Chemotherapy for Melanoma: The Resultant of Conflicting Vectors

Mitchell, Malcolm S.

doi:10.1200/jco.2004.03.976

Cited by 7 publications

(5 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Human melanoma cells arising from pigmented cells—melanocytes, express a wide variety of differences in the degree of pigmentation, cell morphology, and growth rate. These qualities of melanomas, defined as their phenotypic heterogeneity, are generally followed by an inherent or acquired drug resistance during treatment and a very poor response to conventional radiation 10,11 . Since chemotherapeutic agents usually function as inducers of apoptotic cell death, drug resistance of melanoma cells is assumed to be, in part, due to a defect of apoptotic pathways induced by the chemotherapeutic agents 12,13 .…”

Section: Discussionmentioning

confidence: 99%

“…These qualities of melanomas, defined as their phenotypic heterogeneity, are generally followed by an inherent or acquired drug resistance during treatment and a very poor response to conventional radiation. 10,11 Since chemotherapeutic agents usually function as inducers of apoptotic cell death, drug resistance of melanoma cells is assumed to be, in part, due to a defect of apoptotic pathways induced by the chemotherapeutic agents. 12,13 Moreover, cytotoxic effect of alkylating agents on melanoma cells is accomplished through the formation of interstrand cross-links within the molecule of DNA.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Viability of a Human Melanoma Cell after Single and Combined Treatment with Fotemustine, Dacarbazine, and Proton Irradiation

Petrović

Korićanac

Todorović

et al. 2007

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

Viability of human HTB140 melanoma cells after being exposed to fotemustine (FM) and dacarbazine (DTIC) as well as to proton irradiation was studied. Effects of 100 and 250 microM drugs were assessed after incubation of 6, 24, 48, 72, and 96 h. Irradiations were performed with 62 MeV therapeutic protons, delivering to the cell monolayer single doses of 2, 4, 8, 12, and 16 Gy. Viability was evaluated 7 days after irradiation. Inactivation level was estimated using microtetrasolium (MTT) and sulforhodamine B (SRB) assays. Combined effects of each drug and protons, were carried out using the same drug concentrations. Proton doses applied were those used in therapy, that is, 12 and 16 Gy. With the increase of drug concentration or irradiation dose, level of cell inactivation reached approximately 60%, 48 h after drug treatment or 7 days after irradiation at 16 Gy. Considering the rate of drug concentrations used, as well as the level of doses applied, it appears that HTB140 cells are more resistant to proton irradiation than to alkylating agents tested. The combined treatment with FM or DTIC and protons did not show significant changes of cell viability as compared to the effects of single agents. Since the time point for measuring cumulative effects of drug and irradiation was 48 h post irradiation, it seems that the obtained level of viability could be attributed primarily to the effects of drugs.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Viability of a Human Melanoma Cell after Single and Combined Treatment with Fotemustine, Dacarbazine, and Proton Irradiation

Petrović

Korićanac

Todorović

et al. 2007

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

show abstract

“…Untreated patients with distant metastasis have a poor prognosis with a median overall survival of 9 months (3). However, recently developed systemic treatments such as the B-RAF inhibitors or the CTLA-4 antibody ipilimumab are now licensed as standard therapies and are likely to displace earlier chemotherapies where long-term survival and clinical responses were very rarely observed (4). Treatment with the B-RAF inhibitor vemurafenib results in clinical responses in a high proportion of patients, but recurrence occurs rapidly in essentially all of them (5).…”

Section: Introductionmentioning

confidence: 99%

Circulating CD4+ T Cells That Produce IL4 or IL17 When Stimulated by Melan-A but Not by NY-ESO-1 Have Negative Impacts on Survival of Patients with Stage IV Melanoma

Zelba

Weide

Martens³

et al. 2014

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: We initially observed that the presence of circulating NY-ESO-1-and/or Melan-A-specific T cells in patients with stage IV melanoma was significantly associated with prolonged survival. Here, we report the ways in which the phenotypes and functions of these T cells differentially affect survival in patients preselected for NY-ESO-1 and/or Melan-A reactivity.Experimental Design: We assayed functional antigen-reactive T cells recognizing NY-ESO-1 and/or Melan-A after in vitro stimulation using overlapping peptide pools. After restimulation, we assayed six cytokines simultaneously by intracellular cytokine staining. This allowed us to analyze the functional antigen response of both CD4 þ and CD8 þ T cells at the single-cell level.Results: We observed that NY-ESO-1 stimulated mainly CD4 þ T cells, whereas Melan-A more often stimulated CD8 þ T cells. NY-ESO-1 reactivity was not associated with an additional impact on survival, whether CD4 þ T cells, CD8 þ T cells, or both types of T cells were responding. In contrast, recognition of Melan-A by CD4 þ T cells was associated with reduced survival in our cohort of patients preselected for NY-ESO-1 and/or Melan-A reactivity (that is, in patients with exceptionally long survival). We further observed a negative effect on survival in patients with CD4 þ T cells producing IL4 and IL17 upon Melan-A stimulation. Their prognosis was comparable to patients without any Melan-A reactivity. Conclusions:The nature and prognostic impact of specific T-cell responses is different according to targeted antigen. Independent from phenotype and functional aspects, NY-ESO-1 reactivity is associated with good prognosis. In terms of Melan-A, antigen-specific CD8 þ but not CD4 þ responses are associated with prolonged survival.

show abstract

“…In 2006 there were 60,000 new cases of cutaneous melanoma in the European Union, and in 13,000 deaths (www.europeancancerleagues.org). Metastatic melanoma in its disseminated form is largely untreatable by cytotoxic chemotherapy [4,5]. There is an urgent need for new therapeutic strategies to improve prognosis and identification of novel targets is critical for providing alternative treatment options.…”

Section: Introductionmentioning

confidence: 99%

2D-DIGE analysis of phospho-enriched fractions from dasatinib-treated melanoma cell lines

Eustace

Dowling

Henry

et al. 2011

Journal of Proteomics

View full text Add to dashboard Cite

Chemotherapy for Melanoma: The Resultant of Conflicting Vectors

Cited by 7 publications

References 12 publications

Viability of a Human Melanoma Cell after Single and Combined Treatment with Fotemustine, Dacarbazine, and Proton Irradiation

Viability of a Human Melanoma Cell after Single and Combined Treatment with Fotemustine, Dacarbazine, and Proton Irradiation

Circulating CD4+ T Cells That Produce IL4 or IL17 When Stimulated by Melan-A but Not by NY-ESO-1 Have Negative Impacts on Survival of Patients with Stage IV Melanoma

2D-DIGE analysis of phospho-enriched fractions from dasatinib-treated melanoma cell lines

Contact Info

Product

Resources

About