Vasculature is essential for the sustained growth of solid tumors and metastases. Tumor cells surviving vascular-disruptive therapeutic intervention (especially those present at the tumor rim) can contribute to tumor regrowth. The aim was to strengthen, by carrier-mediated delivery of a chemotherapeutic, the curative effects of a bifunctional anti-vascular oligopeptide capable of inducing vascular shutdown and tumor shrinkage. For the in vitro experiments and animal therapy, ACDCRGDCFC-GG-(D)(KLAKLAK)(2) peptide (900 microM in D-PBSA, i.e.
Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
PURPOSE: To test ribozymes targeting mouse telomerase RNA (mTER) for suppression of the progression of B16-F10 murine melanoma metastases in vivo. EXPERIMENTAL DESIGN: Hammerhead ribozymes were designed to target mTER. The ribozyme sequences were cloned into a plasmid expression vector containing EBV genomic elements that substantially prolong expression of genes delivered in vivo. The activity of various antitelomerase ribozymes or control constructs was examined after i.v. injection of cationic liposome:DNA complexes containing control or ribozyme constructs.
Proceedings of the National Academy of Sciences of the United States of America
Recent studies have demonstrated a role for telomerase in driving tumor progression, but its mechanism of action remains unclear. Here we show that stable, ribozyme-mediated suppression of mouse telomerase RNA reduced telomerase RNA expression, telomerase activity, and telomere length, which significantly reduced tumor invasion and metastatic potential. Our studies reveal that previously unidentified effects of telomerase may mediate its tumor-promoting effects.
Essential oils extracted from aromatic plants exhibit important biological activities and have become increasingly important for the development of aromatherapy for complementary and alternative medicine. The essential oil extracted from Cinnamomum cassia Presl (CC-EO) has various functional properties; however, little information is available regarding its anti-tyrosinase and anti-melanogenic activities. In this study, 16 compounds in the CC-EO have been identified; the major components of this oil are cis-2-methoxycinnamic acid (43.06%) and cinnamaldehyde (42.37%).
The effect of cystone, a polyherbal ayurvedic preparation, on the nephrotoxicity and antitumor activity of cisplatin is studied in C57BL/6J mice bearing B16F1 melanoma. Intraperitoneal administration of cisplatin 6 mg/kg, resulted in significant reduction of body weight, elevation of blood urea nitrogen (BUN) and serum creatinine levels on day 5. Cystone was found to protect tumor-bearing mice from cisplatin-induced nephrotoxicity, when given i.p. 1 h before cisplatin. At 1000 mg/kg, it showed 46, 57 and 66% protection on body weight, BUN and serum creatinine levels, respectively.
Exosomes released from tumor cells having been shown to induce interleukin-6 release from myeloid-derived suppressor cells in a Toll-like receptor 2/Stat3-dependent manner. In this study, we show that exosomes released from tumor cells re-isolated from syngeneic mice are capable of inducing interleukin-6 in a Toll-like receptor 2-independent manner, whereas the data generated from exosomes of tumor cells having undergone numerous in vitro passages induce interleukin-6 in a Toll-like receptor 2-dependent manner.
Galectin-1 (Gal-1) has been shown to play a major role in tumor immune escape by inducing apoptosis of effector leukocytes and correlating with tumor aggressiveness and disease progression. Thus, targeting the Gal-1/Gal-1 ligand axis represents a promising cancer therapeutic approach.
Galectin-1 (Gal-1), a β-galactoside-binding protein, can alter fate and effector function of Th cells; however, little is known about how Gal-1 induces Th cell differentiation. In this article, we show that both uncommitted and polarized Th cells bound by Gal-1 expressed an immunoregulatory signature defined by IL-10. IL-10 synthesis was stimulated by direct Gal-1 engagement to cell surface glycoproteins, principally CD45, on activated Th cells and enhanced by IL-21 expression through the c-Maf/aryl hydrocarbon receptor pathway, independent of APCs.
Isolated perfusion of the limbs (ILP) allows the delivery of high dose rTNF alpha in a closed system with acceptable side-effects. A protocol with a triple-drug regimen was based on the reported synergism of rTNF alpha with chemotherapy, with interferon-gamma, and with hyperthermia. In melanoma-in-transit metastases (stage IIIA or AB) we obtained a 91% complete response compared with 52% after ILP with melphalan alone.
Crassocephalum rabens (Asteraceae) is a popular anti-inflammatory folk medicine and food supplement. We investigated the cancer chemopreventive bioactivity of C. rabens phytocompounds in vitro and in vivo using cell- and gene-based bioassays and a mouse B16 melanoma model. The bioactive glyceroglycolipid 1,2-di-O-alpha-linolenoyl-3-O-beta-galactopyranosyl-sn-glycerol (dLGG) that was identified from C. rabens was found in vitro and in vivo to be a potent nitric oxide (NO) scavenger.