| 1. |
- Bu, H, et al.
(författare)
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Significance of glutathione S-transferases M1, T1 and P1 polymorphisms in Swedish melanoma patients.
- 2007
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Ingår i: Oncology Reports. - 1021-335X .- 1791-2431. ; 17:4, s. 859-864
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Tidskriftsartikel (refereegranskat)abstract
- Polymorphisms of GSTM1, GSTT1 and GSTP1 were examined in melanoma patients and tumor-free individuals. Relationships between the polymorphisms and tumor characteristics and pigment phenotypes of the patients were analyzed. There was no significant difference in GSTM1 null and GSTT1 null genotypes nor GSTP1 GG genotype between melanoma patients and controls. In melanoma patients, these polymorphisms were not correlated with early or later onset of melanomas or gender of the patients. Frequency of GSTM1 null genotype was higher in patients with melanoma >2.5 mm than in those with tumors <1.0 mm, and higher frequency was found in nodular melanoma than in the other tumor types. GSTP1 GG genotype was more often found in the patients with brown and mixed eye color or brown and black hair than those with blue and green eyes or blond hair. It is unlikely that polymorphisms of GSTM1, GSTT1 and GSTP1 are general risk factors for melanoma in the Swedish population. GSTM1 null genotype was correlated with Breslow thickness and tumor type, which might serve as an additional biomarker for a rapid tumor progression. GSTP1 GG increases risk for melanoma in the subgroup of individuals with dark eyes or hair.
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| 2. |
- Zhang, Hong, 1957-, et al.
(författare)
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All-trans retinoic acid (atRA) differentially induces apoptosis in matched primary and metastatic melanoma cells - A speculation on damage effect of atRA via mitochondrial dysfunction and cell cycle redistribution
- 2003
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 24:2, s. 185-191
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Tidskriftsartikel (refereegranskat)abstract
- All-trans retinoic acid (atRA) has been suggested to exert its cytotoxicity via apoptosis but the mechanisms behind the damage effects have not been fully understood. In this study, we investigated the cytotoxic effects of atRA in eleven primary and matched metastatic cutaneous melanoma cell lines. All the primary and metastatic melanoma cell lines examined expressed the retinoic acid receptors. The cultured melanoma cells treated with atRA showed dysfunction of mitochondria and altered cell cycle distribution, inhibited cell proliferation and apoptosis. The cytotoxic effects of atRA were dose- and time-dependent. The dysfunction of mitochondria and altered cell cycle distribution, inhibited cell proliferation and apoptosis. The cytotoxic effects of atRA were dose- and time-dependent. The dysfunction of mitochondria and induction of apoptosis were more pronounced in the primary tumor cells than in the metastatic cell lines from the same patients. The data indicate that the cytotoxic effect of atRA was mediated through dysfunction of mitochondria, alterations in cell cycle and induction of apoptosis. Melanoma in early stage may have better response to atRA adjuvant therapy than the melanoma in late stage, suggesting the early utility of atRA in melanoma chemotherapy.
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| 3. |
- Zhang, Hong, 1957-, et al.
(författare)
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Bcl-xL and bcl-2 proteins in melanoma progression and UVB-induced apoptosis.
- 2006
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Ingår i: International Journal of Oncology. - 1019-6439 .- 1791-2423. ; 28:3, s. 661-666
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Tidskriftsartikel (refereegranskat)abstract
- Whether bcl-xL and bcl-2 play an essential role in melanoma progression and UVB-induced apoptosis is not completely understood. We investigated the expression of bcl-xL and bcl-2 in matched primary and metastatic melanoma tumors and melanoma cell lines from the same melanoma patients to clarify the importance of bcl-xL and bcl-2 in melanoma progression and in UVB-induced apoptosis. The expression of bcl-xL and bcl-2 proteins was examined by immunohisto(cyto)chemistry and Western blot in melanoma tumors and melanoma cells. Cellular viability and apoptosis were estimated after the melanoma cells were exposed to 30, 60 and 180 mJ/cm2 UVB. Both primary melanoma tumors and melanoma cells showed lower expression of bcl-xL and bcl-2 proteins estimated as frequency of positive cells than their matched metastatic tumors and cells in vitro. After exposure to UVB, the cell viability decreased and the number of apoptotic cells increased in both primary and metastatic melanoma cell lines. These changes were more pronounced in the primary melanoma cells than in the matched metastatic cells. After UVB exposure, the expression of bcl-xL protein decreased in primary melanoma cells in a dose- and time-dependent manner, but the expression of bcl-2 was not influenced. The expression of bcl-xL and bcl-2 proteins was increased during melanoma progression from primary to metastatic melanoma. Reduction of bcl-xL, but not bcl-2 expression was involved in UVB-induced apoptosis in primary melanoma cells.
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| 4. |
- Zhang, Hong, 1957-, et al.
(författare)
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Deletion in p16INK4a and loss of p16 expression in human skin primary and metastatic melanoma cells.
- 2004
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Ingår i: International Journal of Oncology. - 1019-6439 .- 1791-2423. ; 24:2, s. 331-335
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Tidskriftsartikel (refereegranskat)abstract
- p16INK4a gene mapped at chromosome 9p21 region encodes a tumor suppressor protein p16 which is frequently inactivated in human cancers, including skin melanoma. In order to clarify the importance of p16 alterations in melanoma, we examined the deletions of p16INK4a and expression of p16 protein in eight unselected primary and metastatic melanoma cell lines from human skin melanomas. Normal skin melanocytes were used as controls. Deletions of entire exons in the p16INK4a gene were detected by PCR technique and expression of the p16 protein was examined by Western blotting and immunocytochemistry. Results showed that the fragments from exons 2A, 2C and 3 in p16INK4a gene were totally deleted in the metastatic melanoma cell line, FM28.7 and the fragment from exon 3 was deleted in the metastatic melanoma cell line, FM55M2. P16 protein was strongly expressed in two of the primary melanomas cell lines (FM55P and RaH3). The p16 protein was weakly expressed in one of the metastatic melanoma cell lines (FM55M1) and negative in the other metastasis (FM55M2) as compared to their matched primary melanoma cells (FM55P). The p16 protein was strongly expressed in normal skin melanocytes. Immunocytochemistry showed that p16 protein was mainly localized in the nuclei of the melanoma cells and normal melanocytes, if it was expressed. Deletions of p16INK4a gene was uncommon and loss of p16 protein expression was common event in melanoma, especially in the later stages of melanoma.
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| 5. |
- Zhang, Hong, 1957-, et al.
(författare)
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Expression of oncogenes, tumour suppressor, mismatch repair and apoptosis-related genes in primary and metastatic melanoma cells.
- 2001
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Ingår i: International Journal of Oncology. - 1019-6439 .- 1791-2423. ; 19:6, s. 1149-1153
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Tidskriftsartikel (refereegranskat)abstract
- Several genetic alterations have been implicated in the development of malignant melanoma, but the expression of oncogenes, tumour suppressor, mismatch repair and apoptosis-related genes and their interactions in melanoma have not been completely clarified. We simultaneously examined the expression of p73, c-erbB-2, ras, p53, Mdm2, p27, DCC, hMLH-1, hMSH-2, bcl-2, Bax and NF-kappaB, by immunocytochemistry, in both primary and metastatic melanoma cell lines derived from melanoma patients. p73 was expressed in 7/8 cell lines, but stronger expressed in the metastatic cells than in the primary melanoma cells. c-erbB-2 was detected in all 8 cell lines and ras in 2/5 metastases. p53 was found in all the cell lines and Mdm2 in 1/8 of the cell lines. In the same patient, the intensity of p27 expression was decreased from the primary to the metastatic tumours. bcl-2 was expressed in all the cell lines. Bax was absent in 5/8 cell lines. In the same patient, Bax was weakly expressed in the primary tumour but lacking in the metastases. The data demonstrate that overexpression of p73, c-erbB-2, p53 and bcl-2, and loss of Mdm2 and Bax may interact and play important roles in the development and aggressiveness of human melanoma.
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| 6. |
- Zhang, Hong, 1957-, et al.
(författare)
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Expression of p16, p27, p53, p73 and Nup88 proteins in matched primary and metastatic melanoma cells.
- 2002
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Ingår i: International Journal of Oncology. - 1019-6439 .- 1791-2423. ; 21:1, s. 43-48
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Tidskriftsartikel (refereegranskat)abstract
- Cutaneous melanoma is a tumor with high metastatic potential, but the mechanisms leading to progression are still not fully understood. In this study, we examined whether p16, p27, p53, p73 and Nup88 proteins were involved in the progression from primary to metastatic melanomas by immunocytochemistry and Western blotting in eleven melanoma cell lines from five matched primary and metastatic melanomas. We demonstrated that the primary and metastatic melanomas expressed differently p16, p27, p73 and Nup88 proteins. When expressed in the primary melanoma cells p16 and p27 were lost or reduced in almost all the metastatic melanoma cell lines. In contrast, p73 and Nup88 were expressed in most of the tested melanoma cell lines and were increased in the metastatic melanomas. p53 was expressed at the same level in both the primary and metastatic melanoma cells. These data suggest that a reduced expression of p16 and p27 and an enhanced expression of p73 and Nup88 might play an important role in the progression of melanoma from primary tumor to metastasis.
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| 7. |
- Zhang, Hong, 1957-, et al.
(författare)
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Expression of p27 and MAPK proteins involved in all-trans retinoic acid-induced apoptosis and cell cycle arrest in matched primary and metastatic melanoma cells.
- 2004
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Ingår i: International Journal of Oncology. - 1019-6439 .- 1791-2423. ; 25:5, s. 1241-1248
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Tidskriftsartikel (refereegranskat)abstract
- We investigated whether p27 and mitogen-activated protein kinase (MAPK) proteins were involved in all-trans retinoic acid (atRA)-induced apoptosis and cell cycle arrest. Matched primary and metastatic melanoma cells were exposed to atRA. Apoptosis and cell cycle were detected by flow cytometry. Expression of p27, Ras, B-raf, Mek and Erk proteins was examined. Results showed that atRA induced apoptosis and cell cycle arrest in both primary and metastatic melanoma cells. The primary melanoma cells were more vulnerable than their matched metastatic cells. Expression of p27 was increased, while MAPK proteins were decreased, this response was dose- and time-dependent. Alterations of these proteins were more pronounced in primary melanoma cells than in the matched metastases. These data indicate that up-regulation of p27 and down-regulation of MAPK proteins were involved in atRA-induced apoptosis and cell cycle arrest in melanoma.
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| 8. |
- Zhang, Hong, 1957-, et al.
(författare)
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Expression profiles of Id1 and p16 proteins in all-trans-retinoic acid-induced apoptosis and cell cycle re-distribution in melanoma
- 2005
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Ingår i: Cancer Letters. - : Elsevier BV. - 0304-3835 .- 1872-7980. ; 217:1, s. 33-41
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Tidskriftsartikel (refereegranskat)abstract
- All-trans-retinoic acid (atRA) exerts its effects via apoptosis and cell cycle re-distribution. However, the mechanisms behind the effects have not been fully understood. In this study, we used a model system of matched primary and metastatic melanoma cells to investigate whether expression of Id1 and p16 proteins were involved in atRA-induced apoptosis and cell cycle re-distribution. Melanoma cells were exposed to 0.1 or 10 μM atRA for 1-96 h. Apoptosis and cell cycle were measured by flow cytometry. Expression of Id1 and p16 proteins was examined by Western blotting and immunocytochemistry. After exposure to atRA we found a marked increase in apoptosis and cell cycle re-distribution in both primary and metastatic melanoma cells. Expression level of Id1 protein was decreased and the p16 was increased in a dose- and time-dependent (P<0.05) manner after treatment with atRA. Alterations of these proteins were more pronounced in the primary melanoma cells than the matched metastases (P<0.05). These data suggested that the alterations of Id1 and/or p16 proteins were involved in atRA-induced apoptosis and cell cycle re-distribution in melanoma. These expression profiles of Id1 and p16 proteins may provide molecular evidence for better chemotherapy primarily for early stages of melanoma.
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| 9. |
- Zhang, Hong, 1957-, et al.
(författare)
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Expression profiles of p53, p21, bax and bcl-2 proteins in all-trans-retinoic acid treated primary and metastatic melanoma cells.
- 2004
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Ingår i: International Journal of Oncology. - 1019-6439 .- 1791-2423. ; 25:2, s. 303-308
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that all-trans-retinoic acid (atRA) induces apoptosis in melanoma cells and primary melanoma cells are more sensitive to the exposure of atRA than the matched metastases. However, mechanisms behind the atRA-induced apoptosis have not been studied. In this study, we used a similar cell culture model system of matched primary and metastatic melanoma cells from the same patient to investigate whether p53 and bcl-2 family proteins were involved in atRA-induced apoptosis. The primary and metastatic melanoma cells were exposed to 0.1 and 10 micro M atRA in serum-free RPMI 1640 cell culture medium in the dark for up to 96 h. The protein expression of p53, p21, bax and bcl-2 were examined by Western blotting and immunocytochemistry. Expression of p53, p21 and bax was increased, and bcl-2 was decreased in melanoma cells after exposure to atRA at different concentrations for various periods of time. The changes of p53, p21, bax, and bcl-2 protein levels were dose- and time-dependent. The primary melanoma cells were more sensitive to the atRA treatments than cells from matched metastatic melanoma. These data indicate that p53, p21, bax and bcl-2 proteins were involved in atRA-induced apoptosis in melanoma cells. Modification of these protein levels in the tumour cells might be beneficial for early treatment of melanoma.
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| 10. |
- Zhang, Hong, 1957-, et al.
(författare)
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Ultraviolet A and B differently induce intracellular protein expression in human skin melanocytes - A speculation of separate pathways in initiation of melanoma
- 2003
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 24:12, s. 1929-1934
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Tidskriftsartikel (refereegranskat)abstract
- Ultraviolet (UV) irradiation has been involved in both initiation and promotion of carcinogenesis in melanoma. Alterations of cellular proliferation proteins, such as p73, Nup88, Id1 and p27 have been considered to play critical roles in melanoma development. However, the molecular mechanisms behind melanoma carcinogenesis are still poorly understood. In this study, we used human skin melanocytes as an experimental model system to investigate effects of UV irradiation on protein expression concerning cellular proliferation. The melanocytes prepared from human foreskin were separately exposed to various doses of UVA or UVB and post-cultivated for 24 or 48 h. Total proteins were isolated from the melanocytes, and expression of p73, Nup88, Id1, p27, bcl-2 and proliferating cell nuclear antigen (PCNA) proteins was examined by western blotting and immunocytochemistry. Results showed that expression of p73 and Nup88 was enhanced by UVA irradiation in a dose- and time-dependent manner. However, expression of Id1, p27, bcl-2 and PCNA proteins was not changed upon exposure to the UVA. Id1 and p27 proteins were over-expressed by exposure to UVB, but expression of p73, Nup88, bcl-2 and PCNA proteins was not changed by the UVB irradiation. The data suggested that UVA and UVB irradiation might lead to alterations of the different intracellular proteins. UVA enhanced protein expression concerning cell growth (p73 and Nup88) and UVB might over-express proteins concerning cellular proliferation (Id1 and p27). UVA and UVB may induce initiation of melanoma via separate intracellular pathways.
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