Use of monoclonal antibody therapy in hematologic patients with mild-to-moderate COVID-19: A retrospective single-center experience.

INTRODUCTION: In November 2020, the FDA issued an emergency use authorization (EUA) for monoclonal antibody (mAb) therapy in patients with mild-to-moderate COVID-19 at high risk for disease progression. METHODS: We retrospectively reviewed 38 adult hematology patients who received mAbs from 11/2020 to 2/2021. RESULTS: Thirty (79%) patients received bamlanivimab and 8 (21%) casirivimab-imdevimab. Four (11%) patients were hospitalized due to COVID-19, two (5%) progressed to severe disease and one patient (3%) died within 30 days from COVID-19 disease. Most patients (n = 34, 89%) ultimately tested negative for SARS-CoV-2, with 34% (n = 13) clearing the virus within 14 days after mAb infusion. The median time to clearance of viral shedding was 25.5 days (range: 7-138). After mAb infusion, most patients with hematological malignancies (HM) (n = 10/15; 67%) resumed therapy for underlying disease with a median delay of 21.5 days (range: 12-42). We observed a significant difference in hospitalization among patients who received a HCT versus non-HCT (0% n = 0/26 and 36% n = 4/11, respectively; p < 0.01). CONCLUSIONS: This study demonstrates that SARS-CoV-2 specific mAb was safe and may reduce hospitalization compared to what is reported in malignant hematology patients at high risk for disease progression. Our HCT cohort patients had less hospitalization rate compared with HM cohort patients.

Possibilities of targeted therapy for myelofibrosis: Moscow experience

Background. for many years the primary aim of treatment strategy for ph-negative myeloproliferative neoplasms has been to restrain disease progression, with lasting relief and management of symptoms to improve patients' quality of life. Generally, this did not lead to a significant increase in life expectancy with primary myelofibrosis and didn't decrease the risk of fibrosis in patients with polycythemia vera and essential thrombocythemia. To date a new class of targeted drugs has been developed, it is JAK2 inhibitors with pathogenetic effects. The results of clinical trials showed the high efficacy of the first registered drug of this its kind - ruxolitinib - that includes a faster reduction in the symptoms of tumor intoxication and in symptoms associated with the development of splenomegaly and increase in the overall survival rates. It is known that the data obtained during clinical trials of medicines may differ from the results obtained in routine clinical practice. In actual practice drugs are used in a much wider heterogeneous population of patients, less limited first of all by age and comorbid characteristics. It is possible to analyze cohorts of patients including a larger number of clinical cases with a longer follow-up period. In this regard of great interest is the actual clinical experience of long-term use of ruxolitinib in patients whose set is limited only by clinical contraindications for prescribing the drug. Aim. To present our own actual experience of targeted therapy of myelofibrosis and compare the results obtained with the data of clinical trials. Materials and methods. Our analysis includes data from 141 patients (67 (47.5 %) men and 74 (52.5 %) women) in a chronic phase myelofibrosis. All patients received ruxolitinib. Of these, 109 (69 %) patients had primary myelofibrosis, 26 (16 %) - postpolycythemia myelofibrosis, 6 (4 %) - postessential thrombocythemia myelofibrosis. The median age at the start of therapy was 62 (18-84) years. The median disease duration before ruxolitinib was prescribed - 79 (1-401) months. According to the dIpSS (dynamic International prognostic Scoring System) criteria, 13 % of patients were assigned to the low risk group, 38 % - to the intermediate-1, 36 % - to the intermediate-2, 13 % - to the high risk group. Most patients (52 %) had grade 3 bone marrow fibrosis. Results. The median duration of treatment was 18 (range from 1 to 115) months. Symptoms of intoxication were relieved 74 (81 %) of 91 patients, the spleen size decreased in 81 % of patients (the spleen size returned to normal in 25 % of patients). The increase in the median hemoglobin level was 15 %. The proportion of patients requiring blood transfusion decreased by 4 times (from 39 to 9 %). Mean platelet levels normalized in most patients with baseline high and low platelet levels. A complete clinical and hematological response was achieved in 16 % (n = 23) of cases, a partial response - in 26 % (n = 37) of cases, clinical improvement - in 21 % (n = 30), disease stabilization - in 33 % (n = 46) of cases. No response was received in 1 (1 %) patient and in 3 (3 %) cases there was progression of the disease. At the time of analysis, 81 (57 %) of 141 patients were continuing the ruxolitinib treatment. The fatal outcome in 33 (22 %) patients was associated with concomitant diseases, among which 20 (14 %) died from proven COvId-19 infection. Overall survival: 1-year 81 %, 2-year 73 %, 5-year 50 %. Overall survival excluding deaths due to COvId-19: 1-year 92 %, 2-year 85 %, 5-year 70 %. Massive splenomegaly and a high degree of fibrosis were unfavorable predictors of prognosis of overall survival. Conclusion. Target therapy with Janus kinase inhibitor ruxolitinib has demonstrated high efficacy in patients with myelofibrosis in routine clinical practice. The most rapid effect ruxolitinib had on the spleen size and the symptoms of intoxication. Tolerability of ruxolitinib therapy was generally satisfactory. The overall and progression-free survival rates in patients with myelofibrosis, receiving ruxolitinib i the clinical setting was consistent with the results of international multicenter clinical trials. Copyright © 2022 ABV-Press Publishing House. All rights reserved.

SARS-CoV-2-correlated ASGR1 is a novel potential marker for the treatment and identification of multiple human cancers

Objectives: Cancer patients are reported to be more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the COVID-19 (the Corona Virus Disease 2019) patients with cancer suffer from certain serious complications. ASGR1 has been recently identified as a novel receptor of SARS-CoV-2 in human cells;however, there are limited studies on ASGR1 in various human cancers. Method(s): This study utilized a comprehensive analysis of COVID-19-related ASGR1 in multiple human cancers based on 18,589 multi-center samples. Using Wilcoxon rank-sum analysis, a difference in ASGR1 expression between cancer and control tissues was detected. Cox regression analysis, Kaplan-Meier curves, and receiver operating characteristic curves were utilized to determine the correlation between ASGR1 expression and the clinical parameters of cancer patients. The immune relevance and potential mechanisms of ASGR1 in various cancers were also investigated. Result(s): Abnormal ASGR1 mRNA expression was observed in 16 of 20 different cancers (e.g., it was upregulated in colon adenocarcinoma but downregulated in cholangiocarcinoma;P < 0.05). ASGR1 was related to prognosis, e.g., overall survival, in 14 cancers (P < 0.05), such as adrenocortical carcinoma. The gene was also found to be a potential marker that can be utilized to distinguish eleven cancers from controls with moderate to high accuracy (e.g., the area under the curve for cholangiocarcinoma = 1.000). ASGR1 expression was related to DNA methyltransferases, mismatch repair genes, immune checkpoints, levels of tumor mutational burden, microsatellite instability, neoantigen count, and immune infiltration levels in certain cancers (P < 0.05). The gene plays a role in multiple cancers by affecting four signaling pathways, such as cytokine-cytokine receptor interaction. Cancer patients with high ASGR1 expression are sensitive to 25 drugs, including ulixertinib. Conclusion(s): SARS-CoV-2-correlated ASGR1 is a novel marker that can be used for treating and identifying multiple human cancers. Copyright © 2022 E-Century Publishing Corporation. All rights reserved.

EXPERIENCE WITH HIGH-THROUGHPUT SEQUENCING, BONE MARROW TRANSPLANTATION AND TARGETED THERAPY FOR ACUTE MYELOID LEUKEMIA WITH A POOR PROGNOSIS

The study presents a clinical case of treating acute myeloid leukemia with an unfavorable genetic prognosis due to genotyping by high-throughput sequencing. The patient underwent related allogeneic bone marrow transplantation with targeted chemotherapy. The disease manifested itself after a new coronavirus infection. Mutations R140Q in the IDH2 gene and P799S in the DNMT3A gene were detected by high throughput sequencing. Given the unfavorable genetic prognosis, bone marrow transplantation from an HLA-compatible sibling was performed. On day 22, COVID-19 was detected, and ruxolitinib was added to the treatment. On the 25th day, hematopoiesis was restored with the preservation of clinical and hematological remission. Ten months after transplantation, a relapse was diagnosed, for which the patient started targeted therapy with 5-azacytidine with venetoclax in combination with transfusions of donor leukocytes. The second remission was achieved after the first course. The total duration of follow-up was 24 months. © Group of authors, 2022.

Perspectives in Melanoma: meeting report from the Melanoma Bridge (December 2nd - 4th, 2021, Italy).

Advances in immune checkpoint and combination therapy have led to improvement in overall survival for patients with advanced melanoma. Improved understanding of the tumor, tumor microenvironment and tumor immune-evasion mechanisms has resulted in new approaches to targeting and harnessing the host immune response. Combination modalities with other immunotherapy agents, chemotherapy, radiotherapy, electrochemotherapy are also being explored to overcome resistance and to potentiate the immune response. In addition, novel approaches such as adoptive cell therapy, oncogenic viruses, vaccines and different strategies of drug administration including sequential, or combination treatment are being tested. Despite the progress in diagnosis of melanocytic lesions, correct classification of patients, selection of appropriate adjuvant and systemic theràapies, and prediction of response to therapy remain real challenges in melanoma. Improved understanding of the tumor microenvironment, tumor immunity and response to therapy has prompted extensive translational and clinical research in melanoma. There is a growing evidence that genomic and immune features of pre-treatment tumor biopsies may correlate with response in patients with melanoma and other cancers, but they have yet to be fully characterized and implemented clinically. Development of novel biomarker platforms may help to improve diagnostics and predictive accuracy for selection of patients for specific treatment. Overall, the future research efforts in melanoma therapeutics and translational research should focus on several aspects including: (a) developing robust biomarkers to predict efficacy of therapeutic modalities to guide clinical decision-making and optimize treatment regimens, (b) identifying mechanisms of therapeutic resistance to immune checkpoint inhibitors that are potentially actionable, (c) identifying biomarkers to predict therapy-induced adverse events, and (d) studying mechanism of actions of therapeutic agents and developing algorithms to optimize combination treatments. During the Melanoma Bridge meeting (December 2nd-4th, 2021, Naples, Italy) discussions focused on the currently approved systemic and local therapies for advanced melanoma and discussed novel biomarker strategies and advances in precision medicine as well as the impact of COVID-19 pandemic on management of melanoma patients.

Unusual Clinical Experience in BRAF Exon 15 p.K601E-Mutated Lung Cancer: A Case Report and Brief Review of the Literature

Molecular profiling has revolutionized the treatment of metastatic NSCLC. Uncommon mutations have been reported primarily in EGFR and BRAF genes and are frequently associated with atypical clinical presentations. Here, we present a rare case of a patient affected by BRAF exon 15 p.K601E-mutated lung cancer with synchronous peritoneal carcinomatosis. First line treatment with chemo-immunotherapy combinations provided a PFS of 8–9 months, whereas a second line treatment with BRAF and MEK inhibitors elicited a dissociated response. The latter clinical outcome suggests that these inhibitors have only partial activity against this rare mutation.

Pan-Cancer Analysis, Reveals COVID-19-Related BSG as a Novel Marker for Treatment and Identification of Multiple Human Cancers.

Background: Coronavirus disease 2019 (COVID-19) has been a public threat and healthcare concern caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. During the period of the pandemic of COVID-19, cancer patients should be paid more attention as more severe events are found in cancer patients infected with SARS-CoV-2. Basigin (BSG) is an essential factor for the infection and progression of COVID-19 and tumorigenesis of multiple tumors, which may serve as a novel target for the effective treatment against COVID-19 and multiple human cancers. Methods: A total of 19,020 samples from multiple centers were included in our research for the comprehensive investigation of the differences in BSG expression among human organs, cancer cells, cancer tissues, and normal tissues. Cox regression analysis and Kaplan-Meier curves were utilized to explore the prognosis factor of BSG in cancers. Correlation analyses were used to determine associations of BSG expression with tumor mutational burden, the immune microenvironment, etc. Gene set enrichment analysis was applied to explore the underlying mechanisms of BSG in cancers. Results: Compared with normal tissues, BSG expression was high in 13 types of cancers (cholangiocarcinoma, etc.) and low in colon adenocarcinoma and rectum adenocarcinoma. BSG expression was related to the prognosis of eight cancers (e.g., invasive breast carcinoma) (p < 0.05). The gene also demonstrated a pronounced effect in identifying 12 cancers (cholangiocarcinoma, etc.) from their control samples (AUC >0.7). The BSG expression was associated with DNA methyltransferases, mismatch repair genes, immune infiltration levels, tumor mutational burden, microsatellite instability, neoantigen, and immune checkpoints, suggesting the potential of BSG as an exciting target for cancer treatment. BSG may play its role in several cancers by affecting several signaling pathways such as drug cytochrome metabolism P450 and JAK-STAT. Conclusion: BSG may be a novel biomarker for treating and identifying multiple human cancers.

Rationale and design of interleukin-1 blockade in recently decompensated heart failure (REDHART2): a randomized, double blind, placebo controlled, single center, phase 2 study.

BACKGROUND: Heart failure (HF) is a global leading cause of mortality despite implementation of guideline directed therapy which warrants a need for novel treatment strategies. Proof-of-concept clinical trials of anakinra, a recombinant human Interleukin-1 (IL-1) receptor antagonist, have shown promising results in patients with HF. METHOD: We designed a single center, randomized, placebo controlled, double-blind phase II randomized clinical trial. One hundred and two adult patients hospitalized within 2 weeks of discharge due to acute decompensated HF with reduced ejection fraction (HFrEF) and systemic inflammation (high sensitivity of C-reactive protein > 2 mg/L) will be randomized in 2:1 ratio to receive anakinra or placebo for 24 weeks. The primary objective is to determine the effect of anakinra on peak oxygen consumption (VO2) measured at cardiopulmonary exercise testing (CPX) after 24 weeks of treatment, with placebo-corrected changes in peak VO2 at CPX after 24 weeks (or longest available follow up). Secondary exploratory endpoints will assess the effects of anakinra on additional CPX parameters, structural and functional echocardiographic data, noninvasive hemodynamic, quality of life questionnaires, biomarkers, and HF outcomes. DISCUSSION: The current trial will assess the effects of IL-1 blockade with anakinra for 24 weeks on cardiorespiratory fitness in patients with recent hospitalization due to acute decompensated HFrEF. TRIAL REGISTRATION: The trial was registered prospectively with ClinicalTrials.gov on Jan 8, 2019, identifier NCT03797001.

COVID-19 mRNA Vaccine in Patients With Lymphoid Malignancy or Anti-CD20 Antibody Therapy: A Systematic Review and Meta-Analysis.

BACKGROUND: The humoral response to vaccination in individuals with lymphoid malignancies or those undergoing anti-CD20 antibody therapy is impaired, but details of the response to mRNA vaccines to protect against COVID-19 remain unclear. This systematic review and meta-analysis aimed to characterize the response to COVID-19 mRNA vaccines in patients with lymphoid malignancies or those undergoing anti-CD20 antibody therapy. MATERIALS AND METHODS: A literature search retrieved 52 relevant articles, and random-effect models were used to analyze humoral and cellular responses. RESULTS: Lymphoid malignancies and anti-CD20 antibody therapy for non-malignancies were significantly associated with lower seropositivity rates (risk ratio 0.60 [95% CI 0.53-0.69]; risk ratio 0.45 [95% CI 0.39-0.52], respectively). Some subtypes (chronic lymphocytic leukemia, treatment-naïve chronic lymphocytic leukemia, myeloma, and non-Hodgkin's lymphoma) exhibited impaired humoral response. Anti-CD20 antibody therapy within 6 months of vaccination decreased humoral response; moreover, therapy > 12 months before vaccination still impaired the humoral response. However, anti-CD20 antibody therapy in non-malignant patients did not attenuate T cell responses. CONCLUSION: These data suggest that patients with lymphoid malignancies or those undergoing anti-CD20 antibody therapy experience an impaired humoral response, but cellular response can be detected independent of anti-CD20 antibody therapy. Studies with long-term follow-up of vaccine effectiveness are warranted (PROSPERO registration number: CRD42021265780).

Predictors of poor seroconversion and adverse events to SARS-CoV-2 mRNA BNT162b2 vaccine in cancer patients on active treatment.

PURPOSE: Initial findings in patients with cancer suggest a lower seroconversion to SARS-CoV-2 vaccination possibly related to myelo-immunosuppressive therapies. We conducted a prospective study to assess factors predicting poor seroconversion and adverse events following immunisation (AEFI) to the BNT162b2 vaccine in patients on active treatment. PATIENTS AND METHODS: Cancer patients, candidates to two doses of BNT162b2 SARS-CoV-2 vaccination, were enrolled. Patients on active surveillance served as controls. The primary endpoint was poor seroconversion (anti S1/S2 IgG < 25 AU/mL) after 21 days from the second dose. RESULTS: Between March and July 2021, 320 subjects were recruited, and 291 were assessable. The lack of seroconversion at 21 days from the second dose was 1.6% (95% CI, 0.4-8.7) on active surveillance, 13.9% (8.2-21.6) on chemotherapy, 11.4% (5.1-21.3) on hormone therapy, 21.7% (7.5-43.7) on targeted therapy and 4.8% (0.12-23.8) on immune-checkpoint-inhibitors (ICI). Compared to controls, the risk of no IgG response was greater for chemotherapy (p = 0.033), targeted therapy (0.005) and hormonotherapy (p = 0.051). Lymphocyte count < 1 × 109/L (p = 0.04) and older age (p = 0.03) also significantly predicted poor seroconversion. Overall, 43 patients (14.8%) complained of AEFI, mostly of mild grade. Risk of AEFI was greater in females (p = 0.001) and younger patients (p = 0.009). CONCLUSION: Chemotherapy, targeted therapy, hormone therapy, lymphocyte count < 1 × 109/L, and increasing age predict poor seroconversion after two doses of BNT162b2 in up to 20% of patients, indicating the need for a third dose and long-term serological testing in non-responders. AEFI occur much more frequently in women and younger subjects who may benefit from preventive medications. CLINICALTRIALS. GOV IDENTIFIER: NCT04932863.

Identification of potential hits against novel coronavirus-targeting glycoprotein for multi-target approach

Coronavirus disease (COVID-19) is an infectious disease caused by a novel coronavirus impacting more than 75 million people across 220 countries. The pharma and biotech industries, along with research institutes, strive to develop an effective vaccine against the novel coronavirus. Efforts are also underway for finding drugs through drug repurposing and novel drug discovery methods. In this study, we have used a multi-target drug approach. The objective is to identify phytochemicals from plant sources effective against novel coronavirus. Natural products having good medicinal properties are known to have minimal side effects compared to synthetic drugs. Therefore, the medicinal products from natural sources are of significance in drug discovery research. In this study, compounds from three common plants were selected for analysis, namely, Tinospora cordifolia, Withania somnifera, and Punica granatum. The primary target selected for this study was glycoprotein. Glycoproteins are known to play a key role in the regulation of cell proliferation, growth, and signaling pathways. We also investigated the effect of screened compounds on other targets in order to have a multi-target therapy. The target proteins chosen for drug design are Spike glycoprotein, Main Protease, and uridylate-specific Endoribonuclease (EndoU). The spike glycoprotein (S) of coronavirus, is a trimeric transmembrane protein, which facilitates entry into cells and is the main target of antibodies. The spike glycoprotein is highly sensitive to mutation. The main protease (MPro) of SRAS-CoV-2 plays an essential role in disease propagation by processing the polyproteins necessary for its replication. Inhibiting the main protease by designing agonists/antagonists can serve in the repair mechanism—the uridylate-specific Endoribonuclease (EndoU) of SRAS-CoV-2 causes a delay in the host sensor system. The objective of this study was to identify potential natural hit compounds which could target multiple proteins of coronavirus. Compounds that can target all the three, namely, Spike glycoprotein, EndoU, and MPro will have better therapeutic index and efficacy than a single target approach. Therefore, the compounds were screened against all these three structural targets. The compounds targeting only one of the proteins were filtered and only those compounds showing activity against all the three structural proteins were retained for further analysis. Drug design methods, including Absorption, Distribution, Metabolism and Elimination (ADME) profiling and molecular docking studies, have been used in the study to identify potential hit molecules. The twenty four hits obtained targeted all the three selected proteins. This will pave the way for developing lead molecules from the screened compounds effective against all three proteins of novel coronavirus: Main protease, Spike glycoprotein, and Endoribonuclease. © 2021, Trends In Carbohydrate Research. All rights reserved.

Identification of potential hits against novel coronavirus-targeting glycoprotein for multi-target approach

Coronavirus disease (COVID-19) is an infectious disease caused by a novel coronavirus impacting more than 75 million people across 220 countries. The pharma and biotech industries, along with research institutes, strive to develop an effective vaccine against the novel coronavirus. Efforts are also underway for finding drugs through drug repurposing and novel drug discovery methods. In this study, we have used a multi-target drug approach. The objective is to identify phytochemicals from plant sources effective against novel coronavirus. Natural products having good medicinal properties are known to have minimal side effects compared to synthetic drugs. Therefore, the medicinal products from natural sources are of significance in drug discovery research. In this study, compounds from three common plants were selected for analysis, namely, Tinospora cordifolia, Withania somnifera, and Punica granatum. The primary target selected for this study was glycoprotein. Glycoproteins are known to play a key role in the regulation of cell proliferation, growth, and signaling pathways. We also investigated the effect of screened compounds on other targets in order to have a multi-target therapy. The target proteins chosen for drug design are Spike glycoprotein, Main Protease, and uridylate-specific Endoribonuclease (EndoU). The spike glycoprotein (S) of coronavirus, is a trimeric transmembrane protein, which facilitates entry into cells and is the main target of antibodies. The spike glycoprotein is highly sensitive to mutation. The main protease (MPro) of SRAS-CoV-2 plays an essential role in disease propagation by processing the polyproteins necessary for its replication. Inhibiting the main protease by designing agonists/antagonists can serve in the repair mechanism-the uridylate-specific Endoribonuclease (EndoU) of SRAS-CoV-2 causes a delay in the host sensor system. The objective of this study was to identify potential natural hit compounds which could target multiple proteins of coronavirus. Compounds that can target all the three, namely, Spike glycoprotein, EndoU, and MPro will have better therapeutic index and efficacy than a single target approach. Therefore, the compounds were screened against all these three structural targets. The compounds targeting only one of the proteins were filtered and only those compounds showing activity against all the three structural proteins were retained for further analysis. Drug design methods, including Absorption, Distribution, Metabolism and Elimination (ADME) profiling and molecular docking studies, have been used in the study to identify potential hit molecules. The twenty four hits obtained targeted all the three selected proteins. This will pave the way for developing lead molecules from the screened compounds effective against all three proteins of novel coronavirus: Main protease, Spike glycoprotein, and Endoribonuclease.

Embryonic Origin and Subclonal Evolution of Tumor-Associated Macrophages Imply Preventive Care for Cancer.

Macrophages are widely distributed in tissues and function in homeostasis. During cancer development, tumor-associated macrophages (TAMs) dominatingly support disease progression and resistance to therapy by promoting tumor proliferation, angiogenesis, metastasis, and immunosuppression, thereby making TAMs a target for tumor immunotherapy. Here, we started with evidence that TAMs are highly plastic and heterogeneous in phenotype and function in response to microenvironmental cues. We pointed out that efforts to tear off the heterogeneous "camouflage" in TAMs conduce to target de facto protumoral TAMs efficiently. In particular, several fate-mapping models suggest that most tissue-resident macrophages (TRMs) are generated from embryonic progenitors, and new paradigms uncover the ontogeny of TAMs. First, TAMs from embryonic modeling of TRMs and circulating monocytes have distinct transcriptional profiling and function, suggesting that the ontogeny of TAMs is responsible for the functional heterogeneity of TAMs, in addition to microenvironmental cues. Second, metabolic remodeling helps determine the mechanism of phenotypic and functional characteristics in TAMs, including metabolic bias from macrophages' ontogeny in macrophages' functional plasticity under physiological and pathological conditions. Both models aim at dissecting the ontogeny-related metabolic regulation in the phenotypic and functional heterogeneity in TAMs. We argue that gleaning from the single-cell transcriptomics on subclonal TAMs' origins may help understand the classification of TAMs' population in subclonal evolution and their distinct roles in tumor development. We envision that TAM-subclone-specific metabolic reprogramming may round-up with future cancer therapies.

Applications and analytical tools of cell communication based on ligand-receptor interactions at single cell level.

BACKGROUND: Cellular communication is an essential feature of multicellular organisms. Binding of ligands to their homologous receptors, which activate specific cell signaling pathways, is a basic type of cellular communication and intimately linked to many degeneration processes leading to diseases. MAIN BODY: This study reviewed the history of ligand-receptor and presents the databases which store ligand-receptor pairs. The recently applications and research tools of ligand-receptor interactions for cell communication at single cell level by using single cell RNA sequencing have been sorted out. CONCLUSION: The summary of the advantages and disadvantages of analysis tools will greatly help researchers analyze cell communication at the single cell level. Learning cell communication based on ligand-receptor interactions by single cell RNA sequencing gives way to developing new target drugs and personalizing treatment.

Drug-Related Pneumonitis in Cancer Treatment during the COVID-19 Era.

Interstitial lung disease is recognized as a group of diseases with a different etiopathogenesis characterized by chronic lung inflammation with the accumulation of inflammatory cells, lymphocytes and macrophages, and the consequent release of proinflammatory cytokines. Various degrees of pulmonary fibrosis can be associated with this inflammatory condition. Interstitial lung disease related to oncological drugs is a relevant problem in clinical practice. The etiopathogenetic mechanisms underlying this adverse event are not completely known but can be partly explained by the mechanism of action of the drug involved. Therefore, knowledge of the relevance of this potentially fatal adverse event supported by the reported safety data of pivotal studies becomes fundamental in the management of patients. The prompt diagnosis of drug-related pneumonia and the consequent differential diagnosis with other forms of pneumonia allow a rapid suspension of treatment and the establishment of an immunosuppressive treatment if necessary. In the context of the health emergency related to SARS CoV2 infection and COVID-19-related interstitial lung disease, such knowledge holds decisive relevance in the conscious choice of cancer treatments. Our intent was to describe the oncological drugs most correlated with this adverse event by reporting, where possible, the percentages of insurgency in pivotal studies to provide an overview and therefore promote greater awareness of this important toxicity related to oncological treatment.

MicroRNAs and Long Non-Coding RNAs as Potential Candidates to Target Specific Motifs of SARS-CoV-2.

The respiratory system is one of the most affected targets of SARS-CoV-2. Various therapies have been utilized to counter viral-induced inflammatory complications, with diverse success rates. Pending the distribution of an effective vaccine to the whole population and the achievement of "herd immunity", the discovery of novel specific therapies is to be considered a very important objective. Here, we report a computational study demonstrating the existence of target motifs in the SARS-CoV-2 genome suitable for specific binding with endogenous human micro and long non-coding RNAs (miRNAs and lncRNAs, respectively), which can, therefore, be considered a conceptual background for the development of miRNA-based drugs against COVID-19. The SARS-CoV-2 genome contains three motifs in the 5'UTR leader sequence recognized by selective nucleotides within the seed sequence of specific human miRNAs. The seed of 57 microRNAs contained a "GGG" motif that promoted leader sequence-recognition, primarily through offset-6mer sites able to promote microRNAs noncanonical binding to viral RNA. Similarly, lncRNA H19 binds to the 5'UTR of the viral genome and, more specifically, to the transcript of the viral gene Spike, which has a pivotal role in viral infection. Notably, some of the non-coding RNAs identified in our study as candidates for inhibiting SARS-CoV-2 gene expression have already been proposed against diverse viral infections, pulmonary arterial hypertension, and related diseases.

HMGB1: A pleiotropic activity.

High-mobility group box 1 (HMGB1) is a nuclear protein involved in DNA replication, transcription, recombination, and repair. In the extracellular space, the HMGB1 plays an essential role in the onset and perpetuation of inflammation, belonging to the group of damage-associated molecular pattern (DAMP) molecules, also called alarmins. For this, HMGB1 has been studied in several acute and chronic inflammatory diseases as an early biomarker of inflammation. An increased concentration of HMGB1 has been detected in serum, as the expression of systemic inflammation, and in specific samples (such as stool, synovial fluid, nasal lavage fluid, sputum, and cerebrospinal fluid), as the expression of local production, in several infectious and/or inflammatory diseases. These data are particularly important because they open new futuristic possibilities for target therapies, potentially also for the COVID-19 treatment.

Severe Acute Respiratory Syndrome-Coronavirus-2 Infection and Patients With Lung Cancer: The Potential Role of Interleukin-17 Target Therapy.

The coronavirus disease 2019 outbreak is evolving rapidly worldwide. The lungs are the target of the primary infection and patients with lung cancer seem to have a poor prognosis. To our knowledge, this is the first reported investigation of a possible role of interleukin-17 target therapy in patients with lung cancer and concomitant severe acute respiratory syndrome-coronavirus-2 infection.