bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2668: Efficacy study of immuno-checkpoint antibodies in humanized CDX and PDX models
Authors: Zhang Feifei , Yang Yang , Chen Hongkui , Jia Lijun , Ouyang Kedong , Wen Danyi , Chen Taiping 
Published: July 2017

Abstract
Immune therapeutic intervention has been accepted widely for many hematopoietic malignancies and solid malignancies in past several years. Preclinical animal models with reconstitution of immune cells and target-expressing tumor cells were urgently needed for prove of concept studies demonstrating stimulatory immune system activation. Here we describe two established models of human PBMC co-transplantation of CDX and PDX. The study design was based on co-inoculation of human PBMC and PD-L1 expressing cell in NOG mice for reconstitution of immuno-checkpoint blockage. A therapeutic anti-PD1 antibody was applied for immune system activation and tumor growth inhibition measurement. After drugs were administrated i.p. for three weeks, 95 % TGI for A375 CDX model were observed. At the termination of the efficacy study at 28 days post therapeutic intervention, tumors of vehicle (tumor only, PMBC only), PD1 Ab treated groups were collected for immunostaining of CD45. Infiltrating T-cell with CD45+ label was found within the tumors when co-inoculated with human PBMC. PBMC humanized PDX models of ovarian cancer was implanted into mice which reconstituted with human PBMC for therapeutic intervention. Results showed that 85% TGI for PBMC humanized ovarian PDX models was observed. In conclusion, the models established here are feasible for immunotherapeutic evaluation and further additional immune therapeutic test articles can be explored with similar approaches.
Citation Format: Feifei Zhang, Yang Yang, Hongkui Chen, Lijun Jia, Kedong Ouyang, Danyi Wen, Taiping Chen. Efficacy study of immuno-checkpoint antibodies in humanized CDX and PDX models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2668. doi:10.1158/1538-7445.AM2017-2668
Abstract 2677: Role of CLEC4D in inflammation-driven liver carcinogenesis
Authors: Riboldi Elena , Tommaso Luca Di , Clemente Nausicaa , Raggi Chiara , Forti Elisa , Merlin Simone , Pasqualini Fabio , Follenzi Antonia , Sica Antonio 
Published: July 2017

Abstract
Hepatocellular carcinoma (HCC) accounts for approximately 90% of all primary liver tumors and is the second most deadly cancer in the world. HCC commonly arises in a chronically damaged liver that contains large amounts of inflammation and fibrosis. Indeed, interactions among hepatocytes, stromal, and inflammatory cells create a complex microenvironment permissive to tumor development. Myeloid cells are crucial players in cancer-related inflammation. From transcriptional profiling of liver myeloid cells, we identified the gene encoding for the C-type lectin receptor CLEC4D as one of the genes upregulated during the inflammatory response that precedes cancer development in a spontaneous model of murine HCC. We hypothesized that CLEC4D may be involved in the molecular mechanisms that drive HCC pathogenesis. We used the murine model of diethylnitrosamine (DEN)-induced liver carcinogenesis and evaluated tumor growth in genetically modified mice lacking CLEC4D (CLEC4D KO mice), as compared to C57BL/6 wild type (WT) mice. We observed that tumor burden (number of tumors per mouse and tumor dimensions) was reduced in CLEC4D KO mice compared to WT mice. Gene expression analysis of tumor lesions showed that the tumor microenvironment of CLEC4D KO mice was less inflammatory. CLEC4D expression was then evaluated in surgical specimens and tissue microarrays from HCV+ HCC patients. CLEC4D-positive inflammatory cells (macrophages and granulocytes) were present both in the peritumor and in the tumor areas. The percentage of intratumor CLEC4D-positive cells inversely correlated with the degree of the lesion: CLEC4D expression was higher in dysplastic nodules compared to high grade HCCs. Our results indicate that the CLEC4D-dependent pathway contributes to the initiation and the progression of HCC. By targeting CLEC4D, we could modulate immune responses and provide an environment less favorable to tumor growth. An intervention at this level could represent a chemopreventive strategy to arrest the development of HCC in a cirrhotic liver.This work has been supported by Fondazione Cariplo, grant n° 2014-0962.
Citation Format: Elena Riboldi, Luca Di Tommaso, Nausicaa Clemente, Chiara Raggi, Elisa Forti, Simone Merlin, Fabio Pasqualini, Antonia Follenzi, Antonio Sica. Role of CLEC4D in inflammation-driven liver carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2677. doi:10.1158/1538-7445.AM2017-2677
Abstract 2678: Novel host-pathogen interactions of Helicobacter pylori and their implications to gastric cancer
Authors: Maiorov Emine Guven , Nussinov Ruth , Tsai Chung-Jung 
Published: July 2017

Abstract
About 20% of the cancer incidences worldwide have been estimated to be associated with infections. There is a strong correlation of some pathogens with various cancer types. Although presence of commensal microbiome helps chemotherapy to be more effective, pathogenic microbiota increases the cancer risk. Invading pathogens interact with the host mainly through proteins. To subvert host defense, pathogens hijack host pathways by mimicking the binding surfaces (interfaces) of host proteins. This similarity in interfaces permits the pathogenic protein to compete with host proteins to bind to a target protein, alter the physiological signaling and cause persistent infections as well as cancer. Detection of host-pathogen interactions (HPIs) and mapping the re-wired HPI network - along with its structural details - is critical for in-depth understanding of the underlying pathogenesis mechanisms of infections and pathogen-triggered cancers, and developing efficient therapeutics. Here, we developed a novel computational approach to identify novel HPIs by employing “interface mimicry”, We applied this approach to Helicobacter pylori, dominant species in gastric microbiome that greatly increases the gastric cancer risk in order to understand how they modulate host immunity and lead to tumorigenesis. We found that its proteins interfere with the functioning of host apoptosis pathway, cytokine and chemokine pathways, and also cell-cell adhesions. Our results shed light on the molecular mechanisms of resistance to apoptosis, immune evasion and loss of cell junctions that are seen in Helicobacter pylori-infected host cells. In conclusion, HPIs can help us unravel which human pathways are targeted by the pathogenic proteins and how they contribute to pathogenesis of infections and pathogen-triggered cancer. With a better grasp on immunomodulatory strategies of pathogens, we can develop better therapies against them.
Citation Format: Emine Guven Maiorov, Ruth Nussinov, Chung-Jung Tsai. Novel host-pathogen interactions of Helicobacter pylori and their implications to gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2678. doi:10.1158/1538-7445.AM2017-2678
Abstract 2683: The gastrointestinal microbiome and its composition are critical for antitumor efficacy of immune checkpoint inhibition by anti-PD-L1
Authors: Cuiffo Benjamin G. , Parello Caitlin S. , Ritchie Chelsea , Pedrick Katie , Kury Alexandra , Costa Catarina , Dam Brett Van , Jung Jonathan , Lyng Gregory D. , Sonis Stephen T. 
Published: July 2017

Abstract
The intestinal microbiome has become increasingly appreciated as a significant mediator of systemic antitumor immunity/response in both naïve and treatment contexts. In naïve contexts, an intact intestinal microbiome has been demonstrated to enhance tumorigenesis, and its composition to mediate primary tumor growth kinetics. In the context of cancer treatment, antibiotic depletion of the intestinal microbiota has been reported to inhibit the efficacy of cyclophosphamide and that of the immune checkpoint inhibitor αCTLA4. Compositional modulation of the intestinal microbiota has been found to be sufficient to enhance the antitumor efficacy of αPD-L1. Here, we assessed the relative importance of the intestinal microbiota in mediating αPD-L1 antitumor efficacy in a B16.F10.SIY murine model of melanoma, by performing parallel efficacy studies in C57BL/6 germ-free (Taconic) or specific pathogen free (Taconic or Jackson) mice. We observed that αPD-L1 treatment provided significant antitumor efficacy of in Taconic mice carrying an intact microbiome; however, this efficacy was abolished in germ-free Taconic mice. Furthermore, we observed that tumors of Jackson mice carrying an intact but compositionally different microbiome did not respond to αPD-L1 treatment. Phenotyping of local tumor and systemic immune responses, as well as characterization of the intestinal microbiome in responder vs nonresponder animals provided mechanistic insights. Taken together, these observations suggest that rational modulation of the microbiome may enhance response to immune checkpoint inhibition, and indicate that the gastrointestinal microbiome and its composition are critical for the antitumor efficacy of αPD-L1.
Citation Format: Benjamin G. Cuiffo, Caitlin S. Parello, Chelsea Ritchie, Katie Pedrick, Alexandra Kury, Catarina Costa, Brett Van Dam, Jonathan Jung, Gregory D. Lyng, Stephen T. Sonis. The gastrointestinal microbiome and its composition are critical for antitumor efficacy of immune checkpoint inhibition by anti-PD-L1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2683. doi:10.1158/1538-7445.AM2017-2683
Abstract 2684: Multiplex immunofluorescence profiling of tumor infiltrating immune subsets in HNSCC biopsies provides a powerful tool when combined with patient outcome data
Authors: Levin Matt , Lingen Mark , Schwartz David , Snyder Helen 
Published: July 2017

Abstract
Head and neck squamous cell carcinoma (HNSCC) is one of the growing number of tumors for which an anti-tumor immune response is implicated to play a role in the course of the disease. Profiling of the tumor microenvironment including specific infiltrating lymphocyte subsets, antigen presenting cells, expression of regulatory molecules on both tumor and immune cells and spatial relationships between cells could lead to predictive signatures for responsiveness to both conventional and immune modulatory therapies. While flow cytometry results in multi-parametric analysis of immune populations within the tumor, their context i.e. the spatial relationship of these cells to tumor and to other immune cells, is lost. In this current study we use Cell IDx’s novel UltraPlex technology, which is based on a simple two-step, autostainer compatible protocol using hapten labeled primary antibody cocktails followed by fluor labeled anti-hapten secondary cocktails to simultaneously detect 4 cellular markers on the same cell in tumor biopsies. Image registration of serial sections increases multiplexing to 12-16 markers. This technology, which allows generation of full immune subset profiling, quantitative marker expression and relative cellular localization, was applied to a HNSCC tumor microarray as a test system. Data are presented showing the potential of this technology for correlation of tumor “immune signature” with patient outcome.
Citation Format: Matt Levin, Mark Lingen, David Schwartz, Helen Snyder. Multiplex immunofluorescence profiling of tumor infiltrating immune subsets in HNSCC biopsies provides a powerful tool when combined with patient outcome data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2684. doi:10.1158/1538-7445.AM2017-2684
Abstract 2692: Inflammatory patterns exhibited by African American colon tumor-derived cell lines
Authors: Sanchez Jenny E. Paredes , Ji Ping , Munoz-Sagastibelza Maria , Martello-Rooney Laura , Williams Jennie 
Published: July 2017

Abstract
Despite progress in closing the gap, health disparities still persist among African American (AA) colon cancer patients both in incidence and death rates. Previous studies from our group reported that colon tumors from AAs displayed hypermethylation of DNA regions in inflammatory genes such as NELL1, GDF1, ARHGEF4, and ITGA4 when compared to Caucasian Americans (CA). To assess potential differences in the inflammatory response, we utilized two AA colon cancer cell lines generated in our laboratory and compared them with the commercially available CAs colon cancer cell lines, Caco-2 and HT-29. Recent experiments by our group with the anti-inflammatory drugs Ibuprofen, Sulindac and Aspirin, showed significantly higher IC50 values in proliferation assays for AA cell lines compared to CA cell lines. Therefore, we evaluated the anti-inflammatory effects of these drugs by determining secretion of inflammatory cytokines and MAPKs activation in response to the pro-inflammatory cytokine TNF-alpha. The same parameters were tested for the anti-inflammatory cytokine IL-10. As hypothesized, our results in the CA cell lines demonstrated down-regulation of MAPKs activation in response to TNF-alpha after pre-treatment with Ibuprofen. On the contrary, Ibuprofen concentrations as high as the IC50 values for the CA cell lines were not able to induce down-regulation of MAPKs in the AA cell lines. Interestingly, IL-10 treatment was more effective in the AA compared to the CA cell lines, suggesting that the main anti-inflammatory cytokine of the colon will be more effective in controlling inflammation in AA colon tumors. Further studies are needed to elucidate the major differences in inflammatory responses between AA and CA colon cancer cell lines and their potential role in CRC health disparities. As it has been documented that AA colon cancer patients are less responsive to the chemotherapeutics Fluorouracil and Capecitabine, in future studies we will evaluate the effect of these therapeutic agents on AA and CA cell lines in terms of inflammation, cell viability, apoptosis and invasion.
Citation Format: Jenny E. Paredes Sanchez, Ping Ji, Maria Munoz-Sagastibelza, Laura Martello-Rooney, Jennie Williams. Inflammatory patterns exhibited by African American colon tumor-derived cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2692. doi:10.1158/1538-7445.AM2017-2692
Abstract 2693: Inflammatory signalling in the colon tumour microenvironment enhances stromal cell mediated suppression of anti-tumour immune responses
Authors: O'Malley Grace , Lynch Kevin , Naicker Serika , Lohan Paul , Rigalou Athina , Ritter Thomas , Egan Laurence J. , Ryan Aideen E. 
Published: July 2017

Abstract
The colon tumour microenvironment (TME) comprises many cell types including endothelial cells, stromal cells and immune cells. Recent evidence suggests that high tumour stromal cell density correlates with a poor prognosis for colon cancer patients. The majority of these stromal cells are of mesenchymal origin (MSCs) and are known contributors to tumour angiogenesis and invasiveness. Little is known about the role of their immunosuppressive potential in the colon TME. We investigated the molecular regulation of the induced immunosuppressive, tumour-promoting phenotype of tumour-associated MSCs, and the effect of inflammation on this process. Balb/c bone marrow derived MSCs were treated with conditioned medium from untreated CT26 tumour cells (MSCTCM) or TNF-α treated CT26 cells (MSCTNF-TCM). Cell surface analysis of MSCs after 72h revealed an increased expression of TCR ligands MHC-I, MHC-II and PD-L1 compared to MSCControl. This was further potentiated by TNF-α induced tumour cell inflammation. MSCTCM co-cultured with syngeneic activated T cells displayed an enhanced ability to suppress CD8+ T cell proliferation, which was further potentiated by inflammatory activation of CT26 (MSCTNF-TCM). This effect was dependent on induced PD-L1 expression on MSCs as PD-1 blockade restored CD8+ T cell proliferation, activation and granzyme B secretion. In an immunocompetent Balb/c syngeneic model, we assessed tumour growth and anti-tumour immune responses following sub-cutaneous injection of CT26 cells alone or co-injection with MSCControl/MSCTNF-TCM. Co-injection of MSCControl significantly promoted tumour growth, and this was further potentiated by the co-injection of MSCTNF-TCM. This effect was associated with significantly reduced tumour infiltration of CD8 Granzyme B secreting T cells. We showed that this stromal cell mediated tumour promotion could be reversed by administration of a PD-1 blocking antibody, via restoration of granzyme B secreting CD8+ T cells. We show for the first time that stromal cells in the inflammatory TME directly modulate anti-tumour immune responses via PD-L1. This data could lead to better stratification of patients for immunotherapeutic regimens resulting in more targeted and durable responses to overcome stromal mediated tumour immunosuppression in colon cancer.
Citation Format: Grace O'Malley, Kevin Lynch, Serika Naicker, Paul Lohan, Athina Rigalou, Thomas Ritter, Laurence J. Egan, Aideen E. Ryan. Inflammatory signalling in the colon tumour microenvironment enhances stromal cell mediated suppression of anti-tumour immune responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2693. doi:10.1158/1538-7445.AM2017-2693
Abstract 270: Trends in colorectal cancer survival in Arab World, 1990-2009
Authors: Zaidi Zoubida , Cherif Mokhtar Hamdi 
Published: July 2017

Abstract
Introduction: Cancer survival is a key measure of the effectiveness of health-care systems. Globally, colon and rectum cancer ranked third for cancer incidence and fourth for cancer death in 2013. For developed countries it ranked second for incidence and mortality, and in developing countries it ranked fourth for both incidence and mortality. An increasing trend in incidence is reported from various registries of Arab world, Kuwait and Saudi Arabia present the highest incidences worldwide.
Objective: To describe the trends of the survival of colorectal cancer patients diagnosed in Arab countries.
Material and Methods: This report is a summary of the two survival figures of CONCORD study 1 (1990-1994) and CONCORD study 2 (1995-2009). Individual colon and rectum tumour records were submitted by 06 population-based cancer registries in Arab countries (Jordan, Saoudi Arabia, Qatar, Algeria, Lybia and Tunisia) for 9050 patients (15-99 years) diagnosed during 1990-2009 and followed up to 31 December 2009 . Estimated five-year net survival, adjusted for background mortality by single year of age, sex, calendar year in each country.
Results : For patients diagnosed during the period 2005-2009, the age-standardized five-years net survivals were respectively higher 68,2% for colon cancer and 77,8% for rectum cancer in Qatar and the lowest rate for rectal cancer 21% in Jordan, between 1995-1999 and 2005-2009, Survival increased in Algeria, but this trend is less reliable
Conclusions: Comparison of population-based cancer survival CONCORD study showed very wide variations in survival from colorectal cancer in Arab world. Cancer survival research is being used to formulate cancer control and the need to implement effective strategies of primary prevention.
Note: This abstract was not presented at the meeting.
Citation Format: Zoubida Zaidi, Mokhtar Hamdi Cherif. Trends in colorectal cancer survival in Arab World, 1990-2009 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 270. doi:10.1158/1538-7445.AM2017-270
Abstract 2700: Intestinal Vitamin D receptor deficiency increases susceptibility for the DSS-induced colon disease
Authors: Kim Jung-Hwan , Yamaori Satoshi , Gonzalez Frank J. 
Published: July 2017

Abstract
To investigate the function of the intestinal Vdr gene in inflammatory bowel disease (IBD), in conjunction with the discovery of possible metabolic markers for IBD using intestine-specific Vdr knockout mice. VdrΔIEpC mice were generated, phenotyped and treated with a time-course of 3% dextran sulfate sodium (DSS) to induce colitis. Colitis was diagnosed by evaluating clinical symptoms and intestinal histopathology. Gene expression analysis was carried out. In addition, metabolic markers of IBD were explored by metabolomics. VdrΔIEpC mice showed abnormal body size, colon structures and feces color. Calcium, collagen, and intestinal proliferation-related gene expression were all decreased, and serum alkaline phosphatase was highly increased. In the acute model which was treated with 3% DSS for six days, VdrΔIEpC mice showed a high score of IBD symptoms; enlarged mucosal layer and damaged muscularis layer. In the recovery experiment model, where mice were treated with 3% DSS for four days and water for three days, VdrΔIEpC mice showed a high score of IBD symptoms; severe damage of mucosal layer and increased expression of genes encoding proinflammatory cytokines. Feces metabolomics revealed decreased concentrations of taurine, taurocholic acid, taurodeoxycholic acid and cholic acid in Vdr ΔIEpC mice. In conclusion, disruption of the intestinal Vdr gene showed phenotypical changes. These factors combined may exacerbate IBD. Taken together, the results suggest that VDR may play an important role in IBD.
Citation Format: Jung-Hwan Kim, Satoshi Yamaori, Frank J. Gonzalez. Intestinal Vitamin D receptor deficiency increases susceptibility for the DSS-induced colon disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2700. doi:10.1158/1538-7445.AM2017-2700