tbuckley/cabot-search huggingface dataset:
Abstract 294: Altered <i>ARID1A</i> expression in colorectal cancer
Authors: Mehran Erfani, Seyed Vahid, Maral Mokhtari, Mozhdeh Zamani, Kamran Tahmasebi, Mahvash Alizadeh, Alireza Taghavi, John Carethers, Minoru Koi, Hassan Brim, Pooneh Mokarram, Hassan Ashktorab
Journal: Cancer Research (2020)

Abstract Background: ARID1A has been described as a tumor suppressor gene, participating in chromatin re-modeling, epithelial-mesenchymal-transition and many other cellular and molecular processes. It has been cited as a contribute in tumorigenesis. The role of ARID1A in CRC is not yet defined. Aim: To investigate the role ARID1A methylation and CNV in its expression in CRC cell lines and to examine the relationship between ARID1A status with survival and clinicopathologic characteristics in patients with CRC. Methods: We used RT-PCR to determine both CNV and expression of ARID1A from six CRC cell lines. And used MSP to evaluate methylation of ARID1A. We used (IHC) to ARID1A protein expression, and, evaluate both MSI and EMAST status in 18 paired CRC and adjacent normal tissues. Statistical analysis was performed to establish correlations between ARID1A expression and other parameters. Results: Among the 18 CRC tumors studied, 7 (38.8 %) and 5 tumors (27.7%) showed no or low ARID1A expression, respectively. We observed no significant difference in ARID1A expression for overall patient survival, and no difference between clinicopathological parameters including MSI and EMAST. However, lymphatic invasion was more pronounced in the low/no ARID1A expression group when compared to moderate and high expression group (33% VS. 16.6% respectively. ARID1A promoter methylation was observed in 4/6 (66%) of cell lines and correlated with ARID1A mRNA expression level ranging from very low in SW48, to more pronounced in HCT116 and HT-29/219. Treatment with the methyltransferase inhibitor 5-Azacytidine (5-aza) resulted in a 25.4-fold and 6.1-fold increase in ARID1A mRNA expression in SW48 and SW742 cells, respectively, while there was no change in SW480 and LS180 cells. No ARID1A CNV was observed in the CRC cell lines. Conclusion: ARID1A expression is downregulated in CRC tissues correlate with it being a tumor suppressor protein. This finding confirms ARID1A loss of expression in CRC development. Our in-vitro results suggest high methylation status associates with reduced ARID1A expression and contribute to CRC tumorigenesis. There was no significant association between the ARID1A loss of expression and clinicopathological characteristics. ARID1A might be a useful biomarker for colorectal cancer. Future in- vivo analysis is warranted to further established this role. Citation Format: Mehran Erfani, Seyed Vahid, Maral Mokhtari, Mozhdeh Zamani, Kamran Tahmasebi, Mahvash Alizadeh, Alireza Taghavi, John Carethers, Minoru Koi, Hassan Brim, Pooneh Mokarram, Hassan Ashktorab. Altered ARID1A expression in colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 294.
pH-sensitive and bubble-generating mesoporous silica-based nanoparticles for enhanced tumor combination therapy
Authors: Zhiming Zhang, Chenlu Huang, Li Zhang, Qing Guo, Yu Qin, Fan Fan, Boxuan Li, Bao Xiao, Dunwan Zhu, Linhua Zhang
Journal: Acta Pharmaceutica Sinica B (2020)

Chemotherapy has been a major option in clinic treatment of malignant tumors. However, single chemotherapy faces some drawbacks, such as multidrug resistance, severe side effects, which hinder its clinic application in tumor treatment. Multifunctional nanoparticles loading with chemotherapeutic agent and photosensitizer could be a promising way to efficiently conduct tumor combination therapy. In the current study, a novel pH-sensitive and bubble-generating mesoporous silica-based drug delivery system (denoted as M(a)[email protected]) was constructed. Ammonium bicarbonate (NH4HCO3; abc) and chemotherapeutic agent doxorubicin (DOX) were loaded into the pores of mesoporous silica. Indocyanine green (ICG) as a photothermal and photodynamic agent was loaded onto the polydopamine (PDA) layer surface. The synthesized nanoparticles displayed a narrow polydispersity (PDI) and small particle size as characterized through dynamic light scattering-autosizer analysis. The nanoparticles also showed high targeting efficacy through RGD modification as indicated by cellular uptake and animal studies. DOX release analysis confirmed that the nanoparticles were pH-dependent and that NH4HCO3 accelerated drug release. At the same time, the nanoparticles had obvious photothermal and photodynamic effects performed by ICG which restrained tumor growth remarkably. In summary, the multifunctional nanoparticles presented a promising system for combination therapy.
A genome-wide association study of asthma hospitalizations in adults
Authors: Qi Yan, Erick Forno, Esther Herrera-Luis, Maria Pino-Yanes, Ge Yang, Sam Oh, Edna Acosta-Pérez, Donglei Hu, Celeste Eng, Scott Huntsman, José R. Rodriguez-Santana, Michelle M. Cloutier, Glorisa Canino, Esteban G. Burchard, Wei Chen, Juan C. Celedón
Journal: Journal of Allergy and Clinical Immunology (2020)
Abstract 295: Protein phosphatase, Mg2+/Mn2+ dependent 1G promotes proliferation via modulating phosphorylation of retinoblastoma protein and associates with poor outcome in hepatocellular carcinoma
Authors: Wen Hu, Xin Yuan Guan, Lei Li, Yinghui Zhu, Yan Li, Ting Ting Zeng, Yun Fei Wen
Journal: Cancer Research (2020)

Abstract The serine/threonine protein phosphatase family has been demonstrated involved in a variety of cellular processes. Here, we identified that protein phosphatase, Mg2+/Mn2+ -dependent 1G (PPM1G) is an oncogene-associated protein in hepatocellular carcinoma (HCC), and is associated with the progression of HCC. In this study, we carried out a series of in vitro (MTT, colony formation, immunoblot analysis, IHC, and Q-PCR) as well as in vivo (Hepatocellular carcinoma cell xenograft mouse model) experiments to determine the biological roles of PPM1G in HCC. Our results showed that PPM1G expression was significantly increased in HCC tissues, compared with the adjacent non-tumorous tissues. Further analysis revealed that high expression of PPM1G is associated with advanced clinical characters including advanced clinical stage and tumor recurrence. Kaplan-Meier analysis suggested that a high level of PPM1G is correlated to unfavorable overall survival (P &amp;lt; 0.0001) as well as disease-free survival (P = 0.004) in patients with HCC. Furthermore, overexpression of PPM1G promoted cell proliferation while this effect can be attenuated by the knockdown of PPM1G in in vitro and in vivo studies. Notably, our findings showed that the tumor suppressor gene expression (e.g. pRb phosphorylation and p53 protein) was inhibited upon the silencing of PPM1G. Taken together, our study demonstrated that PPM1G plays an crucial role in HCC cell proliferation by modulating pRb phosphorylation as well as p53 expression. Furthermore, this study provides strong clinical implications of PPM1G in prognostic prediction in patients with HCC. Citation Format: Wen Hu, Xin Yuan Guan, Lei Li, Yinghui Zhu, Yan Li, Ting Ting Zeng, Yun Fei Wen. Protein phosphatase, Mg2+/Mn2+ dependent 1G promotes proliferation via modulating phosphorylation of retinoblastoma protein and associates with poor outcome in hepatocellular carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 295.
Mental Health Inequities in the Context of COVID-19
Authors: Ruth S. Shim
Journal: JAMA Network Open (2020)

Catherine K. Ettman, BA; Salma M. Abdalla, MD, MPH; Gregory H. Cohen, MPhil, MSW, PhD; Laura Sampson, PhD; Patrick M. Vivier, MD, PhD; Sandro Galea, MD, DrPH
Association of New-Onset Atrial Fibrillation After Noncardiac Surgery With Subsequent Stroke and Transient Ischemic Attack
Authors: Konstantinos C. Siontis, Bernard J. Gersh, Susan A. Weston, Ruoxiang Jiang, Anthony H. Kashou, Véronique L. Roger, Peter A. Noseworthy, Alanna M. Chamberlain
Journal: JAMA (2020)

Outcomes of postoperative atrial fibrillation (AF) after noncardiac surgery are not well defined.To determine the association of new-onset postoperative AF vs no AF after noncardiac surgery with risk of nonfatal and fatal outcomes.Retrospective cohort study in Olmsted County, Minnesota, involving 550 patients who had their first-ever documented AF within 30 days after undergoing a noncardiac surgery (postoperative AF) between 2000 and 2013. Of these patients, 452 were matched 1:1 on age, sex, year of surgery, and type of surgery to patients with noncardiac surgery who were not diagnosed with AF within 30 days following the surgery (no AF). The last date of follow-up was December 31, 2018.Postoperative AF vs no AF after noncardiac surgery.The primary outcome was ischemic stroke or transient ischemic attack (TIA). Secondary outcomes included subsequent documented AF, all-cause mortality, and cardiovascular mortality.The median age of the 452 matched patients was 75 years (IQR, 67-82 years) and 51.8% of patients were men. Patients with postoperative AF had significantly higher CHA2DS2-VASc scores than those in the no AF group (median, 4 [IQR, 2-5] vs 3 [IQR, 2-5]; P < .001). Over a median follow-up of 5.4 years (IQR, 1.4-9.2 years), there were 71 ischemic strokes or TIAs, 266 subsequent documented AF episodes, and 571 deaths, of which 172 were cardiovascular related. Patients with postoperative AF exhibited a statistically significantly higher risk of ischemic stroke or TIA (incidence rate, 18.9 vs 10.0 per 1000 person-years; absolute risk difference [RD] at 5 years, 4.7%; 95% CI, 1.0%-8.4%; HR, 2.69; 95% CI, 1.35-5.37) compared with those with no AF. Patients with postoperative AF had statistically significantly higher risks of subsequent documented AF (incidence rate 136.4 vs 21.6 per 1000 person-years; absolute RD at 5 years, 39.3%; 95% CI, 33.6%-45.0%; HR, 7.94; 95% CI, 4.85-12.98), and all-cause death (incidence rate, 133.2 vs 86.8 per 1000 person-years; absolute RD at 5 years, 9.4%; 95% CI, 4.9%-13.7%; HR, 1.66; 95% CI, 1.32-2.09). No significant difference in the risk of cardiovascular death was observed for patients with and without postoperative AF (incidence rate, 42.5 vs 25.0 per 1000 person-years; absolute RD at 5 years, 6.2%; 95% CI, 2.2%-10.4%; HR, 1.51; 95% CI, 0.97-2.34).Among patients undergoing noncardiac surgery, new-onset postoperative AF compared with no AF was associated with a significant increased risk of stroke or TIA. However, the implications of these findings for the management of postoperative AF, such as the need for anticoagulation therapy, require investigation in randomized trials.
Shear Wave Elastography Using High-Frame-Rate Imaging in the Follow-Up of Heart Transplantation Recipients
Authors: Aniela Petrescu, Stéphanie Bézy, Marta Cvijic, Pedro Santos, Marta Orlowska, Jürgen Duchenne, João Pedrosa, Jan M. Van Keer, Eric Verbeken, Stephan von Bardeleben, Walter Droogne, Jan Bogaert, Johan Van Cleemput, Jan D’hooge, Jens-Uwe Voigt
Journal: JACC. Cardiovascular imaging (2020)
Abstract 1218: Pimavanserin induces autophagy mediated apoptosis in pancreatic cancer and suppresses pancreatic tumor growth
Authors: Sharavan Ramachandran, Sanjay K. Srivastava
Journal: Cancer Research (2020)

Abstract Pancreatic cancer patients have limited treatment options in spite of several advanced treatment strategies. Pancreatic tumors exhibit high basal autophagy compared to other cancers. Several studies including from our lab reported that enhanced autophagy can lead to apoptosis in cancer cells. In this study, we have demonstrated that pimavanserin (PVT) suppresses pancreatic tumor growth by inducing autophagy-mediated apoptosis. Our results indicated that PVT induced apoptosis and reduced the proliferation of pancreatic cancer cells with IC50 ranging between 3-9µM after 24, 48 and 72 hours of treatment. In addition, PVT inhibited the colony formation of pancreatic cancer cells. Treatment of pancreatic cancer cells with increasing concentrations of PVT resulted in a concentration-dependent increase in autophagy as evaluated by acridine orange assay by flow cytometry. PVT induced the expression of autophagy markers ULK1, FIP200, Atg101, Beclin-1, LC3B and p62 in a concentration-dependent manner in several pancreatic cancer cells. Apoptotic effects of PVT in pancreatic cancer cells was validated by increase in cleavage of caspase3 and PARP. Oral administration of PVT suppressed BxPC3 tumor xenografts by 50% in athymic nude mice. In another in vivo experiment, PVT treatment inhibited the growth of orthotopicaly implanted PANC1 tumors by 75%. Autophagy and apoptosis was confirmed in the tumors of PVT treated mice by immunohistochemistry and western blotting. Chronic administration of PVT did not exhibit any general signs of toxicity or behavioral side effects in mice. Moreover, long-term administration of PVT did not alter the clinical chemistry parameters like ALT, AST, total serum protein, calcium and albumin. Collectively, our results indicate that PVT mediated pancreatic tumor growth suppression was associated with induction of autophagy and apoptosis. Since PVT is already available in the clinic with an established safety profile, our results will accelerate its clinical development for pancreatic cancer therapy. Citation Format: Sharavan Ramachandran, Sanjay K. Srivastava. Pimavanserin induces autophagy mediated apoptosis in pancreatic cancer and suppresses pancreatic tumor growth [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1218.
Bifunctional supramolecular nanofiber inhibits atherosclerosis by enhancing plaque stability and anti-inflammation in apoE<sup>-/-</sup> mice
Authors: Yuna Shang, Chuanrui Ma, Jing Zhang, Zhongyan Wang, Chunhua Ren, Xin Luo, Rong Peng, Jingfei Liu, Jingyuan Mao, Yang Shi, Guanwei Fan
Journal: Theranostics (2020)

Background and Purpose: Atherosclerosis is vascular disease of chronic inflammation and lipid disorder, which is a major cause of coronary heart disease. Foam cell formation is key progress during the atherosclerosis development. Insulin-like growth factor (IGF)-1 is a growth hormone that plays a crucial role in growth, metabolism, and homeostasis. Previous studies have demonstrated that increase in circulating IGF-1 can reduce atherosclerotic burden. However, active IGF-1 is characterized with poor tissue retention and is at a very low level in circulation system. Therefore, supplementation of exogenous IGF-1 to restore the physiological level is a promising approach to inhibit atherosclerosis. In this study, we develop a self-assembling, anti-inflammatory drug-modified peptide derived from IGF-1 to mimic IGF-1 bioactivity and simultaneously with an anti-inflammatory property for the treatment of atherosclerosis. Methods: ApoE-/- mice were subcutaneously (s.c.) injected with the different hydrogels or natural IGF-1 protein solution per week and simultaneously fed a high-fat diet for 16 weeks. Atherosclerotic lesion formation and stability were assessed after treatment. Moreover, peritoneal macrophage and serum samples were collected to determine lipid profile and inflammatory cytokines. Concurrently, we determined the effect of bifunctional supramolecular nanofibers/hydrogel on cholesterol efflux, foam cell formation, phenotypic transformation of VSMC to macrophage-like cells, and macrophage polarization in vitro or in vivo. Results: Bifunctional supramolecular nanofibers/hydrogel for the treatment of atherosclerosis was formed by a short peptide consisting of a tetrapeptide SSSR from C-region of growth factor IGF-1, an anti-inflammatory drug naproxen (Npx), and a powerful self-assembling D-peptide DFDF. The resulting hydrogel of Npx-DFDFGSSSR (Hydrogel 1, H1) possessed both the anti-inflammatory and IGF-1 mimicking properties, and it efficiently promoted the expression of ABCA1 and ABCG1, thereby significantly reducing cholesterol accumulation in macrophages and preventing foam cell formation. Moreover, H1 markedly inhibited the transformation of vascular smooth muscle cells (VSMCs) into macrophage-like cells which also contributed to foam cell formation. In addition, H1 significantly reduced the inflammatory response in vitro and in vivo. Most importantly, the IGF-1 mimetic peptide showed comparable performance to IGF-1 in vivo and inhibited atherosclerosis by markedly reducing lesion area and enhancing plaque stability. Conclusions: Our study provides a novel supramolecular nanomaterial to inhibit pathological progress of atherosclerosis through regulating cholesterol efflux and inflammation, which may contribute to the development of a promising nanomedicine for the treatment of atherosclerosis in the clinic.
Abstract 1661: Temozolomide suppresses a doxorubicin resistant follicular dendritic cell sarcoma in a patient derived orthotopic xenograft mouse model
Authors: Hiromichi Oshiro, Yasunori Tome, Robert M. Hoffman, Kotaro Nishida
Journal: Cancer Research (2020)

Abstract Introduction: Follicular dendritic cell sarcoma (FDCS) is a very rare and highly refractory soft tissue sarcoma. The CHOP chemotherapy has been used as systemic therapy for FDCS, which includes cyclophosphamide, doxorubicin (DOX), vincristine, and prednisolone. However, FDCS has poor clinical outcome even though CHOP therapy was administered. A FDCS patient tumor was previously implanted orthotopically in the biceps femoris of nude mice to establish a patient-derived orthotopic xenograft (PDOX) model in our laboratory at AntiCancer Inc. The FDCS patient had resistance to DOX in clinical setting. We previously found the FDCS PDOX model had resistance to DOX as well as clinical settings. In the present study, we evaluated the efficacy of temozolomide (TMZ), trabectedin (TRAB), and pazopanib (PAZ) on the DOX resistant FDCS PDOX model. Methods: The FDCS PDOX mouse model was established and randomized into five groups of eight mice, respectively. Group 1, Control (Ctrl) treated with PBS, i.p.; Group 2, DOX, 2.4 mg/kg, i.p., weekly; Group 3, PAZ, 50 mg/kg, oral gavage, daily; Group 4, TRAB, 0.15 mg/kg, i.v., weekly; Group 5, TMZ, 25 mg/kg, oral gavage, daily. Treatment term was for 2 weeks. Treatment efficacy was evaluated based on tumor volume ratio (tumor volume after treatment relative to tumor volume at the beginning of treatment) and histopathology. Adverse event was evaluated based on body weight ratio. Tumor volume and body weight were assessed 2 times per week. Results: Tumor volume ratio was the Ctrl group: 11.35±4.50, DOX: 8.24±1.87, PAZ: 9.67±4.66, TRAB: 6.97±3.23, TMZ: 4.28±1.41, respectively. TMZ significantly arrested the FDCS PDOX model compared to the control group (p&amp;lt;0.05). PAZ and TRAB did not have significant efficacy compared to the Ctrl group (p=0.93, p=0.41). In H&amp;E-staining, partial necrosis was detected only in PDOX tumors treated with TMZ. There was no significant difference of body weight among all groups. Conclusion: The FDCS PDOX model was resistant to DOX as well as in the clinical settings demonstrating concordance of the FDCS model and clinic. TMZ was the most effective for the FDCS PDOX mouse model established from a patient who failed DOX treatment. There is possibility that TMZ has effective to FDCS patients who has resistant to the first line chemotherapy. Citation Format: Hiromichi Oshiro, Yasunori Tome, Robert M. Hoffman, Kotaro Nishida. Temozolomide suppresses a doxorubicin resistant follicular dendritic cell sarcoma in a patient derived orthotopic xenograft mouse model [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1661.
Chronic activation of 4-1BB signaling induces granuloma development in tumor-draining lymph nodes that is detrimental to subsequent CD8+ T cell responses
Authors: Seon-Hee Kim, Rohit Singh, Chungyong Han, Eunjung Cho, Yu I. Kim, Don G. Lee, Young H. Kim, Sang Soo Kim, Dong Hoon Shin, Hye Jin You, Hyeon-Woo Lee, Byoung S. Kwon, Beom K. Choi
Journal: Cellular and Molecular Immunology (2020)

The antitumor capabilities of agonistic anti-4-1BB mAbs have made them an attractive target for tumor immunotherapy. However, the adverse side effects associated with agonist antibodies have hindered their clinical development. Here, we aimed to study the immune-related adverse events of repeated doses and long-term use of agonistic anti-4-1BB mAbs. We show that chronic activation of 4-1BB signals induced the accumulation of IFN-γ-producing PD-1
Abstract 315: Multifaceted functional assessment of checkpoint inhibitor efficacy using 3D tumor spheroids
Authors: Katy A. Lassahn, Kathryn M. Appleton, Ashley Elrod, Aaron L. Carlson, Teresa M. DesRochers
Journal: Cancer Research (2020)

Abstract Three-dimensional (3D) culture of immortalized cell lines and patient-derived primary cells has been shown to be a more representative in vitro model of tumor biology compared to standard 2D techniques. For immune-oncology, animal models continue to lack the ability to fully recapitulate the human immune system. The use of 3D models to study immunotherapies provides the opportunity to mimic the complex interactions between immune cells and the tumor microenvironment in a fully human system. However, standard well-based assays that measure cell viability prevent the obtainment of useful knowledge on tumor-immune cell interactions and immunotherapy effect on immune cell numbers and viability. To address these limitations, we have developed an in vitro based assay for the visualization and quantitation of T-cell-mediated cell death using fluorescently labeled live tumor cells in a 3D spheroid platform. Enhanced T-cell mediated tumor cell killing using immune checkpoint inhibitors can be detected allowing for real-time evaluation of tumor-specific apoptosis in the presence of cytotoxic T-cells. Moreover, the cytotoxic effects can be inhibited by co-treatment with a blocking anti-CD8 antibody, demonstrating a specific requirement for CD8+ T-cells. In order to detect changes to tumor biology induced by T-cells as well as immune-oncology drug treatments, we monitored dynamic fluctuation of PD-L1 and MHC-I expression using immunofluorescence in the spheroids. Finally, we detected changes in T-cell populations, such as T-cell activation, and changes in CD8+:Treg ratios, induced by tumor spheroids with or without drug treatment using flow cytometry. In summary, we can observe T-cell mediated tumor cell killing and relate drug efficacy back to identified changes in tumor cell and T-cell phenotypes. This multifaceted approach is ideal for the functional evaluation of preclinical I/O agents and for identifying drug combinations as it represents a holistic perspective of drug response. Citation Format: Katy A. Lassahn, Kathryn M. Appleton, Ashley Elrod, Aaron L. Carlson, Teresa M. DesRochers. Multifaceted functional assessment of checkpoint inhibitor efficacy using 3D tumor spheroids [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 315.