bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 6232: Ulipristal acetate, a selective progesterone receptor modulator, induces cell death via inhibition of STAT3/CCL2 signaling pathway in uterine sarcoma
Authors: Hwang Jae Ryoung , Cho Young-Jae , Ryu Ji-Yoon , Choi Ju-Yeon , Choi Jung-Joo , Lee Jeong-Won 
Published: April 2023

Abstract
Purpose: Ulipristal acetate (UPA) is used for the treatment of uterine leiomyoma as a selective progesterone receptor modulator. Until now, there has been no experimental research on the effect of UPA on uterine sarcoma. In this study, we examined the efficacy of UPA in uterine sarcoma with in vitro and in vivo animal models.
Experimental Design: The cytotoxicity of UPA was determined in uterine sarcoma cell lines (MES-SA, SK-UT-1, and SK-LMS-1) by MTT and caspase-3 activity assays. A migration assay was done using a Transwell chamber, and MMP-2 was measured with its specific ELISA kit. Apoptotic genes and signaling pathways affected by UPA were analyzed by complementary DNA (cDNA) microarray of uterine sarcoma cell lines and western blot, respectively. The in vivo efficacy of UPA was examined in uterine sarcoma cell line- and patient-derived xenograft mice models.
Results: UPA inhibited cell growth and increased apoptosis in cell lines including uterine sarcoma (MES-SA) and leiomyosarcoma (SK-UT-1 and SK-LMS-1) in a dose-dependent manner. UPA also inhibited cell migration and the expression of MMP-2. cDNA microarray analysis revealed that CCL2 was commonly down-regulated by UPA in investigated cell lines. The UPA-mediated inhibition of CCL2 expression was confirmed by ELISA. The phosphorylation and the total expression of STAT3, downstream from the CCL2 signaling pathway, was also inhibited by UPA. We also found that UPA reduced cell growth and increased caspase-3 activity in primary culture cells from leiomyosarcoma patient-derived xenografts (PDX-C). Moreover, we found that STAT3/CCL2 inhibition by UPA was independent of the expression of progesterone receptor. In vivo studies with MES-SA and SK-UT-1 cell line-derived xenografts and a PDX model with leiomyosarcoma demonstrated that UPA significantly decreased tumor growth.
Conclusions: UPA had significant anti-tumor effects in uterine sarcoma through the STAT3/CCL2 signaling pathway and might be a potential therapeutic agent to treat this disease.
Citation Format: Jae Ryoung Hwang, Young-Jae Cho, Ji-Yoon Ryu, Ju-Yeon Choi, Jung-Joo Choi, Jeong-Won Lee. Ulipristal acetate, a selective progesterone receptor modulator, induces cell death via inhibition of STAT3/CCL2 signaling pathway in uterine sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6232.
Abstract 6753: Non-HIV cryptococcal patients with hematological malignancies: A retrospective analysis of a ten-year study from a Peruvian oncologic center
Authors: Meza Kelly , Cuellar Luis E. 
Published: April 2023

Abstract
Background Globally, cryptococcal infection has become a public health challenge. However, relatively little is known about cryptococcal infection in people with hematological disorders.
Methods We developed a retrospective cohort study that includes hematological patients who had cryptococcosis infection seen in the Instituto Nacional de Enfermedades Neoplasicas between 2007 and 2017.
Results During the 11-year study period, a total of 21 cases of cryptococcosis (incidence rate of 13,4 per 1000 hematological malignancies). The time of diagnosis of cryptococcosis since hematologic malignancy diagnosis was 42 (18-161) days. Non-Hodgkin lymphoma (NHL) was the most frequent malignancy (47.6%), followed by leukemias (23.8%), multiple myeloma in (19.1%), and HL (9.5%). Three cases of adult T-cell leukemia/lymphoma associated with HTLV-1 infection were identified in the NHL. Cryptococcemia was the most frequent diagnosis (85.7%) followed by pulmonary (52.4%) and CNS (38.1%) involvement. Regarding clinical presentation, f ever was the most common symptom in meningeal cryptococcosis (76.2%) and dyspnea in pulmonary cryptococcosis (61.9%). The use of immunosuppressant chemotherapy within a month before the diagnosis of cryptococcosis was the most common risk factor. The main characteristics between patients with cryptococcosis and type of neoplasms (NHL vs other hematological neoplasms) such as age at admission, site of presentation of cryptococcosis, and lymphocyte count at admission were different significantly between these groups. In the NHL group, there was less involvement of the lungs. Overall survival (OS) in 15 and 120 days were 70% (95%CI: 0.43-0.86) and 51% (95%CI: 0.26-0.72), respectively. OS for patients with NHL was 57% at 15 days (95% CI: 0.17-0.83) and 42% at 120 days (95%CI:0.09-0.73). OS for other hematological malignancies was 90% at 15 days (95%CI:0.47-0.98) and 60% at 120 days (95%CI: 0.25-0.82).
Conclusions CNS cryptococcal infection was more frequent in patients with NHL.
Citation Format: Kelly Meza, Luis E. Cuellar. Non-HIV cryptococcal patients with hematological malignancies: A retrospective analysis of a ten-year study from a Peruvian oncologic center. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6753.
Abstract 6781: Spatial omics using spatially-resolved laser-activated cell sorting for cancer biomarker discovery
Authors: Lee Amos C. , Lee Sumin , Kwon Sunghoon 
Published: April 2023

Abstract
Cancer is spatially heterogeneous in terms of genetic molecules. Revealing genomic, epigenomic, transcriptomic, and epitranscriptomic features that are unique to the malignant cell populations within cancer lead to cancer biomarker discoveries that can be translated into diagnostic or therapeutic tools. Here, we introduce spatially-resolved laser-activated cell sorting (SLACS) technology coupled to next generation sequencing and mass spectrometry that analyzes genetic molecules from regions of interest within spatial context. Specifically, we demonstrate application of SLACS in various cancers such as breast cancer, glioblastoma, glioma, meningioma, multiple myeloma, and leukemia. Examples of discovering cancer biomarker and their mechanism of action within spatial context are also provided. Specifically, we describe Select-seq which isolates the regions of interest as small as single cells from the immunofluorescence stained tissue and obtains the full-length transcriptome data. We demonstrated Select-seq on tumor tissue section from triple negative breast cancer patient who have received neoadjuvant chemotherapy. Select-seq produced full-length spatial transcriptome data, with which we analyzed the transcriptomic and epitranscriptomic features including alternative splicing variant, complementarity-determining region analysis of B cells, and even adenosine-to-inosine base editing. We were also able to analyze the immune- and stem-cell-like microniches, in which the complex mechanisms behind ferroptosis inhibition might suggest therapeutic options for the TNBC patients. Bridging spatial technologies to omics technologies, the discovery of specific markers within spatial context will provide insights into the next generation diagnostics and cancer therapeutics such as cancer vaccines.
Citation Format: Amos C. Lee, Sumin Lee, Sunghoon Kwon. Spatial omics using spatially-resolved laser-activated cell sorting for cancer biomarker discovery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6781.
Abstract 6796: PoxSTG, a novel chimeric poxvirus with improved oncolytic potency
Authors: Erbs Philippe , Findeli Annie , Foloppe Johann , Kempf Juliette , Farine Isabelle , Moreau Baptiste , Hortelano Julie , Pichon Christelle , Deforges Jules , Quemeneur Eric 
Published: April 2023

Abstract
Oncolytic virus (OV) therapy has emerged as a promising approach for cancer treatment with the potential to be less toxic and more efficient than classic cancer therapies. Various types of OVs in clinical development, including Vaccinia virus (VACV)-derived OVs, have shown good safety profiles, but limited therapeutic efficacy as monotherapy in some cancer models. Many different methods have been employed to improve the oncolytic potency of OVs. We used a directed evolution process, pooling multiple species of orthopoxviruses to generate chimeric poxviruses with increased oncolytic properties. Through selective pressure by successive passages on human tumor cells, a new chimeric oncolytic poxvirus, named PoxSTG, was derived. The chimeric viral genome contains, in addition to sequences from several strains of Vaccinia virus, sequences of Rabbitpox virus and Cowpox virus. Compared with its parental viruses, PoxSTG has demonstrated superior oncolytic characteristics, and was notably attenuated in normal primary cells. PoxSTG has superior secretion of extracellular-enveloped virus (EEV) compared to all parental strains inducing higher dissemination of the virus into the tumors and more resistance to neutralization. PoxSTG was saved and showed potent antitumor effects in several syngeneic and xenograft mouse models of cancers. Furthermore, PoxSTG exerted low-dose antitumor effects in virus-injected and non-virus-injected distant tumors in a CRC xenograft model, demonstrating strong virus spread to distant tumors. All these data demonstrate the potential of PoxSTG as a novel therapeutic agent for cancer treatment.
Citation Format: Philippe Erbs, Annie Findeli, Johann Foloppe, Juliette Kempf, Isabelle Farine, Baptiste Moreau, Julie Hortelano, Christelle Pichon, Jules Deforges, Eric Quemeneur. PoxSTG, a novel chimeric poxvirus with improved oncolytic potency. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6796.
Abstract 683: Vaccination against androgen receptor splice variant induces anti-tumor adaptive immune responses
Authors: Marek Robert D. , Wei Junping , Wang Tao , Yang Xiao-Yi , Lei Gangjun , Hartman Zachary C. 
Published: April 2023

Abstract
Background: Androgen receptor (AR) signaling has been the central target for standard-of-care prostate cancer therapies, although de novo resistance to these therapies occurs in many metastatic prostate cancer patients within 2-3 years. Resistance to AR targeting agents most often develops through overexpression of AR and expression of truncated, constitutively active RNA splice variants of AR. While clinical use of PD-1/PD-L1 immune checkpoint blockade has failed to demonstrate clinical success in treating resistance prostate cancers, the slower progression of prostate cancer provides an opportunity for immune targeted interventions. Cancer specific vaccines have the potential to enable and enhance tumor specific immune responses by stimulating and directing T cell immunity to important oncologic targets. We hypothesized that a cancer vaccine designed to induce a T cell response against cells expressing high levels of AR would result in an anti-tumor effect and potentially prevent or delay the development of therapeutic resistance.
Methods: To evaluate AR and AR variants as potential immunological targets, we produced adenoviral vaccines against AR (Ad-AR) or AR splice variant 7 (Ad-AR-V7). We vaccinated naïve mice and examined AR and AR variant specific immunity in peptide restimulation. We further tested our vaccines in prophylactic and therapeutic regimens using multiple subcutaneous syngeneic tumor models (including prostate tumor lines, such as TrampC2) which were engineered to express AR or AR-V7.
Results: Adenoviral vaccines targeting AR or AR-V7 produced robust T-cell responses against the N-terminal domain of AR. Notably, vaccination with both Ad-AR or Ad-AR-V7 induced significant anti-tumor immune responses, inducing complete tumor clearance against tumors expressing AR-V7 and allowing for long-term survival in the majority of vaccinated mice.
Conclusions: These data demonstrate the potential of AR and AR splice variants as immunologic targets of prostate cancer vaccines, which elicit AR specific T cell immunity and produce anti-tumor responses in prostate cancers.
Citation Format: Robert D. Marek, Junping Wei, Tao Wang, Xiao-Yi Yang, Gangjun Lei, Zachary C. Hartman. Vaccination against androgen receptor splice variant induces anti-tumor adaptive immune responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 683.
Abstract 707: High major histocompatibility complex class I expression overcomes cancer immunotherapy resistance due to interferon gamma signaling pathway defects
Authors: Kawase Katsushige , Kawashima Shusuke , Nagasaki Joji , Inozume Takashi , Yamamoto Hiromasa , Kawazu Masahito , Hanazawa Toyoyuki , Togashi Yosuke 
Published: April 2023

Abstract
IFN-γ signaling pathway defects such as JAK mutations are well-known mechanisms of resistance to immune checkpoint inhibitors (ICIs). However, some patients respond to ICIs despite IFN-γ signaling pathway defects, and the detailed mechanisms remain unclear. Here, we created JAK-deleted cancer cell lines and evaluated antitumor immunity. As a result, several tumors responded to PD-1 blockade despite JAK deletion. Such sensitive tumors had high major histocompatibility complex class I (MHC-I) expression despite IFN-γ signaling pathway defects, whereas MHC-I expression was reduced by JAK deletion in resistant tumors. In particular, if cancer cells had high MHC-I expression despite defects in IFN-γ signaling pathways, chemokines that recruit effector T cells were mainly produced by immune cells rather than cancer cells in the tumor microenvironment. Accordingly, we found a response to ICIs in a patient with JAK-negative head and neck squamous cell carcinoma, whose human leukocyte antigen class I (HLA-I) expression level was maintained. In addition, clustered regularly interspaced short palindromic repeats (CRISPR) screening to identify molecules with elevated MHC-I expression independent of IFN-γ signaling pathways demonstrated that guanine nucleotide-binding protein subunit gamma 4 (GNG4) maintained MHC-I expression via the NF-κB signaling pathway. Our results indicate that patients with IFN-ɤ signaling pathway defects are not always resistant to ICIs, and highlight the importance of MHC-I expression among the pathways, including inhibitory effects on cellular proliferation or chemokine production, and the possibility of NF-κB-targeted therapies to overcome such resistance.
Citation Format: Katsushige Kawase, Shusuke Kawashima, Joji Nagasaki, Takashi Inozume, Hiromasa Yamamoto, Masahito Kawazu, Toyoyuki Hanazawa, Yosuke Togashi. High major histocompatibility complex class I expression overcomes cancer immunotherapy resistance due to interferon gamma signaling pathway defects [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 707.
Abstract 71: Melanoma alters the bone marrow immune composition in an age-related manner
Authors: Carey Alexis Erasta , Chhabra Yash , Black Ethan , Rocha Murilo Ramos , Fane Mitchell , Wang Vania , Zabransky Daniel , Bravante Gloria , Hueser Laura , Weeraratna Ashani 
Published: April 2023

Abstract
Melanoma accounts for the most skin cancer-related deaths in the United States. As patients age, anti-tumor responses decline, making age a negative independent prognostic factor of overall survival in melanoma. Despite advances in immunotherapeutic modalities, there remains a subset of patients who do not benefit from these treatments. Understanding cancer and age-related changes to immune cell development in the bone marrow can improve patient outcomes. We hypothesize that during aging, the bone marrow niche is reshaped, driving precursor cells to become immunosuppressive. This ultimately decreases the anti-tumor response to melanoma due to the skewing of hematopoiesis to yield decreased immune function. In order to tackle this hypothesis, flow cytometry was used to analyze immune compositional changes in the bone marrow of mice challenged with melanoma. Our preliminary data suggests that when melanoma is present in the skin, there are changes to the bone marrow niche, such as an increase in total myeloid cells. Specifically, in the bone marrow of aged tumor-bearing mice, we see a decrease in Ly6C+Ly6G+ granulocytic progenitor cells and an increase in Ly6C+Ly6G- monocytic progenitor cells compared to the bone marrow of young tumor-bearing mice. We predict that the secretome of the aged bone marrow niche will impact immune cell development by producing more immature myeloid cells that can travel to the tumor site. We also saw an increase in the proportion of CD4+ T-cells in the aged bone marrow when melanoma is present. Thus, there appears to be a shift in cell populations in the aged bone marrow niche when the mice are burdened with melanoma. As a future direction, we plan to investigate the role of the aged bone marrow niche and its secretome on the effectiveness of immunotherapies, such as anti-PD-1. These insights could lead to improved outcomes for elderly patients with melanoma.
Citation Format: Alexis Erasta Carey, Yash Chhabra, Ethan Black, Murilo Ramos Rocha, Mitchell Fane, Vania Wang, Daniel Zabransky, Gloria Bravante, Laura Hueser, Ashani Weeraratna. Melanoma alters the bone marrow immune composition in an age-related manner [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 71.
Abstract 993: Epigenetic immune cell profiling in B-non-Hodgkin lymphoma biopsies
Authors: Werner Jeannette , Walter Steffi , Sachsenmaier Christoph , Schulze Janika , Phippard Deborah , Olek Sven , Seliger Barbara , Wickenhauser Claudia 
Published: April 2023

Abstract
Early detection and differential diagnosis of Non-Hodgkin lymphoma (NHL) is essential for the initiation of suitable therapy options. Biopsy based diagnosis allows allocation to World Health Organization (WHO) sub-classification groups but prognosis often needs identification of specific genetic aberrations or gene expression patterns. Despite this strategy, prognosis is difficult, since diseases, like e.g. mantel cell lymphoma, can be indolent or aggressive. Here we report the characterization of NHL biopsies using epigenetic immune cell quantification. This approach is based on the identification of specifically demethylated regions in individual immune cell types. These regions are then quantified using methylation-sensitive qPCR after bisulfite conversion. This highly reproducible and objective method allows in depth immunophenotyping of the tumor microenvironment. Next to CD4+ and CD8+ T cells, B cells and NK cells more specialized immune cells like regulatory T cells (Tregs), follicular T helper cells, PD-1 expressing cells and Myeloid derived suppressor cells (MDSC) were quantitatively determined in formalin-fixed tissue samples of 251 patients with different B cell Non-Hodgkin lymphomas. As a result, characteristic immune cell distribution patterns were identified for the different lymphoma entities, including chronic lymphocytic leukemia (B-CLL) (n=41), mantle cell lymphoma (MCL) (n=32), follicular lymphoma (FL) (n=33), diffuse large B cell lymphoma (DLBCL) (n=74), marginal zone lymphoma (MZL) (n=40) and B cell acute lymphoblastic leukemia (B-ALL) (n=26). In addition, substantial heterogeneity within the entities was observed that may correlate with disease prognosis. Among others, this is particularly the case for MDSC in B-CLL patients as well as for NK cells and Tregs in MCL and PD-1+ cells in FL patients. Currently clusters within the different disease groups are analyzed with regard to the clinical outcome to investigate if disease prognosis can be predicted by epigenetic immune cell quantification. In conclusion, epigenetic immune cell quantification is a suitable method to analyze the tumor microenvironment of NHL patients with the potential to support patient’s prognosis.
Citation Format: Jeannette Werner, Steffi Walter, Christoph Sachsenmaier, Janika Schulze, Deborah Phippard, Sven Olek, Barbara Seliger, Claudia Wickenhauser. Epigenetic immune cell profiling in B-non-Hodgkin lymphoma biopsies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 993.
Abstract 995: Evaluation of plasma cytokines and chemokines as potential biomarkers for colorectal cancer detection
Authors: Caraballo Elba V. , Centeno-Girona Hilmaris , Macias Yilda , Ocasio Madeline M. Mártir , Cruz-Correa Marcia R. 
Published: April 2023

Abstract
Despite evidence suggesting that current Colorectal Cancer (CRC) screening strategies reduce mortality rates, screening compliance is suboptimal; for this, our study aimed to evaluate the discriminatory potential of plasma cytokine and chemokine levels for CRC detection in plasma samples in a Hispanic subpopulation. Using a retrospective case-control study design, we evaluated plasma samples in 20 CRC cases and 20 age-gender matched controls from the Puerto Rico Familial Colorectal Cancer Registry (PURIFICAR). BD CBA Human Th1/Th2/Th17 Cytokine and Human Chemokine kits were used to prepare plasma samples for flow cytometric analysis (Becton-Dickinson & Co). Mann-Whitney-U test was used to detect differences between biomarkers and case-control groups. Measures of diagnostic accuracy were estimated for comparisons according to CRC disease stage. We compared multivariable models to determine the best CRC case-classifier. The median levels of six of the cytokines evaluated (IL-2, IL-4, IL-6, IL-10, TNF, and IL-17A) and one chemokine (CXCL10-/IP-10) significantly differed between cases and controls (P&lt;0.05). ROC plots and logistic regression analysis showed that these seven biomarkers displayed good to excellent accuracy (AUC: 0.6-0.9). Multivariate analysis showed that the best-case classifying model included the seven statistically significant markers. Our findings suggest that discriminatory biomarker levels between CRC cases and controls observed show their great potential as targets in novel blood-based screening tests for CRC. The development of a non-invasive CRC screening test will provide an alternative to increasing adherence, early detection, survivorship, and a tool for a population-based prevention strategy approach.
Citation Format: Elba V. Caraballo, Hilmaris Centeno-Girona, Yilda Macias, Madeline M. Mártir Ocasio, Marcia R. Cruz-Correa. Evaluation of plasma cytokines and chemokines as potential biomarkers for colorectal cancer detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 995.