tbuckley/cabot-search huggingface dataset:
Mastering the Tools: Natural versus Artificial Vesicles in Nanomedicine
Authors: Loredana Leggio, Giuseppe Arrabito, Vittorio Ferrara, Silvia Vivarelli, Greta Paternò, Bianca Marchetti, Bruno Pignataro, Nunzio Iraci
Journal: Advanced Healthcare Materials (2020)

Abstract Naturally occurring extracellular vesicles and artificially made vesicles represent important tools in nanomedicine for the efficient delivery of biomolecules and drugs. Since its first appearance in the literature 50 years ago, the research on vesicles is progressing at a fast pace, with the main goal of developing carriers able to protect cargoes from degradation, as well as to deliver them in a time‐ and space‐controlled fashion. While natural occurring vesicles have the advantage of being fully compatible with their host, artificial vesicles can be easily synthetized and functionalized according to the target to reach. Research is striving to merge the advantages of natural and artificial vesicles, in order to provide a new generation of highly performing vesicles, which would improve the therapeutic index of transported molecules. This progress report summarizes current manufacturing techniques used to produce both natural and artificial vesicles, exploring the promises and pitfalls of the different production processes. Finally, pros and cons of natural versus artificial vesicles are discussed and compared, with special regard toward the current applications of both kinds of vesicles in the healthcare field.
Post-registration experience of nivolumab in advanced hepatocellular carcinoma: an international study
Authors: Petros Fessas, Ahmed Kaseb, Yinghong Wang, Anwaar Saeed, David Szafron, Tomi Jun, Sirish Dharmapuri, Abdul Rafeh Naqash, Mahvish Muzaffar, Musharraf Navaid, Uqba Khan, ChiehJu Lee, Anushi Bulumulle, Bo Yu, Sonal Paul, Neil Nimkar, Dominik Bettinger, Francesca Benevento, Hannah Hildebrand, Tiziana Pressiani, Yehia I Abugabal, Nicola Personeni, Yi-Hsiang Huang, Lorenza Rimassa, Celina Ang, Thomas Marron, David J Pinato
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Nivolumab is Food and Drug Administration approved in sorafenib-experienced, advanced hepatocellular carcinoma (HCC). Post-registration data of treatment in a real-world setting is lacking. Patients and methods We performed an international, multicenter observational study to confirm safety and efficacy of nivolumab in 233 patients treated outside clinical trials from eight centers in North America, Europe and Asia. Results Patients received nivolumab for Barcelona Clinic Liver Cancer stage C (n = 191, 92.0%) and Child-Pugh (CP) A (n = 158, 67.8%) or B (n = 75, 32.2%) HCC as first (n = 85, 36.5%) or second to fourth systemic therapy line (n = 148, 63.5%). Objective response rate (ORR) was 22.4% and disease control rate was 52.1%. Median overall survival (OS) was 12.2 months (95% CI 8.4 to 16.0) and median progression-free survival was 10.1 months (95% CI 6.1 to 14.2). Treatment-related adverse events of grade &gt;2 occurred in 26 patients (11.2%). Efficacy and safety were similar across CP classes and therapy line. OS was shorter in CP-B than A (7.3 months vs 16.3 months, p&lt;0.001) and in post-first line use (10.4 months vs 16.3 months, p = 0.05). Achievement of an objective response predicted for improved OS (25.4 months vs 13.2 months, p&lt;0.001). Conclusions This study confirms safety and efficacy of nivolumab in advanced HCC across various lines of therapy and degrees of liver dysfunction. Despite equal ORR and toxicity to nivolumab, patients with CP-B functional class have shorter survival than the patients with CP-A.
Abstract 2402: Apoptosis induced by non-thermal atmospheric pressure bio-compatible soft jet plasma on brain tumor through p38/MAPK signaling pathways
Authors: Ihn Han
Journal: Cancer Research (2020)

Abstract Brain tumor is one of the most lethal forms of cancer to human beings, among which Glioblastoma astrocytoma is the most familiar and quickly progressing type of astrocytic brain tumor in adults with poor prognosis are still a therapeutic challenge. Current therapy options at diagnosis are multimodal and include surgical resection, radiation, and chemotherapy but difficulty to failure of drug delivery through the blood-brain barrier, tumor response to chemotherapy and intrinsic resistance of tumor cells. Therefore new therapy is needed that can afford selective targeting of proliferating cells to promote current therapies. Non-thermal plasma can be considered as a potential cancer therapy for the alteration of biological and clinical applications by generating reactive oxygen species (ROS) and reactive nitrogen species (RNS). In our study, we designate the effects of a NBP-J device to U87MG cell line. Previous research work established that jet plasma could induce apoptosis of various cancer cells, in particular indicative the selective cytotoxicity of cancer cells over normal cells. In this study, we assessed the effects of NBP-J on the U87MG brain cancer cell line including different effects and the physicochemical and biological correlation between the RONS cascade and p38/MAPK signaling pathway on the dose (time) dependent manner. The results of this study shows that the soft jet plasma significantly inhibits cell proliferation, inhibit survival pathway and induce apoptosis by p38/MAPK pathway in U87MG cells. The current results reveal that soft jet plasma has a powerful cytotoxic effect against brain cancer cells. Taken together, our results showed that NBP-J can become potential applications for effective and safe clinical trials for cancer therapy. Keywords: Non-thermal atmospheric-pressure plasma, soft jet plasma, Human glioblastoma, Cancer therapy. Acknowledgement This work was supported by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea (NRF- 2016K1A4A3914113) funded by the Ministry of Science, ICT, and Future Planning (MSIP) of the Korean Government for EH. Choi, I. Han. Also this work was supported by the Basic Science Research Program through the Ministry of Science ICT of Korea (2019R1H1A2101686) for I. Han. Citation Format: Ihn Han. Apoptosis induced by non-thermal atmospheric pressure bio-compatible soft jet plasma on brain tumor through p38/MAPK signaling pathways [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 2402.
Integrating climate action for health into covid-19 recovery plans
Authors: Kristine Belesova, David L Heymann, Andy Haines
Journal: BMJ (2020)

The covid-19 pandemic caused over a half a million deaths in its first four months and triggered a global recession that threatens to increase poverty and amplify the health effects of the pandemic.At the same time climate change is adversely affecting health, and the effects are projected to intensify worldwide through a range of direct and indirect pathways, including increased frequency and intensity of heatwaves, floods, and droughts.
Abstract 5652: Dual CD73 enzyme blocker to reverse immune suppression
Authors: Jijun Yuan
Journal: Cancer Research (2020)

Abstract Abstract: CD73 is a cell surface enzyme that converts adenosine monophosphate to adenosine, a well-known immunosuppressive mediator that inhibits the cytotoxic function of T cells and natural killer cells. Tumors utilize this mechanism to escape attack by the immune system. Many attempts were made to antagonize the enzyme activity of CD73, including antibody drugs and small molecules. However, most current CD73 enzyme blockers were screened against tumor membrane CD73 and focused only on the membrane format of CD73. Our recent findings show that not only the membrane enzyme on tumor cells, but also the soluble format of CD73 shed off by tumor cells play important roles in generating immunosuppressive adenosine. To reverse the immune suppression exerted by CD73, both the membrane and the soluble format need to be blocked. We screened hundreds of anti-CD73 antibodies against soluble CD73 presented in tumor patient (CRC/LC/HCC/Melanoma) serum, and two candidates GB7002-01 and GB7002-04 were selected with great inhibition potency against tumor membrane CD73 and soluble CD73 in patient serum. GB7002-01/04 exhibited superior T cell proliferation promoting abilities in immune suppressive environment. To be precise, GB7002-01/04 totally reversed the T cell proliferation suppressive effects of pathological concentration of AMP. Moreover, this release of immune suppression was translated to better tumor killing by PBMC in the presence of GB7002-01/04. Humanized GB7002-01/04 has been put into in vivo efficacy study, preliminary toxicity and PK study. As we are observing anti-tumor efficacy, safety, and stability of these two candidates, they are promising agents for extended clinical exploration in several cancer indications. Citation Format: Jijun Yuan. Dual CD73 enzyme blocker to reverse immune suppression [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 5652.
Evaluating the role of transient elastography post chronic hepatitis C treatment to predict hepatocellular carcinoma
Authors: Jacob H. Charette, Kelly W. Burak, Carla S. Coffin, Stephen E. Congly, Samuel S. Lee, Heidi Israelson, Sarah Williams, Matthew Sadler, Meredith A. Borman, Alexander I. Aspinall, Mark G. Swain, Abdel-Aziz Shaheen
Journal: Journal of Hepatology (2020)
Abstract 4549: Evaluation of GUCY2c-CD3 bispecific targeting GI cancers in an orthotopic colorectal tumor model
Authors: Johnny Yao, Divya Mathur, Sharon Yang, Roger Conant, Jessica Kearney, Vlad Buklan, Jonathan Golas, Edward Rosfjord
Journal: Cancer Research (2020)

Abstract GUCY2c is a tumor target expressed in &amp;gt;90% of colorectal cancer (CRC). It is also expressed on the apical side of intestinal epithelial tight junctions, where it regulates intestinal fluidity. PF-07062119, a GUCY2c-CD3 bispecific antibody that recruits T cells to GUCY2c expressing gastrointestinal tumors, has shown anti-tumor efficacy in several subcutaneous colorectal cancer models without any signs of intestinal toxicity. Here we describe the effects of PF-07062119 in an intestinal orthotopic xenograft model, created surgically in NSG mice using LS1034 CRC cells expressing luciferase. To establish this model, LS1034-luc tumor fragments were sutured onto the cecum proximal to the colon. Tumor growth was monitored through detection of luciferin bioluminescence. PF-07062119 was administered at 0.03, 0.1 and 0.3 mg/kg iv weekly, along with an adoptive transfer of 2x106 human T cells the day after bispecific compound dosing. At 0.3 mg/kg dose, the bioluminescence signal was significantly reduced compared with the isotype control group. Necropsies at the end of study revealed complete tumor clearance, or residual calcified or fibrotic tissues, at the tumor implant site in all animals of the 0.3 mg/kg group, compared with tumor presence in 9 of 9 animals and liver metastases in 2 of 9 animals in the isotype control group. The average tumor weight of 0.1 mg/kg dose group decreased relative to the control group, but the difference did not reach statistical significance. The results of histological examination indicate enhanced T cell infiltration in the tumor tissues compared with the normal intestinal tissues in PF-07062119 treated animals. No body weight loss or other clinical signs were observed in all groups. These results demonstrate that PF-07062119 can eliminate LS1034 orthotopic tumors and potential metastasis with no observable toxicities. This supports our hypothesis that apical restriction of GUCY2c expression in normal intestine creates tumor-vs-normal differential for selective targeting of GUCY2c positive tumors, and the GUCY2c-CD3 bispecific antibody redirects T cells to lyse the CRC tumor cells. Citation Format: Johnny Yao, Divya Mathur, Sharon Yang, Roger Conant, Jessica Kearney, Vlad Buklan, Jonathan Golas, Edward Rosfjord. Evaluation of GUCY2c-CD3 bispecific targeting GI cancers in an orthotopic colorectal tumor 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 4549.
THU0037 Class specific rheumatoid factors and interleukin-13 in rheumatoid arthritis
Authors: A Spadaro, T Rinaldi, M Bombardieri, R Scrivo, V Riccieri, E Taccari, G Valesini
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> In rheumatoid arthritis (RA) the production of rheumatoid factor (RF) by B-lymphocytes could depend on the action of different cytokines. <h3>Objectives</h3> Aim of this study was to detect interleukin 13 (IL-13), a potent modulator of B-cell functions<sup>1</sup>, in sera of RA patients in order to investigate the relationship of this cytokine, with different class specific RFs. <h3>Methods</h3> We studied 36 consecutive patients with RA, classified according to Arnett criteria and 20 healthy subjects matched for age and sex. In all patients, we evaluated the main clinical and laboratory parameters including the determination of IgM-RF, IgA-RF, IgG-RF and IL-13 by immunoenzimatic methods. <h3>Results</h3> We found detectable levels of IL-13 (&gt;1.56 pg/ml) in 86.1% of RA patients and in 40% of controls (p &lt; 0.0006). The IL-13 serum levels were significantly (p &lt; 0.00001) higher in patients with RA (mean/lower and upper 95% CI = 165.4/99.3–231.6 pg/ml) respect to the controls (mean/lower and upper 95% CI = 3.9/0.8–7.0 pg/ml). The serum levels of IL-13 correlated with those of IgM-RF (r = 0.591; p &lt; 0.0001) and IgA-RF (r = 0.505; p &lt; 0.002), while we didn't find any relationship with IgG-RF, IgM, IgA and IgG levels. IgA-RF levels correlated with those of IgM-RF (r = 0.548; p &lt; 0.0005) and IgG-RF (r = 0.543; p &lt; 0.0006), while no relationship between IgM-RF and IgG-RF (r = 0.222; n.s.) was found. The comparison of patients with or without the different class specific RFs revealed that patients with IgM-RF had significantly (p &lt; 0.018) higher levels of IL-13 respect to the patients without (mean/lower and upper 95% CI = 202.4/125.8–278.9 vs 12.6/2.2–22.9 pg/ml), while this finding was not observed for IgA-RF (mean/lower and upper 95% CI = 191.1/114.3–267.9 vs 59.3/-58.6–177.2 pg/ml) and IgG-RF(mean/lower and upper 95% CI = 239.4/48.6–430.2 vs 147.6/74.5–220.7 pg/ml). We didn't find any relationship of serum IL-13 levels with clinical and other laboratory signs of disease activity. <h3>Conclusion</h3> In conclusion our results show that IL-13 is involved in pathogenetic mechanism of RA, suggesting that IL-13 source could derive from an excessive joint or intravascular production by immune system. A relevant action of IL-13 seems to be related with a selective isotype production of IgM-RF. <h3>Reference</h3> Punnonen J, Aversa G, Cocks BG, McKenzie ANJ, Menon S, Zurawski G, De Waal Malefty R, De Vries JE. Interleukin 13 induces interleukin-4-indipendent IgG4 and IgE synthesis and CD23 expression by human B cells. Proc Natl Acad Sci USA 1993;90:3730–4
Abstract A29: Association of support group attendance with quality-of-life metrics in head and neck cancer patients
Authors: Kyohei Itamura, David Lam, Brian Cameron, Tamara Chambers, Niels Kokot, Dennis Maceri, Uttam Sinha, Mark Swanson, Brenda Villegas
Journal: Clinical Cancer Research (2020)

Abstract Quality of life has emerged as an increasingly prominent metric of interest for those with head and neck cancer during the course of their recovery. Although many factors have been shown to affect quality of life, the effect of support group attendance has been limited and mixed in the head and neck cancer literature. There is still controversy with regard to the efficacy of support groups. This study aims to add to the literature by reporting the association of support group attendance on quality-of-life measures in head and neck cancer patients. Our findings will help with recommendations for implementing support groups into head and neck cancer care. This is a cross-sectional, survey-based study employing the University of Washington head and neck cancer quality-of-life questionnaire. This survey has been previously validated in the literature as an objective quality of life measurement tool for head and neck cancer patients. All study participants are head and neck cancer patients who have received treatment. Study participants were separated into two separate groups: 1) patients who have never attended support group in the past; 2) patients who have utilized support group. Survey scores are compared between the two groups via unpaired Mann-Whitney U test. Patients who attended support group (N=32) compared to those who have not (N=52) showed significantly greater quality-of-life median scores on appearance (support group median score = 75 vs. no support group median score = 50, U=513, p=0.02), activity (75 vs. 50, U=463, p=0.004), recreation (75 vs. 50, U=404, p&amp;lt;0.001), mood (75 vs. 50, U=310, p&amp;lt;0.001), anxiety (100 vs. 30, U=164, p&amp;lt;0.001), and overall sense of quality of life (80 vs. 60, U=365, p&amp;lt;0.001). There were no statistically significant differences between the two groups for scores in pain, swallowing, chewing, speech, shoulder mobility, taste, or recent changes in subjective sense of quality of life. Our data suggest that support group attendance is associated with a higher quality of life specifically related to mental health and social well-being. There was no observable benefit in physical functional recovery with support group attendance. There appear to be psychosocial benefits from incorporating support groups into head and neck cancer rehabilitation. Citation Format: Kyohei Itamura, David Lam, Brian Cameron, Tamara Chambers, Niels Kokot, Dennis Maceri, Uttam Sinha, Mark Swanson, Brenda Villegas. Association of support group attendance with quality-of-life metrics in head and neck cancer patients [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A29.
Abstract CT164: A phase 1 study of abemaciclib in Chinese patients with advanced and/or metastatic cancers
Authors: Xichun Hu, Nong Yang, Jian Zhang, Chunhua Zhou, Dongmei Ji, Weina Shen, Wenhua Li, Rubing Han, Yi Lu, Sonya C. Chapman
Journal: Cancer Research (2020)

Abstract Background: Abemaciclib, a cyclin-dependent kinase 4 &amp; 6 inhibitor, is approved in combination with endocrine therapy or as a single agent for HR+/HER2- advanced breast cancer patients (pts) outside of China. The safety and PK profile has not been established in Chinese pts. Patients and methods: In this multicenter, open-label, phase 1 trial, pts were randomized to receive abemaciclib 150 mg or 200 mg orally every 12 hours on a 28-day cycle. The primary objective was to evaluate the safety and tolerability of abemaciclib monotherapy in Chinese pts with advanced and/or metastatic cancers. The secondary objective was to assess PK and antitumor activity. Results: A total of 25 pts were treated with abemaciclib: 12 in 150 mg cohort and 13 in 200 mg cohort. Pts had a median age of 54 years (range: 29-69) and a median of 4 prior systemic therapies (range: 1-7) for metastatic disease. In two dose cohorts, common (≥25%) treatment emergent adverse event (TEAE) related to study treatment included diarrhea, neutrophil count decreased, white blood cell count decreased, decreased appetite, blood creatinine increased, malaise, anemia, platelet count decreased, nausea, alanine aminotransferase increased and cough. The majority of TEAEs were Grade 1 or 2 in severity. Study treatment related Grade ≥3 TEAE (≥10%) included neutrophil count decreased (32%), platelet count decreased (24%), embolism (16%), diarrhea (12%) and white blood cell count decreased (12%). Four pts (16%) discontinued treatment due to AE. The PK characteristics of abemaciclib and its two major active metabolites (LSN2839567 and LSN3106726) were comparable to those observed in previous studies in non-Chinese populations. No CR was observed. Two pts (8%) achieved PR with one confirmed responder. The disease control rate (CR + PR + SD) was 68% (n=17). Conclusion: Abemaciclib was well tolerated at both cohorts evaluated in Chinese pts with advanced and/or metastatic cancers. The safety profile and PK characteristics in Chinese pts were similar to those in previous studies in non-Chinese populations. Preliminary antitumor activity was observed and supported further development of abemaciclib in Chinese pts. ClinicalTrials.gov no.: NCT02919696 Citation Format: Xichun Hu, Nong Yang, Jian Zhang, Chunhua Zhou, Dongmei Ji, Weina Shen, Wenhua Li, Rubing Han, Yi Lu, Sonya C. Chapman. A phase 1 study of abemaciclib in Chinese patients with advanced and/or metastatic cancers [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 CT164.
Abstract 3177: Panel-derived tumor mutational burden (TMB) is associated with the response to the immune checkpoint inhibitors (ICIs) in urothelial cancers
Authors: Yi-Lin Hsieh, Pei-Ning Yu, Yi-Hua Jan, Meng-Shao Lai, Woei-Fuh Wang, De-Wei Zhuo, Shu-Jen Chen, Jen-Hao Cheng, Kien Thiam Tan, Yu-Li Su
Journal: Cancer Research (2020)

Abstract Background: Tumor mutational burden (TMB) has been emerging as a relatively new biomarker that is independent of PDL1 for the prediction of response to the immune checkpoint inhibitor (ICI) treatment. A recent study has shown that whole exome sequencing (WES)-derived TMB correlates well with panel-derived TMB that is estimated using targeted sequencing. Here, we evaluate the correlation between panel-derived TMB with response to ICI treatment in urothelial cancers. Methods: FFPE tumor tissues from 30 patients with urothelial cancers who had previously received ICI as monotherapies or combination with chemotherapies at Chang Gung Memorial Hospital were retrospectively underwent targeted next-generation sequencing (ACTOncoTM) for the identification of nonsynonymous variants across 440 cancer- associated genes. Tumor mutational burden (TMB) was calculated by using the sequenced regions of ACTOncoTM to estimate the number of somatic nonsynonymous mutations per megabase of all protein-coding genes. The TMB calculation predicted somatic variants and applied a machine learning model with a cancer hotspot correction. RECIST criteria were used to categorize tumor response to the treatment. Results: Patients were defined as responders (CR/PR) and non-responders (SD/PD) according to the RECIST evaluation. In the cohort receiving ICI monotherapy, the responders (CR/PR, n=8) had significantly higher TMB than non-responders (SD/PD, n=15) (Median 16.2 muts/Mb vs. 6.5 muts/Mb, p=0.0035). One patient with moderate TMB (11.0 muts/Mb) who exhibited disease progression following ICI therapy harbored biallelic JAK2 inactivation. Three high-TMB tumors exhibited mutational signature of aristolochic acid exposure. Conclusions: Although the cohort size is small, this study showed that panel-derived TMB can serve as an independent predictive biomarker to identify urothelial cancer patients for immune checkpoint inhibitor therapy. Citation Format: Yi-Lin Hsieh, Pei-Ning Yu, Yi-Hua Jan, Meng-Shao Lai, Woei-Fuh Wang, De-Wei Zhuo, Shu-Jen Chen, Jen-Hao Cheng, Kien Thiam Tan, Yu-Li Su. Panel-derived tumor mutational burden (TMB) is associated with the response to the immune checkpoint inhibitors (ICIs) in urothelial cancers [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 3177.