bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 361: Targeting the suppressor of ferroptosis to improve the treament effeciency of glioblastoma
Authors: Wang Jing 
Published: March 2024

Abstract
Glioma is the most frequent tumor in central nervous system (CNS), which makes up about 30% of CNS tumors. The current standard strategy for glioma treatment is surgery plus adjuvant chemotherapy and concurrent radiotherapy. Even though, the prognosis of glioma is still poor. It’s encouraging that temozolomide (TMZ) prolongs the overall survival of glioma patients, but the following TMZ resistance is really frustrating. It’s urgent to figure out efficient ways to improve the long term prognosis of patients, such as antagonizing the TMZ resistance. Ferroptosis was a newly discovered type of regulated cell death characterized by iron-dependent aberrant lipid peroxidation and membrane damage in the last decade. Ferroptosis-associated iron transport proteins modulate the process precisely through controlling the iron content. ZIP14, also known as SLC39A14, is an eight-transmembrane protein which could transport divalent metal ion like Mn2+, Zn2+ and Fe2+. Our preliminary data showed that the expression level of ZIP14 was higher in tumor tissues than paired normal tissue, which was corelated with poor prognosis of glioma. Knock down ZIP14 could induce cell death, and which could be rescued by inhibitors for ferroptosis but not for apoptosis or necrosis. Knock down ZIP14 decreased the ferroptosis inhibition by Ferroptosis suppress protein 1 (FSP1) which through reduction of lipid peroxidation, and sensitized cells to TMZ. Furthermore, we found that ZIP14 formed a complex with Ubiquinone. And it was known that FSP1 is critical in the switch of ubiquinone to ubiquinol. Therefore, we propose that ZIP14 suppress lipid peroxidation through blockage of the transition of ubiquinone to ubiquinol. While ZIP14 was knocked down, the complex with Ubiquinone wad damaged, and could not further change to Ubiquinol, so the suppression to lipid peroxidation was released, and then, ferroptosis was upregulated. In this study, we are going to figure out the molecular mechanism about how ZIP14 suppress ferroptosis and find out efficient small molecule inhibitors to activate ferroptosis by abolishing ZIP14 and improve the prognosis of glioma patients.
Citation Format: Jing Wang. Targeting the suppressor of ferroptosis to improve the treament effeciency of glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 361.
Abstract 3639: ARID1 mutations may serve as a predictor of MSI and TMB levels in gastric cancer
Authors: Xu Chunsheng , Lian Bo , Dai Yujie , Duan Weiming , Zhao Feilong , Li Mengbin 
Published: March 2024

Abstract
Background: ARID1A is a gene that produces a protein called BAF250a, which is a component of the chromatin remodeling complex. This complex plays a critical role in regulating gene expression by altering the structure of chromatin. ARID1A mutations and MSI-H are mutually exclusive in endometrial cancer, but not in ovarian cancer. ARID1A mutations are associated with high TMB in certain types of cancer, such as endometrial and gastric cancer. The relationship between ARID1B mutations and MSI-H/TMB is complex, and this study aims to clarify it in gastric cancer.
Methods: The formalin-fixed paraffin-embedded (FFPE) tissues 337 patients with gastric cancer who have underwent next-generation sequencing (NGS) include 733 genes from Nov, 2019 to Mar, 2023 in 3DMed Clinical Laboratory Inc. were investigated in this study. These patients are still being followed up.
Result: In this study, 337 patients with gastric cancer were analyzed for ARID1A and ARID1B mutations, MSI-H status, and TMB levels. The
results showed that 17.8% of the patients had ARID1A mutations, 8.9% had ARID1B mutations, and 3.6% had both mutations. Additionally, 7.7% of the all patients had MSI-H. The study found that patients with ARID1 mutations had significantly higher rates of MSI-H compared to unselected patients. Specifically, 35% of patients with ARID1A mutations, 30% with ARID1B mutations, and 75% with both mutations had MSI-H, compared to 7.7% in unselected patients. Furthermore, TMB levels were higher in patients with ARID1A or ARID1B mutations compared to wild-type and unselected patients (p&lt;0.0001). There was no significant difference observed between patients with ARID1A and ARID1B mutation subgroups in terms of TMB levels (p = 0.3515). However, TMB levels were lower in patients with ARID1A or ARID1B mutations compared to patients with both mutations (p = 0.0036, p = 0.0104). These findings suggest that ARID1 mutations may cause genomic and chromosomal instability in gastric cancer, leading to higher rates of MSI-H and TMB.
Conclusion: The study highlights the potential clinical significance of ARID1 mutations as a biomarker for predicting MSI-H and TMB levels in gastric cancer, which could help guide personalized treatment strategies for patients with this disease. However, further research
is needed to confirm these findings and to determine the clinical implications of ARID1 mutations in gastric cancer.
Citation Format: Chunsheng Xu, Bo Lian, Yujie Dai, Weiming Duan, Feilong Zhao, Mengbin Li. ARID1 mutations may serve as a predictor of MSI and TMB levels in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3639.
Abstract 3643: Molecular pathogenesis of lung cancer associated with interstitial pneumonia
Authors: Mizuno Daisuke , Shien Kazuhiko , Matsuoka Atsushi , Ohki Masayoshi , Tomida Shuta , Yoshichika Ryo , Higashihara Tomoaki , Mukohara Fumiaki , Hayashi Naohiro , Habu Tomohiro , Yoshikawa Mao , Suzawa Ken , Yamamoto Hiromasa , Ennishi Daisuke , Toyooka Shinichi 
Published: March 2024

Abstract
Background: Interstitial pneumonia (IP) is known to be associated with a high risk of developing lung cancer. While common mechanisms have been reported to be involved in the pathogenesis of IP and lung cancer, including genetic and epigenomic alterations or specific signaling pathway activations, many of the molecular mechanisms of lung cancer development in IP lesions remain unknown.
Methods: To clarify the detailed mechanisms of the pathogenesis of lung cancer associated with IP, we performed spatially resolved transcriptomics on lung cancer specimens obtained from usual interstitial pneumonia (UIP) associated lung cancer patients. In a total of 10 patients, including five lung cancers that developed inside the UIP and five lung cancers that originated outside the UIP, regions of interest (ROIs) were selected in the tumoral tissues and their adjacent non-tumor tissues. Then, gene expression profiles were comprehensively analyzed by using GeoMx digital spatial profiler in each ROI.
Results: In the UIP lesions adjacent to lung cancer, increased gene expressions associated with pulmonary fibrosis, such as COL1A1, COL3A1, and APOE, were observed, and gene set enrichment analysis (GSEA) revealed that they were associated with autoimmunity-related pathways. When we compared the tumor lesions developed inside the UIP with outside the UIP, increased gene expressions related to IP mortality were observed in the tumor cells developed inside the UIP. Interestingly, GSEA revealed that the gene set for neutrophil extracellular trap (NETs) formation was found to be upregulated in the tumor cells developed inside the UIP, suggesting that NETs plays an important role in the pathogenesis of lung cancer developed in IP lesion.
Conclusions: In our study, spatially resolved transcriptomics revealed a novel pathway related to the pathogenesis of lung cancer associated with IP.
Citation Format: Daisuke Mizuno, Kazuhiko Shien, Atsushi Matsuoka, Masayoshi Ohki, Shuta Tomida, Ryo Yoshichika, Tomoaki Higashihara, Fumiaki Mukohara, Naohiro Hayashi, Tomohiro Habu, Mao Yoshikawa, Ken Suzawa, Hiromasa Yamamoto, Daisuke Ennishi, Shinichi Toyooka. Molecular pathogenesis of lung cancer associated with interstitial pneumonia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3643.
Abstract 3727: Synergistic effect of CD47 blockade and EPHA3 treatment on recurrent head and neck cancers
Authors: Kim Song Hee , Han Myung Woul , Kim Ji Won , Kim Seong Who 
Published: March 2024

Abstract
CD47 acts as a “don’t eat me “signal and suppresses it through its interaction with signal regulatory protein (SIRP-a) on the macrophage. CD47 is expressed in many human cancer cells, including head and neck cancer. Additionally, we reported in a previous study that EphA3 is overexpressed in radioresistant head and neck cancer and may play an important role in the development of radioresistance in head and neck cancer. In our present study, we demonstrated that the blockade of EPHA3 and CD47 attenuates the function of M2-like macrophages and may contribute to macrophage polarization toward the M1 phenotype. Here, we combined a therapeutic strategy of an anti-EPHA3 and an anti-CD47 antibody. Using mRNA sequencing and fluorescence imaging, we showed that the combination treatment could significantly enhance the effectiveness of anti-EPHA3 and anti-CD47 antibodies, in reactivating macrophages and reversing macrophage polarization. In addition to using flow cytometry in vivo, combination treatments can alter the proportion of tumor-associated macrophages (TAMs). Collectively, our findings suggested that the combination treatment of anti-EphA3 and the anti-CD47 antibodies could significantly improve tumor suppression, increase the proportion of M1 macrophages, and decrease the proportion of M2 macrophages.
Citation Format: Song Hee Kim, Myung Woul Han, Ji Won Kim, Seong Who Kim. Synergistic effect of CD47 blockade and EPHA3 treatment on recurrent head and neck cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3727.
Abstract 3760: The importance of optimizing DNA extraction conditions for formalin fixed paraffin embedded tissues
Authors: Butler Matthew G. , Forson Benedicta , Cowen Maria , Ramprakash Jayanthi , Lowe Dana Ruminski , Konigshofer Yves 
Published: March 2024

Abstract
The pre-analytic extraction of Formalin Fixed Paraffin Embedded Tissues (FFPETs) appears to have a profound effect on the ability to obtain meaningful data from the DNA therein. FFPETs represent important materials in Pathology that are used to diagnose and analyze cancer. As part of preparing FFPETs, the formalin fixation step preserves the structure of tissues through covalent modifications but can also damage nucleic acids through that same process. Over the last decade, the emergence of Molecular Pathology, which benefits from gentler fixation compared to Histopathology and especially Immunohistopathology, has led to changes in how FFPETs are prepared. However, the remnant FFPETs from over a decade ago may be far from representative of what is now prepared for Molecular Pathology by many laboratories. Here we discuss our optimization of FFPET extraction for gently fixed samples. When we prepared our Seraseq FFPE Homologous Recombination Deficiency (HRD) reference standards using fixation conditions that are recommended for Molecular Pathology and extracted the resulting FFPETs using generic conditions, our initial coverage data from Whole Genome Shotgun (WGS) sequencing was difficult to analyze for changes in copy number across the genome. A major contributor to nonuniform coverage was identified as the formalin reversal step, where deparaffinized proteinase K-digested tissue is heated in water to near boiling to attempt to detach formaldehyde from nucleic acids through hydrolysis. Given the gentler fixation conditions, this step was found to be mostly unnecessary, and omitting it improved the resulting data substantially. A reason for this appears to be that the gentler fixation conditions that are now in use may not protect the DNA from the effects of near-boiling water, where the lack of salt lowers the melting temperature of double stranded DNA fragments and causes them to denature unless they have a higher GC content. Different kits used for the extraction of nucleic acids from FFPETs may benefit from different optimizations to obtain improved sequencing data from today’s Molecular pathology samples, and reference standards that represent such samples provide a useful tool for such optimizations.
Citation Format: Matthew G. Butler, Benedicta Forson, Maria Cowen, Jayanthi Ramprakash, Dana Ruminski Lowe, Yves Konigshofer. The importance of optimizing DNA extraction conditions for formalin fixed paraffin embedded tissues [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3760.
Abstract 3762: 11,000-plex aptamer based proteomics of bladder cancer urine for the discovery of novel disease biomarkers
Authors: Mohan Chandra , Vanarsa Kamala , Castillo Jessica , Wang Long , Lotan Yair 
Published: March 2024

Abstract
In search of more accurate, non-invasive biomarkers of bladder cancer (BC), a comprehensive aptamer-based screen of urine proteins was conducted using urine samples from a BC cohort, followed by systems biology analyses. Following an initial 1317-plex screen, an extended 11,000 plex aptamer-based proteomic screen is in progress. Based on the initial screen, 30 urine proteins were next ELISA validated in an independent cohort of 68 subjects, and the results are shown in Table 1. Of 21 urine proteins that discriminated BC from urology clinic controls (UC), urine D-dimer displayed the highest ROC AUC value (0.96) and sensitivity (95%) (Table 1). Furthermore, 9 urine proteins significantly discriminated more advanced BC (T1-T4) from earlier stages (Ta-Tis), with IL-8 and MMP-12 being the best performers. Urine MMP12 exhibited the highest specificity of 80% at fixed sensitivity for identifying advanced BC. Systems biology analysis implicated molecular functions related to extracellular matrix, collagen, integrin, heparin and transmembrane tyrosine kinase signaling in BC susceptibility, with HNF4A and NFKB1 emerging as key molecular regulators. STEM analysis of the dysregulated pathways implicated a functional role for the immune system, complement and interleukins in BC disease progression. Urine C2, D-dimer, and Elastase were additionally ELISA validated in a second BC cohort of Chinese ethnicity. Thus, comprehensive proteomics and independent ELISA validation have uncovered novel urine biomarkers for initial BC diagnosis and subsequent disease progression, that warrant further head to head comparison with current diagnostic tests.
Citation Format: Chandra Mohan, Kamala Vanarsa, Jessica Castillo, Long Wang, Yair Lotan. 11,000-plex aptamer based proteomics of bladder cancer urine for the discovery of novel disease biomarkers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3762.
Abstract 3774: Evaluation of FibraChek™ for non-invasive detection of hepatic fibrosis and hepatocellular carcinoma
Authors: Tanaka Sunao , Xie Guoxiang , Furuya Hideki , Jia Wei , Rosser Charles J. 
Published: March 2024

Abstract
Introduction and Objectives: The incidence of hepatocellular carcinoma (HCC) has almost tripled since the early 1980s in the United States where it is the fastest rising cause of cancer-related deaths. Advanced liver fibrosis and cirrhosis are ones of major risk factors for HCC. The recent evidence demonstrates that successfully treating the cause of early to moderate hepatic fibrosis may reverse most. For this reason, detecting hepatic fibrosis in an early stage is crucial. Liver biopsy is currently the gold standard for the assessment of hepatic fibrosis in clinical practice. Thus, there is an urgent clinical need for the development of non-invasive blood-based tests because of its ease of obtaining biological material. Previously, we developed FibraChek™, non-invasive blood-based tests. In this study, we tested the performance of FibraChek™ on detecting hepatic fibrosis and HCC in the US.
Methods: The performance of FibraChek™ was evaluated in a single-institutional cohort of 14 prospectively collected subjects presenting for chronic liver disease (NAFLD/NASH) patients with hepatic fibrosis, 19 prospectively collected subjects diagnosed with HCC, and 12 prospectively collected controls from the US. The algorithm uses weighted value of the 5 biomarkers: AST, ALT, Platelet, Taurocholic Acid (TCA) & Tyrosine plus age to derive a risk score. The ability of the test to identify patients harboring hepatic fibrosis or HCC was assessed. Hepatic fibrosis status was confirmed by tissue biopsy or definitive surgery. Diagnostic performance was assessed using AUC.
Results: FibraChek™ provided an AUC of 0.923 with an overall sensitivity of 93.9%, specificity of 81.8%, NPV 91.2% and PPV 81.8%. Interestingly, risk scores in HCC cohort indicated higher than those in patients with hepatic fibrosis. Thus, FibraChek™ may be also able to use for HCC detection.
Conclusions: Serum levels of a biomarker panel enabled the accurate discrimination of hepatic fibrosis and controls. The FibraChek™ test can achieve the easy, efficient, and accurate detection of hepatic fibrosis and HCC in a non-invasive patient setting.
Citation Format: Sunao Tanaka, Guoxiang Xie, Hideki Furuya, Wei Jia, Charles J. Rosser. Evaluation of FibraChek™ for non-invasive detection of hepatic fibrosis and hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3774.
Abstract 3790: HtrA3 promotes malignant progression of colorectal cancer via PI3K-AKT-FOXO1 signaling pathway
Authors: Zheng Jing , Huang Xianhua , Peng Xian-e , Wu Yunli 
Published: March 2024

Abstract
High-temperature requirement protease A3 (HtrA3) is known to contribute to the progression of various carcinomas through tissue-specific actions, yet its precise role in colorectal cancer (CRC) remains unclear. Our study revealed that HtrA3 is significantly upregulated in CRC at both mRNA and protein levels. TCGA database analysis showed that higher HtrA3 expression in colon adenocarcinoma is linked to poorer patient survival. Moreover, increased HtrA3 expression in HCT116 cells boosted their proliferation, migration, and invasion, while decreasing HtrA3 in SW480 cells had the reverse effect. In HCT116 cells with high HtrA3 levels, there was an increase in p-PI3K, p-AKT, and p-FOXO1, which reduced upon treatment with the PI3K inhibitor LY294002. Conversely, in SW480 cells with lowered HtrA3, these molecular levels decreased and rose again after treatment with the PI3K activator 740Y-P. HtrA3 also promoted cell proliferation, migration, and invasion in the presence of LY294002 and 740Y-P. In vivo experiments demonstrated that HtrA3 overexpression accelerated xenograft tumor growth. This study confirms that HtrA3’s overexpression in CRC cells promotes their proliferation, migration, and invasion by activating the PI3K-AKT-FOXO1 signaling pathway. Therefore, HtrA3 could be a significant factor in the advancement of CRC and may serve as a potential prognostic marker for guiding targeted CRC therapies.
Citation Format: Jing Zheng, Xianhua Huang, Xian-e Peng, Yunli Wu. HtrA3 promotes malignant progression of colorectal cancer via PI3K-AKT-FOXO1 signaling pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3790.
Abstract 3795: Possible role of miR-375-3p in cervical lymph node metastasis of oral squamous cell carcinoma
Authors: Saika Masato , Nakashiro Koh-ichi , Tokuzen Norihiko , Shirai Hiroyuki , Uchida Daisuke 
Published: March 2024

Abstract
Latent cervical lymph node metastasis (LNM) is the most important prognostic factor in early oral squamous cell carcinoma (OSCC). However, no clinically useful predictors of LNM in early OSCC are available. In this study, we focused on the microRNAs (miRNAs) involved in the expression of numerous genes and explored those associated with latent cervical LNM in OSCC. Microarray analysis of miRNA expression showed that the expression levels of miR-375-3p were significantly reduced in primary OSCC tissues with latent cervical LNM. Subsequently, we quantified the expression of miR-375-3p by RT-qPCR and digital PCR. Similar to the results of miRNA microarray analysis, miR-375-3p was significantly downregulated in primary OSCC tissues with latent cervical LNM. The results of digital PCR showed a more significant difference than those of RT-qPCR. When the reference value for predicting latent cervical LNM was set to less than 57.85 copies based on the receiver operating characteristic curve, the sensitivity, specificity, accuracy, and area under the curve were 80%, 100%, 90%, and 0.942, respectively. Next, we examined the effects of miR-375-3p mimics on the growth and migration of four human OSCC cell lines (SAS-L1, HSC2, HSC3, and Ca9-22) that do not express miR-375-3p. When an miR-375-3p mimic was introduced into these cells, cell proliferation and migration were significantly suppressed. Total RNA was extracted from these cells reverse-transfected with miR-375-3p mimic for 48 hours. Microarray analysis and Ingenuity Pathway Analysis (IPA) miRNA target filter showed that miR-375-3p overexpression reduced the expression of 266 genes, of which 37 genes had the target sequences of miR-375-3p in their 3’-untranslated region. Among these target genes, CEPT1 and TIMM8A knockdown significantly inhibited the migration of all human OSCC cells, similar to miR-375-3p mimics. Furthermore, IPA core analysis revealed a decrease in expression of genes involved in the activation of PI3K-AKT pathways by miR-375-3p overexpression. These results indicated that downregulating miR-375-3p expression could promote cervical LNM by enhancing cell proliferation and migration in OSCC. We also found that CEPT1 and TIMM8A as novel target genes of miR-375-3p regulated the migration of human OSCC cells. The expression levels of miR-375-3p in primary OSCC tissues appear to be a useful biomarker for predicting latent cervical LNM.
Citation Format: Masato Saika, Koh-ichi Nakashiro, Norihiko Tokuzen, Hiroyuki Shirai, Daisuke Uchida. Possible role of miR-375-3p in cervical lymph node metastasis of oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3795.