tbuckley/cabot-search huggingface dataset:
Abstract 1077: Macrophage PI3Kγ controls T cell activation and T cell memory generation through the production of IL-12
Authors: Hideyuki Takahashi, Ryan M. Shepard, Marc A. Paradise, Sang Min Lee, Ann Shih, Cristina Flores-Arenas, William Kim, Judith A. Varner
Journal: Cancer Research (2020)

Abstract We previously reported that macrophage PI3kinase γ (PI3Kγ) controls a critical switch between immune stimulation and suppression during inflammation and cancer. PI3Kγ inhibition polarizes tumor-associated macrophages (TAMs) into pro-inflammatory macrophages, leading to the recruitment and activation of intratumoral CD8+ T cells, tumor growth inhibition and anti-tumor memory (Kaneda et al 2016). In the present study, we elucidated the role of PI3Kγ in the control of T cell immune responses, including activation, memory generation and exhaustion, in mouse models of head and neck squamous cell carcinomas (HNSCC). High-dimensional single-cell analysis including single-cell RNA sequencing and mass cytometry of HPV+ HNSCC tumors revealed significant differences in intratumoral immune cell clusters in HPV+ HNSCC tumors from WT and Pik3cg−/− mice. Primary tumors from Pik3cg−/− mice exhibited more pro-inflammatory TAMs, more activated CD8+ T cells and fewer exhausted T cells than in tumors from WT mice. Both tumor- and spleen-derived T cells from Pik3cg−/− mice exhibited more IFNγ expression than those from WT mice; this increase could be reversed by the neutralization of IL-12 and MHCII. We observed significantly more effector memory T cells in spleens of Pik3cg−/− mice than WT mice; accordingly, adoptive transfer of Pik3cg−/− but not WT splenic T cells conferred tumor resistance onto naive WT mice, indicating that PI3Kγ inhibition promotes T cell mediated immunological memory. In summary, Pik3cg−/− mice exhibited more activated T cells, T cell mediated immune responses and T cell memory than WT mice, resulting significant and sustained suppression of tumor growth. These results indicate that PI3Kγ-targeted therapy may activate durable T cell immune responses in patients with HNSCC. Citation Format: Hideyuki Takahashi, Ryan M. Shepard, Marc A. Paradise, Sang Min Lee, Ann Shih, Cristina Flores-Arenas, William Kim, Judith A. Varner. Macrophage PI3Kγ controls T cell activation and T cell memory generation through the production of IL-12 [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 1077.
AB0121 Cytostatics effect on the development of malignant and lymphatic proliferative formations during sjorgen?s disease (ss)
Authors: MV Simonova, VI Vasiliev, NS Shornikova
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Treatment of rheumatological pts by alkylating cytostatics is undoubtedly of positive effect on the process of the disease but in a long term can stimulate the development of neoplasms and lymphatic proliferative diseases. <h3>Objectives</h3> To detalise the degree of risk of above mentioned pathologies in SS pts who for a long time took low doses of chlorobutin or cyclophosphane – from 5 to 15 years. <h3>Methods</h3> In the 1st group of 300 pts aged 15–75 years (46.4(1.7) with disease duration of 5–25 years (8.7(1.9) 200 pts took 5 mg of Prednisolone daily, 1.8 g for a year, 0.9–1.8 g for the subsequent years combined with chlorobutin by 2 mg daily; 720 mg for a year and 360–720 mg for the next years. 100 pts had cyclophosphane by 200 mg twice a month i.v.; 4.8 g for a year and in the next 5 years yearly dosage was 2.4–4.8 g. 2nd group included 100 female pts who took only Prednisolone according the same scheme. 3d group of 100 female pts had no antirheumatic therapy. Age of pts in 2nd and 3d groups was 18–78 years (46.2(2.3) and disease duration of 4–26 years (9.2(2.1). Minimal frequency of blastomas and lymphatic proliferative diseases (1.6%) development was in the 1st group (pseudolymphoma in 1 pt, lymphoma – 2 cases, cancer of stomach in 1 and of skin in 1 pt). In the group treated only by GCS 7 cases of lymphoma were found and 1 case of stomach cancer (8%). Pts who had no antirheumatic therapy had 7 pseudolymphomas 9 lymphomas, 2 cases of Valdenstrem crioglobulinemia, 2 cases of stomach cancer and 1 pulmonary cancer (21%). Out of them pseudolymphomas and lymphomas were diagnosed in 18%. <h3>Results</h3> <h3>Conclusion</h3> Long term of taking of low doses of cytistatics (chlorobutin, cyclophosphane) combined with low doses of GCS does not promote the development of blastoma process in SS pts and decreases the frequency of transformation of the disease in malignant lymphomas.
Abstract 5373: Circulating tumor cell as a predictive marker for immunotherapy in advnaced non-small cell lung cancer
Authors: Cheol-Kyu Park, Joon-Young Yoon, Min-Suk Kim, Bo-Gun Koh, Hyun-Ju Cho, In-Jae Oh, Young-Chul Kim
Journal: Cancer Research (2020)

Abstract Background: Circulating tumor cells (CTCs) have potential to provide minimally invasive way for the response monitoring of various cancer. This study aimed to investigate the feasibility of CTCs as a predictive marker for anti-PD-L1 immunotherapy in patients with advanced non-small cell lung cancer (NSCLC). Methods: This study included 37 patients with advanced NSCLC receiving atezolizumab monotherapy as second-line or more from July to November 2019. Blood was collected in a K2-EDTA tube and CTCs were isolated and enriched by using CD-PRIMETM system which is antibody-independent size-based isolation method. By Bioview CCBS system, total CTCs (tCTCs) were identified by a sum of single EpCAM/CK-positive (sCTCs) and double EpCAM/CK-CD45-positive cells (dCTCs). Results: Among 26 response-evaluable patients, objective response rate (ORR) and disease control rate (DCR) were 11.5% (3/26) and 57.7% (15/26), respectively. At cycle 1 (C1), patients with progression (PD) showed higher sCTC count (median, 8.6 vs. 4.3, p=0.065) and sCTC-to-tCTC ratio (median %, 35.9 vs. 9.8, p=0.024) than those without PD. During treatment, tCTC and sCTC count showed significant increase from C1 to C2 (p=0.019 and p=0.022). The subgroup with high sCTC increase from C1 to C2 (more than 2-folds) showed higher DCR than subgroup with low sCTC increase (less than 2-folds) (88.9% vs. 44.4%, p=0.066). Patients with high sCTC-to-tCTC ratio at C1 showed worse progression-free survival (median, 2.1 months) than those with low sCTC-to-tCTC ratio (not reached, hazard ratio 2.87, 95% confidence interval: 1.06-7.75, p=0.082). Conclusion: The baseline sCTC count and sCTC increase (more than 2-folds) at the first 3-week after atezolizumab could be potential biomarkers to predict the disease progression and poor survival in advanced NSCLC. Citation Format: Cheol-Kyu Park, Joon-Young Yoon, Min-Suk Kim, Bo-Gun Koh, Hyun-Ju Cho, In-Jae Oh, Young-Chul Kim. Circulating tumor cell as a predictive marker for immunotherapy in advnaced non-small cell lung 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 5373.
Dalbavancin exposure in vitro selects for dalbavancin-non-susceptible and vancomycin-intermediate strains of methicillin-resistant Staphylococcus aureus
Authors: Brian J. Werth, Nathaniel K. Ashford, Kelsi Penewit, Adam Waalkes, Elizabeth A. Holmes, Dylan H. Ross, Tianwei Shen, Kelly M. Hines, Stephen J. Salipante, Libin Xu
Journal: Clinical Microbiology and Infection (2020)
Abstract 2732: NLRP12 suppresses colorectal cancer progression and invasion via downregulation of the Wnt/b-catenin pathway
Authors: Shahanshah Khan, Hasan Zaki
Journal: Cancer Research (2020)

Abstract Metastatic CRC is associated with increased mortality, underscoring the importance of understanding the molecular mechanism of CRC invasion and metastasis. We recently demonstrated that mice deficient in NLRP12, an innate immune sensor, are susceptible to CRC with increased incidence of invasive adenocarcinoma. Here, we investigated the molecular mechanism of NLRP12-mediated suppression of cancer progression and invasion using mouse models and in vitro biochemical studies. Nlrp12−/− mice treated with azoxymethane plus dextran sodium sulfate developed higher tumor burden and invasive adenocarcinoma compared to WT mice. RNA-seq analysis showed significantly higher levels of protooncogenes, matrix metalloproteinases (Mmp 3, 7,8, 10, 12), and epithelial to mesenchymal transition (EMT) markers (Vim, Fn1, Foxc2, Zeb2, Ezh2) in Nlrp12−/− tumors. To understand the underlying mechanism of increased expression of cancer promoting genes in Nlrp12−/− tumors, we analyzed activation of various cell signaling pathways. To our surprise, there was no major difference in the activation NF-κB, ERK, JNK, and STAT3, which have previously been shown to be downregulated by NLRP12, between WT and Nlrp12−/- tumors. However, we observed strikingly higher levels of β-catenin and expression of Wnt target genes (Ctnnb1, Axin2, Yap1, Tcf3, Lgr5, etc.) in Nlrp12−/− tumors. Consistently, deletion of NLRP12 in APCmin/+ mice led to higher polyp development and activation of the Wnt/β-catenin pathway. Notably, hyperactivation of the Wnt/β-catenin pathway is a hallmark of CRC and about 80% of CRC patients carry mutations in the Wnt/β-catenin pathway. To further explore the link between NLRP12 and the Wnt/β-catenin pathway, we overexpressed NLRP12 in HEK293T cells and CRC cell line MC38. NLRP12-overexpressed cells showed reduced activation of β-catenin and expression of Wnt target genes following stimulation with Wnt3a. An opposite result was observed when NLRP12 was knocked out from these cell lines. Consistently, Nlrp12-KO MC38 cells exhibited increased proliferation, colony formation, and migration. These data for the first time demonstrate that NLRP12 is an intrinsic negative regulator of the Wnt/β-catenin pathway. Overall, these findings reveal a novel CRC suppression pathway involving NLRP12 and suggest that the NLRP12/β-catenin signaling axis could be therapeutically targeted for the treatment of CRC invasion and metastasis. Citation Format: Shahanshah Khan, Hasan Zaki. NLRP12 suppresses colorectal cancer progression and invasion via downregulation of the Wnt/b-catenin pathway [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 2732.
Deep learning-based lumbosacral reconstruction for difficulty prediction of percutaneous endoscopic transforaminal discectomy at L5/S1 level: A retrospective cohort study
Authors: Guoxin Fan, Huaqing Liu, Dongdong Wang, Chaobo Feng, Yufeng Li, Bangde Yin, Zhi Zhou, Xin Gu, Hailong Zhang, Yi Lu, Shisheng He
Journal: International Journal of Surgery (2020)
Abstract B80: Predictive treatment response models for epithelial ovarian cancer: Comparison of 2D, 3D, and in vivo models
Authors: Melica Nourmoussavi, Euridice Carmona, Anne-Marie Mes-Masson
Journal: Clinical Cancer Research (2020)

Abstract Introduction: Epithelial ovarian cancer (EOC) is still a deadly disease, with a 5-year overall survival of 45%. Current research focuses on the development of new targeted and personalized therapies to improve survival in these patients. The drug discovery pipeline is dependent on preclinical models, which have mostly focused on 2D systems because of time and cost efficiency. However, it is currently unclear whether they accurately reflect patient response and whether other in vitro models may better predict therapeutic response. Preliminary data from our laboratory suggest that the sensitivity to carboplatin chemotherapy varies between 2D and 3D in vitro models. We hypothesize that the 3D model will more closely reflect therapeutic response. The primary objective of this study is to characterize the sensitivity to carboplatin of our EOC cell lines in 2D monolayers and 3D spheroids and compare them to their in vivo response using our xenograft mouse models. Methods: We are injecting NOD-RAG mice with 7 EOC cell lines (TOV112D, TOV21G, OV4485, OV4453, OV1946, OV90, OV3133). At 200mm3, weekly carboplatin treatments (group1 = control, group 2= 25mg/kg, group 3= 50mg/kg, group 4= 75mg/kg) are given up to 6 cycles. Tumor volume and survival curves are used to categorize chemosensitivity between cell lines. Furthermore, the same cell lines are seeded in ultra-low attachment microplates to form spheroids over 48hr and are thereafter treated with 24hr of carboplatin. Flow cytometry analyses are done to classify cell lines. Results: The results for the 2D models using clonogenic assays (IC50) of the 7 cell lines have previously been published. Thus far, we have completed a first set of in vivo experiments for TOV21G showing a nonsignificant tumor growth suppression after 6 doses (no difference between the 3 treated and the nontreated group). Tumor growth suppression for OV90 was statistically significant with 50mg/kg and 75mg/kg of carboplatin after 6 doses. This demonstrates thus far that the most resistant cell line in 2D is more sensitive in an in vivo model. Conclusion: The results will help define the most reliable preclinical model with the highest translational potential to predict treatment response. Citation Format: Melica Nourmoussavi, Euridice Carmona, Anne-Marie Mes-Masson. Predictive treatment response models for epithelial ovarian cancer: Comparison of 2D, 3D, and in vivo models [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 B80.
Abstract 6309: Development of protein conformational array ELISA for p53 and SHP2 allosteric regulator screening and analysis
Authors: Xing Wang
Journal: Cancer Research (2020)

Abstract P53 and SHP2 plays important role during cancer development. For p53, more than 50% of cancers were shown to have gene mutation in this tumor suppressor, however how these gene mutations impact the p53 protein conformation and function have not be studies in much detail. A Protein Conformational Array ELISA was developed with 17 polyclonal antibodies covering the whole p53 molecule, by measuring the linear epitope distribution on the surface of the p53 protein, the conformational (Higher Order Structure or HOS) can be described quantitively. Initial studies have shown that in lung cancer cells, the level of p53 is significantly increased and more interestingly, the p53 HOS has changed at its N-terminal as compared with the wild type. For SHP2, a protein phosphatase, a 27-antibody panel was developed to characterize the HOS changes. Because of the generic nature of the phosphate binding site, it has been very challenging to develop phosphatase inhibitors, however studies have shown that allosteric regulators can be identified with excellent anti-tumor activities. Currently, some of the allosteric regulators identified are being tested in the clinic. The SHP2 Conformational Array ELISA will provide a robust platform for the screening and testing of potential allosteric regulators with its molecular resolution and high-throughput capability. This presentation will describe the development of the two conformational arrays and their applications in the study of p53 and SHP2 from different cancer cell lines and the characterization of the allosteric regulators identified. Citation Format: Xing Wang. Development of protein conformational array ELISA for p53 and SHP2 allosteric regulator screening and analysis [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 6309.
Long-term consequences of COVID-19: research needs
Authors: Dana Yelin, Eytan Wirtheim, Pauline Vetter, Andre C Kalil, Judith Bruchfeld, Michael Runold, Giovanni Guaraldi, Cristina Mussini, Carlota Gudiol, Miquel Pujol, Alessandra Bandera, Luigia Scudeller, Mical Paul, Laurent Kaiser, Leonard Leibovici
Journal: The Lancet Infectious Diseases (2020)
David George Edwin Wood
Authors: Bridget Osborne
Journal: BMJ (2020)

After qualifying David George Edwin Wood (“Woody”) moved to Bangor, north Wales, where he rapidly became a GP trainer and course organiser, before moving to Llys Meddyg in Conwy, which allowed him to pursue his interest in medical education. As associate dean for Cardiff University, he championed the All Wales non-principals scheme, ran a course for local …
Abstract 4499: Cancer targets early B-cell precursors to generate metastasis-promoting Bregs by promoting their premature emigration from the bone marrow and expansion in the circulation
Authors: Emeline Ragonnaud, Kanako Moritoh, Monica Bodogai, Soizic Garaud, Chen Chen, Xin Wang, Karen Willard-Gallo, Arya Biragyn
Journal: Cancer Research (2020)

Abstract We previously reported that breast cancer (BC) generates metastasis-promoting regulatory B cells (CD25+ tumor-evoked Bregs). Because phenotypically these cells resembled bone marrow (BM) Rag+ B-cell precursors, such as large Pre-B cells, we hypothesized whether cancer uses them to generate Bregs. To investigate this idea, we used mouse and human BM aspirates, human PBMCs from BC patients, and mice with different orthotopic cancers, such as highly metastatic 4T1 breast cancer cells and EMT6. We report that breast cancer indeed uses BM B-cell precursors to generate Bregs. However, to do this, cancer expresses thymic stromal lymphopoietin (TSLP). Mechanistically, cancer-produced TSLP downregulates surface expression of CXCR4 and α4β1 (VLA-4) of B-cell precursors, thereby impairing their BM retention and increasing their exit into the circulation. TSLP also enables survival and proliferation of these BM emigrants, while other factors such as 5-lipoxygenase metabolites convert them into Bregs. The loss of TSLP expression in cancer cells alone or TSLPR deficiency in B cells not only reduce pre-B cells in the circulation, but also retard lung metastasis. Overall, our data reveal a previously unknown function of cancer-produced TSLP as inducers of premature B-cell precursor emigration from BM to support Breg generation. The results also suggest that the TSLP-pre-B cell axis can be an attractive therapeutic target. Citation Format: Emeline Ragonnaud, Kanako Moritoh, Monica Bodogai, Soizic Garaud, Chen Chen, Xin Wang, Karen Willard-Gallo, Arya Biragyn. Cancer targets early B-cell precursors to generate metastasis-promoting Bregs by promoting their premature emigration from the bone marrow and expansion in the circulation [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 4499.
Abstract 1239: Role of the glutathione antioxidant system in the autophagic process outcome
Authors: Yong J. Lee
Journal: Cancer Research (2020)

Abstract Ferroptosis has been reported as a unique form of cell death. However, in recent years, researchers have increasingly challenged the uniqueness of ferroptosis compared to other types of cell death. In this study, we examined whether ferroptosis shares cell death pathways with other types of cell death, especially autophagy, via the autophagic process. Here, we observed that ferroptosis inducers (artesunate and erastin) and autophagy inducers (bortezomib and XIE62-1004) led to autophagosome formation via the endoplasmic reticulum (ER) stress response. Unlike XIE62-1004, artesunate, erastin, and bortezomib, which affect glutathione production or utilization, induced oxidative stress responses - an increase in the levels of heme oxygenase-1 and lipid peroxidation. Oxidative stress responses were attenuated by deletion of autophagy related gene-5 or treatment with autophagy inhibitors (bafilomycin and chloroquine). Our studies provide an overview of common death pathways - the ER stress response-associated autophagic process in ferroptosis and autophagy. We also highlight the role the glutathione redox system plays in the outcome of the autophagic process. Citation Format: Yong J. Lee. Role of the glutathione antioxidant system in the autophagic process outcome [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 1239.
Association between quadrivalent human papillomavirus vaccination and selected syndromes with autonomic dysfunction in Danish females: population based, self-controlled, case series analysis
Authors: Anders Hviid, Nicklas M Thorsen, Palle Valentiner-Branth, Morten Frisch, Kåre Mølbak
Journal: BMJ (2020)

To evaluate the association between quadrivalent human papillomavirus vaccination and syndromes with autonomic dysfunction, such as chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome.Population-based self-controlled case series.Information on human papillomavirus vaccinations and selected syndromes with autonomic dysfunction (chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome) identified using ICD-10 (international classification of diseases, revision 10) diagnostic codes from Danish nationwide registers.869 patients with autonomic dysfunction syndromes from a cohort of 1 375 737 Danish born female participants aged 10 to 44 years during 2007-16.Self-controlled case series rate ratios (95% confidence intervals) of the composite outcome of chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome, adjusted for age and season, comparing female participants vaccinated and unvaccinated with the quadrivalent human papillomavirus vaccine. Chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome were also considered separately in secondary analyses.During 10 581 902 person years of follow-up, 869 female participants with syndromes of autonomic dysfunction (136 with chronic fatigue syndrome, 535 with complex regional pain syndrome, and 198 with postural orthostatic tachycardia syndrome) were identified. Quadrivalent human papillomavirus vaccination did not statistically significantly increase the rate of a composite outcome of all syndromes with autonomic dysfunction in a 365 day risk period following vaccination (rate ratio 0.99, 95% confidence interval 0.74 to 1.32) or the rate of any individual syndrome in the risk period (chronic fatigue syndrome (0.38, 0.13 to 1.09), complex regional pain syndrome (1.31, 0.91 to 1.90), or postural orthostatic tachycardia syndrome (0.86, 0.48 to 1.54)).When vaccination is introduced, adverse events could occur in close temporal relation to the vaccine purely by chance. These results do not support a causal association between quadrivalent human papillomavirus vaccination and chronic fatigue syndrome, complex regional pain syndrome, or postural orthostatic tachycardia syndrome, either individually or as a composite outcome. An increased risk of up to 32% cannot be formally excluded, but the statistical power of the study suggests that a larger increase in the rate of any syndrome associated with vaccination is unlikely.
Time-dependent lymphocyte count after transplantation is associated with higher risk of graft failure and death
Authors: Amaury Dujardin, Marine Lorent, Yohann Foucher, Christophe Legendre, Clarisse Kerleau, Sophie Brouard, Magali Giral, Gilles Blancho, Julien Branchereau, Diego Cantarovich, Agnès Chapelet, Jacques Dantal, Clément Deltombe, Lucile Figueres, Claire Garandeau, Magali Giral, Caroline Gourraud-Vercel, Maryvonne Hourmant, Georges Karam, Clarisse Kerleau, Aurélie Meurette, Simon Ville, Christine Kandell, Anne Moreau, Karine Renaudin, Anne Cesbron, Florent Delbos, Alexandre Walencik, Anne Devis, Lucile Amrouche, Dany Anglicheau, Olivier Aubert, Lynda Bererhi, Christophe Legendre, Alexandre Loupy, Frank Martinez, Rébecca Sberro-Soussan, Anne Scemla, Claire Tinel, Julien Zuber
Journal: Kidney International (2020)