bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5298: Multiplex immunoassay characterization of 48 cytokines, chemokines, and growth factors in colorectal cancer
Authors: Lie Wen-Rong , Steiner Harold , Williams Sasha , Banerjee Munmun , Saporita Anthony , Gilliam Brooke , Xiao Qiang 
Published: June 2023

Abstract
Cytokines, chemokines, and growth factors are critical mediators of immune system function capable of signaling through autocrine, paracrine, and endocrine mechanisms. Their pleiotropic immunomodulatory properties allow these biomolecules to react to diverse stimuli and regulate the immune response. We developed a novel immunoassay, using Luminex xMAP technology, for the simultaneous measurement of 48 cytokines, chemokines, and growth factors in serum, plasma, and cell culture supernatant. Many of these proteins have been proposed as biomarkers of colorectal cancer (CRC) and as key regulators of the tumor microenvironment (TME). While this complex milieu can support antitumor immunity, CRC is frequently characterized by chronic inflammation driving disease progression, with the TME serving as a potent reservoir from which the cytokines, chemokines, and growth factors exert their influence. The MILLIPLEX Human Cytokine/Chemokine/Growth Factor Panel B (HCYTB-60K) assays were performed in 96-well plates and run on the Luminex LX200™ instrument. Data was acquired via xPONENT v. 4.3 software. Data analysis was performed for all immunoassays using the Belysa Immunoassay Curve Fitting Software. Commercially available serum samples obtained from colorectal cancer patients and healthy controls were evaluated for cytokine, chemokine, and growth factor expression. Of the 48 analytes tested, statistically significant increases in BAFF, sFas, SCF, and MPIF-1 were observed in colorectal cancer serum. In contrast, IL-20 and ENA-78 decreased relative to healthy controls. While the immunoassay was verified for measurement of serum and plasma samples, additional sample types may be of interest to cancer researchers. Therefore, we evaluated the ability of the 48-plex immunoassay to measure these biomarkers in CSF, urine, milk, tumor samples and exosomal isolates, establishing a profile for these proteins in each sample type. Altogether, this study uses a novel multiplex immunoassay to characterize the immunological profile of colorectal cancer serum, focusing on 48 cytokines, chemokines, and growth factors. Additionally, alternative sample types were evaluated to establish the utility of this technology for applications beyond serum, plasma, and cell culture supernatant.
Citation Format: Wen-Rong Lie, Harold Steiner, Sasha Williams, Munmun Banerjee, Anthony Saporita, Brooke Gilliam, Qiang Xiao. Multiplex immunoassay characterization of 48 cytokines, chemokines, and growth factors in colorectal 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 5298.
Abstract 5303: Upregulation of the polycomb group protein SCML2 contributes to aggressive prostate cancer
Authors: Boston Ava M. , Dwead Abdulrahman M. , Al-Mathkour Marwah M. , Khazaw Kezhan , Cinar Bekir 
Published: June 2023

Abstract
Advanced prostate cancer (PC) is the leading cause of death in the US because there is no effective treatment due to the poorly understood disease mechanism. Sex comb on midleg-like-2 (SCML2) is a member of Polycomb repressive complex 1 and regulates homeotic gene expression during development. Using proteomic approaches, we have identified SCML2 as a binding partner of the YAP1 protein complexes isolated from PC cell lines. Both SCML2 and YAP1 regulate basic cellular biology, including stem cell maintenance and carcinogenesis; however, whether SCML2 and YAP1 cooperate to contribute to the aggressive PC in humans remains unknown. We showed that AR-positive cell lines express high levels of SCML2 with a significant increase in castration-resistant PC cells compared to its castration-sensitive cell counter, suggesting a possible role of SCML2 in PC progression. We also showed that androgens regulated the protein-protein interaction between SCML2 and YAP1, as evaluated by proximity ligation assay. In addition, the GST-pulldown assay revealed that SCML2 interacted with the WW/SH3 domain of YAP1, where AR also binds. Besides, our RNAi-aided gene silencing experiment demonstrated that YAP1 and SCML2 might be functionally antagonistic. Moreover, gene silencing and growth assays showed that SCML2 might act as a growth suppressor in castration-sensitive PC cells while acting as a growth mediator or survival factor in castration-resistant PC cells. Furthermore, our analysis of the cancer genome atlas PC data set has indicated that amplification of SCML2 is associated with reduced progression-free survival. These observations suggest that SCML2 and YAP1 interaction is biologically functional, and the degree of their interaction may play a critical role in PC progression downstream of dysregulated androgen/AR signaling.
Citation Format: Ava M. Boston, Abdulrahman M. Dwead, Marwah M. Al-Mathkour, Kezhan Khazaw, Bekir Cinar. Upregulation of the polycomb group protein SCML2 contributes to aggressive prostate 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 5303.
Abstract 5503: Targeting CDK12-mediated DNA damage response to overcome cisplatin resistance in human urothelial carcinoma
Authors: Chow Po-Ming , Dong Jun-Ren , Shi Chung-Sheng , Huang Kuo-How 
Published: June 2023

Abstract
Urothelial carcinoma (UC) accounts for more than 90% of bladder cancer. According to the 2019 Surveillance, Epidemiology and End Results (SEER) Program database, the 5-year survival rates of regional and metastatic bladder cancer are 36.3% and 4.6%, respectively. Patients who received radical cystectomy suffer from a high recurrence rate of up to 30%. As for metastatic UC, only half of the patients respond to standard platinum-based chemotherapy, with 20% of 5-year overall survival. CDK12 shows transcription regulatory effects via regulating RNA polymerase II CTD phosphorylation. In our research, we used CDK12 selective inhibitor SR-4835 to treat the UC cell lines including T24, BFTC905, RT4, and cisplatin-resistant T24/R. MTT assay result has demonstrated the cytotoxicity of SR-4835 against UC cells. Using q-RT-PCR and immunoblotting, we have confirmed the reduction of ATM mRNA and protein expression after the treatment of SR-4835. The expression of DNA damage marker gamma-H2AX was also elevated. Flow cytometry data indicated an increase in apoptotic population after treatment. According to these findings, we presume SR-4835 can lead to a DNA damage-induced apoptosis process. Furthermore, we also observed the inhibition of AKT pathway, which is related to cell survival and proliferation. Due to the effects of DNA-repair inhibition, we aim to combine SR-4835 to enhance the anti-cancer effects of cisplatin. The results of UC mice xenograft have confirmed that SR-4835 and cisplatin display a synergistic effect against UC tumor growth in vivo. We will further dissect the mechanisms of the in vitro synergistic effects between SR-4835 and cisplatin using immunoblotting, RNA-sequencing, comet assay, and various functional assays. Conclusively, our study aims to explore the role of CDK12 in urothelial carcinoma and the therapeutic effects of SR-4835, especially its potential to overcome cisplatin resistance and manage metastatic disease.
Citation Format: Po-Ming Chow, Jun-Ren Dong, Chung-Sheng Shi, Kuo-How Huang. Targeting CDK12-mediated DNA damage response to overcome cisplatin resistance in human urothelial carcinoma. [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 5503.
Abstract 6352: Combination treatment with recombinant murine IL-12 and anti-PD-1 antibody enhanced anti-tumor efficacy through the activation of cytotoxic T cell response
Authors: Yang Yeng-Jey , Tsou Pei-Yi , Chou Shiuh-Dih , Lee Meng-Na , Chen San-Chi 
Published: June 2023

Abstract
Introduction: Immune checkpoint inhibitors (ICIs) are widely used in cancer therapy. Among them, anti-PD-1 antibodies are the most used and have been approved by FDA for the treatment of many types of cancer (1). In our previous studies, combination of anti-PD-1 antibody with IL-12 demonstrated significant synergistic effect on tumor growth inhibition. The elevation of IFN-γ mRNA expression suggested the potential roles of CD8 T cells and NK cells in this process. In this study, we used two syngeneic mice tumor models to investigate the mechanisms of synergistic effect by the combination of IL-12 and anti-PD-1 antibody.
Methods: We used syngeneic mice tumor models with mice cancer cell lines CT-26 and MC-38. The mice inoculated with tumor cells and were treated until tumors grew to 100 mm3. The mice were divided into three groups to receive the treatment, including rmIL-12 alone, anti-PD1-antibody alone, and the combination of rmIL-12 and anti-PD1-antibody (BIW x 3 weeks). At the end of the study, the mice were sacrificed and tumor resection and splenectomy were performed. The tumor infiltrating lymphocyte subpopulations within the tumor microenvironment were analyzed by flow cytometry and gene expression profile by RNA Seq.
Results: The combination of rmIL-12 and anti-PD-1 antibody significantly inhibited tumor growth compared to the treatment with rmIL-12 and anti-PD-1 antibody alone. The combination group demonstrated more CD8+ T cell in the tumor microenvironment via flow cytometry. In addition, RNA Seq showed the combination group increased CD8+ T cells, NK cells, and Th1 populations. The levels of cytotoxicity related genes (IFN-γ, Granzyme B, Perforin) were also higher in combination group.
Conclusion: Combination of rmIL-12 and anti-PD-1 antibody increased immune cells infiltration in the tumor microenvironment and enhanced anti-tumor response suggesting the potential of this combination for cancer treatment.
Citation:(1). Watson, G.A. et al. (2020) “Novel strategies in immune checkpoint inhibitor drug development: How far are we from the paradigm shift?,” British Journal of Clinical Pharmacology, 86(9), pp. 1753-1768. https://doi.org/10.1111/bcp.14355.
Citation Format: Yeng-Jey Yang, Pei-Yi Tsou, Shiuh-Dih Chou, Meng-Na Lee, San-Chi Chen. Combination treatment with recombinant murine IL-12 and anti-PD-1 antibody enhanced anti-tumor efficacy through the activation of cytotoxic T cell response [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 6352.
Abstract 6452: A plasma metabolomic signature of healthy lifestyles and risk of colorectal cancer in the UK Biobank
Authors: Yuan Fangcheng , Yu Danxia , Wen Wanqing , Zheng Wei 
Published: June 2023

Abstract
Background: Lifestyle factors contribute to the etiology of colorectal cancer (CRC). We aimed to derive a metabolomic signature of adherence to healthy lifestyles and examine its association with CRC risk.
Methods: In the analysis, we included 98,898 UK Biobank participants with 168 metabolomic biomarkers measured by nuclear magnetic resonance spectroscopy from baseline plasma samples. A healthy lifestyle score (HLS) was derived from 8 lifestyle factors according to the American Cancer Society (ACS) guidelines. We applied elastic net regularized regressions to identify a metabolomic signature from 130 biomarkers. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of metabolomic signature with CRC risk after adjusting for known confounders.
Results: During a median follow-up time of 8.2 years, 818 incident primary CRC cases were identified after participants were enrolled for more than two years. We observed a strong partial correlation between the metabolomic signature and HLS (r = 0.34), as well as waist-to-hip ratio, sedentary time, red and processed meat intake, and tobacco smoking aspects of the HLS (r = 0.14-0.33). A higher HLS was characterized by a signature of increased levels of linoleic acid, total cholines, and polyunsaturated fatty acids and decreased levels of omega-6 fatty acids, phospholipids in intermediate-density lipoprotein, and phosphatidylcholines. The metabolomic signature showed a significantly inverse association with CRC risk (HR = 0.84; 95% CI = 0.80-0.89 per standard deviation increment). The significantly inverse associations were observed irrespective of sex, educational attainment, and CRC subsite. Stronger associations were seen among participants aged between 50 and 60 years at study enrollment, and those diagnosed with CRC at 60 years old or later.
Conclusion: We identified a metabolomic signature characterizing adherence to the ACS guidelines and showed that the signature was inversely associated with CRC risk.
Citation Format: Fangcheng Yuan, Danxia Yu, Wanqing Wen, Wei Zheng. A plasma metabolomic signature of healthy lifestyles and risk of colorectal cancer in the UK Biobank [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 6452.
Abstract 6464: Antidepressant use and lung cancer risk and mortality: A meta-analysis of observational studies
Authors: Lee Eunkyung , Li David , Park Yongho , Rodriguez-Fuguet Alice , Wang Xiaochuan , Zhang Wen Cai 
Published: June 2023

Abstract
Objectives: Recent preclinical studies suggested potential anticancer effects of antidepressant (AD) use in multiple cancers, but the effect on lung cancer in human studies remains unclear. This meta-analysis examined the effect of AD use on lung cancer incidence and mortality.
Methods: Web of Science, Medline, CINAHL, and PsycINFO databases were searched to identify eligible studies published by June 2022. We conducted a meta-analysis using a random effects model to estimate pooled risk ratio (RR) and 95% confidence interval (CI) for comparing those with AD use and non-use. Heterogeneity was examined using Cochran’s Q test and inconsistency I2 statistics. The methodological quality of selected studies was assessed using the Newcastle-Ottawa Scale for observational studies.
Results: The meta-analysis, including 11 publications involving 1913172 participants, showed that AD use significantly increased lung cancer risk by 11% (RR= 1.11; 95% CI= 1.01, 1.22; I2= 74.3%; n= 6); however, all-cause mortality was not affected by AD use (RR= 1.05; 95% CI= 0.68, 1.58; I2= 90.1%; n= 4) while lung cancer-specific mortality could be reduced by 32% from onse study. Subgroup analysis showed that serotonin and norepinephrine reuptake inhibitors (SNRIs) were associated with an increased lung cancer risk (RR= 1.38; 95% CI= 1.07, 1.78), but selective serotonin reuptake inhibitors (RR= 1.05; 95% CI=0.91, 1.21) and tricyclic antidepressants (RR= 1.09; 95% CI=0.95, 1.26) were not. In addition, variations in the definition of AD use could be the source of heterogeneity of observed effects. The quality of selected studies was good (n= 5) to fair (n= 6).
Conclusions: Evidence suggests that AD use was associated with an elevated risk of lung cancer but not with all-cause mortality. More research is needed to precisely estimate the effect of AD use on lung cancer-specific mortality. (Funding: University of Central Florida Center for Behavioral Health Research and Training; Registration: PROSPERO; registration number: CRD42022350719)
Citation Format: Eunkyung Lee, David Li, Yongho Park, Alice Rodriguez-Fuguet, Xiaochuan Wang, Wen Cai Zhang. Antidepressant use and lung cancer risk and mortality: A meta-analysis of observational studies [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 6464.
Abstract 6621: Simulating the distortion of clonal fractions in ctDNA due to spatially heterogenous selection
Authors: Rachman Thomas W. , Carja Oana , Schwartz Russell 
Published: June 2023

Abstract
Time-series circulating tumor DNA (ctDNA) sequencing has the potential to reveal emerging variants in the tissue in real time, and there is now substantial evidence that it can detect tumor growth and treatment-resistant mutations long before growth is visible. However, the reliability of ctDNA for profiling the primary tumor may be compromised by spatial heterogeneity in the tumor genetics, for example due to selective effects of differential drug penetration, immune infiltration, and oxygenation. We explore the influence of spatial factors on tumor genetics through a lattice-based branching process model of solid tumor evolution and ctDNA shedding with the goal of understanding where spatially variable selection pressure could lead to a significant difference between the clonal fractions in the blood and the tissue. The lattice model divides space into regions with different growth rates which result in different rates of driver mutation accumulation. The effects of regional differences in selection cause different apoptosis rates to correlate with the location of expanding driver clones. Using these rates to simulate ctDNA shedding, our model found that clones fit enough to invade a hostile region are temporarily amplified in the blood compared to their tissue frequency by as much as 300% for a limited window of time before the population expands further and the clonal fraction in the blood returns to close agreement with tissue. The results suggest evolutionary contexts in which liquid biopsy might provide highly biased estimates of tumor state, but also shows how this effect might be exploited to provide more sensitive detection of clonal expansion with implications for blood-based detection of recurrence and metastasis.
Citation Format: Thomas W. Rachman, Oana Carja, Russell Schwartz. Simulating the distortion of clonal fractions in ctDNA due to spatially heterogenous selection [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 6621.
Immuno-PET Imaging of CD69 Visualizes T-Cell Activation and Predicts Survival Following Immunotherapy in Murine Glioblastoma
Authors: Nisnboym Michal , Vincze Sarah R. , Xiong Zujian , Sneiderman Chaim T. , Raphael Rebecca A. , Li Bo , Jaswal Ambika P. , Sever ReidAnn E. , Day Kathryn E. , LaToche Joseph D. , Foley Lesley M. , Karimi Hanieh , Hitchens T. Kevin , Agnihotri Sameer , Hu Baoli , Rajasundaram Dhivyaa , Anderson Carolyn J. , Blumenthal Deborah T. , Pearce Thomas M. , Uttam Shikhar , Nedrow Jessie R. , Panigrahy Ashok , Pollack Ian F. , Lieberman Frank S. , Drappatz Jan , Raphael Itay , Edwards Wilson B. , Kohanbash Gary 
Published: June 2023

Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults. Immunotherapy may be promising for the treatment of some patients with GBM; however, there is a need for noninvasive neuroimaging techniques to predict immunotherapeutic responses. The effectiveness of most immunotherapeutic strategies requires T-cell activation. Therefore, we aimed to evaluate an early marker of T-cell activation, CD69, for its use as an imaging biomarker of response to immunotherapy for GBM. Herein, we performed CD69 immunostaining on human and mouse T cells following in vitro activation and post immune checkpoint inhibitors (ICI) in an orthotopic syngeneic mouse glioma model. CD69 expression on tumor-infiltrating leukocytes was assessed using single-cell RNA sequencing (scRNA-seq) data from patients with recurrent GBM receiving ICI. Radiolabeled CD69 Ab PET/CT imaging (CD69 immuno-PET) was performed on GBM-bearing mice longitudinally to quantify CD69 and its association with survival following immunotherapy. We show CD69 expression is upregulated upon T-cell activation and on tumor-infiltrating lymphocytes (TIL) in response to immunotherapy. Similarly, scRNA-seq data demonstrated elevated CD69 on TILs from patients with ICI-treated recurrent GBM as compared with TILs from control cohorts. CD69 immuno-PET studies showed a significantly higher tracer uptake in the tumors of ICI-treated mice compared with controls. Importantly, we observed a positive correlation between survival and CD69 immuno-PET signals in immunotherapy-treated animals and established a trajectory of T-cell activation by virtue of CD69-immuno-PET measurements. Our study supports the potential use of CD69 immuno-PET as an immunotherapy response assessment imaging tool for patients with GBM.

Significance:
Immunotherapy may hold promise for the treatment of some patients with GBM. There is a need to assess therapy responsiveness to allow the continuation of effective treatment in responders and to avoid ineffective treatment with potential adverse effects in the nonresponders. We demonstrate that noninvasive PET/CT imaging of CD69 may allow early detection of immunotherapy responsiveness in patients with GBM.
Karakteristik Klinis Pasien Laserasi Kelopak Mata Akibat Trauma di Pusat Mata Nasional Rumah Sakit Mata Cicendo
Authors: Riza Afdal , Kartiwa Raden Angga 
Published: June 2023

Introduction : Trauma of eyelids due to sharp object, blunt object, road traffic accidents etc. are the major causes resulting in injuries to eyelids. A good identification and prompt treatment can improve the outcome of palpebral laceration.
Purpose : To describe clinical characteristics of eyelids laceration due to trauma without involvement of lacrimal system and other orbital
Methods : A retrospective descriptive cross sectional study was conducted. Data is taken from medical records of patients diagnosed as eyelid laceration from January 2016 to November 2020. Age, gender, laterality, first reference, place, onset, cause, site of trauma, depth, outcome, complication and System for Peri-Ocular Trauma (SPOT) classification was reviewed.
Results : This study comprised of total 157 patients. Most of them were males 119 (75.80%) with median of age 24. The main mechanism of injury was direct trauma 88 (56.05%). The location where the injury occured was road side accidents 81 (51.59%). Superior eyelid was the most affected 96 (61.15%). Subcutaneus tissue as wound base 68 (43.31%) and affected to margin of eyelid 36 (22.92%). Hypertropic scar was the most complication found in 40 (25.47%). The most common SPOT type injury were Type IA.
Conclusion : Eyelids laceration due to trauma is common in male productive age, mainly affecting superior palpebra, mostly because of road side accidents. Hypertropic scar was most complication beside traumatic ptosis, lagophthalmos and lid margin notching. The SPOT classification can simplify a recording of palpebral injuries.