bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2592: New technologies and capabilities supporting the development of novel molecular radiotherapy agents
Authors: Belderbos Sarah , Mothes Celine , Bernhard Claire , Denat Franck , Adumeau Pierre , Chevalier Merari Tumin , Llop Jordi , Kownacka Agnieszka , Tihansky Calmen , Ruch Marie , Claron Michael , Moreau Mathieu , Berthet Cyril , Koumarianou Eftychia 
Published: March 2024

Abstract
At Oncodesign-Services we aim to provide cutting-edge technologies and products to support the development of radiopharmaceuticals for theranostics.
Starting from the optimization of lead compounds, the site-specific bioconjugation chemistry of a bifunctional chelator to large biological compounds, such as antibodies, can preserve the biological profile and the reliable batch production. Thanks to new technologies we can conjugate a variety of payloads (cytotoxins, radioactive chelates, fluorescent dyes) on antibodies at targeted lysine residues of the Fc region, independent of Fc glycosylation.
Moreover, we aim to use relevant models for valuable translational results. In line with this, we established tumor spheroids to finely monitor the diffusion and subcellular distribution of novel fluorescent and radioactive probes in a 3D environment.
Furthermore, we are currently generating two animal tumor models for optimal target expression levels and recapitulation of the human tumor microenvironment. Our first model is a PSMA+ expressing tumour model, in a non radiosensitive rodent strain allowing improved assessment of novel radiopharmaceuticals. Our second tumor model is under development to assess novel FAPI tracers.
Finally, we present in partnership with ImaginAb 89Zr Crefmirlimab Berdoxam​, a minibody (human and murine analog) with high affinity to the CD8α glycoprotein, a valuable PET imaging tool for preclinical tracking and assessment of CD8 cells. This PET imaging can be used to evaluate immunoresponse following treatment, autoimmune, inflammatory and/or infectious diseases models.
To conclude, our continuous efforts aim at expanding our service portfolio to fulfil the needs of our various projects, as presented herein. Our experience and expertise allow us to suggest alternatives based on the latest technological progresses to facilitate and expedite the drug discovery progress from bench to bedside.
Citation Format: Sarah Belderbos, Celine Mothes, Claire Bernhard, Franck Denat, Pierre Adumeau, Merari Tumin Chevalier, Jordi Llop, Agnieszka Kownacka, Calmen Tihansky, Marie Ruch, Michael Claron, Mathieu Moreau, Cyril Berthet, Eftychia Koumarianou. New technologies and capabilities supporting the development of novel molecular radiotherapy agents [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 2592.
Abstract 2628: Generation of multi-antigen specific T cells for ovarian cancer using Prussian Blue nanoparticles and photothermal therapy
Authors: Grundy Erin E. , Lee Abigail , Chin Samantha , Hadley Melissa , Schmidt Danielle , Wang Loretta , Cox Olivia , Omar Khadra , Bollard Catherine M. , Fernandes Rohan , Chiappinelli Katherine B. 
Published: March 2024

Abstract
The immunosuppressive nature of ovarian cancer (OC) allows these tumors to evade the immune system, contributing to late-stage diagnoses and poor clinical outcomes for patients. However, a higher number of tumor-infiltrating lymphocytes is associated with improved clinical outcomes in OC. One type of lymphocyte, the T cell, can traffic to the tumor and kill tumor cells. We have shown that treating tumor cells with Prussian Blue nanoparticles and photothermal therapy (PBNP-PTT) results in immunogenic cell death, a form of cell death that is visible to the immune system, including T cells. PBNP-PTT-treated tumor cells were then used to expand tumor-specific T cells from partially genetically matched healthy donors against breast and brain cancer cell lines. These expanded T cells were better able to recognize and kill the target tumor cell lines than bulk unexpanded T cells from the same donors. Hence, we hypothesized that using PBNP-PTT-treated OC cells would allow us to expand a polyclonal tumor-specific T cell product that is cytolytic against OC cells in vitro and in vivo.We first evaluated whether multi-antigen OC-specific T cells could be expanded from partially genetically matched healthy donors and confirmed that PBNP-PTT elicited immunogenic cell death in the HLA-A*02:01 human OC cell lines Hey and TykNu. Using our established in vitro T cell expansion protocol, we then successfully expanded T cells from multiple HLA-A*02:01 healthy donors (n=3) against these cell lines. Functional analyses—including interferon-gamma ELISPOT, multi-color flow cytometry, and cytotoxicity assays—demonstrated that the expanded T cells had enhanced anti-tumor responses against OC cell lines compared to bulk unexpanded T cells derived from the same donors. Current work is expanding this approach to a syngeneic murine setting in C57BL/6J mice. Moreover, we will evaluate HLA-matched T cells and tumor cells from patients with OC ex vivo. Collectively, these efforts serve as a novel approach towards a curative immunotherapy for OC.
Citation Format: Erin E. Grundy, Abigail Lee, Samantha Chin, Melissa Hadley, Danielle Schmidt, Loretta Wang, Olivia Cox, Khadra Omar, Catherine M. Bollard, Rohan Fernandes, Katherine B. Chiappinelli. Generation of multi-antigen specific T cells for ovarian cancer using Prussian Blue nanoparticles and photothermal therapy [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 2628.
Abstract 264: Differentiation therapy: Esculetin as a potent agent to alter cellular plasticity of leukemic & solid tumor stem cells
Authors: Mathur Ankit , Saluja Daman 
Published: March 2024

Abstract
Background The “Differentiation therapy” has been emerging as a promising and more effective strategy against acute leukemia relapses.
Objective In extension to the revolutionising therapeutic outcomes of All Trans Retinoic Acid (ATRA) to induce terminal differentiation of Acute Promyelocytic Leukemic (APL) blast cells, we decipher the potential effect of a natural compound “Esculetin” to serve as a differentiating agent in Acute Myeloid Leukemia (AML) as well as solid tumour cells. Underlaying role of Wnt signaling pathways in esculetin mediated blast cell differentiation was also evaluated.
Methods Human acute myeloid leukemic cells (Kasumi-1) with t(8;21/AML-ETO) translocation were used as a model system. Growth inhibitory and cytotoxic activity of esculetin were analysed using growth kinetics and MTT assay. Morphological alterations, cell scatter characteristics, NBT reduction assay and cell surface marker expression pat- terns were analysed to detect terminally differentiated phenotypes. We employed RT2profiler PCR array system for the analysis of transcriptome profile of Wnt signaling components. Calcium inhibitors (TMB8 and Amlodipine) and Transforming growth factor beta (TGF-β) were used to modulate the Wnt signaling axes. To investigate whether esculetin exerts the similar effects on the invasive solid tumour cancer stem cells subset, we used a cellular model system of colon carcinoma HCT116 cells reflecting EMT phenotype.
Results We illustrate cytotoxic as well as blast cell differentiation potential of esculetin on Kasumi-1 cells. Morphological alterations akin to neutrophilic differentiation as well as the corresponding acquisition of myeloid lineage markers indicate terminal differentiation potential of esculetin in leukemic blast cells. Exposure to esculetin also resulted in downregulation of canonical Wnt axis while upto ~ 21 fold upregulation of non-canonical axis associated genes. Esculetin also showed potential to revert the CSC marker expressions and concurrent EMT consistent with reduced functional aggressiveness in colon cancer cells.
Conclusions Our study highlights the importance of selective use of calcium pools as well as “axis shift” of the canonical to non-canonical Wnt signaling upon esculetin treatment which might abrogate the inherent proliferation to release maturation arrest and induce the differentiation in leukemic blast cells as well as CSC stem cells. The current findings provide further therapeutic interventions to consider esculetin as a potent differentiating agent to counteract relapses.
Citation Format: Ankit Mathur, Daman Saluja. Differentiation therapy: Esculetin as a potent agent to alter cellular plasticity of leukemic & solid tumor stem 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 264.
Abstract 2692: ELK3 is a key regulator as the response of natural killer cell therapy in triple-negative breast cancer
Authors: Jung Hae-Yun , Lee Yebin 
Published: March 2024

Abstract
Triple-negative breast cancer (TNBC) is the most challenging subtype of breast cancer because of its aggressive behavior and the limited therapeutic strategies available. In the last decade, immunotherapy has become a promising treatment to prolong survival in advanced solid cancers including TNBC. However, the efficacy of immunotherapy in solid cancers remains limited because solid tumors contain few tumor-infiltrating lymphocytes. Here, we show that targeting an ETS transcription factor ELK3 (ELK3) enhances the response of nature killer (NK) cells through intracellular and extracellular signaling. In extracellular signaling, ELK3 depletion increases CXCL16 expression level and promotes NK cell cytotoxicity through CXCL16-mediated NK cell recruitment in TNBC. In intracellular signaling, ELK3 depletion controls mitochondrial fission-fusion status to induce NK cell-mediated cell death. In silico analysis showed that ELK3 is negatively correlated with CXCL16 or MID51 expression in breast cancer patient samples. Low expression of ELK3 and high expression of CXCL16 or MID51 were associated with a better prognosis. Low expression of ELK3 and high expression of CXCL16 or MID51 were associated with increased expression of NK cell-related genes. Our findings demonstrate that ELK3-CXCL16 axis controls NK cell recruitment to target cancer cells and ELK2-MID51 axis triggers mitochondrial dysfunction-mediated apoptosis during NK cell therapy, suggesting that targeting the ELK3 gene could be an adjuvant strategy for increasing the efficacy of immunotherapy in TNBC
Citation Format: Hae-Yun Jung, Yebin Lee. ELK3 is a key regulator as the response of natural killer cell therapy in triple-negative 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 2692.
Abstract 2695: A higher percentage of M2 macrophages in non-tumor part predict the tumor recurrence in patients with hepatocellular carcinoma after surgical resection
Authors: Lin Po-Ting , Ku Wei-Ting , Wu Tsung-Han , Wu Cheng-Heng , Yang Chan-Keng , Teng Wei , Lin Yung-Chang , Lin Chun-Yen 
Published: March 2024

Abstract
The primary hurdle in improving outcomes for hepatocellular carcinoma (HCC) patients after curative treatment is the high early recurrence rate. The existing literature indicates the presence of type 2 macrophages (M2), renowned for their immunosuppressive capabilities, has been implicated in creating a microenvironment conducive to tumor growth and recurrence. However, the intricate interplay involving M2 macrophages and the recurrence of HCC is underexplored. Therefore, we conducted an analysis involving HCC patients who underwent hepatectomy at our hospital between 2013 and 2017. We collected samples from both the tumor and non-tumor regions and subjected them to bulk RNA sequencing for comprehensive molecular profiling. The proportion of immune cells was calculated by CIBERSORTx.In our study, we enrolled fifty patients, with sixty percent presenting with cirrhosis and seventy-three percent having viral hepatitis. Twenty-three patients experienced tumor recurrence, with a median time to recurrence of 12.6 months. First, we found no correlation between five TIMR subtypes defined by TIMELASER (Xue R, Nature, 2022) and recurrence. However, as for the proportions of immune cell, a significantly lower NK/Treg ratio (p= 0.0163) and high within the resected tumor section in recurrent group was found. On the other hand, the ratio of M2 macrophages to total macrophages (M2/M) was significantly higher within the non-tumor region in patients experiencing tumor recurrence after hepatectomy (p=0.0357). Furthermore, the expression of the ACGT2 gene in non-tumor part, which strongly correlates with Treg function, was significantly higher (p=0.0056) in recurrent group. In addition, the innate T cells score was increased in non-tumor pat in recurrent group but with borderline significance (p=0.0628). However, in multivariable analysis, only a higher M2/M ratio within the non-tumor region (HR 3.756, p=0.0072) were identified as independent risk factors for tumor recurrence. We also found that patients with a higher M2/M ratio had a lower percentage of cirrhotic patients (p=0.0049) and less association with TIME-IA (immune activation) subtype of HCC by TIMELASER classification (p=0.0030). In conclusion, a higher M2/M ratio within the non-tumor region predict the tumor recurrence in patients with hepatocellular carcinoma.
Citation Format: Po-Ting Lin, Wei-Ting Ku, Tsung-Han Wu, Cheng-Heng Wu, Chan-Keng Yang, Wei Teng, Yung-Chang Lin, Chun-Yen Lin. A higher percentage of M2 macrophages in non-tumor part predict the tumor recurrence in patients with hepatocellular carcinoma after surgical resection [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 2695.
Abstract 2749: DHX36 may promote the growth and metastasis of lung cancer
Authors: Li Ting , Luo Na , Fu Jiewen , Wei Chunli , Fu Junjiang 
Published: March 2024

Abstract
Introduction: Helicase is a kind of protein molecular motor that widely exists in eukaryotic cells, viruses and bacterial cells, and participates in DNA replication, transcription and other life activities. DHX36, a kind of helicase, is a new homologous gene of human DNA/RNA helicase cloned by our laboratory by homologous molecular cloning which used the sequence of the maleless gene (mle) of Drosophila. Studies have shown that DHX36 upregulates the expression of proto oncogene and promotes the occurrence of cancer. At present, there are few studies on DHX36 in lung cancer. This study aims to clarify the relationship between DHX36 and lung cancer and provide a new molecular target for the diagnosis, treatment and prognosis of lung cancer.
Methods: Twenty-eight pairs of clinical tumor samples from lung adenocarcinoma and adjacent tissues were collected, and the protein expression of DHX36 in different tissues was detected by western blot. Correlation between DHX36 expression and survival prognosis of lung cancer patients was analyzed by online database. Over-expression of DHX36 in A549 and H460 cells and knockdown of DHX36 in A549 and H1975 cell lines, then the migration, invasion and growth index of cells were analyzed by real-time cell analyzer. After DHX36 stable knock-down cell line was established in H1975 cells, they were injected into nude mice by subcutaneous injection and tail vein injection respectively at the same time as the control cells, and the growth of subcutaneous tumors and the metastasis of lung tissues in nude mice were recorded and collected respectively. The tissues were analyzed by histology, immunohistochemistry, and western blot.
Results: In 28 pairs of clinical lung cancer tumor samples, we found that DHX36 was higher in cancer tissues than in adjacent tissues in 23 pairs, which indicated that DHX36 might be a kind of proto oncogene to promote the occurrence and development of lung cancer. Bioinformatics analysis revealed that the high expression of DHX36 was related to the low survival of lung cancer patients. The results of RTCA showed that the abilities of growth, invasion and migration of cells in the over-expressed DHX36 groups were higher than those in the control groups. After DHX36 was knocked down, the growth, invasion and invasion of lung cancer cells were inhibited.
Conclusion: DHX36 is expected to be a new molecular target of lung cancer. Next, we will knock out DHX36 in lung cancer cells to observe the tumor growth and lung metastasis in mice.
Citation Format: Ting Li, Na Luo, Jiewen Fu, Chunli Wei, Junjiang Fu. DHX36 may promote the growth and metastasis of lung 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 2749.
Abstract 2809: Bifidobacterium species BB_003 identified through metatranscriptomic analysis with experimentally validated antitumor actions
Authors: Piao Xuan-Mei , Min Kyungchan , Byun Young Joon , Zheng Chuang-Ming , Kim Seon-Kyu , Park Seong-Hwan , Moon Sungmin , Kim Kyeong , Kang Ho Won , Kim Won Tae , Yun Seok Joong , Park Hansoo 
Published: March 2024

Abstract
Introduction & Objectives: A host's microbiome influences both gene expression and phenotype. Whole transcriptome sequencing (WTS) provides information about the microbiome in addition to gene expression. This research probes the correlation between microbial abundance, host gene transcription, and therapeutic efficacy, pinpointing a beneficial microbial strain and its mechanism of action.
Materials & Methods: Bladder tissue biopsies from NMIBC patients underwent WTS and subsequent bioinformatic analysis. After in silico evaluation, in vitro assays including WST, quantitative PCR, and immune cell profiling were performed on mouse splenocytes. These assays were followed by in vivo assessment in both subcutaneous and orthotopic murine tumor models.
Results: Among 59 biopsies, non-recurrence correlated with heightened presence of Lactococcus species LC_001 and Bifidobacterium species BB_003. Notably, BB_003 was associated with an extended recurrence-free survival (RFS). Gene set enrichment analysis (GSEA) implicated BB_003 in mediating a pro-inflammatory cascade, accentuating macrophages and interferons. In vitro WST assays showed the antitumor potential of BB_003_β, characterized by upregulated pro-inflammatory gene transcription. This strain increased effector CD8 T cells and M2 macrophages. In vivo, direct live BB_003_β introduction into subcutaneous tumors curtailed tumor proliferation. An increase in effector CD8 T cell populations within tumors and elevated cDC1 and M1 macrophage counts in tumor-draining lymph nodes were observed. Intravesical administration of live bacteria markedly decreased bladder weight, amplifying interferon alpha and beta gene expressions compared to controls.
Conclusions: According to this study, BB_003_β inhibits tumor growth and is involved in immune response. Our study confirmed the antitumor properties of BB_003_β and suggested that cytokine and immune cell stimulation play a key role in its mechanism of action. Augmented insights warrant further exploration, particularly in synergy with intravesical BCG treatment.
Citation Format: Xuan-Mei Piao, Kyungchan Min, Young Joon Byun, Chuang-Ming Zheng, Seon-Kyu Kim, Seong-Hwan Park, Sungmin Moon, Kyeong Kim, Ho Won Kang, Won Tae Kim, Seok Joong Yun, Hansoo Park. Bifidobacterium species BB_003 identified through metatranscriptomic analysis with experimentally validated antitumor actions [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 2809.
Abstract 281: The function of FGFR2+ cancer-associated fibroblasts on cancer stem cell expansion of esophageal squamous cell carcinoma
Authors: Wang Ying , Feng Ping , Jiang Tong-chao , Guan Xin-yuan , Xia Yun-fei 
Published: March 2024

Abstract
Aims: FGFR2+ fibroblasts were reported to promote tumor progression, but the mechanisms remained unexplored in esophageal squamous cell carcinoma (ESCC).Methods: Multiplex immunohistochemistry (mIHC) displayed the distributions of FGFR2+ fibroblasts and cancer stem cells (CSCs). After FGFR2+ fibroblast isolation, tumor cells were stimulated with fibroblasts supernatant to assess radioresistance and CSC properties. RNA-seq analysis identified the downstream BMP5 expression.Results: In our preliminary study, the immunohistochemistry results showed that FGFR2+ fibroblasts were always represented in the area near cancer stem cells (CSCs), and FGFR2+ fibroblasts infiltration was associated with poor outcomes. When we cocultured FGFR2+ fibroblasts with tumor cells, we found the proportion of CSCs were upregulated. The results of RNA sequencing and ELISA showed that FGFR2+ fibroblasts overexpressed BMP5. Using FGFR2+ fibroblasts or BMP5 to stimulate cancer cells, the proportion of cancer stem cells was increased, the capabilities of sphere formation and survival after radiation were enhanced. Both RNA sequencing and immunoblotting results indicated that BMP5 affected H2AX phosphorylation in DNA repair pathway and activated its potential upstream pathway MAPK signaling pathway. In vivo experiments also showed that FGFR2+ fibroblasts could upregulate CSCs proportions.Conclusions: Our findings suggested that BMP5 derived from FGFR2+ fibroblasts might induce CSCs expansion and led to poor prognosis in the ESCC.
Citation Format: Ying Wang, Ping Feng, Tong-chao Jiang, Xin-yuan Guan, Yun-fei Xia. The function of FGFR2+ cancer-associated fibroblasts on cancer stem cell expansion of esophageal 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 281.