Background: Protein tyrosine kinase (PTK) inhibition has been identified as a promising strategy in the development of new selective therapies, targeting the signaling pathways in melanoma progression. Gleevec, a nove...Background: Protein tyrosine kinase (PTK) inhibition has been identified as a promising strategy in the development of new selective therapies, targeting the signaling pathways in melanoma progression. Gleevec, a novel class of anti-tumor drugs, may have a potential therapeutic benefit in melanoma, which involves abnormal activation of abl, c-kit, and platelet-derived growth factor (PDGF) tyrosine kinases. Methods: Tumor biopsies from 13 patients with metastatic melanoma were screened by immunohistochemistry for PTK [c-kit, C-abl, Abl-related gene (ARG), PDGF receptor-α(PDGFR-α) and PDGFR-β] expression before and after being treated with Gleevec @ 400 mg bid for 2weeks. Both, percentage of positive cells and staining intensity were evaluated. Results: We found a statistically significant (p < 0.01) selective loss of PTK expression in the follow-up biopsy, both in intensity and number of positive cells. PDGFR-αand -βhad the highest level of expression reduction. One patient had a durable clinical response, and the follow-up biopsy showed negative expression for four of the PTKs,namely c-abl, ARG, PDGFR-α, and β. Conclusions: Our study reports for the first time the in vivo effect of Gleevec in the induction of apparently selective reduction of PTKs expression under anti-tyrosine kinases treatment, suggesting its potential role in melanoma treatment.展开更多
The association between cutaneous melanoma and non-Hodgkin’ s lymphoma (NHL) has been described. Herein we describe two cases in which lymphoma was detected in the draining lymph node basin at the time of the finding...The association between cutaneous melanoma and non-Hodgkin’ s lymphoma (NHL) has been described. Herein we describe two cases in which lymphoma was detected in the draining lymph node basin at the time of the finding of intransit metastasis of cutaneous melanoma. In both of these cases, sentinel lymph node biopsy at the time of the excision of the primary melanoma showed no evidence of metastatic melanoma or lymphoma. The temporal and spatial correlation of melanoma and NHL in these two cases suggests the possibility of a local failure in immune surveillance.展开更多
糖蛋白非转移性黑色素瘤蛋白B(glycoprotein non-metastatic melanoma protein B,GPNMB)是一种I型跨膜蛋白,多富集在癌细胞表面,在巨噬细胞和小胶质细胞中呈高表达。GPNMB在肿瘤进展及免疫反应中发挥了重要作用,其胞外结构域与整合素相...糖蛋白非转移性黑色素瘤蛋白B(glycoprotein non-metastatic melanoma protein B,GPNMB)是一种I型跨膜蛋白,多富集在癌细胞表面,在巨噬细胞和小胶质细胞中呈高表达。GPNMB在肿瘤进展及免疫反应中发挥了重要作用,其胞外结构域与整合素相互作用,能促进免疫抑制,并能促进血管生成细胞募集到肿瘤微环境,从而影响肿瘤的免疫反应,有可能可作为免疫治疗及靶向治疗的潜在靶点。展开更多
文摘Background: Protein tyrosine kinase (PTK) inhibition has been identified as a promising strategy in the development of new selective therapies, targeting the signaling pathways in melanoma progression. Gleevec, a novel class of anti-tumor drugs, may have a potential therapeutic benefit in melanoma, which involves abnormal activation of abl, c-kit, and platelet-derived growth factor (PDGF) tyrosine kinases. Methods: Tumor biopsies from 13 patients with metastatic melanoma were screened by immunohistochemistry for PTK [c-kit, C-abl, Abl-related gene (ARG), PDGF receptor-α(PDGFR-α) and PDGFR-β] expression before and after being treated with Gleevec @ 400 mg bid for 2weeks. Both, percentage of positive cells and staining intensity were evaluated. Results: We found a statistically significant (p < 0.01) selective loss of PTK expression in the follow-up biopsy, both in intensity and number of positive cells. PDGFR-αand -βhad the highest level of expression reduction. One patient had a durable clinical response, and the follow-up biopsy showed negative expression for four of the PTKs,namely c-abl, ARG, PDGFR-α, and β. Conclusions: Our study reports for the first time the in vivo effect of Gleevec in the induction of apparently selective reduction of PTKs expression under anti-tyrosine kinases treatment, suggesting its potential role in melanoma treatment.
文摘The association between cutaneous melanoma and non-Hodgkin’ s lymphoma (NHL) has been described. Herein we describe two cases in which lymphoma was detected in the draining lymph node basin at the time of the finding of intransit metastasis of cutaneous melanoma. In both of these cases, sentinel lymph node biopsy at the time of the excision of the primary melanoma showed no evidence of metastatic melanoma or lymphoma. The temporal and spatial correlation of melanoma and NHL in these two cases suggests the possibility of a local failure in immune surveillance.
文摘糖蛋白非转移性黑色素瘤蛋白B(glycoprotein non-metastatic melanoma protein B,GPNMB)是一种I型跨膜蛋白,多富集在癌细胞表面,在巨噬细胞和小胶质细胞中呈高表达。GPNMB在肿瘤进展及免疫反应中发挥了重要作用,其胞外结构域与整合素相互作用,能促进免疫抑制,并能促进血管生成细胞募集到肿瘤微环境,从而影响肿瘤的免疫反应,有可能可作为免疫治疗及靶向治疗的潜在靶点。
