United States

Hypoxia, or low oxygen, is a common feature of solid tumors correlating with poor survival in cancer patients. Tumors attempt to re-acquire oxygen by forming new blood vessels from nearby, pre-existing vessels, a process known as angiogenesis. In tumors, angiogenesis is notoriously dysfunctional resulting in leaky, under-perfused blood vessels which cannot adequately deliver oxygen and exacerbates hypoxia. One important immune cell affected by hypoxia is the macrophage. Normally, macrophages activate killer T cells to eliminate cancer and promote new blood vessel formation. However, tumor-associated macrophages (TAMs) suppress the proliferation and activity of killer T cells preventing them from eliminating cancer cells, and TAM overactivation leads to dysfunctional angiogenesis that perpetuates the treatment-resistant, hypoxic tumor environment. Thus, molecular mechanisms in which macrophages respond to hypoxia has been investigated as potential therapeutic targets. Hypoxia stabilizes hypoxia inducible transcription factor HIF-1α. Our previous work suggested HIF-1α prompts a pro-hypoxic phenotype in macrophages. We hypothesize that macrophage HIF-1α affects the recruitment of macrophage precursors, free endothelial cells, and T cells throughout tumor progression. Understanding where these differences occur may provide insight as to when best to start treatment or when treatment is no longer effective. 


2023 AMA Research Challenge

Hypoxia regulates vessel-modifying macrophages and vice versa in solid tumors


poster

Welcome to the **largest national, multi-specialty research** event featuring research from nearly 700 medical students, residents, fellows, and international medical graduates.

Use the buttons below or navigation menu to access the event.
 


[![](https://assets.underline.io/uploads/markdown_image/1/image/3e33a8c754cc49610b30950617d813e7.png)](https://underline.io/events/434/sessions?searchGroup=all)
 
[![](https://assets.underline.io/uploads/markdown_image/1/image/551404d429c4e274f9a54cbdd7081918.png)](https://underline.io/events/434/posters?searchGroup=all)
 
[![](https://assets.underline.io/uploads/markdown_image/1/image/677d92f566b880cebd36905fc738fc10.png)](https://underline.io/events/434/lounge)
 
[![](https://assets.underline.io/uploads/markdown_image/1/image/c7392833c7261c3874c5b43fa2f4df19.png)](https://underline.io/events/434/help-desk)
 

#### Event Details

The 2023 American Medical Association Research Challenge includes a poster symposium hall and a semifinals hall with the top scored research. **Log in at any time throughout the event to:**

* **View posters and presentations** on a variety of topics and specialties
* **Score posters in the semifinals** to help decide the top five finalists (AMA member exclusive opportunity)
* **Connect with participants** and provide feedback to help advance their research
* **Attend education sessions** with physician experts on key research topics

At the conclusion of this event, the AMA will announce the top five finalists who will advance to the AMA Research Challenge finals, present their research to an elite panel of judges, and compete to win a $10,000 grand prize sponsored by Laurel Road. 

### Grand Prize Sponsor

AMA would like to thank Laurel Road for sponsoring a $10,000 grand prize for the winner of the AMA Research Challenge. Laurel Road is not involved in the judging or scoring process to select the winner. The winner will be announced on February 4, 2024 during the AMA Research Challenge finals. Payment of the grand prize will be directly from Laurel Road. See the AMA Research Challenge Official Rules for terms and conditions.

![](https://assets.underline.io/uploads/markdown_image/1/image/611e331d4a0eba0920f240cfc04b4d77.png)

**There is no registration fee for this event! **

Register to explore research in a variety of topics. AMA members get exclusive access to score posters in the semifinals.

**Please use this link [here](https://www.ama-assn.org/about/events/ama-research-challenge) to register for free.**

Registration Is Required

Join the AMA Research Challenge poster symposium and semifinals to explore top research posters, score posters in the semifinals (an AMA member exclusive opportunity) and attend education sessions with experienced physicians to learn tips to advance your research and career. 

Background: Sterile inflammation and constitutive activation of pro-fibrotic cells in the stromal vascular fraction (SVF) of adipose tissue (AT) are hallmarks of obesity. Macrophages and AT progenitors play a key role in the development and progression of this pathology in fat depots. EphB2, a member of the EphB receptors, has been reported to promote hepatic and renal fibrogenesis in mice. The goal of this investigation is to test the hypothesis that defective EphB2 signalling in macrophages could potentially mitigate adipose tissue fibro-inflammation and insulin resistance in obesity. 

Methods: Disease phenotyping was performed in males and females' wild type (WT); EphB2KO (EphB2-/-); leptin-deficient ob/ob mice and in EphB2 specific deletion in macrophages (Cre+). Mice with EphB2-specific deletion in macrophages were generated by crossing EphB2-flox/flox mice with CSF1R-iMer-Cre-iMer & CX3CR1-CreERT2 and phenotype induced with tamoxifen. Mice were fed the obesogenic Gubra-Amylin NASH (GAN) diet for 6-26 weeks. Weight was recorded and glucose tolerance test (GTT) and Insulin tolerance test (ITT) performed. Mice were euthanized at the end of the study via isoflurane anesthesia in nonfasted state; liver tissue, inguinal white adipose tissue (iWAT), brown adipose tissue (BAT), epididymal white adipose tissue (eWAT) and heart were collected and weighed. Histology (H&E, Masson-trichrome and phosphor-EphB2 immunohistochemistry) was performed in iWAT and eWAT. Stromal vascular fraction and adipocyte were isolated from iWAT and eWAT and subjected to flow cytometry, and qPCR. 

Results: EphB2 receptors and EfnB2 ligands mRNA transcripts are upregulated in fat depots and liver of ob/ob mice. H&E staining, and Masson-trichrome staining of iWAT and eWAT, depicting accumulation of immune cells and fibrosis in crown-like structure of these fat depots. Immunohistochemistry of phosphoEphB1/2 shows EphB2 activation in adipose tissue of obese mice in the SVF. EphB2-/- mice displayed a reduced weight and improved glucose tolerance when fed an obesogenic diet compared to EphB2 wild type mice. Deletion of EphB2 in macrophages showed recapitulation of global knockout phenotype and diminished quantity of pro inflammatory M1 macrophages with increased M2 macrophages and polymorphonucleated neutrophils evaluated through flow cytometry. 

Conclusion: EphB/EfnB mRNA transcripts are upregulated in fat depots of obese mice and more specifically in the stromal vascular fraction of iWAT and eWAT. EphB2 signaling is activated in the stromal vascular fraction of eWAT. EphB2 deficiency mitigates weight gain and improves glucose tolerance in DIO mice. Deletion of EphB2 receptor in macrophages reduces weight gain, improves glucose tolerance, and dampens inflammatory response in obese mice producing similar phenotype to that of the global knockout. 


Dysregulation of macrophages EphB2 mitigates diet-induced obesity in mice

Background: Glycans are carbohydrate structures that can be found embedded within glycoproteins or glycolipids. They play an important role in cell membrane structure, cell signaling, and cell adhesions. Abnormal glycan expression caused by genetic mutations or cellular stressors is known in disease states like cancer. Thus, identifying variations of glycan expression in cancer tissue can be useful for diagnosis and staging. Previous research has shown that breast cancer tumor tissue has abnormal high mannose, complex, and hybrid glycan expression when compared to the surrounding unaffected tissue. The goal of our research is to look specifically at which glycans at different stages of breast cancer were abnormally expressed in tumor tissue when compared to the surrounding unaffected tissue.
Methods: Breast tissue tumor samples were collected from 39 breast cancer patients at the time of diagnosis and provided for analysis by the Prisma Health Cancer Institute Biorepository. Breast tissue “controls” were collected via sampling of surrounding unaffected tissue of the same breast cancer patients. Samples were analyzed and glycomic profiles were obtained using MALDI-TOF Mass Spectroscopy by the Emory Glycomics and Molecular Interactions Core. One-way ANOVA statistical analysis was performed using JMP statistical software.
Ó 2023 American Medical Association. All rights reserved.
Results: Significantly elevated expression of a number of glycans from all three groups (high mannose, complex, and hybrid) was detected in stage I breast cancer tumor tissue when compared with the surrounding unaffected breast tissue (p<0.05). In total, we detected 5 high mannose glycans, 19 complex glycans, and 5 hybrid glycans with significantly elevated expression in stage I breast cancer tumor tissue. when compared to the surrounding unaffected tissue.
Conclusion: Our data supports and expands previous research in the area of glycomic profiling of cancers. High mannose glycans have been shown to be elevated in breast and other, and our findings support this data in specifically stage I breast cancer tissue. Elevated expression of complex and hybrid glycans are interesting findings that could be additional promising breast cancer biomarkers for diagnosis, screening, or treatment. Further research into the cellular function of these glycans in cancer could help better understand how cancer progresses and metastasizes.

Elevated glycan expression in stage I breast cancer tumors

Background: Cancer is a leading health concern and the second highest cause of death in the United States. When considering cancer from a genomic standpoint, genes can be divided into two main categories. One category includes oncogenes, which, when mutated, develop a gain of function. The second category consists of tumor suppressor genes, which in mutated state lose their ability to protect the cell. Both oncogenes and tumor suppressor genes are known as cancer-critical genes. This analysis evaluates 50 cancer-critical genes for presence of hotspot mutations affecting various signaling pathways. Specifically, we focused on nine pathways: RTK/RAS/MAP, TGFβ, PI3K, Wnt, GPCR, p53, JAK/STAT, Notch, and the cell cycle pathway. Our study aims to enhance understanding of the impact of hotspot mutations in these 50 cancer-critical genes. Additionally, the study will aim in integration of artificial intelligence (AI) to predict personalized treatments based on the identified mutations.

Methods: We conducted an analysis of previously identified mutations in 35 breast cancer patients and 39 lung cancer patients from the Prisma Health Cancer Institute. We utilized genomic databases, including ClinVar, to gather available information and published literature about these mutations. We analyzed and recorded characteristics of each mutation, including predicted changes in protein folding, clinical significance and associated pathological conditions, possible variations, and affected signaling pathways.

Results: Among the 50 cancer-critical genes previously sequenced for hotspot mutations, we identified a total of 79 different hotspot mutations in the studied group of 74 cancer patients. Notably, for 9 of these mutations we did not find any available information. Furthermore, one mutation (KDR p.Gln472His) exhibited a very high prevalence among cancer patients. We suggest further investigation of this group of mutations for potential clinical significance.

Conclusion: The identified unknown mutations in cancer-critical genes may have clinical significance and require further investigation. The information collected in this study will contribute to the development of a comprehensive cancer patient database accessible to clinicians and researchers. Moreover, the data will be further utilized in AI applications to predict personalized treatment approaches for cancer patients.


Improving Diagnosis and Prognosis: Analysis of Gene Mutations in Breast and Lung Cancer Patients

**Scoring is only possible in the semifinals hall**

**Abstract:**



The Impact of the Tumor Microbiome on Anti-tumor Immunity in Mucosal Melanoma

Background 
Cancer-induced cachexia is a complex multifactorial syndrome characterized by loss of muscle mass and function that affects up to 80% of cancer patients which contributes to the morbidity and mortality of the disease. Despite the extensive research on cancer cachexia, its exact etiology remains unknown. There is also no consensus on effective treatment for the loss of muscle mass, which subsequently impacts the tolerance and response to anti-cancer therapies. Furthermore, little is known about the effect of muscle wasting on the neuromuscular junction (NMJ), the vital synaptic connection between the motor neuron and skeletal muscle. The primary purpose of this study is to analyze the stability of the NMJs from cachectic muscles during the initiation and progression of the muscle-wasting event. To this end, we use the genetically engineered mouse model of colorectal cancer (Apc) Min/+ that has shown tumor growth and cachexia. 

Methods 
Sternomastoid, gastrocnemius, extensor digitorum longus, soleus, and diaphragm muscles were extracted from (Apc) Min/+ and age-matched controls at 16 and 24 weeks of age. The muscles were then fixed in 4% paraformaldehyde and bathed with Alexa488™ alpha-bungarotoxin to specifically label nicotinic acetylcholine receptors (nAChRs) at the postsynaptic junctional folds. Fluorescently labeled muscles were then imaged at the confocal microscope to analyze the synapse morphology, or with an inverted fluorescence microscope to quantify fluorescence intensity. The area and the density of nAChRs were then analyzed using ImageJ. To capture relevant changes in the NMJs, we performed in vivo experiments to determine the turnover rate of nAChRs at the synapse before severe weight loss occurred. To this end, we labeled sternomastoid muscles in vivo and assessed fluorescence intensity decay over time. 

Results 
At early stages of cancer-induced cachexia (16 weeks), all muscles except sternomastoid showed a significant decrease in nAChRs density in (APC) Min/+ mice compared to controls. In advanced stages of cachexia (24 weeks), all muscles from (APC) Min/+ mice showed a significant decrease in nAChRs density. All muscles showed a significant decline in the total NMJ area in (APC) Min/+ at 16 weeks and 24 weeks. 

Conclusion 
The decreased nAChR density and NMJ area in both fast and slow twitch muscles demonstrates postsynaptic NMJ alteration in cancer-induced cachectic mice. Analysis of presynaptic cells (motor neuron and Schwann cell) will be performed to further look at the pathology of the NMJ in cancer-induced cachexia, as well as younger mice to determine when the degeneration starts. 


The Impact of Cancer-induced Cachexia on the Neuromuscular Synapse

Background
Chimeric antigen receptor (CAR) T cells have shown remarkable clinical efficacy in hematological cancers but still face significant obstacles in the treatment of solid tumors, such as pancreatic ductal adenocarcinoma (PDAC). Two major hurdles in developing effective CAR T therapies for PDAC are the identification of tumor-associated antigens (TAA) and overcoming a complex immunosuppressive tumor microenvironment (TME). We hypothesize that the optimal CAR T cell to treat PDAC recognizes an ideal TAA and protects itself from TME immunosuppression. We propose a novel CAR T cell to target the Muc16-ectodomain (Muc16CD) combined with antagonism of the vasoactive intestinal peptide (VIP) checkpoint pathway in the PDAC TME as a viable therapy to treat pancreatic tumors. 

Methods
Patient data was assessed based upon data generated by the TCGA Research Network. Primary human T cells were retrovirally transduced to express Muc16CD-directed CARs with or without secretion of VIPR antagonists. PDAC PDX tumors and CAR T cells assayed by flow cytometry for phenotype and functional profile. In vivo, Panc1-Muc16CD-GFPffLuc tumors were engrafted into SCID/Beige mice and treated with CAR T cells.

Results
Muc16 expression is significantly increased in PDAC patient tissues compared to normal pancreas and associated with decreased overall survival. Congruently, we found that PDAC PDX tumors demonstrate robust expression of both Muc16CD and VIP and are vulnerable to Muc16CD-directed CAR T cell cytotoxicity. Additionally, VIP limits the proliferative capacity of CAR T cells, which is reversed by VIPR antagonist peptides (antVIPR). Therefore, we engineered anti-Muc16CD CARs to secrete antVIPR peptides to provide continuous and localized delivery within the TME. We find that antVIPR expression by CAR T cells enhances viability, activation profile, and demonstrate less-differentiated and less exhaustive phenotypes. Functionally, antVIPR CAR T cells have enhanced activation and proliferative advantage after chronic antigen-stimulation. In a xenograft model of PDAC, antVIPR CAR T cells reduce tumor burden and improve overall survival in mice bearing human VIP-expressing PDAC tumors. At 118 days, antVIPR CAR T-treated mice have more circulating CAR T cells than parental CAR T-treated mice. 

Conclusion
Muc16CD is a clinically relevant target for CAR T therapy in PDAC. Furthermore, antagonizing the VIP checkpoint pathway in CAR T cells produces enhanced phenotypic and functional profiles. Collectively, this data demonstrates that the combination of targeting Muc16CD and VIP with a novel CAR T cell can improve anti-tumor efficacy against PDAC. The long-term goal of this work is translating antVIPR-secreting CAR T cells for the treatment of PDAC.


Using CAR T Cell-Secreted Antagonistic Peptides to Target Distinct Immune Checkpoint Pathway in Pancreatic Tumors

Background
High-throughput single-cell RNA-seq (scRNA-seq) is used to describe complex tissues by characterizing transcriptional states of individual cells. Defining a cell's position, both in regard to tissue margins and its social context, is essential for understanding the intrinsic and extrinsic variables that effect the transcriptional identity of individual cells. Conventional high-throughput scRNA-seq assays, however, decouple cells from their original locations within tissues. In situ hybridization readouts of gene expression and in situ sequencing preserve spatial information in tissues, but currently have a lower total read threshold than NextGen sequencing – imposing a restriction on either cell throughput or transcriptional breadth. Combining the above methods or using regional barcodes to define 2D positions have spatially-reconstructed tissue regions but are seldom employed in unspecialized laboratories.

Methods
We describe SEgmentation by Exogenous Perfusion (SEEP), a rapid, integrated, method for providing 3D spatial-segmentation to scRNA-seq data. Tissues are divided into layers based on accessibility of a fluorescent dye allowing sorted cells to be characterized by transcriptomic and regional identity.

Results
We use SEEP to explore how the transcriptional states of cells in high-grade serous ovarian cancer vary with respect to intratumoral position. We describe an integrated method for correlating 3D radial-spatial cell positions with scRNA-seq data. By employing a basic stain-and-sort method using an off-the-shelf live-dead stain, we are able to correlate transcriptional profiles with radial-spatial positions in both radially symmetric tissues (e.g., spheroids, organoids, spherical tumor masses) and linear tissue samples (e.g., punch biopsies). SEEP uses an imaging-based calibration step to inform the parameters of a FACS and sequencing based measurement step.

Conclusion
Across spheroid, organoid, and PDX models of high-grade serous ovarian cancer, we find common positional transcriptomic profiles, ranging from single-gene proclivities to multi-gene-set enrichments across tissue layers. The results validate long-standing beliefs regarding the relationship between cell state and position while also revealing new concepts on how the spatially unique microenvironment of individual cells within tumors influences cell identity.

High-throughput spatial reconstruction of cell states within ovarian cancer structures

Background
Breast cancer (BC) is the most common cancer affecting women and is associated with multiple genetic and environmental factors. To better understand individual’s genetic risk for disease, polygenic risk scores (PRSs) were developed using genome-wide association studies (GWASs). BC PRS have been developed with the hopes of improving risk stratification, but their replication is often limited. We worked with a population of genetically similar Dutch and American women to investigate the use of BC PRSs.

Methods
Two published PRSs utilizing 313 and 3280 single nucleotide polymorphisms (SNPs) were used to score 468 BC cases and 4,337 cancer negative controls from the integrated Cancer Repository for Cancer Research and cancer negative controls from the Netherland Twin Register. Blood samples were used to extract DNA and subjects were genotyped using the Illumina Global Screening Array and underwent standardized quality control, and 20 averaged runs of imputation, and polygenic scoring. Percentile scores were then compared via ANOVA testing, variability assessment, and area under the curve analysis.

Results
Results showed that the PRSs of BC cases were significantly greater than the controls at 52.81 and 48.07 (p<0.001), respectively, for the 313 PRS and 55.45 and 49.81 (p<0.001) for the 3820 PRS, respectively. The AUC was 0.596 (95% CI: 0.569-.624) for the 313 PRS and 0.603 (95% CI: 0.576-0.630) for the 3820 PRS, with both slightly underperforming the originally published AUC of 0.639 and 0.646 for the 313 and 3820 PRS, respectively. Variability of PRSs across imputation was 2.17% for the 313 PRS and 2.99% for the 3820 PRS, with a subset with increased score ranges.

Conclusion
Our study provides further evidence that BC PRSs are reproducible in our study populations with slightly less predictive capacity. In addition, we found that scores varied 2-3% between various imputation runs with some increased variability in subjects carrying many rare alleles, indicating that imputation methodology can have an impact an individual’s reported PRS. This may affect the clinical implementation of PRSs and may be worth considering as this new tool enters clinical use.

Exploration of breast cancer polygenic risk scores in a population of breast cancer patients

Background
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy, largely due to its high rate of early metastasis. PDAC remains almost uniformly refractory to T cell-based immunotherapies that have transformed treatment in many other cancers, and there is a critical need to identify new therapeutic approaches. The abundance and functions of eosinophils in PDAC have not been explored despite increasing evidence for important roles of eosinophils in other tumor types. Here, we quantified tumor eosinophilia in preclinical PDAC models and a large PDAC patient cohort, and we assessed whether modulation of eosinophils impacts primary tumor growth or metastasis. 

Methods
We used flow cytometry and immunohistochemistry to quantify eosinophil abundance in PDAC patient samples and in subcutaneous, orthotopic, and genetically engineered mouse models (GEMMs) of PDAC. We used single cell RNA-sequencing (scRNA-seq) and cytokine arrays to study the mechanism by which eosinophils are recruited into pancreatic tumors. Using an eosinophil-deficient mouse model (dblGATA), genetically engineered cytokine-overexpressing cell lines, and systemic injection of exogenous interleukin-33 (IL-33), we studied the effects of eosinophil depletion, expansion, and activation on primary tumor growth and metastasis in murine PDAC. We used scRNA-seq to study mechanisms by which intratumoral eosinophils may impact PDAC metastasis. 

Results
Eosinophils were abundant in PDAC samples from human patients and murine models. They are likely recruited into tumors via local production of eotaxin-1 and eotaxin-2 by distinct populations of cancer associated fibroblasts and macrophages. Eosinophil expansion or depletion does not impact the growth of primary pancreatic tumors, but mice lacking eosinophils are more likely to develop spontaneous lung metastases. Treating mice with recombinant IL-33 expands eosinophils systemically and reduces rates of metastasis. Wild-type and eosinophil-deficient mice have similar metastasis burdens after intravenous injection of tumor cells, suggesting that eosinophils do not limit metastasis by impacting the pre-metastatic niche. Rather, eosinophils may interact with other intratumoral cell types to limit the entry of cancer cells into circulation. Indeed, scRNA-seq reveals that eosinophil deficiency is associated with a significant shift in the proportions of intratumoral endothelial cell (EC) subpopulations from tip-like to stalk-like ECs. 

Conclusion
Eosinophils are recruited by locally produced cytokines into the PDAC TME, where they shape the endothelial compartment and regulate the metastatic spread of tumor cells. Further studies are warranted to better delineate the mechanisms underlying this phenotype and to determine whether tumor eosinophilia can serve as a useful therapeutic target or prognostic biomarker in PDAC patients.

Eosinophils regulate metastasis in pancreatic cancer

In order to function correctly, cells must regulate gene expression; chemical modification of DNA is an important method by which they achieve this. For example, cytosine can be methylated to form 5-methylcytosine (5mC), a repressive epigenetic marker. 5mC can be oxidized by Ten-Eleven-Translocation (TET) enzymes to produce additional forms of cytosine. One of these derivatives, 5-hydroxymethylcytosine (5hmC), is an activator of gene expression and ͏can be further oxidized to 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). Subsequently, 5caC is excised and replaced with unmodified cytosine. This process by which 5mC is converted back to cytosine is known as active demethylation (AD).
Improper control of methylation and demethylation can impair development and is a hallmark of many cancers. Ubiquitin-like Modifier with PHD and Ring Finger Domain 2 (UHRF2) is a DNA-interacting protein that plays an important but poorly characterized role in active demethylation. Previous work suggests that UHRF2 is required for the maintenance of 5hmC levels in somatic cells but does not demonstrate a mechanism. Furthermore, a paralog of this protein, UHRF1, binds to 5mC via its Set and Ring Associated (SRA) domain to preserve methylation levels in DNA. Thus, we proposed a related model where UHRF2 binds to 5hmC via its SRA domain and prevents further oxidation by TET enzymes. 
In this study, we overexpressed UHRF2 and TET2 in wild-type U2OS (human osteosarcoma) cells and U2OS cells with endogenous UHRF2 expression knocked out. We also conducted domain-deletion experiments to determine which domains of UHRF2 are required to preserve 5hmC levels.
As expected, we demonstrated that excess TET2 increased 5hmC levels in both cell lines, but concurrent overexpression of UHRF2 appeared to amplify this effect. We also determined that the plant homeodomain (PHD), tandem Tudor domain (TTD), and SRA domain are each necessary for UHRF2 to preserve 5hmC levels. Furthermore, we found that simultaneous overexpression of TET2 and UHRF2 increased levels of 5fC more than overexpressing TET2 alone, suggesting that UHRF2 may have a more complex role in regulating the AD cycle. Eventually, a better understanding of UHRF2 function will elucidate its role in cancer and may guide future research and therapeutics.

Premium content

Hypoxia regulates vessel-modifying macrophages and vice versa in solid tumors

Next from 2023 AMA Research Challenge

Dysregulation of macrophages EphB2 mitigates diet-induced obesity in mice

Stay up to date with the latest Underline news!

PRESENTATIONS

CONFERENCES

COMPANY

RESOURCES