Biological Evaluation of Triorganotin Derivatives as Potential Anticancer Agents.

Metal-derived platinum complexes are widely used to treat solid tumors. However, systemic toxicity and tumor resistance to these drugs encourage further research into similarly effective compounds. Among others, organotin compounds have been shown to inhibit cell growth and induce cell death and autophagy.

Poly(ADP-Ribose) Polymerase Inhibitors for Arsenic Trioxide-Resistant Acute Promyelocytic Leukemia: Synergistic In Vitro Antitumor Effects with Hypomethylating Agents or High-Dose Vitamin C.

Arsenic trioxide (ATO) is an anticancer agent used for the treatment ofacute promyelocytic leukemia (APL). However, 5%-10% of patients fail to respond or experience disease relapse. Based on poly(ADP-ribose) polymerase (PARP) 1 involvement in the processing of DNA demethylation, here we have tested the in vitro susceptibility of ATO-resistant clones (derived from the human APL cell line NB4) to PARP inhibitors (PARPi) in combination with hypomethylating agents (azacitidine and decitabine) or high-dose vitamin C (ascorbate), which induces 5-hydroxymethylcytosine (5hmC)-mediated DNA demethylation.

Biomolecular Fishing for Calixarene Partners by a Chemoproteomic Approach.

MS-based chemical-proteomics technology is introduced herein as a third general strategy to study the biomolecular recognition properties of given calixarene derivatives. In particular, we demonstrate that a simply designed calix[4]arene derivative 1 a bearing acetamido groups at the exo rim (pAC), when linked to a solid support, is able to fish out a specific protein (PDI protein) from a crude extract of HeLa cells. Western blot and surface plasmon resonance studies confirmed the direct interaction between PDI and the linker-free pAC derivative 1 b with considerable affinity, and in vitro tests showed its inhibition of PDI chaperone activity.

Exogenous control of the expression of Group I CD1 molecules competent for presentation of microbial nonpeptide antigens to human T lymphocytes.

Group I CD1 (CD1a, CD1b, and CD1c) glycoproteins expressed on immature and mature dendritic cells present nonpeptide antigens (i.e., lipid or glycolipid molecules mainly of microbial origin) to T cells.

Detection of circulating tumor cells is improved by drug-induced antigen up-regulation: preclinical and clinical studies.

(51)Cr-prelabelled colon cancer cells (simulating 'circulating tumor cells', CTCs) were added to human peripheral blood and exposed to staurosporine (ST) to increase carcinoembryonic antigen (CEA) expression. CTCs were captured with immunomagnetic beads coated with Ber-EP4 monoclonal antibody, recognizing the common epithelial antigen present in the majority of cancer cells of epithelial origin, with capture efficiency of more than 80%. Moreover, ST treatment increased CEA expression without compromising Ber-EP4 capture efficiency.

Combined effects of 5-fluorouracil, folinic acid and oxaliplatin on the expression of carcinoembryonic antigen in human colon cancer cells: pharmacological basis to develop an active antitumor immunochemotherapy.

Background: Five-fluorouracil (FU), mainly associated with leucovorin (L), plays an essential role in chemotherapy of colorectal carcinoma. Moreover, FU +/- L has been found to increase the expression of tumor-associated carcinoembryonic antigen (CEA), that may be an important target in therapeutic protocols of active specific immunotherapy. FU + L (FUL) are frequently combined with oxaliplatin (OXA) in advanced colon cancer patients.

BCG-infected adherent mononuclear cells release cytokines that regulate group 1 CD1 molecule expression.

Increasing evidence is now available showing that CD1-restricted T cell responses against non-peptide mycobacterial antigens could play a role in the immune resistance against tuberculosis. BCG, widely used in anti-tubercular vaccination, shares various constituents with Mycobacterium tuberculosis, but does not provide full protection. In the present study we have investigated the pattern of group 1 CD1 molecule expression in adherent mononuclear cells (AMNC) of human peripheral blood, infected in vitro with BCG.

Dendritic cell-mediated cross-presentation of antigens derived from colon carcinoma cells exposed to a highly cytotoxic multidrug regimen with gemcitabine, oxaliplatin, 5-fluorouracil, and leucovorin, elicits a powerful human antigen-specific CTL response with antitumor activity in vitro.

Gemcitabine, oxaliplatin, leucovorin, and 5-fluorouracil (GOLF) is a novel multidrug regimen inducing high levels of necrosis and apoptosis in colon carcinoma cells. This regimen is also able to promote a process of Ag remodeling including up-regulation of immunotherapy targets like carcinoembryonic Ag (CEA), thymidylate synthase (TS). We have conducted a preclinical study aimed to investigate whether these drug-induced modifications would also enhance colon cancer cell immunogenicity.

Combined effects of protein kinase inhibitors and 5-fluorouracil on CEA expression in human colon cancer cells.

Previous studies showed that 5-fluorouracil (5-FU) and Staurosporine (ST), a protein kinase inhibitor (PKI), were able to increase the expression of carcinoembryonic antigen (CEA) in human colon cancer cells. In the present study, we examined the in vitro effects of five PKIs, i.e.

Drug-induced increase of carcinoembryonic antigen expression in cancer cells.

Most of gastrointestinal, breast and lung cancer cells express carcinoembryonic antigen (CEA). Therefore, this protein represents a suitable target for innovative diagnostic and immunotherapeutic strategies of various tumours. Presently CEA can be involved in three main approaches concerning cancer detection and therapy, i.

Treatment of colon and breast carcinoma cells with 5-fluorouracil enhances expression of carcinoembryonic antigen and susceptibility to HLA-A(*)02.01 restricted, CEA-peptide-specific cytotoxic T cells in vitro.

Cancer vaccines directed against tumor associate antigen (TAA) have produced encouraging results in preclinical models but not in cancer patients. A major limitation of this strategy is the relative degree of tolerance to these antigens and the low and heterogeneous tumor cell expression of TAA and major histocompatibility complex (MHC). Previous studies have shown that 5-fluorouracil (5-FU) can upregulate the expression of membrane-associated carcino-embryonic antigen (CEA), and MHC molecules in colon and breast carcinoma cell lines.

Pharmacological modulation of carcinoembryonic antigen in human cancer cells: studies with staurosporine.

Preliminary studies, performed in our laboratory, showed that staurosporine (ST), a protein-kinase (PK) inhibitor, increases the expression of the carcinoembryonic antigen (CEA) in a human colon cancer cell line. The present study explores the cellular and molecular effects of ST on the CEA expression in breast cancer MCF-7 line and in a number of colon cancer cell lines characterized by the different basal levels of the antigen, including two cloned sublines (i.e.