bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5155: CD8+ T cells and CD4+central memory T cells as biomarkers of perioperative anti-PD-1 therapy in combination with concurrent chemoradiotherapy for locally advanced G/GEJ adenocarcinoma
Authors: Wang Yue , Chen Yawei , Yang Ju , Zhou Xiaoyu , Wei Yutao , Liu Qin , Yang Yang , Guan Wenxian , Liu Baorui , Wei Jia 
Published: March 2024

Abstract
Background: Gastric or gastroesophageal junction (G/GEJ) adenocarcinoma is one of the most common lethal malignancies in the world. Near half of the G/GEJ adenocarcinoma are locally advanced at diagnosis and with poor prognosis. Several clinical trials including SHARED (ChiCTR1900024428), which conducted in our center, demonstrated that perioperative anti-PD-1 therapy in combination with concurrent chemoradiotherapy for locally advanced G/GEJ cancers, could raise the pCR rate over 30%. However, the biomarkers for patients with pCR are nor clear.
Methods: Baseline tumor biopsies and post-treatment surgical tissues were collected for next-generation sequencing (NGS) and mass cytometry (CyTOF). The overall survival (OS) was measured from the date of surgery to the date of death or the last follow-up visit.
Results: 34 patients with locally advanced G/GEJ cancer received anti-PD-1 therapy (Sintilimab) in combination with concurrent chemoradiotherapy in our center. Our results met the pre-specified primary endpoint, with a pCR rate of 38.2% (13/34) and median DFS of 17.0 months. Tumor mutation burden (TMB) analyzed by NGS was higher in the pCR group than those not achieving pCR (non-pCR). Deletion of cytoband 7q35, where TPK1 locates, was significantly enriched in pCR groups. The RNA sequencing data revealed an enrichment of dendritic cells (DC), CD8+ T cells and cytotoxic cell signatures in the pCR group. Conversely, the signature for CD4+ central memory T cells (TCM) was observed to be lower in the pCR group. On the other hand, CyTOF data also demonstrated that the proportion of CD8+ T cells, CD8+ effector memory T cells (TEM) were both higher in pCR group at baseline, while CD4+ TCM was lower. Moreover, the proportion of specific subtype characterized by CD127+CD27+CD45RO+CXCR5-CD4+ TCM was significantly lower in pCR patients and significantly reduced after treatment. As continuous variable, only CD8+ T cells correlated with OS.
Conclusions: It seemed that CD8+ T cells and CD4+ TCM cells could be predictive biomarkers of perioperative anti-PD-1 therapy in combination with cCRT for locally advanced G/GEJ. Furthermore, we found a new CD4+ TCM subtype defined with CD127+CD27+CD45RO+CXCR5- could be novel biomarkers.
Citation Format: Yue Wang, Yawei Chen, Ju Yang, Xiaoyu Zhou, Yutao Wei, Qin Liu, Yang Yang, Wenxian Guan, Baorui Liu, Jia Wei. CD8+ T cells and CD4+central memory T cells as biomarkers of perioperative anti-PD-1 therapy in combination with concurrent chemoradiotherapy for locally advanced G/GEJ adenocarcinoma [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 5155.
Abstract 516: The role of clathrin-mediated endocytosis of EGFR in glioblastoma cell viability and cell cycle progression
Authors: Deter Aaron , Tsung Andrew J. , Guda Maheedhara R. , Asuthkar Swapna , Velpula Kiran 
Published: March 2024

Abstract
Glioblastoma (GBM) is characterized by poor prognosis and overexpression of epidermal growth factor receptor (EGFR). EGFR signaling is regulated through endocytosis, including clathrin-mediated endocytosis. We hypothesized that clathrin-mediated EGFR endocytosis promotes GBM cell viability and proliferation. Analysis of patient data from the Gliovis database revealed decreased overall survival in GBM patients with above-median clathrin expression (n=262) compared to below-median expression (n=263, p&lt;0.05). Immunocytochemistry and Western blot analysis confirmed increased clathrin levels in GBM patient samples compared to normal brain tissue (n=15, p&lt;0.01). To determine the functional effect of inhibiting clathrin-mediated endocytosis, U87 and U251 GBM cells were treated with 15 μM Pitstop-2, a clathrin inhibitor, for 24 hours. Pitstop-2 significantly reduced clathrin levels and cell viability by 40% compared to control (p&lt;0.001, n=3). Cell cycle analysis by flow cytometry revealed Pitstop-2 treatment led to G2/M arrest in both cell lines versus control (p&lt;0.01, n=3). Together, these findings indicate clathrin-mediated endocytosis of EGFR may promote GBM cell viability and proliferation. Further studies on the effects of clathrin inhibition on EGFR signaling and tumor growth in vivo will elucidate the therapeutic potential of targeting this pathway.
Citation Format: Aaron Deter, Andrew J. Tsung, Maheedhara R. Guda, Swapna Asuthkar, Kiran Velpula. The role of clathrin-mediated endocytosis of EGFR in glioblastoma cell viability and cell cycle progression [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 516.
Abstract 5169: Circulating levels of ANGPTL3, PCSK9, apoCIII and lipoprotein (a) in high-grade serous ovarian cancer
Authors: Chong Emilie Wong , Joncas France-Hélène , Douville Pierre , Bachvarov Dimcho , Calon Frédéric , Seidah Nabil , Diorio Caroline , Gangloff Anne 
Published: March 2024

Abstract
Background: Ovarian cancers require abundant amounts of lipids for their growth. Recent years have highlighted the role of ANGPTL3, PCSK9, ApoCIII and Lp(a) as key players in lipid metabolism. But circulating levels of these factors in ovarian cancers have not been thoroughly investigated to date.
Objective: We assessed the profiles of plasma ANGPTL3, PCSK9, ApoCIII and Lp(a) in ovarian high-grade serous carcinoma (HGSC).
Methods: Plasma samples collected from women diagnosed with an HGSC (n=31) or a benign ovarian lesion (BOL, n=40) were analyzed for plasma lipid profile (ApoB, total cholesterol, HDL, triglycerides, Lp(a) levels) on a clinical modular platform (Roche). ApoCIII, ANGPTL3 and PCSK9 levels were measured with commercially-available ELISA kits. Differences between HGSC and BOL were assessed by two-group comparisons. Pairwise correlation strength between variables was evaluated with Spearman’s rank order tests. Logistic regression modelling was used to further examine the associations between selected variables and HGSC diagnoses.
Results: ANGPTL3 levels increased in HGSC (84.1 ng/ml, SD=29.2ng/ml, n=31) compared to BOL (66.9ng/ml, SD=30.7 ng/ml, n=40; HGSC vs BOL p=0.02). Receiver operating characteristic (ROC) curve suggested that plasma ANGPTL3 levels were moderately associated with HGSC (AUC=67.7%, p=0.005 1) and did not increase predictive performance of ovarian tumor biomarkers CA125 and HE4 in multivariable model. Associations between ANGPTL3 levels and cholesterol (HDL, non-HDL, LDL and total) could be observed in the control group but not in the HGSC group. The same dissociation was observed for the inverse correlation between HDL and triglycerides in HGSC. Furthermore, moderate associations were observed between PCSK9 & CA19-9 in the entire cohort (rho=0.34, n=53, p=0.013) and Lp(a) & CA125 in HGSC cases (rho=0.51, p= 0.017).
Conclusion: In this cohort of 71 women, we report increased levels of ANGPTL3 in HGSC with an effect size (Cohen’s D) of 0.57. Confirmation of this result in larger cohort studies (minimal n&gt;50 in each group) would warrant further investigation into the roles of circulating ANGPTL3. Its inhibition may allow to tackle deregulated lipid metabolic pathways contributing to ovarian cancer progression.
Citation Format: Emilie Wong Chong, France-Hélène Joncas, Pierre Douville, Dimcho Bachvarov, Frédéric Calon, Nabil Seidah, Caroline Diorio, Anne Gangloff. Circulating levels of ANGPTL3, PCSK9, apoCIII and lipoprotein (a) in high-grade serous ovarian 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 5169.
Abstract 5197: Identification of novel molecular biomarkers for predicting postoperative recurrence of ampulla of Vater carcinoma
Authors: Kim Hyemin , Choi Jin Ho , Jeong Hyoung-oh , Kim Aryoung , Lee Se-Hoon , Lee Kwang Hyuck , Lee Kyu Taek , Lee Jong Kyun , Lee Semin , Park Joo Kyung 
Published: March 2024

Abstract
Background: Ampulla of Vater (AoV) carcinoma is a rare tumor that accounts for 20 % of periampullary cancers. Surgical resection is the only treatment that can expect cure of disease, and there is still an unmet need to predict postoperative recurrence. In this study, we investigated the novel molecular biomarkers that can predict the risk of recurrence after surgery with AoV carcinoma.
Methods: In this retrospective study, we collected the surgically resected tissue and medical records of patients who were diagnosed with AoV carcinoma at Samsung Medical Center from January 2005 to December 2020. Patients were classified patients according to the initial stage and experience of tumor recurrence. Whole transcriptomic analysis using primary AOV tumor and recurred tumor tissue samples was conducted to identify the molecular biomarker for tumor recurrence.
Results: A total of 40 tumor tissue from primary site in non-recurrence group, 22 tumor tissue from primary site in recurrence group, and paired 22 tumor tissue from recurrence site were analyzed. A total of 1005 genes differentially expressed between primary tumor of non-recurrence group and recurrence group were found. Gene set enrichment analysis showed that pathways related to fatty acid metabolism, adipogenesis, oxidative phosphorylation, and hypoxia were upregulated, and pathways associated with interferon gamma response, and mTOR signaling were downregulated in recurrence group. These pathways were significantly affecting the recurrence free survival which was verified with TCGA data, and we further identified some candidate genes including PIM3, IGFBP4, SLC19A1, HIF1A and CXCL11 to predict tumor recurrence . Moreover, we found candidates for single gene level biomarkers to predict early tumor recurrence in N0 stage. Low expression of UQCC3 and high expression of CLCNKB was related to early tumor recurrence.
Conclusions: We found the candidates for novel molecular level biomarker to predict postoperative recurrence of AoV carcinoma. In the future, it is necessary to develop a predictive model for the risk of recurrence after surgical resection for AoV carcinoma.
Citation Format: Hyemin Kim, Jin Ho Choi, Hyoung-oh Jeong, Aryoung Kim, Se-Hoon Lee, Kwang Hyuck Lee, Kyu Taek Lee, Jong Kyun Lee, Semin Lee, Joo Kyung Park. Identification of novel molecular biomarkers for predicting postoperative recurrence of ampulla of Vater 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 5197.
Abstract 5199: Protease-activated CDCP1 as a marker for aggressive primary prostate cancer and castration resistance
Authors: Merivirta Ruusu-Maaria , Lehto Timo-Pekka , Rannikko Antti , Mirtti Tuomas , Koistinen Hannu 
Published: March 2024

Abstract
CUB domain-containing protein 1 (CDCP1) is a type 1 transmembrane protein overexpressed in many cancers, including prostate cancer. CDCP1 has been associated with tumor progression, metastasis, drug resistance and poor prognosis in prostate cancer, making it a potential prognostic biomarker and therapeutic target. It has been shown to be overexpressed in a subset of castration resistant prostate cancers (CRPC) and cooperate with the loss of tumor suppressor PTEN to promote metastatic dissemination. Extracellular serine proteases activate CDCP1 by cleaving it into an N-terminal and C-terminal fragments. Proteolytic cleavage has been associated with the tumor-promoting functions of CDCP1. We studied the expression of full-length and cleaved form of CDCP1 in grade group 2-4 primary prostate cancer tissues and CRPCs using immunohistochemistry. Total CDCP1 staining was observed in 60% of primary prostate cancer samples, while the staining of cleaved CDCP1 was somewhat less frequently observed (45%). The results will be further analyzed regarding the PTEN status and for association with survival of the patients. In conclusion, so far, our results have indicated that cleaved CDCP1, which likely represents activated CDCP1, is detectable in GG 2-4 prostate cancers.
Citation Format: Ruusu-Maaria Merivirta, Timo-Pekka Lehto, Antti Rannikko, Tuomas Mirtti, Hannu Koistinen. Protease-activated CDCP1 as a marker for aggressive primary prostate cancer and castration resistance [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 5199.
Abstract 5200: Multiparametric MRI along with machine learning informs on molecular underpinnings, prognosis, and treatment response in pediatric low grade glioma
Authors: Nabavizadeh Ali , Kraya Adam , Rathi Komal , Kim Meen Chul , Khalili Nastaran , Familiar Ariana , Kesherwani Varun , Anderson Hannah , Gandhi Deep , Mahtabfar Aria , Bagheri Sina , Huang Xiaoyan , Zhu Yuankun , Sickler Alexander , Phul Saksham , Mueller Sabine , Koptyra Mateusz P , Storm Philip B , Ware Jeff , Song Yuanquan , Fisher Michael J , Vossough Arastoo , Davatzikos Christos , Resnick Adam C , Kazerooni Anahita Fathi 
Published: March 2024

Abstract
We report a comprehensive radiogenomic analysis, including multiparametric MRI and RNA sequencing of 502 tumors across 13 histological types of pediatric low-grade glioma (PLGG). Through an unsupervised analysis of treatment-naïve imaging, we were able to identify 3 distinct imaging clusters that were associated with different molecular pathways according to transcriptomic pathway analysis. Using xCell enrichment scores as input for clustering, we discovered three distinct immunological groups based on immune cell infiltration. The results suggested the presence of an ‘immune-hot” cluster within the tumors with a poorer prognosis, which may potentially benefit from emerging immunotherapies. We subsequently generated a radiomic signature that was able to predict immunological profiles. We also developed a clinicoradiomic predictive model that can assess patients’ risk of progression and predict treatment response. Finally, we evaluated the transcriptomic pathways that were most predictive of clinicoradiomic risk scores and identified the biological pathways most predictive of risk of progression in PLGG, when adjusting for molecular subtype, race, reported gender, age at diagnosis, and the anatomic location of the tumor. This is the first large-scale radiogenomic analysis in PLGG that can aid in prognostication, assessing patients’ risk of progression, predicting treatment response in conventional therapies, and early stratification of patients to identify potential candidates for targeted therapies.
Citation Format: Ali Nabavizadeh, Adam Kraya, Komal Rathi, Meen Chul Kim, Nastaran Khalili, Ariana Familiar, Varun Kesherwani, Hannah Anderson, Deep Gandhi, Aria Mahtabfar, Sina Bagheri, Xiaoyan Huang, Yuankun Zhu, Alexander Sickler, Saksham Phul, Sabine Mueller, Mateusz P Koptyra, Philip B Storm, Jeff Ware, Yuanquan Song, Michael J Fisher, Arastoo Vossough, Christos Davatzikos, Adam C Resnick, Anahita Fathi Kazerooni. Multiparametric MRI along with machine learning informs on molecular underpinnings, prognosis, and treatment response in pediatric low grade glioma [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 5200.
Abstract 5226: A 3D ECM embedded tumoroid platform for testing antibody drugs and engineered TCRs for immune oncology
Authors: Danen Erik H. J. 
Published: March 2024

Abstract
We developed a screening platform for immune oncology using an assay based on automated image guided injection of tumoroids in wells of multi-well plates preloaded with a collagen-rich ECM. The identical x-y-z position and size of the ECM-embedded tumoroids in each well facilitates automated real time confocal microscopy and quantitative image analysis algorithms. The model is used to generate quantitative data for T cell recruitment to tumoroids and killing of tumoroids by T cells. We have applied this to screening a panel of CD3:Her2 bispecific antibodies (BsAb) binding with different affinities to CD3 or Her2 or displaying high affinity interactions with different epitopes on Her2. Exposure to fresh, non-activated peripheral blood mononuclear cell (PBMC) derived T cells shows an initial phase of random T cell movement throughout the ECM followed by a BsAb-dependent phase of active T cell recruitment to tumoroids (day 2-4) and a subsequent phase of tumoroid killing (day 4-6). We show that the wave of T cell recruitment following initial T cell-tumoroid contact involves chemotactic signaling. Decreased affinity at the Her2 or CD3 arm can be compensated for by increasing BsAb concentrations. However, we detect major differences in efficacy for different high affinity epitopes. I.e., of two BsAbs interacting with high affinity with distinct Her2 epitopes and each causing effective tumor cell killing in 2D co-culture, only one was able to trigger a wave of T cell recruitment and subsequent tumoroid killing in 3D. We have applied the same setup to testing the efficacy of T cells expressing engineered TCRs aimed at application in adoptive T-cell therapy. Kinetics of experiments using these activated engineered T cells are considerably shorter (24 hours instead of ~6 days) but show a similar pattern of T cell recruitment and subsequent tumoroid killing. We demonstrate successful generation of quantitative data for T cell recruitment and tumoroid killing for engineered T cells targeting tumor antigens expressed on TNBC and uveal melanoma tumoroids.
Citation Format: Erik H. J. Danen. A 3D ECM embedded tumoroid platform for testing antibody drugs and engineered TCRs for immune oncology [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 5226.
Abstract 523: Aronia berry and oligomeric proanthocyanidins synergistically exhibit anticancer effects in colorectal cancer by inhibiting LMNB1
Authors: Li Yuan , Xu Caiming , Goel Ajay 
Published: March 2024

Abstract
Background: Colorectal cancer (CRC) is one of the most common and recurrent diseases globally, ranking as the second leading cause of mortality. The high mortality rates associated with this disease are largely due to the ineffectiveness of current treatments and the development of chemotherapeutic resistance to conventional therapies. In recent years, several natural agents, such as Aronia berry extract (ABE) and oligomeric proanthocyanidins (OPCs), have shown promise in providing a safe, cost-effective, and synergistically multi-targeted treatment approach across various cancers. Herein, we hypothesized that the combined treatment with ABE and OPCs may synergistically regulate multiple oncogenic pathways, thereby presenting a more potent anti-cancer activity, particularly targeting CRC. Methods: We performed a series of cell culture experiments to evaluate the synergistic anticancer effect of the combination of ABE and OPCs in CRC cell lines. By performing genome-wide transcriptomic profiling, we identified specific growth-signaling pathways targeted by the combined treatment and subsequently validated these findings in cell lines and patient-derived 3D organoids. Results: The combined treatment with ABE and OPCs exhibited superior synergistic anti-tumor potential, affecting cell viability, proliferation, migration, and invasion in CRC cells. The transcriptomic analysis identified that LMNB1, associated with the cell apoptosis pathway Fold enrichment [FC]: 4.29, P =0.005), plays a crucial role in the anti-tumorigenic effects of these two natural products. Moreover, the combination of ABE and OPCs significantly altered the expression of key proteins involved in cell apoptosis and suppressed the expression level of LMNB1 in HCT116 (Combination vs. ABE, FC= 0.28; Combination vs. OPCs, FC= 0.24) and SW480 (Combination vs. ABE, FC= 0.65; Combination vs. OPCs, FC= 0.47), thereby inhibiting downstream Akt phosphorylation. Finally, we successfully demonstrated that the combined treatment displayed a superior anti-cancer activity in 3D organoids, significantly reducing both their number and size (P &lt; 0.05). Conclusion: We present novel evidence for the synergistic anticancer effects of ABE and OPCs in CRC cells, which are in part achieved by regulating cellular apoptosis and the oncogene LMNB1 within the Akt signaling pathway.
Citation Format: Yuan Li, Caiming Xu, Ajay Goel. Aronia berry and oligomeric proanthocyanidins synergistically exhibit anticancer effects in colorectal cancer by inhibiting LMNB1 [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 523.