bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4045: Dependence of human immune cell type, and impact of IL-7R or TLR1/2 agonism, upon trastuzumab-mediated ADCC
Authors: Bryant Mark , Tut Gokhan , Harrison Neale , Welsh Emma , Morano Ines , Kaur Arshpreet , Pegg Ashley , Chan Hujo , Li Zhi , Cowley Jamie , Brady Catherine , Gordon John , Barnes Nicholas , Qureshi Omar 
Published: March 2024

Abstract
Targeting of tumors over-expressing HER2 using trastuzumab provides clinical benefit for patients by inhibiting HER2 signalling and enhancing immune responses against the tumor by antibody-dependent cell-mediated cytotoxicity (ADCC). Cytokines such as IL-7 augment cytotoxic anti-viral responses through up-regulation of FasL, whereas TLR1/2 agonists enhance T cell cytotoxic responses but may also promote tumor cell survival. We therefore investigated the ability of IL-7R or TLR1/2 agonism to enhance trastuzumab-mediated ADCC.
We first determined the contribution of various human immune cell subsets (e.g. monocytes, T cells, NK cells) to deliver ADCC of human tumor cells using a live high-content imaging assay in both 2D and 3D formats. Our results demonstrate that trastuzumab evoked immune cell dependent, concentration-dependent killing of tumor cells that exhibited some differential sensitivity dependent upon the cell culture format. We then tested trastuzumab-mediated killing in the absence or presence of IL-7R or TLR1/2 agonism, and noted evident donor and immune cell dependent modulation of the cytotoxic response. Modulation of this cytotoxic response was associated with differential immune cell marker expression when analysed by flow cytometry.
Our findings provide mechanistic insight into trastuzumab-mediated ADCC and highlight how cytokine receptor and TLR pathways may modulate this response.
Citation Format: Mark Bryant, Gokhan Tut, Neale Harrison, Emma Welsh, Ines Morano, Arshpreet Kaur, Ashley Pegg, Hujo Chan, Zhi Li, Jamie Cowley, Catherine Brady, John Gordon, Nicholas Barnes, Omar Qureshi. Dependence of human immune cell type, and impact of IL-7R or TLR1/2 agonism, upon trastuzumab-mediated ADCC [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 4045.
Abstract 4101: Immune inhibition of murine colorectal cancer by a p53 peptide mucosal vaccine
Authors: Wang Suhe , Cao Zhengyi , Janczak Katarzyna W. , Feng Ying , Green Maranne , Fearon Eric R. , Baker Jr James R. 
Published: March 2024

Abstract
Colorectal cancer (CRC) is among the most common cancers with high morbidity and mortality for patients despite multi-modality treatment options. Immune checkpoint inhibitors often have impact in the 15% of CRC patients with microsatellite instability-high status CRCs but have limited utility in the remaining 85% of CRC patients. Given the presence of p53 mutations in CRC, we pursued a vaccine approach against tumor cells expressing murine CRC Trp53 codon 270 missense alleles (codon 273 mutation in human cancer) using a combination of R270H p53 peptide, wild type p53 recombinant protein and used a mucosal adjuvant (MA) to drive epithelial immune responses. The vaccine (p53/MA) was studied in a CDX2-CreERT2 (tamoxifen-induced Cre-Lox) transgenic mouse CRC model where tumors arise in the cecum and proximal colon epithelium following combined ApcΔ580, KrasG12D, and Trp53R270H mutations (AKP model). The p53/MA vaccine treatment was administered intranasally to the mice at defined time points after tamoxifen tumor induction. p53/MA vaccinated animals had increased anti-p53 IgG (p&lt;0.01), IgG2a (p&lt;0.01), and IgG2b (p&lt;0.001) in sera compared to control mice. The treatment enhanced antigen-specific Th1 and Th17 cellular immune responses, as shown by increasing of IFN-ɤ (p&lt;0.05), IL-17a (p&lt;0.01) and IL-2 (p&lt;0.01) both in splenocytes and draining lymph nodes measured by Luminex assay. Vaccinated mice also showed significant more cells producing IFN-ɤ (p&lt;0.001) and IL-17a (p&lt;0.001) as analyzed by ELISpot. Importantly, the immunized animals had decreased tumor size/volume (p&lt;0.001) and prolonged survival (p&lt;0.05) compared to control animals that received only saline or MA respectively. Tumors from vaccinated mice also showed more mononuclear cell infiltrates than tumors from the control animals. In conclusion, novel p53/MA vaccinations can induce significant p53-specific immune responses and anti-tumor effects in the mouse AKP CRC model.
Citation Format: Suhe Wang, Zhengyi Cao, Katarzyna W. Janczak, Ying Feng, Maranne Green, Eric R. Fearon, James R. Baker Jr. Immune inhibition of murine colorectal cancer by a p53 peptide mucosal vaccine [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 4101.
Abstract 4123: Attenuating breast cancer metastasis with BCL-XL-targeting PROTACs
Authors: Carelock Madison E. , Zhang Peiyi , Jiao Mo , De Umasankar , Jin Zeng , Stump Rachel M. , Williams Sarah G. , Zheng Guangrong , Zhang Weizhou 
Published: March 2024

Abstract
B-cell lymphoma X-large (BCL-XL) emerges as a significant player in cancer progression. In our recent findings, we unveil the efficacy of proteolysis-targeting chimeras (PROTACs) directed against BCL-XL, demonstrating their capacity to not only eliminate cancer cells but also target tumor-induced regulatory T cells (TI-Tregs). Notably, BCL-XL's role in promoting breast cancer metastasis extends beyond its anti-apoptotic function. We posit that BCL-XL-targeting PROTACs (BCL-XL-Ps) hold promise for treating metastatic breast cancer. Their potential lies in directly eliminating circulating tumor cells during vulnerable stages and/or triggering anti-cancer immunity through Treg cell depletion. Our experiments underscore the potency of IAP-based PROTACs in facilitating BCL-XL degradation via the ubiquitin-proteasome system (UPS) while mitigating on-target platelet toxicity. Treatment of breast cancer-bearing mice with these compounds demonstrates a tangible reduction in breast cancer metastasis to the lungs. Additionally, our studies reveal a significant depletion of tumor-infiltrating Tregs in mice treated with BCL-XL-Ps. While affirming BCL-XL as a viable therapeutic target for breast cancer metastasis, further exploration into the mechanisms behind BCL-XL-P targeting is imperative. Our future endeavors will be devoted to unraveling whether our BCL-XL-Ps effectively target both tumor-intrinsic BCL-XL, potentially inducing tumor cell death, and tumor-infiltrating Tregs, thereby fostering an adaptive immune response against the tumor cells.
Citation Format: Madison E. Carelock, Peiyi Zhang, Mo Jiao, Umasankar De, Zeng Jin, Rachel M. Stump, Sarah G. Williams, Guangrong Zheng, Weizhou Zhang. Attenuating breast cancer metastasis with BCL-XL-targeting PROTACs [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 4123.
Abstract 4138: Evaluation of breast triple-negative 4T1-derived tumor metastatic development in gender-different mouse
Authors: Shao Chunhong , He Melanie , Tsai Luke Tsung-Huang 
Published: March 2024

Abstract
Background and Objective: Breast cancer in men is a rare and less-studied case, with therapeutic strategies predominantly relying on clinical treatment protocols established for women. To support the clinical treatment concept, Dr. Martin-Martinez's lab observed no differences in the time of orthotopic breast mammary fat pad tumor development, necrosis, or color change of tumor tissue between male and female mice. However, the clinical treatment readout, especially tumor metastasis, is different in men and women, and current models for breast cancer are inadequate due to the absence of metastases. It is necessary to evaluate the development of breast cancer 4T1-derived tumor metastasis in male and female mice.
Method and Result: 4T1-Luc breast cancer cells were implanted in male and female Balb/c mice via various routes, including inguinal fat pad injection, tail vein injection, caudal artery injection, portal vein injection, and Intratibial Injection. Illuminance images showed no significant differences in tumor metastatic development between genders for inguinal fat pad, tail vein, and intratibial injections. However, following caudal artery injection, early-stage metastasis differed; male mice developed femoral head metastasis, while female mice developed lung metastasis. In the late stage, male mice displayed lung and femoral bone metastasis, while female mice primarily showed lung metastasis with barely bone metastasis.
Conclusion: While both male and female mice showed similar primary breast tumor development, mouse gender affected tumor metastasis differently, particularly when tumor cells went through the caudal artery. Male mice presented earlier femoral head metastasis and less lung metastasis than female mice. Based on this work, sex hormones would affect both hormone-related and nonhormone-related tumor metastasis. To elucidate whether this phenomenon is caused by estrogen or androgen or to test if a drug has any beneficial effects, HD Biosciences provides established tumor metastatic cell-delivering platforms and over 1000 cancer cell lines for target validation and drug efficacy study.
Citation Format: Chunhong Shao, Melanie He, Luke Tsung-Huang Tsai. Evaluation of breast triple-negative 4T1-derived tumor metastatic development in gender-different mouse [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 4138.
Abstract 4141: Quantitative measurement of 3D tumor spheroid invasion using live cell time-lapse imaging
Authors: Yang Grace , Wang Tian , Ye Peifang , Zhang Xiaoyu 
Published: March 2024

Abstract
90% of the death of cancer individuals is related to cancer metastasis1. The invasion and migration of cancer cells into surrounding tissues and chambers is the first step of metastasis2. To have a better and more in-depth understanding of the pathophysiological activities involved in metastatic cancer, accurate and reliable methods for evaluating cell invasion are urgently needed. Compared to the 2D cell model, the 3D system mimics the natural physiological properties and conditions, such as structure, physiology, biological signals of living tissues, cell-matrix interactions4. In this study, we followed the commonly used protocol for 3D tumor invasion assay3 to generate spheroids in Ultra-Low-attachment (ULA) round bottom 96-well plate and subsequently embedded them in Matrigel® (5 mg/mL). After polymerization, the Matrigel that contains tumor spheroid was submerged in 100 μL cell culture media. The invasion of the 3D spheroid in the presence or absence of drug treatment was monitored and quantified using the brightfield and fluorescence live cell time-lapse image acquisition and image analysis functions of the Agilent xCELLigence RTCA eSight. The progress of spheroid invasion and the drug-inhibitory effects on tumor invasion were quantified by tracking and calculating the area of invasive protrusion from the spheroid. Our data show that 1) different types of cancer cells had different metastatic potentials demonstrated by the level of invadopodium extending into the Matrigel at desired time points; 2) the invasion of 3D HT1080 spheroid was inhibited by cytochalasin D (Cyto D), an inhibitor of actin polymerization, and GM6001, a potent broad-spectrum inhibitor of matrix metalloproteinases (MMP), in a dose-dependent manner; 3) Cyto D exhibited higher efficacy of inhibiting tumor invasion than GM6001. In summary, our approach by combining the 3D tumor spheroid invasion model with the RTCA eSight’s capability of live cell imaging and automatic quantification of the area of invasive protrusion can facilitate and enhance the development of new treatments at the preclinical stage in the future.
Citation Format: Grace Yang, Tian Wang, Peifang Ye, Xiaoyu Zhang. Quantitative measurement of 3D tumor spheroid invasion using live cell time-lapse imaging [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 4141.
Abstract 4188: Kyinno PBMC humanized mouse platform: Pioneering service in biomedical research
Authors: Liu Tongtong , Wu Guojin , He Feng , Luo Longtan , Guo Zhengcheng , Li Shuliang , Ning Jinying , Hao Feng 
Published: March 2024

Abstract
Tumor immunotherapy is the use of the human immune system to kill tumors. Compared with traditional chemotherapy and radiotherapy, immunotherapy has significant advantages such as significant efficacy, long-lasting effects, and low toxicity. Wild-type mice are widely used as preclinical models for immunotherapy due to their normal immune system, but they have many shortcomings, such as only being able to inoculate mouse tumor cells, differences between mouse and human immune systems, etc., which cannot accurately simulate the interaction between drugs and tumor cells in the human body. Humanized mouse models include PBMCs humanized mouse models, HSC humanized mouse models, and human embryonic bone, liver, and thymus tissue (BLT) transplantation models. Among them, the PBMCs humanized mouse model is widely used due to its simple preparation, short cycle, and high levels of hCD3+ T cells in the peripheral blood of mice. To assist in the development of immunotherapy, KYINNO has established a PBMC humanized mouse platform that can perform in vivo drug efficacy verification of various immunotherapeutic drugs such as CD3 bispecific antibodies or multi-specific antibodies, immune checkpoint inhibitors, etc. We screen many PBMC donors and select PBMC donors with light GvHD and good hCD3+ T cell reconstruction effects. The drug administration window of the PBMC humanized model has been extended to 6 weeks. Platform verification has been performed on subcutaneous and intravenous injection models of various tumors. Overall, we successfully established the PBMC humanized mouse platform, which is a powerful tool for immunotherapy.
Citation Format: Tongtong Liu, Guojin Wu, Feng He, Longtan Luo, Zhengcheng Guo, Shuliang Li, Jinying Ning, Feng Hao. Kyinno PBMC humanized mouse platform: Pioneering service in biomedical research [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 4188.
Abstract 4200: A novel 3D culture platform, E-slice, retains intact tumor microenvironment and tumor infiltrating immune cells
Authors: Leyva-Aranda Viridiana , Gallup Thomas , Maldonado Jose , Margain Corina , Yun Sang , Gallup David , Kim Min , Yun Kyuson 
Published: March 2024

Abstract
Human cancer tissue is a complex ecosystem with heterogeneous cell types that communicate with each other dynamically to promote tumor progression and immune evasion. Hence, experimental systems that destroy or select for cancer cells in culture have often failed to accurately predict clinical responses of new drugs. Therefore, a technology that can retain the intact tumor microenvironment (TME) and accurately predict cancer patient’s response to anti-cancer treatments, including immunotherapies, will greatly benefit patients and dramatically reduce the cost of new drug development.
E-slice is a proprietary 3D human tumor culture platform that maintains individual patient tumor’s unique ecosystem and the TME ex vivo for up to 30 days. It is generated by making thin sections of intact, fresh tumor tissues and culturing them in serum-free, defined media. As such, immune components and the TME in E-slices faithfully recapitulate human tumors ex vivo. We demonstrate that E-slices can be used to: 1) measure viability changes upon anti-cancer agent treatment longitudinally; 2) retain the native TME and tissue architecture since E-slices are never dissociated or artificially reconstituted; 3) culture any solid tumor types from patient needle biopsy cores or surgical samples, PDX, or mouse models; 4) perform high content drug screening on human tissues; 5) discover secreted biomarkers and to 6) discover or validate molecular mechanisms of action or therapy resistance; and 7) measure immunotherapy responses ex vivo from human tissues.
Importantly, it has been shown to accurately predict individual patient treatment responses to chemotherapies and targeted therapies in 4-8 days, paving the way for evidence-based personalized treatment selections in a clinically actionable time frame. Furthermore, single cell RNA-sequencing analysis demonstrates that E-slices can retain the viability and molecular phenotypes of tumor infiltrating immune cells for up to 8 days ex vivo, providing a unique platform to study human tumor-immune interactions and evaluate efficacy of immune modulators on human tumor tissues ex vivo.
Citation Format: Viridiana Leyva-Aranda, Thomas Gallup, Jose Maldonado, Corina Margain, Sang Yun, David Gallup, Min Kim, Kyuson Yun. A novel 3D culture platform, E-slice, retains intact tumor microenvironment and tumor infiltrating immune cells [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 4200.
Abstract 4227: Human-derived hydrogels to support phenotypic changes in ER+ breast cancer cell line
Authors: Sanchez Cecilia G. , Hamel Katie , Rogers Emma , Robinson Jordan , Lassiter Haley , Frazier Trivia , Williams Christopher 
Published: March 2024

Abstract
Adipose tissue plays a critical role in breast cancer incidence, progression, and response to therapy. The development of human derived 3D culture systems can accelerate the understanding of the role of environmental factors in the progression of Breast cancer as well as a model for preclinical studies during drug development. MCF-7 spheroids were cultured in Obatala Sciences’ Obavate and human-derived hydrogels ObaGel® and ObaGel®-ECM and control media. Organoid structure and phenotypic changes were analyzed via live cell imaging on the Incucyte S3. Migration studies were performed and gene expression analysis of EMT markers. Finally, adipocyte-breast cancer cell crosstalk was evaluated using pooled adipocytes co-cultured with MCF-7 spheroids. The results demonstrated that ObaGel® and ObaGel®-ECM 3D cultures support the growth and proliferation of MCF-7 tumorspheres during an extended culture period. In addition, MCF-7 cells exhibit the characteristic morphology of tumorsphere-forming cells when cultured in Obavate, with morphological changes in the ObaGel® and ObaGel®-ECM 3D. ObaGel® and ObaGel®-ECM differentially supports MCF-7 migratory behavior and phenotypic changes characteristic of EMT. Conclusions: Human derived hydrogels are developed to support 3D culture of breast cancer cells and to recapitulate the phenotypic changes associated with their metastatic potential. Furthermore, the use of a human derived 3D coculture system provides a platform for the understanding of adipose tissue-breast cancer cell interactions as it relates to breast cancer initiation, progression, and treatment response. Defining these interactions will support the development of a tool for future use in patient stratification and precision medicine in identifying underlying causes of breast cancer progression and response to treatments.
Citation Format: Cecilia G. Sanchez, Katie Hamel, Emma Rogers, Jordan Robinson, Haley Lassiter, Trivia Frazier, Christopher Williams. Human-derived hydrogels to support phenotypic changes in ER+ breast cancer cell line [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 4227.
Abstract 427: A molecular signature for the G6PC3/SLC37A2/SLC37A4 interactors in glioblastoma disease progression and in the acquisition of a brain cancer stem cell phenotype
Authors: Torabidastgerdooei Sima , Annabi Borhane 
Published: March 2024

Abstract
Background: Glycogen plays an important role in glucose homeostasis and contributes to key functions related to brain cancer cell survival in glioblastoma multiforme (GBM) disease progression. Such adaptive molecular mechanism is dependent on the glycogenolytic pathway and intracellular glucose-6-phosphate (G6P) sensing by brain cancer cells residing within those highly hypoxic tumors. The involvement of components of the glucose-6-phosphatase (G6Pase) system remains however elusive.
Objective: We questioned the gene expression levels of components of the G6Pase system in GBM tissues and their functional impact in the control of the invasive and brain cancer stem cells (CSC) phenotypes.
Methods: In silico analysis of transcript levels in GBM tumor tissues was done by GEPIA. Total RNA was extracted and gene expression of G6PC1-3 as well as of SLC37A1-4 members analyzed by qPCR in four human brain cancer cell lines and from clinically annotated brain tumor cDNA arrays. Transient siRNA-mediated gene silencing was used to assess the impact of TGF-β-induced epithelial-to-mesenchymal transition (EMT) and cell chemotaxis. Three-dimensional (3D) neurosphere cultures were generated to recapitulate the brain CSC phenotype.
Results: Higher expression in G6PC3, SLC37A2, and SLC37A4 was found in GBM tumor tissues in comparison to low-grade glioma and healthy tissue. The expression of these genes was also found elevated in established human U87, U251, U118, and U138 GBM cell models compared to human HepG2 hepatoma cells. SLC37A4/G6PC3, but not SLC37A2, levels were induced in 3D CD133/SOX2-positive U87 neurospheres when compared to 2D monolayers. Silencing of SLC37A4/G6PC3 altered TGF-β-induced EMT biomarker SNAIL and cell chemotaxis.
Conclusion: Two members of the G6Pase system, G6PC3 and SLC37A4, associate with GBM disease progression and regulate the metabolic reprogramming of an invasive and CSC phenotype. Such molecular signature may support their role in cancer cell survival and chemoresistance and become future therapeutic targets.
Citation Format: Sima Torabidastgerdooei, Borhane Annabi. A molecular signature for the G6PC3/SLC37A2/SLC37A4 interactors in glioblastoma disease progression and in the acquisition of a brain cancer stem cell phenotype [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 427.