Background And Aims: induction of alcoholic chronic pancreatitis (ACP) causes significant acinar damage, increased fibroinflammatory response, and heightened activation of cyclic response element binding protein 1 (CREB) when compared with alcohol (A) or chronic pancreatitis (CP) mediated pancreatic damage. However, the study elucidating the cooperative interaction between CREB and the oncogenic (*) in promoting pancreatic cancer progression with ACP remains unexplored.
Methods: Experimental ACP induction was established in multiple mouse models, followed by euthanization of the animals at various time intervals during the recovery periods.
Progesterone (PR) is an endogenous steroid hormone that activates the progesterone receptor (PgR) and is known to play a critical role in cancer progression. Herein, we report the development of cationic lipid-conjugated PR derivatives by covalently conjugating progesterone with cationic lipids of varying hydrocarbon chain lengths ( = 6-18) through a succinate linker. Cytotoxicity studies performed on eight different cancer cell lines reveal that PR10, one of the lead derivatives, exerts notable toxicity (IC = 4-12 μM) in cancer cells irrespective of their PgR expression status and remains largely nontoxic to noncancerous cells.
View Article and Find Full Text PDFPaclitaxel (PTX) is a widely used chemotherapeutic agent in the clinic. However, its clinical benefit is limited due to its low water solubility, off-target toxicity, and for being a multidrug-resistant (MDR) substrate. To overcome these limitations in this study, a tumor-targeting peptide (CRGDK peptide, a ligand for NRP-1 receptor) conjugate of α-tocopheryl succinate (α-TOS) was synthesized and modified on PTX-loaded lipid aggregate (TL-PTX) to leverage the benefits of α-TOS, which include a) anti-cancer activity, b) increased PTX loading, and c) inhibition of MDR activity.
View Article and Find Full Text PDFThymoquinone (TQ) has potential anti-inflammatory, immunomodulatory and anticancer effects but its clinical use is limited by its low solubility, poor bioavailability and rapid clearance. To enhance systemic bioavailability and tumor-specific toxicity of TQ. Cationic liposomal formulation of TQ (D1T) was prepared via ethanol injection method and their physicochemical properties, anticancer effects in orthotopic xenograft pancreatic tumor model and pharmacokinetic behavior of D1T relative to TQ were evaluated.
View Article and Find Full Text PDFHigh mortality rate in colon cancer patients is often attributed to late diagnosis. To overcome the conventional chemotherapy associated challenges, chemotherapeutic drugs (single or combination) or genetic drugs are often delivered using ligand-modified delivery systems that selectively target over expressed receptors or particular receptors that act abnormally in cancer cells. In the current investigation, first we assessed anti-colon cancer effect of a cationic estrogenic molecule, ESC8 which was earlier shown to act against estrogen receptor (ER) ± breast cancer cells.
View Article and Find Full Text PDFHydrocortisone, a natural glucocorticoid secreted by adrenal and extra-adrenal tissues, locally governs the transcription of genes involved in inflammation, immune response, metabolism, and energy homeostasis binding to its cognate glucocorticoid receptor (GR). In this study, we show that modified hydrocortisone (HC16), a cancer-selective cytotoxic molecule, showed synergism in combination with drugs like Doxorubicin and docetaxel, self-assembled into vesicles, entrapped docetaxel and complexed with anti-cancer plasmid DNA for enhanced killing of cancer cells. These vesicles exhibited GR-mediated nuclear localization, delivery of the p53 gene, and also inhibited cell viability selectively in RKO, HCT15, and CT26 colon cancer cells but not in normal cells like CHO and HEK293T.
View Article and Find Full Text PDFStilbene-based compounds are largely described for their antioxidant activity. But their use as anticancer chemotherapeutics is hampered by poor pharmacokinetic properties and non-selectivity towards cancer and non-cancer potency. To overcome these drawbacks, twin chain cationic lipid conjugated, methoxy-enriched stilbene derivatives were designed, synthesized and evaluated for their anticancer potency.
View Article and Find Full Text PDFCationic lipids are well-known excipients for nanometric liposomal gene delivery systems. However, because of the suspected, collateral toxicity in normal cells, the use of cationic lipids for the treatment of human tumor is largely limited. Recently, we developed a glucocorticoid receptor (GR)-targeted liposomal, anticancer delivery system (DXE nano-lipoplex), which carried cationic lipid of saturated twin aliphatic chains.
View Article and Find Full Text PDFMicrobial infections due to biofilms on medical implants can be prevented by antimicrobial coatings on biomaterial surfaces. Mesoporous silica nanoparticles (MSNPs) were synthesized via base-catalyzed sol-gel process at room temperature, functionalized with phenazine-1-carboxamide (PCN) and characterized by UV-visible, FT-IR, DLS, XRD spectroscopic techniques, SEM, TEM, TGA and BET analysis. Native MSNPs, PCN and PCN-MSNPs were evaluated for anti-Candida minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), Candida albicans (C.
View Article and Find Full Text PDFThe clinical success of dendritic cell (DC)-based genetic immunization remains critically dependent on the availability of effective and safe nano-carriers for targeting antigen-encoded DNA vaccines to DCs, the most potent antigen-presenting cells in the human body in vivo. Recent studies revealed the efficacies of mannose receptor-mediated in vivo DC-targeted genetic immunization by liposomal DNA vaccine carriers containing both mannose-mimicking shikimoyl and transfection enhancing guanidinyl functionalities. However, to date, the efficacies of this approach have not been examined for metal-based nanoparticle DNA vaccine carriers.
View Article and Find Full Text PDFPorphyrins are well-known anticancer agents because of their high binding affinity for G-quadruplex DNA and excellent photophysical properties. Several studies carried out using TMPyP4 established it as an efficient chemotherapeutic and a photodynamic therapeutic (PDT) agent, but its use as a lead molecule has been restricted because of its high level of binding to double-stranded DNA (dsDNA), which may have side effects on normal cells and tissues. To minimize its interaction with dsDNA and to enhance internalization into cells, an analogue of TMPyP4 (5Me) was synthesized.
View Article and Find Full Text PDFMany cancers including the late stage ones become drug-resistant and undergo epithelial-to-mesenchymal transition (EMT). These lead to enhanced invasion, migration, and metastasis toward manifesting its aggressiveness and malignancy. One of the key hallmarks of cancer is its overdependence on glycolysis as its preferred energy metabolism pathway.
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