bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4482: MTAP regulates cell malignancy and is novel prognostic factor for kidney cancer
Authors: Huang Carissa , Xu Jihao , Wu Yichin , Weiss Robert H. , Chen Ching-Hsien 
Published: August 2018

Abstract
Renal cell carcinoma (RCC), the 6th most common cancer in the US, is now considered a metabolic disease, which is increasing in incidence and demonstrates resistance usually within 2 years to all available therapies. Given that patients with metastatic RCC have unusually poor prognosis, it is urgent to discover potential molecules for predicting malignant changes that will lead to RCC. Herein, we have identified S-methyl- 5'-thioadenosine phosphorylase (MTAP) and its substrate methylthioadenosine (MTA) as a possible biomarker for early detection of RCC. In a screen of patients with RCC, we found that low MTAP expression is accompanied by high MTA level in RCC specimens, whereas concomitant high level of MTAP and low MTA abundance are detected in adjacent normal kidney tissues. Datasets for RCC (n=538) from The Cancer Genome Atlas (TCGA) showed that the patients with low MTAP levels have a significantly shorter overall survival as compared to the high MTAP group. Immunohistochemistry staining of normal kidney tissues confirmed an increase of MTAP protein expression compared to RCC tissues, and MTAP gene expression is inversely proportional to tumor grade. Accumulation of the metabolite MTA, a major substrate of MTAP, was observed in high-grade tumors showing high malignant potential. MTAP-knockout RCC cells displayed an elongated, spindle-like morphology with extended pseudopodial branches. Genetic manipulation of MTAP studies demonstrated that MTAP expression inhibits epithelial-mesenchymal transition, invasion and migration of RCC cells. Loss of MTAP resulted in an activation of IGF1R signaling in RCC cells. Taken together, our findings indicate a major contribution of MTAP loss to kidney cancer cell malignancy and provide a viable biomarker for tumor detections.
Citation Format: Carissa Huang, Jihao Xu, Yichin Wu, Robert H. Weiss, Ching-Hsien Chen. MTAP regulates cell malignancy and is novel prognostic factor for kidney cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4482.
Abstract 4485: VGLL3 is a novel outlier in African American prostate tumors and its expression is associated with a tumor suppressor phenotype in prostate cancer
Authors: Kang Hongjun 
Published: August 2018

Abstract
Higher incidence, progression and mortality of prostate cancer (PCa) have been noted in African American (AA) men compared with Caucasian (CA) men. In fact AA race is an independent predictor of biochemical recurrence for all stage of PCa (Dr. Schaeffer's data analysis, n=1634 of AA patients). The etiology of PCa racial disparities is likely multi-factorial with increasing support of biologic contributors to these differences. By analyzing large cohort of PCa, we have demonstrated that AA PCa exhibits a unique spectrum of molecular subtypes. For example, AA men presented with PCa have a significant decrease in fusion proteins such as ERG, ETS and SPINK, with an enrichment of fusion unknown (FU; triple negative) cases. Given the increased mortality of PCa in AA populations and the enrichment of FU cases among AA tumors, there is an urgent need to define and explore individual outlier as race-based modifiers of disease aggressiveness. By utilizing a large multi-institutional cohort of prostate cancer cases of mixed racial composition, we have identified novel outliers enriched in AA among FU group by COPA outlier analysis.VGLL3 is one of the top outliers enriched in AA. VGLL3 positive cases are associated with low stage (less LNI, p=0.001; SVI, p&lt;0.001; and EPE, p=0.009) and low grade disease (less Gleason &gt;7, p=0.012) of higher protective phenotype of adverse cancer grade and stage. This preliminary work on VGLL3 expression suggests it may be associated with a tumor suppressor-like phenotype with reductions in expression with increasingly aggressive PCa. Studies of VGLL3 in cancer are limited and the role of VGLL3 in prostate has not been explored at all. The goal of this study is to investigate the role of VGLL3 as a novel outlier in AA prostate cancer that modulates disease aggressiveness. We found that mRNA expression levels of VGLL3 were lower in prostate cancer epithelial cells than in normal epithelial cells or stromal cells. By establishing and characterizing PCa models overexpressing VGLL3 in vitro and in vivo, our data demonstrate that VGLL3 significantly reduced migration and invasion of PCa cells and inhibited primary tumor cell growth. Our preliminary data also indicate VGLL3 inhibits PCa metastasis. Furthermore, VGLL3 seems to negatively affect both hippo and AR activity in PCa cells and these might be the mechanisms that VGLL3 inhibits tumor cell growth. These data is consistent with our clinical data suggesting tumor suppressive role of VGLL3 in advanced PCa.
Citation Format: Hongjun Kang. VGLL3 is a novel outlier in African American prostate tumors and its expression is associated with a tumor suppressor phenotype in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4485.
Abstract 4487: Gene expression changes elicited by crosstalk between adipocytes and breast cancer cells
Authors: Lovejoy Leann A. , Costantino Nicholas S. , Shriver Craig D. , Iida Geogre , Ellsworth Rachel E. 
Published: August 2018

Abstract
Background: No longer considered simply an inert energy depot, adipose in the breast is increasingly recognized as an active endocrine tissue. Given the increasing rates of obesity in the US, choice of breast conserving surgery and use of autologous fat grafting, it is critical to understand how signals from adipocytes affect breast tumor cells and vice versa.
Methods: Human subcutaneous preadipocytes were co-cultured for 3 days. Triple negative cell lines MDA-MB-231, SUM-149 and HCC-38 were then added and grown for a total of 10 days, with exposure to mature adipocytes for 7 days. Adipocytes and tumors cells were lysed from the plate and total RNA was isolated. Libraries were prepared for RNAseq and sequenced using a HiSeq2000. Differentially expressed genes were detected using the edge R package in R (v 3.3.3).
Results: Co-culturing breast tumor cells demonstrated 110 differentially expressed genes compared to unexposed tumor cells including 6-fold lower expression of CLCA2 and 9-fold higher expression ZBTB16 in exposed tumor cells compared to controls. Pathway analysis demonstrated upregulation of 23 pathways such in the FoxO signaling and longevity regulating pathways and downregulation of tryptophan metabolism. In co-cultured adipocytes, 89 genes, including 9-fold higher expression of WNT7B and 13-fold lower expression of ADIPOQ. Pathways such as ECM-receptor interaction were upregulated and fat digestion and absorption were downregulated in co-cultured adipocytes.
Conclusions: Exposure of adipocytes to tumor cells alters pathways involved in lipolysis and fatty acid metabolism in the adipocytes which may serve as a fuel source for tumor cells. In conjunction, exposure to adipocytes alters gene expression profiles in tumor cells associated with proliferation, migration and metastasis. These data demonstrate that proximity of breast tumor cells to adipocytes elicit significant gene expression changes in both cell types which synergistically promote tumorigenesis. The views expressed in this abstract are those of the author and do not reflect the official policy of the Department of Army, Navy, Air Force, Department of Defense, or U.S. Government. The identification of specific products, scientific instrumentation, or organization is considered an integral part of the scientific endeavor and does not constitute endorsement or implied endorsement on the part of the author, DoD, or any component agency.
Citation Format: Leann A. Lovejoy, Nicholas S. Costantino, Craig D. Shriver, Geogre Iida, Rachel E. Ellsworth. Gene expression changes elicited by crosstalk between adipocytes and breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4487.
Abstract 4488: Osteosarcoma cells interact with bronchial cells in lung to drive production of pro-metastatic cytokines
Authors: Hinckley John M. , Gross Amy , Roberts Ryan 
Published: August 2018

Abstract
The survival rate for patients diagnosed with osteosarcoma (OS) drops from 70% to an abysmal 20% when diagnosed with lung metastasis. We have shown that metastatic colonization of lungs by OS cells depends on the production of IL6 and CXCL8 by tumor cells, which seems to increase within the metastatic niche of the lung. Identification of key tumor-host interactions that drive this phenomenon will facilitate the development of novel therapies aimed at prevention of metastases in patients diagnosed with OS. We hypothesized that OS cells interact with lung tissues in ways that establish paracrine signal amplification loops, where IL6 and CXCL8 stimulate lung-resident cells to produce secondary signaling molecules that, in turn, further stimulate tumor cell production of IL6 and CXCL8 in a feed-forward mechanism. Co-culture experiments have identified strong interactions between OS cells and primary cultures of bronchial epithelial cells and lung smooth muscle cells. Exposure of OS cells to conditioned supernatants from the primary cell cultures show that these interactions result from exchange of soluble mediators secreted by each cell type. Proteomic profiling of bronchial cell supernatants following incubation with OS conditioned media identified a number of intriguing candidate mediators, which might facilitate the growth and survival of OS cells within the microenviroment of the lung. Some of those same candidate mediators trigger expression of IL6 and CXCL8 in OS cell cultures. These results suggest a paracrine loop mechanism, where OS cells trigger a response from lung stromal cells that promotes survival and proliferation of the OS cells, establishing a favorable niche for the development of metastasis.
Citation Format: John M. Hinckley, Amy Gross, Ryan Roberts. Osteosarcoma cells interact with bronchial cells in lung to drive production of pro-metastatic cytokines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4488.
Abstract 4492: Aggressive breast cancer cells reduce CCL5 and Nodal expression in response to a human adipose-derived stromal cell microenvironment
Authors: Berrebi Daniel , Yadav Abhishek , Lundstrom Eric , Werwie Nicole , Muttillo Dominic , Seftor Richard E. , Seftor Elisabeth A. , Vona-Davis Linda 
Published: August 2018

Abstract
Clinical studies indicate that obesity is correlated with poor outcomes in breast cancer patients. Obese individuals have a high proportion of adipose tissue, which is abundant in stem and progenitor cells. Human adipose-derived stromal cells (hADSCs) secrete several cytokines including CCL5, an inflammatory chemokine shown to increase tumor metastatic ability in vitro. We previously identified that CCL5 is secreted into the microenvironment when hADSCs are co-cultured with breast tumor cells. When the clinical relevance of CCL5 was assessed using cBioPortal, an open-source genomics database, we found that CCL5 mRNA overexpression was correlated with increased overall survival in breast cancer patients, which counters what we and others have observed in vitro. In this study, we compared the expression of CCL5 and Nodal, a potent embryonic morphogen re-expressed by aggressive cancer cells, in either hADSC or MDA-MB-231 breast cancer cells in response to three-dimensional collagen matrices conditioned by hADSCs or breast cancer cells. After preconditioning a three-dimensional collagen matrix with either hADSCs or MDA-MB-231 cells (and following removal of the cells), the denuded three-dimensional matrices were reseeded with the opposite cell type. We found that the expression of both CCL5 and Nodal was significantly reduced in the breast cancer cells plated on the hADSC-preconditioned matrix. However, hADSCs did not express Nodal or alter CCL5 protein expression when grown on a MDA-MB-231-preconditioned matrix. MDA-MB-231 cells plated onto a hADSC-preconditioned matrix appeared more mesenchymal and stem-like, while the adipose stem cells placed into a tumor-preconditioned matrix were induced into a more aggressive cancer cell phenotype by engaging in vasculogenic mimicry. Furthermore, we found there was no change in cell proliferation of any cells grown under these different conditions. These observations suggest a relationship between hADSCs and the breast tumor microenvironment where human adipose-derived stem cells appear to inhibit the expression of CCL5 and Nodal by the aggressive tumor cells without altering tumor cell proliferation.
Citation Format: Daniel Berrebi, Abhishek Yadav, Eric Lundstrom, Nicole Werwie, Dominic Muttillo, Richard E. Seftor, Elisabeth A. Seftor, Linda Vona-Davis. Aggressive breast cancer cells reduce CCL5 and Nodal expression in response to a human adipose-derived stromal cell microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4492.
Abstract 4503: The paracrine role of p53 in skin
Authors: Terzian Tamara , Sobhani Nema , Mylavarapu Rohan , Kharbili Manale El , Parker Andrew , Little Colleen , Krauspe Ethan , Box Neil 
Published: August 2018

Abstract
Exposure to ultraviolet radiation (UVR) in sunlight activates both defensive and repair pathways in the skin. As the major cell type affected by UVR, keratinocytes coordinate critical aspects of the skin response. Molecularly, the transcription factor p53 is induced by UVR in keratinocytes leading to their cell death by apoptosis (peeling). p53 also stimulates the expression of paracrine melanocyte growth factors involved in tanning defined as increase in melanocyte proliferation and melanin synthesis. Here, we investigate the less defined role of p53 in tanning. For this, we use a mouse model that has high p53 levels in keratinocytes and presents with elevated melanocyte number and melanin production. Interestingly, loss of p53 in keratinocytes completely abrogates the hyperpigmentation phenotype. These data demonstrate in a powerful way the paracrine role of p53 expressed in keratinocytes on melanocyte behavior and function. Moreover, it provides an excellent tool to examine molecular and cellular changes that accompany the melanocyte response to sunburn. Sunburn increases melanoma risk in epidemiological studies. To elucidate the role of the p53 response in melanoma, we treated mice with “sunburning” doses of UVB and followed melanocyte proliferation and the expression of keratinocyte-induced melanocyte growth factors. We present our latest findings reinforcing the signs of cross-talk between keratinocytes and melanocytes which support a paracrine role for p53 expressed in keratinocyte on promoting melanocyte proliferation through the release of paracrine factors.
Citation Format: Tamara Terzian, Nema Sobhani, Rohan Mylavarapu, Manale El Kharbili, Andrew Parker, Colleen Little, Ethan Krauspe, Neil Box. The paracrine role of p53 in skin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4503.
Abstract 4518: Prevalence of high-grade prostatic adenocarcinoma in a black African population
Authors: Nnakenyi Emeka F. , Nnakenyi Ifeyinwa D. , Okafor Okechukwu C. , Ugwumba Fred O. 
Published: August 2018

Abstract
INTRODUCTION:
Prostate cancer is the second most common type of cancer in men worldwide. Despite this, screening is currently disputed because studies in the western world have shown that more men die with the disease than from it. Black men have been documented to have a greater prevalence of prostate cancer which runs an aggressive course. Therefore, we aimed to determine the prevalence of high grade prostatic adenocarcinoma among Nigerian men.
METHOD:
This was a retrospective study of Nigerian men attending the urology clinic at University of Nigeria Teaching Hospital, Enugu, south-east Nigeria. Data on prostate histology were retrieved from the histopathology laboratory records for the last 5 years as thus: age, prostate diagnosis, gleason score. Histologic slides from core-needle biopsies had been reviewed by two Pathologists independently. If adenocarcinoma was diagnosed, Gleason system was used to grade the tumors, and a consensus was reached by both Pathologists. The data were analyzed with SPSS statistical software.
RESULTS:
Three hundred and forty-five (345) requests for histology on prostate biopsies were received, of which 118 (34.2%) were diagnosed with prostatic adenocarcinoma (PCa) at a mean age(sd) of 69(8.4) years. Minimum and maximum gleason scoring observed were 4 and 10.
Gleason systemNo. of prostatic adenocarcinoma (%)Gleason score 2 – 6 (well differentiated PCa with excellent prognosis)22 (18.6%)Gleason score 7 (3+4 moderately differentiated PCa)19 (16.1%)Gleason score 7 (4+3 moderate to poorly differentiated PCa)11 (9.4%)Gleason score 8-10 (poorly differentiated with aggressive biologies)66 (55.9%)
CONCLUSION:
A high prevalence of high grade PCa was observed in this study, which are less likely to be cured. Therefore, early detection is crucial to prevent mortality. This may justify the need for prostate cancer screening in our African environment.
Citation Format: Emeka F. Nnakenyi, Ifeyinwa D. Nnakenyi, Okechukwu C. Okafor, Fred O. Ugwumba. Prevalence of high-grade prostatic adenocarcinoma in a black African population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4518.
Abstract 4524: Immunohistochemistry and alternative FISH testing in breast cancer with HER2 equivocal amplification
Authors: Agersborg Sally , Mixon Christopher , Nguyen Thanh , Aithal Sramila , Blocker Forrest , Weiss Lawrence , Gasparini Robert , Jiang Shiping , Chen Wayne , Hess Gregory , Albitar Maher 
Published: August 2018

Abstract
PURPOSE
While HER2 testing is well established in directing appropriate treatment for breast cancer, a small percentage of cases show equivocal results by IHC and FISH. Alternative probes may be used in equivocal cases. We present a single community-based institution's experience in further evaluating these cases.
PATIENTS AND METHODS
Between 2014-2016, 4255 samples were submitted for HER2 amplification testing by alternative probes, TP53, RAI1, and RARA. Of patients tested by FISH, 505/3908 (12.9%) also had IHC data.
RESULTS
Most (73.9%) FISH equivocal cases remained equivocal after IHC testing. Duplicate testing by IHC using a different paraffin block resulted in poor reproducibility as 44% of IHC negative became equivocal and 40% of IHC equivocal became negative. Of the equivocal cases by IHC, 52.3% became positive by alternative FISH. However, 50.5% of cases equivocal by conventional FISH were classified as HER2 amplified by alternative probes. Most cases were positive by more than one probe; 78% of positive cases were positive by RAI1 and 73.9% by TP53. There was a significant difference between IHC and FISH alternative testing (P&lt;0.0001) among the equivocal cases by conventional FISH testing, 44% of IHC negative cases became positive while 36% of the positive IHC cases became negative by alternative FISH testing. Available data showed that 41% of patients were treated with palbociclib and were positive by alternative FISH.
CONCLUSION
The prevalence of double HER2 equivocal cases and the discrepancy between IHC and alternative FISH testing suggest that FISH alternative testing using both RAI1 and TP53 probes is necessary for conclusive classification. Due to the significant difference between IHC repeat testing, reflexing on IHC alone in this group of cases may not be reproducible. Because almost half of FISH equivocal cases converted to HER2 amplified upon alternative testing, clinical studies to determine benefit of anti-HER2 therapy in these patients is urgently needed.
Alternative FISHIHC Score 0 NegativeIHC Score 1 NegativeIHC Score 2 EquivocalIHC Score 3 PositiveNo%No%No%No%Negative1463.65454.517847.7436.4Positive836.44545.519552.3763.6Total22100.099100.0373100.011100.0
Citation Format: Sally Agersborg, Christopher Mixon, Thanh Nguyen, Sramila Aithal, Forrest Blocker, Lawrence Weiss, Robert Gasparini, Shiping Jiang, Wayne Chen, Gregory Hess, Maher Albitar. Immunohistochemistry and alternative FISH testing in breast cancer with HER2 equivocal amplification [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4524.