The phospholipid- and calcium-dependent protein kinase as a target in tumor chemotherapy

Grunicke, H.; Hofmann, Johann; Maly, Karl; Überall, Florian; Posch, Lydia; Oberhuber, Hermann; Fiebig, Helmut

doi:10.1016/0065-2571(89)90072-1

Cited by 25 publications

(12 citation statements)

References 25 publications

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“…Nevertheless the experimental basis for the notion that inhibition of PKC activity is causally associated with ability to arrest growth has been tenuous, particularly in view of the fact that most so-called 'PKC inhibitors' possess only modest specificity for PKC, or none at all. Some evidence for such a link was provied by experiments on quercetin, staurosporine (Hofmann et al, 1988) and the alkyllysophospholipid BM 41440 (Grunicke et al, 1989) in 3T3 fibroblasts, even though these compounds are clearly promiscuous in their ability to inhibit kinases. In these cells the dose-effect relationship with regard to inhibition of PKC was found to be similar to the dose-response curves for depression of replication.…”

Section: Discussionmentioning

confidence: 99%

Comparison of ability of protein kinase C inhibitors to arrest cell growth and to alter cellular protein kinase C localisation

Courage

Budworth²,

Gescher³

1995

Br J Cancer

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Section: Discussionmentioning

confidence: 99%

Comparison of ability of protein kinase C inhibitors to arrest cell growth and to alter cellular protein kinase C localisation

Courage

Budworth²,

Gescher³

1995

Br J Cancer

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“…More over, K252a, staurosporine, and quercetin inhibit PKC at its catalytic domain, which is homologous to other serine/ threonine and tyrosine kinases [16,17]. These compounds are, therefore, though very potent, less specific.…”

Section: Discussionmentioning

confidence: 99%

“…The IC50 values were 0.024,0.061, and 3 \xM, respec tively. Sphingosine and tamoxifen, which both inhibit PKC in vitro at the regulatory domain [16,17], exerted lower in hibitory activity with a maximum inhibition of 36.0 ±5.8 and 18.0 ±7.2% at a concentration of 10 \iM ( fig. 1)…”

Section: Experiments With Nonselective Pkc Inhibitorsmentioning

confidence: 99%

Pharmacological Studies on the Role of Protein Kinase C in Signal Transduction of Human Basophils

Amon

Stebut

Dietz

et al. 1992

Int Arch Allergy Immunol

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Recent investigations have demonstrated that activation of basophils involves the activation of protein kinase C (PKC). In the present study the effects of different nonselective and selective PKC inhibitors on IgE-mediated histamine release from human basophils were investigated. While potent but nonselective inhibitors such as staurosporine exerted a dose-dependent inhibition of Fc_ε-receptor-mediated histamine release, staurosporine derivatives with high selectivity for PKC potentiated the IgE-mediated response. The results provide evidence that the histamine release-inhibiting activity of protein kinase inhibitors is inversely correlated with their specificity for PKC. This may confirm the hypothesis that PKC exerts a negative modulatory role during the process of stimulus secretion-coupling following receptor aggregation in basophils. Moreover, investigations with phorbol esters and diacylglycerol derivatives as potent PKC activators show that direct cellular PKC activation and antigen-stimulated mediator release are not closely correlated.

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“…21 The modulation of cAMP has also been reported to interfere with cisplatin cytotoxicity. 22,23 As stimulatory G proteins play an important role in the production of cAMP, polymorphisms in the gene GNAS1, encoding the G-protein subunit Galphas (Gs), might be related to therapy outcome.…”

Section: Introductionmentioning

confidence: 99%

GNAS1 T393C polymorphism is associated with histopathological response to neoadjuvant radiochemotherapy in esophageal cancer

et al. 2009

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Recent studies have shown an association between the GNAS1 T393C polymorphism and clinical outcome for various solid tumors. In this study, we genotyped 51 patients from an observational trial on cisplatin/5-FU-based neoadjuvant radiochemotherapy of locally advanced esophageal cancer (cT2-4, Nx, M0) and genotyping was correlated with histomorphological tumor regression. The C-allele frequency in esophageal cancer patients was 0.49. Pearson's w 2 -test showed a significant (Po0.05) association between tumor regression grades and T393C genotypes. Overall, 63% of the patients in the T-allele group (TT þ CT) were minor responders with more than 10% residual vital tumor cells in resection specimens, whereas T(À) genotypes (CC) showed a major histopathological response with less than 10% residual vital tumor cells in 80%. The results support the role of the T393C polymorphism as a predictive molecular marker for tumor response to cisplatin/5-FU-based radiochemotherapy in esophageal cancer.

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The phospholipid- and calcium-dependent protein kinase as a target in tumor chemotherapy

Cited by 25 publications

References 25 publications

Comparison of ability of protein kinase C inhibitors to arrest cell growth and to alter cellular protein kinase C localisation

Comparison of ability of protein kinase C inhibitors to arrest cell growth and to alter cellular protein kinase C localisation

Pharmacological Studies on the Role of Protein Kinase C in Signal Transduction of Human Basophils

GNAS1 T393C polymorphism is associated with histopathological response to neoadjuvant radiochemotherapy in esophageal cancer

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