Melanoma: Martin L

Coit DG, Andtbacka R, Bichakjian CK, Dilawari RA, Dimaio D, Guild V, Halpern AC, Hodi FS, Kashani-Sabet M, Lange JR, Lind A, Martin L, Martini MC, Pruitt SK, Ross MI, Sener SF, Swetter SM, Tanabe KK, Thompson JA, Trisal V, Urist MM, Weber J, Wong MK, Anonymous00048. · No affiliation provided · J Natl Compr Canc Netw. · Pubmed #19401060 No free full text.

This publication has no abstract.

Gilmore BF, Lynas JF, Scott CJ, McGoohan C, Martin L, Walker B. · School of Pharmacy, Queens University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK. · Biochem Biophys Res Commun. · Pubmed #16769036 No free full text.

Abstract: Dipeptidyl peptidase IV (DPP-IV) and seprase belong to a small group of membrane-bound, proline-specific serine proteases, the serine integral membrane proteases (SIMPs). Whilst DPP-IV is the most exhaustively studied peptidase in this class, relatively less is known about the inhibitor/substrate specificity of its close homolog seprase. Additionally, whereas, DPP-IV expression is largely ubiquitous, seprase expression is restricted to tumour and tissue remodelling sites in vivo. Consequently, the highly restricted expression and distribution of seprase potentially make it an excellent therapeutic target for the modulation of neoplastic invasion and metastasis. Against this background, we now wish to report on the design, synthesis, and kinetic testing of a series of dipeptide proline diphenyl phosphonates, against DPP-IV and seprase. The most potent inhibitor of DPP-IV and seprase was found to be Gly-ProP(OPh)2, which exhibited overall second-order rate constants of inactivation of 5.24 x 105 M-1 min-1 and 1.06 x 104 M-1 min-1 against DPP-IV and seprase, respectively. Both proteases displayed differing profiles of susceptibility towards the other members of the series of inhibitors synthesised. In addition, Gly-ProP(OPh)2 and Tyr-ProP(OPh)2 were found to exert a considerable, dose-dependent anti-invasive effect on the LOX melanoma cell line, in vitro.

Gallus S, Naldi L, Martin L, Martinelli M, La Vecchia C, Anonymous00030. · Mario Negri Institute of Pharmacological Research, Milan, Italy. · Melanoma Res. · Pubmed #16432461 No free full text.

Abstract: Several studies have investigated the effect of various anthropometric factors on the risk of cutaneous malignant melanoma (CMM). As the results are controversial, we analysed this issue in a case-control study conducted in Italy. The roles of several body size measures were investigated in a hospital-based case-control study of CMM conducted in Italy. The cases were 542 patients with CMM and the controls were 538 subjects admitted to the same hospitals as the cases for non-dermatological and non-neoplastic diseases. The odds ratios for the highest versus the lowest quartile were 2.06 [95% confidence interval (CI), 1.39-3.05] for weight, 1.16 (95% CI, 0.80-1.68) for height, 1.90 (95% CI, 1.28-2.80) for the body mass index (BMI) and 1.87 (95% CI, 1.28-2.72) for the body surface area (BSA). When allowing for BMI and BSA in the same model, the odds ratios were 1.55 (95% CI, 0.92-2.62) for BMI and 1.41 (95% CI, 0.85-2.33) for BSA. The present findings confirm that obesity increases the risk of CMM. BSA is also related to the risk of CMM. In terms of the population attributable risk, overweight and obesity would account for 31% of the cases of CMM in this Italian population, indicating the scope of prevention.

Binley K, Askham Z, Martin L, Spearman H, Day D, Kingsman S, Naylor S. · Oxford BioMedica (UK) Ltd, Medawar Centre, Oxford Science Park, Oxford, UK. · Gene Ther. · Pubmed #12646859 No free full text.

Abstract: Hypoxia is a common physiological feature of tumours. It activates a signalling cascade that culminates in the stabilization of the HIF-1 transcription factor and activation of genes that possess a hypoxia response element (HRE). We have used an optimized hypoxia responsive promoter (OBHRE) to investigate hypoxia-targeted gene expression in vivo in the context of an adenovirus vector. The OBHRE promoter showed limited activity in the liver or spleen such that expression was 1000-fold lower than that driven by the strong CMV/IE promoter. However, in the context of the tumour microenvironment, the OBHRE promoter achieved expression levels comparable to that of the CMV/IE promoter. Next, we showed that an adenovirus expressing the human cytochrome P450 (CYP2B6) regulated by the OBHRE promoter delays tumour growth in response to the prodrug cyclophosphamide (CPA). Finally, we exploited the hepatotropism of adenovirus to investigate whether the OBHRE promoter could mitigate the hepatotoxicity of a recombinant adenovirus expressing thymidine kinase (TK) in the context of the prodrug ganciclovir (GCV). High-dose Ad.CMVTK/GCV treatment caused significant liver necrosis whereas the same dose of Ad.HRETK was well tolerated. These in vivo data demonstrate that hypoxia-targeted gene expression via the OBHRE promoter can be used to increase the therapeutic window of cytotoxic cancer gene therapy.