Sonodynamic Therapy for Gliomas. Perspectives and Prospects of Selective Sonosensitization of Glioma Cells

Malignant glial tumors (gliomas) are the second (after cerebral stroke) cause of death from diseases of the central nervous system. The current routine therapy, involving a combination of tumor resection, radio-, and chemo-therapy, only modestly improves survival. Sonodynamic therapy (SDT) has been broadly defined as a synergistic effect of sonication applied in combination with substances referred to as “sonosensitizers”. The current review focuses on the possibility of the use of tumor-seeking sonosensitizers, in particular 5-aminolevulinic acid, to control recurring gliomas. In this application, SDT employs a principle similar to that of the more widely-known photodynamic therapy of superficially located cancers, the difference being the use of ultrasound instead of light to deliver the energy necessary to eliminate the sensitized malignant cells. The ability of ultrasound to penetrate brain tissues makes it possible to reach deeply localized intracranial tumors such as gliomas. The major potential advantage of this variant of SDT is its relative non-invasiveness and possibility of repeated application. Until now, there have been no clinical data regarding the efficacy and safety of such treatment for malignant gliomas, but the preclinical data are encouraging

5-Aminolevulinic acid-mediated sonosensitization of rat RG2 glioma cells in vitro

Sonodynamic therapy (SDT) is a promising technique based on the ability of certain substances, called sonosensitizers, to sensitize cancer cells to non-thermal effects of low-energy ultrasound waves, allowing their destruction. Sonosensitization is thought to induce cell death by direct physical effects such as cavitation and acoustical streaming as well as by complementary chemical reactions generating oxygen free radicals. One of the promising sonosensitizers is 5-aminolevulinic acid (ALA) which upon selective uptake by cancer cells is metabolized and accumulated as protoporphyrin IX. The objective of the study was to describe ALA-mediated sonodynamic effects in vitro on a rat RG2 glioma cell line. Glioma cells, seeded at the bottom of 96-well plates and incubated with ALA (10 µg/ml) for 6 h, were exposed to the sinusoidal US pulses with a resonance frequency of 1 MHz, 1000 µs duration, 0.4 duty-cycle, and average acoustic power varying from 2 W to 6 W. Ultrasound waves were generated by a flat circular piezoelectric transducer with a diameter of 25 mm. Cell viability was determined by MTT assay. Structural cellular changes were visualized with a fluorescence microscope. Signs of cytotoxicity such as a decrease in cell viability, chromatin condensation and apoptosis were found. ALA-mediated SDT evokes cytotoxic effects of low intensity US on rat RG2 glioma cells in vitro . This cell line is indicated for further preclinical assessment of SDT in in vivo conditions

New Perspectives for Eye-Sparing Treatment Strategies in Primary Uveal Melanoma

Uveal melanoma is the most common intraocular malignancy and arises from melanocytes in the choroid, ciliary body, or iris. The current eye-sparing treatment options include surgical treatment, plaque brachytherapy, proton beam radiotherapy, stereotactic photon radiotherapy, or photodynamic therapy. However, the efficacy of these methods is still unsatisfactory. This article reviews several possible new treatment options and their potential advantages in treating localized uveal melanoma. These methods may be based on the physical destruction of the cancerous cells by applying ultrasounds. Two examples of such an approach are High-Intensity Focused Ultrasound (HIFU)—a promising technology of thermal destruction of solid tumors located deep under the skin and sonodynamic therapy (SDT) that induces reactive oxygen species. Another approach may be based on improving the penetration of anti-cancer agents into UM cells. The most promising technologies from this group are based on enhancing drug delivery by applying electric current. One such approach is called transcorneal iontophoresis and has already been shown to increase the local concentration of several different therapeutics. Another technique, electrically enhanced chemotherapy, may promote drug delivery from the intercellular space to cells. Finally, new advanced nanoparticles are developed to combine diagnostic imaging and therapy (i.e., theranostics). However, these methods are mostly at an early stage of development. More advanced and targeted preclinical studies and clinical trials would be needed to introduce some of these techniques to routine clinical practice

From Molecular Biology to Novel Immunotherapies and Nanomedicine in Uveal Melanoma

Molecular biology studies of uveal melanoma have resulted in the development of novel immunotherapy approaches including tebentafusp—a T cell–redirecting bispecific fusion protein. More biomarkers are currently being studied. As a result, combined immunotherapy is being developed as well as immunotherapy with bifunctional checkpoint inhibitory T cell engagers and natural killer cells. Current trials cover tumor-infiltrating lymphocytes (TIL), vaccination with IKKb-matured dendritic cells, or autologous dendritic cells loaded with autologous tumor RNA. Another potential approach to treat UM could be based on T cell receptor engineering rather than antibody modification. Immune-mobilizing monoclonal T cell receptors (TCR) against cancer, called ImmTAC TM molecules, represent such an approach. Moreover, nanomedicine, especially miRNA approaches, are promising for future trials. Finally, theranostic radiopharmaceuticals enabling diagnosis and therapy with the same molecule bring hope to this research

Ozone disinfection of community pharmacies during the COVID-19 pandemic as a possible preventive measure for infection spread

The COVID-19 pandemic is currently one of the major global health and economic challenges. An efficient method for reducing the transmission of the virus is a still unmet medical need. Existing experimental data have shown that coronavirus survival is negatively impacted by ozone, high temperature, and low humidity. Therefore, it is feasible to use area ozonation in pharmacies - the front line of the healthcare system. Nevertheless, further work is needed to evaluate the effectiveness of ozone disinfection to reduce the transmission of this virus in pharmacies, hospitals, and other public environments. Med Pr. 2021;72

Readiness and Willingness to Provide Immunization Services after Pilot Vaccination Training: A Survey among Community Pharmacists Trained and Not Trained in Immunization during the COVID-19 Pandemic in Poland

Background: Immunization rates among the adult population in Poland are below desired targets, urging the need to expand this service in the community. During the COVID-19 pandemic, the ultimate goals for limiting the spread of the infection are vaccines against SARS-CoV-2. Pharmaceutical companies are in a race for the fastest possible way to deliver vaccines. Community pharmacists in Poland are recognised as an accessible yet underutilised group of medical professionals. Therefore, involving pharmacists in vaccinations may have beneficial results for the healthcare system. Objectives: The objectives of this study were to assess the readiness and willingness of community pharmacists following the Pharmacist Without Borders project who had either been trained or not in providing immunization services, and to identify the factors that may support the implementation of such services in Poland. Methods: This study was conducted among pharmacists between February and August 2020 in Poland. A survey was developed to determine their readiness to provide vaccination services in their pharmacies, to recognise any barriers to vaccinations, as well as the factors necessary to implement vaccination services in Polish pharmacies. Results: A total of 1777 pharmacists participated in the study, comprising 127 (7.1%) pharmacists trained in vaccinations during the Pharmacists Without Borders project and 1650 (92.9%) pharmacists not participating in the workshops. Pharmacists participating in the workshops more often indicated that providing vaccinations in community pharmacies would improve the overall vaccination rate (p = 0.0001), and that pharmacists could play an important role in advertising and promoting vaccinations (p = 0.0001). For the pharmacists not participating in the workshops, they indicated to a much greater extent possible barriers affecting the readiness to provide vaccinations in pharmacies. They most often pointed out that vaccination services would result in a significant workload increase (p = 0.0001), that pharmacies were not adapted to immunization, and that there were not enough training courses for pharmacists (p = 0.0001). Conclusion: The pharmacists working in community pharmacies indicated many advantages of vaccinations in pharmacies. This study identified barriers to the introduction of vaccinations and factors necessary to implement these services in pharmacies. The pharmacists trained during the immunization programme of the Pharmacists Without Borders project showed a greater readiness to provide immunization services