tbuckley/cabot-search huggingface dataset:
Abstract 1654: Myeloid-dominated spontaneous tumor models as the tool for the evaluation of immune modulators
Authors: Xianzhi Zhai, Yuying Yang, Haoxia Zhao, Jingjing Jiang, Xuzhen Tang, Qunsheng Ji
Journal: Cancer Research (2021)

Abstract BACKGROUND:Myeloid cells, such as TAMs and MDSCs and their correlation with solid tumor progression have been widely recognized. As researchers are turning their interests to explore myeloid related tumor models, spontaneous tumor models, which represent a natural development/progression of tumor under certain immune microenvironment, would be a valuable tool for such studies. Some traditional targeted drugs have been re-evaluated for their immune effects, for example, CDK inhibitors can trigger anti-tumor immunity beyond its cell cycle regulation. Methods:In prior studies we have identified two myeloid-dominant spontaneous tumor models, APCmin and MMTV-PyMT, which represented a myeloid-enriched(especially for gMDSCs) and low T cell infiltrated microenvironment compared to the congenic mice. Immune modulators including checkpoint inhibitors (aCTLA-4),NSAID (Celecoxib) and CDK4/6 inhibitor(Palbociclib) were applied to evaluate their efficacy to the two models and their influences on the immune microenvironment. RESULTS:As a result, CDK inhibitor Palbociclib showed a better curative effect on MMTV-PyMT model compared to aCTLA-4. It seems when aCTLA-4 only up-regulated T cell level, CDK inhibitor can both increase the tumor infiltrating T cells as well as decrease Treg and myeloid, which explain its good response on this myeloid-dominated model. In APCmin model, Celecoxib reduce adenomas and alleviate the anemia symptoms with its significant immune benefit: the increase of lymphocyte infiltration and the reversal of myeloid cell elevation. SUMMARY:In summary, APCmin and MMTV-PyMT can be used as good tool models for the evaluation of myeloid-related immune modulators. Citation Format: Xianzhi Zhai, Yuying Yang, Haoxia Zhao, Jingjing Jiang, Xuzhen Tang, Qunsheng Ji. Myeloid-dominated spontaneous tumor models as the tool for the evaluation of immune modulators [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1654.
Progressive improvement in long-term graft survival in kidney transplantation patients in a single Spanish center. A retrospective study
Authors: M. Ramos-Cebrián, A. Budía Alba, I. Beneyto, E. Broseta-Rico, A. Ventura, S. Arlandis-Guzman, D. Ramos-Escorihuela, F. Boronat-Tormo
Journal: European Urology (2021)
Abstract 628: Ophtalmological manifestations of acute leukemias at university hospital center Yalgado Ouedrago
Authors: Kalo Roland Millogo, Delphine Kabore, Solo Traore
Journal: Cancer Research (2021)

Abstract Acute leukaemias constitute 9.04% of malignant hemopathies (Burkina Faso, 2015). Their manifestations are mainly haematological, however other less frequent attacks are possible. We report here for the first time in Burkina Faso, three cases of ocular localizations in young adults. Observation 1: S.I, male, 17-year-old patient, student living in Ouagadougou with a history of recurrent sore throat and ear infections. He was admitted for asthenia and pallor in the context of polytransfusion. The myelogram showed a rich marrow marked by the presence of 15% blast cells. Ophthalmologic examination reported visual acuity of 1/10, stage II proptosis and lower chemosis, and massive retinal and macular hemorrhage. Chemotherapy could not be performed. he died a week later. Observation 2: TB, male, 23-year-old patient, welder, suffering from acute lymphoblastic leukemia diagnosed in front of a severe recurrent anemia and confirmed by a myelogram, showing a rich marrow infiltrated by lymphoblasts representing 47% of the medullary cells. The ophthalmologic examination revealed conjunctival-palpebral infiltration by acute leukemia with myogenic ptosis. The evolution was marked by an improvement in symptoms after a cure according to the Vincristine-Prednisone protocol and he was discharged from hospital weeks later. He was subsequently lost to follow-up. Observation 3: KK male, 25-year-old patient, artisanal miner residing in Ouagadougou with a history of peptic ulcer disease, carrier of acute myeloid leukemia (AML) confirmed by a myelogram. The ophthalmologic examination concludes with a bilateral inflammatory orthopathy with an exposure keratitis on site of AML. He received transfusion of concentrates of red blood cells and platelets, as well as corticosteroid therapy for 04 days. The following was marked by a rapid worsening of the symptoms and the death of the patient a week later. Conclusion: The extra-haematological manifestations of acute leukemia are rare. They are associated with a pejorative prognosis. This series of 03 cases that we report is the first described to date in our context. Citation Format: Kalo Roland Millogo, Delphine Kabore, Solo Traore. Ophtalmological manifestations of acute leukemias at university hospital center Yalgado Ouedrago [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 628.
Abstract 232: The abscopal effect: modelling and predicting the effect of radiation therapy on non-irradiated tumour when combined with immune checkpoint blockers
Authors: Frances Brightman, Fernando Ortega, David Orrell, Christophe Chassagnole
Journal: Cancer Research (2021)

Abstract We have developed preclinical and clinical ‘Virtual Tumour' (‘VT') models that can predict how a tumour will respond to drug exposure. This agent-based method is particularly suitable for modelling not only tumour cells, but also those involved in the immune response, and interactions between cells (1-3). The purpose of the study was to extend the VT platform to be able to model simultaneously i) the response of a tumour treated with radiation only or in combination with immune-checkpoint blockers, ii) the tumour response in areas where radiation has not been performed in the absence/presence of an immune-checkpoint blocker. Building on previous work, in which the VT platform was extended by the addition of a module that captures the synergistic of PD(L)-1 blockade with conventional anticancer therapies, we have further expanded the model to integrate the immune-checkpoint blocker module with other immune species activated by irradiation of the target tumour - in particular circulating CD8+ T cells - in order to be able to mimic the systemic abscopal effect. Ultimately, this expansion enables us to simulate the effect of tumour growth control on out-of-field tumour lesions when delivered in combination with an immune-checkpoint blocker. Through preclinical case studies derived from the literature (4) we demonstrate that the extended VT can be applied to simulate the efficacy of diverse radiation regimens in combination with immune-checkpoint blockers, and correctly describe the combination treatment effect on the progression of irradiated and non-irradiated tumours. Furthermore, we demonstrate that the model can be applied to optimize the timing of the combination in order to maximize the systemic efficacy of the treatment. Our enhanced VT capability represents a key step towards a strategic tool for optimizing dosing and scheduling of immune-checkpoint block and radiation combinations. [1] Brightman, FA et al., Abstract 680. Cancer Res 75, 4866-66 (2015). [2] Ortega, F et al., Abstract 4866. Cancer Res 79, (13 Suppl) (2019). [3] Orrell, DA et al., Abstract 4918. Cancer Res 71, (8 Suppl) (2011). [4] Dovedi, S et al., Clin Cancer Res 23(18); 5514-26 (2017). Citation Format: Frances Brightman, Fernando Ortega, David Orrell, Christophe Chassagnole. The abscopal effect: modelling and predicting the effect of radiation therapy on non-irradiated tumour when combined with immune checkpoint blockers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 232.
Abstract 383: Efficacy of immune checkpoint inhibitors in lung cancer patients with EGFR P719A mutation: A case report
Authors: Fuyu Gong, Kai Zheng
Journal: Cancer Research (2021)

Abstract Background: Results from previous studies indicated that lung cancer patients harboring EGFR sensitizing mutations may receive unfavorable outcomes from immunotherapy. The present study aims to investigate the efficacy of inhibitors of programmed cell death protein-1in lung cancer patients with driver oncogene EGFR P719A mutations and strong positive PD-L1 expression in one special case. Methods: Tissue samples were subjected to NGS in our College of American Pathologists-certified and Clinical Laboratory Improvement Amendments-accredited lab for driver oncogene mutations and PD-L1 expression. Results: A 52-year-old male never-smoker who complained of a persistent cough was examined by computed tomography (CT), which revealed a 39 mm wide tumor in the upper region of the right lobe of the lung in May 2019. Tumor biopsy pathology revealed that the patient had a stage IIIB (T2N3M0) adenocarcinoma. NGS performed on a formalin-fixed, paraffin-embedded tumor specimen to identify genomic aberrations. The tumor was positive for EGFR, EGFR P719A mutation. The PD-L1 expression have been tested by FDA-approved 22C3 antibodies, and PD-L1 expression level of 95%. The patients received anti-PD-1 combination treatment. He has reached partial response (PR) after 4 cycle treatment. After ten months, he has the opportunity to receive the operation. The following anti-PD-1/L1 monotherapy is still ongoing until now. Conclusion: Our real-world study supported that NSCLC patients harboring sensitizing oncogenic mutations may potentially benefit from anti-PD-1/L1 especially for those with positive indicators of immunotherapy with strong positive PD-L1 expression. Citation Format: Fuyu Gong, Kai Zheng. Efficacy of immune checkpoint inhibitors in lung cancer patients with EGFR P719A mutation: A case report [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 383.
Abstract 3116: Designing a model system for the study of CD44-Ezrin interactions in breast cancer progression and drug resistance
Authors: Rayanna Jane Birtch, Peter Greer, Yan Gao, Victoria Hoskin
Journal: Cancer Research (2021)

Abstract Triple-negative breast cancer (TNBC) has the highest risk of relapse and is thought to be the most aggressive subtype of BC. This subtype is known to express high levels of the cancer stem cell (CSC) marker CD44. The tumor-initiating properties of CSC's, as well as their resistance to chemotherapy, contribute to the difficulty in successfully treating TNBCs.CD44 is a transmembrane glycoprotein that mediates communication between cells and the extracellular matrix. In doing so, it acts as a central node in several cancer-related signaling pathways through interactions with binding partners such as Ezrin to promote tumor growth, invasion and survival. Furthermore, expression of CD44 is associated clinically with positive lymph node status, recurrence and poor overall survival in BC. We aimed to validate CD44's role in these cancer promoting properties and develop a genetically tractable and engraftable TNBC cell model to study CD44 in the context of interactions with the Ezrin adaptor protein. We first hypothesize that disrupting CD44 expression will attenuate the metastatic and drug resistant potential of TNBC cells. To address this, we utilized CRISPR-Cas9 gene editing to knockout (KO) CD44 expression in the MDA-MB-231 human TNBC cell line and then subjected CD44 KO cells, KO cells rescued with wild type CD44, or the parental MDA-MB-231 cells to a variety of in vitro assays to assess proliferative, migratory and drug resistant potential, as well as mouse lung metastatic seeding in vivo. We show that the transmembrane glycoprotein CD44 plays an important role in cancer cell proliferation, migration, and chemotherapeutic resistance in vitro as well as having an essential role in metastatic seeding in vivo in the MDA-MB-231 cell model of TNBC. Our results validate the utility of this CRISPR-Cas9 KO and rescue TNBC cell model for the study of CD44 involvement in drug resistance and metastasis. More importantly we have set the stage for further investigating CD44's role in the context of interactions with the Ezrin adaptor protein. Citation Format: Rayanna Jane Birtch, Peter Greer, Yan Gao, Victoria Hoskin. Designing a model system for the study of CD44-Ezrin interactions in breast cancer progression and drug resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3116.
Salvage Therapies for PSMA PET/CT-positive nodal-only recurrent prostate cancer: Impact on survival, functional outcomes and health-related quality of life
Authors: A. Kretschmer, J. Milow, A. Buchner, M. Li, H. Ilhan, V. Wenter, C.G. Stief, C. Belka, N. Schmidt-Hegemann
Journal: European Urology (2021)
Abstract 497: Human CD73 knock-in mice facilitate evaluation of <i>in vivo</i> efficacy of anti-human CD73 cancer immunotherapies
Authors: Chengzhang Shang, Huilin Li, Jing Zhang, Eugene Lin, Luke (Zhaoxue) Yu, Yuelei Shen
Journal: Cancer Research (2021)

Abstract In recent years, immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, most patients with solid cancers do not respond to the current ICIs against PD-1/PD-L1 or CTLA-4 alone. Stimulating an effective anti-tumor immune response may require countering additional immunosuppressive pathways in the tumor microenvironment (TME). Adenosinergic pathways are critical to maintain normal immune system homeostasis, and tumors could exploit them to avoid immune attack. CD73 (NT5E) is a surface enzyme that catalyzes the final hydrolysis of AMP to adenosine, which impairs immune function through adenosine receptors like A2AR (see our poster on humanized A2AR mice) on immune cells. Some tumors overexpress CD73 driven by hypoxia in the TME, which associates with poor prognosis in some cases. It is also expressed on the surface of multiple immune cells that infiltrate tumors, including T-cells, B-cells, NK cells, macrophages, and myeloid-derived suppressor cells. Several anti-CD73 antibodies have started early stage clinical trials as a treatment for advanced cancers. Combined anti-CD73, anti-PD-1, and anti-CTLA4 therapies synergize to reduce tumor burden and extend survival. Thus, there is a need for pre-clinical models to evaluate the safety and efficacy of CD73-targeted therapeutics before they enter human trials. Biocytogen has generated a human CD73 knock-in (KI) mouse (B-hCD73) and a human CD73-expressing MC38 cell line (MC38-hCD73) for both in vitro functional validation and in vivo efficacy evaluation of CD73-specific antibodies. Human CD73 (hCD73) whole coding sequence was inserted following exon 2 of the mouse Cd73 gene. B-hCD73 mice did not exhibit any immune or developmental abnormalities compared to wild-type mice, but splenic Tregs of B-hCD73 mice and not wild-type expressed hCD73. Anti-hCD73 antibodies bound well only to splenocytes of hCD73 KI mice and also blocked the enzyme activity of CD73. Using our MC38-hCD73 tumor model, we showed robust efficacy of anti-hCD73 antibodies in inhibiting tumor growth in vivo. Furthermore, in PD-1/PD-L1/CD73 triple KI humanized mice implanted with MC38 tumors, combined CD73 and PD-1/PD-L1 blockade showed greater tumor inhibition than monotherapies. Taken together, CD73 humanized mice and their variants are useful tools for in vivo efficacy evaluation of candidate human CD73 antibodies and combination therapies being considered for clinical trials. Citation Format: Chengzhang Shang, Huilin Li, Jing Zhang, Eugene Lin, Luke (Zhaoxue) Yu, Yuelei Shen. Human CD73 knock-in mice facilitate evaluation of in vivo efficacy of anti-human CD73 cancer immunotherapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 497.
Operating in a Climate Crisis: A State-of-the-Science Review of Life Cycle Assessment within Surgical and Anesthetic Care
Authors: Jonathan Drew, Sean D. Christie, Peter Tyedmers, Jenna Smith-Forrester, Daniel Rainham
Journal: Environmental Health Perspectives (2021)

Both human health and the health systems we depend on are increasingly threatened by a range of environmental crises, including climate change. Paradoxically, health care provision is a significant driver of environmental pollution, with surgical and anesthetic services among the most resource-intensive components of the health system.This analysis aimed to summarize the state of life cycle assessment (LCA) practice as applied to surgical and anesthetic care via review of extant literature assessing environmental impacts of related services, procedures, equipment, and pharmaceuticals.A state-of-the-science review was undertaken following a registered protocol and a standardized, LCA-specific reporting framework. Three bibliographic databases (Scopus®, PubMed, and Embase®) and the gray literature were searched. Inclusion criteria were applied, eligible entries critically appraised, and key methodological data and results extracted.From 1,316 identified records, 44 studies were eligible for inclusion. The annual climate impact of operating surgical suites ranged between 3,200,000 and 5,200,000 kg CO2e. The climate impact of individual surgical procedures varied considerably, with estimates ranging from 6 to 1,007 kg CO2e. Anesthetic gases; single-use equipment; and heating, ventilation, and air conditioning system operation were the main emissions hot spots identified among operating room- and procedure-specific analyses. Single-use equipment used in surgical settings was generally more harmful than equivalent reusable items across a range of environmental parameters. Life cycle inventories have been assembled and associated climate impacts calculated for three anesthetic gases (2-85 kg CO2e/MAC-h) and 20 injectable anesthetic drugs (0.01-3.0 kg CO2e/gAPI).Despite the recent proliferation of surgical and anesthesiology-related LCAs, extant studies address a miniscule fraction of the numerous services, procedures, and products available today. Methodological heterogeneity, external validity, and a lack of background life cycle inventory data related to many essential surgical and anesthetic inputs are key limitations of the current evidence base. This review provides an indication of the spectrum of environmental impacts associated with surgical and anesthetic care at various scales. https://doi.org/10.1289/EHP8666.
Abstract 1430: <i>In vivo</i> PoC study and design for Phase I clinical study of SJP1604, a nucleolin-targeted therapeutic agent to treat entire population of relapsed/refractory acute myeloid leukemia patients
Authors: Jihyun Um, Dohyeong Lee, So Hee Kim, Eun-Hye Huh, Yongbin Park, Sung Hwan Moon, Soo Jin Lee, Je-Hwan Lee, Min-Hyo Ki
Journal: Cancer Research (2021)

Abstract SJP1604 (APTA-16) is an aptamer-drug conjugate (APTA-DC) specifically targeting nucleolin, which is highly expressed only on the cell membrane of acute myeloid leukemia (AML) cells including relapsed/refractory aute myeloid leukemia (R/R AML). We previously presented the outstanding anti-leukemic activity of SJP1604 on AML cells including drug-resistant AML cells while standard chemotherapies showed no efficacy in vitro and in vivo. Therefore, we were able to conclude that only SJP1604 exhibits excellent resistance overcoming efficacy regardless of genetic defects of AML cells. Additionally, we recently identified that SJP1604 markedly eradicated AML cell engraftment with decreasing expression level of nucleolin protein in the bone marrow cells of MOLM-13 xenograft mouse model. These findings demonstrate that SJP1604 contributes to anti-leukemic effects through the regulation of nucleolin protein. We also figured out that nucleolin as a clinical biomarker was significantly highly expressed on AML and R/R AML patient-derived bone marrow cells. In particular, nucleolin expression is highly overexpressed in the bone marrow cells of entire population of R/R AML patients. Upto recent, considered as one of the major targeted therapeutics for AML, FLT3 inhibitors can target 25-30% of AML patients only. Therefore, our results mentioned above are very noteworthy finding showing the high potential of SJP1604 to be further developed as the first innovative targeted therapy to treat entire population of R/R AML patients. Herein, we show a phase I clinical trial design of SJP1604 to perform an open-label, first-in-human, dose escalation study to evaluate the safety, tolerability, pharmacokinetics and anti-tumor activity in patients with R/R AML. Citation Format: Jihyun Um, Dohyeong Lee, So Hee Kim, Eun-Hye Huh, Yongbin Park, Sung Hwan Moon, Soo Jin Lee, Je-Hwan Lee, Min-Hyo Ki. In vivo PoC study and design for Phase I clinical study of SJP1604, a nucleolin-targeted therapeutic agent to treat entire population of relapsed/refractory acute myeloid leukemia patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1430.
Inverse correlation between central hypogonadism and circulating IL-10 levels in males with severe COVID-19
Authors: G. Amodio, S. Gregori, M. Pontillo, P. Capogrosso, M. Tassara, A.M. Ferrara, C. Carenzi, C. Abbate, D. Cignoli, L. Boeri, G. Landoni, P. Rovere Querini, F. Ciceri, F. Montorsi, A. Salonia
Journal: European Urology (2021)
PI3K Inhibition with Idelalisib for Optimized Production of Chimeric Antigen Receptor T Cells
Authors: Sophia Stock, Jean-Marc Hoffmann, Lei Wang, Wenjie Gong, Angela Hückelhoven, Brigitte Neuber, Maria-Luisa Schubert, Ulrike Gern, Anita Schmitt, Carsten Müller-Tidow, Peter Dreger, Michael Schmitt, Leopold Sellner
Journal: Blood (2017)
Cytotoxic T-Lymphocyte Antigen–4 Haploinsufficiency Cutaneous Manifestations
Authors: Fiore Casale, Cristina Nguyen, Suzanne W. Birmingham, Natasha Atanaskova Mesinkovska
Journal: JAMA Dermatology (2021)

This case report describes a female teenager with mild eczema and patchy alopecia areata presenting with a severe headache, gastrointestinal distress, fatigue, arthralgias, and skin eruption on bilateral extremities.