The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
David Guthrie - One of the best experts on this subject based on the ideXlab platform.
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meta analysis of the role of Platinum Compounds in advanced ovarian carcinoma the advanced ovarian cancer trialists group
Seminars in Oncology, 1992Co-Authors: C J Williams, Lesley A Stewart, Mahesh K B Parmar, David GuthrieAbstract:This paper presents a systematic overview or meta-analysis of 54 randomized clinical trials testing a variety of chemotherapeutic approaches in advanced ovarian carcinoma. Prolonged follow-up data are available for most patients and individual patient data were made available for all patients; analysis was made on the basis of "intention to treat." Our report concentrates on two comparisons: (1) Platinum alone versus Platinum in combination, which appears to show a long-term survival advantage for the combination (however, the Platinum dose in the single-agent arm was relatively low); and (2) carboplatin versus cisplatin, which shows no obvious survival differences. It is striking that no single study to date has been large enough to detect the modest survival differences expected from current therapy. Consequently, a series of international studies have been initiated. The International Collaborative Ovarian Neoplasm (ICON) group will examine the role of adjuvant chemotherapy in early ovarian cancer (ICON 1) and will compare carboplatin with cisplatin, doxorubicin, and cyclophosphamide in more advanced disease (ICON 2).
Eddie Reed - One of the best experts on this subject based on the ideXlab platform.
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excision repair cross complementing group 1 gene expression and Platinum resistance review parameters in human breast cancer
International Journal of Molecular Medicine, 2004Co-Authors: Ramin Altaha, Xiaobing Liang, Eddie ReedAbstract:Abstract Platinum Compounds induce their cytotoxic effect by binding to a DNA molecule in the form of a Platinum-DNA-adduct. Many previous studies have shown that the level of Platinum-DNA-adduct correlats with response to Platinum-based chemotherapy. Although the mechanism of Platinum resistance in vivo is not clearly understood, laboratory studies on cancer cell lines suggest that nucleotide excision repair (NER) is the main mechanism responsible for this resistance by increased Platinum-DNA-adduct removal. NER pathway is a network of many proteins gathered in a DNA-repair system. The excision repair cross complementing-group 1 (ERCC1) gene has the leading role in NER-pathway because of its damage recognition and excision ability. In this report we reviewed the pathway leading to ERCC1 gene transcription and translation in cancer cells when exposed to cisplatin. We summarized data from different cancer cell lines and human cancers showing that the high level of ERCC1-mRNA and/or ERCC1 protein is associated with resistance to Platinum Compounds with direct impact on cancer patient survival and finally we analyzed drugs interfering with ERCC1 gene expression and causing the reversal of the Platinum resistance when given to cancer cells prior to Platinum-based chemotherapy.
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Oxaliplatin, tetraplatin, cisplatin, and carboplatin: Spectrum of activity in drug-resistant cell lines and in the cell lines of the national cancer institute's anticancer drug screen panel
Biochemical pharmacology, 1996Co-Authors: Olivier Rixe, Eddie Reed, Manuel Alvarez, Waldo Ortuzar, Ricardo J. Parker, Ken Paull, Tito FojoAbstract:The present study was designed to explore the activity of Platinum Compounds in cisplatin-resistant cell lines, the unselected cell lines of the National Cancer Institute's Anticancer Drug Screen, and the potential for use in combination. The activities of four Platinum Compounds in cisplatin-resistant KB and A2780 cells were investigated. The cells were highly resistant to cisplatin and cross-resistant to carboplatin, but less than one-tenth as resistant to oxaliplatin and tetraplatin. Cellular accumulation of all Platinum Compounds was decreased in both resistant cell lines. When the activities of cisplatin and oxaliplatin were evaluated in the National Cancer Institute's Anticancer Drug Screen, marked differences were observed. Evaluation of the activity profile using the COMPARE program revealed a different pattern for both agents: the cisplatin activity profile was similar to those of other diamine-Platinum Compounds, alkylating agents including melphalan, and camptothecin analogs, whereas the activity profile of oxaliplatin resembled those of other "dach" (diaminocyclohexane) Platinum Compounds and of acridine derivatives. The sensitivity profiles are influenced by the target(s)/mechanism(s) of action and the mechanism(s) of resistance of a drug. The dissimilarity in profiles suggests that these two Platinum Compounds have a different target(s)/mechanism(s) of action, a different mechanism(s) of resistance, or most likely both. Studies evaluating combinations of cisplatin/oxaliplatin suggest that the activities of these two agents are at least additive and possibly synergistic. Oxaliplatin has a different spectrum of activity and low cross-resistance to cisplatin and should be valuable in cisplatin refractory patients or in combination with cisplatin.
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ercc1 and ercc2 expression in malignant tissues from ovarian cancer patients
Journal of the National Cancer Institute, 1992Co-Authors: Meenakshi Dabholkar, Frieda Bostickbruton, Charles E Egwuagu, Vilhelm A Bohr, Eddie ReedAbstract:Abstract ERCC1 and ERCC2 are human DNA repair genes that are associated with in vitro resistance to selected DNA-damaging agents. Fresh tumor tissues from 26 patients with ovarian cancer were analyzed for the RNA levels of expression of these genes to determine possible clinical relevance. Tumor tissues were harvested from patients immediately before they entered a cisplatin- or carboplatin-based treatment protocol. Clinical response was assessed by standard criteria. Gene expression level was assessed by slot blot analysis, using beta-actin as a control. Relative expression levels were determined by comparing each tumor sample with a Chinese hamster ovary cell line that had a stable transfection of the human ERCC1 gene. Patients who were clinically resistant to Platinum-based therapy had a 2.6-fold higher expression level of ERCC1 in their tumor tissue than did patients who responded to that therapy (P = .015). Results obtained by slot blot analysis were qualitatively confirmed by polymerase chain reaction analysis. Relative levels of expression of ERCC2 did not differ significantly between responders and nonresponders. We conclude that ERCC1 expression levels in human tumor tissue may have a role in clinical resistance to Platinum Compounds. These data appear to be consistent with the assertion that ERCC1 serves as an excision nuclease, whereas ERCC2 serves as a helicase.
Peter Muller - One of the best experts on this subject based on the ideXlab platform.
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preparation characterization and structural analysis of d8 palladium and Platinum Compounds containing amino acid ester derivatized diimine ligands observation of liquid crystal behavior
Journal of Coordination Chemistry, 2017Co-Authors: Richard S Herrick, Christopher J Ziegler, Tang Ding, Janet L Shaw, Iwona E Wrona, Matthew Beaver, Joshua Giguere, Caroline Maus, Peter MullerAbstract:AbstractEight new Compounds, M(pyca(CH2)xCOOR)Cl2, M = Pd, Pt; R = Me, Et; x = 2, 3, 5, 11, were prepared. The resulting new complexes were characterized by 1H and 13C NMR spectroscopy and each was also structurally elucidated by X-ray crystallography. The Compounds share general structural features, but there are differences in the alignment of the alkyl chain; as the chain lengthens, the chain straightens relative to the plane of the metal complex. For the dodecanoic ester derivatives, a nearly linear alkyl chain was observed. These longer alkyl derivatives show mesogenic behavior.
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preparation characterization and structural analysis of d8 palladium and Platinum Compounds containing amino acid ester derivatized diimine ligands observation of liquid crystal behavior
Journal of Coordination Chemistry, 2017Co-Authors: Richard S Herrick, Christopher J Ziegler, Tang Ding, Janet L Shaw, Iwona E Wrona, Caroline Maus, Matthew G Beaver, Joshua R Giguere, Peter MullerAbstract:Eight new Compounds, M(pyca(CH2)xCOOR)Cl2, M = Pd, Pt; R = Me, Et; x = 2, 3, 5, 11, were prepared. The resulting new complexes were characterized by 1H and 13C NMR spectroscopy and each was also st...
Viktor Brabec - One of the best experts on this subject based on the ideXlab platform.
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cytotoxic Platinum coordination Compounds dna binding agents
Coordination Chemistry Reviews, 2017Co-Authors: Viktor Brabec, Ondrej Hrabina, Jana KasparkovaAbstract:Abstract Despite the widespread use of antineoplastic Platinum drugs, a number of accompanying disadvantages exist. In connection with attempts to circumvent these problems new Platinum Compounds have been prepared and mechanisms underlying their biological activity have been extensively investigated. These mechanistic investigations involve research focused on understanding interactions of Platinum agents with DNA since DNA binding and recognition of DNA modified by these metallodrugs are the important processes responsible for their anticancer properties. In this review, we discuss how various classes of Platinum(II) complexes, which can interact with DNA by coordination, intercalation and other noncovalent modes of binding or by combination of these DNA binding modes, can alter the cellular response induced by conventional Platinum drugs. We describe that these alterations can be achieved by changing: (i) the nature and structure of the DNA lesion induced; (ii) conformational alterations induced in DNA by these lesions; and (iii) various cellular signaling pathways initiated by Platinum-DNA damage. We anticipate that summarization of the results on DNA binding of cytotoxic Platinum Compounds may help to shed light on their potency and will make it possible to create new strategies to design rationally new anticancer Platinum Compounds and/or combine Platinum drugs with other cytotoxic agents.
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cytotoxicity mutagenicity cellular uptake dna and glutathione interactions of lipophilic trans Platinum complexes tethered to 1 adamantylamine
Journal of Inorganic Biochemistry, 2008Co-Authors: Anna Halamikova, Giovanni Natile, Jana Kasparkova, Pavla Heringova, Francesco P Intini, Alina Nemirovski, Dan Gibson, Viktor BrabecAbstract:Cytotoxicity and mutagenicity of trans,trans,trans-[PtCl2(CH3COO)2(NH3)(1-adamantylamine)] [trans-adamplatin(IV)] and its reduced analog trans-[PtCl2(NH3)(1-adamantylamine)] [trans-adamplatin(II)] were examined. In addition, the several factors underlying biological effects of these trans-Platinum Compounds using various biochemical methods were investigated. A notable feature of the growth inhibition studies was the remarkable circumvention of both acquired and intrinsic cisplatin resistance by the two lipophilic trans-Compounds. Interestingly, trans-adamplatin(IV) was considerably less mutagenic than cisplatin. Consistent with the lipophilic character of trans-adamplatin complexes, their total accumulation in A2780 cells was considerably greater than that of cisplatin. The results also demonstrate that trans-adamplatin(II) exhibits DNA binding mode markedly different from that of ineffective transplatin. In addition, the reduced deactivation of trans-adamplatin(II) by glutathione seems to be an important determinant of the cytotoxic effects of the complexes tested in the present work. The factors associated with cytotoxic and mutagenic effects of trans-adamplatin complexes in tumor cell lines examined in the present work are likely to play a significant role in the overall antitumor activity of these complexes.
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dna interactions of new antitumor Platinum complexes with trans geometry activated by a 2 metylbutylamine or sec butylamine ligand
Biochemical Pharmacology, 2004Co-Authors: Radim Prokop, Jana Kasparkova, Carmen Navarroranninger, Olga Novakova, Victoria Marini, Ana M Pizarro, Viktor BrabecAbstract:Abstract The global modification of mammalian and plasmid DNAs by novel Platinum Compounds, trans -[PtCl 2 (NH 3 )(Am)], where Am=2-methylbutylamine or sec- butylamine was investigated in cell-free media using various biochemical and biophysical methods. These modifications were analyzed in the context of the activity of these new Compounds in several tumor cell lines including those resistant to antitumor cis -diamminedichloroPlatinum(II) (cisplatin). The results showed that the replacement of one amine group by 2-methylbutylamine or sec- butylamine ligand in clinically ineffective trans -diamminedichloroPlatinum(II) (transplatin) resulted in a radical enhancement of its activity in tumor cell lines so that they are more cytotoxic than cisplatin and exhibited significant antitumor activity including activity in cisplatin-resistant tumor cells. Importantly, this replacement also markedly altered DNA binding mode of transplatin and reduced the efficiency of repair systems to remove the adducts of the new analogues from DNA. The results support the view that one strategy to activate trans geometry in bifunctional Platinum(II) Compounds including circumvention of resistance to cisplatin may consist in a chemical modification of the ineffective transplatin which results in an increased efficiency to form DNA interstrand cross-links.
Tito Fojo - One of the best experts on this subject based on the ideXlab platform.
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identification of non cross resistant Platinum Compounds with novel cytotoxicity profiles using the nci anticancer drug screen and clustered image map visualizations
Critical Reviews in Oncology Hematology, 2005Co-Authors: Tito Fojo, Waldo Ortuzar, Nick Farrell, Hideyuki Tanimura, John N Weinstein, Timothy G MyersAbstract:The widespread clinical use of Platinum Compounds in cancer chemotherapy has prompted a search for new Platinum agents. To search for Platinum agents with novel profiles of activity, we used clustered image maps, the COMPARE algorithm, and other numerical methods to analyze Platinum Compounds submitted to the National Cancer Institute's anticancer drug screen and tested against the screen's 60 diverse human cancer cell lines (the NCI-60). A total of 107 Platinum Compounds for which the data were adequate could be clustered into 12 groups, 11 of which were characterized by distinctive activity profiles against the cell lines. Each group (except the mixed one) was then found to have a characteristic chemical structure as well. Four of the groups were subjected to further analysis. Mean graph representations of the averaged activity profiles of the different groups served to highlight their similarities and differences. To identify Compounds that might retain activity in the setting of resistance to clinically used Platinum Compounds, we determined the activity levels of 38 of the Compounds (representative of the different activity-structure groups) against cisplatin and oxaliplatin-resistant ovarian cancer cell lines. Many of the Compounds retained activity against the resistant cells, providing evidence that they differ from cisplatin and oxaliplatin, not only in their selective activity against the various NCI-60 cell types, but are also in their susceptibility to mechanisms of resistance. Since Platinum Compounds have generally been classified as alkylating agents, we also compared their patterns of activity with those of representative alkylating agents, with NCI-60 growth rates, and with the profiles of 1582 molecular markers in the NCI-60 cells. Much more analysis remains to be done, but the absence of any definitive, biologically interpretable molecular predictor of activity is consistent with the idea that Platinum Compounds have multiple intracellular targets and that cells can have multiple mechanisms of resistance.
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Oxaliplatin, tetraplatin, cisplatin, and carboplatin: Spectrum of activity in drug-resistant cell lines and in the cell lines of the national cancer institute's anticancer drug screen panel
Biochemical pharmacology, 1996Co-Authors: Olivier Rixe, Eddie Reed, Manuel Alvarez, Waldo Ortuzar, Ricardo J. Parker, Ken Paull, Tito FojoAbstract:The present study was designed to explore the activity of Platinum Compounds in cisplatin-resistant cell lines, the unselected cell lines of the National Cancer Institute's Anticancer Drug Screen, and the potential for use in combination. The activities of four Platinum Compounds in cisplatin-resistant KB and A2780 cells were investigated. The cells were highly resistant to cisplatin and cross-resistant to carboplatin, but less than one-tenth as resistant to oxaliplatin and tetraplatin. Cellular accumulation of all Platinum Compounds was decreased in both resistant cell lines. When the activities of cisplatin and oxaliplatin were evaluated in the National Cancer Institute's Anticancer Drug Screen, marked differences were observed. Evaluation of the activity profile using the COMPARE program revealed a different pattern for both agents: the cisplatin activity profile was similar to those of other diamine-Platinum Compounds, alkylating agents including melphalan, and camptothecin analogs, whereas the activity profile of oxaliplatin resembled those of other "dach" (diaminocyclohexane) Platinum Compounds and of acridine derivatives. The sensitivity profiles are influenced by the target(s)/mechanism(s) of action and the mechanism(s) of resistance of a drug. The dissimilarity in profiles suggests that these two Platinum Compounds have a different target(s)/mechanism(s) of action, a different mechanism(s) of resistance, or most likely both. Studies evaluating combinations of cisplatin/oxaliplatin suggest that the activities of these two agents are at least additive and possibly synergistic. Oxaliplatin has a different spectrum of activity and low cross-resistance to cisplatin and should be valuable in cisplatin refractory patients or in combination with cisplatin.