tbuckley/cabot-search huggingface dataset:
Abstract 817: Establishing a niche to improve Africa’s contribution to cancer research
Authors: Usman A. Malami, Sani A. Malami, Uchechukwu E. Nwokwu, Usman W. Mohammed, Faruk Mohammed
Journal: Cancer Research (2024)

Abstract Africa has been a key source of scientific discoveries to the global community, especially in areas of scientific experiments and implementation. However, Africans are underrepresented in their contribution to global science and within the African countries, access to adequate funding and infrastructure to do high quality science is limited. These inequities contribute to the 10/90 gap in which only an estimated 10% of global health research funding is used to address health problems in Africa. Thus, it is not surprising that today, Africa contributes just about 2 percent of world research output, 1.3 percent of research spending, and 0.1 percent of all patents. To bridge the aforementioned gaps, mitigate the effect of brain drain and structural constraints and improve support for the next generation scientists, the Nigerian Government recently established the National Institute for Cancer Research and Treatment (NICRAT). It is worthy to note that cancer incidence and mortality rates in Africa are increasing 1.1 million new cases, with 711,000 deaths reported in 2020. This indicate a mortality-to-incidence ratio (MIR) of 0.64. These cancer challenges in Africa necessitates a concerted approach towards effective cancer control and management. Here, we show in detail how the NICRAT support improving science while integrating with Nigerian national development plans and strategies. We also show how the NICRAT is establishing a mechanism for domestic funding, while fostering national and international collaborations for African scientists and encouraging women into careers in cancer research. Currently, the NICRAT’s key task also includes centralizing cancer control efforts, mobilizing funding from different sources for cancer research, and coordinating cancer treatment activities across Nigeria. In addition, the institute facilitates collaboration between researchers, healthcare providers, and patients, and provides guidance for cancer policy formulation and implementation. The establishment of NICRAT by Nigeria’s government as well as similar centers elsewhere in Africa may improve active participation of African scientists in scientific practice, discourse, and decision making and spotlight their intellectual contributions towards solving science-associated global problems. Citation Format: Usman A. Malami, Sani A. Malami, Uchechukwu E. Nwokwu, Usman W. Mohammed, Faruk Mohammed. Establishing a niche to improve Africa’s contribution to cancer research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 817.
Abstract 1057: A blood-based multi-omics test for multicancer early detection: Combined retrospective and prospective studies
Authors: Mao Mao, Shiyong Li, Qingqi Ren, Yi Luan, Weijie Liang, Shuaipeng Geng, Dao-Ling Huang, Dandan Zhu, Yinyin Chang, Wei Wu, Yingying Zhang, Linfeng Zhang, Yan Wang, Yumin Feng, Bing Wei, Jie Ma, Chaohui Duan, Guanghui Long
Journal: Cancer Research (2024)

Abstract Background: Recent studies have demonstrated that blood-based multi-cancer early detection (MCED) approaches may hold promise for identifying asymptomatic cancer patients from general population. However, most studies only exploit a single aspect of cancer hallmarks, which is challenging for the biological reasons as cancer is a heterogenous disease with a wide spectrum of pathological and clinical behaviors. Here we report a multi-omics MCED assay named SeekInCare, a CE-IVD Mark blood test, which incorporates genomic hallmarks: copy number aberrations, fragment size, end motifs and oncogenic viruses via shallow whole genome sequencing from cfDNA, and seven plasma protein tumor markers in 8 ml blood. Methods: SeekInCare was developed using several retrospective cohorts and the method has been described in a publication (DOI: 10.1016/j.jmoldx.2021.06.003) IF: 4.1 Q2. Results: We present the validation in a retrospective cohort consisting of 584 non-cancer individuals and 617 cancer patients covering 27 cancer types. SeekInCare achieved 65.5% sensitivity at 97.9% specificity, resulting in an AUC of 0.936. The sensitivities were 46.9%, 60.0%, 68.9%, 81.8% in stage I, II, III, IV patients. The sensitivities of 10 common cancer types are as the following: breast (46.2%), stomach (46.4%), colorectum (56.5%), gallbladder (60.0%), lung (62.8%), pancreas (64.7%), lymphoma (68.5%), esophagus (70.0%), liver (77.5%), and leukemia (86.7%). These cancer types account for 73.5% of cancer incidence and 81.8% of cancer-related mortality in China. We prospectively evaluated SeekInCare in a real-world cohort consisting of 1203 individuals who received the test as a laboratory developed test (median follow-up time: 753 days) in which it achieved 60.0% sensitivity, 96.1% specificity, 11.5% PPV and 99.7% NPV. Conclusion: The performances of SeekInCare in both retrospective and prospective studies demonstrate that SeekInCare is an effective blood-based MCED test with similar performance as Grail’s Galleri test, which paves the way for clinical utility as a cancer screening test in average-risk populations. Citation Format: Mao Mao, Shiyong Li, Qingqi Ren, Yi Luan, Weijie Liang, Shuaipeng Geng, Dao-Ling Huang, Dandan Zhu, Yinyin Chang, Wei Wu, Yingying Zhang, Linfeng Zhang, Yan Wang, Yumin Feng, Bing Wei, Jie Ma, Chaohui Duan, Guanghui Long. A blood-based multi-omics test for multicancer early detection: Combined retrospective and prospective studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1057.
Abstract 840: Serum concentrations of per- and polyfluorinated substances and risk of non-Hodgkin lymphoma
Authors: Jongeun Rhee, Jani Koponen, Joshua N. Sampson, Alexander P. Keil, Mary H. Ward, Jonathan N. Hofmann, Wen-Yi Huang, Debra T. Silverman, Panu Rantakokko, Mark P. Purdue
Journal: Cancer Research (2024)

Abstract Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants, some immunotoxic, that are detectable in the serum of most U.S. adults. Some studies of highly-exposed individuals have suggested positive associations between PFAS and non-Hodgkin lymphoma (NHL); however, it is unknown whether associations exist at lower exposure levels that are more common in the general population. To address this knowledge gap, we conducted a nested case-control study investigating serum PFAS concentrations and NHL within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We measured pre-diagnostic serum concentrations (collected between 1993-2001) of five PFAS among 706 cases and 706 controls individually matched on the basis of age at baseline, sex, self-reported race and ethnicity, study center, calendar year of blood collection, and number of prior serum thaws. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for PFAS concentrations in relation to NHL, both overall and for selected histologic subtypes [diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), lymphoplasmacytic lymphoma (LPL), and marginal zone lymphoma (MZL)] using conditional logistic regression. We found no evidence of a positive association with NHL for any of the five PFAS in analyses adjusting for all measured PFAS. In analyses of histologic subtypes, we observed a positive association between perfluorohexane sulfonate (PFHxS) and DLBCL (OR per doubling in concentration=1.27, 95% CI=1.07, 1.50) which remained for cases diagnosed ≥10 years after blood collection (OR=1.34, 95% CI=1.09, 1.64). We also observed inverse associations with PFNA for all subtypes (DLBCL, OR=0.84, 95% CI=0.72, 0.98; FL, OR=0.86, 95% CI=0.69, 1.08; LPL/MZL, OR=0.86, 95% CI=0.66, 1.12), although these associations were null among participants with blood drawn prior to 1997 (DLBCL: OR&amp;lt;1997=0.95, OR≥1997=0.67, Pinteraction=0.001; FL: OR&amp;lt;1997=1.01, OR≥1997=0.77, Pinteraction =0.08; LPL/MZL: OR&amp;lt;1997=1.26, OR≥1997=0.88, Pinteraction =0.03). In conclusion, our findings from a cohort study with PFAS serum concentrations comparable to that of the general population do not support an association with increased risk of NHL overall. The suggestive evidence of a positive association between PFHxS and DLBCL warrants further investigation. Citation Format: Jongeun Rhee, Jani Koponen, Joshua N. Sampson, Alexander P. Keil, Mary H. Ward, Jonathan N. Hofmann, Wen-Yi Huang, Debra T. Silverman, Panu Rantakokko, Mark P. Purdue. Serum concentrations of per- and polyfluorinated substances and risk of non-Hodgkin lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 840.
Abstract 831: Occupational-related exposure to benzene and risk of breast cancer: Systematic review and meta-analysis
Authors: Vincent DeStefano, Darshi Shah, Veer Shah, Monireh Sadat Seyyedsalehi, Mattia Bonetti, Paolo Boffetta
Journal: Cancer Research (2024)

Abstract Purpose: Benzene is a recognized carcinogen as evidenced by its association with leukemia; however, its association with breast cancer is not well established. Hence, a meta-analysis of cohort and case-control studies was performed to determine the association between benzene exposure and the risk of breast cancer. Methods: A systematic literature review was conducted and 7221 publications were identified, from which 21 cohort and case-control studies were retained, and evaluated using meta-analyses (fixed effects model). PECOS criteria and STROBE guidelines were followed, and the study protocol was registered in the PROSPERO database (Registration No. 379720). Study quality was assessed using a modified Newcastle-Ottawa scale (NOS). Results: The summary relative risk (RR) for ever-benzene exposure was 1.08 (95% CI=1.02-1.14, I2=43.6%, n=21); corresponding RR for cancer incidence and mortality were 1.08 (95% CI=1.02-1.14, I2=58.6%, n=15) and 1.09 (95% CI=0.87-1.38, I2&amp;lt;0.001%, n=9), respectively. These main results were confirmed in sub-analyses by geographical region, industry type, publication year, and levels of exposure. No heterogeneity was detected amongst geographical regions (p-het=0.19), industry of employment (p-het=0.05) or and duration of the dose (low, high; p-het=0.64). Studies published before 2003 reported a summary RR of 1.24 (95% CI=1.13-1.37), compared to a summary RR of 1.02 (95% CI=0.95-1.08) for studies published later (p-het=0.001). Heterogeneity was observed when evaluating studies at and above, or below the NOS mean (p-het=0.00), with a summary RR of 1.25 (95% CI=1.13-1.28, I2&amp;lt;0.001%, n=9) for studies below the median NOS score. Sub-group analysis of study design demonstrated heterogeneous results (p-het=0.001) with a summary RR of 1.19 (95% CI=1.10-1.29, I2&amp;lt;0.001%, n=16) for cohort studies while compared to the findings of case-control studies. Publication bias was detected (p=0.04). Conclusions: Our meta-analysis identified an association between occupational benzene exposure and risk of breast cancer. The association was restricted to studies published before 2003, below the median NOS score, and cohort studies. Residual confounding variables cannot be excluded, which, together with potential bias, prevents conclusions of causality. Citation Format: Vincent DeStefano, Darshi Shah, Veer Shah, Monireh Sadat Seyyedsalehi, Mattia Bonetti, Paolo Boffetta. Occupational-related exposure to benzene and risk of breast cancer: Systematic review and meta-analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 831.
Abstract 84: StarBright Dyes: Fluorophores with superior performance for multiplexing in flow cytometry and Western blotting
Authors: Sharon Sanderson, Oliver Rosenwasser, Michael Blundell
Journal: Cancer Research (2024)

Abstract New StarBrightTM Dyes from Bio-Rad are bright fluorescent fluorophores ideal for many antibody-based applications, for example, western blotting and flow cytometry. Traditional fluorophores can be dim, have high cross laser excitation, or don’t work with all protocols, leading to poor data. StarBright Dyes have been designed to address these pain points. Western blotting secondary antibodies are available conjugated to StarBright Blue 700 and StarBright Blue 520 Dyes. Their brightness, the short exposure time required, and low background make them ideal for detection of a single target, or as shown here for multiplex detection of several proteins in combination with other common fluorophores. For flow cytometry, we have a full range of 32 StarBright Dyes excited by the most common laser lines: 355 nm, 405 nm, 488 nm, 561 nm, or 640 nm. They are available conjugated to highly cited clones against common immunophenotyping targets. Data shown here on the ZE5 Cell Analyser demonstrates how the features of StarBright Dyes can improve multiplexing immunophenotyping data. They have narrow excitation and emission spectral profiles, which reduce compensation and spread. This, combined with their exceptional brightness, enables high resolution of cell populations. They work in all buffers and fixatives, so including them in existing panels does not require a change in protocol. They can also be premixed in a master mix for over six months with no loss in performance. Premixes are ideal when using the same panel over an extended period, such as in clinical and longitudinal studies, to ensure reproducible results, also saving time and money. StarBright Dyes are ideal for multiplexing assays in both western blotting and flow cytometry. BIO-RAD and STARBRIGHT are trademarks of Bio-Rad Laboratories, Inc. in certain jurisdictions. All trademarks used herein are the property of their respective owner. Citation Format: Sharon Sanderson, Oliver Rosenwasser, Michael Blundell. StarBright Dyes: Fluorophores with superior performance for multiplexing in flow cytometry and Western blotting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 84.
Abstract 1695: Genomic clustering tendency of transcription factors reflects phase-separated transcriptional condensates at cancer super-enhancers
Authors: Zhenjia Wang, Shengyuan Wang, Chongzhi Zang
Journal: Cancer Research (2024)

Abstract Many transcription factors (TFs) have been shown to bind to super-enhancers, forming transcriptional condensates to activate transcription in various cellular systems including cancer. However, the genomic and epigenomic determinants of phase-separated transcriptional condensate formation remain poorly understood. Questions regarding which TFs tend to associate with transcriptional condensates and what factors influence their association are largely unanswered. Here we systematically analyzed 528 DNA sequence motifs across the human genome and 6,650 TF binding profiles across different cell types to identify the molecular features contributing to the formation of transcriptional condensates. We found that the genomic distributions of sequence motifs for different TFs exhibit distinct clustering tendencies. Notably, TF motifs with a high genomic clustering tendency are significantly associated with super-enhancers. TF binding profiles showing a high genomic clustering tendency are further enriched at cell-type-specific super-enhancers. TFs with a high binding clustering tendency also possess high liquid-liquid phase separation abilities. Compared to non-clustered TF binding, densely clustered TF binding sites are more enriched at cell-type-specific super-enhancers with higher chromatin accessibility, elevated chromatin interaction, and stronger association with cancer outcomes. Our results indicate that the clustered genomic binding patterns and the phase separation properties of TFs collectively contribute to the formation of transcriptional condensates at cancer super-enhancers. Citation Format: Zhenjia Wang, Shengyuan Wang, Chongzhi Zang. Genomic clustering tendency of transcription factors reflects phase-separated transcriptional condensates at cancer super-enhancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1695.
Abstract 1689: CRISPR functional genetic screening for immune enhancers of inhibitor receptors in human primary CD8 T cells
Authors: Ping Wang, Josephine R. Giles, Hua Huang, Junwei Shi, E.John Wherry
Journal: Cancer Research (2024)

Abstract The restrained efficacy of T cell therapies in cancer treatment is associated with T cell exhaustion (TEX), an impaired effector function state that is marked by distinct epigenetic landscape. These unique epigenetic features promoted the progression of TEX, hindered reinvigoration of TEX state and controlled the abnormal expression of inhibitor receptors (IRs), which could serve as target sites in cancer treatment. Thus, deciphering the regulatory elements in primary human T cells will deeply reveal the mechanism controlling TEX and provide novel therapeutic strategies to promote clinical response. However, how enhancers can be effectively applied in anti-cancer treatment is still poorly understood because high throughput identifying the functional enhancers of inhibitor receptors at scale is technically limited in human T cells. Here, we first developed a pooled screening platform that employs a compact CRISPRi system and enabled efficient one-step delivery of pooled screening libraries to primary human T cells. Leveraging this platform, we screened large genomic regions (~300kb) at saturation around key TEX genes, two IRs—PDCD1, HAVCR2 and one transcription factor (TF)—TBX21 to interrogate functional enhancers in human primary CD8 T cells. We identified two enhancers for PDCD1, three enhancers for HAVCR2 and three enhancers for TBX21, all of which are located over 12kb away from each gene’s transcription start sites. Then, to parse the essential sequences that fulfill enhancer function, we employed Cas9-based in-situ saturation mutagenesis screening to the identified enhancers of PDCD1 and HAVCR2. We found disrupt essential sequences impaired the entire enhancer function, quantitatively phenocopied the effect of targeting the entire enhancer with CRISPRi. Transcription factor motifs analyses of these sequences revealed potential regulation of ZFX for controlling PDCD1 expression and STAT for HAVCR2 expression. Finally, we explored the functional consequences of applying enhancers to anti-cancer treatment. Indeed, targeting the identified enhancers of PDCD1 and HAVCR2 in CAR T cells lead to enhanced cancer cell killing efficiency in vitro. Together, our study provides a platform and paradigm to interrogate functional enhancers in human T cells, illuminated the great potential of manipulating enhancers in T cell therapies. Citation Format: Ping Wang, Josephine R. Giles, Hua Huang, Junwei Shi, E.John Wherry. CRISPR functional genetic screening for immune enhancers of inhibitor receptors in human primary CD8 T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1689.
Abstract 1161: Deep spatial proteomics: A new approach for obtaining insight into the glioblastoma microenvironment
Authors: Kartikey Saxena, Rune Daucke, Vilde Pedersen, Pia Helene Klausen, Erwin Schoof, Bjarne Winther Kristensen
Journal: Cancer Research (2024)

Abstract Glioblastoma is the most frequent and malignant brain tumor, with a median survival of approximately 14 months. The tumor microenvironment is composed of different cell types and is known to support the glioblastoma cells and contribute to poor patient prognosis. Since accumulating studies report discordance between mRNA and protein abundances both on population and single-cell levels, and since proteins are the effector molecules of the cells and the actual target molecules of most drugs, our aim is to dissect the tumor microenvironment by spatial LC-MS based proteomics. Glioblastoma formalin-fixed paraffin-embedded (FFPE) tissue was sectioned and placed on membrane glass slides suitable for laser capture microdissection (LCM), followed by precise isolation of single cells from the heterogeneous tumor microenvironment. We used the Zeiss Palm MicroBeam laser microdissection instrument, combined with an Orbitrap Eclipse Tribrid Mass Spectrometer running our in-house sensitivity tailored Data Independent Acquisition method (WISH-DIA) to analyze and quantify the proteomes. We obtained up to 3000 proteins out of only 100 cells and were able to demonstrate the feasibility of collecting and analyzing various cell types at the single-cell level. The proteins identified belonged to many different classes/families of proteins and were able to distinguish the different cell types. In conclusion, this on-going study demonstrates our ability to isolate single cells from the highly heterogeneous tumor microenvironment of glioblastoma with ultra-high sensitivity, thereby allowing the characterization of the proteome of the glioblastoma microenvironment followed by identification of potential therapeutic and/or diagnostic targets. Citation Format: Kartikey Saxena, Rune Daucke, Vilde Pedersen, Pia Helene Klausen, Erwin Schoof, Bjarne Winther Kristensen. Deep spatial proteomics: A new approach for obtaining insight into the glioblastoma microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1161.