bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3520: Designing a dendritic cell-targeted immunotherapy for the treatment of pancreatic ductal adenocarcinoma
Authors: Vaskovich-Koubi Daniella , kleiner Ron , Eldar-Boock Anat , Pozzi Sabina , Ben-Shushan Dikla Dikla , Florindo Helena F. , Satchi-Fainaro Ronit 
Published: June 2022

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death. Low response rate, acquired resistance, severe side effects, highly desmoplastic, and immunosuppressive microenvironment have limited the clinical outcomes of immunotherapy in PDAC. To overcome these hurdles, we set to design novel immunotherapy that would be safe, efficacious, and selective to PDAC. The failure of immunotherapies to yield clinical response in PDAC is partially attributed to the inefficient antigen presentation by dendritic cells (DC) which results in insufficient T cells stimulation despite their expression of tumor-associated antigens (TAA). DC have an important role in the initiation and regulation of the innate and adaptive immune system. By efficient presentation of antigens, DC elicit an antigen-specific immune response. Trp53R172H is among the most common TP53 mutations in human PDAC, and is known as one of PDAC TAA. Despite the poor clinical outcomes, longer survival time was observed in PDAC patients with tumors that express high number of TAA combined with an abundant presentation of CD8+ T cell. To that end, we designed a DC-targeted nanoparticle (NP) containing PDAC Trp53R172H TAA and immune potentiators, with the DC targeting moiety, mannose, that was covalently conjugated to the NP, to enhance TAA presentation on DC. Thus, promote specific activation of T cells against PDAC’s TAA. The therapeutic activity of the NP was evaluated in vitro by our newly established 3D PDAC spheroids model, which composed of freshly isolated murine stromal cells, therefore, better imitates the complex microenvironment found in PDAC in vitro. Along with an in vivo PDAC model, we evaluated the safety profile and therapeutic effect of our NP. The NP proposed herein successfully activated splenocytes and induced a specific cytotoxic reaction against PDAC cells ex vivo, which may result in an improved survival rate.
Citation Format: Daniella Vaskovich-Koubi, Ron kleiner, Anat Eldar-Boock, Sabina Pozzi, Dikla Dikla Ben-Shushan, Helena F. Florindo, Ronit Satchi-Fainaro. Designing a dendritic cell-targeted immunotherapy for the treatment of pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3520.
Abstract 3525: Lactobacillus plantarum IMB19 enhances anti-tumor immune response by modulating multi-layered innate and adaptive immunity
Authors: Sharma Garima , Sharma Amit , Kim Inhae , Lee SooWoong , Lee Hae-Na , Park ChangWook , Im Sin-Hyeog 
Published: June 2022

Abstract
Intestinal commensals are being increasingly appreciated for their role in modulating the therapeutic efficacy of cancer therapies. Human-associated bacterial strains with demonstrable modulation of anti-tumor immune responses have great potential to be developed as biotherapeutics.We developed the AVATIOME࣪ model, a screening prototype based on murine primary immune cells, rationally targeting the innate and adaptive immune system to identify immuno-stimulating commensals.Our lead Lactobacillus plantarum IMB19 (Lp IMB19), suppresses tumor progression in pre-clinical models of melanoma, renal cancer, and NSCLC. LpIMB19 efficiently potentiates the therapeutic effect of anti-PD-L1 in murine tumor models. A capsular component of LpIMB19, structurally defined as rhamnose-rich hetero-polysaccharide (RHP) recapitulates the anti-tumor efficacy of live bacteria.The TLR2 agonist specifically targets macrophages towards an inflammatory phenotype followed by an increase in the activity of CD8+ IFNy+ T-cells. LpIMB19 and RHP enhance iron sequestration by activated macrophages in the tumor microenvironment through a defined mechanism. Thus, depriving tumor cells of iron and suppressing tumor cell proliferation. Translational investigations revealed the efficacy of LpIMB19 in urinary bladder xenograft studies.LpIMB19 mediated iron sequestration by inflammatory tumor macrophages, a byproduct of innate immune activation along with systemic CD8+ T-cells activation leads to enhancement of anti-tumor immunity. Our data on human cancers suggests the applicability of LpIMB19 as a potential onco-microbiotic. Currently, LpIMB19 is being progressed for clinical investigation as a live bio-therapeutic product (LBP) in combination with immune check-point inhibitors.
Citation Format: Garima Sharma, Amit Sharma, Inhae Kim, SooWoong Lee, Hae-Na Lee, ChangWook Park, Sin-Hyeog Im. Lactobacillus plantarum IMB19 enhances anti-tumor immune response by modulating multi-layered innate and adaptive immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3525.
Abstract 3561: Pan-cancer-specific engineered oncolytic vaccinia virus
Authors: Yoo So Young 
Published: June 2022

Abstract
Here, we developed a novel oncolytic vaccinia virus (NOV) with the dual advantages of cancer selectivity and normal vessel reconstructive activity by replacing the viral thymidine kinase (vTk) and vaccinia growth factor (VGF) genes with genes encoding TNF-related apoptosis-inducing ligand (TRAIL) and angiopoietin 1 (Ang1), respectively. The pan-cancer-specific oncolytic potency of NOV was confirmed in various human and mouse cancer cell lines (colon, lung, liver, pancreas, cholangiocarcinoma, cervical cancer, osteosarcoma, and melanoma). Vaccinia virus (VV) treatment directly induced early apoptosis in tumors within 24 h, and this effect was enhanced with further engineering; VGF and Tk deletion with Ang1 and TRAIL insertion. Meanwhile, treatment with the conventional anti-cancer drug cisplatin did not induce apoptosis. A virus-treated mouse colon/lung cancer syngeneic model showed attenuated tumor growth, which was in accordance with the results of percent survival measurement, CD8 expression analysis, and TUNEL staining with advanced genetic engineering. Taken together, our results indicate that NOV induces cancer tissue apoptosis and anti-tumor immunity and may constitute a highly advantageous therapeutic agent for next-generation solid tumor virotherapy with pan-cancer-specific oncolytic activity and high biosafety.
Citation Format: So Young Yoo. Pan-cancer-specific engineered oncolytic vaccinia virus [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3561.
Abstract 361: MicroRNA expression in murine spontaneous non-small cell lung cancer and human cell lines post-treatment of PRIMA-1
Authors: Perez Melanie , Grier Shaylyn , Gao Li , Duan Wenrui 
Published: June 2022

Abstract
A variety of cancers have been correlated with having a mutation on the TP53 gene, including lung cancer. Lung cancer has been one of the deadliest cancers in the United States. TP53-dependent reactivation and induction of massive apoptosis (PRIMA-1) changes mutant TP53’s conformation, resulting in the restoration of DNA binding and activation of p53 target genes. PRIMA-1 methylated analog, PRIMA-1Met (APR-246, Eprenetapopt) have been used in clinical trials to target cancers containing mutant TP53. It has been reported that PRIMA-1 induced apoptosis through the regulation of microRNAs. Our research group has previously developed a transgenic mice model with a mutant form of TP53 being expressed lung specifically, to closely model human lung cancer development. The aim of the current study is to investigate the effects of PRIMA-1 on miRNA expressions in a murine spontaneous lung cancer mice model, human lung cancer cell lines H211 and H1155. The transgenic FVB/N mice lung tumor model was developed using the lung specific human surfactant protein C (SPC) promoter to control the expression of mutant TP53(273H) following the standard injection method. Tumor bearing mice were identified with a micro-CT and were treated with the PRIMA-1 at a dose of 100mg/kg. Additionally, we treated two human cell lines H211 (containing mutant TP53 R248Q) and H1155 (containing mutant TP53 R273H) with the PRIMA-1. The miRNA expression profile was evaluated with the NanoString nCounter array analysis and qt-PCR array analysis. We found that three miRNAs were up-regulated (&gt;1.5-fold change) in the human lung cancer cells H211, H1155, and murine spontaneous non-small cell lung cancers model post treatment of PRIMA-1. The result of the study showed that miR-200c, miR-181c, and miR-183 was up-regulated in the two human cell lines and the transgenic mice lung tumors after treatment of PRIMA-1. While there was no significant downregulation in miRNA expression in these human lung cancer cells and the murine spontaneous lung cancer model. However, the overall miRNA expression is lower in murine spontaneous lung tumors when compared to the overall miRNA expression of the cell lines post PRIMA-1 treatment. This difference is due to model specific expression. Further investigation is needed to better understand the effects of PRIMA-1 in regulation of micro-RNA expression in the treatment of lung cancers containing mutant p53.
Citation Format: Melanie Perez, Shaylyn Grier, Li Gao, Wenrui Duan. MicroRNA expression in murine spontaneous non-small cell lung cancer and human cell lines post-treatment of PRIMA-1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 361.
Abstract 3666: Dietary potassium and risk of colorectal cancer: Findings from the Singapore Chinese Cohort Study
Authors: Luu Hung N. , Paragomi Pedram , Yu Yi-Chuan , Jin Aizhen , Wang Renwei , Schoen Robert E. , Koh Woon-Puay , Yuan Jian-Min 
Published: June 2022

Abstract
Background: Colorectal cancer (CRC) is a commonly diagnosed subtype of cancer with a high mortality rate. Potassium is a necessary trace element in the human boy and is derived mainly from diet. Prior studies found high intakes of potassium was inversely associated with colorectal cancer occurrence in Western population. No such effort has been made in Asian population. Methods: We examined the associations for dietary potassium with the risk of CRC in the Singapore Chinese Health Study (SCHS), a population-based prospective cohort study that includes 61,321 Chinese men and women in Singapore who were 45-74 years of age at baseline. Daily intake of potassium was derived from the self-reported intake of pre-defined food items using a validated semi-quantitative food frequency questionnaire (FFQ) at baseline according to the Singapore Food Composition Table. Cox proportional hazard regression model was used to estimate the hazard ratios (HRs) and respective 95% confidence intervals (CIs) for CRC associated with higher quartile of potassium compared with the lowest quartile with adjustment for potential confounders. Results: After an average of 17.5 years of follow-up, 2,140 participants developed CRC. Dietary potassium was inversely associated with CRC risk. The multivariable-adjusted HR of CRC for the highest relative to the lowest quarter of daily potassium intake was 0.85 (95% CI 0.75-0.96, Ptrend=0.03). The inverse association between high intake of potassium and CRC risk was more apparent among participants with body mass index (BMI) ≥ 23 kg/m2 (HRQ4vsQ1=0.75, 95% CI: 0.63-0.89; Ptrend=0.003) and those with history of type 2 diabetes (HRQ4vsQ1=0.65, 95% CI: 0.42-1.00; Ptrend=0.36).
Conclusions: In a large population-based prospective cohort study of more than 61,000 Chinese Singaporeans, we found inverse associations between dietary potassium intake and CRC risk. Future studies are warranted to elucidate the biological mechanism for the protective effect of potassium on the development of CRC.
Citation Format: Hung N. Luu, Pedram Paragomi, Yi-Chuan Yu, Aizhen Jin, Renwei Wang, Robert E. Schoen, Woon-Puay Koh, Jian-Min Yuan. Dietary potassium and risk of colorectal cancer: Findings from the Singapore Chinese Cohort Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3666.
Abstract 3687: Implementing geospatial technology to understand the prostate cancer health burdens and socioeconomic status in Alabama
Authors: Alagan Ram , Aladuwaka Seela , Singh Rajesh , Manne Upender , Mishra Manoj K. 
Published: June 2022

Abstract
Socioeconomic status and health disparities are a significant liability for the prevalence of many diseases, including cancer. Among many contributing factors, lack of socioeconomic advancement and inequality in resource distribution is closely associated with prostate cancer occurrence. The State of Alabama has one of the highest rates of prostate cancer in the nation and the third cancer epidemic at the state level. Due to widespread disparities in infrastructure development, political willpower, equal healthcare, and education opportunity, Alabama's Black Belt region has been further divided by socioeconomic statuses among the majority (Whites) and minority (African American) populations. The purpose of this research is to recognize Alabama's health burdens and socioeconomic status using geo-spatial technology (GIS) to examine prostate cancer health disparity. GIS has become a valuable decision-making tool in understanding the public health care sectors, including prostate cancer prevalence. GIS supports assembling spatial and non-spatial data, displays the spatial distribution of health disparities, and underlines further interconnectivity of policy-related questions. This research incorporates county-level prostate cancer data using GIS and outlining the correlation between prostate cancer prevalence and socioeconomic factors to understand Alabama's cancer health disparity and equity. A combination of socioeconomic factors and state and federal-level cancer epidemic data sources underline Alabama's black belt region (predominantly African American) prostate cancer prevalence is higher than the non-black belt. The GIS analysis demonstrated that effective cancer prevention programs are needed to eliminate health disparities and enhance health equity among underserved populations of Alabama.
Citation Format: Ram Alagan, Seela Aladuwaka, Rajesh Singh, Upender Manne, Manoj K. Mishra. Implementing geospatial technology to understand the prostate cancer health burdens and socioeconomic status in Alabama [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3687.
Abstract 3714: The antitumor activity of cannabis sativa and CBD in prostate cancer PC3 cells
Authors: Motadi Lesetja Raymond , Moleya Nonhlanhla B. 
Published: June 2022

Abstract
Prostate cancer is the second most frequently occurring carcinoma in males worldwide and one of the leading causes of death in men around the world. Recent studies estimate that over 1.4 million males are diagnosed with prostate cancer on an annual basis, with approximately 375 000 succumbing to the disease annually. With current treatments continuing to show severe side effects, there is a need for new treatments. In this study we looked at the effect of cannabis sativa extract, cannabidiol and cisplatin on prostate cancer cells, PC3.
Methods: In addressing the above questions, we employed the MTT assay to measure the antiproliferative effect on PC3 cells following treatment with varying concentrations of Cannabis sativa extract, cisplatin and cannabidiol. xCELLigence was also used to confirm the IC50 activity in which cells were grown in a 16 well plate coated with gold and monitor cell. Caspase 3/7 activity was also measured using 96 well-plate following treatment. Western-blot and qRT-PCR was also used to measure the gene expression of tumor suppressor genes, p53, Bax and Bcl2. Animal studies were employed to measure the growth of PC3-mouse derived cancer to evaluate the effect of compounds in vivo.
Results: From the treatment with varying concentrations of Cannabis sativa extract, cannabidiol and cisplatin, we have observed that the three compounds induced antiproliferation of PC3 cancer cell lines through the activation of caspase 3/7 activity. We also observed induction of apoptosis in these cells following silencing of retinoblastoma binding protein 6 (RBBP6), with upregulation of p53 and bax mRNA expression, and a reduction in Bcl2 gene expression. The growth of tumors in the mouse models were reduced following treatment with cisplatin and cannabidiol.
Conclusion: We demonstrated that cannabidiol is a viable therapy to treat prostate cancer cells, in combination with silencing of RBBP6. This suggests that cannabidiol rather Cannabis sativa extract may play an important role in reducing cancer progression.

Citation Format: Lesetja Raymond Motadi, Nonhlanhla B. Moleya. The antitumor activity of cannabis sativa and CBD in prostate cancer PC3 cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3714.
Abstract 3717: KMT2D loss cooperates with PTCH loss for medulloblastoma genesis
Authors: Dhar Shilpa S. , Brown Calena J. , Rizvi Ali S. , Abraham Janak R. , Sillitoe Roy V. , Chen Kaifu , Lee Min Gyu 
Published: June 2022

Abstract
We have previously reported that the histone H3 lysine 4 methyltransferase KMT2D (also called MLL4, MLL2, and ALR; a transcriptional coactivator) is required for neuronal differentiation of human neuron-committed NT2/D1 embryonal carcinoma stem cells. Notably, we have shown that brain-specific knockout of Kmt2d alone induces spontaneous medulloblastoma (MB) in mice and that Kmt2d loss in the brain highly upregulates several oncogenic signaling programs and downregulates tumor suppressor genes. Consistent with this, our analysis of several publicly available databases indicates that Kmt2d is the most frequently mutated epigenetic modifier (8%‒10%) in MB. In this study, we sought to assess whether Kmt2d loss cooperates with another oncogenic event in MB genesis. Particularly, PTCH (also known as PTCH1), a potent MB-signaling suppressor, is one of the most frequently mutated genes in MB, and KMT2D mutations co-occur with PTCH mutations more than with many other mutations in MB. Therefore, we determined the effect of Kmt2d loss on of Ptch+/--driven MB genesis by generating and analyzing Nestin-Cre Kmt2dfl/+ Ptch+/- mice. Our results showed that heterozygous loss of Kmt2d strongly increased the genesis and incidence of Ptch+/--driven MB. Supporting this, immunohistochemistry staining of Ki-67 (a proliferation marker) showed that heterozygous loss of Kmt2d in Ptch+/--driven MB highly increased the proliferation of MB cells. Our transcriptomic analysis showed that heterozygous Kmt2d loss upregulated tumor-promoting programs, including G-protein-coupled receptor signaling and oxidation-reduction process. In line with this, heterozygous Kmt2d loss upregulated oncogenic kinases (e.g., phospho-AKT1 and phospho-ERK) that may be downstream of G-protein-coupled receptor signaling. Mechanistically, our results indicate that these tumor-promoting programs are repressed, at least in part, by the transcription-repressive and tumor-suppressive factor (s) NCOR2, whose expression is activated by KMT2D. Our results would be the first to provide molecular insights into how co-losses of an epigenetic modifier and an MB-signaling suppressor cooperate for MB genesis. Our new mouse model would be helpful in future preclinical therapeutic experiments for MB treatment. Our findings suggest that targeting oncogenic effectors downstream of KMT2D loss can be considered a potential therapeutic strategy for MB treatment.
Citation Format: Shilpa S. Dhar, Calena J. Brown, Ali S. Rizvi, Janak R. Abraham, Roy V. Sillitoe, Kaifu Chen, Min Gyu Lee. KMT2D loss cooperates with PTCH loss for medulloblastoma genesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3717.
Abstract 3731: Epigenetic control of tumor cell killing by natural killer cells
Authors: Pasion Joyce , Barisic Darko , Meydan Cem , Ng Kong Y. , Lafoz Maria Tello , Huse Morgan , Melnick Ari , Wendel Hans-Guido 
Published: June 2022

Abstract
Immunotherapies including the activation of endogenous immune cells have stimulated great interest for their anti-tumor functions. An initial focus has been on genetic lesions such as loss of MHC class I and class II molecules that facilitate tumor cell escape. More recently, epigenetic mechanisms such as the disruption of the SWI/SNF remodeling complex PBAF have been implicated in regulating tumor sensitivity to CD8 T cell-mediated killing. Here, I used an unbiased genetic screening approach to examine resistance and sensitivity of breast cancer cells to Natural Killer (NK) cells. Among expected hits including caspases, interferon receptors, and cell death executioners, the screen revealed a surprising role of alternate SWI/SNF complexes in controlling NK cell-mediated cytotoxicity that relate to interferon-γ and perforin/granzyme B, and may be pharmacologically reversible. Altogether, I will discuss a new epigenetic mechanism that affect NK cell-mediated cytotoxicity with a focus on SWI/SNF complexes.

Citation Format: Joyce Pasion, Darko Barisic, Cem Meydan, Kong Y. Ng, Maria Tello Lafoz, Morgan Huse, Ari Melnick, Hans-Guido Wendel. Epigenetic control of tumor cell killing by natural killer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3731.
Abstract 3778: Mitochondrial dynamics in cancer restored by a bioactive fraction of fermented wheat germ extract
Authors: Bencze Gyula 
Published: June 2022

Abstract
Bioactive fraction of Fermented Wheat Germ Extract (A250) was shown to be effective in increasing gene expression of mitochondrial proteins in a dose-dependent manner. According to the STRING protein network analysis these proteins are linked to the Krebs cycle and apoptosis. However, the in vivo therapy had no effect on the white blood cell count, and the increase in the immune cell profile was favorable, indicating that its effect was specific to tumor cells.
Citation Format: Gyula Bencze. Mitochondrial dynamics in cancer restored by a bioactive fraction of fermented wheat germ extract [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3778.