Role of B cells in intratumoral MBTA immunotherapy of murine pheochromocytoma model.

Immunotherapy represents a revolutionary advancement in cancer treatment, which has traditionally focused on T cells; however, the role of B cells in cancer immunotherapy has gained interest because of their role in antigen presentation, antibody production, and cytokine release. In this study, we examined the role of B cells in previously developed intratumoral MBTA therapy (mannan-BAM, TLR ligands, and anti-CD40 antibody) in murine models of MTT pheochromocytoma. The results indicated that B cells significantly enhance the success of MBTA therapy, with wild-type mice exhibiting a lower tumor incidence and smaller tumors compared with B cell-deficient mice. Increased IL-6 and TNF-alpha levels indicated severe inflammation and a potential cytokine storm in B cell-deficient mice. Neutralization of TNF-alpha ameliorated these complications but resulted in increased tumor recurrence. The results highlight the important role of B cells in enhancing the immune response and maintaining immune homeostasis during MBTA therapy. Our findings offer new insights into improving therapeutic outcomes.

Long-term zinc treatment alters the mechanical properties and metabolism of prostate cancer cells.

The failure of intracellular zinc accumulation is a key process in prostate carcinogenesis. Although prostate cancer cells can accumulate zinc after long-term exposure, chronic zinc oversupply may accelerate prostate carcinogenesis or chemoresistance. Because cancer progression is associated with energetically demanding cytoskeletal rearrangements, we investigated the effect of long-term zinc presence on biophysical parameters, ATP production, and EMT characteristics of two prostate cancer cell lines (PC-3, 22Rv1). Prolonged exposure to zinc increased ATP production, spare respiratory capacity, and induced a response in PC-3 cells, characterized by remodeling of vimentin and a shift of cell dry mass density and caveolin-1 to the perinuclear region. This zinc-induced remodeling correlated with a greater tendency to maintain actin architecture despite inhibition of actin polymerization by cytochalasin. Zinc partially restored epithelial characteristics in PC-3 cells by decreasing vimentin expression and increasing E-cadherin. Nevertheless, the expression of E-cadherin remained lower than that observed in predominantly oxidative, low-invasive 22Rv1 cells. Following long-term zinc exposure, we observed an increase in cell stiffness associated with an increased refractive index in the perinuclear region and an increased mitochondrial content. The findings of the computational simulations indicate that the mechanical response cannot be attributed exclusively to alterations in cytoskeletal composition. This observation suggests the potential involvement of an additional, as yet unidentified, mechanical contributor. These findings indicate that long-term zinc exposure alters a group of cellular parameters towards an invasive phenotype, including an increase in mitochondrial number, ATP production, and cytochalasin resistance. Ultimately, these alterations are manifested in the biomechanical properties of the cells.

Cyanine dyes in the mitochondria-targeting photodynamic and photothermal therapy.

Mitochondrial 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. Cyanine dyes, with strong mitochondrial selectivity, show significant potential in enhancing PDT and PTT. The potential and limitations of cyanine dyes for mitochondrial PDT and PTT are discussed, along with their applications in combination therapies, theranostic techniques, and optimal delivery systems. Additionally, novel approaches for sonodynamic therapy using photoactive cyanine dyes are presented, highlighting advances in cancer treatment.

Engine shutdown: migrastatic strategies and prevention of metastases.

Most 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. In this review we focus on anti-invasive and antimetastatic strategies that hold promise for the treatment of solid tumors. The best targets for migrastatic therapy would be those that are required by all forms of motility, such as ATP availability, mitochondrial metabolism, and cytoskeletal dynamics and cell contractility.

Safety assessment and redox status in rats after chronic exposure to cannabidiol and cannabigerol.

Cannabidiol (CBD) and cannabigerol (CBG) are the two main non-psychotropic phytocannabinoids with high application potential in drug development. Both substances are redox-active and are intensively investigated for their cytoprotective and antioxidant action in vitro. In this study, we focused on an in vivo safety evaluation and the effect of CBD and CBG on the redox status in rats in a 90-d experiment. The substances were administered orogastrically in a dose of 0.66 mg synthetic CBD or 0.66 mg/1.33 mg CBG/kg/day. CBD produced no changes in the red or white blood count or biochemical blood parameters in comparison to the control. No deviations in the morphology or histology of the gastrointestinal tract and liver were observed. After 90 d of CBD exposure, a significant improvement in redox status was found in the blood plasma and liver. The concentration of malondialdehyde and carbonylated proteins was reduced compared to the control. In contrast to CBD, total oxidative stress was significantly increased and this was accompanied by an elevated level of malondialdehyde and carbonylated proteins in CBG-treated animals. Hepatotoxic (regressive changes) manifestations, disruption in white cell count, and alterations in the ALT activity, level of creatinine and ionized calcium were also found in CBG-treated animals. Based on liquid chromatography-mass spectrometry analysis, CBD/CBG accumulated in rat tissues (in the liver, brain, muscle, heart, kidney and skin) at a low ng level per gram. Both CBD and CBG molecular structures include a resorcinol moiety. In CBG, there is an extra dimethyloctadienyl structural pattern, which is most likely responsible for the disruption to the redox status and hepatic environment. The results are valuable to further investigation of the effects of CBD on redox status and should contribute towards opening up critical discussion on the applicability of other non-psychotropic cannabinoids.