Trends Mol Med
August 2025
Preventing metastasis remains a major challenge in cancer therapy. Effective strategies should combine immune activation with the inhibition of cancer cell migration and invasion. In this Opinion article, we propose a multimodal approach that integrates migrastatic agents with photodynamic therapy (PDT) and intratumoral immunotherapy (ITI).
View Article and Find Full Text PDFWe report the design, synthesis, and biological evaluation of novel hybrid anticancer agents bearing three pharmacophores in one molecule: benzothiazole, cyclobut-2-ene-1,2-dione and hydrazone moieties. Several derivatives have demonstrated potent anticancer activity and high selectivity towards T-lymphoblastic leukaemia (CCRF-CEM) and colorectal cancer (HCT116) cell lines. The effects of in situ formed metal complexes on anticancer activity were investigated, revealing that the Fe(III) complexes of some derivatives were more active than the parental ligands, whereas the Cu(II) and Zn(II) complexes did not enhance cytotoxicity.
View Article and Find Full Text PDFDespite the natural ability of the immune system to recognize cancer and, in some patients, even to eliminate it, cancer cells have acquired numerous evading mechanisms. With the increasing knowledge and focus shifting from targeting rapidly proliferating cells with chemotherapy to modulating the immune system, there have been recent efforts to integrate (e.g.
View Article and Find Full Text PDFThe critical role of the immune system in brain function and dysfunction is well recognized, yet development of immune therapies for psychiatric diseases has been slow due to concerns about iatrogenic immune deficiencies. These concerns are emphasized by the lack of objective diagnostic tools in psychiatry. A promise to resolve this conundrum lies in the exploitation of extracellular vesicles (EVs) that are physiologically produced or can be synthetized.
View Article and Find Full Text PDFExosomes, nanosized extracellular vesicles released by various cell types, are intensively studied for the diagnosis and treatment of cancer and neurodegenerative diseases, and they also display high usability in regenerative medicine. Emphasizing their diagnostic potential, exosomes serve as carriers of disease-specific biomarkers, enabling non-invasive early detection and personalized medicine. The cargo loading of exosomes with therapeutic agents presents an innovative strategy for targeted drug delivery, minimizing off-target effects and optimizing therapeutic interventions.
View Article and Find Full Text PDFNeoadjuvant immunotherapy represents a pioneering approach in the preoperative treatment of cancer, providing new strategies for tumor reduction and improved patient outcomes by modulating the immune response. This study investigated neoadjuvant immunotherapy using intratumoral administration of mannan-BAM, Toll-like receptor ligands, and anti-CD40 antibody (MBTA therapy) followed by surgery in murine models of MTT pheochromocytoma, B16-F10 melanoma, and 4T1 and E0771.lmb mammary carcinomas.
View Article and Find Full Text PDFACS Pharmacol Transl Sci
November 2024
Head and neck cancers (HNC) are aggressive, difficult-to-treat tumors that can be caused by genetic factors but mainly by lifestyle or infection caused by the human papillomavirus. As the sixth most common malignancy, it presents a formidable therapeutic challenge with limited therapeutic modalities. Curcumin, a natural polyphenol, is appearing as a promising multitarget anticancer and antimetastatic agent.
View Article and Find Full Text PDFFront Med (Lausanne)
October 2024
The concept of intratumoral microbiota is gaining attention in current research. Tumor-associated microbiota can activate oncogenic signaling pathways such as NF-κB, thereby promoting tumor development and progression. Numerous studies have demonstrated that curcumin and its analogs possess strong antitumor effects by targeting the NF-κB signaling pathway, along with potent antibacterial properties.
View Article and Find Full Text PDFMitochondrial autophagy (mitophagy) is very important process for the maintenance of cellular homeostasis, functionality and survival. Its dysregulation is associated with high risk and progression numerous serious diseases (e.g.
View Article and Find Full Text PDFMitochondrial dysregulation plays a significant role in the carcinogenesis. On the other hand, its destabilization strongly represses the viability and metastatic potential of cancer cells. Photodynamic and photothermal therapies (PDT and PTT) target mitochondria effectively, providing innovative and non-invasive anticancer therapeutic modalities.
View Article and Find Full Text PDFTo advance our knowledge of disease mechanisms and therapeutic options, understanding cell cycle regulation is critical. Recent research has highlighted the importance of reactive oxygen species (ROS) in cell cycle regulation. Although excessive ROS levels can lead to age-related pathologies, ROS also play an essential role in normal cellular functions.
View Article and Find Full Text PDFBackground: Angiotensin-converting enzyme (ACE) is responsible for the production of angiotensin II, and increased production of angiotensin II is observed in diabetes. What is more, polymorphisms may play a role in the development of diabetic nephropathy. The aim of this study was to assess the role of selected polymorphisms (rs4343 and rs4646994) in the risk of development of diabetic nephropathy and in the likelihood of renal replacement therapy.
View Article and Find Full Text PDFImmune checkpoints regulate the immune system response. Recent studies suggest that flavonoids, known as phytoestrogens, may inhibit the PD-1/PD-L1 axis. We explored the potential of estrogens and 17 Selective Estrogen Receptor Modulators (SERMs) as inhibiting ligands for immune checkpoint proteins (CTLA-4, PD-L1, PD-1, and CD80).
View Article and Find Full Text PDFChemistryOpen
March 2024
A simple, sensitive and quick HPLC method was developed for the determination of ketoprofen in cell culture media (EMEM, DMEM, RPMI). Separation was performed using a gradient on the C18 column with a mobile phase of acetonitrile and miliQ water acidified by 0.1 % (v/v) formic acid.
View Article and Find Full Text PDFPentamethinium indolium salts are promising fluorescence probes and anticancer agents with high mitochondrial selectivity. We synthesized two indolium pentamethinium salts: a cyclic form with quinoxaline directly incorporated in the pentamethinium chain (cPMS) and an open form with quinoxaline substitution in the γ-position (oPMS). To better understand their properties, we studied their interaction with mitochondrial phospholipids (cardiolipin and phosphatidylcholine) by spectroscopic methods (UV-Vis, fluorescence, and NMR spectroscopy).
View Article and Find Full Text PDFTET proteins (methylcytosine dioxygenases) play an important role in the regulation of gene expression. Dysregulation of their activity is associated with many serious pathogenic states such as oncological diseases. Regulation of their activity by specific inhibitors could represent a promising therapeutic strategy.
View Article and Find Full Text PDFBiomed Pharmacother
July 2023
Treatment of metastatic cancer is one of the biggest challenges in anticancer therapy. Curcumin is interesting nature polyphenolic compound with unique biological and medicinal effects, including repression of metastases. High impact studies imply that curcumin can modulate the immune system, independently target various metastatic signalling pathways, and repress migration and invasiveness of cancer cells.
View Article and Find Full Text PDFMost cancer-related deaths among patients with solid tumors are caused by metastases. Migrastatic strategies represent a unique therapeutic approach to prevent all forms of cancer cell migration and invasion. Because the migration machinery has been shown to promote metastatic dissemination, successful migrastatic therapy may reduce the need for high-dose cytotoxic therapies that are currently used to prevent the risk of metastatic dissemination.
View Article and Find Full Text PDFInterleukin 6 (IL-6) belongs to a broad class of cytokines involved in the regulation of various homeostatic and pathological processes. These activities range from regulating embryonic development, wound healing and ageing, inflammation, and immunity, including COVID-19. In this review, we summarise the role of IL-6 signalling pathways in cancer biology, with particular emphasis on cancer cell invasiveness and metastasis formation.
View Article and Find Full Text PDFBiomed Pharmacother
November 2022
Dysregulation of iron homeostasis is one of the important processes in the development of many oncological diseases, such as pancreatic cancer. Targeting it with specific agents, such as an iron chelator, are promising therapeutic methods. In this study, we tested the cytotoxicity of novel azulene hydrazide-hydrazone-based chelators against pancreatic cancer cell lines (MIA PaCa-2, PANC-1, AsPC-1).
View Article and Find Full Text PDFInt J Mol Sci
September 2022
Targeting of epigenetic mechanisms, such as the hydroxymethylation of DNA, has been intensively studied, with respect to the treatment of many serious pathologies, including oncological disorders. Recent studies demonstrated that promising therapeutic strategies could potentially be based on the inhibition of the TET1 protein (ten-eleven translocation methylcytosine dioxygenase 1) by specific iron chelators. Therefore, in the present work, we prepared a series of pyrrolopyrrole derivatives with hydrazide () or hydrazone (-) iron-binding groups.
View Article and Find Full Text PDFBiomed Pharmacother
October 2022
Mitochondria generate energy and building blocks required for cellular growth and function. The notion that mitochondria are not involved in the cancer growth has been challenged in recent years together with the emerging idea of mitochondria as a promising therapeutic target for oncologic diseases. Pentamethinium salts, cyan dyes with positively charged nitrogen on the benzothiazole or indole part of the molecule, were originally designed as mitochondrial probes.
View Article and Find Full Text PDFIL-6 signaling is involved in the pathogenesis of a number of serious diseases, including chronic inflammation and cancer. Targeting of IL-6 receptor (IL-6R) by small molecules is therefore an intensively studied strategy in cancer treatment. We describe the design, synthesis, and characteristics of two new bis-pentamethinium salts and (meta and para) bearing indole moieties.
View Article and Find Full Text PDFHistochem Cell Biol
November 2022
Recent evidence indicates that targeting IL-6 provides broad therapeutic approaches to several diseases. In patients with cancer, autoimmune diseases, severe respiratory infections [e.g.
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