Platinum-based chemotherapy in metastatic breast cancer: current status

Decatris, Marios P.; Sundar, Santhanam; O’Byrne, Kenneth J.

doi:10.1016/s0305-7372(03)00139-7

Cited by 188 publications

(142 citation statements)

References 181 publications

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“…A breast adenocarcinoma cell line was adopted, since the efficacy of neutron therapy and these chemotherapeutic agents in the treatment of breast cancer is limited by normal tissue toxicity and tumor resistance. 5,6,23,24 Moreover, similar results were observed in a human glioblastoma cell line. The human Egr1 gene encodes a zinc finger transcription factor, induced after cellular injury or stress, that in turn activates downstream genes involved in growth and differentiation.…”

Section: Discussionsupporting

confidence: 76%

“…Furthermore, these agents may lead to the development of primary and secondary drug resistance in tumor cells, thereby limiting their clinical success. 23,24 There is therefore scope for targeted combinational therapies that can enhance the efficacy of these standard treatments while minimizing side effects. In the present work, synthetic promoters containing CArG elements from the Egr1 gene were found to be activated by neutron irradiation, cisplatin and doxorubicin, and to be able to control efficient experimental suicide gene therapy.…”

Section: Discussionmentioning

confidence: 99%

“…22 ''Chemogenetic'' therapy may represent a novel and promising avenue for combinational therapy, since the efficacy of these antineoplastic agents is often limited by normal tissue toxicity and tumor resistance. 23,24 In the present work, we first investigated the response of synthetic promoters containing isolated CArG elements to clinically relevant doses of neutrons for experimental gene therapy. Second, the activation of such promoters in the presence of the chemotherapeutic drugs cisplatin and doxorubicin was evaluated.…”

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confidence: 99%

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Gene therapy vectors containing CArG elements from the Egr1 gene are activated by neutron irradiation, cisplatin and doxorubicin

et al. 2005

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Gene therapy vectors containing CArG elements from the Egr1 gene are activated by neutron irradiation, cisplatin and doxorubicin

et al. 2005

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“…Cisplatin-induced toxicity can also alter the outcome of treatment by limiting the dose of drug administered, with nephrotoxicity and neuropathy as the main dose-limiting toxicities [14,15]. Peripheral neuropathy is permanent in approximately 30−50% of patients receiving treatment [15].…”

Section: Introductionmentioning

confidence: 99%

Susceptibility loci involved in cisplatin-induced cytotoxicity and apoptosis

Shukla

Duan²,

Badner³

et al. 2008

Pharmacogenetics and Genomics

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Objectives-Cisplatin is a widely used chemotherapeutic agent; however, nephrotoxicity and neuropathy are obstacles for drug efficacy. Little is known about the genes or genetic variants contributing to the risk of developing these toxicities or chemotherapeutic response. Thus, we have applied a cell-based model to identify and characterize previously unknown genes that may be involved in cellular susceptibility to cisplatin.Methods-Lymphoblastoid cell lines from 27 large Centre d'Etude du Polymorphisme Humain pedigrees were used to elucidate the genetic contribution to cisplatin-induced cytotoxicity. Phenotype was defined as cell growth inhibition following exposure of cell lines to increasing concentrations of cisplatin for 48 h.Results-Significant heritability, ranging from 0.32 to 0.43 (P < 10 −7 ), was found for the cytotoxic effects of each concentration (1, 2.5, 5, 10, and 20 μmol/l) and IC50, the concentration required for 50% cell growth inhibition. Linkage analysis revealed 11 genomic regions on six chromosomes with logarithm of odds (LOD) scores above 1.5 for cytotoxic phenotypes. The highest LOD score was found on chromosome 4q21.3−q35.2 (LOD = 2.65, P = 2.4 × 10 −4 ) for 5 μmol/l cisplatin. Quantitative transmission disequilibrium tests were performed using 191 973 nonredundant single nucleotide polymorphisms (SNPs) located in the 1 LOD confidence interval of these 11 regions. Twenty SNPs, with 10 SNPs located in five genes, were significantly associated with cisplatin-induced cytotoxicity (P ≤ 1 × 10 −4 ). Four of these 20 SNPs were found to explain over 10% of the variation in cisplatininduced apoptosis.Conclusions-Our results suggest that genetic factors involved in cytotoxicity also contribute to cisplatin-induced apoptosis. These cell lines provide a paradigm to identify previously unknown pharmacogenetic variants associated with drug cytotoxicity.

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“…This drug has been proved to be effective alone or in addition to other drugs or cytokines for the treatment of a variety of human and animal malignancies, 10 but its administration in humans shows many side effects such as nausea, nephrotoxicity and neurotoxicity. 11 In addition, its applicability is still limited to a relatively few number of tumours. This effect occurs because of the natural resistance to cisplatin or because of the resistance that happens after the initial treatment.…”

Section: Introductionmentioning

confidence: 99%

Citotoxicity and immune response induced by organopalladium(II) compounds in mice bearing Ehrlich ascites tumour

Rocha¹,

Santana²,

Ananias³

et al. 2007

J. Braz. Chem. Soc.

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Os ciclometalados de paládio(II) são compostos inorgânicos reativos empregados em vários estudos biológicos devido a seu potencial antitumoral e interação com o sistema imune. Neste estudo, a resposta imune e citotóxica induzida por dois complexos organopaladados: [{Pd(N,C-dmba)} 2 (μ-NCS) 2 ] (1), [Pd(C-dmba)(NCS)(dppp)] (2) [dmba = N,N'-dimetilbenzilamina, dppp = 1,3-bis(difenilfosfino)propano] e cisplatina (cis-DDP), como padrão, foram investigados em camundongos portadores do tumor ascítico de Ehrlich. Os camundongos foram divididos em cinco grupos e inoculados com (1) ou (2) ou cis-DDP ou apenas veículo ou solução salina tamponada de fosfatos (PBS). Diversos parâmetros foram avaliados, tais como a porcentagem de células tumorais presentes no exsudato peritoneal, os níveis de óxido nítrico (NO) e fator de necrose tumoral (TNF-α) séricos e o aumento na expectativa de vida. Os dados obtidos demonstram que o composto (2) apresentou atividade similar à da cis-DDP, como, por exemplo, aumento na expectativa de vida, diminuição dos níveis séricos de TNF-α e aumento da produção de NO.Cyclometallated palladium(II) complexes are reactive inorganic compounds employed in several biological studies because of their antitumour potential and interaction with immune system. In the present study, the immune and citotoxic response induced by two organopalladated complexes: [{Pd(N,C-dmba)} 2 (μ-NCS) 2 ] (1), [Pd(C-dmba)(NCS)(dppp)] (2) [dmba = N,N'-dimethylbenzylamine, dppp = 1,3-bis(diphenylphosphino)propane] and cisplatin (cis-DDP), as standard, were investigated in mice bearing Ehrlich ascites tumour. The mice were divided into five groups and inoculated with the compounds (1) or (2) or cisplatin, or only vehicle or phosphatebuffered saline (PBS). Many parameters were evaluated, such as tumour cell percentage in the peritoneal exsudate, levels of seric nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and increase in life span. Analysis of all data revealed, for compound (2), an activity similar to that presented by cisplatin, resulting in increased life span, lower levels of seric TNF-α and increase in NO production.Keywords: palladium(II) complexes, Ehrlich ascites tumour, macrophages, nitric oxide, tumour necrosis factor-alpha. IntroductionCancer is a disease in which unremitting clonal expansion of somatic cells kills by invading, subverting, and eroding normal tissues. 1 Millions of people die every year from the metastatic spread of cancer that occurs through blood and lymphatic vessels or directly into tissues and body cavities. 2 Between the several types of cancer, breast cancer is the most common malignancy in women worldwide. 3 In some cases, immune cells constitute a prominent component of the host response to cancer, but their participation in tumour pathogenesis remains not completely understood. Dense intratumoral lymphocyte cis-Diamminedichloroplatinum(II), 9 a clinically important antitumour drug, acts like a classical alkylating agent in chemotherapy against some types of cancers. It is a potent ...

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Platinum-based chemotherapy in metastatic breast cancer: current status

Cited by 188 publications

References 181 publications

Gene therapy vectors containing CArG elements from the Egr1 gene are activated by neutron irradiation, cisplatin and doxorubicin

Gene therapy vectors containing CArG elements from the Egr1 gene are activated by neutron irradiation, cisplatin and doxorubicin

Susceptibility loci involved in cisplatin-induced cytotoxicity and apoptosis

Citotoxicity and immune response induced by organopalladium(II) compounds in mice bearing Ehrlich ascites tumour

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