tbuckley/cabot-search huggingface dataset:
Abstract 3083: Role of S100A10 in the metastatic colonization of breast cancer stem cells
Authors: Yohei Shimono, Hisano Yanagi, Takashi Watanabe, Tatsunori Nishimura, Takanori Hayashi, Seiji Okada, Motoshi Suzuki, Kenji Kawada, Hironobu Minami, Noriko Gotoh
Journal: Cancer Research (2021)

Abstract Breast cancer is now the most frequently diagnosed cancer and the leading global cause of cancer death in women. Despite advances in the diagnosis and treatment of human breast cancer, advanced stage, metastatic breast cancers are difficult to cure. Among the common target organs for breast cancer metastasis, post recurrence survival is worst when multiple metastasis was observed in the liver. Cancer stem cells (CSCs) are a sub-population of the cells that retain high tumorigenic capacity and, at the same time, are able to sustain the formation of tumors that recreate the cellular diversity of the parent lesions from which they have been originally isolated. We and others have shown that in epithelial malignancies such as breast and colorectal cancers, self-renewal ability of cancer cells with CSC properties is epigenetically regulated by their expression of microRNAs, such as with miR-200c, miR-142 and miR-221. Because of their highly tumorigenic properties, CSCs with are associated with metastatic progression, especially at the initial steps of metastases. We have previously established the breast cancer patient-derived tumor xenograft (PDX) mouse model in which CSC marker CD44+ cancer cells formed spontaneous microscopic metastases in the liver. Comparison of gene expression profiles between the CD44+ human breast cancer cells metastasized to the liver (‘metastasized CSCs') and those in the primary site (‘primary CSCs') revealed that S100A10 was upregulated in metastasized CSCs than in primary CSCs. Knockdown of S100A10 in breast cancer cells reduced the matrix metalloproteinase activity and suppressed their invasion abilities in transwell cell invasion assays in which upper surface of transwell inserts were precoated with Matrigel. Knockdown of S100A10 suppressed, and overexpression of S100A10 enhanced the 3D organoid formation capacities of breast cancer PDX cells in vitro. Finally, constitutive knockdown of S100A10 significantly reduced their metastatic ability to the liver in vivo. Upregulation of S100 family protein expression is observed in many human cancers, including breast, lung, bladder and gastric cancers. These findings suggest that S100A10 functions as a metastasis promoter of breast CSCs by conferring both invasion ability and CSC properties in breast cancers. Citation Format: Yohei Shimono, Hisano Yanagi, Takashi Watanabe, Tatsunori Nishimura, Takanori Hayashi, Seiji Okada, Motoshi Suzuki, Kenji Kawada, Hironobu Minami, Noriko Gotoh. Role of S100A10 in the metastatic colonization of breast cancer stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3083.
High SARS-CoV-2 infection rate after resuming professional football in São Paulo, Brazil
Authors: Bruno Gualano, Gisele Mendes Brito, Ana Jéssica Pinto, Italo Ribeiro Lemes, Luciana Diniz Nagem Janot Matos, Ana Lúcia de Sá Pinto, Irineu Loturco
Journal: British Journal of Sports Medicine (2021)

Objective To examine the SARS-CoV-2 infection rate in a cohort of 6500 professional athletes and staff during the 2020 football (soccer) season in São Paulo, Brazil. Methods This retrospective cohort study included 4269 players (87% male, age: 21.7±4.2 years) and 2231 staff (87% male, age: 42.6±11.9 years) from 122 teams (women: n=16) involved in eight leagues (women: n=2), which took place in São Paulo, Brazil. Between 4 July 2020 and 21 December 2020, swab samples were collected weekly (n=29 507) and tested for SARS-Cov-2 via reverse transcription-PCR by an accredited laboratory commissioned by the São Paulo Football Federation. We contacted the medical staff of each team with positive cases to collect information on disease severity. Results Among 662 PCR-confirmed cases, 501 were athletes and 161 were staff. The new infection rate was 11.7% and 7.2% for athletes and staff, respectively. Athletes were more susceptible to infection than staff (OR: 1.71, 95% CI: 1.42, 2.06, p&lt;0.001), although with lower chance for moderate to severe disease (OR: 0.06, 95% CI: 0.01, 0.54, p=0.012). Six teams had ≥20 individuals testing positive for SARS-CoV-2, whereas 19 teams had ≥10 confirmed cases. Twenty-five mass outbreaks were identified (≥5 infections within a team in a 2-week period). The prevalence of SARS-CoV-2 infections was similar in athletes and staff as the general population in São Paulo. Conclusion Despite weekly testing and other preventive measures, we found a high SARS-CoV-2 infection rate in athletes and staff after resuming football, which coincides with the high prevalence of infection in the community during the same period. These data may assist policy-makers and sports federations for determining if and when it is safe to resume competitions.
Abstract LB122: The complete estrogen receptor antagonist (CERAN) OP-1250 shrinks ER+ brain metastases in an intracranial xenograft tumor model expressing mutant ESR1
Authors: Leslie Hodges-Gallagher, Alison D. Parisian, Richard Sun, David C. Myles, Pamela M. Klein, Cyrus L. Harmon, Peter J. Kushner
Journal: Cancer Research (2021)

Abstract Estrogen receptor-positive (ER+) breast cancer can undergo metastatic spread to the brain, which occurs in up to 15% of HER2-/ER+ metastatic breast cancer patients. Although endocrine therapy is not explicitly approved for brain metastasis and clinical trials are lacking, anecdotal reports of clinical responses by endocrine agents motivate further investigation. One such agent is the ER antagonist tamoxifen, which has previously been shown to reach high levels in brain tissue and ER+ brain metastases in patients with breast cancer*. We previously reported that OP-1250, a novel, oral complete ER antagonist (CERAN), penetrates the brain and is efficacious at shrinking tumors in a xenograft brain metastasis model in which patient derived human ER+ tumors were intracranially transplanted into immunocompromised mice**. Here we compare the ability of OP-1250 to shrink brain tumors in this model with tamoxifen and other agents. Whereas tamoxifen indeed had therapeutic effects in this brain xenograft model, the effect was not as profound as that of OP-1250, which was able to completely clear the tumors in many animals, as determined by MRI. * Lien et al. Distribution of tamoxifen and metabolites into brain tissue and brain metastases in breast cancer patients. Br. J. Cancer, 1991, 63, 641-645.**Hodges-Gallagher, et al. OP-1250 a complete estrogen receptor antagonist that penetrates the brain and prevents lethality from an intracranial xenograft tumors expressing mutant ESR1, abstract, AACR 2020 Citation Format: Leslie Hodges-Gallagher, Alison D. Parisian, Richard Sun, David C. Myles, Pamela M. Klein, Cyrus L. Harmon, Peter J. Kushner. The complete estrogen receptor antagonist (CERAN) OP-1250 shrinks ER+ brain metastases in an intracranial xenograft tumor model expressing mutant ESR1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB122.
Abstract 2391: Computation of a user-friendly composite score from three prostate cancer biomarkers
Authors: Gargi Pal, Emmanuel Asante-Asamani, Leslie Liu, Olorunseun O. Ogunwobi
Journal: Cancer Research (2021)

Abstract Summary: Prostate cancer (PCa) is the most commonly diagnosed solid organ cancer in men worldwide. Current diagnosis of PCa includes use of initial prostate specific antigen assay which has a high false positive rate, low specificity, and low sensitivity. Consequently, it results in overdiagnosis and overtreatment, leaving patients with unintended health complications from the side effects of unnecessary prostate biopsies and treatment. PCa biomarkers are being discovered to address this unmet need. Here, we report creation of a composite score based on three PCa biomarkers, plasmacytoma variant translocation 1 exon 4A, exon 4B, and exon 9. Statistical analysis of copy numbers derived from a real-time quantitative polymerase chain reaction - based assay showed these PCa biomarkers to be linearly separable. We trained a supervised learning algorithm using support vector classifiers to generate a classification hyperplane from which a composite score is developed. Our aggregate score when applied to test data from non-cancerous prostate epithelial cells and PCa cells accurately classified 100% PCa cells. Creation of this 3-biomarker based composite score lays the groundwork for clinical trial of its use in PCa diagnosis. Citation Format: Gargi Pal, Emmanuel Asante-Asamani, Leslie Liu, Olorunseun O. Ogunwobi. Computation of a user-friendly composite score from three prostate cancer biomarkers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2391.
Abstract 2103: Distinct methylation patterns correlate with unique clinical and genomic profiles of brainstem gliomas
Authors: Lee H. Chen, Changcun Pan, Sizhen Wang, Hai Yan, Liwei Zhang
Journal: Cancer Research (2021)

Abstract Gliomas of the brainstem and surrounding regions are devastating brain tumors with the highest mortality rates among all cancers. The locations of tumors make surgical resection difficult due to the risk of perioperative mortality. To understand the genetics and molecular biology of this disease, we performed a comprehensive study, combining epigenetic and genomic analyses with clinical features on 126 brainstem gliomas, including 33 diffuse intrinsic pontine gliomas. Based on DNA methylation data, we identified four distinct clusters named H3-Pons, H3-Medulla, IDH, and PA-like, each associated with unique genomic and clinical profiles. Most of the tumors within H3-Pons and H3-Medulla harbored H3F3A mutations, but tumors in these two clusters use different escaping mechanisms for DNA damage response pathway. Most of the tumors in H3-Pons showed TP53 mutations, while H3-Medulla contain PPM1D mutations. We also analyzed the lengths of telomeres in these tumors by whole genome sequencing data, showing striking difference between clusters, suggesting the mechanisms of telomere maintenance differ between different subtypes of brainstem gliomas. Structural variations and alternative splicing based on RNA sequencing demonstrated possible different transcriptome profiling in methylation clusters, and pathway analysis showed different mechanisms in these samples. Our findings suggest that the integration of DNA methylation data into diagnosis could be utilized to better understand brainstem glioma and better defining the classification, therefore guiding future clinical management of patients. Citation Format: Lee H. Chen, Changcun Pan, Sizhen Wang, Hai Yan, Liwei Zhang. Distinct methylation patterns correlate with unique clinical and genomic profiles of brainstem gliomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2103.
Lard diet accelerates prostate cancer development with modulation of systematic and local inflammation and gut microbiota alteration in a Pten-deficient mouse model
Authors: H. Sato, S. Narita, M. Ishida, S. Kashima, R. Yamamoto, A. Koizumi, T. Nara, M. Huang, K. Numakura, M. Saito, S. Shigeru, T. Yoshioka, T. Habuchi
Journal: European Urology (2021)
Abstract 2973: Establishment of organoids and patient derived cancer cell lines from gastric cancer body fluids as preclinical models for personalized therapy
Authors: Sun Kyoung Kang, Hyun Joo Bae, Woo Sun Kwon, Tae Soo Kim, Sujin Lee, Sang Woo Cho, Hyun Cheol Chung, Sun Young Rha
Journal: Cancer Research (2021)

Abstract Gastric cancer (GC), the second leading cause of cancer-related deaths worldwide, is especially prevalent in Asian countries. Despite advances in therapeutics, GC patients with peritoneal metastasis is frequent and when ascites has developed, the prognosis is very poor. Also, the number of anticancer drugs successfully marketed is rare in GC. Therefore, a faithfully in vitro model that can test various drugs and perform patient-specific personalized therapy is needed. We isolated cancer cells from ascites or pleural fluids of gastric cancer patients and established 19 patient-derived organoids and matched patient-derived cancer cell lines (PDCC). Organoid success rate was 60.7 % while PDCC was about 28.5 %. The time required to establish organoids was 1-2 months, while PDCC was 3-4 months. Organoids showed various growth characteristics and morphology, which reflects the clinical behavior of the patients including adenocarcinoma or signet ring cell carcinoma. In addition, drug-sensitive to each organoid and matched PDCC were identified using various chemotherapeutics and targeted agents. Then, patients' clinical information and comparative analysis were performed, suggesting the potential sensitive drug to each patient. Currently, the genetic information of each organoid is ongoing with WES/RNA Seq, and the sensitivity and comparative analysis of the drug will be performed. Therefore, our results provide a potential infrastructure for personalized therapy by comprehensive analysis of the patient's genomic data and organoid/PDCC model. Citation Format: Sun Kyoung Kang, Hyun Joo Bae, Woo Sun Kwon, Tae Soo Kim, Sujin Lee, Sang Woo Cho, Hyun Cheol Chung, Sun Young Rha. Establishment of organoids and patient derived cancer cell lines from gastric cancer body fluids as preclinical models for personalized therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2973.
Genomic diversity and ecology of human-associated Akkermansia species in the gut microbiome revealed by extensive metagenomic assembly
Authors: Nicolai Karcher, Eleonora Nigro, Michal Punčochář, Aitor Blanco-Míguez, Matteo Ciciani, Paolo Manghi, Moreno Zolfo, Fabio Cumbo, Serena Manara, Davide Golzato, Anna Cereseto, Manimozhiyan Arumugam, Thi Phuong Nam Bui, Hanne L. P. Tytgat, Mireia Valles-Colomer, Willem M. de Vos, Nicola Segata
Journal: Genome biology (2021)

Abstract Background Akkermansia muciniphila is a human gut microbe with a key role in the physiology of the intestinal mucus layer and reported associations with decreased body mass and increased gut barrier function and health. Despite its biomedical relevance, the genomic diversity of A. muciniphila remains understudied and that of closely related species, except for A. glycaniphila , unexplored. Results We present a large-scale population genomics analysis of the Akkermansia genus using 188 isolate genomes and 2226 genomes assembled from 18,600 metagenomes from humans and other animals. While we do not detect A. glycaniphila , the Akkermansia strains in the human gut can be grouped into five distinct candidate species, including A. muciniphila , that show remarkable whole-genome divergence despite surprisingly similar 16S rRNA gene sequences. These candidate species are likely human-specific, as they are detected in mice and non-human primates almost exclusively when kept in captivity. In humans, Akkermansia candidate species display ecological co-exclusion, diversified functional capabilities, and distinct patterns of associations with host body mass. Analysis of CRISPR-Cas loci reveals new variants and spacers targeting newly discovered putative bacteriophages. Remarkably, we observe an increased relative abundance of Akkermansia when cognate predicted bacteriophages are present, suggesting ecological interactions. A. muciniphila further exhibits subspecies-level genetic stratification with associated functional differences such as a putative exo/lipopolysaccharide operon. Conclusions We uncover a large phylogenetic and functional diversity of the Akkermansia genus in humans. This variability should be considered in the ongoing experimental and metagenomic efforts to characterize the health-associated properties of A. muciniphila and related bacteria.
Non-invasive ventilatory support and high-flow nasal oxygen as first-line treatment of acute hypoxemic respiratory failure and ARDS
Authors: Domenico Luca Grieco, Salvatore Maurizio Maggiore, Oriol Roca, Elena Spinelli, Bhakti K. Patel, Arnaud W. Thille, Carmen Sílvia V. Barbas, Marina Garcia de Acilu, Salvatore Lucio Cutuli, Filippo Bongiovanni, Marcelo Amato, Jean-Pierre Frat, Tommaso Mauri, John P. Kress, Jordi Mancebo, Massimo Antonelli
Journal: Intensive Care Medicine (2021)
Abstract 2859: Understanding metastatic cancer biology
Authors: Ditte Sigaard Christensen, Johanne Ahrenfeldt, Nicolai Juul Birkbak
Journal: Cancer Research (2021)

Abstract Introduction: Metastatic disease is responsible for 90% of all cancer death. Understanding the process of how primary tumors achieve metastatic potential is of great importance and paramount to the development of precision medicine that may limit the aggressive distant spread of metastatic cancer. It is hypothesized that during cancer evolution, cells within the primary tumor obtain metastatic potential through acquisition of specific somatic alterations. However, the defining ability that allows metastasis remains unknown. By comparing genomic profiles of primary and metastatic cancers we wish to investigate if potential metastatic gate-keeper mutations exist, defined as alterations to individual genes or pathways that are required to facilitate metastatic dissemination. Material and methods: Here, we analyzed panel-based DNA sequencing datasets from the GENIE (Genomics Evidence Neoplasia Information Exchange) project. Analyses were performed on 123 shared genes from the 6 most common panels, selected to include as many patients as possible while analyzing as many genes as possible. In total 43,323 patients had mutations in one or more of the 123 shared genes across 37 different cancer types. Using bioinformatic tools, we compared genomic alterations in primary versus metastatic samples. Results: Out of the 123 genes we found 26 significantly enriched genes and 30 significantly depleted genes in metastatic disease in at least one cancer type. Overall, TP53 was the most mutated gene across all cancer types and the most enriched gene with significant enrichment in metastatic prostate cancer, non-small cell lung cancer and soft tissue sarcoma. Out of the 30 depleted genes we identified CTNBB1 as significantly depleted in four different cancer types and PIK3CA significantly depleted in two. PIK3CA is one of the most commonly mutated cancer genes, and a target of several precision therapies. Finding of the gene being depleted may indicate a less significant role in the development of metastatic disease. Additionally, we found a higher tumor mutation burden and increased levels of chromosomal instability for metastatic samples compared to primary. Conclusions: With this analysis we demonstrate how the power of large datasets can be utilized to make novel inferences on cancer biology. We observed significant enrichment in overall mutation counts and copy number alterations. Furthermore, we identified both enrichments and depletions of specific alterations in metastatic disease potentially revealing how certain driver gene combinations associate with cancer progression more commonly than others. Citation Format: Ditte Sigaard Christensen, Johanne Ahrenfeldt, Nicolai Juul Birkbak. Understanding metastatic cancer biology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2859.
18f-FDG PET-CT Assessment of Responses to Salvage Therapy and Autologous Stem Cell Transplant (ASCT) in Relapsed/Refractory Classical Hodgkin Lymphoma (cHL)
Authors: Maciej Tatarczuch, Catherine Hildyard, Manil Subesinghe, Toby A. Eyre, Graham Collins
Journal: Blood (2017)
Somatic features of response and relapse in non-muscle invasive bladder cancer treated with intravesical Bacillus Calmette–Guérin
Authors: D.C. Müller, J.V.W. Bacon, E. Ritch, S.G. Dugas, G. Vandekerkhove, M. Annala, P.C. Black, H. Seifert, L. Bubendorf, A.W. Wyatt, C.A. Rentsch
Journal: European Urology (2021)
Abstract 77: MSC loaded oncolytic virus and expressing immunomodulators have therapeutic efficacy in advanced melanomas
Authors: Nobuhiko Kanaya, Maria Lopez Vazquez, Arnaldo J. Franco Torres, Yohei Kitamura, Genevieve M. Boland, Khalid Shah
Journal: Cancer Research (2021)

Abstract Patients with advanced melanoma have a high propensity to metastasize to the brain and numerous investigational treatments with targeted agents have shown modest response in melanoma brain metastatic patients. Therefore, there is an urgent need to develop innovative therapies for such tumors. Oncolytic herpes simplex virus (oHSV) that selectively replicate in tumor cells and illicit an antitumor effect via oncolysis and production of neoantigens is among the recently approved promising therapies for primary melanoma patients. However, virus neutralization, and inefficient extravasation are the major barriers to the effective systemic delivery of oHSV to target metastatic tumor lesions in the brain. We have previously shown that mesenchymal stem cells (MSC) armed with different oHSV variants (MSC-oHSV) home to metastatic tumor lesions and have therapeutic benefits in melanoma brain metastases (MBM) models. To enhance therapeutic efficacy for metastasis melanoma, we investigated the novel combined therapy using MSC loaded with oHSV and simultaneously MSC releasing GM-CSF. Based on our TCGA data indicating significant loss of PTEN expression in late-stage metastatic melanoma, we tested MSC based therapeutics in PTEN mutant mouse melanomas. We show that MSC loaded oHSV effectively kills PTEN mutant syngeneic tumor cells in vitro. Next, we established MSC secreting GM-CSF and tested the abscopal effects as well as the antitumor efficacy in combination with MSC-oHSV in PTEN mutant syngeneic bilateral subcutaneous tumor model. The combined MSC based therapy showed significant therapeutic effects at both the treated and untreated site compared to control therapies. Interestingly, when these mice after combination therapy were re-challenged with mouse melanoma cells injected into brain, all mice remained tumor free. The combined MSC therapy induced effector memory CD8 and central memory CD8 cells in spleen and there was no toxicity in major organs post-therapy. In conclusion, our data indicate that combined MSC-oHSV/GM-CSF therapy is a promising novel therapy for advanced melanomas. Citation Format: Nobuhiko Kanaya, Maria Lopez Vazquez, Arnaldo J. Franco Torres, Yohei Kitamura, Genevieve M. Boland, Khalid Shah. MSC loaded oncolytic virus and expressing immunomodulators have therapeutic efficacy in advanced melanomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 77.