tbuckley/cabot-search huggingface dataset:
409. Expression of Mouse CD47 in Human Cancer Cells Profoundly Increases Tumor Metastasis in Murine Models
Authors: Armando Rivera, Xinping Fu, Lihua Tao, Xiaoliu Zhang
Journal: Molecular Therapy (2015)

Although there are many well established tumor cell lines that have been widely used as xenografts in murine models, many of them do not efficiently metastasize to other organ tissues after local inoculation. Lack of reliable metastatic human cancer models is hindering many aspects of cancer research, in particular, for drug development. The underlying reason for the inability of human xenografts to metastasize in immunodeficient mice is currently unclear. We hypothesize that innate immune cells such as macrophages play a pivotal role in dictating cancer cell metastasis. Specifically, macrophages can limit cancer cell metastasis by clearing tumor cells that do not express the correct CD47, the "don't eat me" signal. To test our hypothesis, we transduced the murine CD47 (mCD47) gene into the human prostate cancer cell line PC-3, to establish PC-3-CD47-GFP-Luc. A control cell line transduced with GFP-Luc only, PC-3-GFP-Luc, was also established. We then compared PC-3-CD47-GFP-Luc with PC-3-GFP-Luc and with PC-3M-Pro4, a more metastatic line established by repeatedly inoculating and harvesting PC-3 cells from prostates of athymic nude mice, for their metastatic efficiency in mice with different severity of immunodeficiency. In CB17Scid mice, which have an intact macrophage activity but lack functional T and B cells, tumor metastasis was detected in both sentinel lymph node and lung from subcutaneously implanted PC-3-CD47-GFP-Luc cells but not from the other two cell lines. In NOD-Scid and NSG mice, which have similar deficiency in T and B cells but have a diminished macrophage activity as compared to CB17Scid, tumor metastasis to the sentinel lymph node, lung and liver was detected from all the three cells implanted subcutaneously (in NOD-Scid mice) or orthotopically (in NSG mice). However, PC-3-CD47-GFP-Luc cells produced 2-3 times more tumor nodules than other two cells. The metastatic nodules from PC-3-CD47-GFP-Luc cell implantation were also visibly larger than in the other two groups. When quantified by luciferase activity, radiance from the metastatic tumor nodules in PC-3-CD47-GFP-Luc group was up to 11 times higher than that in the other two groups. Together, these data demonstrate that CD47 plays an important role in dictating tumor cell metastatic potential by providing the "don't eat me" signal to host's macrophages.
Abstract 435: Adipocyte-derived monocyte chemotactic protein-1 (MCP-1) promotes prostate cancer progression through matrix metalloproteinase (MMP-2) mediated extracellular matrix degradation
Authors: Yusuke Ito, Hitoshi Ishiguro, Naohito Kobayashi, Hisashi Hasumi, Masatoshi Watanabe, Masahiro Yao, Hiroji Uemura
Journal: Cancer Research (2015)

Abstract Background: Obesity is known to be associated with prostate cancer development and progression, but the detailed mechanism is not clear. Monocyte chemotactic protein-1 (MCP-1) is secreted from cancer cells, stromal cells and adipocytes, and it is involved in prostate cancer progression. Here we investigated the biological role of MCP-1 secreted from adipocytes for prostate cancer cells. Methods: Human pre-adipocytes (HPAds) were cultured and differentiated to mature adipocytes. Conditioned medium (CM) from HPAd cells was obtained using phenol red-free RPMI1640 medium. We performed a cytokine membrane array analysis to detect cytokines in the CM. To characterize the physiological function of MCP-1 in the CM, we performed an MTT-assay, a wound-healing and invasion assay with anti-MCP-1 antibody using three prostate cancer cell lines: DU145, LNCaP, and PC-3. Matrix metalloproteinase (MMP)-2 and MMP-9 activities were evaluated by gelatin zymography. A qPCR and Western blotting were used to examine the mRNA and protein expression levels of MMP-2. Results: The cytokine membrane array of the CM showed a strong signal of MCP-1compared to the control medium, and we thus focused our attention on MCP-1 in the CM. The CM up-regulated the cancer cell proliferation, and the neutralization by anti-MCP-1 antibody inhibited the proliferative effect of the prostate cancer cell lines. The CM greatly increased the invasive activity in the prostate cancer cell lines, and anti-MCP-1 antibody decreased the invasiveness. Gelatin zymography revealed that the CM markedly enhanced the enzymatic activity of MMP-2, and anti-MCP-1 antibody down-regulated its effect. MMP-2 mRNA expression was undetected and the MMP-2 protein level was unchanged between the control medium and CM in DU145 cells. Conclusions: MCP-1 from adipocytes enhances the growth and invasion activity of prostate cancer cells. The inhibition of MCP-1 derived from adipocytes might be an effective treatment for prostate cancer. Citation Format: Yusuke Ito, Hitoshi Ishiguro, Naohito Kobayashi, Hisashi Hasumi, Masatoshi Watanabe, Masahiro Yao, Hiroji Uemura. Adipocyte-derived monocyte chemotactic protein-1 (MCP-1) promotes prostate cancer progression through matrix metalloproteinase (MMP-2) mediated extracellular matrix degradation. [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 435. doi:10.1158/1538-7445.AM2015-435
P0050 : Neurological syndrome ‘de novo’ in familial amyloidotic polyneuropathy after liver transplant
Authors: E.M.D.S. Mateus, I. Mega, A. Morbey, J. Veloso, R. Perdigoto, H. Glória, J. Machado, A. Martins, E. Barroso
Journal: Journal of Hepatology (2015)
Co-occurring Mutations of Tumor Suppressor Genes, <i>LATS2</i> and <i>NF2</i>, in Malignant Pleural Mesothelioma
Authors: Robin Tranchant, Lisa Quetel, Anne Tallet, Clement Meiller, Annie Renier, Leanne de Koning, Aurelien de Reynies, Francoise Le Pimpec-Barthes, Jessica Zucman-Rossi, Marie-Claude Jaurand, Didier Jean
Journal: Clinical Cancer Research (2016)

Abstract Purpose: To better define malignant pleural mesothelioma (MPM) heterogeneity and identify molecular subtypes of MPM, we focus on the tumor suppressor gene LATS2, a member of the Hippo signaling pathway, which plays a key role in mesothelial carcinogenesis. Experimental Design: Sixty-one MPM primary cultures established in our laboratory were screened for mutations in LATS2. Gene inactivation was modeled using siRNAs. Gene and protein expressions were analyzed by quantitative RT-PCR, Western blot analysis, and reverse phase protein array. Cell proliferation, viability, apoptosis, mobility, and invasion were determined after siRNA knockdown or YAP (verteporfin), mTOR (rapamycin), and mTOR/PI3K/AKT (PF-04691502) inhibitor treatment. Results: The LATS2 gene was altered in 11% of MPM by point mutations and large exon deletions. Genetic data coupled with transcriptomic data allowed the identification of a new MPM molecular subgroup, C2LN, characterized by a co-occurring mutation in the LATS2 and NF2 genes in the same MPM. MPM patients of this subgroup presented a poor prognosis. Coinactivation of LATS2 and NF2 leads to loss of cell contact inhibition between MPM cells. Hippo signaling pathway activity, mTOR expression, and phosphorylation were altered in the C2LN MPM subgroup. MPMs of this new subgroup show higher sensitivity to PF-04691502 inhibitor. The MOK gene was identified as a potential biomarker of the C2LN MPM subgroup and PF-04691502 sensitivity. Conclusions: We identified a new MPM molecular subgroup that shares common genetic and transcriptomic characteristics. Our results made it possible to highlight a greater sensitivity to an anticancer compound for this MPM subgroup and to identify a specific potential biomarker. Clin Cancer Res; 23(12); 3191–202. ©2016 AACR.
Molecular Signature of Migratory Human Mesenchymal Stromal Cells; Influence of the Cell Cycle.
Authors: Marijke W. Maijenburg, Christian Gilissen, Joris A Veltman, Marion Kleijer, Cris Mudde Jadra, Kees Weijer, Claudia M van Tiel, Carlie J.M. de Vries, C. Ellen Van der Schoot, Carlijn Voermans
Journal: Blood (2009)
Abstract B10: Function and therapeutic implications of p53 in the stroma of pancreatic cancer
Authors: Maya Ridinger, Annabelle Kraus, Miranda Cox, Mark Wade, Christopher Liddle, Michael Downes, Ron Evans, Geoffrey Wahl
Journal: Cancer Research (2015)

Abstract Pancreatic ductal adenocarninoma (PDA) is one of the most aggressive human cancers and is characterized by a predominant stromal compartment mainly composed of fibroblastic and immune cells. Pancreatic stellate cells (PSCs) are the main fibroblastic cells in the pancreatic tumor microenvironment. During tumor progression, they evolve into activated and proliferative myofibroblast-like cells that synthesize copious amounts of extracellular matrix (ECM) proteins and have diminished lipid storage capacity. They produce a dense fibrous stroma that obstructs intratumoral vasculature to create physical and biological therapeutic barriers. These observations suggest that strategies that normalize the stroma may enhance anti-tumor treatment strategies. Activated PSCs in pancreatic cancers encode wild type p53, raising the possibilities that p53 activation could prevent their proliferation, and induce other paracrine anti-tumor effects. Nutlin-3a is a small-molecule p53 agonist that blocks the binding of its major negative regulator, Mdm2. As Nutlin derivatives are currently in clinical trials, we tested the consequences of activating p53 by Nutlin-3a in PSCs. The data to be presented show that Nutlin-3a induces transcriptional regulation of genes that induce multiple changes consistent with quiescence. Using PSCs from patient samples, we show that p53 activation induces lipid droplet formation, decreases expression of αSMA (ACTA2), and produces growth arrest. We also observed that p53 activation inhibits TGFβ-induced transcription of genes involved in PSC activation. To assess the genome-wide effects of p53, we performed transcriptome analysis of PSCs grown in the presence or absence of Nutlin-3a. This analysis revealed that p53 inhibits the expression of genes associated with the activation of PSCs such as ECM components and induces the expression of genes implicated in lipid metabolism characteristic of the quiescent state. P53 activation also decreased expression of genes with tumor-supporting potential including cytokines, growth factors and signaling molecules. Ongoing investigations are designed to determine the consequences of stromal p53 activation on cancer cells using in vitro co-culture systems and mouse models of pancreatic cancer. Citation Format: Maya Ridinger, Annabelle Kraus, Miranda Cox, Mark Wade, Christopher Liddle, Michael Downes, Ron Evans, Geoffrey Wahl. Function and therapeutic implications of p53 in the stroma of pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B10.
Phase II Trial of Lenalidomide, Cyclophosphamide, and Dexamethasone (CRd) for Newly Diagnosed Myeloma.
Authors: Shaji Kumar, Suzanne R. Hayman, Francis K. Buadi, Martha Q. Lacy, Keith Stewart, Philip R. Greipp, Stephen Russell, Steven Zeldenrust, Morie A. Gertz, Leif Bergsagel, Rafael Fonseca, Jacob Allred, Megan Campbell, John A. Lust, Thomas E. Witzig, Robert A. Kyle, S. Vincent Rajkumar, Angela Dispenzieri
Journal: Blood (2007)
Multivalent DNA Aptamer-Based Therapeutic Agents for Lymphoma and Leukemia.
Authors: Prabodhika Mallikaratchy, Alessandro Ruggiero, William Maguire, Kelly Piersanti, Jeffrey Gardner, Carlos Villa, Freddy Escorcia, Maria Lia Palomba, Mark Heaney, Michael R. McDevitt, David A. Scheinberg
Journal: Blood (2009)
Dual PI3K and mTOR Inhibition in Waldenstrom Macroglobulinemia
Authors: Emanuel N. Husu, Aldo M. Roccaro, Antonio Sacco, Molly R. Melhem, Abdel kareem Azab, Xiaoying Jia, Hai T. Ngo, Feda Azab, Judith Runnels, Phong Quang, Xavier Leleu, Kenneth C. Anderson, Irene M. Ghobrial
Journal: Blood (2008)
Abstract 1276: CD169-positive sinus macrophages in regional lymph nodes are associated with better survival in patients with malignant melanoma
Authors: Yoichi Saito, Koji Ohnishi, Azusa Miyashita, Satoshi Nakahara, Yukio Fujiwara, Hasita Horlad, Takanobu Motoshima, Satoshi Fukushima, Masatoshi Jinnin, Hironobu Ihn, Motohiro Takeya, Yoshihiro Komohara
Journal: Cancer Research (2015)

Abstract CD169 (sialoadhesin) is a sialic acid receptor that is expressed on the particular macrophages such as lymph node sinus macrophages. Animal studies suggested that CD169+ macrophages in lymph nodes have tumor-preventing properties, but the role of these cells in human tumors has not been clarified. Therefore, we speculated that CD169+ macrophages in regional lymph nodes (RLNs) are suggested to be essential to the anti-tumor immunity and involved in the prognosis of cancer patients. To determine the significance of CD169+ macrophages in patients with malignant melanoma (MM), we examined the expression of CD169 in paraffin-embedded tissue samples from 93 patients by immunohistochemistry and their relationship with overall survival and clinicopathological factors. A high density of CD169+ cells was significantly associated with longer overall survival in patients with MM (P = 0.001). Multivariate analysis showed that the density of CD169+ cells was an independent prognostic factor. We also found that the density of CD169+ macrophage was positively correlated with the number of CD8+ cytotoxic T cells infiltrating into tumor tissues. Furthermore, interferon (IFN)-α induced strong CD169 expression on human macrophages in vitro, and IFN-α-producing cells were indeed detected surrounding CD169+ cells in lymph node. Our data support that IFN-α-producing cells may be plasmacytoid dendritic cells (pDCs) known to produce IFN-α. These results suggest that CD169+ macrophages in RLNs are intimately involved in T-cell-mediated antitumor immunity and may be a helpful marker for assessing clinical prognosis and monitoring antitumor immunity in patients with MM. Citation Format: Yoichi Saito, Koji Ohnishi, Azusa Miyashita, Satoshi Nakahara, Yukio Fujiwara, Hasita Horlad, Takanobu Motoshima, Satoshi Fukushima, Masatoshi Jinnin, Hironobu Ihn, Motohiro Takeya, Yoshihiro Komohara. CD169-positive sinus macrophages in regional lymph nodes are associated with better survival in patients with malignant melanoma. [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 1276. doi:10.1158/1538-7445.AM2015-1276
Characterization of serum HER2 extracellular domain (ECD) level in patients with metastatic colorectal cancer
Authors: Hiroko Hasegawa, Hiroya Taniguchi, Toshiki Masuishi, Yukiya Narita, Azusa Komori, Motoo Nomura, Shigenori Kadowaki, Masashi Andoh, Takashi Ura, Kei Muro
Journal: Annals of Oncology (2015)
Pixantrone (PIX) Inhibition of Doxorubicinol (DOXOL) Formation in Human Myocardium: Implications for Cardiac Safety in Non-Hodgkin Lymphoma (NHL) Patients with Prior Anthracycline Treatment
Authors: Emanuela Salvatorelli, Odalys Gonzalez Paz, Elvio Covino, Massimo Chello, Jack Singer, Pierantonio Menna, Giorgio Minotti
Journal: Blood (2011)
Evaluation of the targeted therapy everolimus on cognitive functions and cerebral plasticity in an animal model.
Authors: M. Dubois, N. Lapinte, V. Le Joncour, V. Roy, M. Tonon, P. Gandolfo, F. Joly, P. Hilber, H. Castel
Journal: Journal of Clinical Oncology (2011)

e13589 Background: Cancer and treatments can induce cognitive impairments in patients, called “chemofog” such as deficits of visual and spatial memories and decline of psychomotor processing speed. Although direct effect of chemotherapy on cognitive functions and neurogenesis has been shown, the impact of targeted therapies has never been investigated. Everolimus, which blocks the mTOR pathway, alters cell proliferation, metabolism and neoangiogenesis. Gene expression in hippocampus implicated in memory processes is regulated by the mTOR signalling pathway. Thus, we used a validated behavioral animal model to test the potential cognitive troubles induced by Everolimus. In addition, ex vivo analyses were conducted on neural cell plasticity involved in hippocampus-dependent behavioral tasks. Methods: Everolimus (5 mg/kg) was daily per os administered in adult C57BL/6J Rj mice for two weeks. Learning and memory processes were evaluated 7 days after the end of the treatment period by means of the Morris water maze and the object recognition tests. Ex vivo, hippocampal neurogenesis was investigated in mice that received BrdU during the 5 last days of the treatment period. Results: Everolimus slowed body weight gain from the last day of the treatment period until the end of behavioral sessions. One week after the end of the treatment, emotional reactivity, spontaneous activity, spatial learning and memory performances, as well as behavioral flexibility and object recognition memory were not impaired by Everolimus. Ex vivo analyses of the number of neural stem cells in neurogenic area showed no modification in treated mice at the end of the period of therapy. Conclusions: At short term, Everolimus did not modify cognitive functions evaluated by means of the hippocampal- and prefrontal-dependent behavioral tasks. These observations differ from our previous studies demonstrating that chemotherapy (5-fluorouracil) led to selective long-term cognitive deficits, i.e. behavioral flexibility and recognition memory, sustained by altered neurogenesis. These results reinforce the interest of developing targeted therapies for cancer treatment.
Abstract 562: Alterations in chromatin remodeling pathways as a predictive biomarker of cisplatin therapy in non-small cell lung cancer
Authors: Erica Hlavin Bell, Arup Ratan Chakraborty, Xiaokui Molly Mo, David Carbone, Arnab Chakravarti
Journal: Cancer Research (2015)

Abstract BRG1 (SMARCA4) and BRM (SMARCA2) are two important catalytic (ATPase) components of the mammalian chromatin remodeling complex SWI/SNF. Alterations of these components have been implicated in many cancers including lung, prostate, pancreatic, breast, and colon. Several studies have reported that both BRG1 and BRM actively participate in DNA damage repair by inducing phosphorylation of γ-H2AX, stimulating nucleotide excision repair, and also regulating interstand cross-link repair. BRG1 is frequently deleted in many primary tumors and lung cancer cell lines. Therefore, we hypothesized that reduced DNA repair capacity due to loss of BRG1 may enhance the sensitivity to DNA-damaging agents and may serve as predictive biomarkers of sensitivity for these agents. The purpose of this study was to evaluate the association between BRG1 and/or BRM alterations and the outcome of platinum-based chemoradiation in resected non-small cell lung cancer (NSCLC). Using the gene profiling of the patient tumor samples from the North American Intergroup phase III trial of adjuvant cisplatin plus vinorelbine (JBR.10), we found that patients with low BRG1 (SMARCA4) or low BRM (SMARCA2) had significantly longer overall survival (OS) if they had adjuvant chemotherapy (both p&amp;lt;0.05, vs no-adjuvant treatment patients). Interestingly, no significant differences in the OS were observed with high SMARCA4 or high SMARCA2 expression. Collectively, this study suggests that reduced expression of SMARCA4 and SMARCA2 may serve as putative predictive biomarkers of cisplatin therapy and warrants further investigation. This study was supported by funds from the Lung Cancer Research Foundation (to EB), the Paul P. Carbone Memorial Foundation (to EB), The Ohio State University Comprehensive Cancer Center (to AC); NIH/NCI 1U10CA180850-01(to AC); NIH/NCI 1RC2CA148190 (to AC); NIH/NCI 2K12CA133250-06 (to AC); NIH/NCI/CTEP 1R01CA169368 (to AC); NIH/NCI 1R01CA11522358 (to AC), and RTOG (to AC). Citation Format: Erica Hlavin Bell, Arup Ratan Chakraborty, Xiaokui Molly Mo, David Carbone, Arnab Chakravarti. Alterations in chromatin remodeling pathways as a predictive biomarker of cisplatin therapy in non-small cell lung 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 562. doi:10.1158/1538-7445.AM2015-562
Increased Plasma VWF Antigen over Decreased ADAMTS13 Activity in Patients with Liver Cirrhosis: Relationship to Degree of Liver Disturbance and Clinical Features.
Authors: Masahito Uemura, Seiji Kato, Masanori Matsumoto, Hiromichi Ishizashi, Ayami Isonishi, Hisahide Hiura, Tomomi Matsuyama, Hideo Yagi, Masatoshi Ishikawa, Masao Fujimoto, Hideyuki Kojima, Hitoshi Yoshiji, Yoshihiro Fujimura, Hiroshi Fukui
Journal: Blood (2006)
Fertility preservation for cancer patients: Role of nursing attitudes.
Authors: Maria C. Grabowski, Deborah Spitzer, Shaghayegh Rezale, Catherine Close, Sonja Stutzman, Daiwai Olson
Journal: Journal of Clinical Oncology (2016)

110 Background: Nurses play a pivotal role in ensuring adherence to quality guidelines. The 2006 American Society of Clinical Oncology - Quality Oncology Practice Initiative guidelines state that infertility risks should be discussed prior to initiation of fertility-reducing therapies for patients in their reproductive years. Despite this guideline on fertility preservation (FP), national compliance is only 6% (Tallent, 2013). Research is lacking in the understanding of nurses’ attitudes and behaviors towards FP and no tools exist from which to examine this problem. The purpose of this study is to gain increased understanding of potential barriers for nurses to recommend FP as an option for newly diagnosed patients. Methods: This instrument development study was developed by content experts and field tested with staff nurses. Next, an online survey method was used to examine factors associated with nursing recommendation for FP of newly diagnosed cancer patients. An anonymous online survey was sent to oncology nurses at UT Southwestern and members of the Oncology Nursing Society (Dallas Fort Worth Chapter). The endpoint of the study is a sound survey to assess nursing behaviors toward FP in diagnosed cancer patients. Standardized descriptive measures of central tendency were used to describe baseline characteristics for the sample. Factor analysis was completed using SAS v9.3 with orthogonal rotation. Scree plot was examined for factors and loading &gt; 0.30 were retained. Results: Analysis of the first 67 returned surveys (Phase 1) supports a 15-item (5-factor) survey tool. Preliminary results suggested the need for education, referral availability, and system refinement. Phase 2 surveys of additional 200 was initiated in August 2015, with an expected close of enrollment date of December 2015. Conclusions: Cancer patients of childbearing age worry how treatment will affect their ability to have a child. This survey may be beneficial in identifying nursing attitudes regarding FP. All members of the care team should be sensitive to this concern and should recommend appropriate action. This study will identify nursing barriers to patient education, and will support system-wide implementation of a comprehensive FP program.
Chemoimmunotherapy Combining Vincristine, Dexamethasone and Epratuzumab (hLL2) As Salvage Regimen for Older Relapsed/Refractory, CD22+ B-Acute Lymphoblastic Leukemia (B-ALL) Patients: Results of the French Non-Intensive Phase 2 Prospective Cheprall Study
Authors: Patrice Chevallier, Françoise Huguet, Emmanuel Raffoux, Anne Etienne, Thibaut Leguay, Françoise Isnard, Nelly Robillard, Thierry Guillaume, Jacques Delaunay, Pierre Peterlin, Aude Charbonnier, Arnaud Pigneux, Claire Le Houerou, David M Goldenberg, William A Wegener, Hervé Dombret
Journal: Blood (2014)