Metastatic melanoma has a poor prognosis due to resistance to multiple chemotherapy regimens. The mainstay of treatment remains dacarbazine, with cisplatin being a commonly used alternative. Melanoma displays marked resistance to the DNA-damaging effects of these drugs. Intrinsic and acquired resistance involves multiple cellular pathways of damage recognition, repair and apoptosis. Increased understanding of these pathways is identifying novel targets that it is hoped will make inroads into the treatment of this lethal disease.
Routine measurement of VGCC antibodies in patients without clinical LEMS is unlikely to assist either in management of SCLC or in assessment of prognosis.
A case of type 1 (adult) Gaucher's disease with a late onset tapeto-retinal degeneration and an initially dopamine responsive extrapyramidal syndrome is described. The literature reporting neurological involvement in type 1 Gaucher's disease is reviewed, and it is concluded that the absence of symptoms and signs of nervous system involvement cannot be used as the sole basis for the classification of this type of Gauchers disease.
The matrix metalloproteinase (MMP) family of proteins mediates various cellular pathways, including apoptosis and angiogenesis. Polymorphisms of MMP genes are associated with increased esophageal adenocarcinoma (EAC) risk. Gastroesophageal reflux disease (GERD) is an established EAC risk factor. We examined whether MMP polymorphism-EAC risk is modified by GERD. In total, 309 EAC patients and 279 frequency-matched healthy controls underwent MMP1 1G/2G, MMP3 6A/5A, MMP12 −82A/G and MMP12 1082A/G genotyping. Questionnaires collected GERD history. EAC risk was analyzed using logistic regression, adjusted for key covariates and stratified by GERD. Joint effects models explored GERD severity and duration, whereas additional models explored genotype–GERD interactions in EAC risk. We determined that each MMP1 and MMP3 minor (variant) allele was independently associated with increased EAC risk (adjusted odds ratio (AOR) 3.2, 95% confidence interval (CI) 2.0–5.1, p < 0.001 and AOR 1.8, 95% CI 1.1–2.7, p = 0.01, respectively) only among those with GERD but not in GERD-free individuals (all p = nonsignificant). There were significant interactions between the MMP1 variants and the presence of GERD (p = 0.002) and between MMP3 variants and GERD (p = 0.04). There was an equally strong interaction between cumulative GERD severity and MMP1 (p = 0.002). The AOR of each variant allele was 14.9 (95% CI 1.6–136) for individuals with severe GERD, 1.7 (95% CI 1.0–2.7) for mild-moderate GERD and 0.98 (95% CI 0.7–1.4) for those without GERD. This was further reflected in separate analyses of frequency and duration of GERD. In conclusion, MMP1 1G/2G (and possibly MMP3 6A/5A) polymorphisms alter EAC risk differentially for GERD and GERD-free individuals.
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