Targeting CD38 in Neoplasms and Non-Cancer Diseases

CD38 is a myeloid antigen present both on the cell membrane and in the intracellular compartment of the cell. Its occurrence is often enhanced in cancer cells, thus making it a potential target in anticancer therapy. Daratumumab and isatuximab already received FDA approval, and novel agents such as MOR202, TAK079 and TNB-738 undergo clinical trials. Also, novel therapeutics such as SAR442085 aim to outrank the older antibodies against CD38. Multiple myeloma and immunoglobulin light-chain amyloidosis may be effectively treated with anti-CD38 immunotherapy. Its role in other hematological malignancies is also important concerning both diagnostic process and potential treatment in the future. Aside from the hematological malignancies, CD38 remains a potential target in gastrointestinal, neurological and pulmonary system disorders. Due to the strong interaction of CD38 with TCR and CD16 on T cells, it may also serve as the biomarker in transplant rejection in renal transplant patients. Besides, CD38 finds its role outside oncology in systemic lupus erythematosus and collagen-induced arthritis. CD38 plays an important role in viral infections, including AIDS and COVID-19. Most of the undergoing clinical trials focus on the use of anti-CD38 antibodies in the therapy of multiple myeloma, CD19- B-cell malignancies, and NK cell lymphomas. This review focuses on targeting CD38 in cancer and non-cancerous diseases using antibodies, cell-based therapies and CD38 inhibitors. We also provide a summary of current clinical trials targeting CD38

Modulation of Blood–Brain Barrier Permeability by Activating Adenosine A2 Receptors in Oncological Treatment

The blood–brain barrier (BBB) plays an important protective role in the central nervous system and maintains its homeostasis. It regulates transport into brain tissue and protects neurons against the toxic effects of substances circulating in the blood. However, in the case of neurological diseases or primary brain tumors, i.e., gliomas, the higher permeability of the blood-derived substances in the brain tissue is necessary. Currently applied methods of treatment for the primary brain neoplasms include surgical removal of the tumor, radiation therapy, and chemotherapy. Despite the abovementioned treatment methods, the prognosis of primary brain tumors remains bad. Moreover, chemotherapy options seem to be limited due to low drug penetration into the cancerous tissue. Modulation of the blood–brain barrier permeability may contribute to an increase in the concentration of the drug in the CNS and thus increase the effectiveness of therapy. Interestingly, endothelial cells in cerebral vessels are characterized by the presence of adenosine 2A receptors (A2AR). It has been shown that substances affecting these receptors regulate the permeability of the BBB. The mechanism of increasing the BBB permeability by A2AR agonists is the actin-cytoskeletal reorganization and acting on the tight junctions. In this case, the A2AR seems to be a promising therapy target. This article aims to assess the possibility of increasing the BBB permeability through A2AR agonists to increase the effectiveness of chemotherapy and to improve the results of cancer therapy

Contrast Media Adverse Drug Reactions in Highly Polluted Environment

Iodinated- (ICM) and gadolinium-based (GCM) contrast media are used in radiology imaging techniques, such as computer tomography (CT) and magnetic resonance (MR), respectively. The paper aims to analyze the adverse drug reactions of ICM and GCM on different sites of the body in a highly polluted environment. We analyzed the pharmacovigilance in contrast media on the basis of reports submitted to the Regional Center for Monitoring of Adverse Drug Reactions (ADR) at the Department of Clinical Pharmacology in Wrocław. Safety profiles were compared between different ICM and GCM and at the system organ level using the proportional reporting ratio (PRR). We analyzed 124 reports of adverse reactions related to contrast agents between 2006 and 2021. Our findings revealed that ADR combinations occurred more frequently after the use of iodinated contrast agents (72.08%) than gadolinium contrast agents (27.92%). Iomeprol and Iopromide were identified as the most frequently reported media. Each medium presented a different safety profile. Skin disorders are the most common adverse drug reactions among patients using both iodine- and gadolinium-based contrast media. Gadolinium-based contrast agents are characterized by similar organ toxicity. Conversely, iodine-based contrast agents are more diverse—some of which show tissue specificity, such as Iodixanol for the gastrointestinal system or Iohexol for the respiratory tract. This study shows relatively high occurrence of respiratory tract related ADRs in Wrocław. We also prove that it is possible to choose the most optimal contrast agent for patients with specific organ site problems to omit the possible complications

Oxidative Effects during Irreversible Electroporation of Melanoma Cells—In Vitro Study

Irreversible electroporation (IRE) is today used as an alternative to surgery for the excision of cancer lesions. This study aimed to investigate the oxidative and cytotoxic effects the cells undergo during irreversible electroporation using IRE protocols. To do so, we used IRE-inducing pulsed electric fields (PEFs) (eight pulses of 0.1 ms duration and 2–4 kV/cm intensity) and compared their effects to those of PEFs of intensities below the electroporation threshold (eight pulses, 0.1 ms, 0.2–0.4 kV/cm) and the PEFs involving elongated pulses (eight pulses, 10 ms, 0.2–0.4 kV/cm). Next, to follow the morphology of the melanoma cell membranes after treatment with the PEFs, we analyzed the permeability and integrity of their membranes and analyzed the radical oxygen species (ROS) bursts and the membrane lipids’ oxidation. Our data showed that IRE-induced high cytotoxic effect is associated both with irreversible cell membrane disruption and ROS-associated oxidation, which is occurrent also in the low electric field range. It was shown that the viability of melanoma cells characterized by similar ROS content and lipid membrane oxidation after PEF treatment depends on the integrity of the membrane system. Namely, when the effects of the PEF on the membrane are reversible, aside from the high level of ROS and membrane oxidation, the cell does not undergo cell death

Boosting the Immune Response—Combining Local and Immune Therapy for Prostate Cancer Treatment

Due to its slow progression and susceptibility to radical forms of treatment, low-grade PC is associated with high overall survival (OS). With the clinical progression of PC, the therapy is becoming more complex. The immunosuppressive tumor microenvironment (TME) makes PC a difficult target for most immunotherapeutics. Its general immune resistance is established by e.g., immune evasion through Treg cells, synthesis of immunosuppressive mediators, and the defective expression of surface neoantigens. The success of sipuleucel-T in clinical trials initiated several other clinical studies that specifically target the immune escape of tumors and eliminate the immunosuppressive properties of the TME. In the settings of PC treatment, this can be commonly achieved with radiation therapy (RT). In addition, focal therapies usually applied for localized PC, such as high-intensity focused ultrasound (HIFU) therapy, cryotherapy, photodynamic therapy (PDT), and irreversible electroporation (IRE) were shown to boost the anti-cancer response. Nevertheless, the present guidelines restrict their application to the context of a clinical trial or a prospective cohort study. This review explains how RT and focal therapies enhance the immune response. We also provide data supporting the combination of RT and focal treatments with immune therapies

LAG-3 as a Potent Target for Novel Anticancer Therapies of a Wide Range of Tumors

LAG-3 (Lymphocyte activation gene 3) protein is a checkpoint receptor that interacts with LSEC-tin, Galectin-3 and FGL1. This interaction leads to reduced production of IL-2 and IFN-γ. LAG-3 is widely expressed in different tumor types and modulates the tumor microenvironment through immunosuppressive effects. Differential expression in various tumor types influences patient prognosis, which is often associated with coexpression with immune checkpoint inhibitors, such as TIM-3, PD-1 and CTLA-4. Here, we discuss expression profiles in different tumor types. To date, many clinical trials have been conducted using LAG-3 inhibitors, which can be divided into anti-LAG-3 monoclonal antibodies, anti-LAG-3 bispecifics and soluble LAG-3-Ig fusion proteins. LAG-3 inhibitors supress T-cell proliferation and activation by disallowing for the interaction between LAG-3 to MHC-II. The process enhances anti-tumor immune response. In this paper, we will review the current state of knowledge on the structure, function and expression of LAG-3 in various types of cancer, as well as its correlation with overall prognosis, involvement in cell-based therapies and experimental medicine. We will consider the role of compounds targeting LAG-3 in clinical trials both as monotherapy and in combination, which will provide data relating to the efficacy and safety of proposed drug candidates

Oxidative Effects during Irreversible Electroporation of Melanoma Cells—In Vitro Study

Irreversible electroporation (IRE) is today used as an alternative to surgery for the excision of cancer lesions. This study aimed to investigate the oxidative and cytotoxic effects the cells undergo during irreversible electroporation using IRE protocols. To do so, we used IRE-inducing pulsed electric fields (PEFs) (eight pulses of 0.1 ms duration and 2–4 kV/cm intensity) and compared their effects to those of PEFs of intensities below the electroporation threshold (eight pulses, 0.1 ms, 0.2–0.4 kV/cm) and the PEFs involving elongated pulses (eight pulses, 10 ms, 0.2–0.4 kV/cm). Next, to follow the morphology of the melanoma cell membranes after treatment with the PEFs, we analyzed the permeability and integrity of their membranes and analyzed the radical oxygen species (ROS) bursts and the membrane lipids’ oxidation. Our data showed that IRE-induced high cytotoxic effect is associated both with irreversible cell membrane disruption and ROS-associated oxidation, which is occurrent also in the low electric field range. It was shown that the viability of melanoma cells characterized by similar ROS content and lipid membrane oxidation after PEF treatment depends on the integrity of the membrane system. Namely, when the effects of the PEF on the membrane are reversible, aside from the high level of ROS and membrane oxidation, the cell does not undergo cell death.This article belongs to the Special Issue Novel Physical and Chemical Methods for Facilitated Drug DeliveryThis research was financially supported by the Ministry of Health Subsidy according to number STM.D260.20.142 from the IT Simple system of Wroclaw Medical University and partially by Statutory Subsidy Funds of the Department of Molecular and Cellular Biology no. SUB.D260.20.009. The publication was supported by FAST II (WCA) programme no. GMIN.D260.20.010

The Impact of COVID-19 on the Mental Well-Being of College Students

The COVID-19 pandemic has caused an overall increase in stress and depression in society. The aim of the present research was to evaluate the psychological condition of college students during the COVID-19 pandemic and explore factors influencing their daily functioning. The study focused on four main aspects such as mental well-being, sexuality, concern about financial status, and trust in medical authorities. The study was based on a specially designed survey. The questionnaire was created using Google Forms and shared on social media sites. A total of 630 students participated in the survey, 17 surveys were excluded due to incomplete data and 613 surveys (97.30%) were considered for the final analysis. During isolation, 68.0% of students experienced fear of missing out (FOMO). A total of 73.4% were frustrated due to spending a lot of time in front of a computer. A significant decrease in motivation to study was reported by 78.1% of the respondents. Students showed significantly different attitudes towards sexuality. Concern about the financial situation was reported by 48.7% of respondents. The state of the Polish economy was of concern to 86.4% of respondents. A total of 74.5% of students declared concern about their career development. During the pandemic, 59.0% of respondents became concerned about their health. The attitude towards vaccination was described as positive by 82.5% of the respondents. The percentage of respondents experiencing negative psychological effects relative to the overall epidemiological situation of COVID-19 is troubling. Given the unexpected length and severity of the pandemic, we suggest that students’ concerns be more thoroughly understood and addressed

Prognostic and Therapeutic Role of CD15 and CD15s in Cancer

CD15 (Lewis X/Lex) is a fucosyl (3-fucosly-N-acetyl-lactosamine) moiety found on membrane proteins of various cancer cells. These cancers include renal cancer, prostate and bladder cancers, acute leukaemias, hepatocellular carcinoma, breast cancer and melanoma. The biological role of CD15 is interaction with E-, L- and P-selectins (adhesion molecules), allowing for adhesion with endothelial cells. In this way, cancer cells start to interact with the endothelia of blood vessels and consequently move out from the blood flow to the surrounding tissues. Blockage of the antigen’s function results in reduced metastatic potential. Moreover, the molecule may be a therapeutic target against cancer in monoclonal antibody-based therapies. CD15 may serve as a prognostic marker for patients and there are high hopes for its use in the immunotherapeutic treatment of tumours. CD15s is a sialyl derivative of CD15 that possesses its own unique characteristics. Its soluble form may act as a competitive inhibitor of the interaction of cancer cells with epithelial cells and thus disallow migration through the vessels. However, the prognostic relevance of CD15 and CD15s expression is very complex. This review presents a comprehensive description of the role of CD15 and CD15s in cancer development and metastasis and overviews its significance for clinical applications