bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 37: Understanding the social determinants of guideline-based mammography adherence across race/ethnicity: Results from the 2016 California Health Interview Survey
Authors: Johnson Roman , Thomeer Mieke Beth 
Published: June 2022

Abstract
Purpose: There is not a consensus concerning recommendations about breast cancer screening which has generated confusion about when and how often to undergo mammography screening in the population, yet there is limited population-based data about the extent to which patients adhere to various mammographic screening guidelines in practice. Our purpose was to evaluate population-based adherence to mammographic screening using criteria from major guideline-producing organizations across race/ethnicity to understand what social determinants of mammography adherence are associated with each guideline producing institution.
Methods: Women aged 45-79 in the 2016 California Health Interview Survey were included. Self-reported mammographic screening within 1 or 2 years, according to major guideline-producing organizations (American Cancer Society [ACS], US Preventative Services Task Force [USPSTF], American College of Radiology [ACR], American College of Obstetricians and Gynecologists [ACOG]) was calculated with logistic regression, adjusting for demographics, health care, insurance status, and BMI.
Results: 7,551 women were included in this study. By age category, cross-sectional adherence to ACR/ACOG (annual screening) (65 to 67%) and USPSTF guidelines (biennial screening) ranged from 82-83% and with increasing age being generally associated higher adherence. The highest proportions of women undergoing mammographic screening were seen in women ages 60-69 (67% within last year, 85% within last 2 years). Statistically significant predictors of adherence to mammography screening included Latina race (OR 1.62, 0.18 SE), full time employment (OR 0.73, 0.09 SE), and not having a usual healthcare provider (OR 0.50, 0.12 SE), adjusted for demographics, health care, insurance status, and BMI.
Conclusion: Frequency of screening increases with age with highest screening proportions in women ages 65-69 (66% within last year, 81% within last 2 years). For ACR/ACOG screening guidelines, adherence to mammography screening remains poorer in women with no usual source of care, given that their odds of exhibiting adherence was half that of women who did have a regular source of care and nearly 65 percent lower odds of those women with USPSTF mammography adherence.
Key Words: Breast cancer, screening, race/ethnicity, guideline-based care
Citation Format: Roman Johnson, Mieke Beth Thomeer. Understanding the social determinants of guideline-based mammography adherence across race/ethnicity: Results from the 2016 California Health Interview Survey [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 37.
Abstract 3707: Moonlighting function of mitochondrial protein VDAC2 provides a potent pharmacological strategy against selective killing of hepatocellular carcinoma
Authors: Mishra Piyush 
Published: June 2022

Abstract
Voltage dependent anion channels (VDACs) family of proteins are the most abundant proteins in the outer mitochondrial membrane (OMM). There are three isoforms of VDAC, that are structurally and functionally conserved as far as their ion transport function is concerned. However, there are isoform-specific functions that support distinct pathways. For VDAC2 isoform, an established isoform-specific function is the targeting of the pro-apoptotic Bak protein to the OMM, which stabilizes Bak, leading to its elevated cellular levels. On the surface of OMM, activation and oligomerization of Bak and Bax, another pro-apoptotic protein leads to OMM perforation and release of pro-apoptotic proteins from intermembrane space to the cytoplasm. This is an irreversible step that stimulates the downstream events of apoptotic pathway. Hepatocellular carcinoma (HCC) ranks third in cancer mortality and in the advanced stages is associated with poor prognosis. We observed that unexpectedly, HCC cells are vastly more sensitive to tBid induced apoptosis compared to normal hepatocytes. tBid is a BH3-only pro-apoptotic Bcl-2 family protein, the effect of which is primarily mediated by Bak. We have shown that, in the absence of VDAC2, the Bid-Bak apoptosis pathway is suppressed. VDAC2 protein expression is the lowest in liver and lung among different tissues. We also determined the protein abundances in the HCC lines and normal hepatocytes and found elevated VDAC2 and Bak levels in HCC. Our findings are in line with multiple datasets that show an elevation of VDAC2/Bak expression in human HCC suggesting a potential clinical relevance. We found that combination of an inhibitor of the anti-apoptotic proteins (S63845, a selective Mcl-1 inhibitor), which normally suppresses Bak activation, with an activator of the tBid pathway (TRAIL) enhanced the death of hepatocarcinoma cells with little effect on normal hepatocytes. This treatment strategy was also effective at reducing tumor growth in vivo, but only in tumors expressing VDAC2. Thus, we postulate that increased VDAC2 expression in HCC leads to elevated Bak recruitment to the OMM, which in turn sensitizes HCC to tBid. Therefore, this differential expression provides an excellent opportunity for selective elimination of HCC cells.
Citation Format: Piyush Mishra. Moonlighting function of mitochondrial protein VDAC2 provides a potent pharmacological strategy against selective killing of hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3707.
Abstract 3796: Deeper insight into intratumoral heterogeneity by MRI and PET-guided stereotactic biopsies from glioblastoma patients
Authors: Anand Atul , Petersen Jeanette Krogh , Burton Mark , Larsen Martin Jakob , Andersen Lars van , Harwood Dylan Scott , Pedersen Christian Bonde , Poulsen Frantz Rom , Grupe Peter , Kruse Torben A. , Thomassen Mads , Kristensen Bjarne Winther 
Published: June 2022

Abstract
Glioblastoma is one of the most aggressive cancers, but the molecular evolution is not fully understood. We used PET imaging combined with deep sequencing of glioblastoma biopsies at both the RNA and DNA levels to get a deeper insight into molecular evolution. In the clinical setting, PET imaging provides information about metabolically active tumor areas, but the molecular interpretation is unclear. Our primary objective was to perform an intratumoral spatial comparison of biopsies from potentially aggressive and less aggressive areas in glioblastomas according to PET scans. We used MRI co-registered with 11C-MET-PET (amino acid) and 18F-FDG PET (glucose) in order to obtain representative neurosurgical stereotactic biopsies from tumor areas with high accumulation of these two metabolites (hotspot), low accumulation (coldspot), and no accumulation as the periphery of six glioblastoma patients that were processed for whole genome, exome, and transcriptome sequencing. Differential gene expression and gene ontology analysis showed that hotspots were enriched in gene sets associated with DNA replication, cell cycle, and ligand-receptor interaction. Genome and exome analysis suggested hotspots and coldspots have similar mutational profiles. However, a limited number of hotspot-specific mutations and novel fusion transcripts indicated that hotspot-associated tumor cells developed from coldspot-associated tumor cells and point at the potential role of hotspot driver genes in glioblastoma evolution. Our findings reveal that hotspots in glioblastomas represent a more advanced stage of molecular evolution than coldspots.
Citation Format: Atul Anand, Jeanette Krogh Petersen, Mark Burton, Martin Jakob Larsen, Lars van Andersen, Dylan Scott Harwood, Christian Bonde Pedersen, Frantz Rom Poulsen, Peter Grupe, Torben A. Kruse, Mads Thomassen, Bjarne Winther Kristensen. Deeper insight into intratumoral heterogeneity by MRI and PET-guided stereotactic biopsies from glioblastoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3796.
Abstract 3821: Rapid acceleration of KRAS-mutant pancreatic carcinogenesis via remodeling of tumor immune microenvironment by PPARD
Authors: Liu Yi , Deguchi Yasunori , Wei Daoyan , Moussalli Micheline J. , Liu Fuyao , Deguchi Eriko , Li Donghui , Wang Huamin , Valentin Lovie Ann , Colby Jennifer K. , Wang Jing , Zheng Xiaofeng , Ying Haoqiang , Gagea Mihai , Ji Baoan , Shi Jiaqi , Yao James C. , Zuo Xiangsheng , Shureiqi Imad 
Published: June 2022

Abstract
Pancreatic intraepithelial neoplasia (PanIN) is a precursor of pancreatic ductal adenocarcinoma (PDAC), which commonly occurs in the general populations with aging. Although most PanIN lesions (PanINs) harbor oncogenic KRAS mutations that initiate pancreatic tumorigenesis, PanINs rarely progress to PDAC. Critical factors that promote this progression, especially targetable ones, remain poorly defined. We show that peroxisome proliferator-activated receptor-delta (PPARD), a lipid nuclear receptor, is upregulated in PanINs in humans and mice. Furthermore, PPARD ligand activation by a high-fat diet or GW501516 (a highly selective, synthetic PPARD ligand) in mutant KRASG12D (KRASmu) pancreatic epithelial cells strongly accelerates PanIN progression to PDAC. This PPARD activation induces KRASmu pancreatic epithelial cells to secrete CCL2, which recruits immunosuppressive macrophages and myeloid-derived suppressor cells into pancreas via the CCL2/CCR2 axis to orchestrate an immunosuppressive tumor microenvironment and subsequently drive PanIN progression to PDAC. Our data identify PPARD signaling as a potential molecular target to prevent PDAC development in subjects harboring PanINs.
Citation Format: Yi Liu, Yasunori Deguchi, Daoyan Wei, Micheline J. Moussalli, Fuyao Liu, Eriko Deguchi, Donghui Li, Huamin Wang, Lovie Ann Valentin, Jennifer K. Colby, Jing Wang, Xiaofeng Zheng, Haoqiang Ying, Mihai Gagea, Baoan Ji, Jiaqi Shi, James C. Yao, Xiangsheng Zuo, Imad Shureiqi. Rapid acceleration of KRAS-mutant pancreatic carcinogenesis via remodeling of tumor immune microenvironment by PPARD [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3821.
Abstract 3839: RASSF1C and tumor microenvironment
Authors: Amaar Yousef G. , Reeves Mark E. 
Published: June 2022

Abstract
Introduction: Tumor microenvironment (TME) plays a vital role in tumor invasion and metastasis and provides a rich environment for identifying novel therapeutic targets. The TME landscape consists of extracellular matrix (ECM) and stromal cells. ECM is a major component of TME that mediates interaction between cancer cells and stromal cells to promote invasion and metastasis. We have shown in published work that RASSF1C promotes cancer stem cell development, migration, and drug resistance, in part, by promoting EMT through a mechanism that involves up-regulation of the PIWIL1-piRNA gene axis. Interestingly, one of the target genes identified by our microarray study to be upregulated by RASSF1C is P4HA2. In cancer, P4H2A is vital for collagen posttranslational modification and folding. This leads to formation of a stiff ECM and induction of cancer stem cell marker gene expression, resulting in metastatic dissemination. High expression of P4HA2 is associated with significantly lower survival of lung cancer patients. Thus, RASSF1C could promote tumor cell ECM remodeling to induce lung cancer cell stemness, invasion and metastasis by up-regulating a novel PIWIL1-P4HA2 gene axis expression.
Methods: Analysis of a microarray study using H1299 cells over-expressing RASSF1C or control vector backbone identified P4HA2 as a RASSF1C gene target. RT-PCR, immunoblots, and immunofluorescence techniques were used to confirm P4HA2 gene expression using specific primers and antibodies in cells over-expressing RASSF1C or PIWIL1 along with control cells. Kaplan-Meier analysis was performed to determine the relationship of P4HA2 expression to lung adenocarcinoma patient survival using data from The Cancer Genome Atlas (TCGA).
Results: Analysis of microarray data from H1299 cells over-expressing RASSF1C or control vector backbone shows that RASSF1C up-regulates P4HA2 gene expression 2-fold. The up-regulation of P4HA2 expression by RASSF1C was confirmed by RT-PCR, immunoblots, and immunofluorescence using P4HA2 gene specific primers and antibodies. Further, H1299 cells over-expressing PIWIL1 show increased P4HA2 gene expression on immunoblots. Kaplan-Meier analysis shows that high P4HA2 expression in lung adenocarcinoma patients negatively correlates with patient survival. Thus, our findings suggest the hypothesis that RASSF1C may promote lung cancer cell ECM remodeling to induce lung cancer cell stemness, invasion and metastasis, in part, by up-regulating a novel pathway involving a PIWIL1-P4HA2 gene axis.
Conclusions: Investigating the role of a RASSF1C-PIWIL1-P4HA2 gene axis in ECM remodeling in lung cancer cells will provide important mechanistic information that could, in turn, lead to identification of useful biomarkers for lung cancer prognosis and targets for therapy.
Citation Format: Yousef G. Amaar, Mark E. Reeves. RASSF1C and tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3839.
Abstract 3843: TIMP1 and TIMP2 re-educate TGFβ induced pro-inflammatory/pro angiogenic decidual-like NK cells phenotype
Authors: Albini Adriana , Gallazzi Matteo , Palano Maria Teresa , Carlini Valentina , Calabrone Luana , Ricotta Riccardo , Stetler-Stevenson William G. , Noonan Douglas M. 
Published: June 2022

Abstract
Background: Tissue inhibitors of metalloproteases (TIMPs) have been reported to exert dual roles in cancer, based on the different cancer type and interactions with the tumor microenvironments. As inhibitors of Matrix metalloproteases (MMP) they downregulate invasion, metastasis and angiogenesis. However, TIMP1 levels have been found increased in patients with different types of cancer. Natural Killer cells have been found to be phenotypically and functionally compromised in several solid and hematological cancers. We were the first in characterizing NK pro-angiogenic phenotype in the peripheral blood and tumor tissues of patients with Non-small Cell Lung cancer, colorectal cancers, prostate of patients. Also, we found that pro-angiogenic NK cells in the peripheral blood of colorectal cancer patients release of TIMP-1 and TIMP-2, in a STAT3/STAT5-independent manner. Here, we investigated the effects of TIMP-1 and TIMP-2 recombinant proteins, using a TGFβ-mediated NK cell polarization model, in vitro.
Methods: We investigated the effects of TIMP1 and TIMP2 recombinant proteins in hindering decidual-like markers in NK cells, generated by polarizing cytolytic NK cells with TGFβ. The effects of TIMP1 or TIMP2 on NK cell surface antigens were determined by multicolor flow cytometry.
Results: We found that TIMP1 and TIMP2 were effective in interfering with TGFβ induced NK cell polarization towards a decidual-like-phenotype. TIMP1 and TIMP2 counteracted the effect of TGFβ in increasing the percentage of CD56bright, CD16-, CD9+ and CD49a+, and restoring normal levels for TIMP 1 and 2 also inhibited decrease levels of the activation marker NKG2D induced by TGFβ and decreased the TGFβ upregulated exhaustion marker TIM-3. NK cell degranulation capabilities against K562 cells were also decreased by TGFβ and not by TIMP1 or TIMP2. TIMP1 treatment could partially restore degranulation marker CD107a expression.
Conclusions: Our results suggest a potential role of TIMPs in controlling the tumor-associated cytokine TGFβ-induced NK cell polarization. TGFβ stimulation represents a model to prove TIMP's new properties, further studies will help defining TIMPs immunomodulatory activities of NK cells in cancer, and their possible future diagnostic-therapeutic roles.
Citation Format: Adriana Albini, Matteo Gallazzi, Maria Teresa Palano, Valentina Carlini, Luana Calabrone, Riccardo Ricotta, William G. Stetler-Stevenson, Douglas M. Noonan. TIMP1 and TIMP2 re-educate TGFβ induced pro-inflammatory/pro angiogenic decidual-like NK cells phenotype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3843.
Abstract 385: iRGD mediated delivery of neoantigens to enable immunotherapy in integrin b5-rich tumors
Authors: de Mendoza Tatiana Hurtado , Mose Evangeline S. , Botta Gregory P. , Braun Gary B. , Kotamraju Venkata R. , French Randall P. , Suzuki Kodai , Miyamura Norio , Sun Siming , Patel Jay , Teesalu Tambet , Ruoslahti Erkki , Sugahara Kazuki N. , Lowy Andrew M. 
Published: June 2022

Abstract
Pancreatic duct adenocarcinomas are known for their abundant desmoplastic stroma that acts as a barrier for drug penetration and reduces treatment efficacy. iRGD is a tumor-penetrating peptide that initially targets αv integrins expressed on tumor vasculature with its RGD motif and then is proteolytically processed to expose a CendR motif (R/KXXR/K) that interacts with neuropilin-1 (NRP-1), leading to extravasation. We investigated the mechanism of iRGD tissue penetration and found that iRGD initially targets Carcinoma Associated Fibroblasts (CAFs) and then spreads to the tumor cells in a time dependent manner. CAF targeting was dependent on integrin β5 expression and CAFs induced upregulation of integrin β5 in the adjacent tumor cells in a TGF- β dependent manner. Drugs conjugated or co-administered with iRGD can penetrate deep into tumor tissue, significantly increasing the efficacy of chemotherapeutic agents in a variety of solid tumors. Our recent data shows that KrasLSL-G12D/+ Trp53LSL-R172H/+ Pdx1-Cre (KPC) mice treated with iRGD co-administered with Gemcitabine increased survival compared to drug alone. In addition, we are using iRGD to deliver neoantigens to breast and pancreatic cancers to enable immunotherapy. These tumors have a low mutational burden and a very immunosuppressive microenvironment, rendering them resistant to such therapies. We have used iRGD, to deliver the ovalbumin 257-264 (OVAI) peptide to triple negative breast tumors, followed by adoptive T cell transfer of OT1 CD8 T cells, in order to elicit an antitumor immune response. Our preliminary data showed tumor regression in 70%, and complete response in 42% of the mice treated with iRGD plus OVA1. We are now working on adapting this strategy to pancreatic cancer.
Citation Format: Tatiana Hurtado de Mendoza, Evangeline S. Mose, Gregory P. Botta, Gary B. Braun, Venkata R. Kotamraju, Randall P. French, Kodai Suzuki, Norio Miyamura, Siming Sun, Jay Patel, Tambet Teesalu, Erkki Ruoslahti, Kazuki N. Sugahara, Andrew M. Lowy. iRGD mediated delivery of neoantigens to enable immunotherapy in integrin b5-rich tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 385.
Abstract 3861: Microscope-based sorting of highly motile cancer-associated fibroblasts using a photoconvertible fluorescent protein
Authors: Lee Sieun , Ahn Young-Ho 
Published: June 2022

Abstract
In the tumor microenvironment, cancer-associated fibroblasts (CAFs) are known to play key roles in promoting cancer cell invasion and cancer progression. CAFs are also highly invasive compared with normal fibroblasts in a 3-D co-culture system with lung cancer cells. Due to CAF heterogeneity, there are various differences in cell motility even within a CAF population. To classify CAFs according to their motility, we named less motile CAFs as “static CAFs” and more motile CAFs as “motile CAFs”. To separate and isolate these static CAFs and motile CAFs from a 3-D co-culture system, CAFs were transfected with a green-to-red photoconvertible fluorescent protein, Dendra2. Dendra2-transfected CAFs at specific areas (i.e., static or motile CAFs) were UV-irradiated using a confocal microscope. CAFs with red fluorescence were then isolated by flow cytometry and were subjected to RNA sequencing. In gene ontology and gene set enrichment analyses, two types of CAFs showed significant differences in global gene expression patterns. These data suggest that heterogeneous CAFs with different motility have distinct roles in the regulation of various signaling pathways in the tumor microenvironment.
Citation Format: Sieun Lee, Young-Ho Ahn. Microscope-based sorting of highly motile cancer-associated fibroblasts using a photoconvertible fluorescent protein [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3861.
Abstract 3869: A human in-vitro T cell exhaustion model for assessing immuno-oncology therapies
Authors: Goral Paulina , Brackenbury Louise , Nunan Robert , Jenkinson Rhiannon 
Published: June 2022

Abstract
Chronic stimulation of CD8 T cells either as a result of viral infection or within the tumor microenvironment can lead to a state of exhaustion, whereby T cells no longer make a productive effector response. Remobilisation of exhausted tumor specific CD8 T cells (TEX) presents a possible therapeutic strategy for driving anti-tumor T cell responses. The success of biologics targeting receptors and ligands associated with exhausted T cells such as PD-1/PD-L1 and CTLA-4 has spurred an acceleration of research to unravel the molecular processes that drive or maintain the exhausted state with the goal of developing treatments that target them. Effective therapeutic development necessitates reliable human in-vitro models that closely mimic disease conditions. To achieve this we adapted an in-vitro TEX model via application of flowing cytometry and time-lapse imaging techniques to kinetically assess TEX cell phenotype and function. Persistent and repeated rounds of polyclonal human CD8 T cell stimulation recapitulated distinctive characteristics of exhausted T cells including high expression of checkpoint receptors and upregulation of transcription factors known to suppress immune activation. Over 8 days and 4 rounds of stimulation TEX cells lost effector capabilities, producing lower levels of pro-inflammatory cytokines and became refractory to re-stimulation through the TCR. In functional cytotoxicity assays TEX cells exhibited substantial deficits in target killing compared to donor matched Teff cell counterparts. Checkpoint receptor blockade partially restored Teff function by enhancing immune mediated target cell death. Overall, this in-vitro TEX assay models key aspects of CD8 T cell exhaustion and offers a versatile and accessible platform to test novel therapeutics targeting exhaustion pathways either individually or in combination with checkpoint inhibitors to test if they fully restore effector function.
Citation Format: Paulina Goral, Louise Brackenbury, Robert Nunan, Rhiannon Jenkinson. A human in-vitro T cell exhaustion model for assessing immuno-oncology therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3869.