bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5825: Reduced miR-371b-5p expression drives tumor progression via CSDE1/RAC1 regulation in triple-negative breast cancer
Authors: Park Jong Hoon , Kim Yesol , Ko Je Yeong , Lee Soo-Been , Park Minah 
Published: June 2022

Abstract
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer; however, specific prognostic biomarkers have not yet been developed. In this study, we identified dysregulated microRNAs (miRNAs) in TNBC by profiling miRNA and mRNA expression. In patients with TNBC, miR-371b-5p expression was reduced, and miR-371b-5p overexpression significantly mitigated TNBC cell growth, migration, and invasion. In addition, we found that expression of cold shock domain-containing protein E1 (CSDE1), a direct target gene of miR-371b-5p, was upregulated in TNBC cells, and inhibition of CSDE1 expression alleviated TNBC cell growth by regulating RAC1 transcription. Mechanistically, CSDE1, phosphorylated C-terminal domain (p-CTD) of RNA polymerase II (RNAPII), and CDK7 form a complex, and downregulation of CSDE1 leads to weak interaction between RNAPII p-CTD and CDK7, resulting in a decrease in RNAPII p-CTD expression to reduce RAC1 transcript levels in CSDE1-deficient TNBC cells. Our data demonstrate that miR-371b-5p is a tumor-suppressive miRNA that regulates the CSDE1/Rac1 axis and could be a potential prognostic biomarker for TNBC.
Citation Format: Jong Hoon Park, Yesol Kim, Je Yeong Ko, Soo-Been Lee, Minah Park. Reduced miR-371b-5p expression drives tumor progression via CSDE1/RAC1 regulation in triple-negative breast cancer [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 5825.
Abstract 5826: Autophagy regulates cancer stem cell properties in triple negative breast cancer via miR-181a-mediated regulation of ATG5/ATG2B
Authors: Park Jong Hoon , Park Jee Won , Kim Yesol , Jun Jaehee , Ahn Yejin 
Published: June 2022

Abstract
Autophagy has a dual role in the maintenance of cancer stem cells (CSCs), but the precise relationship between autophagy and cancer stemness requires further investigation. In this study, it was found that luminal and triple-negative breast cancer require distinct therapeutic approaches because of their different expressions of autophagy flux. We identified that autophagy flux was inhibited in triple-negative breast cancer (TNBC) CSCs. Moreover, miRNA-181a (miR-181a) is upregulated both in TNBC CSCs and patients. ATG5 and ATG2B participate in the early formation of autophagosomes and were revealed as targets of miR-181a. Inhibition of miR-181a expression led to attenuation of TNBC cancer stemness and an increase in autophagy flux. Furthermore, treatment with curcumin led to attenuation of cancer stemness in TNBC CSCs; the expression of ATG5 and ATG2B was enhanced and there was an increase of autophagy flux. These results indicated that ATG5 and ATG2B are involved in the suppression of cancer stemness in TNBC. In summary, autophagy inhibits cancer stemness through the miR-181a-regulated mechanism in TNBC. Promoting tumor-suppressive autophagy using curcumin may be a potential method for the treatment of TNBC.
Citation Format: Jong Hoon Park, Jee Won Park, Yesol Kim, Jaehee Jun, Yejin Ahn. Autophagy regulates cancer stem cell properties in triple negative breast cancer via miR-181a-mediated regulation of ATG5/ATG2B [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 5826.
Abstract 5844: A comprehensive pan-cancer analysis of MDM2/MDM4 gene amplification in Chinese solid cancer patients
Authors: sun xiangyu , Fu Zhichao 
Published: June 2022

Abstract
Background: Many patients with cancer have benefited from immunotherapy represented by the blockade of immune checkpoint PD-1/PD-L1. However, about 4-29% of cancer patients treated with immunotherapy developed hyper-progressive diseases(HPD) with accelerated tumor growth. MDM2/MDM4 amplification was suggested as genomic correlates for elevated risk hyperprogression. The objective of this study was to evaluate the frequency of amplification of MDM2/MDM4 in the Chinese solid tumor patients and to provide advice on the selecting of optimal treatment decisions.
Methods: Tumor or blood samples were collected from 2,937 patients with solid cancer, genetic mutations and amplification was detected using the next-generation sequencing(NGS).
Results: A total 112 patients with MDM2/MDM4 amplification were identified, including lung cancer 50.9% (57/112), colorectal cancer 14.3% (16/112), gastric cancer 8.0% (9/112), liver cancer 5.4% (6/112), Biliary tract cancers 4.5% (5/112), breast cancer 2.7% (3/112), and pancreatic ductal adenocarcinoma 2.7% (3/112). TMB value was identified, The median TMB for lung cancer was 9.13 mutations/Mb, median TMB for colorectal cancer was 13.8 mutations/Mb, a high TMB value in gastric cancer (median TMB=20.22 mutations/Mb), and median TMB for liver cancer was 17.9 mutations/Mb. Meanwhile, MSI was detected in 8% of patients with MDM2/MDM4 amplification, of which 3 in lung cancer, 5 in colorectal cancer, and 1in gastric cancer.
Conclusions: Although amplification of MDM2/MDM4 was observed only in a small proportion of patients, it demonstrated an association with high TMB in several common cancer types. In addition, our data indicate that amplification of MDM2/MDM4 in different types of cancer is heterogeneous and that an appropriate immunotherapy strategy for patients with solid cancer should be noted.
Citation Format: xiangyu sun, Zhichao Fu. A comprehensive pan-cancer analysis of MDM2/MDM4 gene amplification in Chinese solid cancer 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 5844.
Abstract 5890: The effect of healthy eating on breast cancer-specific outcomes: A systematic review and meta-analysis
Authors: Han Eric , Kady Vanessa , Montan Kayla , Normuminova Marjona , Eum Soomin , Rovito Michael , Lee Eunkyung 
Published: June 2022

Abstract
Background:  Breast cancer (BC) survivors attempt to change their diet after diagnosis to improve cancer-specific outcomes; however, there are many sets of guidelines available, and cancer survivors are not sure which ones are best to follow. Therefore, we examined the effect of different dietary quality indices on BC-specific outcomes in BC survivors.
Methods:  Web of Science and EBSCOhost were searched for relevant publications using the key terms in June 2021. Covidence software was then used for the screening and extraction of these publications. Characteristics for the included studies such as, participants, and dietary quality index were examined, and summary effect sizes were estimated for BC recurrence and BC-specific mortality using a random-effects model.
Results: Across the 10 included studies (9 BC-specific mortality and 1 Recurrence; 8 Post-diagnosis and 3 pre-diagnosis diet studies), a total of 25,194 BC survivors were included in the meta-analysis, and 2,550 BC-specific deaths and 461 recurrences were observed over a follow up period of 6-17.2 years. The dietary indices evaluated were ACS (n=2), CHFP (n=2), MDS (n=2), DASH (n=3), HEI (n=8), DQIR (n=1), and RFS (n=1). Meta-analysis showed that adhering to dietary guidelines after diagnosis was associated a 4~36% reduction in BC-specific mortality with varying degrees of significance: ACS (HR=0.96, 95% CI=0.72-1.29), CHFP (HR=0.64, 95% CI=0.49-0.83), MDS (HR=0.93, 95% CI=0.70-1.24), DASH (HR=0.79, 95% CI=0.64-0.98), and HEI (HR=0.93, 95% CI=0.70-1.24). Subgroup analysis with DASH guidelines showed that the strength of the association was greater for those with ER-positive, PR-negative, or HER2-positive cancer, physically active, and older survivors compared to their respective counterparts. Only one study evaluated BC recurrence, which was insufficient to perform meta-analysis, and pre-diagnosis adherence to dietary guidelines was not associated with BC-specific mortality (HR=0.98, 95% CI=0.81-1.17).
Conclusions:  Healthcare providers may find it best to encourage BC survivors to comply with the DASH or CHFP dietary guidelines to improve cancer-specific mortality. Additional research should be performed to strengthen the relationship found between adherence to dietary indices and breast cancer-specific outcomes.
Keywords: dietary guidelines, diet quality, breast cancer mortality, DASH, meta-analysis
Citation Format: Eric Han, Vanessa Kady, Kayla Montan, Marjona Normuminova, Soomin Eum, Michael Rovito, Eunkyung Lee. The effect of healthy eating on breast cancer-specific outcomes: A systematic review and meta-analysis [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 5890.
Abstract 5900: Integrating prior knowledge of transcription factor occupied elements with transcriptome-wide association analysis identifies 153 breast cancer susceptibility genes
Authors: Guo Xingyi , He Jingni , Beeghly-Fadiel Alicia , Chen Zhishan , Cao Chen , Shu Xiao-ou , Zheng Wei , Long Quan 
Published: June 2022

Abstract
Transcriptome-wide association studies (TWAS) have been successful in uncovering large numbers of putative disease susceptibility genes. TWAS approaches such as S-PrediXcan, FUSION and TIGAR, show comparable overall performance for susceptibility gene discovery; however, integrating prior disease-specific regulatory information is lacking. To improve accuracy of gene expression prediction by integrating information on susceptible transcription factor (sTF) occupancy in target cells and tissues, we developed an analytical framework, called sTF-TWAS. We evaluated six sets of putative regulatory variants selected from sTF-occupied sites, and performed generalized Berk-Jones (GBJ) analysis to combine sets and quantify overall associations. We demonstrated that sTF-TWAS outperforms S-PrediXcan in both simulation and real data analyses. Using summary statistics data from the Breast Cancer Association Consortium (BCAC), we also incorporated alternative splicing (sp) data in TF-TWAS and identified 76 and 88 significant genes for breast cancer risk at a Bonferroni-corrected P &lt;0.05 from sTF-TWAS and sp-sTF-TWAS, respectively. Of 153 putative susceptibility genes from both sTF-TWAS and sp-sTF-TWAS, 14 genes in 12 loci had novel associations with breast cancer risk and 90 genes were previously unreported by breast cancer GWAS. We also provide strong evidence for 15 previously unreported genes, including 11 essential for breast cell proliferation and five suggested cancer predisposition or driver genes: RAD50, IGHMBP2, ATXN3, KANSL1, and IL6ST. Overall, we demonstrated that our approach has significant advantages over regular TWAS and our findings provide additional insights into the genetic susceptibility of breast cancer.
Citation Format: Xingyi Guo, Jingni He, Alicia Beeghly-Fadiel, Zhishan Chen, Chen Cao, Xiao-ou Shu, Wei Zheng, Quan Long. Integrating prior knowledge of transcription factor occupied elements with transcriptome-wide association analysis identifies 153 breast cancer susceptibility genes [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 5900.
Abstract 5923: Rapid spectroscopic liquid biopsy for the early detection of brain tumors
Authors: Sala Alexandra , Theakstone Ashton G. , Brennan Paul M. , Jenkinson Michael D. , Mills Samantha J. , Syed Khaja , Rinaldi Christopher , Xu Yun , Goodacre Royston , Butler Holly J. , Palmer David S. , Smith Benjamin R. , Baker Matthew J. 
Published: June 2022

Abstract
To support the early detection and diagnosis of brain tumors we have developed a rapid, cost-effective and easy to use spectroscopic liquid biopsy based on the absorbance of infrared radiation. We have previously reported highly sensitive results of our approach which can discriminate patients with a recent brain tumor diagnosis and asymptomatic controls. Other liquid biopsy approaches (e.g., based on tumor genetic material) report a lower classification accuracy for early-stage tumors. In this manuscript we present an investigation into the link between brain tumor volume and liquid biopsy test performance. In a cohort of 177 patients (90 patients with high-grade glioma (glioblastoma (GBM) or anaplastic astrocytoma), or low-grade glioma (astrocytoma, oligo-astrocytoma and oligodendroglioma)) tumor volumes were calculated from magnetic resonance imaging (MRI) investigations and patients were split into two groups depending on MRI parameters (T1 with contrast enhancement or T2/FLAIR (fluid-attenuated inversion recovery)). Using attenuated total reflection (ATR)-Fourier transform infrared (FTIR) spectroscopy coupled with supervised learning methods and machine learning algorithms, 90 tumor patients were stratified against 87 control patients who displayed no symptomatic indications of cancer, and were classified as either glioma or non-glioma. Sensitivities, specificities and balanced accuracies were all greater than 88%, the area under the curve (AUC) was 0.98, and cancer patients with tumor volumes as small as 0.2 cm3 were correctly identified. Our spectroscopic liquid biopsy approach can identify gliomas that are both small and low-grade showing great promise for deployment of this technique for early detection and diagnosis.
Citation Format: Alexandra Sala, Ashton G. Theakstone, Paul M. Brennan, Michael D. Jenkinson, Samantha J. Mills, Khaja Syed, Christopher Rinaldi, Yun Xu, Royston Goodacre, Holly J. Butler, David S. Palmer, Benjamin R. Smith, Matthew J. Baker. Rapid spectroscopic liquid biopsy for the early detection of brain 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 5923.
Abstract 5967: ROSA: An ambassador program facilitating bidirectional partnerships between communities and basic scientists
Authors: Ruiz Gabriela , Lee Amanda 
Published: June 2022

Abstract
Background: Community Outreach and Engagement (COE) is integral in NCI-designated Cancer Centers. COEs work with community stakeholders identifying community needs, communicating research, and catalyzing significant activities to Cancer Center’s catchment areas. To facilitate this, the University of Arizona Cancer Center (UACC) Office of COE established the Research Outreach for Southern Arizona (ROSA) program, supporting bidirectional partnerships between basic scientists and underrepresented communities in catchment areas.
Objective: To describe a community and student ambassador program developed as ROSA, bridging gaps between basic science programs and community needs in UACC catchment areas.
Methods: The UACC catchment areas include five southern Arizona counties where 40% of residents are Hispanic, compared to 18.3% in the US. Moreover, ambassadors were bilingual/bicultural Hispanic undergraduate students (n=4) and Hispanic community members (n=4). The ambassador program held weekly cancer educational discussions, research methods, monthly Meet the Scientist events, and presentations on experiences. Evaluations for ROSA were completed by all affiliates.
Results: Overall, ROSA ambassadors reported increased knowledge of research and increased confidence sharing cancer information. Facilitators of ROSA community members included a bilingual/bicultural team, outreach collaborations, and participant compensation. Barriers included payments for undocumented members, lack of Spanish-speaking scientists, and reduced in-person activities. As a result of ROSA partnerships, scientists, healthcare professionals, and stakeholders is developing Scientific Cafes where scientists present research proposals for community feedback. The workgroup will select a community-driven project to implement in the future.
Discussion: Based on positive ambassador evaluations and working group collaborations, ROSA is successful in growing authentic partnerships between scientists and communities. Recently, a community-based survey was developed by members to examine perceptions of cancer and willingness of clinical research participation. This survey will inform how basic scientists align research within community needs. ROSA will continue to be valuable in providing bidirectional engagement from basic scientists and community members in cancer research.
Citation Format: Gabriela Ruiz, MEd., Amanda Lee. ROSA: An ambassador program facilitating bidirectional partnerships between communities and basic scientists [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 5967.
Abstract 6026: A novel humanized mouse model based on NOG-FcgR-/-mice recapitulates anti-tumor immune reactions by human immune systems in response to anti-PD-1 antibody (Nivolumab)
Authors: Katano Ikumi , Hanazawa Asami , Otsuka Iyo , Yamaguchi Takuya , Mochiduki Misa , Kawai Kenji , Ito Ryoji , Goto Motohito , Kagawa Takahiro , Takahashi Takeshi 
Published: June 2022

Abstract
Humanized mice with human hematopoietic and immune systems have been frequently used for examining in vivo anti-cancer effects of various drugs, including immune checkpoint inhibitors (ICIs) like anti-PD-1 or anti-CTLA-4 antibodies, yet the reliability of the mouse models to be improved. We have recently developed NOD-scid, IL-2Rγ KO (NOG) mice deficient for the mouse FcεRI and FcγIIb genes, thus lacking the expression of functional mouse FcγRs, (NOG-FcγR-/-) and the activity of endogenous antibody-dependent cellular cytotoxicity (ADCC). Reconstitution experiments with human hematopoietic stem cells (HSC) showed that NOG-FcγR-/- mice had higher engraftment capacity for human leucocytes than NOG mice, namely the numbers of HSC-derived human CD19+ B cells and CD33+ myeloid cells, but not CD3+ T cells, were higher in the various tissues in NOG-FcγR-/- mice than those in NOG mice. In tumor-bearing experiments using those reconstituted mice, it was of interest that humanized NOG-FcγR-/- mice (huNOG-FcγR-/-) could invoke strong tumor growth suppression or rejection in response to anti-PD-1 antibody (Nivolumab) treatment in several cancer cell lines, which was absent in conventional huNOG mice. Accordingly, Nivolumab treatment in huNOG-FcγR-/- mice induced a significant increase of human T cells in number in the spleen and infiltration of human T cells with Granzyme B and Perforin-expression into tumor. Furthermore, the composition of activated T cells was different between huNOG-FcγR-/- and huNOG mice. HuNOG-FcγR-/- mice had elevated numbers of activated T cells, both T central memory cells (TCM) and T effector memory cells (TEM), whereas huNOG mice showed an opposite trend, reduced TCM and TEM and increase of naïve T cells. Our results suggest that the novel NOG-FcγR-/- mice become a good model for elucidating the cellular and molecular mechanisms of human tumor rejection by human T cells, and that they will provide a superior in vivo platform for evaluation of anti-cancer drugs, especially, in combination with ICIs like Nivolumab.
Citation Format: Ikumi Katano, Asami Hanazawa, Iyo Otsuka, Takuya Yamaguchi, Misa Mochiduki, Kenji Kawai, Ryoji Ito, Motohito Goto, Takahiro Kagawa, Takeshi Takahashi. A novel humanized mouse model based on NOG-FcgR-/-mice recapitulates anti-tumor immune reactions by human immune systems in response to anti-PD-1 antibody (Nivolumab) [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 6026.
Abstract 6030: Reconstructed Pancreas: A tumor-specific 3D culture platform for accurate evaluation of therapeutic agents in pancreatic cancer
Authors: Kirshner Eleanore J. , Ahlawat Aayushi , Ryou Matthew 
Published: June 2022

Abstract
As it is rarely diagnosed early, the prognosis for patients with pancreatic cancer is grim. The average 5-year survival rate is 10% and only 3% for patients with metastatic disease. Partially because of the late diagnosis and partially because of its biology, treatment options for patients with pancreatic cancer are limited and new interventions are desperately needed to gain the upper hand on this disease. One of the challenges faced by the drug developers looking for agents against pancreatic cancer is capturing the elements of the tumor microenvironment, which provides both a physical barrier and stroma-driven resistance to therapeutic agents. We developed a tumor-specific Reconstructed Pancreas (r-Pancreas) model, which recapitulates the cellular and extracellular elements of the pancreatic tumor microenvironment. In the r-Pancreas model, tumor and stromal cells are embedded in a dense extracellular matrix (ECM) characteristic of pancreatic tumors. Pancreatic tumor cell lines, MiaPaca-2, Panc-1, and Bx-PC3 robustly proliferate and survive for 14 days providing an extended therapeutic window to test anti-tumor compounds in the context of pancreas-specific ECM. Mimicking clinical response pancreatic tumor cells grown in r-Pancreas are sensitive to gemcitabine (IC50=0.4-0.6µM) but are resistant to 5-fluorouracil (IC50=not reached). These cell lines were also 5-10 times less sensitive to gemcitabine when cultured in Matrigel (IC50=3-6µM), soft ECM rich in collagen IV/laminin neither of which is abundant in the pancreas. Incorporating a collagen-rich capsule into the r-Pancreas model further expands its physiological relevance as human pancreatic tumors have been shown to have an outer layer of stiff ECM, which provides a physical barrier that impedes drug access to the tumor. Finally, establishing a co-culture of pancreatic tumor cell lines with primary pancreatic stromal cells creates a complete model enabling testing of novel therapeutic agents within the pancreatic tumor microenvironment. Taken together these data suggest that to be clinically useful in vitro tumor models not only need to allow for 3-dimensional cell growth but also have to incorporate tumor-specific elements of the microenvironment.
Citation Format: Eleanore J. Kirshner, Aayushi Ahlawat, Matthew Ryou. Reconstructed Pancreas: A tumor-specific 3D culture platform for accurate evaluation of therapeutic agents in pancreatic cancer [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 6030.