bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2246: Prevalence of mycobacterium tuberculosis among PAP smear samples of cervical cancer suspects
Authors: Awoke Wondimu Ashagre 
Published: April 2023

Abstract
Introduction: Cervical cancer is one of the most common cancers in women around the world. The Pap smear test is the most common method of detecting abnormal cells that may develop into cancer. In addition, we want to know how common mycobacterium tuberculosis is among those who provide Pap smear samples.
Objectives: The purpose of this study is to examine the knowledge, attitudes, and practices of working women in Addis Abeba, Ethiopia, regarding cervical cancer and Pap smear tests, as well as the associations between knowledge, attitudes, and practices and socio-demographic factors. In addition, we will investigate the prevalence of mycobacterium tuberculosis from smears among those who provide Pap smear samples.
Methods: This will be a cross-sectional questionnaire-based study of 100 Ethiopian females' attending at Arsho medical laboratories from September to December 2022, knowledge, attitudes, and practices, as well as the prevalence of tuberculosis. All women between the ages of 20 and 65 who wanted to be diagnosed with cervical cancer were eligible.
Expected outcome: To teach and recall common cervical cancer symptoms such as menstrual bleeding, the appropriate age for Pap smear tests, and the interval between tests. Examine their use of hormonal contraception and their attitude toward Pap smear testing over the last five years. It will also be useful to know the prevalence of cervical tuberculosis.
Citation Format: Wondimu Ashagre Awoke. Prevalence of mycobacterium tuberculosis among PAP smear samples of cervical cancer suspects [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 2246.
Abstract 226: Targeted transcriptome sequencing enables exponential scaling of combinatorial barcoding in AML samples
Authors: Kim Grace , Papalexi Efthymia , Matulich Peter , Koehler Ryan , Schroeder Sarah , Tran Vuong , Roco Charles , Rosenberg Alexander 
Published: April 2023

Abstract
In the thirteen years since its inception, single-cell RNA-sequencing (scRNA-seq) has rapidly spread across multiple fields of research, leading to many new discoveries. As technologies have matured, the number of cells that can be processed in a single experiment has seen exponential growth with workflows now assaying up to one million cells in an individual experiment.
While high throughput sequencing methods have facilitated the discovery and characterization of various cell types, sequencing costs can be prohibitively high for routine use. Many applications of scRNA-seq are focused on cell type identification, gene regulatory networks, or biomarker discovery. These applications often do not require surveying the entire transcriptome, but rather require the interrogation of specific sets of well-characterized genes. In these cases, sequencing the entire transcriptome may be adding unnecessary project costs. To increase throughput and minimize sequencing costs, the development of a targeted gene enrichment method is required.
Here we extend our whole transcriptome split-pool combinatorial barcoding technology, to enable enrichment of a subset of genes in the final single cell sequencing libraries. To illustrate the power of our technology, we enriched a whole transcriptome library of human bone marrow mononuclear cells (BMMCs) from four acute myeloid leukemia (AML) donors and four control donors. From a library of 27,000 cells, we used our immune gene panel to enrich 1,000 genes representing canonical immune cell markers and pathways. Our method increased the percent of reads on target from as low as 1.6% in the whole transcriptome libraries to 75% in the targeted libraries. Furthermore, despite a nearly ten-fold reduction in sequencing reads between unenriched and enriched libraries, the resulting clustering yielded very high concordance of cell type identities and preserved AML-specific signatures such as FLT3, MKI67, and CD19.
Overall, we demonstrate our modular enrichment strategy preserves biological structure of the data and allows for deep characterization of gene signatures in health and disease. We envision our approach will enable researchers to simultaneously reduce sequencing costs while drastically scaling up the number of cells and samples across experiments.
Citation Format: Grace Kim, Efthymia Papalexi, Peter Matulich, Ryan Koehler, Sarah Schroeder, Vuong Tran, Charles Roco, Alexander Rosenberg. Targeted transcriptome sequencing enables exponential scaling of combinatorial barcoding in AML samples [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 226.
Abstract 2264: Role of first-line immune checkpoint inhibitors monotherapy for oncogene-driven non-small cell lung cancer
Authors: Chen Ying-Yin , Lin Chen-Wen , Hsein Yenh-Chen , Chen Chung-Yu 
Published: April 2023

Abstract
Though improvement of overall survival in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) was observed, their efficacy varies greatly among different immune and molecular profiles in tumors. Particularly, the clinical significance of ICIs for oncogene-driven NSCLC has been controversial. In this study, after excluding NSCLC patients harboring driven oncogenes as EGFR, ALK and ROS1 mutation, twenty NSCLC patents with higher Programmed cell death 1 ligand 1 (PD-L1) expression (PD-L1 ≧ 50%, immunohistochemical stained by SP263 or 22C3) were administered with Pembrolizumab alone as first-line immunotherapy. NSCLC patients with more higher PDL1 expression (PD-L1 ≧ 80%) had longer progression-free survival (PFS) PD-L1 ≧ 80% v.s. PD-L1 &lt; 80%, PFS, median, 11.2 v.s 7.0 months, hazard ratio [HR]: 0.52, p = 0.03). 10 of them had other driven oncogenes (5 for KRAS, 3 for MET, 1 for BRAF and 1 for NRAS) were detected by next-generation sequencing (NGS) (Illumina iSeq 100 Sequencing System; AmpliSeq for Illumina Focus Panel). Patients harboring driven oncogene had shorter PFS by first-line immunotherapy as Pembrolizumab (With driven oncogene v.s. without, PFS, median, 4.2 v.s.10.8 months, HR: 2.76, p = 0.001). In conclusion, NGS analysis was recommended even the NSCLC patients with higher PD-L1 expression before immunnotherapy. First-line ICIs monotherapy should be cautious for oncogene-driven NSCLC patients.
Citation Format: Ying-Yin Chen, Chen-Wen Lin, Yenh-Chen Hsein, Chung-Yu Chen. Role of first-line immune checkpoint inhibitors monotherapy for oncogene-driven non-small cell lung cancer [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 2264.
Abstract 227: In vivo functional genomics screen to uncover tumor intrinsic negative regulators of NK cell-mediated tumor cell killing
Authors: Duval Kayla , Krall Elsa , Piccioni Federica , Monberg Maria , Spatz Marianne , Ehrenberger Tobias , Follmer Nicole 
Published: April 2023

Abstract
Natural killer cells are innate immune cells whose activity is gated by activating and inhibitory receptors that bind ligands on potential target cells. NK cell gene signatures are associated with improved survival in several indications, and NK cell therapies have shown some encouraging results in the clinic. These data highlight the relevance of this cell type in anti-tumor immunity and has given rise to interest in amplifying NK responses to cancer as a complementary therapeutic strategy to current T cell based immunotherapies. The goal of this project is to identify tumor cell intrinsic negative regulators of NK cell-mediated tumor cell killing through in vivo CRISPR/Cas9 screening, with identification of both PD-1 blockade-dependent and -independent regulators. The syngeneic B16F10 model in C57Bl6 mice was used with or without NK depletion and with or without anti-PD1 treatment, with a custom library of 900 genes split into four subpools (one guide per gene per subpool). B16F10 cells were transduced in vitro and inoculated into mice ten days after spinfection. On day 14 after inoculation, tumors were harvested and subsequently the gDNA was isolated and sequenced. QC analysis indicated good guide recovery and screen performance. There were several hits from this screen that were depleted in the NK+ context but not in the NK depleted context, indicating their potential role in regulating NK mediated cell killing. Of the hits, several expected genes scored including B2M which is a known negative regulator of NK cell killing. Validation efforts include confirmation of dropout in other models as well as in vitro co-culture assays to assess enhanced NK killing of single gene KO cells. The hits identified in the screen will increase our understanding of anti-tumor immunity and serve as potential novel Oncology targets.
Citation Format: Kayla Duval, Elsa Krall, Federica Piccioni, Maria Monberg, Marianne Spatz, Tobias Ehrenberger, Nicole Follmer. In vivo functional genomics screen to uncover tumor intrinsic negative regulators of NK cell-mediated tumor cell killing [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 227.
Abstract 2322: Precision immuno-oncology (IO) ISH/IF multiplex panel: Spatial detection of cytokines and IO biomarkers
Authors: Dennison Brenna , Allen Stephanie , Patel Bhavika , Stapleton Jacob , Archuleta Roni , Rath Mary Lou , Mehra Navi , Talwalkar Sameer S. 
Published: April 2023

Abstract
Cytokines have a large impact on the tumor microenvironment by affecting cell growth, survival, inflammation, and differentiation. Understanding the spatial biology within the tumor microenvironment, including the cytokine organization within specific cell types, can lead to better treatment plans for patients. We developed a hybrid multiplex panel, using RNA in-situ hybridization (ISH) and immunofluorescence (IF) to investigate the spatial biology of the tumor microenvironment. This panel also enabled us to simultaneously detect the RNA of cytokines and protein of specific immuno-oncology (IO) biomarkers. This allows us to visualize spatially, not only the organization of cell types but also to identify the cellular sources of specific cytokines. In this study, we analyzed the tumor microenvironment of samples from non-small cell lung cancer (NSCLC) and breast cancer in two panels for cytokine RNAs and IO protein biomarkers. Panel 1 included TNFa and IL-2 cytokines combined with the CD68 and CD163 IO protein biomarkers. Panel 2 consisted of IL-6 and IL-2 cytokines with the PAX5 and CD3 IO protein biomarkers. Staining was completed on the Leica Bond RX autostainer, and slides were scanned using the PhenoImager™ Fusion. Visiopharm® software was used to analyze the tumor microenvironment of tissue samples and localize cytokines in specific cell types. CD163 positive macrophages (M2 phenotype) were seen predominantly within the tumors (NSCLC and breast cancer) whereas CD68 positive macrophages were identified towards the periphery in the non-tumor microenvironment. NSCLC tumor cells showed higher expression levels of IL-2, IL-6 and TNFa compared to breast cancer tumor cells. Predominance of CD3 positive T cells was noted with relative lack of PAX5 positive B cells within both NSCLC and breast cancer tumors. Multiplexing enabled assessment of relative expression levels of IL-2, IL-6 and TNFa in T lymphocytes and macrophages and TNFa in dendritic cells. Our hybrid multiplex panel can provide insights into the visualization of spatial organization of tumor microenvironment. It also enables semi-quantitative assessments for the expression levels of cytokines and their relative expression within tumor and immune cells, thereby helping to correlate response to treatment, especially with checkpoint inhibitors.
Citation Format: Brenna Dennison, Stephanie Allen, Bhavika Patel, Jacob Stapleton, Roni Archuleta, Mary Lou Rath, Navi Mehra, Sameer S. Talwalkar. Precision immuno-oncology (IO) ISH/IF multiplex panel: Spatial detection of cytokines and IO biomarkers [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 2322.
Abstract 2323: ZGGS18, a bispecific drug candidate of anti-VEGF and TGFbeta-trap, inhibiting tumor proliferation and improving tumor microenvironment with I/O therapy
Authors: Liu Ruifeng , Suarez Alfonso , Liban Tyler , Zhang Bin , Dai Tongcheng , Karow Margaret , Sheng Jackie , Sheng Zelin , Lv Binhua , Zhu Bing 
Published: April 2023

Abstract
ZGGS18 is a bifunctional fusion protein targeting both human vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β), which consist of a monoclonal antibody against VEGF and an engineered extracellular domain of TGF-β receptor II (TGF-βRII ECD). In vitro studies show ZGGS18 specifically and simultaneously binding towards various VEGFs and capturing different TGF-β isoforms by trap domains that play a synergistic role to block signaling of VEGF/TGF-β with their receptors. For instance, ZGGS18 inhibits human VEGF121 and 165 induced HUVEC proliferation; ZGGS18 also neutralizes TGF-β1 and -β3 related growth arrest of HT-2 cells. Further studies show that ZGGS18 does not induce ADCC- or CDC-dependent killing tumor cells expressing two soluble targets, suggesting its binding affinities towards Fc-gamma and complement C1q receptors without effector functions. These results support functional depletion of VEGF/TGF-β in tumor microenvironment (TME) by ZGGS18 essentially for its MOA to inhibit tumor growth. A dose-dependent in vivo anti-tumor efficacy of ZGGS18 (1, 3 and 15 mg/kg) has been found in PBMC humanized H460 lung cancer xenograft model. In addition, ZGGS18 has enhanced efficacies to kill tumor growth in MC38 xenograft models when it is combined with anti-PD-1 antibodies (keytruda), support the improvement of TME for I/O reagents by ZGGS18 in cooperation with its role in anti-proliferation and anti-angiogenesis. Toxicity and safety pharmacology studies with weekly repeat doses for four weeks in cynomolgus monkeys indicate that ZGGS18 is well tolerated over the dose range 13, 40 and 120 mg/kg without obviously toxic or adverse effects (NOAEL =120 mg/kg). PK/TK analyses indicate that ZGG18 has a prolonged half-life in plasma, attribute to its human neonatal Fc receptor (FcRn) binding and pH-dependent interaction for mAb recycling. The IND application of ZGGS18 has been approved by both FDA and Chinese NMPA for clinical trials in treatment of advanced tumors as monotherapy and/or in combined with PD-1/PD-L1 based I/O therapies.
Citation Format: Ruifeng Liu, Alfonso Suarez, Tyler Liban, Bin Zhang, Tongcheng Dai, Margaret Karow, Jackie Sheng, Zelin Sheng, Binhua Lv, Bing Zhu. ZGGS18, a bispecific drug candidate of anti-VEGF and TGFbeta-trap, inhibiting tumor proliferation and improving tumor microenvironment with I/O therapy [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 2323.
Abstract 2333: Verteporfin demonstrates antitumoral effect in murine cholangiocarcinoma models
Authors: Lee Jihye , Wang Xin , Bian Jing , Cam Maggie , Xie Changqing 
Published: April 2023

Abstract
Cholangiocarcinoma (CCA) is a heterogenous malignancy that is derived from the biliary epithelium. There is growing concern as CCA incidence in United States has steadily increased. Additionally, CCA disproportionately affects different populations, and overall prognosis remains poor with a 5-year survival rate of 10%. Moreover, the Hippo/yes-associated protein (YAP) pathway has been reported to affect various aspects of tumorigenesis and recent reports showed that higher expression of YAP is negatively associated with the survival rate in CCA patients. Thus, we investigated the antitumoral effect of verteporfin, a YAP pathway inhibitor, in YAP/Akt and Notch/Akt hydrodynamic tail vein injected murine models. Our results demonstrated reduced liver weight in verteporfin treated groups compared to the vehicle treated group. Single cell RNA sequence analysis noted the verteporfin treated group had reduced stemness-related expressing cells in the malignant cell population. Furthermore, B cell, CD8+ T cell, and Tumor-Associated Macrophages M1 (TAM M1) populations increased following verteporfin treatment. In summary, this study indicates that verteporfin reduces tumorigenesis in CCA by the regulation of cancer stemness and modulation of immune cells, which includes anti-tumoral/pro-inflammatory TAM M1 in CCA animal models.
Citation Format: Jihye Lee, Xin Wang, Jing Bian, Maggie Cam, Changqing Xie. Verteporfin demonstrates antitumoral effect in murine cholangiocarcinoma models [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 2333.
Abstract 2337: Overcome solid tumor immunosuppression for T cells-mediated cancer elimination
Authors: Shi Lei , Bian Zhen , Zen Jane , Stylli Harry , Liu Yuan 
Published: April 2023

Abstract
T cell immunotherapy to solid tumor requires not only sufficient numbers of cancer cell-specific cytotoxic T cells, but also their infiltration into tumor tissues and the ability to resist hostile TME immunosuppression.
Through a proprietary process, we have identified a unique reagent, termed KX147, of which treatment of tumor potently repolarizes the TME, resulting in abrogation of multi-axes immunosuppressive signal transduction pathways reprograme of the TME for innate and adaptive immunity against cancer. We found that immunotherapy-refractory solid tumors under therapies generally fail to induce intratumoral macrophages for proinflammatory phenotypic change, nor did they reprogram the TME towards anti-tumor immunogenicity. Rather, these tumors arbitrate strong resistance through increasing IL-10 production, TGFβ signaling (TGFBR1 and TGFBR2), and CCL2 chemokine that attracts MDSC, leading to wound healing and reinforcement of tumor immunosuppression. In stark contrast, tumors treated with KX147 exhibit completely different TME responses to checkpoint blockade, RT and other immune-modulatory therapies, and reshape intratumoral macrophages from immunosuppression to potent proinflammation, featuring high expressions of TNFα, IFNγ, IL-1β, IL-6, IL-12, IL-17, IL-18, etc., while abating IL-10 and TGFβ. Moreover, KX147 also induces a prominent immunogenic antigen presentation machinery with elevated cell surface MHC-I, MHC-II, and costimulatory molecules CD80, CD86, CD40, OX40L on macrophages, which through antigen presentation induces large expansion of tumor-specific T cells for tumor elimination. Together, our studies demonstrate a novel immunotherapy strategy with KX147 combination, which holds promises for rapid and systemic elimination of solid tumors and metastases to achieve cure.
Citation Format: Lei Shi, Zhen Bian, Jane Zen, Harry Stylli, Yuan Liu. Overcome solid tumor immunosuppression for T cells-mediated cancer elimination [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 2337.
Abstract 2343: Targeting EPHB2/ABL1 restores anti-tumor immunity in a preclinical model of ependymoma
Authors: Ren Jun , Amoozgar Zohreh , Zhao Yuhui , Lei Pinji , Ho William W. , Robergea Sylvie , Huang Peigen , Duda Dan G. , Xu Lei , Jain Rakesh K. 
Published: April 2023

Abstract
Ependymoma is a common type of brain tumor in children, often resistant to available cytotoxics. Molecular profiling studies have led to a better understanding of ependymoma pathology and revealed a critical role of EPHB2. However, the immune system's role in tumor progression and treatment response remains poorly understood. Here, we show that the multikinase inhibitor dasatinib potently inhibits EPHB2 and ABL1 and the growth of ependymoma both in vitro and in vivo. Using an immunocompetent mouse model of ependymoma that faithfully recapitulates its immune microenvironment, we found an increased frequency of M2-like tumor-associated macrophages (TAMs), which proportionally increased with tumor size. Treatment with dasatinib reprogrammed the immune microenvironment of ependymoma by polarizing the TAMs toward an M1-like phenotype and increasing CD8 T cell activation. Dasatinib treatment induced complete regression of established mEPN-Ephb2 tumors in 78% of the animals and protected survivors against tumor recurrence. These studies indicate that dasatinib may be an effective therapy for this molecular subgroup of pediatric brain tumors and should be tested in clinical trials.
Citation Format: Jun Ren, Zohreh Amoozgar, Yuhui Zhao, Pinji Lei, William W. Ho, Sylvie Robergea, Peigen Huang, Dan G. Duda, Lei Xu, Rakesh K. Jain. Targeting EPHB2/ABL1 restores anti-tumor immunity in a preclinical model of ependymoma [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 2343.