Anti-tumour platinum complexes : relationships between chemical properties and activity

Cleare, M. J.; Hydes, P. C.; Malerbi, B.W.; Watkins, Davita L.

doi:10.1016/s0300-9084(78)80568-9

Cited by 170 publications

(43 citation statements)

References 9 publications

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“…3D 2 ] may form adducts with Hb with loss of 2 H 2 O molecules. The hydrated species is the major species of the nonenzymatic transformation products of oxaliplatin, as reported previously (5,7,12,14 ).…”

Section: Characterization Of Intact Hb-oxaliplatin Adductssupporting

confidence: 82%

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Characterization of Intact Hemoglobin and Oxaliplatin Interaction by Nanoelectrospray Ionization Tandem Mass Spectrometry

Peng¹,

Mandal²,

Sawyer

et al. 2005

Clinical Chemistry

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Background: Mass spectrometric (MS) detection of intact hemoglobin (Hb) adducts presents considerable analytical challenges because of the noncovalent association of the 4 subunits of Hb, and MS characterization of the interaction of intact Hb with platinum drugs has not been reported. We developed a technique for detecting intact Hb and its drug adduct and studied the interactions between intact Hb and oxaliplatin. Methods: We incubated a series of mixtures of Hb and oxaliplatin at 37°C for 24 h or 5 days to investigate adduct formation. Blood samples from colorectal cancer patients undergoing oxaliplatin treatment were analyzed for novel adducts of intact Hb-oxaliplatin, which were characterized with nanoelectrospray ionization quadrupole time-of-flight MS. Results: Two intact Hb adducts, one with the whole oxaliplatin molecule and the other with oxaliplatin losing the oxalate ligand, were identified. Analysis of erythrocytes from the cancer patients provided direct evidence that oxaliplatin accumulated as Hb adducts in erythrocytes. A higher fraction (ϳ70%) of Hb was bound to oxaliplatin in erythrocytes from a patient who could not tolerate oxaliplatin treatment than in erythrocytes from another patient who benefited from this treatment. Conclusions:The nanoelectrospray tandem MS technique enabled determination of the intact Hb tetramer and its association with oxaliplatin. Hb-oxaliplatin ad-

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Section: Characterization Of Intact Hb-oxaliplatin Adductssupporting

confidence: 82%

“…3 -platinum moiety is more active than other stereochemical conformations (5,6 ). Oxaliplatin, which is used in combination with 5-fluorouracil or related drugs, is the only platinum drug that is effective against colorectal cancer (7 ).…”

Section: The Trans-1-(rr)-12-diaminocyclohexane (Dach)mentioning

confidence: 99%

Characterization of Intact Hemoglobin and Oxaliplatin Interaction by Nanoelectrospray Ionization Tandem Mass Spectrometry

Peng¹,

Mandal²,

Sawyer

et al. 2005

Clinical Chemistry

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“…(16) To date, platinum analogs (e.g. carboplatin and oxaliplatin) (17) have been developed to overcome these CDDP-related disadvantages. Consequently, these analogs have become the standard drugs for ovarian (18) and colon (19) cancers.…”

Section: Nc-6004: Cisplatin-incorporating Micellar Nanoparticlementioning

confidence: 99%

Preclinical and clinical studies of anticancer agent‐incorporating polymer micelles

2009

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The size of anticancer agent-incorporating micelles can be controlled within the diameter range of 20-100 nm to ensure that they do not penetrate normal vessel walls. With this development, it is expected that the incidence of drug-induced side-effects may be decreased owing to the reduced drug distribution in normal tissue. Micelle systems can also evade non-specific capture by the reticuloendothelial system because the outer shell of a micelle is covered with polyethylene glycol. Consequently, a polymer micelle carrier can be delivered selectively to a tumor by utilizing the enhanced permeability and retention effect. Moreover, a water-insoluble drug can be incorporated into polymer micelles. Presently, several anticancer agent-incorporating micelle carrier systems are under preclinical and clinical evaluation. Furthermore, nucleic acid-incorporating micelle carrier systems are also being developed. (Cancer Sci 2009; 100: 572-579) N anotechnology is one of the fast-moving technologies and is presently contributing significantly to the progress of medical science. Drugs categorized under the drug delivery system (DDS) are made primarily by utilizing nanotechnology. In the field of oncology, DDS drugs have been produced and evaluated in preclinical or clinical trials, with some already approved for clinical use (Table 1). More specifically, DDS can be used for active or passive targeting of tumor tissues. Passive targeting refers to the development of monoclonal antibodies directed against tumor-related molecules, allowing targeting of a tumor from the specific binding of antibodies with respective antigens. However, the application of DDS using monoclonal antibodies is restricted to tumors expressing high levels of related antigens.Passive targeting can be achieved by utilizing the enhanced permeability and retention (EPR) effect.(1,2) This effect is based on the pathophysiological characteristics of solid tumor tissues, namely, hypervascularity, incomplete vascular architecture, secretion of vascular permeability factors stimulating extravasation within cancer tissue, and absence of effective lymphatic drainage from tumors that impedes the efficient clearance of macromolecules accumulated in solid tumor tissues (Fig. 1A,B).Several techniques have been developed to maximally utilize the EPR effect such as modification of drug structures and development of drug carriers. Polymeric micelle-based anticancer drugs were originally developed by Kataoka et al. in the late 1980s or early 1990s. (3-5) Polymeric micelles were expected to increase the accumulation of drugs in tumor tissues by utilizing the EPR effect as well as to incorporate various kinds of drugs into their inner core with relatively high stability by chemical conjugation or physical entrapment. Also, the size of micelles can be controlled within the diameter range of 20-100 nm to ensure that they do not penetrate normal vessel walls. With this development, it is expected that the incidence of drug-induced side-effects may be decreased owing to the r...

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“…The antitumour effects against a spectrum of transplantable rodent tumours indicate that CHIP has an antitumour effect equal to, or greater than, that of Neoplatin (Cleare et al, 1978). Whilst the clinical efficacy of Neoplatin against a number of human tumours has been demonstrated, its unpleasant side effects necessitate the introduction of a less toxic congener into clinical use.…”

Section: Discussionmentioning

confidence: 99%

“…Many others have been screened at other centres throughout the world (Cleare et al, 1978). From these data, we selected 8 compounds for further preclinical evaluation (Wilkinson et al, 1978).…”

mentioning

confidence: 99%

Criteria for the selection of second-generation platinum compounds

Shepherd¹,

Kuśnierczyk²,

Jones³

et al. 1980

Br J Cancer

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Summary.-Our selection of a potential second-generation platinum compound began with an initial short list of 8 compounds selected on the basis of antitumour and toxicity studies in mice. We now report further, more detailed investigations of the renal toxicity and antitumour activity of one of these compounds, cis-dichloro trans-dihydroxy bis isopropylamine platinum (IV) (CHIP), in comparison with cis-dichloro diammine platinum (II) (Neoplatin). CHIP was a more effective antitumour agent against both alkylating-agent sensitive and resistant strains of the Yoshida sarcoma (YSs and YSR respectively) than was Neoplatin. In addition CHIP produced negligible kidney toxicity as measured by blood urea levels.We have also compared the effects of these two drugs on nuclear-protein phosphorylation, in an attempt to gain insight into their molecular mode of action. Both Neoplatin and CHIP induced increased nuclear-protein phosphorylation in the YSs tumour cells, and loss of condensed chromatin. However, CHIP also induced increased nuclear-protein phosphorylation and loss of condensed chromatin in the YSR tumour cells. These changes correlated well with cell death. In addition Neoplatin, but not CHIP, treatment caused increased nuclear-protein phosphorylation in kidney tissues. This correlated with kidney damage as measured by blood urea levels.These selection criteria suggested that CHIP would be a more selective antitumour agent than Neoplatin, and will provide a basis for its comparison with the other 7 compounds.FOLLOWING EARLY REPORTS by Rosenberg et al. on the anti-bacterial effects of the soluble salts of platinum (Rosenberg et al., 1965(Rosenberg et al., , 1967 and, subsequently, on

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Anti-tumour platinum complexes : relationships between chemical properties and activity

Cited by 170 publications

References 9 publications

Characterization of Intact Hemoglobin and Oxaliplatin Interaction by Nanoelectrospray Ionization Tandem Mass Spectrometry

Characterization of Intact Hemoglobin and Oxaliplatin Interaction by Nanoelectrospray Ionization Tandem Mass Spectrometry

Preclinical and clinical studies of anticancer agent‐incorporating polymer micelles

Criteria for the selection of second-generation platinum compounds

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