bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2660: The gene mutation profile in HCC patients with different AFP levels at diagnosis
Authors: Kui Xiang , Wu Liqun , Ke Yang , Wang Yan , Li Hai , Zhao Juan , He Tingting , Wang Lin 
Published: July 2021

Abstract
Background: Alpha-fetoprotein (AFP) blood level in Hepatocellular carcinoma (HCC)is an important marker widely used in clinical practice. Although different AFP levels indicate the different prognosis of HCC patients, the gene mutation profile is still unclear. The research was to conduct a comprehensive study of the gene mutation profile in HCC patients with different AFP levels at diagnosis.
Methods: Retrospective analysis was carried out on medical records of HCC patients who had received a hepatectomy between January 2016 and December 2018. Formalin-fixed, paraffin-embedded (FFPE) HCC tissues and matched blood samples were collected for targeted next-generation sequencing (NGS) assay at OrigiMed (Shanghai, China), a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Genomic variants including single nucleotide variations (SNV), short/long insertion/deletions (Indel), copy number alterations and gene rearrangements were analyzed.
Results: A total of 180 HCC cases were enrolled in the study. The patients were categorized into AFP&lt;10ng/ml (n=63) group, 10ng/ml≤AFP&lt;1000ng/ml (n=71) group, and AFP≥1000ng/ml (n=46) group. The higher AFP level at diagnosis was positively correlated with younger incidence age (P=0.012), lower blood glucose (P=0.008), larger diameter of tumor nodules (P=0.006), more microvascular invasion (P=0.01), higher grade of tumor differentiation (P&lt;0.001), poorer overall survival (P=0.023), and recurrence free survival (P=0.007). AXIN1 mutation frequency significantly increased with the rise of the APF level: AFP&lt;10ng/ml (7.9%), 10ng/ml≤AFP&lt;1000ng/ml (25.4%), and AFP≥1000ng/ml (42.2%, P&lt;0.001), while TP53 mutation frequency decreased with the rise of the AFP level: AFP&lt;10ng/ml (65.1%), 10ng/ml≤AFP&lt;1000ng/ml (57.7%), and AFP≥1000ng/ml (48.9%) with only near significance (P=0.095) among three groups. Furthermore, we identified 11q13 (FGF3, FGF4, FGF19, CCND1) amplification frequency increased with AFP level: AFP&lt;10ng/ml 4.8%, 10ng/ml≤AFP&lt;1000ng/ml 12.7%, and AFP≥1000ng/ml 20.9%, P=0.015.
Conclusion: We demonstrated AXIN1 mutation frequency increased with the rise of the AFP level. Because these AXIN1 mutations can result in inactivating the AXIN1 protein and the AXIN1 is a known negative regulator of the Wnt/β-catenin signaling pathway, we reason that the Wnt/β-catenin signaling pathway has a deleterious effect on the poor prognosis in the higher AFP groups, and/or directly on the rise of the AFP level.
Citation Format: Xiang Kui, Liqun Wu, Yang Ke, Yan Wang, Hai Li, Juan Zhao, Tingting He, Lin Wang. The gene mutation profile in HCC patients with different AFP levels at diagnosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2660.
Abstract 2840: HK1 induces epithelial-mesenchymal transition and promotes metastasis of colorectal cancer
Authors: Zheng Xiaobin , Liu Huashan , Zhong Xiaoli , Liu Xuanhui , Cai Zerong , Chen Yufeng , He Xiaosheng , Lan Ping , Wu Xiaojian 
Published: July 2021

Abstract
Hexokinase 1 (HK1) has been implicated in tumorigenesis. However, its role in tumor metastasis and progression has not been evaluated. The aim of this study is to evaluate the role of HK1 in the metastasis in CRC.
Methods: The expression level of HK1 was detected using quantitative RT-PCR and western blot in 9 CRC cell lines and 1 human colon epithelial cell line NCM460 (Figure 1A). HK1 was overexpressed via lentiviral vector system and silenced using specific small interference RNA (si-HK1) in DLD1 and HCT8. Then wound-healing, migration assay and invasion assay were carried out to investigate the function of HK1 in CRC cells. RT-PCR and Western blot was performed to detect the change of Snail2 following the up-regulated expression of HK1.
Results: HK1 expression was overexpressed by HK1-cDNA and was inhibited by si-HK1 in DLD1 and HCT8 (Figure 1B and 1C). Ectopic expression of HK1 promoted cell migration and invasion in CRC cells and promoted lung metastasis in mouse models (Figure 1D). Furthermore, HK1 induced migration and invasion in CRC cells was found to activate expression of Snail2 and in turn, induce epithelial-mesenchymal transition (EMT) and cancer progression (Figure 1E).
Conclusions: High expression of HK1 could activate expression of Snail2 and in turn, induce EMT. Our findings suggest that HK1 may be a potential prognostic biomarker and therapeutic target for CRC invasion and metastasis.
Keywords: Colorectal Cancer, HK1, Migration, Invasion
Figure 1. A. The expression level of HK1 in 10 cell lines. B, C. HK1 expression was overexpressed by HK1-cDNA and was inhibited by si-HK1 in DLD1 and HCT8. *P&lt; 0.05. D. Overexpression of HK1 in HCT8 increased the capacity of cell migration and invasion in vitro and in vivo. E. Expression levels of Snail2 and EMT were induced after HK1 overexpression.
Citation Format: Xiaobin Zheng, Huashan Liu, Xiaoli Zhong, Xuanhui Liu, Zerong Cai, Yufeng Chen, Xiaosheng He, Ping Lan, Xiaojian Wu. HK1 induces epithelial-mesenchymal transition and promotes metastasis of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2840.
Abstract 2869: Blockade of oxidative phosphorylation by metformin promotes anoikis
Authors: Adeshakin Funmilayo Oladunni , Zhang Guizhong , Adeshakin Adeleye O. , Wan Xiaochun 
Published: July 2021

Abstract
Metastasis remains the foremost cause of death in cancer patients. Cells with metastasizing potentials are equipped to evade anoikis, a form of cell death resulting from cell detachment from extracellular matrix. Evasion of anoikis signals avails cells the ability to detach, migrate, and invade secondary sites, colonizing these sites thereby promote cancer metastasis. Cellular reprogramming has been identified as a crucial factor for tumor metastasis and yet to be fully explored. Our data showed upregulation in oxidative phosphorylation (OXPHOS) related genes in detached cells compared to adherent cells, suggesting that OXPHOS activity may enhance resistance to anoikis. Accordingly, treatment with metformin, a mitochondrial complex 1 inhibitor promoted anoikis in different cancer cells (cervical cancer - Hela, breast - MCF7, melanoma -B16F10 and Lewis Lungs carcinoma - LLC). Furthermore, metformin decreased spheroid formation, repressed ATP production, accumulated misfolded protein, and sensitized cells to anoikis via activation of caspase 3 and ROS production. More importantly, targeting OXPHOS with metformin inhibited pulmonary tumor metastasis, impaired lung nodules formation, and reduced lung weight in the B16F10 tumor model of balb/c nude mice. Collectively, our findings suggest therapeutic targeting of energy metabolism using metformin as a promising approach to enhance anoikis and attenuate tumor metastasis.
Citation Format: Funmilayo Oladunni Adeshakin, Guizhong Zhang, Adeleye O. Adeshakin, Xiaochun Wan. Blockade of oxidative phosphorylation by metformin promotes anoikis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2869.
Abstract 3053: Armed oncolytic virus for treatment of pediatric diffuse intrinsic pontine glioma
Authors: Gupta Sumit , Laspidea Virginia , Fueyo Juan , Becher Oren , Nguyen Teresa , Shin Dong Ho , Jiang Hong , Sohoni Sagar , Fan Xuejun , Yi Yanhua , Gumin Joy , Lang Frederick , Gomez-Manzano Candelaria , Alonso Marta M. 
Published: July 2021

Abstract
Diffuse Intrinsic Pontine Glioma (DIPG) is the leading cause of pediatric death by brain tumors with a median survival of only 9 months, in spite of the current standard of therapy which includes radiation. The purpose of our study is to explore the use of oncolytic adenoviruses as a new therapeutic modality. Our group is leading a phase I clinical trial in naive DIPGs treated with the oncolytic adenovirus Delta-24-RGD, also named DNX-2401 (NCT03178032), which results are still pending. Of interest, clinical trials using Delta-24-RGD in adult gliomas resulted in encouraging results with long-term survivors and the presence of a strong anti-tumor immunity. In this study, we aim to test the effect of armed Delta-24-RGD with immune costimulatory ligands such as GITRL (Delta-24-GREAT) and OX-40L (Delta-24-RGDOX or DNX-2440) for the treatment of DIPGs. We used a panel of murine DIPG cell lines (NP53 and XFMA) to test the effect of these armed-oncolytic adenoviruses. Infectivity assay using an Ad-RGD-GFP vector and flow cytometry showed the expression of the ectopic GFP in more than 80% of the NP53 cells (50 MOIs) and XFMA cells (30 MOIs). Consistent results were obtained using flow cytometry and western blot to detect the expression of the ectopic ligands GITRL and OX-40L in these cultures. These cells were semipermissive for viral replication as assessed by the detection of the viral structural protein hexon in western blot analysis. Preliminary in vivo data using immunocompetent mice models where DIPG cells have been implanted into the pons showed a dose-dependent effect and the generation of immune memory. Our results suggest that oncolytic adenoviruses expressing positive immunocheckpoints might prove be a new effective modality for treating DIPG and hence, increase survival in children suffering this dismal disease.
Citation Format: Sumit Gupta, Virginia Laspidea, Juan Fueyo, Oren Becher, Teresa Nguyen, Dong Ho Shin, Hong Jiang, Sagar Sohoni, Xuejun Fan, Yanhua Yi, Joy Gumin, Frederick Lang, Candelaria Gomez-Manzano, Marta M. Alonso. Armed oncolytic virus for treatment of pediatric diffuse intrinsic pontine glioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3053.
Abstract 3067: Exploring strategies to modulate mitochondrial metabolism to alleviate tumor hypoxia
Authors: Benej Martin , Wu Jinghai , Kreamer McKenzie , Vibhute Sandip , Papandreou Ioanna , Denko Nicholas C. 
Published: July 2021

Abstract
Radiation therapy is a standard type of treatment modality used as a part of curative or palliative treatment in more than 50% of all cancer patients. However, tumor hypoxia reduces the effectiveness of radiation therapy by limiting the biologically effective dose. Here, we explore and compare strategies to alleviate hypoxia by modifying the oxygen supply or demand within mouse tumor models. We used pODD-Luc, a dynamic in vivo luciferase reporter system that monitors relative levels of tumor hypoxia in real time. We show that in mouse tumor models, contrary to the reported results of human clinical trials, acute manipulation of systemic oxygen delivery significantly reduces the level of hypoxia. We then examined pharmacological manipulation of oxygen demand, which is an emerging trend in therapeutic efforts to sensitize tumors to anti-cancer therapy. Mitochondrial oxygen consumption (OCR) constitutes more than 90% of cellular oxygen demand by coupling carbon source oxidation with ATP generation in a series of redox reactions transferring electrons from reduced cofactors to molecular oxygen. Mechanistically, a decrease in mitochondrial OCR would lead to increased oxygen availability within the tumor, allowing initially hypoxic areas to become re-oxygenated. We found that strategies that directly stimulate mitochondrial OCR exacerbate levels of hypoxia while OCR suppression in turn promotes tumor re-oxygenation. We have previously shown that papaverine, an FDA-approved phosphodiesterase 10A (PDE10A) inhibitor effectively reduces hypoxic tumor fractions in vivo by an off-target effect that inhibits mitochondrial complex I. Here we show that its novel derivative SMV-32 that acts as complex I inhibitor with reduced PDE10A effect mediates superior OCR inhibition in both orthotopic and heterotopic mouse tumor models. These findings further establish the direct impact of OCR manipulation on tumor hypoxia and support the role of mitochondrial metabolism as an attractive target to alleviate tumor hypoxia and overcome treatment resistance.
Citation Format: Martin Benej, Jinghai Wu, McKenzie Kreamer, Sandip Vibhute, Ioanna Papandreou, Nicholas C. Denko. Exploring strategies to modulate mitochondrial metabolism to alleviate tumor hypoxia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3067.
Abstract 498: ZL-1201, a differentiated CD47 therapeutic antibody with improved hematological safety profile
Authors: Wan Bing , Fang Xu , Li Shou , Shi Wenhua , Li Holly , Bellovin David , Wang Lei , Zhu Yusong , Lin Yuan , Qi Shali , Yin Sophia , Tao Frank , Kang Lishan , Kabbarah Omar , Zhou Haiying , Veiby Petter , Yan James , Hsu Karl 
Published: July 2021

Abstract
The interaction between CD47 that is overexpressed on tumor cells and SIRPα on macrophages facilitates a “don't-eat-me” signal that inhibits macrophage-mediated phagocytosis of tumor cells. Blockade of the CD47/SIRPα interaction using antibodies against CD47 or SIRPα-Fc fusion proteins promotes phagocytosis and tumor cell destruction, which represents a promising strategy for tumor immunotherapy. However, CD47 is ubiquitously expressed on all cells including erythrocytes and platelets, which form a large antibody sink and lead to potential hematological toxicities. In fact, anemia and thrombocytopenia have been observed in non-human primates and tumor patients that are subjected to anti-CD47 treatment in preclinical and clinical studies. We have developed ZL-1201, a recombinant, humanized monoclonal antibody that specifically targets CD47. ZL-1201 was engineered to reduce Fc-mediated antibody effector function. Preclinical in vitro studies show that ZL-1201 displays potent binding to CD47 thereby blocking interaction with SIRPα and effectively facilitates macrophage-mediated phagocytosis of hematological and solid tumor cells. Importantly, ZL-1201 induces minimal red blood cell (RBC) phagocytosis and does not induce hemagglutination, though it does bind to human RBCs and platelets. In vivo studies demonstrate that ZL-1201 possesses potent antitumor efficacy in rodent xenograft tumor models, while displaying remarkably improved hematological safety profile as compared with the benchmark antibody in a toxicology study in cynomolgus monkeys. Thus, ZL-1201 treatment represents an effective CD47-targeting therapy with improved hematological safety consequences. A Ph1 dose escalation study to assess the safety of ZL-1201 is currently ongoing in patients with solid tumors, and future combination studies are planned for both hematologic and solid tumor indications.
Citation Format: Bing Wan, Xu Fang, Shou Li, Wenhua Shi, Holly Li, David Bellovin, Lei Wang, Yusong Zhu, Yuan Lin, Shali Qi, Sophia Yin, Frank Tao, Lishan Kang, Omar Kabbarah, Haiying Zhou, Petter Veiby, James Yan, Karl Hsu. ZL-1201, a differentiated CD47 therapeutic antibody with improved hematological safety profile [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 498.
Abstract 704: Sex and age differences in telomere length and susceptibility to COVID-19
Authors: Kamal Manar Ahmed , Alamiry Kareem Reda , Zaki Mahmoud 
Published: July 2021

Abstract
Background: Telomeres are the ends of a chromosome and play a fundamental role as vanguards contra the chromosomal decay. Due to the inability of DNA polymerase to replicate chromosomal ends, a reduction in telomeres length happens after each cell division. The existence of shorter telomeres in older people is related to diminished immune functions. Viral infections able to stimulate remodeling of cells, stress responses, and telomere shortening. Moreover, telomere shortening can be caused by extrinsic environmental variables which induce oxidative stress under conditions of inflammation.
Aim: To identify the correlation between telomere shortening and susceptibility to Novel Coronavirus Disease 2019 (COVID-19). In addition to clarifying changes in telomere length according to the viral infection, the effect of sex and age differences in telomere length in confirmed positive COVID-19 cases are also reviewed.
Conclusion: There is a correlation between telomere length and COVID-19 infection with higher susceptibly of elderly patients and males due to shortening in their telomere length. Approximately 53% of (111,428) infected cases (≥50) years old are males, and 47% of (111,428) infected cases (≥50) years old are females.
Citation Format: Manar Ahmed Kamal, Kareem Reda Alamiry, Mahmoud Zaki. Sex and age differences in telomere length and susceptibility to COVID-19 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 704.
Abstract 714: From cancer to COVID-19- development of a dendritic cell-targeted nano-vaccine for prevention and therapy of COVID-19
Authors: Vaskovich-Koubi Daniella , Kleiner Ron , Liubomirski Yulia , Yeini Eilam , Tiram Galia , Pozzi Sabina , Eldar-Boock Anat , Florindo Helena F. , Satchi-Fainaro Ronit 
Published: July 2021

Abstract
Dendritic cells (DC) are antigen-presenting cells with an important role in the initiation and regulation of the innate and adaptive arms of the immune system. By efficient presentation of antigens, DC elicit an antigen-specific immune response. Therefore, we previously established in our laboratory a melanoma-DC-targeted NP that was evaluated and validated against aggressive melanoma. Although DC-therapy is mainly exploited in the treatment of cancer, DC are becoming a key therapeutic target in other pathologies such as infectious diseases. Viral pathogens, similarly, to cancer, modulate the host defense mechanisms to their benefit. COVID-19, an ongoing pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally and is already infecting tens of millions of people worldwide. Historically, vaccines are among therapies with the greatest impact in health and constitute an unmet medical need against coronavirus disease-19 (COVID-19) pandemic. To that end, we repurposed our recently published melanoma-targeted NP to co-deliver modulators of host immune response and SARS-CoV-2 specific antigen epitopes discovered by a computational approach integrating 3D information with large-scale statistical analysis. The immune response kinetics in patients infected with SARS-CoV-2 is poorly understood, but recent reports show that germinal B cells and active follicular T-helper cells, IgM/IgG SARS-CoV-2 antibodies, in addition to an enhanced cellular immunity, are found in patients with mild-to-moderate SARS-CoV-2 infection. Our preliminary data demonstrated that our nano-vaccine was able to activate specific immune cell response of effector T cells and B cells and decrease the regulatory activity of T cells, compared to controls. Moreover, we found that our DC-targeted SARS-CoV-2 NP successfully induced antigen-specific secretion of IgM and IgG antibodies with high binding affinity to the antigens. Importantly, our nano-vaccine elicited specific neutralization of Spike virus like particles (VLPs) by sera of immunized mice. We hypothesize that implementing our novel nano-vaccine platform for COVID-19 will lead to a safe and efficacious COVID-19 vaccine ready for first-in-human clinical trials.
Citation Format: Daniella Vaskovich-Koubi, Ron Kleiner, Yulia Liubomirski, Eilam Yeini, Galia Tiram, Sabina Pozzi, Anat Eldar-Boock, Helena F. Florindo, Ronit Satchi-Fainaro. From cancer to COVID-19- development of a dendritic cell-targeted nano-vaccine for prevention and therapy of COVID-19 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 714.
Abstract 786: Geography and adolescent and young adult cancer stage and survival
Authors: Johnson Kimberly J. , Wang Xiaoyan , Barnes Justin , Delavar Arash 
Published: July 2021

Abstract
Background. Survival improvement in adolescents and young adults (AYA) diagnosed with cancer has lagged behind other age groups. Few studies have focused on geographic factors and outcomes in AYA. Our objective was to evaluate evidence for geographic disparities in cancer diagnosis stage and overall survival in AYAs. We also examined whether stage mediated survival associations.
Methods. National Cancer Database data on AYA 15-39 years diagnosed from 2010-2014 were obtained. Rural/metro residence at diagnosis was defined using Rural Urban Continuum Codes. Distance between the case's residence and the reporting hospital was classified as short (&lt;12.5 miles), intermediate (&gt;12.5 and &lt;50 miles), and long (&gt;50 miles). Logistic and Cox proportional hazards regression models were used for analyses.
Results. The stage and survival analyses included 146,418 and 178,688 AYA. The odds of a late vs. early stage diagnosis (stages 3 and 4 vs. 1 and 2) were 1.22 (95% CI 1.10 to1.35) times higher for AYA living in rural vs. metro counties and 1.23 (1.19 to1.28) times higher for AYA living at long vs. short distances. The hazard of death was 1.18 (1.04 to 1.34) and 1.37 (1.31 to 1.43) times higher for those living in rural vs. metro counties and for long vs. short distances. Stage mediated 41% and 27% of the associations between survival and rural/metro residence and residential distance.
Conclusions. Rural residence and living long distances from the reporting hospital were associated with later-stage diagnoses and lower survival in AYA cancer patients. Further research is needed to understand mechanisms.
Citation Format: Kimberly J. Johnson, Xiaoyan Wang, Justin Barnes, Arash Delavar. Geography and adolescent and young adult cancer stage and survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 786.