Newer Anticancer Agents

Knock, Frances E.

doi:10.1016/s0025-7125(16)33478-2

Cited by 13 publications

(15 citation statements)

References 73 publications

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“…The changes in calcium metabolism during this trial were investigated fully and have already been reported (Parsons, Baum and Self, 1967 Unfortunately the drug has serious side effects and these were often seen in the very cases that seemed to show tumour sensitivity. In view of this it would perhaps be more ethical to await the development of a readily available method of testing a tumour sample for sensitivity against a battery of chemotherapeutic agents (Knock, 1967).…”

Section: Effect On Calcium Metabolismmentioning

confidence: 99%

A clinical trial of mithramycin in the treatment of advanced malignant disease

Baum¹

1968

Br J Cancer

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Section: Effect On Calcium Metabolismmentioning

confidence: 99%

A clinical trial of mithramycin in the treatment of advanced malignant disease

Baum¹

1968

Br J Cancer

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“…DNA alkylators such as busulfan and melphalan have been clinically used since the early 1950’s and 1960’s, respectively [9–10]. It is commonly assumed that their cytotoxic effects are related to the induction of DNA interstrand crosslinks (ICLs), which block replication forks and cause DNA strand breaks when cells attempt to repair the DNA lesions [11].…”

Section: Introductionmentioning

confidence: 99%

Epigenetic modifiers enhance the synergistic cytotoxicity of combined nucleoside analog-DNA alkylating agents in lymphoma cell lines

Valdez

Nieto

Murray

et al. 2012

Experimental Hematology

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Hematopoietic stem cell transplantation (HSCT) is used for treatment of lymphoma. In an attempt to design an efficacious and safe pre-HSCT conditioning regimen, we investigated the cytotoxicity of the combination of busulfan (B), melphalan (M) and gemcitabine (G) in lymphoma cell lines in the absence or presence of drugs that induce epigenetic changes. Cells were exposed to drugs individually or in combination and analyzed by the MTT proliferation assay, flow cytometry, and Western blotting. We used ~IC10 drug concentrations (57 μM B, 1 μM M and 0.02 μM G) which individually did not have major effects on cell proliferation. Their combination resulted in 50% inhibition of proliferation. Reduction to almost half concentration (20 μM B, 0.7 μM M and 0.01 μM G) did not have significant effects, but addition of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA; 0.6 μM) to this combination resulted in a marked (~65%) growth inhibition. The cytotoxicity of these combinations correlates with the activation of the ATM-CHK2 pathway, phosphorylation of KAP1, epigenetic changes such as methylation and acetylation of histone 3, and activation of apoptosis. The relevance of epigenetic changes is further shown by the induction of DNA methyltransferases in tumor cells with low constitutive levels of DNMT3A and DNMT3B. The addition of 5-aza-2′-deoxycytidine (DAC) to [BMG+SAHA] further enhances cell killing. Overall, BMG combinations are synergistically cytotoxic to lymphoma cells. Epigenetic changes induced by SAHA and DAC further enhance the cytotoxicity. This study provides a rationale for an ongoing clinical trial in our institution using [BMG+SAHA] as pre-HSCT conditioning for lymphoma.

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“…This common chemical denominator of protein-SH groups participating in regulation from the lowest to the highest forms of life on an evolutionary basis, from cell membrane to nucleus, may now emerge as less surprising, perhaps another example of nature's pro found simplicity in a common chemical type of regulator from cell surface to chromosomal proteins [6,11,17].…”

Section: Discussionmentioning

confidence: 99%

“…Because selected SH inhibitors have been found to show marked activity against nonhistone chromosomal proteins of HeLa cancer cells [2], investigation of their activity at the cell surface appeared desirable from the histochemical studies [6]. For this, the scanning electron microscope offers certain advantages.…”

Section: Inmentioning

confidence: 99%

“…With both animal and human cancers, the selected SH inhibitors are seen to react histochemically with protein-SH groups of cell surface, nuclear membranes and chromosomal proteins [6], The SH inhibitor iodoacetate plus adjuncts menadiol and heparin has been found to be especially useful clinically [4] and the iodoacetate alone for inducing immunity against Ehrlich ascites cells in Ajax mice, from results of Apffel et al…”

mentioning

confidence: 99%

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Selected Sulfhydryl Inhibitors Capable of Inducing Immunity against Cancer in Mice

Knock¹,

Galt²,

Oester³

et al. 1979

Oncology

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Selected sulfhydryl inhibitors show greater toxicity to some animal and human cancers than to normal cells, both clinically and in drug sensitivity tests. Such selected SH inhibitors can induce immunity against cancer in mice, unlike other commonly used antitumor agents. Scanning electron micrographs of the surface of Ehrlich ascites cancer cells treated with the sulfhydryl inhibitors show blunting to absence of microvilli and modification of the surface texture of the cancer cells.

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Newer Anticancer Agents

Cited by 13 publications

References 73 publications

A clinical trial of mithramycin in the treatment of advanced malignant disease

A clinical trial of mithramycin in the treatment of advanced malignant disease

Epigenetic modifiers enhance the synergistic cytotoxicity of combined nucleoside analog-DNA alkylating agents in lymphoma cell lines

Selected Sulfhydryl Inhibitors Capable of Inducing Immunity against Cancer in Mice

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