Concepts for Immunotherapies in Gliomas

2018 ◽  
Vol 38 (01) ◽  
pp. 062-072 ◽  
Author(s):  
Michael Platten ◽  
David Reardon

Strategies to empower the immune system to successfully attack cancers, including vaccination approaches, adaptive T cell therapies, and immune checkpoint modulators, have recently achieved remarkable success across a spectrum of cancer indications. Nonetheless, with rare exception, only a minority of patients with a given type of cancer respond to an immunotherapeutic when administered as single-agent therapy. Although under extensive laboratory and clinical investigation, the role of these approaches for glioma patients remains to be determined. While the central nervous system (CNS) is no longer regarded as an immunoprivileged sanctuary, nuances regarding immune responses in the CNS may impact on the activity of immunotherapy treatments of brain tumor patients. Furthermore, many common CNS tumors such as World Health Organization grade III and IV (high grade) gliomas utilize myriad, nonoverlapping strategies to dampen or extinguish antitumor immune responses. For these reasons, critical research efforts are focused on identifying biomarkers that predict patients with a heightened likelihood of therapeutic benefit as well as evaluating rationally designed combinatorial immunotherapy approaches with potentially complementary mechanisms of immune-activation for brain cancer patients.

2021 ◽  
Vol 22 (15) ◽  
pp. 8289
Author(s):  
Paula M. Wagner ◽  
César G. Prucca ◽  
Beatriz L. Caputto ◽  
Mario E. Guido

Gliomas are solid tumors of the central nervous system (CNS) that originated from different glial cells. The World Health Organization (WHO) classifies these tumors into four groups (I–IV) with increasing malignancy. Glioblastoma (GBM) is the most common and aggressive type of brain tumor classified as grade IV. GBMs are resistant to conventional therapies with poor prognosis after diagnosis even when the Stupp protocol that combines surgery and radiochemotherapy is applied. Nowadays, few novel therapeutic strategies have been used to improve GBM treatment, looking for higher efficiency and lower side effects, but with relatively modest results. The circadian timing system temporally organizes the physiology and behavior of most organisms and daily regulates several cellular processes in organs, tissues, and even in individual cells, including tumor cells. The potentiality of the function of the circadian clock on cancer cells modulation as a new target for novel treatments with a chronobiological basis offers a different challenge that needs to be considered in further detail. The present review will discuss state of the art regarding GBM biology, the role of the circadian clock in tumor progression, and new chrono-chemotherapeutic strategies applied for GBM treatment.


2021 ◽  
Vol 12 ◽  
Author(s):  
Gislane Lelis Vilela de Oliveira ◽  
Camilla Narjara Simão Oliveira ◽  
Camila Figueiredo Pinzan ◽  
Larissa Vedovato Vilela de Salis ◽  
Cristina Ribeiro de Barros Cardoso

COVID-19 is an infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), and according to the World Health Organization (WHO), to date, SARS-CoV-2 has already infected more than 91.8 million people worldwide with 1,986,871 deaths. This virus affects mainly the respiratory system, but the gastrointestinal tract (GIT) is also a target, meanwhile SARS-CoV-2 was already detected in oesophagus, stomach, duodenum, rectum, and in fecal samples from COVID-19 patients. Prolonged GIT manifestations in COVID-19, mainly the diarrhea, were correlated with decreased richness and diversity of the gut microbiota, immune deregulation and delayed SARS-CoV-2 clearance. So, the bidirectional interactions between the respiratory mucosa and the gut microbiota, known as gut-lung axis, are supposed to be involved in the healthy or pathologic immune responses to SARS-CoV-2. In accordance, the intestinal dysbiosis is associated with increased mortality in other respiratory infections, due to an exacerbated inflammation and decreased regulatory or anti-inflammatory mechanisms in the lungs and in the gut, pointing to this important relationship between both mucosal compartments. Therefore, since the mucous membranes from the respiratory and gastrointestinal tracts are affected, in addition to dysbiosis and inflammation, it is plausible to assume that adjunctive therapies based on the modulation of the gut microbiota and re-establishment of eubiosis conditions could be an important therapeutic approach for constraining the harmful consequences of COVID-19. Then, in this review, we summarized studies showing the persistence of SARS-CoV-2 in the gastrointestinal system and the related digestive COVID-19 manifestations, in addition to the literature demonstrating nasopharyngeal, pulmonary and intestinal dysbiosis in COVID-19 patients. Lastly, we showed the potential beneficial role of probiotic administration in other respiratory infections, and discuss the possible role of probiotics as an adjunctive therapy in SARS-CoV-2 infection.


BioMedica ◽  
2020 ◽  
Vol 36 (2S) ◽  
pp. 97-99
Author(s):  
Rabia Anjum

<p>Coronavirus disease 19 (COVID-19) has been promptly spreading to different countries becoming a global pandemic, to the reports of the World Health Organization (WHO). Sufficient immune responses over whelming the virus in the first or second phase without immune over-reaction can be seen in patients with competent immune functions and no obvious risk factors like old age, co-morbidities, etc. There is high sensitivity and specificity of saliva specimens in detecting respiratory viruses by an automated multiplex molecular assay while comparing with those of nasopharyngeal aspirate. The beneficial role of saliva as a quick and non-invasive diagnostic bio sample has been established.</p>


Author(s):  
Paula M. Wagner ◽  
Cesar G. Prucca ◽  
Beatriz L. Caputto ◽  
Mario E. Guido

Gliomas are solid tumors of the Central Nervous System (CNS) that originated from different glial cells. The World Health Organization (WHO) classified these tumors into four groups (I-IV) with increasing malignancy. Glioblastoma (GBM) is the most common and aggressive type of brain tumor classified as a grade IV. GBM are resistant to conventional therapies with poor prognosis after diagnosis even when the Stupp protocol that combines surgery and radiochemotherapy is applied. Nowadays, few novel therapeutic strategies have been used to improve GBM treatment, looking for higher efficiency and lower side effects, but with relatively modest results. The circadian timing system temporally organizes the physiology and behavior of most organisms and daily regulates several cellular processes in organs, tissues, and even in individual cells, including tumor cells. The potentiality of the function of the circadian clock on cancer cells modulation as a new target for novel treatments with a chronobiological basis offers a different challenge that needs to be considered in further detail. The present review will discuss state of the art regarding GBM biology, the role of the circadian clock in tumor progression, and new chrono-chemotherapeutic strategies applied for GBM treatment.


Author(s):  
Lara Bittmann

On December 31, 2019, WHO was informed of cases of pneumonia of unknown cause in Wuhan City, China. A novel coronavirus was identified as the cause by Chinese authorities on January 7, 2020 and was provisionally named "2019-nCoV". This new Coronavirus causes a clinical picture which has received now the name COVID-19. The virus has spread subsequently worldwide and was explained on the 11th of March, 2020 by the World Health Organization to the pandemic.


2021 ◽  
Vol 29 (Supplement_1) ◽  
pp. i45-i46
Author(s):  
A Peletidi ◽  
R Kayyali

Abstract Introduction Obesity is one of the main cardiovascular disease (CVD) risk factors.(1) In primary care, pharmacists are in a unique position to offer weight management (WM) interventions. Greece is the European country with the highest number of pharmacies (84.06 pharmacies per 100,000 citizens).(2) The UK was chosen as a reference country, because of the structured public health services offered, the local knowledge and because it was considered to be the closest country to Greece geographically, unlike Australia and Canada, where there is also evidence confirming the potential role of pharmacists in WM. Aim To design and evaluate a 10-week WM programme offered by trained pharmacists in Patras. Methods This WM programme was a step ahead of other interventions worldwide as apart from the usual measuring parameters (weight, body mass index, waist circumference, blood pressure (BP)) it also offered an AUDIT-C and Mediterranean diet score tests. Results In total,117 individuals participated. Of those, 97.4% (n=114), achieved the programme’s aim, losing at least 5% of their initial weight. The mean % of total weight loss (10th week) was 8.97% (SD2.65), and the t-test showed statistically significant results (P&lt;0.001; 95% CI [8.48, 9.45]). The programme also helped participants to reduce their waist-to-height ratio, an early indicator of the CVD risk in both male (P=0.004) and female (P&lt;0.001) participants. Additionally, it improved participants’ BP, AUDIT-C score and physical activity levels significantly (P&lt;0.001). Conclusion The research is the first systematic effort in Greece to initiate and explore the potential role of pharmacists in public health. The successful results of this WM programme constitute a first step towards the structured incorporation of pharmacists in public’s health promotion. It proposed a model for effectively delivering public health services in Greece. This study adds to the evidence in relation to pharmacists’ CVD role in public health with outcomes that superseded other pharmacy-led WM programmes. It also provides the first evidence that Greek pharmacists have the potential to play an important role within primary healthcare and that after training they are able to provide public health services for both the public’s benefit and their clinical role enhancement. This primary evidence should support the Panhellenic Pharmaceutical Association, to “fight” for their rights for an active role in primary care. In terms of limitations, it must be noted that the participants’ collected data were recorded by pharmacists, and the analysis therefore depended on the accuracy of the recorded data, in particular on the measurements or calculations obtained. Although the sample size was achieved, it can be argued that it is small for the generalisation of findings across Greece. Therefore, the WM programme should be offered in other Greek cities to identify if similar results can be replicated, so as to consolidate the contribution of pharmacists in promoting public health. Additionally, the study was limited as it did not include a control group. Despite the limitations, our findings provide a model for a pharmacy-led public health programme revolving around WM that can be used as a model for services in the future. References 1. Mendis S, Puska P, Norrving B, World Health Organization., World Heart Federation., World Stroke Organization. Global atlas on cardiovascular disease prevention and control [Internet]. Geneva: World Health Organization in collaboration with the World Heart Federation and the World Stroke Organization; 2011 [cited 2018 Jun 26]. 155 p. Available from: http://www.who.int/cardiovascular_diseases/publications/atlas_cvd/en/ 2. Pharmaceutical Group of the European Union. Pharmacy with you throughout life:PGEU Annual Report [Internet]. 2015. Available from: https://www.pgeu.eu/en/library/530:annual-report-2015.html


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria Clara Saad Menezes ◽  
Alicia Dudy Müller Veiga ◽  
Thais Martins de Lima ◽  
Suely Kunimi Kubo Ariga ◽  
Hermes Vieira Barbeiro ◽  
...  

AbstractThe role of innate immunity in COVID-19 is not completely understood. Therefore, this study explored the impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection on the expression of Pattern Recognition Receptors (PRRs) in peripheral blood cells and their correlated cytokines. Seventy-nine patients with severe COVID-19 on admission, according to World Health Organization (WHO) classification, were divided into two groups: patients who needed mechanical ventilation and/or deceased (SEVERE, n = 50) and patients who used supplementary oxygen but not mechanical ventilation and survived (MILD, n = 29); a control group (CONTROL, n = 17) was also enrolled. In the peripheral blood, gene expression (mRNA) of Toll-like receptors (TLRs) 3, 4, 7, 8, and 9, retinoic-acid inducible gene I (RIGI), NOD-like receptor family pyrin domain containing 3 (NLRP3), interferon alpha (IFN-α), interferon beta (IFN-β), interferon gamma (IFN-γ), interferon lambda (IFN-λ), pro-interleukin(IL)-1β (pro-IL-1β), and IL-18 was determined on admission, between 5–9 days, and between 10–15 days. Circulating cytokines in plasma were also measured. When compared to the COVID-19 MILD group, the COVID-19 SEVERE group had lower expression of TLR3 and overexpression of TLR4.


Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1346
Author(s):  
Priya Veluswamy ◽  
Max Wacker ◽  
Dimitrios Stavridis ◽  
Thomas Reichel ◽  
Hendrik Schmidt ◽  
...  

The SARS-CoV-2 virus causing COVID-19 disease has emerged expeditiously in the world and has been declared pandemic since March 2020, by World Health Organization (WHO). The destructive effects of SARS-CoV-2 infection are increased among the patients with pre-existing chronic conditions and, in particular, this review focuses on patients with underlying cardiovascular complications. The expression pattern and potential functions of SARS-CoV-2 binding receptors and the attributes of SARS-CoV-2 virus tropism in a physio-pathological state of heart and blood vessel are precisely described. Of note, the atheroprotective role of ACE2 receptors is reviewed. A detailed description of the possible detrimental role of SARS-CoV-2 infection in terms of vascular leakage, including endothelial glycocalyx dysfunction and bradykinin 1 receptor stimulation is concisely stated. Furthermore, the potential molecular mechanisms underlying SARS-CoV-2 induced clot formation in association with host defense components, including activation of FXIIa, complements and platelets, endothelial dysfunction, immune cell responses with cytokine-mediated action are well elaborated. Moreover, a brief clinical update on patient with COVID-19 disease with underlying cardiovascular complications and those who had new onset of cardiovascular complications post-COVID-19 disease was also discussed. Taken together, this review provides an overview of the mechanistic aspects of SARS-CoV-2 induced devastating effects, in vital organs such as the heart and vessels.


2021 ◽  
Vol 14 (1) ◽  
pp. 71
Author(s):  
Katarzyna Kotfis ◽  
Kacper Lechowicz ◽  
Sylwester Drożdżal ◽  
Paulina Niedźwiedzka-Rystwej ◽  
Tomasz K. Wojdacz ◽  
...  

In March 2020, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was declared a global pandemic by the World Health Organization (WHO). The clinical course of the disease is unpredictable but may lead to severe acute respiratory infection (SARI) and pneumonia leading to acute respiratory distress syndrome (ARDS). It has been shown that pulmonary fibrosis may be one of the major long-term complications of COVID-19. In animal models, the use of spironolactone was proven to be an important drug in the prevention of pulmonary fibrosis. Through its dual action as a mineralocorticoid receptor (MR) antagonist and an androgenic inhibitor, spironolactone can provide significant benefits concerning COVID-19 infection. The primary effect of spironolactone in reducing pulmonary edema may also be beneficial in COVID-19 ARDS. Spironolactone is a well-known, widely used and safe anti-hypertensive and antiandrogenic medication. It has potassium-sparing diuretic action by antagonizing mineralocorticoid receptors (MRs). Spironolactone and potassium canrenoate, exerting combined pleiotropic action, may provide a therapeutic benefit to patients with COVID-19 pneumonia through antiandrogen, MR blocking, antifibrotic and anti-hyperinflammatory action. It has been proposed that spironolactone may prevent acute lung injury in COVID-19 infection due to its pleiotropic effects with favorable renin–angiotensin–aldosterone system (RAAS) and ACE2 expression, reduction in transmembrane serine protease 2 (TMPRSS2) activity and antiandrogenic action, and therefore it may prove to act as additional protection for patients at highest risk of severe pneumonia. Future prospective clinical trials are warranted to evaluate its therapeutic potential.


Author(s):  
Diletta Cozzi ◽  
Eleonora Bicci ◽  
Alessandra Bindi ◽  
Edoardo Cavigli ◽  
Ginevra Danti ◽  
...  

The infection caused by novel beta-coronavirus (SARS-CoV-2) was officially declared a pandemic by the World Health Organization in March 2020. However, in the last 20 years, this has not been the only viral infection to cause respiratory tract infections leading to hundreds of thousands of deaths worldwide, referring in particular to severe acute respiratory syndrome (SARS), influenza H1N1 and Middle East respiratory syndrome (MERS). Although in this pandemic period SARS-CoV-2 infection should be the first diagnosis to exclude, many other viruses can cause pulmonary manifestations and have to be recognized. Through the description of the main radiological patterns, radiologists can suggest the diagnosis of viral pneumonia, also combining information from clinical and laboratory data.


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