Search

Changes in protein glycosylation of tumour cells, as detected by lectin histochemistry, have been associated with metastasis formation in several human malignancies. This study analysed the association between lectin binding and metastasis in cutaneous malignant melanoma. In a 10-year retrospective study, sections of 100 primary cutaneous malignant melanomas were histochemically stained for the following 5 lectins: HPA, SNA-I, MAA, WGA and PHA-L, differing in their carbohydrate specificity. Since differences in the results of HPA binding depending on methodology have been reported, an indirect and a biotinylated method were employed for HPA. Kaplan-Meier analysis of time to first metastasis revealed a positive correlation between HPA binding and metastasis for both methods, with the biotinylated HPA method (P < 0.0001) being superior to the 'indirect' method (P = 0.0006). Cox regression analysis demonstrated that even after adjustment for stage, HPA positivity is an independent predictor for metastasis. The results of the present study indicate that N-acetyl-galactosamine/-glucosamine residues, recognized by HPA, are linked to metastasis in malignant melanoma. In contrast, β1-6 branched oligosaccharides or sialic acid residues, both of which were correlated with metastasis in other malignancies, are of no functional importance for metastasis formation in malignant melanoma. Thus, HPA proved to be a useful and independent prognostic marker for the metastatic phenotype of melanoma. [ABSTRACT FROM AUTHOR]

Background:There are no validated markers that predict response in metastatic renal cell cancer (RCC) patients treated with sunitinib. We aim to study the impact of single-nucleotide polymorphisms (SNPs) that have recently been proposed as predictors of outcome to anti-VEGF-targeted therapy in metastatic RCC in an independent cohort of patients.Methods:We genotyped 16 key SNPs in 10 genes involved in sunitinib pharmacokinetics, pharmacodynamics and VEGF-independent angiogenesis in patients with metastatic clear-cell RCC treated with sunitinib as the first-line targeted therapy. Association between SNPs, progression-free survival (PFS) and overall survival (OS) were studied by multivariate Cox regression using relevant clinical factors associated with PFS and OS as covariates.Results:In a series of 88 patients, both PFS and OS were associated significantly with SNP rs1128503 in ABCB1 (P=0.027 and P=0.025), rs4073054 in NR1/3 (P=0.025 and P=0.035) and rs307821 in VEGFR3 (P=0.032 and P=0.011). Progression-free survival alone was associated with rs2981582 in FGFR2 (P=0.031) and rs2276707 in NR1/2 (P=0.047), whereas OS alone was associated with rs2307424 in NR1/3 (P=0.048) and rs307826 in VEGFR3 (P=0.013).Conclusion:Our results confirm former communications regarding the association between SNPs in ABCB1, NR1/2, NR1/3 and VEGFR3 and sunitinib outcome in clear-cell RCC. Prospective validation of these SNPs is now required. [ABSTRACT FROM AUTHOR]

Two recent papers demonstrate that prolactin plays an important role in the induction and progression of mammary tumours. Retinoids have been shown to be potent inhibitors of breast carcinogenesis. We studied expression of prolactin receptor mRNA in human breast cancer cell lines MCF-7, SKBR-3, T47D and BT-20 treated with and without retinoids using Northern blot and a quantitative polymerase chain reaction (PCR) method. In all cell lines, all-trans- and 9-cis-retinoic acid, as well as the retinoic acid receptor gamma (RAR-gamma) selective agonists CD2325 and CD437 (1 microM), were able to down-regulate prolactin receptor. After 1 h, a significant reduction was detectable and maximal effect was achieved after 24 h of treatment. Pretreatment with retinoic acid also reduced the prolactin-/prolactin receptor-dependent signal transduction and activation of transcription 5 (STAT-5) activation in T47D cells. Cycloheximide failed to abrogate the retinoic acid-induced decline in prolactin receptor mRNA levels, indicating that this effect was not dependent upon continuing protein synthesis. Similarly, no change in the stability of prolactin receptor mRNA was observed during 12 h of retinoic acid treatment. In conclusion, our results demonstrate that retinoids are able to inhibit the expression of prolactin receptor message, which encodes an important growth factor receptor in breast cancer cells. This action could be responsible for the anti-tumour effects of retinoids. [ABSTRACT FROM AUTHOR]