bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2817: Metabolic heterogeneity in breast cancer integrative clusters to screen metabolic vulnerabilities for diagnosis and treatment response
Authors: Ros Susana , Wright Alan J. , Bulat Flaviu , Greenwood Wendy , Hu De-en , Callari Maurizio , Chia Ming Li , Serra Violeta , Rueda Oscar , Bruna Alejandra , Caldas Carlos , Brindle Kevin M. 
Published: July 2021

Abstract
Introduction: Metabolic adaptation occurs in transformed cells and can be exploited clinically for diagnosis and disease monitoring. Metabolic profiles can be influenced by genetic heterogeneity, both within and between tumors. Breast tumors show considerable intra and inter tumor genomic heterogeneity, which partly accounts for the variable clinical course of the disease and response to treatment. Imaging tumor metabolism may provide a metabolic signature that can be used to stratify patients.
Methods: We have investigated eight patient-derived xenograft (PDX) models of breast cancer to determine whether metabolic imaging can be linked to different “integrative clusters” (Int-Cluster), which are defined by their distinctive genomic profiles and clinical outcomes. Metabolic imaging was performed using PET measurements of the uptake, phosphorylation, and trapping of the glucose analog, 2-deoxy-2-[18F]fluorodeoxyglucose ([18F]FDG), catalyzed by hexokinase II, and 13C magnetic resonance spectroscopy (MRS) measurements of hyperpolarized 13C label exchange between [1-13C]pyruvate and the endogenous tumor lactate pool, catalyzed by lactate dehydrogenase A.
Results: Lactate labelling was higher in Int-Clusters dominated by ER- basal-like PDXs from patients with a poor short-term prognosis. Lower levels of lactate labelling were observed in Int-Clusters dominated by estrogen receptor positive (ER+) PDXs and the Pam50 subtypes, Luminal A and B, from patients which have an intermediate to good prognosis. More importantly, tumors that had a similar genomic profile nevertheless showed differences in lactate labeling, that was not observed in the [18F]FDGPET measurements. Although lactate labelling was low in the ER+ tumor models, decreases in lactate labeling could be used to detect treatment response, for example to drugs targeted at the most frequently mutated oncogene in this tumor subtype, PI3KCA.
Discussion: These results illustrate the potential importance of metabolism-based stratification of breast cancer and demonstrate that metabolic imaging can provide diagnostic information that could be important for non-invasive diagnosis and for designing and monitoring therapeutic strategies.
Citation Format: Susana Ros, Alan J. Wright, Flaviu Bulat, Wendy Greenwood, De-en Hu, Maurizio Callari, Ming Li Chia, Violeta Serra, Oscar Rueda, Alejandra Bruna, Carlos Caldas, Kevin M. Brindle. Metabolic heterogeneity in breast cancer integrative clusters to screen metabolic vulnerabilities for diagnosis and treatment response [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 2817.
Abstract 2820: A human Claudin-3 monoclonal antibody as a potential multimodal theranostic probe in ovarian cancer
Authors: Oh Sera , Yang Hobin , Oh Ho Rim , Lee Chul-Hee , Kim Young-Hwa , Cheon Gi Jeong , Kang Keon Wook , Shin Young Kee , Youn Hyewon 
Published: July 2021

Abstract
Introduction: Claudin-3 (CLDN3), a tight junction protein, regulates cell-to-cell interactions in epithelial or endothelial cell sheets. During tumorigenesis, epithelial cells are transformed and tumor cells proliferate through out-of-plane division, resulting in external exposure of CLDN3. This alteration of CLDN3 expression is associated with cancer progression, correlating with malignancy in various carcinomas. Since CLDN3 is particularly overexpressed in most ovarian cancers and used as an effective diagnostic marker, we tested the possibility of using a CLDN3-specific antibody as a novel imaging probe.
Materials and Methods: After reducing the CLDN3 specific antibody to expose the -SH group, click chemistry was used to conjugate radioactive isotope 111In or fluorescent protein FNR648. Human ovarian cancer OVCAR-3 cells and human glioblastoma (U87MG) cells were used as CLDN3 positive and negative cells, respectively. Flow cytometry was used to measure the binding of CLDN3 IgG1 monoclonal antibody to theses cell lines. To establish xenograft model, OVCAR-3 cells were injected subcutaneously into the mice. 111In-labeled CLDN3 antibody (370 kBq/50 μl) was administered intravenously to mice with. After 24 hours, organs including tumor were excised and measured with a γ-counter. Images were acquired with IVIS and SPECT/CT.
Results: The labeling efficiency of NOTA-111In or antibody-NOTA-111In was 98.52% or 100%, respectively. FNR648 labeled CLDN3 antibody was bound to the cell surface of OVCAR-3 at 83.4% and to U87MG at 5.7%, respectively. In OVCAR-3 tumor xenografted mice, mice injected with CLDN3 antibody showed 2.5-fold higher tumor uptake (20.4 ± 7.4% ID/g) than mice injected with human IgG (8.8 ± 2.6% ID/g) at 24 hour p.i. The fluorescence signal of CLDN3 antibody peaked at 24 hour p.i.
Conclusion: We successfully conjugated radioisotope and fluorescent protein using the CLDN3 specific antibody. Since the specific binding of CLDN3 antibodies to OVCAR-3 tumors has been validated in a mouse model and diagnostic radionuclides can be replaced with therapeutic radionuclides, this human monoclonal antibody could be used as a useful theranostic probe.
Citation Format: Sera Oh, Hobin Yang, Ho Rim Oh, Chul-Hee Lee, Young-Hwa Kim, Gi Jeong Cheon, Keon Wook Kang, Young Kee Shin, Hyewon Youn. A human Claudin-3 monoclonal antibody as a potential multimodal theranostic probe in ovarian cancer [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 2820.
Abstract 2833: Mesothelin expression in human tumor types: a tissue microarray study on more than 13,000 tumor samples
Authors: Weidemann Sören , Gorbokon Natalia , Höflmayer Doris , Möller Katharina , Dum David , Luebke Andreas , Kluth Martina , Hube-Magg Claudia , Blessin Niclas , Sauter Guido , Izbicki Jakob , Simon Ronald , Steurer Stefan , Marx Andreas , Krech Till , Jansen Kristina , Lennartz Maximilian 
Published: July 2021

Abstract
Mesothelin is a glycoprotein which is normally expressed in only few non-vital tissues. Due to its membranous location and expression in various cancer types, it represents an attractive molecule for target-specific cancer therapies. To examine, what tumor types might benefit most from anti-mesothelin therapies, a set of tissue microarrays containing samples from 13,298 tumors from 122 different tumor types and 608 samples from 76 different normal tissue categories were analyzed for mesothelin expression by immunohistochemistry. Sixty-six (54%) of these 122 tumor types and subtypes showed at least occasional weak staining, including 49 tumor types with at least one strongly positive sample. Tumor types with highest prevalence of mesothelin positivity included ovarian cancers (serous 97%, clear cell 83%, endometroid 77%, mucinous 71%, Müllerian mixed tumors 65%), pancreatic adenocarcinoma (81%), endometrial cancers (clear cell 71%, serous 57%, Müllerian mixed tumors 50%, endometroid 45%), malignant mesothelioma (71%), and lung adenocarcinoma (55%). Mesothelin positivity was particularly rare or absent in urothelial carcinoma (10% positive out of 925), breast cancer (6% of 1,285), renal cell cancer (7% of 1,049), adenocarcinoma of the prostate (0 of 498), thyroid carcinomas (0 of 238), and soft tissue tumors (0 of 920). Significant associations with patient outcome or parameters of malignancy were not observed in 1,072 breast cancers of no special type, 925 urinary bladder cancers, 386 serous ovarian cancers, 266 lung cancers or 373 stomach cancers. Taken together, our systematic and highly standardized analysis identified numerous clinically important cancer types with frequent and high level mesothelin expression. These tumor types might benefit most from future anti-mesothelin therapies. The prognostic relevance of mesothelin appears to be low in the analyzed tumor types.
Citation Format: Sören Weidemann, Natalia Gorbokon, Doris Höflmayer, Katharina Möller, David Dum, Andreas Luebke, Martina Kluth, Claudia Hube-Magg, Niclas Blessin, Guido Sauter, Jakob Izbicki, Ronald Simon, Stefan Steurer, Andreas Marx, Till Krech, Kristina Jansen, Maximilian Lennartz. Mesothelin expression in human tumor types: a tissue microarray study on more than 13,000 tumor samples [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 2833.
Abstract 2857: Asparagine synthetase regulate β-catenin dependent lung cancer metastasis
Authors: Cai Dong-Jing , Hu Cheng-Ping , li Li , Zhang Zi-Yu , Li Yuan-Mao , Li Min 
Published: July 2021

Abstract
Objective: Lung cancer was a malignant tumor with high morbidity and mortality. The lead cause of lung cancer-related death was metastasis. Asparagine synthetase (ASNS) that was a key enzyme to convert glutamine to asparagine played important role in cell metabolism. Based on previous metabolomics data, the high level of asparagine synthase was significantly correlated with tumor metastasis. The purpose of this study was to investigate the role of asparagine synthase in lung cancer metastasis, furthermore for anti-cancer target therapy.
Method: For pursuing high ASNS correlated to metastasis, a cohort were collected from Xiangya hospital. And selected paired lung cancer cell lines were used for discovering potential molecular interactions. Importantly, some key molecules or pathways were found by cell biology study and bioinformatics analysis. In the part of cellular and molecule study, Transwell, scratch test, Western blot, immunofluorescence, immunohistochemistry and co-immunoprecipitation experiments were used. The results of the inquiry were validated by using a mouse metastasis model.
Results: With provided from Xiangya hospital and TCGA cohort, we could validate high ASNS had relations to patient's metastasis and survival. In part of cell biology study, high wild-type ASNS could promote lung cancer cell metastasis and proliferation in vivo and vitro. Overexpression of amidotransferase-dysfunction ASNS had partially potential to drive metastasis but have nothing to increase cell proliferation. Furthermore, Wnt/β-catenin cascades were responsible for tumor mestasis among wild-type and amidotransferase-mutated type groups. The accumulation and nuclear location of β-catenin definitely depend on high ASNS expression even with amidotransferase mutation. With processing, ASNS possible interacted with key proteins located in Wnt/β-catenin signaling pathway to mediate signal conduction. But the activation of ASNS amidotransferase was necessary to promoted tumor proliferation.
Conclusion: ASNS promoted metastasis by mediating Wnt/β-catenin signaling conduction even without ASNS amidotransferase activity, while cell proliferation was required for amidotransferase function. Maybe dual inhibition of ASNS and Wnt/β-catenin would be an effective target for anti-tumor metastasis and proliferation.
Key Words: ASNS, metastasis, lung cancer, β-catenin
Citation Format: Dong-Jing Cai, Cheng-Ping Hu, Li li, Zi-Yu Zhang, Yuan-Mao Li, Min Li. Asparagine synthetase regulate β-catenin dependent lung cancer metastasis [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 2857.
Abstract 2859: Understanding metastatic cancer biology
Authors: Christensen Ditte Sigaard , Ahrenfeldt Johanne , Birkbak Nicolai Juul 
Published: July 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.
Abstract 2860: NOSTRIN-induced inhibition of pancreatic cancer progression involves CCBE1 in an eNOS-independent manner
Authors: Zhang Lin , Yang Shouhui , Wang Limin , He Peijun , Yuuki Ohara , Valenzuela Paloma , Tang Wei , Gaedcke Jochen , Ghadim B. Michael , Gaida Matthias M. , Bergmann Frank , Alexander H. Richard , Hanna Nader , Ryan Brid M , Hussain S. Perwez 
Published: July 2021

Abstract
NOSTRIN represses disease aggressiveness in pancreatic cancer by suppressing eNOS-mediated NO production. We have further explored the NOSTRIN-mediated eNOS-independent pathways that contribute to its tumor inhibitory function. Gene expression analysis identified CCBE1 as a target of NOSTRIN. We provide experimental and clinical evidence that NOSTRIN functions a negative regulator in pancreatic cancer progression through inhibiting the expression of CCBE1. Furthermore, CCBE1 expression is regulated by NOSTRIN independent of eNOS. NOSTRIN attenuates protein-protein interaction between ABL1 and PKD2 resulting in the suppression of PKD2 and NFkB p50 activation. Inhibition of PKD2 and NFkB p50 activation results in the suppression of CTCF, which is as a transcription factor of CCBE1. CCBE1 expression is decreased as the down-stream gene of CTCF. Taken together, CCBE1 may be a potential therapeutic target in pancreatic cancer.
Citation Format: Lin Zhang, Shouhui Yang, Limin Wang, Peijun He, Ohara Yuuki, Paloma Valenzuela, Wei Tang, Jochen Gaedcke, B. Michael Ghadim, Matthias M. Gaida, Frank Bergmann, H. Richard Alexander, Nader Hanna, Brid M Ryan, S. Perwez Hussain. NOSTRIN-induced inhibition of pancreatic cancer progression involves CCBE1 in an eNOS-independent manner [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 2860.
Abstract 2873: Comparison of metastatic and nonmetastatic breast cancer cell survival in glutamine depleted extracellular matrix detached conditions
Authors: Garg Kanika K. , Sheeley Madeline , Teegarden Dorothy 
Published: July 2021

Abstract
For women, breast cancer is the most diagnosed cancer, with metastasis being the primary cause of most breast cancer-related deaths. During metastasis, cells detach from the extracellular matrix (ECM) to move to a secondary site. Unlike normal cells, metastatic cells are resistant to cell death upon ECM detachment. The amino acid glutamine is used as an energy source during metastatic progression via replenishing the TCA cycle. Breast cancer cells have decreased viability in the absence of glutamine, but the effect of glutamine in ECM detached conditions in metastatic cells is not known. We hypothesize that metastatic and non-metastatic cells have a decreased viability in ECM detachment in glutamine deprived conditions. In this study, metastatic MCF10CA1a cells and non-metastatic Harvey-ras oncogene transfected MCF10A-ras cells were employed. As expected, in ECM detached conditions, the MCF10A-ras cells had a greater decrease in viability (58.4%) in comparison to the MCF10CA1a cells (32.7%). However, in glutamine deprived conditions, the MCF10CA1a cells decrease in viability was 15.2% greater compared to the MCF10A-ras cells. mRNA expression of the major glutamine transporter, SLC1A5, was decreased in detached conditions in both cell lines, but to a greater extent in the MCF10A-ras cells (70.04%) compared to the MCF10CA1a cells (20.15%). Additionally, mRNA expression in detached conditions of glutamate dehydrogenase, the enzyme that metabolizes the downstream glutamine metabolite glutamate to α-ketoglutarate (αKG), was decreased by 77% in the non-metastatic cells, but increased by 23% in the metastatic cells. Additionally, mRNA expression of GOT1, a gene which encodes for the transaminase enzyme which synthesizes αKG and aspartate from glutamate and oxaloacetate, decreased 73% in detached conditions in the non-metastatic cells but was unchanged in the metastatic cells. Moreover, following detachment the glutamine synthesizing enzyme, glutamine synthetase mRNA expression was increased by 81.92% in the non-metastatic cells and 88.43% in the metastatic cells. In summary, the greater effect of glutamine depletion on viability, and the maintained expression of glutamine metabolizing enzymes in the metastatic cells suggest greater dependence on glutamine metabolism in ECM detached conditions compared to non-metastatic cells. Comparison of metastatic and non-metastatic breast cancer cells will provide insights to direct the development of new targets for the prevention of breast cancer metastasis.
Citation Format: Kanika K. Garg, Madeline Sheeley, Dorothy Teegarden. Comparison of metastatic and nonmetastatic breast cancer cell survival in glutamine depleted extracellular matrix detached conditions [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 2873.
Abstract 2882: Coronin 1B overexpression promotes invasion of HPV- HNSCC
Authors: Allen Jessica L. , Walk Elyse L. , Rhodes Kristen L. , Markwell Steven M. , Papenberg Brenen W. , Wu Hong , Garcia Marileila , Bear James E. , Weed Scott A. 
Published: July 2021

Abstract
Introduction: Amplification of chromosome 11q13 is the most common DNA aberration in human papilloma virus negative (HPV-) head and neck squamous cell carcinoma. (HSNCC). The 11q13 region encodes various genes known to enhance invasion and drive tumor progression. CORO1B (coronin 1B) flanks the core 11q13 region and is amplified in 7-14% of HNSCC cases. Coronin 1B governs cell motility in fibroblasts by negatively regulating the ability of the Arp 2/3 nucleator cortactin to stabilize the actin cytoskeleton during mesenchymal cell migration. This study seeks to determine the impact of CORO1B amplification and protein overexpression in driving HNSCC progression.
Experimental Procedures: Two patient cohorts were used to assess the impact of CORO1B amplification or overexpression on patient outcome. In addition, HNSCC cell lines lacking or overexpressing coronin 1B were assayed for invadopodia function using gelatin degradation assays. Three-dimensional invasion was analyzed using tumor spheroid and organotypic assays. Invasive and cervical lymph node metastatic potential of CORO1B was evaluated using knockdown and overexpression cells in orthotopic tongue models.
Data Summary: CORO1B amplification and overexpression in patient tumors correlates with enhanced patient decline. Coronin 1B-null cell lines display decreased invadopodia function, with a 30-60% decrease in extracellular matrix-mimicking gelatin degradation. HNSCC tumor spheroids lacking coronin 1B expression decreased 3D invasion in native collagen I, while overexpression enhanced invasive capabilities in both tumor spheroids and organotypic cultures. Coronin 1B knockdown cells show decreased lymph node metastasis, while mice with tumors overexpression coronin 1B have enhanced lymph node metastasis and decreased survival. CORO1B amplification protein overexpression predict poor overall patient survival.
Conclusion: The identification of coronin 1B overexpression as an important mediator in promoting HNSCC invasive processes may define a novel aggressive subset of locoregional involved HNSCC, warranting enhanced clinical intervention.
Citation Format: Jessica L. Allen, Elyse L. Walk, Kristen L. Rhodes, Steven M. Markwell, Brenen W. Papenberg, Hong Wu, Marileila Garcia, James E. Bear, Scott A. Weed. Coronin 1B overexpression promotes invasion of HPV- HNSCC [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 2882.