bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5109: MDM2 regulates intracellular pathways in TNBC and osteosarcoma that affect osteoclastogenesis
Authors: Olivos David J. , Mayo Lindsey D. 
Published: July 2016

Abstract
Advanced cancer cells infiltrate and colonize new organ microenvironments through transformation of the dynamic metastatic niche. In bone, tumor cells secrete soluble factors that distort and manipulate normal bone remodeling leading to osteolytic lesions and inflammation. Clinically, primary high-grade bone sarcomas and secondary metastatic cancers exhibit elevated levels of murine double minute 2 (Mdm2), the principal cellular antagonist and E3 ubiquitin ligase of tumor suppressor p53. We demonstrate a novel function of mdm2, independent of p53, to drive osteolytic disease influenced by the signaling cascade of RANKL, ICAM1, and RANTES. To elucidate the direct influence of Mdm2 in cancer cells on osteoclast differentiation, several cell lines were created to overexpress or silence Mdm2. We found that osteoblast-like osteosarcoma (MG63, Saos2) and metastatic breast cancer cell lines (MDA468, MDA231, TMD-231, T47D, and BT474) lead to significant increased osteoclast differentiation, proliferation, and bone resorption. Co-cultures of Mdm2 over-expressing cancers and normal monocytes resulted in increased numbers of osteoclasts. In cancer cell lines where Mdm2 is silenced, we observed lower number of osteoclasts. The presence of Mdm2 in cancer cells also increased osteoclast resorption in an in vitro organ model. To determine the effects of ICAM1, we used an ICAM antibody to block ICAM1 in the media and showed a decrease in osteoclastogenesis. Understanding the role of Mdm2 in osteoclastogenesis may be amendable to translational benefit in disease models of advanced bone resorption and bone metastases.
Citation Format: David J. Olivos, Lindsey D. Mayo. MDM2 regulates intracellular pathways in TNBC and osteosarcoma that affect osteoclastogenesis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5109.
Abstract 5114: The role of microvesicles on immune function in response to cancer
Authors: Jaiswal Ritu , Pokharel Deep , Bebawy Mary 
Published: July 2016

Abstract
Cell to cell communication is vital for the co-ordination of physiological process and the regulation of an organism's phenotype. More recently communication via extracellular membrane vesicles has gained recognition. We first described a novel mechanism for the spread and dominance of multidrug resistance (MDR) and enhanced metastatic capacity in cancer via submicron microparticles (MPs). MPs are plasma membrane vesicles released spontaneously from various cell types, carrying bioactive material and are implicated in different physiological and pathophysiological processes. Through this communication apparatus, cancer cells can acquire and secure a survival advantage by various mechanisms. This study aims to examine a role of MPs in altering immune cell function in cancer.
The effects of MPs isolated from human breast cancer cells were examined on antigen presenting cells (APC) in vitro. MP-mediated effects on cell phenotype and functionality was assessed by cytokine profiling and migration assay. We observed a cancer cell induced change in immune cell phenotype and functionality which have the potential to support a reduced global immune response in cancer. The elucidation of this pathway provides novel therapeutic strategies which can be exploited for the treatment of cancer.
Citation Format: Ritu Jaiswal, Deep Pokharel, Mary Bebawy. The role of microvesicles on immune function in response to cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5114.
Abstract 512: KRAS mutation in cell-free DNA was correlated with treatment response to gemcitabine/cisplatin chemotherapy in patients with pancreatic cancer
Authors: Kim Min Kyeong , Kyong-Ah Yoon , Sang Myung Woo , Yun Hee Kim , Sang Jae Park , Sun-Young Kong 
Published: July 2016

Abstract
Cell-free DNA (cfDNA) of cancer patients has been known to be a useful marker for minimal residual disease detection and treatment monitoring. However, there are a few studies which showed correlation of cfDNA with pancreatic cancer treatment. Here we investigated applicability of cfDNA as a response and prognosis biomarker through comparing the qualitative and quantitative changes of the KRAS mutant in the patients with pancreatic cancer before and after treatment.
Total of 44 pancreatic cancer patients who treated by gemcitabine and cisplatin included in the study. Serum from the blood samples was separated by centrifugation through the method established. cfDNA was extracted through the QIAamp Circulating Nucleic Acid Kit (Qiagen, Germany) from 0.8 ml of serum. Extracted cfDNA was quantified using the Qubit dsDNA HS Assay Kit (Thermo Fisher Scientific, USA). QX200 Droplet Digital PCR System (Biorad, USA) was applied to measure frequency of KRAS mutation. We performed digital PCR with KRAS screening multiplex droplet digital PCR kit which covers G12A, G12C, G12D, G12R, G12S, G12V and G13D sites (Biorad, USA). Mutant concentration and fractional abundance were analyzed by QuantaSoft software (Biorad, USA).
The positive rate of KRAS mutation was 61% (27/44) and 47% (16/34) in before and after treatment. When we analyzed the treatment response according to the positive presence of KRAS mutation before treatment, 50% and 61% of KRAS mutations were observed in patients who showed either partial response (PR) or stable disease (SD) after chemotherapy, respectively. However, all the 5 patients (100%) with progressive disease (PD) showed KRAS mutation implicating significant correlation (p = 0.046) with treatment response.
The fraction change of KRAS mutation was showed decrease in 18 (58.1%) patients and increase in 13 (41.9%) patients comparing before and after treatment status. When we observed the association the fraction change direction (decrease vs. increase) with the survival, there was no significant difference.
These results implicate that KRAS mutation in cell-free DNA might be associated with treatment response to gemcitabine/cisplatin chemotherapy. In further studies, we will conduct in prospective study for pancreatic cancer patients. (This study was supported by National cancer center, Korea, Grant no. 1510203-1)
Citation Format: Min Kyeong Kim, Yoon Kyong-Ah, Woo Sang Myung, Kim Yun Hee, Park Sang Jae, Kong Sun-Young. KRAS mutation in cell-free DNA was correlated with treatment response to gemcitabine/cisplatin chemotherapy in patients with pancreatic cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 512.
Abstract 5121: Immunomodulating cytokine profiling of docetaxel-treated human prostate cancer specimens
Authors: Mehrotra Debapriya G. , Brijwani Nilesh , Tewary Biplab , Sekar Vasathkumar , Krishnan Abhishek , Pinto Dency D. , Oliyarasi Muthusamy , Majumder Biswanath , Thiyagarajan Saravanan , Radhakrishnan Padhma , Majumder Pradip K. 
Published: July 2016

Abstract
Prostate cancer is one of the leading malignancies in adult males worldwide and existing therapies often result in treatment failure and emergence of castration resistant prostate cancer (CRPC). Outcome of some recent clinical trials highlighted the benefit of Docetaxel as a part of initial therapy in CRPC. However, a significant number of patients still remain chemoresistant. Context dependent response profiling using a clinically oriented functional platform would further improve this scenario. Here, we elucidated the role of different immune cells and type 1 and type 2 cytokines in improving Docetaxel sensitivity to prostatic carcinoma. We tested Docetaxel sensitivity in prostate tumors (n = 10) using CANScriptTM platform, a personalized next generation functional testing tool (Majumder B et al. Nat. Commun 2015, Goldman A et al. Nat. Commun. 2015). Of these 10 tumors, 4 were found to be sensitive to Docetaxel and 6 were insensitive. The immune profiling of these tumors suggested that despite preferential CD45, CD8 and CD4 levels in majority of the responders both responders and non responders display modest numbers at baseline. We also observed similar heterogeneity in CD69 (T cell activation marker) in these two groups. Altered expression of cytokines was observed in Docetaxel sensitive and resistant tumors upon their co-culture with peripheral blood mononuclear cells (PBMC), suggesting a defined role of these cytokines in Docetaxel response. We extended the study further by testing the efficacy of PD-1/ PD-L1 inhibitors in Docetaxel resistant tumors. Our results provide the basis for validation of immune phenotypes and cytokines as therapeutic response biomarkers in Docetaxel treated prostatic tumors.
1. Majumder B et al. Nat. Commun.6:6169 (2015).
2. Goldman A et al. Nat. Commun. 6:6139 (2015).
Citation Format: Debapriya G. Mehrotra, Nilesh Brijwani, Biplab Tewary, Vasathkumar Sekar, Abhishek Krishnan, Dency D. Pinto, Muthusamy Oliyarasi, Biswanath Majumder, Saravanan Thiyagarajan, Padhma Radhakrishnan, Pradip K. Majumder. Immunomodulating cytokine profiling of docetaxel-treated human prostate cancer specimens. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5121.
Abstract 5125: Immunomodulatory activity of bitter melon extract in head and neck squamous cell carcinoma
Authors: Bhattacharya Sourav , Steele Robert , Muhammad Naoshad , Peng Guangyong , Ray Ratna B. 
Published: July 2016

Abstract
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer and leading cause of cancer related mortality worldwide. Despite the advancement in treatment procedures the overall survival rate of patients has not considerably enhanced in the past few decades. Therefore, new strategies to achieve a favorable response for the improvement in the prognosis of HNSCC are urgently needed. In this study we examined the immune modulatory activity of bitter melon extract (BME) in HNSCC tumor microenvironment. For this, mouse head and neck cancer (SCCVII) cells were subcutaneously injected into the flanks of C3H mice. BME was fed orally, and tumor growth was evaluated. We observed that BME treatment significantly inhibits the tumor growth in BME fed mice as compared to control group. Flow cytometry data showed that BME treatment not only decreases the infiltrating T regulatory (Treg) cells in the tumor but also in splenocytes. Additionally, BME treatment reduces Th17 cell population in the tumor and augments in the spleen. However, BME treatment did not alter Th1 and Th2 populations. Further study suggested that BME inhibits cell proliferation as evident from low expression of PCNA and c-Myc in the tumors of BME fed mice as compared to that of control group. To our knowledge, this is the first report showing BME exerts immunomodulatory effect in regressing HNSCC tumor growth in preclinical model.
Citation Format: Sourav Bhattacharya, Robert Steele, Naoshad Muhammad, Guangyong Peng, Ratna B. Ray. Immunomodulatory activity of bitter melon extract in head and neck squamous cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5125.
Abstract 5128: Characterization of tumor immune microenvironment in response to PD-L1 therapy initiated at different time points post inoculation in syngeneic mouse models
Authors: Sharma Geeta , Wu Susan , Mihalek Robert , Fiore Ann , Gale Matthew , Dias Christa , Grant Wendy , Hernandez Nidia 
Published: July 2016

Abstract
The tumor microenvironment is an important aspect of cancer biology that contributes to tumor initiation, progression and responses to therapy. Cells and molecules of the immune system are fundamental components of the tumor microenvironment which have been known to vary widely and are important in determining the anti-tumor immune response. The approval of immune checkpoint inhibitors like PD-1 and CTLA-4 antibodies has resulted in a lot of research activity in immune-oncology. Syngeneic mouse models have been utilized to understand the preclinical immune response as a surrogate to the clinical response. The timing of immune checkpoint inhibitor dosing is supposed to play an important role on the tumor growth in mouse models. In order to understand the correlation of tumor regression, survival and immune response in a preclinical mouse model, we evaluated the effect of different times of treatment initiation with Program Death Ligand-1 (PD-L1) on tumor volume, survival and tumor infiltrating leukocytes (TIL’s). Various dosing regimens evaluated included initiation of PD-L1 therapy on the day of inoculation, 6 and 12 days post inoculation. Tumors were collected from three different syngeneic mouse models (CT26, RENCA and B16F10) and profiled for the presence of tumor infiltrating leukocytes (TIL’s) using flow cytometry. Major sub-population of TIL's examined included T-regulatory cells (Treg’s), Tumor Associated Macrophages (TAM’s) and Myeloid Derived Suppressor Cells (MDSC’s). Finally, an attempt was made to identify any correlation or lack thereof between tumor growth and tumor immune microenvironment.
Citation Format: Geeta Sharma, Susan Wu, Robert Mihalek, Ann Fiore, Matthew Gale, Christa Dias, Wendy Grant, Nidia Hernandez. Characterization of tumor immune microenvironment in response to PD-L1 therapy initiated at different time points post inoculation in syngeneic mouse models. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5128.
Abstract 5139: Adjuvant immunotherapy targeting CSF1R to limit metastatic progression
Authors: Evans Justin , Giles Amber J. , Murgai Meera , Kasai Miki , Reid Caitlin , Kaplan Rosandra Natasha 
Published: July 2016

Abstract
Metastasis is often considered a late stage event, although the first changes in the metastatic site occur very early during localized primary tumor development. Although understanding of these initiating events is limited, immune suppression plays an essential role in allowing for the outgrowth of disseminating tumor cells. Targeting this immune suppressive milieu can hold promise to effectively inhibit metastatic progression. Colony stimulating factor-one (CSF-1) is overexpressed by many diverse tumor types and can induce expansion and recruitment of CSF-1 receptor (CSF-1R) expressing cells. CSF-1R is expressed on a multitude of myeloid cells including inflammatory monocytes, myeloid derived suppressor cells and macrophages, which are key immune suppressive cells in a primary tumor site. Using a metastatic rhabdomyosarcoma model, we have identified expansion of immune suppressive myeloid cells in the early metastatic microenvironment. PLX3397, which is small molecular inhibitor that selectively targets CSF-1R, Kit and Oncogenic FLT3, was used to determine the impact of targeting this immune suppressive microenvironment in limiting metastatic progression. PLX3397 and GW2580, a selective CSF1R inhibitor, reduce the immune suppressive capacity of bone marrow-derived monocytes on activated T cells. Adjuvant therapy with PLX3397 in resected rhabdomyosarcoma reduces metastatic spread. Targeting CSF-1R is associated with an expansion of CD11C expressing antigen presenting cells in the metastatic tissue and in combination with PD-1 blockade improves anti-tumor immunity. Continued investigation of combination immunotherapy with metastatic microenvironment targeting in the adjuvant setting holds promise to limit metastatic spread.
Citation Format: Justin Evans, Amber J. Giles, Meera Murgai, Miki Kasai, Caitlin Reid, Rosandra Natasha Kaplan. Adjuvant immunotherapy targeting CSF1R to limit metastatic progression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5139.
Abstract 5141: Determinants of metastatic competence in breast carcinoma: a role for immune cells
Authors: Joseph Robiya , Soundararajan Rama , Paranjape Anurag , Mani Sendurai 
Published: July 2016

Abstract
Dynamic interactions between cancer cells and their surrounding microenvironment influence tumor survival, growth and metastasis. The tumor microenvironment harbors a complex variety of cells including T lymphocytes and macrophages that produce a host of cytokines, chemokines, growth factors or interleukins, all of which presumably work in coordination to determine net tumor biology. Immune cells can offer a critical check-point in tumor progression. Interestingly however, infiltration of the tumor by immune cells appears to have dual functionality - they can reportedly either be pro-metastatic or anti-metastatic in their contribution. These clearly conflicting roles of immune cells limit our comprehension of their actual input to tumor advancement. Tumor infiltrating lymphocytes, in particular, the infiltration by T cells, has emerged as a good prognostic marker for a variety of cancers. However, the key molecular factors that regulate the cross-talk between tumor cells and T lymphocytes, and the underlying signaling pathways are still ill-defined. Moreover, the impact of T lymphocytes of the inflammatory tumor microenvironment, on the epithelial-mesenchymal plasticity and associated metastatic traits in breast cancer cells, is incompletely understood. We previously demonstrated that two key EMT/CSC factors - FOXC2 and Twist - are critical requirements for breast carcinoma cells to metastasize. The objective of the current study is to systematically investigate the role of regulatory T cells in EMT/CSC-dictated breast tumor progression, using two isogenic breast cancer cell lines (67NR and 4T1) that form primary mammary tumors similarly, but differ drastically in their ability to metastasize.
Citation Format: Robiya Joseph, Rama Soundararajan, Anurag Paranjape, Sendurai Mani. Determinants of metastatic competence in breast carcinoma: a role for immune cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5141.
Abstract 5153: Dual inhibition of STAT3 and IL-8 pathways as a novel therapeutic approach in osteosarcoma
Authors: Cao Yang , Xiao Hui , Wu Xiaojuan , Lin Jiayuh 
Published: July 2016

Abstract
Abstract
Objective: Targeting STAT3 signaling represents a potential therapeutic approach to treatment of osteosarcoma. However, the use of STAT3 inhibitor as a single agent may not be effective for cancer therapy. Identify the pathway(s) that may generate synergy in tumor suppression may be more effective in osteosarcoma therapy.
Methods: Inflammatory cytokines IL-6, IL-11, and IL-8 secretion of osteosarcoma after STAT3 inhibition were determined by ELISA assay. The sensitivity to STAT3 inhibitor was examined by cell viability assay. Cell migration and colony forming ability were evaluated when combination treatment.
Results: In this study, we observed that the levels of IL-11 were significantly decreased and IL-6 was slightly decreased by STAT3 inhibitor. Interestingly, IL-8 levels were increased upon STAT3 inhibition. IL-8 was originally discovered as one of the major chemokines associated with the promotion of neutrophil chemotaxis and inflammatory responses. Previous studies have demonstrated that IL-8 contributes to cancer progression through its induction of tumor cell proliferation, survival, migration, and angiogenesis. Knocking down IL-8 expression using RNA interference resulted in enhanced sensitivity to STAT3 inhibitor. ELISA assay showed that MEK inhibitor (AZD6244 or Trametinib) and P38α inhibitor (LY2228820) had the ability to reduce the levels of IL-8 induced by STAT3 inhibition. Combination treatment of STAT3 and with a MEK inhibitor or with a P38α inhibitor showed more effective cytotoxic effect on osteosarcoma cell lines compared to single agent alone. Furthermore, the combination treatment exhibited stronger inhibition of cell migration and colony forming ability than single agent alone.
Conclusion: These results suggest the IL-8 induction as a possible feedback mechanism for resistance to STAT3 inhibitor and suggest that simultaneous inhibition of STAT3 and IL-8 may be a more effective therapeutic approach in osteosarcoma.
Citation Format: Yang Cao, Hui Xiao, Xiaojuan Wu, Jiayuh Lin. Dual inhibition of STAT3 and IL-8 pathways as a novel therapeutic approach in osteosarcoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5153.