bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2007: Evaluation of the antitumor activity of ca102l, a hyaluronic acid and lenalidomide conjugate, in multiple myeloma
Authors: Tchaparian Eskouhie , Lin Star 
Published: April 2023

Abstract
Multiple Myeloma (MM) is a rare and incurable hematological malignancy. Despite emerging treatments, there is still an unmet medical need for novel therapeutics to target the inherent and acquired drug resistance associated with MM. CA102L is a conjugate of hyaluronic acid and an anticancer drug designed to deliver its payload, Lenalidomide (Len), to MM cells via the CD44 receptor. Lenalidomide is used as a front-line therapy in MM; The CD44 receptor is highly expressed in MM and is associated with advanced clinical stages and poor survival. In addition to the enhancement of the therapeutic efficacy of Len, a reduction in off-target toxicity is suggested. The present study was designed to evaluate the efficacy of CA102L in MM and identify its potential mechanism of action. The antitumor efficacy of CA102L was tested (in vitro and in vivo) in two MM cancer models, IM-9 and NCI-H929. Protein expression was used to identify the potential targets of CA102L in MM. Both in in vitro and in vivo investigations, CA102L as a single agent displayed an improvement in potency in MM models. In CB-17 SCID mice bearing either IM-9 or NCI-H929 cells, tumor growth inhibition was significantly higher (P&lt 0.05) in the CA102L (25 mg/kg) treated group compared to that of Len (25 mg/kg). Further, CD31 and hematoxylineosin (H&E) staining of tumor sections from the IM-9 xenograft mice treated with CA102L resulted in greater antiangiogenic and antiproliferative effects compared to the other groups. Prolonged survival was also observed in CA102L monotherapy in H929 models relative to Len (56% vs 11%). Interestingly, in H929 cell viability studies, CA102L and Len at 400μM showed comparable cytotoxicity with a 60% cell growth inhibition, while superior activity was noted against IM-9-treatments (CA102L 60%, Len 20%). Western blot studies confirmed CRBN as the primary target of CA102L. In summary CA102L as a single agent, exhibited greater efficacy than Len in preclinical MM models, thus representing a promising potential therapeutic strategy for MM. Studies presently are ongoing to further evaluate CA102L’s preclinical profile to advance the candidate into the clinic.
Citation Format: Eskouhie Tchaparian, Star Lin. Evaluation of the antitumor activity of ca102l, a hyaluronic acid and lenalidomide conjugate, in multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2007.
Abstract 201: Establishment of 3D co-culture spheroid model for in- vitro drug screening
Authors: Nelson Christella J. , Cheriyan Vino T. , Pandit Abhishek , Francis Joseph , Tackett Alan 
Published: April 2023

Abstract
Melanoma is an aggressive form of skin cancer that accounts for 75% of deaths of all skin cancers in the United States. Moreover, the number of cases is increasing at an alarming rate than any other cancer worldwide. But what is more alarming is the lack of chemo preventive or therapeutic drugs that are easily accessible to people and the absence of an efficient, effective and reliable model or platform for drug screening. A growing scientific and observational analyses suggests that antioxidants contain in blueberry inhibit tumor growth, and help slow down esophageal, lung, mouth, pharynx, endometrial, pancreatic, prostate, and colon cancers. Lately, the use of 3D multicellular spheroid culture has become a potential link to bridge the gap between monolayer culture and animal model. The treatment of blueberry extract (1mg) on the spheroids of A375 cells showed a disintegration of these spheroids and reduction in their growth. To optimize the culture conditions further herein, we used a novel three-dimensional (3D) coculture system with melanoma (A375), human fibroblast (HF-1) and Human umbilical endothelial cells (HUVECs) to study the effectiveness of drug in vitro. The multicellular nature of the coculture spheroid stimulates the microenvironment of the original tumor which makes it more efficient in drug screening process. The immunofluorescence assay on the 3D spheroid co-culture shows the interactions among these three cells which mimics the tumor microenvironment. We further analyzed the combination of blueberry extract and resveratrol which proved the effectiveness of blueberry extract as a potential chemosensitizer with resveratrol for skin cancer therapy. The complementary effect on the inhibition of A375 cell proliferation were observed when treated with 8 mg blueberry and 10 mM of resveratrol. The results of MTT assay indicates that the blueberry extracts showed potential cytotoxic activity against A375 cell line. 3D spheroid assay and 3D spheroid co-culture assays further confirmed the effectiveness of blueberry and resveratrol combination. Therefore, this platform could be applied for in vitro based drug screening studies. To conclude cytotoxic effects of the blueberry extract in human melanoma cells make them good candidates for further pharmacological studies to discover effective drugs for melanoma therapy.
Citation Format: Christella J. Nelson, Vino T. Cheriyan, Abhishek Pandit, Joseph Francis, Alan Tackett. Establishment of 3D co-culture spheroid model for in- vitro drug screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 201.
Abstract 2066: Visualization and analysis of cancer genomics data using UCSC Xena
Authors: Goldman Mary , Craft Brian , Zhu Jingchun , Haussler David 
Published: April 2023

Abstract
UCSC Xena (http://xena.ucsc.edu/) is a web-based visual integration and exploration tool for multi-omic data and associated clinical and phenotypic annotations. Researchers can easily view and explore public data, their own private data, or both using the Xena Browser. Private data are kept on the researcher's computer and are never uploaded to our public servers. We support Mac, Windows, and Linux.
Questions Xena can help you answer:
* Is overexpression of this gene associated with lower/higher survival?
* What genes are differentially expressed between these two groups of samples?
* What is the relationship between mutation, copy number, expression, etc for this gene?
Xena showcases seminal cancer genomics datasets from TCGA, the Pan-Cancer Atlas, GDC, PCAWG, ICGC, and more; a total of more than 1500 datasets across 50 cancer types. We support virtually any type of functional genomics data: SNPs, INDELs, copy number variation, gene expression, ATAC-seq, DNA methylation, exon-, transcript-, miRNA-, lncRNA-expression and structural variants. We also support clinical data such as phenotype information, subtype classifications and biomarkers. All of our data is available for download via python or R APIs, or using our URL links.
Our signature Visual Spreadsheet view shows multiple data types side-by-side enabling discovery of correlations across and within genes and genomic regions. We also have dynamic Kaplan-Meier survival analysis, powerful filtering and subgrouping, differential gene expression analysis, charts, statistical analyses, genomic signatures, and the ability to generate URLs to live views. We link out to the UCSC Genome Browser as well as MuPIT/CRAVAT and TumorMap.
New features include:
* Genome-wide differential gene expression analysis
* Select samples directly from the screen for filtering and creating subgroups
* Violin plots on any numerical data
* Loading of Microsoft Excel files
Our beta prototype site for visualizing single-cell data delivers million-cell-scale multi-omics data for interactive visualization in a web browser. Contact us for access to our beta prototype site.
If you use us please cite our publication in Nature Biotechnology: https://www.nature.com/articles/s41587-020-0546-8
Citation Format: Mary Goldman, Brian Craft, Jingchun Zhu, David Haussler. Visualization and analysis of cancer genomics data using UCSC Xena [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2066.
Abstract 2071: Detecting somatic DNA copy number differences with DiNAMIC.Duo
Authors: Walter Vonn , Choi Hyo Young , Zhao Xiaobei , Gao Yan , Holt Jeremiah , Hayes D. Neil 
Published: April 2023

Abstract
Somatic DNA copy number alterations (CNAs) arise in tumor tissue because of underlying genomic instability. Recurrent CNAs that occur in the same genomic region across multiple independent samples are of interest to researchers because they may contain genes that contribute to the cancer phenotype. However, differences in copy number states between cancers are also commonly of interest, for example when comparing tumors with distinct morphologies in the same anatomic location. Current methodologies are limited by their inability to perform direct comparisons of CNAs between tumor cohorts, and thus they cannot formally assess the statistical significance of observed copy number differences or identify regions of the genome where these differences occur. We introduce the DiNAMIC.Duo R package that can be used to identify recurrent CNAs in a single cohort or recurrent copy number differences between two cohorts, including when neither cohort is copy neutral. The TCGA studies of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) identified statistically significant CNAs in many known cancer-related genes, including gains of EGFR and losses of CDKN2A in each tumor type separately. By directly comparing the two cohorts, DiNAMIC.Duo detects statistically significant copy number differences for CDKN2A, thus suggesting that losses are more pronounced in LUSC; in contrast, differences for EGFR are not statistically significant, which suggests similar levels of gain. Existing methods that detect recurrent CNAs in a single cohort cannot make this distinction. Recent studies have leveraged TCGA data to find known cancer genes in chr3q, chr14q13, and chr20q11 that are differentially expressed in LUAD vs. LUSC. DiNAMIC.Duo identifies statistically significant copy number differences in these regions, which suggests that the observed expression changes may be driven by underlying differences in copy number.
Citation Format: Vonn Walter, Hyo Young Choi, Xiaobei Zhao, Yan Gao, Jeremiah Holt, D. Neil Hayes. Detecting somatic DNA copy number differences with DiNAMIC.Duo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2071.
Abstract 2082: DNAfusion: An R/Bioconductor package for increased sensitivity of detecting EML4-ALK gene fusions in liquid biopsies from cancer patients
Authors: Maansson Christoffer Trier , Andersen Emma Roger , Ulhoi Maiken Parm , Meldgaard Peter , Sorensen Boe Sandahl 
Published: April 2023

Abstract
EML4-ALK gene fusions are oncogenic drivers in non-small cell lung cancer (NSCLC). Liquid biopsies containing circulating tumor DNA (ctDNA), including EML4-ALK, can be used to study tumor dynamics with next-generation sequencing (NGS). However, the sensitivity of EML4-ALK detection in liquid biopsies varies between different pipelines and analysis tools. We developed an R/Bioconductor package, DNAfusion, which can be applied to BAM files generated by commercially available NGS pipelines, such as AVENIO. 48 blood samples from a training cohort consisting of 41 stage IV EML4-ALK positive NSCLC patients and 7 healthy controls were used to develop DNAfusion. DNAfusion detected EML4-ALK in significantly more samples compared to AVENIO (sensitivity = 61.0% vs. 36.6%, P = 0.046). The newly identified EML4-ALK positive patients were verified using droplet digital PCR. DNAfusion was subsequently validated in a blinded validation cohort comprising 24 EML4-ALK positive and 24 EML4-ALK negative stage IV NSCLC patients. DNAfusion detected significantly more EML4-ALK individuals in the validation cohort compared to AVENIO (sensitivity = 62.5% vs. 29.2%, P = 0.042). DNAfusion demonstrated a specificity of 100% in both the training and the validation cohorts. Monitoring EML4-ALK variants with AVENIO and DNAfusion in serial blood samples from 24 stage IV EML4-ALK positive patients during treatment (n = 72), revealed that DNAfusion can detect EML4-ALK variants at clinically critical timepoints, otherwise missed by AVENIO. Here we present DNAfusion, which increases sensitivity of EML4-ALK detection in liquid biopsies and can be implemented downstream of commercially available NGS pipelines. The high sensitivity of DNAfusion is a necessity for analytical tools used to monitor ctDNA in serial plasma samples in order to implement liquid biopsies in the clinic. The simplistic way of operating the R package makes it easy to set up in the clinical setting enabling wider expansion of liquid biopsy and NGS based diagnostics.
Citation Format: Christoffer Trier Maansson, Emma Roger Andersen, Maiken Parm Ulhoi, Peter Meldgaard, Boe Sandahl Sorensen. DNAfusion: An R/Bioconductor package for increased sensitivity of detecting EML4-ALK gene fusions in liquid biopsies from cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2082.
Abstract 2161: Quinolinic acid phosphoribosyl transferase (QPRT) is an essential liability of non-small cell lung cancer
Authors: Kashfi Hossein , Ward Nathan , Ilter Didem , Drapela Stanislav , Falzone Aimee , Gardell Stephen , DeNicola Gina M. , Gomes Ana P. 
Published: April 2023

Abstract
Lung cancer is the second most diagnosed type of cancer and the leading cause of cancer-related mortality. 85% of all lung cancer cases are non-small cell lung cancer (NSCLC), a large proportion of which are only diagnosed at advanced stages (II-IV) due to lack of early diagnostic techniques. Standard first-line treatment for late-stage inoperable NSCLC still is chemotherapy regiments. However, most NSCLC patients fail to respond to these regimens or relapse upon treatment. Thus, there is a pressing need to identify novel therapeutic targets that can more effectively treat NSCLC. Quinolinic acid phosphoribosyl transferase (QPRT) is a rate-limiting enzyme in the tryptophan catabolic pathway which fuels de novo NAD+ production, whose expression as previously been shown to have a prognostic value in certain cancers. Here, we demonstrate that high QPRT levels is a feature of a large proportion of NSCLC cell lines and that QPRT induction occurs in genetically engineered models of NSCLC (KP and KL) when compared to the normal lung. Considering the critical role of NAD+ levels to enable high rates of proliferation, we hypothesized that QPRT induction enables lung cancer cells to thrive. Strikingly, QPRT knockdown in a panoply of NSCLC cell lines results in pronounced suppression of tumor cells both in 2D and 3D conditions. Interestingly, we observe that QPRT suppression does not affect proliferation or cell cycle progression but rather due to pronounced induction of cell death. Surprisingly, while we observed DNA damage upon QPRT suppression, NAD+ levels were not affected by QPRT suppression indicating that QPRT’s effects in NSCLC are independent of its contribution to the NAD+ pools. Together, our results point for QPRT as a novel and effective therapeutic target for NSCLC.
Citation Format: Hossein Kashfi, Nathan Ward, Didem Ilter, Stanislav Drapela, Aimee Falzone, Stephen Gardell, Gina M. DeNicola, Ana P. Gomes. Quinolinic acid phosphoribosyl transferase (QPRT) is an essential liability of non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2161.
Abstract 2361: Prevalence of mature tertiary lymphoid structures and association with tumor mutational burden in patients with solid tumors
Authors: Brunet Maxime , Vanhersecke Lucile , Loarer Francois Le , Soubeyran Isabelle , Italiano Antoine 
Published: April 2023

Abstract
Background: Mature Tertiary Lymphoid Structures (mTLS) are organized lymphoid structures containing B-lymphocytes admixed to CD23+ follicular dendritic cells, which play a key role in antitumor immune response. We and others have demonstrated that presence of mature TLS is higly predictive of benefot of anti-PD1/PDL1 antibodies in patients with solid tumors (Vanhersecke et al Nature Cancer 2021, Italiano et al Nature Medicine 2022). However, the relative prevalence of mature TLS in the different tumor types has not been investigated with an uniform methodological approach.
Methods: We screened the presence of mature TLS (mTLS) on tumor samples from patients included in an institutional molecular profiling program (BIP, NCT02534649). mTLS were screened using HES, CD20 (clone L26, Ventana) and CD23 (clone 1B12, Novocastra) stainings, performed on serial sections. TLS were defined as lymphoid aggregates of CD20+ B-lymphocytes of more than 50 immune cells within 1mm of the tumor front. mTLS were defined as TLS containing either a visible germinal center on HES or a meshwork of CD23+ follicular dendritic cells or isolated CD23+ dendritic cell if the cell harbored a morphology fitting with dendritic differentiation. If plasma sample of patient was available, bTMB was assessed by Foundation Medicine, with bTMB-high defined as at least 10 mutations/megabase (mut/Mb).
Results: We characterized 1,393 samples. mTLS were present in 467 cases (33.5%) across all tumor histotypes: 36.2% of carcinoma (N = 392/1080 cases), 24.8% of sarcoma (N =69/209 cases) and 25% of neuroendocrine tumor (N= 4/12 cases).
Among 569 cases with evaluable bTMB, the proportion of patients with bTMB-high was significantly higher in the mTLS group (16.7%, N=31/185) compared to absence of mTLS group (8.5%, N=30/353) (p=0.036).
Conclusion: mTLS are present in variable proportions in almost all tumor types even in those considered as resistant to current immune checkpoint inhibitors.
Prostate Bladder Kidney Head and neck Gynecologic (except ovary) Ovary mTLS+% of patients (N) 34% (28) 33% (19) 25% (6) 53% (17) 33% (19) 44% (26) mTLS-% of patients (N) 66% (55) 67% (38) 75% (18) 47% (15) 67% (39) 55% (32) Upper gastro intestinal tract Pancreatic Biliary tract Breast Thyroid Sarcoma mTLS+% of patients (N) 37% (19) 50% (13) 40% (21) 30% (38) 49% (24) 25% (69) mTLS-% of patients (N) 63% (33) 50% (13) 60% (32) 70% (90) 51% (25) 75% (209)
Citation Format: Maxime Brunet, Lucile Vanhersecke, Francois Le Loarer, Isabelle Soubeyran, Antoine Italiano. Prevalence of mature tertiary lymphoid structures and association with tumor mutational burden in patients with solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2361.
Abstract 2368: Pilot characterization of the salivary microbiome in pediatric cancer patients
Authors: Garduño Alejandra Beatriz Cervantes , García Milca de la O , Nagano Jesús Adolfo Yamamoto , Cardos Rocio Del Socorro Cardenas , Hidalgo Liliana Velasco , García Blanca Olivia Almazán , Celis Gabriela Elisa Mercado 
Published: April 2023

Abstract
Microbial populations in the oral cavity have been linked with some malignant diseases, however, the evidence in this regard is poor. Oral microorganisms increase cytokine production and other mediators may be related to carcinogenesis. However, the role of the oral microbiome and its taxonomic composition in pediatric cancer has not been studied. We report a pilot study to assess to compare the microbial diversity of saliva in pediatric patients with cancer and without cancer. Materials and methods: Total saliva samples were collected from 3 cases and 3 controls with cancer, with prior informed consent and assent. Metagenomic sequencing was performed and data was analyzed using CosmosID bioinformatics software. Results: the mean age for the cases is 8.67 years and for the 8-year-old controls, the percentage by sex was 33.3% male and 66.6% female. In the shared analysis of bacterial diversity we found a total of 93 genera, the three genera with the highest abundance in the cases were: Prevotella, Streptococcus and Morococcus. A total of 153 species with differential abundance were identified, in the cases the species with the highest abundance were: Neisseria mucosa, Vellodela dispar, Prevotella melaninogenica and Morococcus cerebrosus. We found differences in bacterial diversity and abundance between cases and controls. The main species that we found in greater abundance in the cases have been related to various processes in the oral cavity, Streptococcus sp increases child caries, Prevotella melaninogenica a broad profile of resistance to families of antibiotics, and Morococcus cerebrosus has been associated with the mineralization of the supragingival dental plaque. Finally Vellodela dispar has been associated with bacteremia in cancer patients. In this pilot study a small number of samples were analyzed, the differences in bacterial diversity should be confirmed by conducting studies with a larger number of samples.
Citation Format: Alejandra Beatriz Cervantes Garduño, Milca de la O García, Jesús Adolfo Yamamoto Nagano, Rocio Del Socorro Cardenas Cardos, Liliana Velasco Hidalgo, Blanca Olivia Almazán García, Gabriela Elisa Mercado Celis. Pilot characterization of the salivary microbiome in pediatric cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2368.