COVID-19 and Cancer最新文献

{"title":"Abstract 721: Early death in acute lymphoblastic leukemia during COVID-19 pandemic: A single institution cohort study","authors":"Daniel Enriquez-Vera, Ali Al-kassab-Córdova, Lizbeth Lachira-Yparraguirre, Gustavo Sandival-Ampuero, B. Valcárcel, C. Samánez, Juan Haro-Varas, Shirley Quintana-Truyenque, L. Malpica, Henry Gomez-Leonidas, Tatiana Vidaurre-Rojas","doi":"10.1158/1538-7445.AM2021-721","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-721","url":null,"abstract":"Background: COVID-19 is a condition caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing a systemic inflammatory response and respiratory failure. Patients with acute leukemia are presumed to be at the highest risk among all cancer patients, given their state of severe immunosuppression from both the disease and aggressive therapy. Therefore, we aimed to determine if COVID-19 increases the early-mortality risk of ALL patients during the induction phase. Methods: We conducted a retrospective cohort study by reviewing medical records of newly diagnosed ALL patients between March 2020 and September 2020 at a single Peruvian institution (INEN, Lima-Peru). We included patients older than 14 years, with the initial intent of intensive treatment. The proposed protocol was the CALGB10403 with asparaginase modification. COVID-19 was determined by a +ve nasopharyngeal SARS-CoV-2 RT-PCR or serology. The outcomes were 30-day and 60-day mortality and treatment response at the end of induction. Results: Of 63 patients with ALL in induction therapy, 22 (35%) had COVID-19, and 41 (65%) did not. Overall, the median age was 30 (IQR 21 - 42), and 59% were males. Table 1 shows that age, sex, ALL subtype, and laboratory characteristics had a similar distribution between both groups. The mortality rate of ALL patients with COVID-19 was non-statistically different from non-COVID-19 patients at 30 (23% versus 12%, p=0.466) and 60 days (32% versus 20%, p=0.434). Multivariate logistic regression did not find a significant association between COVID-19 and complete treatment response (aOR: 0.44, 95% CI: 0.02-4.54). Similarly, patients with COVID-19 did not had an increased mortality risk at 30 days (aHR: 2.37, 95% CI: 0.64-8.75) and 60 days (aHR: 1.98, 95% CI: 0.7-5.64). Conclusion: In our cohort, COVID-19 did not increase the risk of early death in newly diagnosed patients with ALL. Citation Format: Daniel J. Enriquez-Vera, Ali Al-kassab-Cordova, Lizbeth Lachira-Yparraguirre, Gustavo Sandival-Ampuero, Bryan Valcarcel, Cesar Samanez, Juan Haro-Varas, Shirley Quintana-Truyenque, Luis Malpica, Henry Gomez-Leonidas, Tatiana Vidaurre-Rojas. Early death in acute lymphoblastic leukemia during COVID-19 pandemic: A single institution cohort study [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 721.","PeriodicalId":417728,"journal":{"name":"COVID-19 and Cancer","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122384950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 703: An inflammatory leptomeningeal signature in cancer patients with neurologic manifestations of COVID-19","authors":"Jessica A. Wilcox, Ján Remšík, N. Babady, T. McMillen, B. Vachha, N. Halpern, V. Dhawan, M. Rosenblum, C. Iacobuzio-Donahue, Edward K. Avila, B. Santomasso, A. Boire","doi":"10.1158/1538-7445.AM2021-703","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-703","url":null,"abstract":"Background: COVID-19 is associated with a wide spectrum of neurologic manifestations, which can emerge weeks to months after the initial infection. Cancer patients are at a heightened risk of severe infections due to their immunocompromised status. Leading hypotheses predict that SARS-CoV-2 neuroinvasion or neurologic toxicity from the systemic cytokine storm may account for neurologic dysfunction. Methods: We prospectively evaluated cancer patients with confirmed SARS-CoV-2 infection and subsequent neurologic manifestations at an NCI-designated cancer center. Evaluations included neurologic examinations, brain imaging, electroencephalogram, and cerebrospinal fluid (CSF) analysis for SARS-CoV-2 detection by RT-PCR for viral RNA and ELISA for nucleocapsid (N) and spike (S2) proteins. Additional proteomic analysis compared the CSF of patients with COVID-19 (CoV+) to cancer- and brain metastasis-matched COVID-19-negative controls (CoV-), and to patients with other cancer-associated neuroinflammatory conditions, including immune effector cell-associated neurotoxicity syndrome (ICANS) and autoimmune encephalitis. Results: Between May and July 2020, we evaluated 18 COVID-19-positive cancer patients with a wide range of solid tumor and hematologic malignancies. Thirteen (72.2%) of our patients received tumor-directed treatment within 30 days of SARS-CoV-2 infection. Neurologic diagnoses include protracted critical care delirium (N=10), limbic encephalitis (N=4), refractory headaches (N=2), rhombencephalitis (N=1), and large-territory infarctions (N=1). A median delay of 19 days (range 0-77) existed between onset of respiratory symptoms and neurologic manifestations. Among 13 patients who underwent CSF analysis, there was no evidence of SARS-CoV-2 neuroinvasion by RT-PCR in the CSF (N=13) or by N and S2 protein detection (N=10). Targeted proteomic analysis detected a significant accumulation of IL-6 and -8, IFN-gamma, CXCL-1, -6, -9, -10, and -11, CCL-8 and -20, MMP-10 and 4E-BP1 in the CSF of CoV+ patients (N=10) relative to matched CoV- controls (pooled, p=0.029). Combined analysis of these 12 inflammatory mediators revealed CoV+ cytokine levels approaching that of ICANS. CSF MMP-10, a marker of neurodegeneration, correlated with neurologic dysfunction by Karnofsky performance status (p=0.011) and by disability rating scale (p=0.086) at the time of lumbar puncture. Conclusion: A durable accumulation of IFN-gamma-mediated cytokines is detected in the CSF of cancer patients with neurologic manifestations of COVID-19, in the absence of detectable neuroinvasion. We hypothesize that cytokine-mediated neuroinflammation is responsible for the prolonged neurologic sequela of COVID-19. Our findings suggest a potential role for anti-inflammatory treatments in the management of such patients. Citation Format: Jessica A. Wilcox, Jan Remsik, N. Esther Babady, Tracy A. McMillen, Behroze A. Vachha, Neil A. Halpern, Vikram Dhawan, Marc Rosenblum, Christine A. Iacobuzi","PeriodicalId":417728,"journal":{"name":"COVID-19 and Cancer","volume":"25 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134115562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 705: SARS-CoV-2 infection of the human heart governs intracardiac innate immune response","authors":"A. Ashton, Liang Zhang, Yan Liang, P. Divakar, Carolos Cordon-Cardo, R. Pestell","doi":"10.1158/1538-7445.AM2021-705","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-705","url":null,"abstract":"Human coronavirus, hCoV-19 (SARS-CoV-2) is associated with pneumonia, severe systemic disease and, in fatal cases, a high prevalence of cardiac dysfunction. Cellular entry requires a cell-surface receptor, angiotensin-converting enzyme 2 (ACE2), and activation of the spike protein by host proteases, including TMPRSS2 and cathepsins. Cardiac toxicity is a serious cause of morbidity and mortality from SARS-CoV-2 with chronic sequelae reducing cardiac function in many survivors. We determined mRNA expression for genes related to SARS-Cov-2 infection in iPSC-derived cardiac myocytes treated with the widely used chemotherapeutic, Doxorubicin (DOX). DOX induced expression of TMPSS2, but not Ace2 or Furin, 4- to 5-fold. Further, DOX treatment enhanced expression of cathepsins A, B and F between 1.2-1.5 fold. Overall these changes promote an environment of enhanced SARS-CoV-2 susceptibility in the myocardium placing cancer patients on DOX therapy at increased risk of cardiac damage. To further characterize the effects of SARS-CoV-2 on the myocardium we examined the local spatial gene expression response in human post-mortem cardiac samples. A genome wide (1,864 genes) and matching proteome analysis on SARS-CoV-2 infected myocardium was conducted using Digital spatial profiling (DSP) (NanoString GeoMxTM). RNAscopeTM, a sensitive form of fluorescence in situ hybridization (FISH), identified SARS-CoV-2 spike RNA in cells enriched for ACE2 and TMPRSS2. Immunohistochemistry on serial sections identified the SARS-CoV-2 spike protein in both myocyte (desmin+) and monocyte (CD45+) populations suggesting multiple targets for viral infection in the myocardium. SCANscopeTM was used to determine the effects of SARS-CoV-2 on cardiac gene. Probes directed to the spike protein were used to identify regions of interest (ROI) for SARS-CoV-2-infection. Unsupervised principal component analysis (PCA) of the differentially expressed gene transcripts separated gene expression of SARS-CoV-2 ROI from control ROI areas in the same patient and was distinct from the PCA of normal myocardium control ROI. PCA of the SARS-CoV-2-associated gene expression of the ROI from male vs. female myocardium identified distinct gender-related gene expression patterns. Further, PCA based on SARS-Cov-2 spike RNA abundance correlated with induction of innate and acquired immunity signaling in the myocardial cells. Moreover, gene ontology (Reactome) analysis of SARS-CoV-2 infected regions of the myocardium displayed characteristic signatures indicating enhanced apoptosis and autophagy, chromatin remodeling and reduced DNA repair, and reduced oxidoreductase activity in regions of SARS-CoV-2 infection compared to uninfected myocardium. These data probe the underlying molecular mechanisms that enhance the risk of death from SARS-CoV-2 for cancer patients and the cardiac remodeling that results in death for many patients with COVID-19. Citation Format: Anthony W. Ashton, Liang Zhang, Yan Liang, Prajan ","PeriodicalId":417728,"journal":{"name":"COVID-19 and Cancer","volume":"2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116666957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 701: The acute phase response identifies cancer patients with adverse outcomes from SARS-CoV-2 infection as quantified by the OnCovid Inflammatory Score","authors":"G. Dettorre, S. Dolly, A. Loizidou, J. Chester, A. Jackson, U. Mukherjee, A. Zambelli, J. Aguilar-Company, M. Bower, C. Sng, R. Salazar, A. Bertuzzi, J. Brunet, R. Mesía, A. Sita-Lumsden, E. Seguí, F. Biello, D. Generali, S. Grisanti, P. Seeva, G. Rizzo, M. Libertini, A. Maconi, C. Moss, J. Tabernero, B. Russell, N. Harbeck, B. Vincenzi, R. Bertulli, D. Ottaviani, Raquel Liñan, A. Marrari, M. Carmona-García, N. Chopra, C. Tondini, O. Mirallas, V. Tovazzi, V. Fotia, C. Cruz, Nadia Saoudi-Gonzalez, E. Felip, A. Roqué, A. Lee, T. Newsom-Davis, A. Patriarca, L. Rimassa, A. Santoro, A. Gennari, N. Diamantis, D. Pinato","doi":"10.1158/1538-7445.am2021-701","DOIUrl":"https://doi.org/10.1158/1538-7445.am2021-701","url":null,"abstract":"","PeriodicalId":417728,"journal":{"name":"COVID-19 and Cancer","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129833308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 700: CellSig: A data-driven model of cytokine activity identifies therapeutic targets for severe COVID-19 and cancer immunotherapy-induced colitis","authors":"Peng Jiang, Yu Zhang, Beibei Ru, E. Ruppin, Kai Wucherpfennig","doi":"10.1158/1538-7445.AM2021-700","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-700","url":null,"abstract":"Studies of cytokine activity are foundational to immunology research. However, the complexity and redundancy of cytokine functions have prevented systematic profiling of signaling activities in biological samples. To address these issues, we developed Cell Signaling Analyzer (CellSig, https://cellsig.ccr.cancer.gov), a data-driven infrastructure to model how cytokines cooperate with and antagonize each other in inflammation processes. We manually curated 20,591 transcriptomic profiles related to human cytokine, chemokine, and growth-factor response. CellSig revealed two main cytokine groups typified by NFKB and interferon-associated signals, respectively. The primary pro-inflammatory members of each group induce a distinct set of secondary signals and are repressed by different anti-inflammatory cytokines. CellSig can reliably predict target activities of 43 cytokines using the transcriptomic data from severe COVID-19 cases, cancer immunotherapy-induced colitis, and immune checkpoint blockade response. Among these clinical applications, the differential activities of the NFKB and interferon cytokine groups revealed potential therapeutic targets for alleviating adverse inflammation without compromising viral clearance or cancer treatment. Citation Format: Peng Jiang, Yu Zhang, Beibei Ru, Eytan Ruppin, Kai Wucherpfennig. CellSig: A data-driven model of cytokine activity identifies therapeutic targets for severe COVID-19 and cancer immunotherapy-induced colitis [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 700.","PeriodicalId":417728,"journal":{"name":"COVID-19 and Cancer","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128656844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 714: From cancer to COVID-19- development of a dendritic cell-targeted nano-vaccine for prevention and therapy of COVID-19","authors":"Daniella Vaskovich-Koubi, Ron Kleiner, Yulia Liubomirski, E. Yeini, G. Tiram, S. Pozzi, A. Eldar-Boock, H. Florindo, R. Satchi‐Fainaro","doi":"10.1158/1538-7445.AM2021-714","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-714","url":null,"abstract":"Dendritic cells (DC) are antigen-presenting cells with an important role in the initiation and regulation of the innate and adaptive arms of the immune system. By efficient presentation of antigens, DC elicit an antigen-specific immune response. Therefore, we previously established in our laboratory a melanoma-DC-targeted NP that was evaluated and validated against aggressive melanoma. Although DC-therapy is mainly exploited in the treatment of cancer, DC are becoming a key therapeutic target in other pathologies such as infectious diseases. Viral pathogens, similarly, to cancer, modulate the host defense mechanisms to their benefit. COVID-19, an ongoing pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally and is already infecting tens of millions of people worldwide. Historically, vaccines are among therapies with the greatest impact in health and constitute an unmet medical need against coronavirus disease-19 (COVID-19) pandemic. To that end, we repurposed our recently published melanoma-targeted NP to co-deliver modulators of host immune response and SARS-CoV-2 specific antigen epitopes discovered by a computational approach integrating 3D information with large-scale statistical analysis. The immune response kinetics in patients infected with SARS-CoV-2 is poorly understood, but recent reports show that germinal B cells and active follicular T-helper cells, IgM/IgG SARS-CoV-2 antibodies, in addition to an enhanced cellular immunity, are found in patients with mild-to-moderate SARS-CoV-2 infection. Our preliminary data demonstrated that our nano-vaccine was able to activate specific immune cell response of effector T cells and B cells and decrease the regulatory activity of T cells, compared to controls. Moreover, we found that our DC-targeted SARS-CoV-2 NP successfully induced antigen-specific secretion of IgM and IgG antibodies with high binding affinity to the antigens. Importantly, our nano-vaccine elicited specific neutralization of Spike virus like particles (VLPs) by sera of immunized mice. We hypothesize that implementing our novel nano-vaccine platform for COVID-19 will lead to a safe and efficacious COVID-19 vaccine ready for first-in-human clinical trials. Citation Format: Daniella Vaskovich-Koubi, Ron Kleiner, Yulia Liubomirski, Eilam Yeini, Galia Tiram, Sabina Pozzi, Anat Eldar-Boock, Helena F. Florindo, Ronit Satchi-Fainaro. From cancer to COVID-19- development of a dendritic cell-targeted nano-vaccine for prevention and therapy of COVID-19 [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 714.","PeriodicalId":417728,"journal":{"name":"COVID-19 and Cancer","volume":"104 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122492082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 713: Inhibition of pseudo SARS-CoV-2 binding activity of a anti-cancer polypharmacological agent analogs","authors":"R. Papineni, A. Adhikary, R. Tandon, Dipanwita Mitra","doi":"10.1158/1538-7445.AM2021-713","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-713","url":null,"abstract":"Severe acute respiratory syndrome coronavirus (SARS-CoV-2), a single-stranded RNA virus with largest genomes (∼ 29,800 bases) of all viruses, causes the infectious disease, COVID-19. SARS-CoV-2 is a zoonotic betacoronavirus transmitted through airborne and fecal-oral routes infecting nasal, lung, and intestinal tissues causing over 26 million confirmed coronavirus disease 2019 (COVID-19) cases and nearly 900,000 associated deaths worldwide as of September 2020. The surface of SARS-CoV-2 is covered with copies of spike glycoprotein (SGP) that plays a pivotal role in virus entry in host cells utilizing angiotensin-converting enzyme 2 (ACE2) as an attachment and entry receptor. We have successfully made a high titer replication-incompetent third-generation lentiviral vector pseudotyped with SARS-2-CoV SGP (pLV-S). Upon successful attachment and entry, the lentiviral vector causes enhanced green fluorescent protein (eGFP) to be expressed in the infected cell. Here, we show how the polypharmacological agent, 2-Deoxy-D-glucose (2-DG), a glucose mimic, and well characterized anti-cancer drug, and its analogs inhibit spike protein binding to the ACE2 receptors. This is as suggested from the 2DG and two analogs inhibition, with a low micromolar affinity, the pLV-S attachment and entry resulting in reduced cell fluorescence of infected HEK293 cells. In addition, we describe 2DG and analogs has the potential to deliver polypharmacological effects on the COVID-through inhibition of glycolysis (at energy status), modulation of inflammatory responses (cytokine storm) and alterations in glycosylation of viral proteins. A unique class of adjuvants and mitigants in the anti-SARS-CoV-2 activity is presented here. Citation Format: Rao V. Papineni, Amitava Adhikary, Ritesh Tandon, Dipanwita Mitra. Inhibition of pseudo SARS-CoV-2 binding activity of a anti-cancer polypharmacological agent analogs [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 713.","PeriodicalId":417728,"journal":{"name":"COVID-19 and Cancer","volume":"53 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125010811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 711: Repurposing 2ndgeneration androgen receptor antagonist Proxalutamide to treat COVID-19","authors":"Liandong Ma, Y. Tong, Q. Guo, Yifeng Zhou, Qianxiang Zhou, H. Yan","doi":"10.1158/1538-7445.AM2021-711","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-711","url":null,"abstract":"To date, as of 17 November 2020, there have been 55 million confirmed cases of COVID-19, including 1,4 million deaths globally, as reported to WHO. It is, therefore, very critical to discovery and development of the available treatment options for COVID-19. We here discuss the repurposing 2nd generation androgen receptor antagonist Proxalutaminde to treat COVID19. We analyzed the gender disparity of disease severity and progression in 1339 patients with COVID-19 and investigated the mechanism of gender disparity in male vs female patients with COVID 19. As androgen-androgen receptor pathway may contribute to the difference in severity and disease progression in male and female patients with COVID-19, we used cell lines derived from lung, prostate cancer and normal lung epithelial cells to determine the effect of androgen and androgen receptor antagonist Proxalutamide on the expression of two key proteins for SARS-CoV-2 to infect and enter the host cells. Angiotensin converting enzyme 2 (ACE2), a host transmembrane protein provides the binding sites for SARS-CoV-2 on the host cell surface, transmembrane protease serine 2 (TMPRSS2), a cellular serine protease, prims the S protein of SARS-Cov-2 to facilitate the viral entry into the host cells. As cytokine store plays a major role in the disease progression of COVID-19, we examined the effect of GT0918 on inducible nitric oxide synthase (iNOS) and Tumor necrosis factor-alpha (TNF-α), the macrophage polarization/activation markers, in mouse macrophage cells. In this study, we demonstrated higher rates of disease progression and mortality of male COVID-19 patients than female patients. Furthermore, we revealed that androgen-AR activation induced the expression of ACE2 and TMPRSS2 under the androgen-dependent condition in cells derived from prostate and lung cancer, which was inhibited by the blockage of AR signaling with Proxalutamide. Importantly, Proxalutamide also inhibited the expression of iNOS and TNF-α, the biomarkers for macrophage polarization/activation. These results support the role of androgen-AR signaling in the disease progression and mortality in male patients with COVID-19. We are currently conducting clinical study in COVID-19 patients with Proxalutamide in Brazil (NCT04446429). Citation Format: Liandong Ma, Youzhi Tong, Qiang Guo, Yifeng Zhou, Qianxiang Zhou, Honghua Yan. Repurposing 2nd generation androgen receptor antagonist Proxalutamide to treat COVID-19 [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 711.","PeriodicalId":417728,"journal":{"name":"COVID-19 and Cancer","volume":"43 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114707148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract LB074: Chymostatin, a cathepsin L inhibitor, inhibits lung cancer cell proliferation and COVID-19 Mproin vitro","authors":"N. Yarla, Gopal Pathuri, S. Terzyan, Yuting Zhang, Anil Singh, M. Scotti, Venkateshwar Madka, C. Rao","doi":"10.1158/1538-7445.AM2021-LB074","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-LB074","url":null,"abstract":"Lung cancer patients are more vulnerable to COVID-19 infection. Treatment of patients with lung cancer during the current COVID-19 pandemic is challenging and development of drugs for COVID-19 and lung cancer is urgently needed. Cathepsin L plays key role in lung cancer progression, invasion and more so, endocytosis of SARS-Cov-2 virus into the lung epithelial cells. Importantly, patients with KrasG12V mutation show agreessive disease and high-resistance to chemotherapy due to over-expression of Cathepsin L. Thus, Cathepsin L is a common target for lung cancer and COVID-19 infection. Chymostatin is a known cathepsin L inhibitor, here we screened it for dual inhibition of COVID-19 Mpro and lung cancer patients with COVID-19. In vitro COVID-19 Mpro fluorometric assay was performed to evaluate its inhibitory efficacy by chymostatin. Chymostatin showed dose-dependent inhibition of COVID-19 Mpro activity with IC50 of 15.81 µM (P Citation Format: Nagendra Sastry Yarla, Gopal Pathuri, Simon Terzyan, Yuting Zhang, Anil Singh, Marcus T. Scotti, Venkateshwar Madka, Chinthalapally V. Rao. Chymostatin, a cathepsin L inhibitor, inhibits lung cancer cell proliferation and COVID-19 Mproin vitro [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 LB074.","PeriodicalId":417728,"journal":{"name":"COVID-19 and Cancer","volume":"23 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134147895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract LB076: Association between regional COVID-19 hospitalizations and treatment delays amongst confirmed cancer patients in England, UK","authors":"L. Fox, A. Aggarwal, R. Sullivan, K. Haire, A. Purushotham, James Spicer, S. Papa, A. Rigg, S. Dolly, M. V. Hemelrijck","doi":"10.1158/1538-7445.AM2021-LB076","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-LB076","url":null,"abstract":"Introduction: The COVID-19 pandemic has had substantial impacts on cancer services. National Cancer Waiting Times (CWT) targets in England stipulate that individuals referred from primary care for suspected cancer must receive treatment for any confirmed cancer within 62 days of referral. This analysis aimed to broadly quantify the association between COVID-19 hospitalizations by England region, and the proportion of confirmed cancer patients breaching the 62-day target in that region a month later, during the first wave of COVID-19 in England. Methods: CWT data were retrospectively obtained from all 135 clinical subregions of the National Health Service (NHS) in England, for the 6-month period from April to September 2020 inclusive. Subregion data were then grouped by each of the seven regions of England: London; South East England; South West England; East of England; the Midlands; North West England; and North East England & Yorkshire. The mean number of monthly cases of confirmed cancer that waited more than 62 days from referral for their treatment (CWT breaches) was calculated amongst subregions within each region, inclusive of all cancer types. These 62-day primary care referrals represent around 73% of all treated cancers. These data were entered into linear regression models for each region, alongside daily UK Government data on numbers of patients in hospital with suspected COVID-19 within each region, with a 30-day lag applied (e.g. CWT breaches that occurred in June were plotted against COVID-19 hospitalization data from May). Results: The regression models showed that regional COVID-19 hospitalizations were significantly positively associated with 62-day CWT breaches the following month, for all regions except for London (all significant at the p Conclusion: Higher rates of regional hospitalizations for suspected COVID-19 during England9s initial wave of SARS-CoV-2 were associated with increased delays to cancer treatments across most England regions. It should be noted that CWT breaches do not necessarily translate directly into clinical harm, due to clinical risk prioritization strategies that were deployed during the initial wave of COVID-19. Citation Format: Louis Fox, Ajay Aggarwal, Richard Sullivan, Kate Haire, Arnie Purushotham, James Spicer, Sophie Papa, Anne Rigg, Saoirse Dolly, Mieke Van Hemelrijck. Association between regional COVID-19 hospitalizations and treatment delays amongst confirmed cancer patients in England, UK [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 LB076.","PeriodicalId":417728,"journal":{"name":"COVID-19 and Cancer","volume":"90 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131610040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}