tbuckley/cabot-search huggingface dataset:
Abstract 5518: Tumor infiltrating B cells and tertiary lymphoid structures are associated with tumor response to PD-L1 blockade in NSCLC
Authors: Namrata S. Patil
Journal: Cancer Research (2020)

Abstract Inhibitors of the programmed cell death-1/programmed cell death ligand1 (PD-1/PD-L1) signaling axis have demonstrated sustained efficacy in NSCLC, however there are gaps in our understanding of the mechanisms of how PD-1/ PD-L1 blockade improve patient outcomes, especially as they relate to long term survival. Differential gene expression analysis in tumors from NSCLC patients who derived &amp;gt;12 months OS benefit on atezolizumab monotherapy showed high expression of B cell transcripts in the randomized phase II POPLAR and phase III OAK studies (&amp;gt; median, HR: 0.61, 95% CI 0.47-0.78, and HR=0.54, CI 0.42-0.7, p&amp;lt;0.001 respectively). Immunofluorescence imaging confirmed the presence of CD79+ B cells in these tumors. High expression of CD79A was associated with the presence of tertiary lymphoid structures (TLS) that in turn were associated with atezolizumab survival benefit. B cell receptor sequencing of patient biopsies pre and post atezolizumab treatment suggest clonal expansion of tumor infiltrating plasma cells in patients responsive to atezolizumab. Collectively, these results suggest that NSCLC tumor patients enriched for CD79A+ B cells and IgG+ plasma cells derive greater overall survival benefit from atezolizumab and emphasize the potential of these genes as actionable biomarkers in NSCLC. Citation Format: Namrata S. Patil. Tumor infiltrating B cells and tertiary lymphoid structures are associated with tumor response to PD-L1 blockade in NSCLC [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5518.
Abstract LB-131: Profile of glucose metabolism in bladder cancer patients and the inhibitory effect of sulforaphane on bladder cancer glycolysis by regulating microRNA expression
Authors: Yujuan Shan, Lei Huang
Journal: Cancer Research (2020)

Abstract Object: We are committed to studying the characteristics of energy metabolism in bladder cancer patients, and to investigate the regulation of sulforaphane (SFN) on glucose metabolism in bladder cancer cells. Methods: Real-time PCR was used to detect the gene level of glycolysis key rate-limiting enzymes in bladder tumors, and para-carcinoma tissues as control. We also measured the activity of glycolysis enzymes in patient serum and bladder cancer cells by ELISA. Then we measured microRNAs level by microarray after SFN treatment. GO function and KEGG pathway enrichment analyses were used to gain insights into the biological roles and the potential pathway of different expression microRNAs. Results: Gene expression results showed that the level of PFK-1 was highly increased in tumor tissues. However, there is no significant differential in serum activity of PFK-1 as compared with control group. SFN obviously elevated microRNA expression related to glucose metabolism, including miR-200c, miR-34a and let-7. The activity of HK2, which can be blocked by miR-34a, was strongly inhibited in bladder cancer cells by incubating with 20 μmol/L SFN for 24 h. Furthermore, functional annotation analysis results suggest that miR-200c target genes were mainly enriched in 82 GO terms and 17 pathways (P &amp;lt; 0.05), including mTOR signaling (p = 0.0154) and AMPK signaling (p = 0.0158), which also involved in the regulation of energy metabolism. Conclusion: Aberrant gene expression of PFK-1 is one of most important causes of glucose metabolic disorders in bladder cancer patients. SFN can significantly down-regulate glucose metabolism in bladder cancer cells by regulating the expression of glycolysis related-microRNAs. Citation Format: Yujuan Shan, Lei Huang. Profile of glucose metabolism in bladder cancer patients and the inhibitory effect of sulforaphane on bladder cancer glycolysis by regulating microRNA expression [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-131.
Abstract 5727: Metabolic status and adaptability of breast cancer stem cells
Authors: Johanna M. Buschhaus, Ayse J. Muniz, Ming Luo, Joseph P. Burnett, Nathan A. Truchan, Michael D. Brooks, Brock A. Humphries, Kathy E. Luker, Joerg Lahann, Duxin Sun, Max S. Wicha, Gary D. Luker
Journal: Cancer Research (2020)

Abstract Breast cancer stem cells (BCSCs) represent the subpopulation of malignant cells that cause tumor initiation, metastasis, and recurrence. BCSCs resist therapy with radiation and standard drugs, emphasizing the need to identify new vulnerabilities as therapeutic targets. Here, we investigated the metabolism of BCSCs at single-cell resolution using molecular imaging and scRNA sequencing techniques. We imaged retention of the fluorescent dye PKH26 or expression of a CRISPR/Cas9-engineered ALDH1A3-mCherry promoter-reporter to identify BCSCs and metabolic state of cells by two-photon microscopy with fluorescence lifetime imaging (FLIM) of endogenous NADH. We previously reported that sorted BCSCs exhibited enhanced metabolic plasticity relative to bulk tumor cells in 2D culture and rapidly metabolically adapted to the glycolysis inhibitor 2-deoxyglucose (2DG). Since cells rewire signaling and metabolism in 3D environments, we utilized two-photon microscopy to quantify metabolism in secondary mammospheres and living animals. In both intact spheres and orthotopic tumor xenografts, BCSCs marked by either fluorescent reporter utilized glycolysis to a greater extent than bulk cancer cells. We validated our findings by correlating cellular entropy as a marker for cancer stem cells with metabolic pathway preferences on a single-cell basis. When treated with 2DG, mammospheres showed increased OXPHOS and a significant decrease in the percentage of ALDH1A3-mCherry+ cells. These data 1) highlight capabilities of FLIM to measure the metabolism of single cancer cells in physiologic environments; 2) correlate molecular phenotypes with real-time molecular imaging profiles of metabolism and stem-ness; and 3) reveal that BCSCs rely on glycolysis, suggesting a potential target for metabolic therapy. Citation Format: Johanna M. Buschhaus, Ayse J. Muniz, Ming Luo, Joseph P. Burnett, Nathan A. Truchan, Michael D. Brooks, Brock A. Humphries, Kathy E. Luker, Joerg Lahann, Duxin Sun, Max S. Wicha, Gary D. Luker. Metabolic status and adaptability of breast cancer stem cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5727.
Abstract 3964: Integrin α2-collagen I axis promotes proliferative and migratory phenotypes in intrahepatic cholangiocarcinoma
Authors: Chotirat Rattanasinchai, Panida Navasumrit, Mathuros Ruchirawat
Journal: Cancer Research (2020)

Abstract Cholangiocarcinoma (CCA) is a deadly cancer of the bile duct and is considered an incurable disease with no efficacious treatment option. CCA arises as a consequence of chronic inflammation and tissue damage to the biliary epithelium. Thus, one of the crucial characteristics of CCA is its tumor microenvironment high in stromal extracellular matrices (ECMs), especially collagen I. Herein, the direct impact of collagen I on intrahepatic CCA (iCCA) cell lines were investigated. Our data demonstrate that iCCA cells mainly interact with collagen I, while cholangiocyte cells preferentially binds to fibronectin in cell adhesion assays. Correspondingly, iCCA cell lines exhibit over 20 fold-upregulation of ITGA2 gene, which encodes collagen-binding integrin α2, when compared with non-cancerous cholangiocyte cells. Furthermore, the result from the GEO dataset of 92 iCCA patients demonstrate that ITGA2 gene expression in iCCA tumors is 13 folds greater than their adjacent normal tissues and is positively correlated with expressions of two isoforms of collagen I gene, COL1A1 and COL1A2. Collagen I is also sufficient to drive proliferation of iCCA cells in a serum-restricted condition and this effect is mediated by integrin α2 as proven by ITGA2 silencing or α2β1-selective inhibitor treatment. In contrast to round-shaped, multicellular colonies of iCCA cells in clonogenic assays, iCCA colonies exhibit migratory phenotypes in the presence of collagen I. Likewise, this phenotype can be inhibited by α2β1-selective inhibitor treatment. Taken together, these data suggest that stromal collagen I could be one of the tumor microenvironmental factors directly facilitating iCCA progression. Thus, targeting the integrin α2-collagen I axis could be a promising therapeutic strategy for combating this cancer. Citation Format: Chotirat Rattanasinchai, Panida Navasumrit, Mathuros Ruchirawat. Integrin α2-collagen I axis promotes proliferative and migratory phenotypes in intrahepatic cholangiocarcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3964.
Interference between rhinovirus and influenza A virus: a clinical data analysis and experimental infection study
Authors: Anchi Wu, Valia T Mihaylova, Marie L Landry, Ellen F Foxman
Journal: The Lancet Microbe (2020)

During the 2009 pandemic of an emerging influenza A virus (IAV; H1N1pdm09), data from several European countries indicated that the spread of the virus might have been interrupted by the annual autumn rhinovirus epidemic. We aimed to investigate viral interference between rhinovirus and IAV with use of clinical data and an experimental model.
Wearable Devices to Monitor and Reduce the Risk of Cardiovascular Disease: Evidence and Opportunities
Authors: Atsushi Mizuno, Sujatha Changolkar, Mitesh S. Patel
Journal: Annual Review of Medicine (2020)

There is a growing interest in using wearable devices to improve cardiovascular risk factors and care. This review evaluates how wearable devices are used for cardiovascular disease monitoring and risk reduction. Wearables have been evaluated for detecting arrhythmias (e.g., atrial fibrillation) as well as monitoring physical activity, sleep, and blood pressure. Thus far, most interventions for risk reduction have focused on increasing physical activity. Interventions have been more successful if the use of wearable devices is combined with an engagement strategy such as incorporating principles from behavioral economics to integrate social or financial incentives. As the technology continues to evolve, wearable devices could be an important part of remote-monitoring interventions but are more likely to be effective at improving cardiovascular care if integrated into programs that use an effective behavior change strategy.
Abstract 3871: Infiltration of CD56dim NK cells regulated by MLH1 into tumor tissue of FAP patients predict better prognosis
Authors: Jun Yang, Hushan Zhang, Wei Qing Liu, Wenliang Li, Shumin Ma, Lei Liang, Zhiyong Kou, Depei Huang, Xudong Shen, Jian Dong
Journal: Cancer Research (2020)

Abstract Backgroud Familial adenomatous polyposis (FAP) is an autosomal dominant-inherited colorectal cancer (CRC) with poor prognosis, and is also considered as model to study the change of CRC from pre-tumor to tumor progression. To better predict and guide clinical applications of immune check point inhibitors(ICI), researchers proposed the classification system of human cancer, termed tumor immunity in the microenvironment (TIME), that four different TIME groups have been identified according to the presence of TILs and B7-H1(PD-L1) expression in tumor biopsies. Therefore, we followed and performed this theory into our research about TIME of FAP, to explore the potential of immunotherapy for FAP, and explore the cancerous mechanism from immune microenvironment. Methods We collected tissue samples of 40 FAP patients from May 2009 to December 2018, followed by detection of PD-L1 by using Dako PD-L1 IHC 22C3 pharmDx, MLH1, PMS2, MSH2, MSH6 were detected by IHC, and CD8+ T cells, tumor associated macrophages (TAM) and NK cells infiltration in the tumor biopsies by multiple fluorescence immunohistochemistry (mICH). Follow-up data of these 40 patients were analyzed. Results CD8+T cells, M1 and M2 TAM, CD56bright NK and CD56dim NK cells were found both in intratumoral region and tumor rim of FAP patients(n=40), no differences have been found between M1and M2 TAM, however, CD56dim NK increased more than CD56bright NK both in intratumoral region and tumor rim(p&amp;lt;0.01). Surprisingly, no positive expression of PD-L1 was detected in the tumor tissue of these FAP patients (Tumor Proportion Score, TPS&amp;lt;1%). Further results shown CD56dim NK mainly increased in the tissue of FAP patients(n=7) with loss of MLH1, and consistent with this, these patients shown better prognosis than patients with wild type MLH1, that is, have longer progression free survival (p&amp;lt;0.005). Conclusions For the TIME characteristics of FAP patient, Immunotherapy targeted PD-1/PD-L1 may not applicable for FAP, however, MLH1, the member of mismatch repair protein, was associated with infiltration of NK cells, especially CD56dim NK cells in the tumor, and also associated with prognosis of FAP patients. Therefore, it can be exploited as potential target of immunotherapy for FAP or even CRC. Citation Format: Jun Yang, Hushan Zhang, Wei Qing Liu, Wenliang Li, Shumin Ma, Lei Liang, Zhiyong Kou, Depei Huang, Xudong Shen, Jian Dong. Infiltration of CD56dim NK cells regulated by MLH1 into tumor tissue of FAP patients predict better prognosis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3871.
Abstract 6177: Triple negative breast cancer patients treated with radiation therapy: Improvement in survival and local control with adjuvant chemotherapy compared to neoadjuvant chemotherapy
Authors: Mary R. Nittala, Eswar K. Mundra, Satya Packianathan, Divyang Mehta, Maria L. Smith, William C. Woods, Shawn McKinney, Barbara S. Craft, Srinivasan Vijayakumar
Journal: Cancer Research (2020)

Abstract Purpose: The objective of this study is to evaluate local control and survival rates of node negative triple negative breast cancer patients (TNBCs) treated with radiotherapy (RT) in our institution. Methods: This is a retrospective analysis of 67 TNBCs (2007 - 2017) at an academic state institution who underwent lumpectomy and /or mastectomy (surgery) followed by adjuvant irradiation to median total dose of 50 Gy (range 40.5-50.40 Gy). Chemotherapy was administered in a neoadjuvant (31) or adjuvant setting (36). For all 67 TNBCs, local control (LC), overall survival (OS) and disease free survival (DFS) were estimated using the Kaplan-Meier method. The significance of survival variables were analyzed using the Cox univariate and multivariate proportional hazards model. A p-value of less than 0.05 was considered statistically significant. The SPSS 24.0 software was used for data analysis. Results: The baseline characteristics of all 67 TNBCs were measured with median follow up of 58 months (range 10-142 months). Patients were stratified into two groups (neoadjuvant chemotherapy-RT (31) vs. adjuvant chemotherapy-RT (36)). The median rates for LC, DFS and OS were 27 % vs. 68 % (p= 0.001), 27.2% vs. 63.2 % (p= 0.034), and 63.4% vs. 92.5% (0.001) respectively. On Cox multivariate analysis, patients who received adjuvant chemotherapy were associated with statistically improved significant LC (p= 0.002) and OS (p=0.005). The variables included were: ethnicity (p=0.251), age (p=0.984), BMI (p=0.032), lump boost (p=0.300), TNM (p=0.162) and tumor grade (p=0.336). Conclusion: Among TNBC patients undergoing RT, adjuvant chemotherapy appears to be better than neoadjuvant chemotherapy in determining the clinical outcomes. Citation Format: Mary R. Nittala, Eswar K. Mundra, Satya Packianathan, Divyang Mehta, Maria L. Smith, William C. Woods, Shawn McKinney, Barbara S. Craft, Srinivasan Vijayakumar. Triple negative breast cancer patients treated with radiation therapy: Improvement in survival and local control with adjuvant chemotherapy compared to neoadjuvant chemotherapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6177.
Abstract 4855: Development of highly selective CDK7 inhibitor Q901 for solid tumors
Authors: Donghoon Yu, Yeejin Jeon, Dongsik Park, Mooyoung Seo, Wongyun Ahn, Jaeseung Kim, Choa Park, Euna Jeong, Sukjoon Yoon, Kiyean Nam
Journal: Cancer Research (2020)

Abstract Cyclin-dependent kinase 7 (CDK7) a member of the cyclin-dependent kinase family, forms a functional CDK-activating kinase (CAK) with cyclin H and MAT1, which regulates the cell cycle by phosphorylating other CDKs. CDK7 is also a component of transcription factor II H (TFIIH) that regulates transcriptional initiation and elongation through the phosphorylation of the RNA polymerase II C-terminal domain (CTD). Inhibition of CDK7 has been reported as a potential cancer therapeutic by addressing aberrant cell cycle regulation and transcription, as these abnormalities are considered main factors for tumor progression in specific types of cancer. Q901 is a novel highly selective CDK7 inhibitor in IND enabling development stage. Q901 shows extreme selectivity by singular inhibition of CDK7 among tested kinome panel. Q901 triggers G1 cell cycle arrest in specific cancer models in vitro and in vivo. Good correlation has been demonstrated between Q901 tumor growth inhibition and target engagement of a pharmacodynamics marker in treated models, suggesting CDK7 is a main driver of tumor progression in the selected models. The Q901 data supports the continued preclinical evaluation and potential of the compound as investigational treatment for patients with multiple solid tumors. Citation Format: Donghoon Yu, Yeejin Jeon, Dongsik Park, Mooyoung Seo, Wongyun Ahn, Jaeseung Kim, Choa Park, Euna Jeong, Sukjoon Yoon, Kiyean Nam. Development of highly selective CDK7 inhibitor Q901 for solid tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4855.
Abstract 1333: High-quality multi-omic analysis of FFPE samples
Authors: Jim Lund, Shannon Bailey, Muhammad Ekram, David Shahbazian, Lorenzo Memeo, Paul Hofman, Richard Williams, Jeff Gulcher
Journal: Cancer Research (2020)

Abstract Next-generation sequencing analysis of formalin-fixed, paraffin-embedded (FFPE) samples has the potential to lead to major advances in cancer treatment and prevention. These samples present a great opportunity for research because they are associated with clinical records, and millions of samples exist that can be used for retrospective analyses. We previously reported high quality whole-genome sequencing (WGS) results from FFPE tissue with an average of 98% of the genome covered at 20X or greater depth for samples as old as 15 years. In this study, we show high-quality results from performing multi-omic analysis including RNA sequencing (RNA-seq), WGS, methylation array, and microRNA sequencing (miRNA-seq) from the same archival sample. This demonstrates that multiomic analysis of existing cancer samples is technically feasible and opens up multi-omic analysis of these archival FFPE tissues. Using archival samples derived from breast, non small-cell lung, colorectal, and melanoma tumors, we extracted high-quality, high molecular weight DNA using the WuXi NextCODE SeqPlus method, and RNA was extracted using a rRNA depletion method. Using these extracts, we performed WGS, methylation chip array, RNA-seq, and miRNA-seq analyses. The resulting WGS data had high uniform coverage, and high-quality data was produced from the methylation chips. Results from the FFPE samples were compared to those found in the TCGA data. Analysis of mutation calls in these WGS samples revealed high concordance with those produced from the fresh-frozen whole-exome sequenced TCGA samples. Methylation patterns from our data clustered with samples of the same cancer type in the TCGA dataset. We also saw a similar clustering with the RNA-seq and miRNA-seq results when compared to the TCGA data. In addition, we found that RNA expression was correlated with promoter methylation, and gene expression changes affected by mutation and methylation were identified. In summary, we found an overall clustering of the FFPE samples with samples of the same cancer type and no systemic differences between fresh and FFPE samples were observed. These data demonstrate the feasibility of performing comprehensive, multi-omic profiling of archival FFPE tissues. Citation Format: Jim Lund, Shannon Bailey, Muhammad Ekram, David Shahbazian, Lorenzo Memeo, Paul Hofman, Richard Williams, Jeff Gulcher. High-quality multi-omic analysis of FFPE samples [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1333.
Abstract 2434: Epigenomic profiling of colorectal cancer to predict patients at high risk of metastasis
Authors: Aniruddha Chatterjee, John McCall, Parry Guilford, Sharon Pattison, Euan Rodger, Priyadarshana Ajithkumar
Journal: Cancer Research (2020)

Abstract Colorectal cancer (CRC) is one of the biggest cause of death world-wide and the second-highest cause of death by cancer in New Zealand with a mortality rate of approximately four deaths/day and 90% of CRC-associated mortality is caused by metastasis. Development of metastasis and the modifications that occur during various stages in the CRC metastatic cascade remains obscure. Emerging evidence indicates that epigenetic alterations have a greater influence on the development of metastasis than genetic mutations, but the current understanding of epigenetic drivers that cause CRC metastasis is limited. In the current project, as a first step in identifying epigenetic drivers for metastasis, whole-genome methylation and transcriptome profiles from paired primary and metastatic samples from the same NZ patients will be compared. Subsequently, the epigenetic drivers will be validated, and it can potentially be used as CRC metastatic markers. Circulating tumour cells (CTCs) represent the conduit between primary and metastatic tumours. They could be used to identify driver epigenetic changes associated with epithelial-to-mesenchymal transition (EMT), migration and invasion which occur during the metastatic cascade. CTCs are obtained from the blood and would provide a clinically less invasive test rather than requiring tissue samples. The recent development of single-cell sequencing technologies has now made it feasible to identify epigenetic changes in individual CTCs. In the second part of this project, protocols for single-cell DNA methylation and expression analysis will be developed using human colon cancer cell lines as a model. These optimised protocols will then be applied to CTCs from patient blood samples to identify epigenetic changes that predispose patients to metastasis. Identification of epigenetic drivers will help to detect individuals at high risk for metastasis prior to metastasis being clinically apparent, allowing for more personalised treatment and contribute to improving survival. Citation Format: Aniruddha Chatterjee, John McCall, Parry Guilford, Sharon Pattison, Euan Rodger, Priyadarshana Ajithkumar. Epigenomic profiling of colorectal cancer to predict patients at high risk of metastasis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2434.