bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PR05: Loss of PRC2 or KMT2D-COMPASS generates two quasi-mesenchymal cell states with distinct metastatic abilities
Authors: Zhang Yun , Donaher Joana Liu , Das Sunny , Li Xin , Reinhardt Ferenc , Krall Jordan A. , Lambert Arthur W. , Thiru Prathapan , Keys Heather R. , Khan Mehreen , Hofree Matan , Wilson Molly M. , Yedier-Bayram Ozlem , Lack Nathan A. , Onder Tamer T. , Bagci-Onder Tugba , Tyler Michael , Tirosh Itay , Regev Aviv , Lees Jacqueline , Weinberg Robert A. 
Published: December 2020

Abstract
The epithelial-mesenchymal transition (EMT) is a key cell-biological program enabling carcinoma cell phenotypic plasticity. Accumulating evidence suggests EMT programs do not operate as a stereotypical program that functions as a binary switch, shifting cells from an epithelial (E) to a mesenchymal (M) state. Instead, EMT programs generate cells that enter into a series of intermediate states arrayed along the E-M phenotypic spectrum. At present, we still lack a coherent understanding of how carcinoma cells control their entrance into and residence in these various intermediate states, and which EMT intermediate state(s) favour the metastatic process. Here we characterize a new level of regulation of EMT, consisting of two chromatin-modifying complexes, PRC2 and KMT2D-COMPASS, that function as critical regulators to maintain stable residence of both normal and neoplastic cells in an epithelial state via regulating the downstream response of EMT-inducing signals. Dysfunction of either of these two complexes causes cells that were previously stably ensconced in an epithelial state to lapse into two distinct quasi-mesenchymal cell states with strongly differing metastatic abilities. These observations uncover a novel mechanism that regulates E-M plasticity, specifies which intermediate EMT state a cell will reside in, and thereby determines the metastatic ability of carcinoma cells.
Citation Format: Yun Zhang, Joana Liu Donaher, Sunny Das, Xin Li, Ferenc Reinhardt, Jordan A. Krall, Arthur W. Lambert, Prathapan Thiru, Heather R. Keys, Mehreen Khan, Matan Hofree, Molly M. Wilson, Ozlem Yedier-Bayram, Nathan A. Lack, Tamer T. Onder, Tugba Bagci-Onder, Michael Tyler, Itay Tirosh, Aviv Regev, Jacqueline Lees, Robert A. Weinberg. Loss of PRC2 or KMT2D-COMPASS generates two quasi-mesenchymal cell states with distinct metastatic abilities [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PR05.
Abstract A01: Fusobacterium nucleatum and clinicopathologic features of colorectal carcinoma: Results from the ColoCare Study
Authors: Eisele Yannick , Mallea Patrick M. , Gigic Biljana , Stephens W. Zac , Warby Christy A. , Buhrke Kate , Lin Tengda , Schrotz-King Petra , Hardikar Sheetal , Huang Lyen C. , Pickron T. Bartley , Scaife Courtney , Koelsch Torsten , Peoples Anita R. , Pletneva Maria A. , Bronner Mary , Schneider Martin , Ulrich Alexis B. , Swanson Eric A. , Toriola Adetunji T. , Hauner Hans , Round June , Ulrich Cornelia M. , Holowatyj Andreana N. , Ose Jennifer 
Published: December 2020

Abstract
Background: Fusobacterium nucleatum (Fn), an oral commensal involved in a wide spectrum of infections, has recently been implicated in colorectal cancer (CRC) etiology. However, the role of Fn in treatment-naïve CRC patients remains unclear. Therefore, we assessed whether Fn abundance is associated with clinicopathologic characteristics among treatment-naïve CRC patients enrolled in the prospective ColoCare Study.
Methods: Quantitative real-time PCR was used to amplify and detect Fn DNA in fecal samples collected prior to surgery from 105 patients. We utilized multivariable regression analysis to investigate associations between Fn abundance and sex, age at surgery, BMI, tumor stage, tumor grade, tumor site, infection with H. pylori, microsatellite instability, alcohol consumption, and smoking history by adjusting for sex, age at surgery, cohort, and BMI.
Results: Compared to patients with undetectable or low abundance of Fn, patients with higher abundance of Fn were more likely to be diagnosed with rectal cancer than colon cancer (Odds Ratio [OR] = 3.01, 95% CI 1.06-8.57 P=0.04). Categorizing the colon into right-sided (proximal) and left-sided (distal) showed that patients with a high abundance of Fn were also more likely to be diagnosed with rectal cancer compared to right-sided colon cancer (OR=5.32, 95% CI 1.23-22.98 P=0.03), thus suggesting an increasing risk of cancer diagnosis along the bowel towards the rectum.
Conclusion: Our study sheds light on the association of high abundance of Fn in fecal biospecimen with colorectal carcinogenesis, which may support future preventive or diagnostic measures.
Citation Format: Yannick Eisele, Patrick M. Mallea, Biljana Gigic, W. Zac Stephens, Christy A. Warby, Kate Buhrke, Tengda Lin, Petra Schrotz-King, Sheetal Hardikar, Lyen C. Huang, T. Bartley Pickron, Courtney Scaife, Torsten Koelsch, Anita R. Peoples, Maria A. Pletneva, Mary Bronner, Martin Schneider, Alexis B. Ulrich, Eric A. Swanson, Adetunji T. Toriola, Hans Hauner, June Round, Cornelia M. Ulrich, Andreana N. Holowatyj, Jennifer Ose. Fusobacterium nucleatum and clinicopathologic features of colorectal carcinoma: Results from the ColoCare Study [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A01.
Abstract A05: Growth rate alterations of human colorectal cancer cells by 157 gut bacteria
Authors: Taddese Rahwa , Garza Daniel R. , Ruiter Lilian , Belzer Clara , Aalvink Steven , Nagtegaal Iris D. , Dutilh Bas E. , Boleij Annemarie 
Published: December 2020

Abstract
Several bacteria in the human gut microbiome have been associated with colorectal cancer (CRC) by high-throughput screens. In some cases, molecular mechanisms have been elucidated that drive tumorigenesis, including bacterial membrane proteins or secreted molecules that interact with the human cancer cells. For most gut bacteria, however, it remains unknown if they enhance or inhibit cancer cell growth. Here, we screened bacteria-free supernatants (secretomes) and inactivated cells of over 150 cultured bacterial strains for their effect on CRC cell growth. Five CRC cell lines and one noncancerous kidney cell line were selected based on their differences in mutational landscapes. We observed family-level and strain-level effects that often differed between bacterial cells and secretomes, suggesting that different molecular mechanisms are at play. Secretomes of Bacteroidaceae, Enterobacteriaceae, and Erysipelotrichaceae enhanced CRC cell growth, while most Fusobacteriaceae cells and secretomes inhibited growth, contrasting prior findings. For some bacterial families, strong cell line-dependent effects were obsevered, such as for Streptococcaceae and HT29 cells. In some bacteria, the presence of specific functional genes was associated with CRC cell growth rates, including the virulence genes TcdA in Clostridiales and FadA in Fusobacteriaceae, which both inhibited growth. Bacteroidaceae cells that enhanced growth were enriched for genes of the cobalamin synthesis pathway, while Fusobacteriaceae cells that inhibit growth were enriched for genes in ethanolamine utilization pathway. Together, our results reveal how different gut bacteria have wide-ranging effects on cancer cells, contribute a better understanding of the effects of the gut microbiome on the human host, and provide a valuable resource for identifying candidate target genes for potential microbiome-based diagnostics and treatment strategies.
Citation Format: Rahwa Taddese, Daniel R. Garza, Lilian Ruiter, Clara Belzer, Steven Aalvink, Iris D. Nagtegaal, Bas E. Dutilh, Annemarie Boleij. Growth rate alterations of human colorectal cancer cells by 157 gut bacteria [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A05.
Abstract A07: The involvement of a type VII secretion system in the interactions between Streptococcus gallolyticus subspecies gallolyticus and colorectal cancer
Authors: Taylor John Culver , Rutherford Jacob , Nunez Maria , Xu Yi 
Published: December 2020

Abstract
Colorectal cancer (CRC) is the 2nd-3rd most common cancer worldwide and is a leading cause of cancer-related death. Increasing evidence suggests that the gut microbiome plays an important role in the development of CRC. One such organism of the gut microbiome that plays an important role in CRC is Streptococcus gallolyticus subspecies gallolyticus (Sgg). Previously, we reported that Sgg stimulates CRC cell proliferation in a β-catenin dependent manner. Using an azoxymethane-induced mouse model of CRC, we have also shown that Sgg-treated mice had significantly higher tumor burden in the colon compared to mice treated with saline or negative control bacteria, suggesting that Sgg actively promotes the development of CRC. The mechanism underlying Sgg’s role in CRC development, however, has yet to be elucidated. The type VII secretion system (T7SS), also called the Esx secretion system, is a specialized secretion system found primarily in Firmicutes and Actinobacteria and has been shown to play an important role in virulence in Staphylococcus aureus and Mycobacterium tuberculosis. Here, we examined the genome of Sgg and found that it encodes a putative T7SS (SggT7SS) highly similar to the T7SS in S. aureus with respect to sequence identity and gene organization. We further showed that the SggT7SS is functional. To investigate if the SggT7SS is involved in the connection between Sgg and CRC, we generated an Sgg mutant lacking the core components of the T7SS secretion machinery. Functional characterization of the mutant indicates that SggT7SS is intimately involved in the interactions between Sgg and CRC cells. Taken together, our results suggest that a T7SS system may be important in inducing specific host responses to Sgg in the context of CRC. Studies to further elucidate the activities of T7SS and its role in Sgg’s contribution to CRC are currently under way.
Citation Format: John Culver Taylor, Jacob Rutherford, Maria Nunez, Yi Xu. The involvement of a type VII secretion system in the interactions between Streptococcus gallolyticus subspecies gallolyticus and colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A07.
Abstract A09: Understanding the role of colorectal cancer-associated microbes in colorectal cancer
Authors: Ternes Dominik , Schmitz Martine , Grandmougin Léa , Tsenkova Mina , Koncina Eric , Ginolhac Aurélien , Karta Jessica , Kuhn Diana , Garcia Javier Ramiro , Greenhalgh Kacy , Wilmes Paul , Letellier Elisabeth , Haan Serge 
Published: December 2020

Abstract
Accumulating evidence suggests that dysbiosis, a state of pathologic imbalance in the human gut microbiome, is present in patients suffering from colorectal cancer (CRC). Several microbiome studies identified specific bacteria that are associated with CRC, among which Fusobacteria were shown to directly interact with cancer or immune cells of their host. However, only a limited number of CRC-associated microbes have been studied for host-microbial interactions; hence, the role of bacteria in the etiology of the disease remains unknown. Accordingly, our work aims at the development of a methodologic workflow for studying CRC-associated bacteria and their role in colon cancer tumor initiation and progression. In a first step, we identified CRC-associated bacteria that are enriched at the tumor site of CRC patients. Therefore, we used publicly available datasets and an in-house patient sample collection. Then, we predicted and optimized bacterial growth in silico by using a genome-scale metabolic reconstruction model combined with a constraint-based modeling approach. Finally, we implemented CRC-associated bacteria together with established primary CRC patient cultures into the microfluidics-based human-microbial crosstalk model (HuMiX). Our workflow allowed to analyze host-microbial interaction mechanisms of CRC-associated bacteria on a transcriptomic, proteomic, and metabolomic level.
Citation Format: Dominik Ternes, Martine Schmitz, Léa Grandmougin, Mina Tsenkova, Eric Koncina, Aurélien Ginolhac, Jessica Karta, Diana Kuhn, Javier Ramiro Garcia, Kacy Greenhalgh, Paul Wilmes, Elisabeth Letellier, Serge Haan. Understanding the role of colorectal cancer-associated microbes in colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A09.
Abstract A11: Betel nut chewing, oral Cyanobacteria, and exposure to cyanotoxins
Authors: Hernandez Brenda Y. , Zhu Xuemei , Sotto Patrick , Paulino Yvette 
Published: December 2020

Abstract
Betel nut from the Areca catechu palm tree, chewed alone or as a quid wrapped in Piper betle leaf, is the 4th most widely used addictive substance globally, primarily in parts of Asia and the Pacific. Betel nut chewing is an independent cause of cancers of the oral cavity and esophagus and has been linked to other malignancies. We evaluated 16S rRNA in oral cavity swabs and saliva obtained from 122 adults (64 current betel nut chewers, 37 former chewers, 21 never chewers) in Guam. Cyanobacteria was detected at 90-fold higher abundance in oral samples from current betel nut compared to both former and never chewers. Cyanobacteria was also the predominant bacterial taxa detected in Areca catechu nuts and Piper betle leaves.16S sequence data were evaluated using PICRUSt to predict gene families and to generate a composite metagenome. AntiSMASH 5.0 was used for the analysis of gene marker data corresponding to secondary metabolites. Cyanotoxins, including microcystins, nodularins, and cylindrospermopsin, as well as other secondary metabolites were identified as putative secondary metabolites. Subsets of oral and plant samples evaluated via ELISA confirmed the presence of these metabolites. The identification of these cyanotoxins in this population suggests their possible contribution to betel nut-associated carcinogenesis.
Citation Format: Brenda Y. Hernandez, Xuemei Zhu, Patrick Sotto, Yvette Paulino. Betel nut chewing, oral Cyanobacteria, and exposure to cyanotoxins [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A11.
Abstract A21: Promotion of colorectal cancer by Streptococcus gallolyticus—a novel mechanism
Authors: Taylor John , Kumar Ritesh , Sarshekeh Amir , Davies Jennifer , Kopetz Scott , Xu Juan , Xu Yi 
Published: December 2020

Abstract
Streptococcus gallolyticus subsp. gallolyticus (Sgg) is an opportunistic gut pathobiont. It has a longstanding clinical association with colorectal cancer (CRC). We previously demonstrated that Sgg stimulates CRC cell proliferation and promotes tumor growth in mouse models of CRC (Kumar et al., 2017). Recent studies also indicated that Sgg induced an immune-tolerant environment in the mouse colon conductive for tumor development (Zhang et al., 2018). These results provide strong experimental support for Sgg being an active promoter of tumor development. The molecular mechanism underlying Sgg’s tumor promoting activity was unknown. We investigated the effect of Sgg on CRC cells by analyzing mass spectrometry proteomics data. We found that several types of collagen were upregulated in Sgg-treated cells compared to cells cultured in media only. The upregulation was further confirmed by RT-qPCR and Western blot. Transforming growth factor beta (TGFbeta) is a master regulator of the extracellular matrix. Therefore, we examined the effect of Sgg on the TGFbeta signaling pathway. The results showed that Sgg-treated cells had significantly higher level of phosphorylated Smad2. Sgg treatment also induced the expression of TGFbeta target genes. The effects of Sgg on CRC cells were significantly decreased in the presence of inhibitors for TGFbeta signaling. In addition, we observed that Sgg induced similar effects in mouse colon. Together, these results demonstrate that Sgg activates the TGFbeta signaling pathway in vitro and in vivo. Furthermore, we found that activation of TGFbeta by Sgg is mediated by specific Sgg genes. Deletion of these genes abolished the effect of Sgg on CRC cells in vitro and its ability to promote tumor growth in a mouse model of CRC. These results suggest that TGFbeta activation is a mechanism underlying Sgg’s contribution to tumor growth. Next, we tried to determine if these findings are relevant to CRC patients. Examination of tumor tissues from CRC patients revealed that Sgg-positive tumors exhibit significantly enhanced TGFbeta activity compared to Sgg-negative tumors, suggesting that Sgg-positivity correlates with stronger TGFbeta signaling activities in CRC patients. Taken together, our results highlight a previously unrecognized mechanism in which a colonic microbe activates the TGFbeta signaling pathway to promote the development of CRC. Studies to further delineate this novel mechanism are currently under way.
Citation Format: John Taylor, Ritesh Kumar, Amir Sarshekeh, Jennifer Davies, Scott Kopetz, Juan Xu, Yi Xu. Promotion of colorectal cancer by Streptococcus gallolyticus—a novel mechanism [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A21.
Abstract A28: Concomitant use of antibiotics and immune checkpoint inhibitors in patients with solid neoplasms: Retrospective data from real-world settings
Authors: Kapoor Akhil , Noronha Vanita , Patil Vijay M. , Joshi Amit , Menon Nandini , Janu Amit , Prabhash Kumar 
Published: December 2020

Abstract
Background: The use of antibiotics is known to alter the gut microbiome and it is hypothesized that use of antibiotics may also alter the response to checkpoint inhibitors (CPI). As data are limited from real-world settings, we performed a retrospective audit of patients who received CPI along with concomitant antibiotics.
Patients and Methods: This study is a retrospective audit of prospectively collected database of patients who received CPI for advanced solid tumors in any line between August 2015 and November 2018 at Tata Memorial Hospital, Mumbai, India. Antibiotic use was recorded from two weeks before the start of CPI and concomitantly with CPI. All statistical calculations were performed using SPSS statistical software for Windows version 20.0.
Results: A total of 155 patients were identified to have received CPI during the study period, of which 70 (44%) patients received antibiotics. Median PFS in patients who received antibiotics was 1.7 months (95% CI: 1.1-2.3) against 3.6 months (95% CI: 2.3-4.8) for patients who did not receive antibiotics (p=0.912). Median OS in the patients who received antibiotics was 3.9 months (95% CI: 1.8-11.4) as compared to 9.2 months (95% CI: 4.2-12.3) for patients who did not receive antibiotics with a trend to significance with p=0.053 (HR-1.023; 95%CI: 1.00-1.04). Among the patients who received antibiotics, median OS for patients who received ≤10 days of antibiotics was 8.8 months (95% CI: 4.2-11.2) while for patients receiving &gt;10 days of antibiotics, it was 2.8 months (95% CI: 1.2-4.4), p=0.025 (HR 2.0, 95% CI: 1.1-3.7).
Conclusions: This study shows that judicious use of antibiotics is required in patients on CPI or scheduled to be started on CPI.
Note: This abstract was not presented at the conference.
Citation Format: Akhil Kapoor, Vanita Noronha, Vijay M. Patil, Amit Joshi, Nandini Menon, Amit Janu, Kumar Prabhash. Concomitant use of antibiotics and immune checkpoint inhibitors in patients with solid neoplasms: Retrospective data from real-world settings [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A28.
Abstract A29: Differential regulation of apoptosis and senescence by the miR-449 family microRNAs and its implications in tumor microenvironments of NSCLC
Authors: Cho Chun-Yu , Chung Shih-Ying , Chuang Shuang-En 
Published: December 2020

Abstract
MicroRNAs (miRNAs) play important roles in various biologic processes, and aberrant miRNA expression is one of the mechanisms of tumorigenesis. Previous studies indicate that oncogenic HPV infection interrupts the expression of tumor-suppressive miR-34a and contributes to the development of cervical cancer. In addition, the traditional Chinese medicine Gynostemma pentaphyllum (Thunb.) Makino may exert its pharmacologic effects through modifying the gut microbiota by regulating hepatic miR-34a expression. MiR-449 miRs are members of the tumor suppressor miR-34 family and are evolutionarily conserved. In this study, we demonstrated that, in lung cancer cells, ectopic expression of miR-449 family, including miR-449a, miR-449b, and miR-449c, decreased the levels of several G1 phase proteins including cyclin D1, cyclin D3, CDK4, and CDK6 via directly targeting their mRNA’s 3’-UTR. We also observed a differential induction of apoptosis vs. senescence by the miR-449 cluster. While miR-449a and miR-449c induced senescence, miR-449b induced apoptosis and sensitized cancer cells to apoptotic stimuli, such as serum deprivation. Interestingly, among this cluster miRNAs, only miR-449a could induce significant senescence-associated secretory phenotype (SASP), e.g., expression of IL-8, IL-6, IL-1b, and TNF-alpha. Moreover, we also found that miR-449a increased NF-kB phosphorylation at S276, but not phosphorylation site of S536, and promoted the expression of IL-8 mRNA. In this regard, the gut microbiota has been indicated to induce proinflammatory cytokines such as IL-8 to influence the outcomes of cancer patients. In addition to MRX34 (a miR-34a mimic) used in clinical trials, miR-449 family may also potentially become a new therapeutic candidate for NSCLC and other solid tumors’ treatment.
Citation Format: Chun-Yu Cho, Shih-Ying Chung, Shuang-En Chuang. Differential regulation of apoptosis and senescence by the miR-449 family microRNAs and its implications in tumor microenvironments of NSCLC [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A29.