Medicinal inorganic chemistry plays an important role in exploring the properties of metal ions for the designing of new drugs. The field has been stimulated by the success of cis-platin, the world best selling anticancer drug and platinum complexes with reduced toxicity, oral activity and activity against resistant tumors are currently on clinical trial. The use of cis-platin is, however, severely limited by its toxic side-effects. This has stimulated chemists to employ different strategies in the development of new metal-based anticancer agents with different mechanisms of action. The discovery of new non-covalent interactions with the classical target, DNA, was the first developing step in the treatment of cancer. The use of organometallic compounds as a medicine is very common now a days because it offers potential advantages over the more common organic-based drugs. In this article we have highlighted the anticancer activity of the organotin(IV) carboxylates published in the last few years (from 2008 to 2016). In most cases they present lower IC50 values than those of cisplatin, which indicates their high activity against the cancer cell lines. The summarized data reveal that every year new organotin(IV) carboxylate complexes are synthesized with the aim of new anticancer agent with much better results than the than the corresponding activity of cis-platin or other clinically approved drugs. In addition to the advantages of high activity, compared to the platinum compound, tin complexes are much cheaper. Thus by using organotin carboxylate for clinical medicine, cost reduction, dosage reduction and effect enhancement will be reached.
The oncofetal antigen -immature laminin receptor protein (OFA/iLRP) has been linked to metastatic tumor spread for several years. The present study, in which 2 highly-specific, high-affinity OFA/iLRP-reactive mouse monoclonal antibodies were examined for ability to suppress tumor cell growth and metastatic spread in the A20 B-cell leukemia model and the B16 melanoma model, provides the first direct evidence that targeting OFA/iLRP with exogenous antibodies can have therapeutic benefit. While the antibodies were modestly effective at preventing tumor growth at the primary injection site, both antibodies strongly suppressed end-organ tumor formation following intravenous tumor cell injection. Capacity of anti-OFA/iLRP antibodies to suppress tumor spread through the blood in the leukemia model suggests their use as a therapy for individuals with leukemic disease (either for patients in remission or even as part of an induction therapy). The results also suggest use against metastatic spread with solid tumors.
A series of murine monoclonal antibodies were generated using recombinant oncofetal antigen - immature laminin receptor protein (OFA/iLRP) as the immunogen. Several of the antibodies detected the 37kD OFA/iLRP but did not recognize the structurally related 67kD mature laminin receptor protein (LRP), as determined by western blot analysis. Additional antibodies demonstrated reactivity with both proteins. Those antibodies specific for the 37kD moiety bound to recombinant OFA/iLRP with high affinity (Kaff = 1-2 x 10-10M; Biacore technology). These antibodies also reacted with native OFA/iLRP on the surface of human tumor cells with high affinity (Kaff = 1-2 x 10-9M) but did not show significant reactivity with normal human epithelial cells or fibroblasts. In contrast, antibodies that interacted with both 37kD OFA/iLRP and 67kD mature LRP were reactive with both tumor cells and normal cells. Antibodies specific to OFA/iLRP were internalized upon binding to the target protein on human tumor cells. Two monoclonal antibodies from this group were tested for anti-tumor activity in a murine model of B-cell leukemia. BALB/c mice were injected with A20 leukemia cells either intramuscularly or intravenously. Mice were given a total of six intraperitoneal 100µg antibody injections over a two-week period following tumor initiation. Both antibodies slowed growth of the intramuscular primary tumor by approximately 45%. More importantly, in the intravenous tumor model, the treatments reduced systemic blood tumor levels by greater than 70% and suppressed liver tumor formation by up to 46%. These high affinity tumor-selective antibodies potentially provide a front-line or adjuvant therapy for hematological malignancies. Citation Format: Shannon D. McClintock, Michael K. Dame, Muhammad N. Aslam, Saqib Ali, Randall N. Knibbs, Roscoe L. Warner, James Varani. Monoclonal antibodies specific for the oncofetal antigen - immature laminin receptor: Tumor selectivity, rapid internalization and in vivo efficacy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2666. doi:10.1158/1538-7445.AM2014-2666
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