysis by FISH of 3,7,9,17 chromosome ploidy, p16, p53, RB deletions and HER-2 amplification. To date, paired samples of both TCC and TCE from 11 pts randomized to PG are available for pharmacogenomic analysis restricted to the quantification of mRNA levels of ERCC1 and RR subunit M1 by PCR real-time. Results: Monosomy of chromosome 7 and 17, and polisomy of chromosome 9 were significantly more frequent in TTC vs. TCE, whereas no significant correlation was found between the genetic alterations and both pT and pN stage. Overexpression of ERCC1 was found in 50 and 30% of TTC and TCE samples, respectively, whereas RRM1 was overexpressed in 30% of both TCC and TCE specimens. To date, 80% and 66% of pts overexpressing ERCC1 and RRM1, respectively experienced disease relapse vs. 20% and 43% of the remaining. Conclusions: These results highlight the role of such a genetic abnormalities in bladder cancer progression. Furthermore, overexpression of ERCC1 seems to predict a higher rate of relapse despite adjuvant PG. These findings are currently being confirmed in a larger sample. A preliminary analysis of survival will be presented (Supported by CNR-MIUR grants 02.00447, 03.00387-ST97) No significant financial relationships to disclose.
Abstract 3657: Preclinical evaluation of water-soluble pyrrolo[3,2-d]pyrimidines as single agents with tubulin and multiple receptor tyrosine kinase inhibition and as antitumor agents
Authors: Khushbu Shah, Aleem Gangjee, Roheeth Pavana, Dybdal-Hargreaves F. Nicholas, Susuan Mooberry
Journal: Cancer Research (2015)

Abstract Multiple classes of microtubule targeting agents have been identified and these include the Vinca alkaloids and colchicine (microtubule-destabilizers) and taxanes (microtubule-stabilizers). Although tubulin targeting agents are some of the most successful drugs used in the treatment of a wide range of malignancies, multidrug resistance due to overexpression of P-glycoprotein (Pgp) and/or βIII-tubulin can severely limit their clinical efficacy. Antitubulin agents like paclitaxel and other taxanes, due to poor water solubility, are formulated with polyethoxylated castor oil which can cause hypersensitivity reactions and require prolonged administration time. Recently, we reported water-soluble pyrrolo[3,2-d]pyrimidine analogs acting as antitubulin agents that circumvent these drawbacks. These analogs also exhibit potency comparable to erlotinib in cancer cell lines overexpressing epidermal growth factor receptor (EGFR) and to that of sunitinib in cancer cell lines overexpressing vascular endothelial growth factor receptor-2 (VEGFR2) and platelet derived growth factor receptor-β (PDGFRβ), in addition to inhibiting tubulin. Promising evidence for the clinical success of combination chemotherapy using multiple RTK inhibitors with antitubulin agents suggests that these dual acting compounds would serve as a single entity with both these activities. To explore the activity of these dual RTK/tubulin inhibitors, compound AG165 was evaluated in in vitro and in vivo xenograft models. In vitro AG165 inhibited the growth of MDA-MB-435 cells with an IC50 of 8.8 nM, comparable to paclitaxel. The compound is also active in paclitaxel resistant cancer cells overexpressing βIII-tubulin or Pgp, thus overcoming two important mechanisms associated with clinical resistance to paclitaxel. Compound AG165 (subcutaneous doses of 75 mg/kg x 7, cumulative dose 525 mg) showed significant (p&amp;lt;0.001) inhibition of tumor growth 15 days after treatment initiation. AG165 caused recoverable weight loss without any evidence of adverse effects. In this study, we have identified a water-soluble, dual acting RTK/ tubulin inhibitory agent that address some critical limitations of existing therapies and demonstrates in vivo antitumor effects with an acceptable toxicity profile. Citation Format: Khushbu Shah, Aleem Gangjee, Roheeth Pavana, Dybdal-Hargreaves F. Nicholas, Susuan Mooberry. Preclinical evaluation of water-soluble pyrrolo[3,2-d]pyrimidines as single agents with tubulin and multiple receptor tyrosine kinase inhibition and as antitumor agents. [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 3657. doi:10.1158/1538-7445.AM2015-3657
Abstract 3976: Targeted delivery of a synthetic microRNA-based mimic as an approach to cancer therapy
Authors: Glen Reid, Marissa Williams, Michaela B. Kirschner, Nancy Mugridge, Jocelyn Weiss, Himanshu Brahmbhatt, Jennifer MacDiarmid, Nico van Zandwijk
Journal: Cancer Research (2015)

Abstract MicroRNA expression is commonly suppressed in cancer, contributing to tumor cell biology. Recently we demonstrated that multiple members of the miR-15/16 family are downregulated and have tumor suppressor functions in malignant pleural mesothelioma (MPM), an asbestos-related cancer for which few treatments are available. These results are similar to previous findings in prostate and non-small cell lung cancer (NSCLC). Using mimics to restore levels of miR 15a, miR-15b or miR-16 led to growth inhibition and induction of apoptosis of MPM cells in vitro. The miR-16 mimic, packaged in bacterially-derived, EGFR antibody-targeted, EDV(TM)nanocells, inhibited xenograft tumor growth in vivo. As multiple microRNAs from the same family are downregulated in MPM, we investigated whether a single synthetic mimic based on the consensus sequence of all family members could restore activity of the entire family. To this end we generated four novel mimics derived from the consensus sequence of the miR-15/16 family and tested them in a range of tumor cell lines. Compared with a mimic corresponding in sequence to native miR-16, the consensus mimics had enhanced growth inhibitory activity in MPM, NSCLC and prostate cancer lines, three tumor types in which miR-15/16 expression is suppressed. They were also active in cell lines derived from breast and colon cancer. When packaged in minicells, the synthetic mimics inhibited growth of MPM xenograft tumors in vivo. Based on these preclinical studies a Phase I clinical trial has been initiated for patients with MPM or NSCLC failing standard therapy. This represents only the second trial of microRNA replacement as a cancer therapy, and the first for thoracic cancer. Citation Format: Glen Reid, Marissa Williams, Michaela B. Kirschner, Nancy Mugridge, Jocelyn Weiss, Himanshu Brahmbhatt, Jennifer MacDiarmid, Nico van Zandwijk. Targeted delivery of a synthetic microRNA-based mimic as an approach to cancer therapy. [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 3976. doi:10.1158/1538-7445.AM2015-3976
Anti–PD-1 antitumor immunity is enhanced by local and abrogated by systemic chemotherapy in GBM
Authors: Dimitrios Mathios, Jennifer E. Kim, Antonella Mangraviti, Jillian Phallen, Chul-Kee Park, Christopher M. Jackson, Tomas Garzon-Muvdi, Eileen Kim, Debebe Theodros, Magdalena Polanczyk, Allison M. Martin, Ian Suk, Xiaobu Ye, Betty Tyler, Chetan Bettegowda, Henry Brem, Drew M. Pardoll, Michael Lim
Journal: Science Translational Medicine (2016)

The immunosuppressive effects of chemotherapy present a challenge for designing effective cancer immunotherapy strategies. We hypothesized that although systemic chemotherapy (SC) exhibits negative immunologic effects, local chemotherapy (LC) can potentiate an antitumor immune response. We show that LC combined with anti-programmed cell death protein 1 (PD-1) facilitates an antitumor immune response and improves survival (P < 0.001) in glioblastoma. LC-treated mice had increased infiltration of tumor-associated dendritic cells and clonal expansion of antigen-specific T effector cells. In comparison, SC resulted in systemic and intratumoral lymphodepletion, with decreased immune memory in long-term survivors. Furthermore, adoptive transfer of CD8+ cells from LC-treated mice partially rescued SC-treated mice after tumor rechallenge. Last, the timing of chemo- and immunotherapy had differential effects on anti-PD-1 efficacy. This study suggests that both mode of delivery and timing have distinct effects on the efficacy of anti-PD-1. The results of this work could help guide the selection and scheduling of combination treatment for patients with glioblastoma and other tumor types.
255. Simultaneous Administration of Cell Therapy with ADSCs and Gene Therapy Using Ad-huPA Reduces Experimental Liver Fibrosis
Authors: Alejandra Meza-Rios, Juan Armendariz-Borunda, Leonel Garcia-Benavides, Jesus Garcia-Bañuelos, Ana Sandoval-Rodriguez
Journal: Molecular Therapy (2015)

BACKGROUND: In experimental models of cirrhosis cell therapy with hADSCs (adipose derived stromal cells) has improved liver function while reduced fibrotic tissue. Also, gene therapy using Ad-huPA has diminished liver fibrosis and increased hepatocyte regeneration. The aim of this study was to evaluate if the simultaneous administration of these therapies presents an enhanced antifibrogenic effect in cirrhotic rats. METHODS: hADSCs were isolated from fat tissue, expanded and characterized by expression of CD105+, CD73+, HLA-ABC+, CD45-, CD34-, HLA-DRII- markers and osteogenic and adipogenic differentiation. Ad-huPA vector was generated by recombination of pMH4-huPA and pJM17ΔE1 Ad-v backbone. CCl4-cirrhotic rats were administered with hADSCs (2X106 cells/rat) or Ad-huPA (3×1011 vp/rat) or both hADSCs/Ad-huPA via ileac vein. 24 hours before initiating treatment all groups were immunosuppressed with 10mg/kg of Cyclosporine A until sacrifice. After 10 days, percentage of fibrotic tissue, collagen fiber staining and mRNA levels of TGF-b1, collagen a1, CTGF, PAI-I and α-SMA were evaluated. Besides, serum levels of ALT, AST and albumin, biodistribution of hADSCs and liver levels of huPA protein were examined. RESULTS: Detection of the DAPI signal revealed that hADSCs mainly homing in liver and few of them were arrested in lung and spleen. Administration of hADSCs, Ad-huPA and Ad-huPA/hADSCs reduces (p<0.01) liver fibrosis in 78.9%, 65.2% and 72% respectively; and diminishes Collagen a1, CTGF and α-SMA mRNA liver levels (p<0.05). Furthermore, TGF-b1 and PAI-I liver mRNA levels (p<0.05) decrease in animals treated with Ad-huPA and hADSCs. Serum levels of albumin increase in the Ad-huPA, hADSCs and Ad-huPA/hADSCs groups (p<0.05) compared with control group. ALT and AST serum levels showed a significant diminish in hADSCs group (p<0.05). huPA protein was expressed in similar levels in liver homogenates of Ad-huPA and Ad-huPA/hADSCs groups. hADSCs, Ad-huPA and hADSC/Ad-huPA administration reduce percentage of collagen staining 4.3, 2.4 and 2.7 fold (p£0.001), respectively. CONCLUSIONS: Xenogenic hADSCs, Ad-huPA and Ad-huPA/hADSCs therapies decreased liver fibrosis and expression of pro-fibrogenic molecules in CCl4-cirrhotic animals. However, simultaneous administration of cell therapy and gene therapy does not appear to improve antifibrogenic effects of individual treatments.
Abstract 4207: Secreted proteins from breast cancer cell lines as a source of cancer biomarkers
Authors: Even Birkeland, Monica Mannelqvist, Lars Andreas Akslen
Journal: Cancer Research (2015)

Abstract Introduction: Breast cancer is a heterogeneous disease whose molecular diversity is not well reflected in clinical and microscopic markers used for prognostic information and treatment decisions. Traditionally, most biomarkers are based on tissue samples. To increase efficiency, precise liquid biopsies are needed to detect breast cancer at an early stage including its molecular phenotype, to monitor disease progression, and to predict treatment response. Cell line secretomes are enriched with proteins already linked to tumorigenesis, many of which will be present in biological fluids. Methods: Here, we studied the secreted proteins in conditioned media (CM) from two basal-like (HS-578, MB-231) and two luminal-like breast cancer cell lines (MCF-7, BT-474), using liquid chromatography-tandem mass spectrometry. The resulting data were analyzed using SearchGUI, PeptideShaker, Progenesis software and DAVID. Results: In total, 954 proteins were identified, of which 93 significantly differentially abundant (P-value ≤ 0.05 Mann-Whitney U, two or more peptides quantified) in the CM between basal-like and luminal-like cell lines. 76 proteins were more abundant in the CM from basal-like cell lines, including several proteins related to angiogenesis and extra-cellular matrix remodeling. Conclusion: This study shows the potential for using the secretome of breast cancer cell lines combined with mass-spectrometry for biomarker discovery. Citation Format: Even Birkeland, Monica Mannelqvist, Lars Andreas Akslen. Secreted proteins from breast cancer cell lines as a source of cancer biomarkers. [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 4207. doi:10.1158/1538-7445.AM2015-4207
Trends in Incidence, Primary Treatment and Survival of Chronic Myelomonocytic Leukemia: A Nationwide Population-Based Study Among 1,359 Patients Diagnosed in the Netherlands from 1989 to 2012
Authors: Avinash G Dinmohamed, Mirian Brink, Otto Visser, Pieter Sonneveld, Arjan A van de Loosdrecht, Mojca Jongen-Lavrencic, Georgine E. de Greef
Journal: Blood (2014)
Pathogenetic Role of Mature and Progenitor Endothelial Cells in Pre-Eclampsia.
Authors: Agostino Cortelezzi, Nicola Stefano Fracchiolla, Michela Cortiana, Maria Cristina Pasquini, Ilaria Silvestris, Irene Cetin, Veronica Cozzi, Giorgio Pardi, Giorgio Lambertenghi Deliliers
Journal: Blood (2006)
Chronic Lymphocytic Leukemia Patients with a V1-69 Gene Rearrangement Do Not Have Inferior Survival with Respect to Patients That Express Other Unmutated VH Genes.
Authors: Irina Panovska, Martin Ivanovski, Marica Pavkovic, Nikola Siljanovski, Liljana Hadzi-Pecova, Aleksandar Stojanovic, Lidija Cevreska, Dimitar G. Efremov
Journal: Blood (2005)
Combinational Therapy of Lenalidomide with Activin A Neutralizing Antibody; Preclinical Rationale for a Novel Anti-Myeloma Strategy
Authors: Tyler Scullen, Sonia Vallet, Loredana Santo, Mariateresa Fulciniti, Homare Eda, Diana D. Cirstea, Kishan Patel, Andrew Yee, Anuj Mahindra, Noopur Raje
Journal: Blood (2012)
OC-094 UK inflamatory bowel disease audit: nurse correlations between 2006 and 2008: Abstract OC-094
Authors: K Kemp
Journal: Gut (2010)

<h3>Introduction</h3> The UK Inflammatory Bowel Disease (IBD) Audit first round (R1) of 2006 was the first UK audit within gastroenterology and demonstrated marked variation in resources and quality of care. Round two (R2) was in 2008. Quality Care Service Standards for Patients with IBD recommends the appointment of an IBD nurse within the IBD team. 2008 R2 audit results are compared between hospitals with an IBD nurse in both rounds, hospitals with an IBD nurse only in round 2 and hospitals with no IBD nurse in either round. <h3>Methods</h3> Standards and questions were based on the BSG document 9Guidelines for the management of inflammatory bowel disease in adults1 along with consensus of the UK IBD Audit Steering Group. A dedicated web tool was used for both audits, with context specific online help, internal logical data checks and feedback for more complete and accurate data. <h3>Results</h3> 150 sites submitted IBD nurse organisational data in both R1 and R2: 55% (83) with IBD nursing in both rounds, 11% (17) gaining an IBD nurse between rounds, 31% (46) with no IBD nurse in R1 and R2. Searchable databases of IBD patients existed in 64% of sites with IBD nursing in both rounds, 69% of sites gaining an IBD nurse and only 9% in sites without IBD nursing in either round. Significant differences were noted in favour of IBD nursing for written information on patient relapse, for patients seen in clinic within 7 days, transitional services between children and adults, and patient forum involvement. <h3>Conclusion</h3> Evidence demonstrates that IBD nurses are instrumental in developing new services enabling better access for patients to healthcare, and are involved in education, training, research and audit, with high patient satisfaction.2 Audit data are observational and no direct causal link with IBD nursing can be inferred. Results do not reflect the number of sessions per week dedicated to IBD care nor how long IBD nurses had been in post. Nevertheless the observed correlations are encouraging in regard to the importance of the IBD nurse, within the multidisciplinary team, in enhancing the quality of care for patients with IBD.
Abstract 3747: Identification of NSCLC biomarkers underlying quantifiable drug-induced clonal fitness
Authors: Katherine L. Jameson, Peter L. Frick, Darren R. Tyson, Thomas E. Yankeelov, Vito Quaranta
Journal: Cancer Research (2015)

Abstract Lung cancer accounts for nearly 20% of all cancer-related deaths worldwide. Subsets of non-small-cell lung cancer (NSCLC; &amp;gt;80% of all lung cancers) harboring activating epidermal growth factor receptor (EGFR) mutations are highly sensitive to erlotinib, a small-molecule EGFR tyrosine kinase inhibitor. However, clinical responses to erlotinib are variable and limited in duration as all tumors eventually relapse. Clonal heterogeneity is thought to be a major cause of relapse, but it has been difficult to quantify in drug-sensitive cancer cell populations. To overcome this obstacle, we quantify clonal fitness via live-cell imaging as a drug-induced proliferation (DIP) rate that incorporates cell division, death, and quiescence into a single metric. This fitness rate varies across cell types from positive (division prevails) to negative (death prevails) and, unlike traditional IC50 measurements, can effectively discriminate intricate degrees of drug sensitivity. Moreover, in monoclonal sublines isolated naïve-to-drug from NSCLC parental cell lines, erlotinib-treated DIP rates calculated in vitro predict the long-term growth rates (250+ days) of in vivo tumor xenografts. Using global proteomics across a panel of monoclonal sublines, we have characterized networks of biomarkers that act as molecular determinants of phenotypic drug fitness. We have identified unsuspected molecular correlates in the EGFR and AKT pathways and are currently investigating whether they can act as lead targets for small molecule inhibition in combination therapies. Our data indicate that a multi-scale systems approach integrating molecular subtyping with quantifiable clonal fitness can yield insights into clonal heterogeneity and lead to novel strategies to overcome tumor relapse. Note: This abstract was not presented at the meeting. Citation Format: Katherine L. Jameson, Peter L. Frick, Darren R. Tyson, Thomas E. Yankeelov, Vito Quaranta. Identification of NSCLC biomarkers underlying quantifiable drug-induced clonal fitness. [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 3747. doi:10.1158/1538-7445.AM2015-3747