tbuckley/cabot-search huggingface dataset:
Abstract 3272: Is PD-L1 expression a decision-making biomarker for immunotherapy: a meta-analysis and cross-sectional study
Authors: Zhijie Wang, Jianchun Duan, Longgang Cui, Shangli Cai, Jie Wang
Journal: Cancer Research (2020)

Abstract Background: PD-L1 expression has been approved by FDA as a diagnosis for anti-PD-(L)1 therapy in several types of cancer, however, there were still discrepancies of the predictive value of PD-L1 expression. Here we aimed to systematically assess the value of PD-L1 expression in determining cancer patients who should be offered anti-PD-(L)1 therapy and to characterize PD-L1 expression in Chinese cancer population. Methods: Cochrane library, PubMed and Embase databases were systematically searched to include relevant studies published between January 2000 and June 2019. We also reviewed the reports from all major conference proceedings. All randomized controlled trials investigating anti-PD-(L)1 efficacy in solid tumors were initially included if overall survival (OS) data were stratified by PD-L1 expression. Differences in OS benefits between PD-L1-positive and PD-L1-negative patients were analyzed. Effect size derived from each study was pooled using a random-effects model. Data regarding PD-L1 expression in Chinese patients were obtained from a CAP-accredited and CLIA-certified laboratory. Results: Twenty-five RCTs involving 14,471 patients were included. OS benefit was observed in patients with either positive (HR=0.68 [0.63-0.73], P&amp;lt;0.00001) or negative (HR=0.86 [0.78-0.95], P=0.003) PD-L1 expression, though significant longer OS was achieved in patients that are PD-L1 positive (P interaction=0.0001). Superior PFS were observed in patients with positive PD-L1 expression (HR=0.69 [0.57-0.82]) while not with negative PD-L1 expression (HR=1.00 [0.85-1.19]). PD-L1-positive patients exhibited significantly improved ORR than those who tested negative for PD-L1 when treated with immunotherapy (OR=0.50 [0.39-0.65], P&amp;lt;0.00001), while no differences were observed among patients given SOC (OR=1.02 [0.86-1.21], P=0.81). Analysis of Chinese patients PD-L1 status revealed that thymoma and small cell lung cancer expressed the highest and the lowest levels of PD-L1, respectively. Conclusion: PD-L1 expression alone is not determinative in patient selection for anti-PD-(L)1 treatment. Multiple modality biomarkers should be considered for cancer patients especially for those with PD-L1-negative tumors. Citation Format: Zhijie Wang, Jianchun Duan, Longgang Cui, Shangli Cai, Jie Wang. Is PD-L1 expression a decision-making biomarker for immunotherapy: a meta-analysis and cross-sectional study [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 3272.
Spatial signatures identify immune escape via PD-1 as a defining feature of T-cell/histiocyte-rich large B-cell lymphoma
Authors: Gabriel K. Griffin, Jason L. Weirather, Margaretha G. M. Roemer, Mikel Lipschitz, Alyssa Kelley, Pei-Hsuan Chen, Daniel Gusenleitner, Erin Jeter, Christine Pak, Evisa Gjini, Bjoern Chapuy, Michael H. Rosenthal, Jie Xu, Benjamin J. Chen, Aliyah R. Sohani, Scott B. Lovitch, Jeremy S. Abramson, Jeffrey J. Ishizuka, Austin I. Kim, Caron A. Jacobson, Ann S. LaCasce, Christopher D. Fletcher, Donna Neuberg, Gordon J. Freeman, F. Stephen Hodi, Kyle Wright, Azra H. Ligon, Eric D. Jacobsen, Philippe Armand, Margaret A. Shipp, Scott J. Rodig
Journal: Blood (2020)
Abstract 4382: Bioinformatics analysis for hub genes and pathways in hepatocellular carcinoma
Authors: Xianzhang Zeng, Lu Ao, Xinjian Lin, Xu Lin, Wannan Chen
Journal: Cancer Research (2020)

Abstract Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a high recurrence rate and mortality. There is no effective treatment for HCC and the molecular mechanisms of HCC are still not fully understood. To identify the potential biomarkers in the carcinogenesis and progression of HCC, microarray datasets GSE101685, GSE121248, GSE38941, GSE62232 and GSE87630 were downloaded from Gene Expression Omnibus (GEO) database. Screening of differential expressed genes (DEGs), and functional enrichment analyses were performed. The protein-protein interaction network (PPI) were constructed and significant module genes and hub genes were identified using STRING and Cytoscape. 149 DEGs were screened, including 114 down-regulated genes and 35 up-regulated genes. Fifteen hub genes were identified and biological process analysis revealed that these genes were mainly enriched in cell cycle, oocyte meiosis and protein binding. Survival analysis and co-expression network analysis showed that TOP2A, TPX2, RACGAP1 and PTTG1 may be involved in the carcinogenesis, invasion or recurrence of HCC. In conclusion, the present study may help us understand the molecular mechanisms underlying the carcinogenesis and progression of HCC, and provide candidate targets for diagnosis and treatment of HCC. Key words: Hepatocellular carcinoma; Differentially expressed genes; Protein-protein interaction; Bioinformatics; Microarray Citation Format: Xianzhang Zeng, Lu Ao, Xinjian Lin, Xu Lin, Wannan Chen. Bioinformatics analysis for hub genes and pathways 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 4382.
Synergistic Antimicrobial Titanium Carbide (MXene) Conjugated with Gold Nanoclusters
Authors: Kaiyuan Zheng, Shuo Li, Lin Jing, Po‐Yen Chen, Jianping Xie
Journal: Advanced Healthcare Materials (2020)

Bacterial resistance toward antibiotics is a world-wide problem, and one potential solution to fight against the resistance is to develop multi-mechanism antimicrobial agents to achieve synergistic performance. Titanium carbide (MXene) is an emerging 2D nanomaterial with antimicrobial ability to physically damage bacterial membrane and chemically induce oxidative stress, and it can be further conjugated with nanomaterials to improve its antibacterial performance. Herein, a synergistic antimicrobial agent is developed through conjugation of the ultra-small gold nanoclusters (AuNCs) on MXene nanosheets. The conjugated AuNCs are effectively delivered into bacteria after bacterial membrane damage caused by MXene, generating localized reactive oxygen species (ROS) of high concentration to effectively oxidize bacterial membrane lipid for enhanced membrane broken, as well as bacterial DNA for violent fragmentation. Thus, the synergistic physical (via MXene) and chemical (via MXene and AuNCs) antimicrobial mechanisms lead to eventual bacterial death of both Gram-positive and Gram-negative bacteria, with low IC50 values of 11.7 µg mL-1 of MXene and 0.04 µm of AuNCs. Moreover, the crumpled MXene-AuNCs structure is constructed to inhibit biofilm formation, which hold synergistic antibacterial ability of MXene-AuNCs conjugation, hydrophobic surface to prevent bacterial attachment, and large surface area containing higher density of bactericides.
Abstract A58: HR-ESI-MS identification of novel triterpenoid antitumor substances in securidaca 1, using activity-guided SRB assay
Authors: Titus Chukwuemeka Obasi, Radu Oprean
Journal: Clinical Cancer Research (2020)

Abstract Background: Securidaca 1 is a triterpenoid saponin fraction obtained from African medicinal plant S. longipedunculata, whose action activated apoptosis via inhibition of PI3K-AKT downstream. Preliminary studies show an IC50 of 7.03 (μg/mL), with RT-qPCR gene expression revealing a fold-change reduction of MCL-1 and BCL2L1 antiapoptotic proteins, as well as the inhibition of AKT-3, VEGFA, and CDH-1. Therefore, considering the role of PI3K-AKT pathway in tumoral resistance of ovarian cancer and epithelial-mesenchymal transition during development, our major aim was to isolate and identify the components of securidaca 1 responsible for the activity. Experimental Procedure: Freeze-dried sample of securidaca 1 was fractionated by FLASH chromatography (RP-C18) and the resultant fractions screened by SRB cytotoxicity assay (96-well format) using HeLa cell line. The most promising subfraction was further purified by semipreparative HPLC (reversed-phase). Isolated substances were identified by HR-ESI-MS and IC50s determined and compared with 5-fluorouracil (5-FU) reference standard. Results: The HR-ESI-MS spectrum under negative ion mode revealed the parent molecular ion peaks of the semipreparative fractions (FR15-6 and FR15-7), whose IC50s were confirmed at 3.84 and 4.83 μg/mL, respectively, on HeLa cell line, more sensitive than 5-FU. MS/MS fragmentation spectra (negative ion mode) show putative fragments of molecular ions 455 and 425 (m/z), respectively, typically indicating oleanine triterpenoid aglycone. Post-TLC derivatization tested positive to Liebermann Burckhard and Carr Price reactions, and sugars. Conclusion: FR15-6 and FR15-7 are potential candidates for anticancer development whose actions may be responsible for antitumor activities previously seen in securidaca 1. Work is ongoing to evaluate their capacities in blocking tumor development via antiapoptotic effectors of PI3K-AKT downstream pathway. Note: This abstract was not presented at the conference. Citation Format: Titus Chukwuemeka Obasi, Radu Oprean. HR-ESI-MS identification of novel triterpenoid antitumor substances in securidaca 1, using activity-guided SRB assay [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A58.
Registering ethnicity for covid-19 research: is the law an obstacle?
Authors: Corrette Ploem, Jeanine Suurmond
Journal: BMJ (2020)

A race equality taskforce has been launched in the UK to explore racial disparities in women’s healthcare and racism in the obstetric and gynaecology workforce.1

The risk of covid-19 related death among some ethnic groups is significantly higher than in those of white ethnicity.2 Without collecting, registering, and using data about patients’ ethnicity we would not be informed about these important (and undesirable) ethnic differences. …
Membranes for Guided Bone Regeneration: A Road from Bench to Bedside
Authors: Paola Aprile, Didier Letourneur, Teresa Simon‐Yarza
Journal: Advanced Healthcare Materials (2020)

Bone resorption can negatively influence the osseointegration of dental implants. Barrier membranes for guided bone regeneration (GBR) are used to exclude nonosteogenic tissues from influencing the bone healing process. In addition to the existing barrier membranes available on the market, a growing variety of membranes for GBR with tailorable physicochemical properties are under preclinical evaluation. Hence, the aim of this review is to provide a comprehensive description of materials used for GBR and to report the main industrial and regulatory aspects allowing the commercialization of these medical devices (MDs). In particular, a summary of the main attributes defining a GBR membrane is reported along with a description of commercially available and under development membranes. Finally, strategies for the scaling-up of the manufacturing process and the regulatory framework of the main MD producers (USA, EU, Japan, China, and India) are presented. The description of the regulatory approval process of GBR membranes is representative of the typical path that medium- to high-risk MDs have to follow for an effective medical translation, which is of fundamental importance to increase the impact of biomedical research on public health.
Impaired angiotensin II type 1 receptor signaling contributes to sepsis-induced acute kidney injury
Authors: Daniel E. Leisman, Tiago D. Fernandes, Vanesa Bijol, Mabel N. Abraham, Jake R. Lehman, Matthew D. Taylor, Christine Capone, Omar Yaipan, Rinaldo Bellomo, Clifford S. Deutschman
Journal: Kidney International (2020)
Abstract 5711: Therapeutic induction of tumor-selective ferroptosis in models of pancreatic cancer
Authors: Michael Badgley, Kathleen DelGiorno, Geoffrey Wahl, Costas Lyssiotis, Kenneth P. Olive
Journal: Cancer Research (2020)

Abstract Pancreatic ductal adenocarcinoma (PDA) is an aggressive cancer with few therapeutic options. Oncogenic signaling from mutant Kras, the driving oncogene of PDA, drives ROS production, making PDA cells reliant on ROS detoxification processes. To detoxify ROS, mammalian cells use thiols derived from the semi-essential amino acid cysteine, which is imported from exogenous pools of cystine via the system xC− cystine/glutamate antiporter. We found that cysteine depletion in multiple human PDA lines induced a rapid, oxidative, iron-dependent form of non-apoptotic cell death called ferroptosis. Confirming work in other systems, we found that glutathione depletion was necessary for the induction of ferroptosis in PDA cells. However, depletion of glutathione alone was not sufficient to induce ferroptosis, indicating that modulation of other cysteine-dependent processes must also play a role in ferroptosis. Using carbon-labelled cystine, we determined that extracellular cystine is quickly incorporated into coenzyme A. Furthermore, dual inhibition of both CoA and GSH synthesis combined to induce ferroptosis, and CoA treatment rescued the induction of ferroptosis following cysteine depletion. To assess whether cysteine depletion could be useful for targeting pancreatic tumors in vivo, we utilized both genetic and pharmacological approaches. First, we generated a dual recombinase mouse model in which the system xC- gene Slc7a11 can be acutely, systemically deleted in mice with established K-ras/p53 mutant PDA. Acute deletion of Slc7a11 in mice with established PDA led to tumor stabilizations/regressions and increased overall survival, and this was fully reversed by co-treatment with the membrane-permeable cysteine analog NAC. Second, we treated the well validated KPC genetic model of PDA with cyst(e)inase, an engineered enzyme that breaks down cysteine and cystine in circulation. Tumor-bearing KPC mice treated with cyst(e)inase also exhibited tumor responses. In both the genetic and pharmacological models, we observed tumor-selective necrosis and confirmed the induction of ferroptosis using several orthogonal techniques, including electron microscopy, immunohistochemistry, histopathology, and laser capture microdissection/RNA sequencing. These data demonstrate the potential therapeutic utility of targeting cystine import in pancreatic cancer. Citation Format: Michael Badgley, Kathleen DelGiorno, Geoffrey Wahl, Costas Lyssiotis, Kenneth P. Olive. Therapeutic induction of tumor-selective ferroptosis in models of pancreatic 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 5711.
Abstract 4696: Endometrial receptivity markers in patients with uterine fibroids and their correlation with air pollution exposure
Authors: Dara O. Ferreira, Giovana D. Maffazioli, Edmund C. Baracat, Katia C. Carvalho
Journal: Cancer Research (2020)

Abstract Uterine leiomyomas (LM) are the most frequent benign tumors in women of reproductive age. They are associated with infertility, pelvic pain, abnormal uterine bleeding and represent a public health challenge. LM are over 4 times more common in African-descendent women. Additionally, this tumor constitutes a major health and financial burden in several countries. Similar to many pathologies, environmental exposure contributes to their origin and development. Air pollution acts as a disruptor in the hormonal activity and in other key pathways leading to enhanced tumor progression and making possible pregnancies difficult. In this study, we evaluated LM samples from women resident in urban (high exposure area) and no-urban areas (low or negative exposure area) for the expression of genes related to endometrial receptivity. We selected a total of 100 patients and among them twenty fill the specific profile of those exposed or not exposed to air pollution. mRNA expression analysis was performed using an array composed by 84 receptivity-related genes (Array Code: CLAH27251A, Qiagen, USA). Gene expression analyses showed PRLR, LITAF, COL6A3, HOXA11, KLRC1, UBE2A e IGFBP5 with higher fold expression (fold &amp;gt;2) in the exposed group. On the other hand, PENK, CALB2, DUOX1, COMP, CXCL14, CTNNA2, TCN1, S100P, WNT5A, ERBB2, MTNR1B and EFNA1 were dowregulated in these samples (fold &amp;lt; - 4). Several other genes exhibited differential regulation between exposed and non-exposed group of patients, but with lower significance. Our results corroborate the expected for these populations, since it is known that women resident in areas with high air pollution have reproductive complications and higher tendency to tumors development. However, this work is the first evidence of the impairment of endometrial receptivity in uterine LM patients associated to air pollution in Brazil. Further studies are ongoing to validate and elucidate the specific roles of these genes in uterine LM origin and development, as well as their reproductive function in this population. Citation Format: Dara O. Ferreira, Giovana D. Maffazioli, Edmund C. Baracat, Katia C. Carvalho. Endometrial receptivity markers in patients with uterine fibroids and their correlation with air pollution exposure [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 4696.
Abstract B20: Endometrial cancer molecular risk stratification in endometrioid ovarian cancers: A novel application of precision medicine
Authors: Pauline Krämer, Aline Talhouk, Tjalling Bosse, Florian Heitz, Naveena Singh, Felix Kommoss, Sara Brucker, Jessica McAlpine, Stefan Kommoss, Martin Koebel, Michael Anglesio
Journal: Clinical Cancer Research (2020)

Abstract Objective: Endometrioid ovarian carcinoma (ENOC) is associated with a generally more favorable prognosis compared to other ovarian carcinoma histotypes. Nonetheless, patients are still treated with a “one size fits all” approach. While tumor staging offers some stratification, the development of personalized treatment concepts remains elusive. Our group has recently validated the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE), to distinguish clinically relevant prognostic groups amongst endometrial carcinomas. ENOC shares risk factors, genomics, and histology with its endometrial counterpart. The aim of our study was to apply and test ProMisE on ENOC. Methods: ProMisE was applied to 509 ENOC after biomarker-assisted review of ENOC histotype. Cases were aligned into low-risk POLE mutant (POLE), moderate-risk mismatch repair deficient (MMRd), high-risk p53 abnormal (p53abn), and a final moderate-risk category lacking these biomarkers (p53wt). Kaplan-Meier and multivariate survival analysis were performed. Results: 4% of cases were POLE, 16% MMRd, 71% p53wt, and 10% p53abn. Groups showed distinct progression-free and overall survival (p &amp;lt;0.001), near identical to profiles of endometrial cancers. 5-year PFS was 54% in p53abn, 82% in MMRd, 85% in p53wt, and 100% in POLEmut cases. Median overall survival was reached in p53 mutant cases only. ProMisE classes of ENOC were independent of stage and residual disease in multivariable analysis. Conclusion: ProMisE risk classification provides additional prognostic information in a large cohort of ENOC. Our findings support introduction of ProMisE-stratified treatment strategies to improve patient care across ENOC. Further, ENOC may benefit from parallel efforts under investigation in endometrial carcinoma. Citation Format: Pauline Krämer, Aline Talhouk, Tjalling Bosse, Florian Heitz, Naveena Singh, Felix Kommoss, Sara Brucker, Jessica McAlpine, Stefan Kommoss, Martin Koebel, Michael Anglesio. Endometrial cancer molecular risk stratification in endometrioid ovarian cancers: A novel application of precision medicine [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr B20.
Abstract 2964: Saffron has enhanced anti-proliferative effect against colorectal cancer cells with deficient DNA mismatch repair
Authors: Amr Amin, Akbar Soleimani, Chandraprabha Murali, Lucie Beresova, Hamid Shoraka, Hassan Brim, Hassan Ashktorab
Journal: Cancer Research (2020)

Abstract Background: Colorectal cancer (CRC) is one of the most common cancers worldwide. A subtype of CRC is associated with defective mismatch repair (dMMR) genes. Saffron has many potentially protective roles against colon malignancy, however, these roles in the context of of dMMR have not been explored. In this study, we aimed to study the effects of saffron in CRC cell lines with dMMR. Methods: Saffron crude extracts and specific compounds (crocin, crocetin and safranal) were used in colorectal cancer cell lines HCT116, HCT116+3 (inserted MLH1), HCT116+5 (inserted MH3) and HCT116+3+5 (Inserted MLH1 and MSH3). CDC25b, p-H.H2AX, TPDP1, and GAPDH were analyzed by Western blot. Cell cycle was analyzed by FACS. Proliferation and cytotoxicity were analyzed by MTT. Wound and migration assays were also performed. Results: Saffron crudes restricted the proliferation in colon cells with deficient MMR (HCT116) compared to proficient MMR. Wound healing assay indicates that deficient MMR cells are doing better than proficient MMR cells. The expression of CDC25b and TDP1 were upregulated in proficient MMR cell compared to deficient MMR cell, while H2AX was significantly upregulated in both cells type particularly at &amp;gt;10 mg/ml saffron in a concentration-dependent manner (after normalization with GADPH as control).The reduction in cellular proliferation and motility might be due to cell cycle arrest at G2-phase rather than to apoptosis. The major active saffron compounds, safranal and crocin reproduced total saffron crudes effects but with lesser outcome. Conclusion: Saffron's anti-proliferative and healing effects is significant in cells with deficient MMR MLH1 and MSH3 genes. This effect may have a therapeutic implications and benefits for the CRC MSI tumors that are generally not recommended for 5FU-based treatment. Citation Format: Amr Amin, Akbar Soleimani, Chandraprabha Murali, Lucie Beresova, Hamid Shoraka, Hassan Brim, Hassan Ashktorab. Saffron has enhanced anti-proliferative effect against colorectal cancer cells with deficient DNA mismatch repair [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 2964.