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.
Iron plays a significant role in the metabolism of cancer cells. In comparison with normal cells, neoplastic ones exhibit enhanced vulnerability to iron. Ferric ions target tumor via the ferroptotic death pathway—a process involving the iron-mediated lipid oxidation. Ferric ion occurs in complex forms in the physiological conditions. Apart from iron, ligands are the other factors to affect the biological activity of the iron complexes. In recent decades the role of iron chelates in targeting the growth of the tumor was extensively examined. The ligand may possess a standalone activity to restrict cancer’s growth. However, a wrong choice of the ligand might lead to the enhanced cancer cell’s growth in in vitro studies. The paper aims to review the role of iron complex compounds in the anticancer therapy both in the experimental and clinical applications. The anticancer properties of the iron complex rely both on the stability constant of the complex and the ligand composition. When the stability constant is high, the properties of the drug are unique. However, when the stability constant remains low, both components—ferric ions and ligands, act separately on the cells. In the paper we show how the difference in complex stability implies the action of ligand and ferric ions in the cancer cell. Iron complexation strategy is an interesting attempt to transport the anticancer Fe2+/3+ ions throughout the cell membrane and release it when the pH of the microenvironment changes. Last part of the paper summarizes the results of clinical trials and in vitro studies of novel iron chelates such as: PRLX 93,936, Ferumoxytol, Talactoferrin, DPC, Triapine, VLX600, Tachypyridine, Ciclopiroxamine, Thiosemicarbazone, Deferoxamine and Deferasirox.
Natural products play significant roles in the development of novel drugs. One of such compounds is vanillin -a natural substance commonly used in food. Anticancer potential of the substance is continually encouraging researchers to conduct further investigations. A rising number of publications describe the role of 4-hydroxy-3-methoxybenzaldehyde (vanillin) in the process of inhibiting tumor growth. Four vanilloid receptors play significant roles in the response of cancer cells to the natural compound. Each of these proteins can be individually affected by vanillin; thus, the substance either leads to inhibition of the cell proliferation or increases the Ca 2+ level. The TRPV1, a non-selective cation channel permeable to calcium, acts on cancer development and progression. Thus, vanilloid receptors have the potential to become the target for therapeutical research. Moreover, selective inhibitors of the receptor have proved their efficacy in vitro. CK2α is an antiapoptotic, cancer-sustaining protein and, therefore, the inhibitor of apoptosis. Thus, drugs that exhibit allosteric and ATP-competitive inhibition of the protein might be crucial for cancer therapy. CAMK4 is a protein kinase expression associated with a wide array of cancers. Also, MARK4 is another kinase responsible for the stability of microtubules, overexpressed in many cancer types. Studies concerning this protein revealed that microtubule impairment might be a cancer therapy direction. This review aims to demonstrate the crucial role of described vanilloid receptors in inhibiting the proliferation of cancer cells and to prove the usefulness of using vanillin and its derivatives in the process of drug design.
Electroporation (EP) allows for the transport of molecules into the cytoplasm with significant effectiveness by forming transient pores in the cell membrane using electric pulses. This can be used for cellular transport (RE—reversible electroporation) or ablation (IRE—irreversible electroporation). The first of described options fortifies medicine with novel possibilities: electrochemotherapy (ECT), which creates promising perspectives for cancer treatment, and gene electrotransfer (GET), a powerful method of DNA delivery as well as immunogen electrotransfer. The review constitutes a comprehensive explanation of the mechanism of EP in the case of GET, its present and prospective employment in medicine, including gene delivery, vaccinations, therapy, and transfection, are also presented.
Literatura odgrywa niekwestionowaną rolę w tworzeniu definicji medycyny, oferując różnorodność obrazów, które w swym metaforycznym wymiarze odnoszą się do ludzkiego życia. Fakt, iż medycyna stanowi gałąź sztuki, w bezmiarze której przesłanie wynikające z bogactwa prozy i poezji znajduje swój wyraz, podkreśla, iż owe dwa, pozornie niezwiązane ze sobą światy przenikają się wzajemnie, nadając sens własnej egzystencji. Literatura, która nie może odwołać się do medycznej rzeczywistości, nie może bowiem dotrzeć do duszy czytelnikai wpłynąć na jego wewnętrzną hierarchię wartości, podczas gdy medycyna, obdarta z wielowymiarowości literackich symboli, staje się przestrzenią pozbawioną duchowości.
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