bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 721: Novel and distinctive anti-HLA-G antibody, IMB-201, inhibits tumor progression by breaking immune escape mechanism and enhancing cytotoxicity
Authors: Kang Hyeonju , Baek Seungil , Lee Inyoung , Ju Manseok , Han Seonggu , Han Eunjung , Kang Sungmuk , Koo Jihye , Kim Yoojin , Park Suho , Cho Eunyoung , Lee Chungmin , Ha Gyongsik 
Published: March 2024

Abstract
Human leukocyte antigen-G (HLA-G), a type of MHC class I, is known to be expressed only in the placenta and acts as an immune suppressor to protect the fetus from maternal immunity. Recent studies have revealed that HLA-G suppresses various tumor-infiltrated immune cells, such as T cells, NK cells, and macrophages, through interaction with inhibitory receptors Ig-like transcript 2 (ILT2). HLA-G has recently emerged as an attractive anticancer target because HLA-G is a highly specific tumor antigen and has a role in immune evasion of cancer cells. Additionally, the expression pattern of ILT2 differs from that of PD-1 in tumor-infiltrated CD8+ T cells. Therefore, an HLA-G targeting strategy is expected to be an alternative to address unmet medical needs for those not responding to anti-PD(L)1 therapies. In this study, we screened the novel anti-HLA-G antibody, IMB-201, using phage display technique and confirmed that IMB-201 selectively bound to the membrane HLA-G of cancer cells. It exhibited superior activities in ILT2 blockade, NK cell activation, and antibody-dependent cellular cytotoxicity (ADCC) compared to the reference antibody. Furthermore, IMB-201 demonstrated more efficient suppression of tumor growth compared to the reference antibody in subcutaneous gastric cancer xenograft model. Notably, the group administered IMB-201 with NK92MI cells (CD16-negative NK cells) in the ovarian cancer xenograft model showed stronger tumor growth inhibition compared to the group treated only IMB-201, indicating that NK92MI cells were activated by IMB-201. This result indicates that one of the mechanisms of action (MoA) of IMB-201 worked effectively in vivo. In addition, to maximize the efficacy of IMB-201 and differentiate it from competitors, various efficacy enhancing modality could be applicable. We aim to develop biopharmaceuticals by selecting the optimized modality. Based on these results, IMB-201 could overcome the limitations of existing cancer immunotherapy, potentially becoming highly influential in cancer treatment as a novel immune checkpoint inhibitor. It is also expected to exhibit higher anticancer efficacy in combination therapy with immune checkpoint inhibitors.
Citation Format: Hyeonju Kang, Seungil Baek, Inyoung Lee, Manseok Ju, Seonggu Han, Eunjung Han, Sungmuk Kang, Jihye Koo, Yoojin Kim, Suho Park, Eunyoung Cho, Chungmin Lee, Gyongsik Ha. Novel and distinctive anti-HLA-G antibody, IMB-201, inhibits tumor progression by breaking immune escape mechanism and enhancing cytotoxicity [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 721.
Abstract 7217: Orthogonal targeting of NAD metabolism and ErbB2/ErbB3 signaling in pancreatic adenocarcinoma
Authors: Chougoni Kranthi Kumar , Kim Nari , Dcona Martin M. , Dcona Diana T. , Malhotra Gautam K. , Grossman Steven R. 
Published: March 2024

Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is now the third leading cause for cancer related deaths in the US with a five-year survival of ~10% that has improved little over the past 20 years. Thus, there is a critical need to fully understand mechanisms of PDAC tumorigenesis in order to develop novel and effective therapies. Nicotinamide Adenine Dinucleotide (NAD), a critical co-factor and energy source required for cellular processes such as DNA repair and epigenetic regulation is frequently upregulated in PDAC. We recently reported a novel oncogenic axis connecting the NAD-dependent epigenetic regulator and oncogene C-terminal Binding Protein (CtBP) with the EGFR family growth factor receptors ErbB2/ErbB3 (ErbB2/3) in PDAC cells and tumors. Indeed, previous reports have shown ~30% of human PDAC tumors overexpress ErbB3, and our work has shown that PDAC tumor cell growth relies on maintenance of ErbB3 expression. Moreover, we show that the majority of PDAC cells with high levels of ErbB3 expression are uniquely sensitive to the ErbB2-targeted tyrosine kinase inhibitor lapatinib. In addition, we have recently shown that co-targeting NAD and CtBP with small molecule inhibitors is an effective and synergistic therapeutic strategy in PDAC model systems.
Methods and Results: In the current study, we demonstrate NAD-dependent regulation of ErbB2/3 signaling in PDAC cells in vitro. Upon depletion of NAD using the NAD salvage pathway inhibitor GMX1778 in human PDAC cells, we observed a striking coordinate decrease in the levels of both ErbB2 and ErbB3. Furthermore, stable knockdown of the limiting enzyme of the complementing Preiss-Handler NAD synthetic pathway, Nicotinamide Adenine Phosphoribosyl Transferase, also resulted in robust downregulation of ErbB2/3 protein levels, suggesting a direct linkage in PDAC cells between the status of NAD metabolism and synthesis and activity of the key growth factor receptors ErbB2/3.
Conclusions: Our findings highlight the novel connection between NAD and ErbB2/3 in PDAC. Furthermore, our data suggests combining chemical or biologic inhibitors of ErbB2/3 with an inhibitor of NAD synthesis may result in highly synergistic cytotoxic effects in PDAC cells and PDAC preclinical models. Such data could support the future development of a human PDAC clinical trial repurposing agents targeting NAD synthesis and ErbB2/3 that are already FDA-approved or currently in clinical testing.
Citation Format: Kranthi Kumar Chougoni, Nari Kim, Martin M. Dcona, Diana T. Dcona, Gautam K. Malhotra, Steven R. Grossman. Orthogonal targeting of NAD metabolism and ErbB2/ErbB3 signaling in pancreatic 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 7217.
Abstract 7220: Emerging combination strategy: FANCI suppression induces PARP1 redistribution to enhance efficacy of PARP inhibitors in breast cancer
Authors: Huang Yu-zhou , Sang Ming-Yi , Xi Pei-Wen , Xu Ruo-Xi , Cai Meng-Yuan , Wang Zi-Wen , Zhao Jian-Yi , Li Yi-Han , Wei Ji-Fu , Ding Qiang 
Published: March 2024

Abstract
While polyADP-ribose polymerase (PARP) inhibitors have made advancements in the treatment of breast cancer, challenges such as chemotherapy resistance and limited application persist. Fanconi AnemiaComplementation Group I (FANCI), a DNA repair protein associated with breast cancer development, represents a potential target for novel combination therapeutic strategies. However, the role of FANCI in breast cancer and its impact on the efficacy of PARP inhibitors require further investigation.
In our study, we analyzed FANCI expression in breast cancer tissues and cell lines, and its correlation with clinical parameters and patient prognosis. Lentiviral vectors were utilized and functional assays were performed to evaluate the effects of FANCI modulation on breast cancer cell growth and migration. Co-immunoprecipitation assays and protein interaction analysis were conducted to identify the interaction between FANCI and PARP1 and determine the specific binding region. The functionality and nuclear distribution of PARP1 were assessed upon FANCI modulation. Finally, the sensitivity of breast cancer cells to the PARP inhibitor talazoparib upon FANCI knockdown was evaluated in vitro and in vivo.
Our findings demonstrated that FANCI was overexpressed in breast cancer and associated with poor prognosis. FANCI significantly promoted breast cancer cell proliferation both in vitro and in vivo. We identified the interaction between FANCI and PARP1, specifically at the FANCI helical domain 2 binding site. FANCI knockdown led to reduced nuclear localization of PARP1 and decreased PARP1 activity. Importantly, combination treatment with FANCI knockdown and talazoparib significantly inhibited cancer growth in vitro and in vivo. Additionally, we found that the cyclin-dependent kinase (CDK) 4/6 inhibitor palbociclib, which effectively suppresses FANCI protein expression, exhibited a robust synergistic effect with talazoparib both in vitro and in vivo.
In conclusion, FANCI is a novel therapeutic target for breast cancer. Suppression of FANCI regulates PARP1 redistribution and activity, making breast cancer cells more responsive to PARP inhibitors. This combination therapeutic strategy shows potential in enhancing the effectiveness of PARP inhibitors for breast cancer treatment, regardless of BRCA mutations.
Citation Format: Yu-zhou Huang, Ming-Yi Sang, Pei-Wen Xi, Ruo-Xi Xu, Meng-Yuan Cai, Zi-Wen Wang, Jian-Yi Zhao, Yi-Han Li, Ji-Fu Wei, Qiang Ding. Emerging combination strategy: FANCI suppression induces PARP1 redistribution to enhance efficacy of PARP inhibitors in breast 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 7220.
Abstract 7229: In situ trans-differentiation therapy effectively terminates the growth and recurrence of glioblastoma
Authors: Zhao Huihui , Li Zhaozhong , Zhang Xiaohui , Zhao Congjian , Zhu Zhao , Liu Yueguang 
Published: March 2024

Abstract
Background: Glioblastoma (GBM) is the most common and malignant brain tumor in adults, and remains almost invariably lethal due to its aggressive and invasive nature. The standard first-line treatment for GBM is surgical resection, postoperative radiotherapy and chemotherapy with temozolomide (TMZ), but it exhibits short-term effects due to a high recurrence rate of GBM is its (up to almost one hundred percent). This long-existing clinical challenge has demanded development of novel and effective therapeutic strategies. In situ cell trans-differentiation therapy which direct reprograms tumor cells into terminally differentiated benign cells represents a novel therapeutic strategy for tumors. We further explored the application of in situ trans-differentiation therapy for glioblastoma.
Results: In the present study, we have conducted a large-scale screen for transcription factors which can reprogram glioblastoma cells into terminally differentiated postmitotic cells. Over-expression of a combo of selected trans-differentiation factors that possess the highest trans-differentiation rate effectively reprogramed human glioma cells into neuronal-like cells with characteristic neuronal morphology and expression of neuronal genes in culture, as a result substantially reducing glioblastoma cell proliferation and tumor development after orthotopic transplantation. With replicable recombinant oncolytic virus vectors, product candidate can specifically replicate in glioma cells, therefore transcription factors can be specifically delivered to all tumor cells rather than normal cells. In either cell line-derived or patient-derived tumor tissue xenograft models, intra-tumoral injection product candidate inhibited glioblastoma cells growth at an exceptionally high efficiency. Remarkably product candidate combination with TMZ resulted in a complete regression of tumor and no recurrence was observed in animal model cases.
Conclusion: In summary, our findings have established a novel therapeutic approach for treating glioblastoma by terminating sustained proliferation of glioma cells via transcription factors-induced in situ cell trans-differentiation and supported further clinic investigations in patients.
Citation Format: Huihui Zhao, Zhaozhong Li, Xiaohui Zhang, Congjian Zhao, Zhao Zhu, Yueguang Liu. In situ trans-differentiation therapy effectively terminates the growth and recurrence 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 7229.
Abstract 7309: Edible mushroom derived antioxidant, vialinin A, prevents melanoma growth and invasion
Authors: Vo Alexandria , Zafar Amber 
Published: March 2024

Abstract
Melanoma is the second leading invasive cancer with a greater capacity to invade and metastasize. Increased oxidative stress has been shown to be involved in melanoma growth and spread. Several antioxidants, vitamins, and other phytochemicals have been shown to prevent melanoma cancer growth. However, the chemopreventive efficacy of vialinin-A, an edible mushroom-derived p-terphenyl antioxidant, on cancer growth and invasion is unknown. We, therefore, hypothesized that with its potent anti-oxidative and anti-inflammatory actions, vialinin-A could prevent melanoma cell growth and invasion. B16-F10 melanoma cells were treated without or with various concentrations of vialinin-A. The cell viability was determined by MTT assay and apoptosis by annexin-V staining. Our results suggest that vialinin-A prevents melanoma cell growth in a dose-dependent manner. Vialinin-A also prevents the invasion and migration of melanoma cells. Further, vialinin-A prevents the generation of reactive oxygen species and promotes apoptosis of B16-F10 cells. In addition, vialinin-A increases the activation of caspase-3 and cleavage of PARP protein. Vialinin-A also regulated the expression of various anti-apoptotic, pro-apoptotic, and inflammatory markers in melanoma cells. In conclusion, our results suggest that vialinin-A, through regulating oxidative stress-modulated apoptotic pathways, could prevent melanoma cell growth and invasion and has potential chemopreventive properties.
Citation Format: Alexandria Vo, Amber Zafar. Edible mushroom derived antioxidant, vialinin A, prevents melanoma growth and invasion [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 7309.
Abstract 7315: Collaboration between NIDCR and NCI promotes innovative research in head and neck cancers
Authors: Chen Zhong , Wang Wendy 
Published: March 2024

Abstract
The Oral and Salivary Cancer Biology Program at National Institute of Dental and Craniofacial Research (NIDCR) supports research activities that improve early detection and treatment of cancers of the oral cavity, pharynx, and salivary glands. We promote basic science research on the regulatory pathways and transformation process of pre-cancerous lesions to primary and metastatic tumors, as well as translational science activities to develop novel technologies and therapeutics for the diagnosis, prognosis, and treatment of cancers. NIDCR and National Cancer Institute (NCI) have established long-term collaborations to promote and co-manage awards funded through The Immuno-Oncology Translational Network (IOTN) of the Cancer Moonshot program, Specialized Programs of Research Excellence (SPOREs), and Early Detection Research Network (EDRN) program. NIDCR and NCI have co-developed Notice of Special Interest (NOSI) and Request for Application (RFA) on Advancing Head and Neck Cancer Early Detection Research (AHEAD), which co-funded seven research projects to discover and develop molecular signatures of early detection and diagnosis of HPV positive and negative head and neck cancer (HNC). To further strengthen NIDCR and NCI collaboration, we jointly organized the symposium to promote HNC early detection and biomarker identification at the American Head and Neck Society (AHNS) 11th International Conference on Head and Neck Cancer in July 2023. In addition, NIDCR has organized a symposium to promote HNC research at the 2024 annual meeting of American Association for Dental, Oral, and Craniofacial Research (AADOCR) to celebrate the 75th anniversary of NIDCR. This AADOCR symposium will feature the collaboration between NIDCR with NCI in the Cancer Moonshot program focusing on immunoprevention and immunotherapy, HNC early detection and biomarker research in AHEAD and EDRN, and investigation of HPV positive and negative HNC and clinical translational research under SPORE. At this 2024 AACR annual meeting, NIDCR and NCI program directors will present the collaborations and funding opportunities between NIDCR and NCI, focusing on early cancer detections and biomarker discovery and validation. Collaboration between NIDCR with NCI provides a unique opportunity to promote basic, translational, and clinical research in advancing HNC early detection to benefit cancer patients.
Citation Format: Zhong Chen, Wendy Wang. Collaboration between NIDCR and NCI promotes innovative research in 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 7315.
Abstract 737: Arrays of 3D ECM-embedded fibroblast clusters for characterization of ECM remodeling by primary cancer associated fibroblasts and for evaluation of drugs attenuating fibrotic ECM remodeling
Authors: Danen Erik H. J. 
Published: March 2024

Abstract
Chronic fibrosis can lead to organ failure and is also associated with cancer, where the tumor is interpreted as a chronic wound, and the fibrotic tumor environment drives disease progression. Fibrosis occurs in an inflammatory environment where macrophages are activated, and fibroblasts transdifferentiate into myofibroblasts. Activated macrophages stimulate the myofibroblasts to produce excessive amounts of collagen-rich ECM. Changes in proteolytic activity and high contractile forces that myofibroblasts apply onto their tissue environment, further lead to extensive remodeling of the healthy tissue matrix into a scar matrix. Similar activity is displayed by cancer-associated fibroblasts (CAFs) in tumors. Intervening with the excessive ECM remodeling by activated fibroblasts represents a candidate therapeutic strategy to normalize the architecture of fibrotic and malignant tissues. We developed a screening platform using an assay based on automated image guided injection of clusters of fibroblasts in wells of multi-well plates preloaded with a collagen-rich ECM network. The identical x-y-z position, spacing, and size of the ECM-embedded fibroblast clusters in each well facilitates automated real time confocal microscopy and quantitative image analysis algorithms. We use this setup for automated quantitative analysis of ECM remodeling activity of CAFs obtained from early-stage colorectal cancer patients. We find that CAFs from these early-stage lesions display increased ECM remodeling capacity as compared to patient matched normal fibroblasts. We then use the same setup to screen a series of compounds for their ability to attenuate ECM remodeling triggered by TGFb-activated primary human fibroblasts. We detect known and novel pathways, and we identify small molecule inhibitors with a promising efficacy versus toxicity profile. Lastly, we detect a previously unknown concentration-dependent side effect of ALK5 inhibitors that leads to the identification of a novel profibrotic pathway and indicates that caution is warranted for the clinical application of ALK5 inhibitors.
Citation Format: Erik H. J. Danen. Arrays of 3D ECM-embedded fibroblast clusters for characterization of ECM remodeling by primary cancer associated fibroblasts and for evaluation of drugs attenuating fibrotic ECM remodeling [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 737.
Abstract 7381: Mathematical modeling and validation of mechanistic target of rapamycin and N-myristoyltransferase signaling pathways in breast cancer
Authors: Meher Abinash , Shrivastav Shailly Varma , Agarwal Anouska , Dube Sheen , Portet Stephanie , Shrivastav Anuraag 
Published: March 2024

Abstract
Hormone receptor-positive (HR+) breast cancer (BC) makes up approximately 65% of all breast cancers diagnosed. The prognosis for early-stage disease is excellent with mainstay endocrine therapy (ET). Despite the effectiveness of standard ET, as many as 41% of HR+ early-stage BC diagnosed women will experience distant recurrence. The resistance to endocrine therapy and recurrence is partly attributed to the activation of the insulin pathway and the independence of HR+ BC cells on the ER pathway for their growth. Earlier, we demonstrated the crosstalk between insulin/mTOR and ER pathways. N-myristoyltransferase (NMT) exists in humans in two paralogues (NMT1 and NMT2) that catalyze myristoylation reaction. Recent studies from our laboratory demonstrated that NMTs are downstream targets of insulin and ER pathways. In this study, we have designed mathematical models using differential equations to study the activation of the insulin pathway and its effect on NMT. The mathematical modeling incorporated the partition of cellular organelles and the sequential flow of information with cascades of equations representing signaling reactions. The activated mathematical model was designed by activating the insulin receptor (IR) or insulin-like growth factor receptor (IGF1R) and compared with the control model. The mathematical models were validated by wet lab experiments. The HR+ BC cells (MCF7) were treated with insulin or IGF1 for short term and long term. The expression patterns of NMT1, NMT2, and mTOR were determined by cell fractionation and western blot analysis. The results revealed the correlation between the differential expression patterns of NMTs and the proliferation of MCF7 cells when the insulin pathway was activated by insulin or IGF. The mathematical modeling was validated by simulations and data fittings. The results demonstrated that differential equation-based mathematical modeling could predict the NMT-related oncogenic changes in HR+ BC cells.
Citation Format: Abinash Meher, Shailly Varma Shrivastav, Anouska Agarwal, Sheen Dube, Stephanie Portet, Anuraag Shrivastav. Mathematical modeling and validation of mechanistic target of rapamycin and N-myristoyltransferase signaling pathways in breast 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 7381.