bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2459: Altered bioenergetics profile in prostate cancer cells treated with andrographolide
Authors: Sosa Jesus , Vázquez María Sánchez , Ayala-Peña Sylvette , Ramos Carlos Torres , Ferrer Magaly Martínez 
Published: July 2021

Abstract
Prostate cancer (PCa) is the second leading cause of cancer deaths in the United States alone. An emerging area of cancer therapeutics is the combination of the standard-of-care treatment with natural products. Andrographolide, a labdane diterpenoid and the main bioactive component of the medicinal plant Andrographis paniculata, has shown a wide range of therapeutic potential, including cancer. Previous studies from our laboratory have demonstrated that Andrographolide induces a DNA damage response, including ATM gene upregulation, involving cell growth suppression, cell cycle arrest, and apoptosis in PCa in vitro. The ATM gene is an important regulator of p53 and is consider a master switch for the p53-family member p63. The p63 is a natural marker of the basal lamina in the normal prostate, while its expression is lost in 99% of prostatic adenocarcinomas. Like p53, the p63 protein is implicated in tumor suppression and inhibition of metastasis, and also plays a role in energy metabolism. In this study, we aim to (1) determine the role of Andrographolide on the expression of p63, and (2) determine the bioenergetics profile of PCa cells. Androgen-dependent (22Rv1) and androgen-independent (PC3) PCa cell lines were treated with Andrographolide (25µM) for 24 h and 48 h. The gene expression of TP63 was assessed by real-time quantitative PCR (RT-qPCR). At the protein level, the expression of p63 was evaluated by immunofluorescence. The bioenergetics profile was performed using the Agilent Seahorse XF Real-Time ATP Rate Assay to determine the ATP production from glycolysis and mitochondria in living PC3 and 22Rv1 PCa cells. RT-PCR analysis showed a significant upregulation of the TP63 gene with a fold-change of 2.2 (p&lt; 0.05) and immunofluorescence analysis showed an increase in expression of p63 protein with a fold-change of 1.8 (p&lt; 0.05) in 22Rv1 cells treated with Andrographolide. The bioenergetics profile of PC3 cells, 48 h after Andrographolide treatment, revealed a shift in the cytoplasmic to mitochondrial ATP production rate from 54.4% to 72.6% and from 45.6% to 27.4%, respectively. Similar results were obtained in 22Rv1 cells. These results confirmed that Andrographolide induces the expression of the tumor protein p63 in androgen-dependent 22Rv1 PCa cells and alters the bioenergetics profile of both PC3 and 22Rv1 PCa cells. Our findings suggest a novel mechanism in which Andrographolide promotes the expression of p63 as in normal cells, and transforms the bioenergetics by increasing glycolytic-ATP.
Citation Format: Jesus Sosa, María Sánchez Vázquez, Sylvette Ayala-Peña, Carlos Torres Ramos, Magaly Martínez Ferrer. Altered bioenergetics profile in prostate cancer cells treated with andrographolide [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 2459.
Abstract 2461: SIRT1 regulates ovarian cancer metastasis via altering the exosome release and glycogen deposition
Authors: Roy Sraddhya , Das Ananya , Vernekar Manisha , Das Subhadip , Chatterjee Nabanita 
Published: July 2021

Abstract
Ovarian cancer is the lethal most gynaecological malignancy which exhibits high metastatic rate in peritoneal cavity, especially leading to metastasis including omentum. According to the histopathological segregation of ovarian cancer, epithelial ovarian cancer (EOC) is considered as the most metastatic in both pre- or post-menopausal state, thus several changes in hormonal level such as estrogen, progesterone etc., increase the risk of developing ovarian cancer in women. Obesity or fat deposition are observed to be the after effects of hormonal transition mainly due the depletion of estrogen level. In this context, stored glycogen or deposited fat in the cancer cells has recently drawn the research concern. Few studies suggested that hypoxic environment (HIF-1) could regulate the accumulation of glycogen in cancer cells leading the metastatic micro-environment. The level of HIF-1 could coordinate with the SIRT1 status in tumor dormancy via regulating oxidative stress and metabolic alterations that confers the ovarian cancer stem cell like properties. Interestingly, SIRT1 also controls the secretion of pro-tumorigenic exosomes in cancer invasion. Exosomes, small bioactive extracellular vesicles, can migrate expediently through body barriers and promotes the homing of migrating cancer cells. We observed that the overexpressed SIRT1 in EOC patients has increased concentration of secreted exosomes as compared to heathy individuals. Simultaneously, we have shown how SIRT1 level in ovarian cancer cells co-relate with exosome secretion in regulating glycogen deposition of post-menopausal females. Furthermore, we also found that post-menopausal EOC patients have shown an increased expression of lipids and glycogen in the cancer cells. Therefore, we can conclude that ovarian cancer cell derived exosomes might facilitate fat deposition via regulating their oncogenic cargoes to metastasize ovarian cancer.
Citation Format: Sraddhya Roy, Ananya Das, Manisha Vernekar, Subhadip Das, Nabanita Chatterjee. SIRT1 regulates ovarian cancer metastasis via altering the exosome release and glycogen deposition [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 2461.
Abstract 247: Identification of an ovarian cancer selective splice variant of mesothelin utilizing the Kiromic proprietary search engine CancerDiff
Authors: Piccotti Lucia , Mirandola Leonardo , Chiriva-Internati Maurizio 
Published: July 2021

Abstract
The advancement of cures for cancer needs the development of novel, more efficacious, and more specific immunotherapeutic approaches through the discovery of novel target candidates displaying differential expression between healthy and malignant tissues. CancerDiff is a proprietary software module for the identification of potential new immunotherapeutic cancer targets that originate from differentially expressed, alternatively spliced transcripts. When utilized to analyze Ovarian Cancer (OV) datasets, CancerDiff identified a selectively upregulated mesothelin (MSLN) splice variant translated into a protein isoform (IsoMSLN) bearing a distinct unique peptide absent in the canonical protein sequence. To validate this prediction and to confirm the upregulation of IsoMSLN in OV, datasets from publicly available proteomic repositories were searched for its unique signature peptide. In agreement with CancerDiff prediction, IsoMSLN peptide was detected in 71% of OV samples and 61% of adjacent normal tissues. Molecular modeling tools predicted this peptide to be part of the extracellular portion of the protein in an antibody accessible region. These results indicate IsoMSLN unique peptide as a suitable target for immunotherapy for OV cancer.
Citation Format: Lucia Piccotti, Leonardo Mirandola, Maurizio Chiriva-Internati. Identification of an ovarian cancer selective splice variant of mesothelin utilizing the Kiromic proprietary search engine CancerDiff [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 247.
Abstract 2476: The oncogenic role of p63 in altered-FGFR3 bladder tumors
Authors: Zambrano Macarena , Moreno-Vega Aura I. , Dufour Florent , Sciacca Marianela , Langle Yanina V. , Radvanyi François , Eiján Ana M. , Bernard-Pierrot Isabelle , Lodillinsky Catalina 
Published: July 2021

Abstract
Recently, a new classification of muscle-invasive bladder cancer (MIBCs) has been proposed (Kamoun, 2020). There are 6 classes of MIBC: the over-expression or activating mutations in Fibroblast Growth Factor Receptor 3 (FGFR3) are associated with luminal subtypes. As typically expected, basal tumors exhibit increased TP63 activity, but interestingly, this is also observed in luminal-papillary (LumP) tumors. LumP are enriched in both, FGFR3 mutations and p63 activation. The regulatory gene pathways and p63 functional role in these tumors remains poorly characterized. Therefore, this is our main objective, together with the study of the link with FGFR3 mutations. We hypothesize that p63 drives a protumoral program in bladder cancer (BC) commanded by the regulation of altered FGFR3. We used human BC cell lines bearing FGFR3 mutations with inducible silencing for p63 in order to identify the functional role of p63 in this context. Loss of p63 led to a decreased 2D and 3D growth (p&lt;0.001). Gelatin degradation and migration ability were significantly lower in p63 depleted cells compared to CRL (p&lt;0,01). In vivo assays showed that tumor volume was significantly lower in p63 depleted tumors compared to CRL (p&lt;0.01), accompanied by a reduction of proliferating cell nuclear antigen (PCNA) expression, indicating that p63 is an essential protein through which the cell mediates its proliferative and migratory mechanism. In order to study the link between both, FGFR3 alterations and p63 activity, we used FGFR3 Knocked down cells and pharmacological inhibitors. FGFR3 inhibition decreased p63 expression associated with a reduction in TP63 activity. It reduced proliferation and cell migration in similar level to those observed by directly silencing p63 in FGFR3 altered cells. Conversely, FGFR3 wt cells were not affected by the inhibitor. Overall, these results show that FGFR3 inhibition blunted the carcinogenic program carried out by p63, suggesting there is a regulation of FGFR3 over p63. Supporting the regulation of p63 by FGFR3, analysis of mRNA levels in human bladder tumors showed that p63 expression was significantly higher in FGFR3 mutated tumors in two different sets of samples. In summary, we experimentally demonstrated the regulation of FGFR3 over the protumoral transcription factor p63 that induces proliferation, migration and tumor growth in bladder cancer.
Citation Format: Macarena Zambrano, Aura I. Moreno-Vega, Florent Dufour, Marianela Sciacca, Yanina V. Langle, François Radvanyi, Ana M. Eiján, Isabelle Bernard-Pierrot, Catalina Lodillinsky. The oncogenic role of p63 in altered-FGFR3 bladder tumors [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 2476.
Abstract 2483: Expression of microRNA and mRNA in U87 glioblastoma cells transfected with PTEN
Authors: Stefanik David , Goldblatt Sidney , Jordan Rick 
Published: July 2021

Abstract
Background: U87 glioblastoma cells (ATCC HTB-14) were transfected with a plasmid containing the wild type PTEN gene. Untransfected U87 cells and U87 cells transfected with a plasmid containing only a fluorescent marker served as controls.
Methods: Cells were assessed for neurosphere formation and growth in soft agar. Genes were assessed for expression of microRNA and messenger RNA by the NanoString nCounter platform.
Results: The PTEN transfectants exhibited reduced neurosphere formation and diminished growth in soft agar. The PTEN transfectants exhibited a 10-fold or greater change in 101 of 799 microRNA species assessed compared to untransfected cells. The change in microRNA expression was strongly influenced by growth in hypoxic conditions. Expression of mRNA was altered in 260 of 760 genes assessed with 8% of the genes showing a 10-fold or greater difference in expression level. A detailed summary of the NanoString results is provided.
Conclusions: (1) The PTEN transfectants demonstrate growth characteristics in vitro suggestive of decreased tumorigenicity. (2) The expression level of multiple genes is affected in the PTEN transfectants. (3) Hypoxic conditions bring out the greatest change in the expression level of microRNA in the PTEN transfected cells.
Citation Format: David Stefanik, Sidney Goldblatt, Rick Jordan. Expression of microRNA and mRNA in U87 glioblastoma cells transfected with PTEN [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 2483.
Abstract 2488: Elucidating the role of G0S2 in breast cancer
Authors: Corbet Andrea K. , Bikorimana Emmanuel , Singh Ratnakar , Fazal Zeeshan , Boyd Raya I. , Freemantle Sarah , Spinella Michael J. 
Published: July 2021

Abstract
Breast cancer has the second-highest cancer mortality rate for women in the United States. There are effective therapies available and a growing list of biomarkers for prognosis. However, new breast cancer targets are critically needed for patients refractory to available therapies. The present study evaluates the role of gap 0 switch 2 (G0S2), in breast cancer. Using online databases, we observed G0S2 expression is downregulated in patients with estrogen receptor-positive (ER+) breast cancer and patients with high G0S2 expression have a lower rate of relapse after treatment. Previously, our lab showed G0S2 overexpression in ER+ breast cancer cell lines resulted in decreased proliferation. Further knockout of G0S2 in murine embryonic fibroblast resulted in higher oncogenic transformation and resistance to mTOR inhibitors. These results suggest that G0S2 has a tumor suppressive function in ER+ breast cancer. To test whether G0S2 has a role in ER-negative breast cancer global knockout of G0S2 was engineered in the ER-negative MMTV-PyMT transgenic mouse model. Slower tumor progression and decreased lung metastasis was observed in G0S2-null transgenic females compared to wild-type transgenic females. These data suggest that the role of G0S2 in breast cancer in dependent on ER-status, where G0S2 functions as a tumor suppressor in ER-positive breast cancer and a tumor promoter in ER-negative breast cancer. Molecular and genetic studies manipulating G0S2 and ER in various breast cancer contexts are ongoing and will help elucidate that precise role of G0S2 in breast cancer and provide clarity on the potential of G0S2 as a novel prognostic marker and therapeutic target.
Citation Format: Andrea K. Corbet, Emmanuel Bikorimana, Ratnakar Singh, Zeeshan Fazal, Raya I. Boyd, Sarah Freemantle, Michael J. Spinella. Elucidating the role of G0S2 in breast 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 2488.
Abstract 2496: CD82 regulation of c-Met in metastatic prostate cells
Authors: Sridhar Suganthi , Brandes Emily , Aller Patrick , Barrie Eddie 
Published: July 2021

Abstract
Metastatic prostate cancer is the second leading cause of cancer deaths among men in the U.S. Metastasis involves regulators, which involve complex cell signaling processes and our current knowledge on how prostate cancer metastasis develops is still under investigation. If these regulators can be identified and the mechanisms fully elucidated, they can be potential targets for oncologic treatment. CD82 (KAI1), a tetraspanin first identified as a metastasis tumor suppressor in prostate cells is one such regulator involved in the metastatic process. Currently, CD82 downregulation is not only observed in prostate but also in a variety of many invasive epithelial tumors which include tumors of the gastric, colon, cervix, breast, skin, bladder, lung, pancreas, liver, and thyroid. CD82 has been well documented as an inhibitor of cell motility and invasion in cancer cells, with varied inhibitory mechanisms. By introducing CD82 in metastatic cell lines (PC3) that do not express CD82, we have shown CD82 to regulate c-Met, a growth factor receptor, a protooncogene that is over expressed and or over activated in prostate tumors. Overactivation of c-Met promotes cell proliferation, migration and invasion. However, it is still not well understood how exactly CD82 regulates c-Met. Using metastatic prostate cell lines (PC3) and comparing them with PC3 clones generated to express CD82, we are using immunofluorescence, immunoprecipitation, flow cytometry, and western blot techniques to analyze the exact mechanism by which CD82 regulates c-Met. Preliminary data indicate CD82 does not colocalize with CD82, nor does it downregulate c-Met expression on the cell surface. However, CD82 expression seems to cause varied distribution of c-Met in the cell and is currently being investigated. Preliminary indications are that CD151, another tetraspanin may be involved in this regulation. CD151 is a known tumor promoter and has been shown to associate with c-Met. Currently, our lab is exploring the redistribution pattern of c-Met upon CD82 expression as a regulatory mechanism, in addition to exploring the CD82 and CD151 expression dynamics as part of or as alternate mechanism to c-Met regulation. The results observed will provide insights into the role CD82 plays in c-Met regulation as well as it may overall play in tumor progression and metastasis in prostate cancer. Notably, the results may also shed more light on CD82 regulation in other tumors where CD82 downregulation is observed.
Citation Format: Suganthi Sridhar, Emily Brandes, Patrick Aller, Eddie Barrie. CD82 regulation of c-Met in metastatic prostate 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 2496.
Abstract 251: Data distribution for easy pancancer analysis
Authors: Lindgren Caleb M. , Minor Chelsie , Olsen Lindsey K. , Henderson Brittany , Investigators CPTAC , Payne Samuel H. 
Published: July 2021

Abstract
A growing number of datasets characterize tumors with quantitative proteomic and genomic data. These emerging datasets are typically specific to a single cancer type. However, analysis of proteogenomic patterns across multiple cancer types allows us to identify common mechanisms in the function of cancer, as well as mechanisms that are unique to specific cancer types. Here we present how a Python data API from the NCI's CPTAC program bridges the gap between different cancer datasets to facilitate pancancer analysis. While we have previously presented this API as a general model for data dissemination, we have yet to display the specific pancancer applications of the tool. Several key aspects of its design optimize its use from a pancancer point of view, including parsing data to a single consistent format for all datasets, and automatically managed data updates for each dataset. Our analyses demonstrate the efficacy of our data model for generalizing an analysis pipeline, applying it to multiple cancer types, and comparing the results. This enables unique discoveries that characterize the overall proteogenomic landscape of cancer.
Citation Format: Caleb M. Lindgren, Chelsie Minor, Lindsey K. Olsen, Brittany Henderson, CPTAC Investigators, Samuel H. Payne. Data distribution for easy pancancer analysis [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 251.
Abstract 2558: Understanding the shared roles of obesity and genetic mutation in the development of endometrial cancer
Authors: Wilson Mike R. , Reske Jake J. , Chandler Ronald L. 
Published: July 2021

Abstract
Up to 20% of all cancer deaths in women can be attributed to excess body weight. Endometrial cancer was the first cancer identified with an increased risk among obese populations, and incidence of endometrial cancer is rising steadily due to the obesity epidemic. Obesity is associated with over 60% of endometrial cancer occurring in the United States, but like many cancers, the causes of endometrial cancer are multi-faceted. Increased estrogen abundance in obese women is considered the primary driver, but obesity-linked complications, including hyperinsulinemia, are also known to contribute to endometrial cancer. However, obesity alone is not sufficient for tumorigenesis. Genetic mutations driving endometrial cancer are well characterized, but these mutations alone are not sufficient for EC pathogenesis as they exist in uteri without cancer. In normal cells, the PI3K pathway maintains metabolic homeostasis, but in cancer the PI3K pathway is activated to promote cell survival. There is an urgent need to understand the mechanisms by which obesity and genetic mutation interact to promote EC. Metabolic signaling influences protein production and folding. The unfolded protein response pathway acts to maintain protein quality control, and is activated upon endoplasmic reticulum stress. During endoplasmic reticulum stress, if proteostasis cannot be achieved, the unfolded protein response is activated, resulting in cell death. Obesity results in systemic endoplasmic reticulum stress, with overabundant estrogen and hyperinsulinemia likely as contributing factors. In our preliminary studies, we have identified a role for PI3K pathway mutations in regulating endoplasmic reticulum stress in the endometrial epithelium. By antagonizing endoplasmic reticulum stress, PI3K pathway mutations may promote survival of endometrial epithelium through resistance to unfolded protein response-mediated cell death mechanisms. Through understanding endoplasmic reticulum stress resistance in the endometrial epithelium, we hope to develop preventative interventions for obese women at risk for endometrial cancer.
Citation Format: Mike R. Wilson, Jake J. Reske, Ronald L. Chandler. Understanding the shared roles of obesity and genetic mutation in the development of endometrial 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 2558.