Epidemiological differences for cutaneous melanoma in a relatively dark-skinned Caucasian population with chronic sun exposure

The aim of this study was to reveal differences in the epidemiology and to identify significant risk factors for cutaneous melanoma (CM) in a relatively dark-skinned, chronically sun-exposed Caucasian population. This group is considered to have a low risk for this tumour. One hundred and ten newly diagnosed patients with primary CM and 110 age- and gender-matched controls, all of Cretan origin, were interviewed and underwent a complete skin examination. Solar keratoses odds ratio (OR) 6.2 and lentigines (OR 2.2), common and atypical naevi (OR 5.4 and 3.0, respectively), blonde or red hair colour (OR 3.1), skin phototypes I/II (OR 1.8), as well as total sun exposure (weeks per year) (OR 1.03), were all significantly associated with CM risk in a multivariate logistic regression analysis. In the relatively dark-skinned Cretan population, sun exposure indices represent the most important risk markers for CM which contrasts with data from fair-skinned Caucasian populations where melanocytic naevi are the main risk factors.     

Prognostic stratification of Dukes B colon cancer by a neoglycoprotein

Disease progression of tumors is accompanied by structural changes of the glycan chains of cellular glycoconjugates. Within the concept of the sugar code the presence of complementary receptors such as lectins translates changes in ligand presentation into biological effects, for example in growth regulation and adhesion. By introducing neoglycoproteins to histopathological colon cancer analysis the questions are addressed as to whether specific binding sites for main N- and O-glycan components are present and whether they harbor potential for prognostic predictions. Synthetic conjugation of fucose, lactose, and mannose derivatives to a carrier protein yielded neoglycoproteins for glycohistochemical analysis. The tumor panel included routinely fixed tissue sections from 67 cancer cases (15 Dukes A, 20 Dukes B, 15 Dukes C, and 17 metastatic tumors) and 6 hepatic metastases as well as 20 normal biopsy specimens as control. Quantitative image analysis determined the labeling index and the mean optical density in each case, separating tumor and peritumoral connective tissue. Specific carbohydrate-dependent binding with inter-individual heterogeneity was observed. The distinct staining profiles were not associated with disease stage or metastasis formation. Strong expression of lactose-binding sites in the peritumoral connective tissue especially in terms of the labeling index was significantly correlated with reduced survival in Dukes B patients (p=0.02). A similar tendency was observed in the Dukes C group. In conclusion, the application of the synthetic markers aimed at lectin detection defines lactose binding as new prognostic marker. It has potential relevance for improving the benefit from adjuvant therapy in Dukes B colorectal cancer patients. Technically, chemical ligand immobilization to an inert carrier can find useful application beyond glycosciences in the quest to extend the panel of tumor markers.     

Embryonic endothelial progenitor cells armed with a suicide gene target hypoxic lung metastases after intravenous delivery

We show that mouse embryonic endothelial progenitor cells (eEPCs) home preferentially to hypoxic lung metastases when administered intravenously. This specificity is inversely related to the degree of perfusion and vascular density in the metastasis and directly related to local levels of hypoxia and VEGF. Ex vivo expanded eEPCs that were genetically modified with a suicide gene specifically and efficiently eradicated lung metastases with scant patent blood vessels. eEPCs do not express MHC I proteins, are resistant to natural killer cell-mediated cytolysis, and can contribute to tumor vessel formation also in nonsyngeneic mice. These results indicate that eEPCs can be used in an allogeneic setting to treat hypoxic metastases that are known to be resistant to conventional therapeutic regimes.     

iNOS promoter variants and severe malaria in Ghanaian children

Nitric oxide is an important mediator in the host defence against Plasmodium falciparum malaria. It has antiparasitic effects in vitro. However, its role in clinical disease remains controversial. Polymorphisms in the inducible nitric oxide synthase promoter (iNOS; -954G-->C, -1173C-->T, -2.6 kb CCTTT(n) microsatellite) may influence susceptibility to and severity of malaria. We tested this hypothesis in a case-control study among Ghanaian children with severe malaria (SM) and asymptomatic parasitaemia, respectively, and in healthy controls. In this study, the respective frequencies of iNOS-954G-->C and -1173C-->T did not differ between groups but > or =13 microsatellite copies were associated with SM. -954G-->C and -1173C-->T were in linkage disequilibrium with CCTTT(8) and CCTTT(13), respectively. -954G-->C/CCTTT(8) protected against hyperparasitaemia whereas -1173C-->T/CCTTT(13) increased fatality. These findings suggest that iNOS promoter haplotypes rather than single nucleotide polymorphisms are associated with malaria in Ghanaian children.     

Global cerebral atrophy in early stages of Huntington's disease: quantitative MRI study

Global brain atrophy was determined in 70 patients suffering from Huntington's disease (HD) and 70 healthy controls, using brain parenchymal fractions calculated from 3D MRI data in a standardized procedure. In HD patients, brain parenchymal fractions were significantly reduced compared to controls in all age groups; the physiological decline with age was less pronounced in HD. However, brain parenchymal fraction values did not allow the prediction of clinical impairment (as assessed by clinical scores). Global brain parenchyma reduction seems to be an early or even constitutional feature of HD, but clinical symptoms appear to reflect regional rather than global atrophy. Overall, MRI-based brain volume quantification correlated with clinical scores clarifies the functional impact of morphological brain alterations.     

Multiple sclerosis -- a coordinated immune attack across the blood brain barrier

Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS). The acquired immune system plays a central role in the pathogenesis of MS although target antigens and effector mechanisms are still poorly defined. Studies in animal models of infectious or autoimmune encephalomyelitis suggest that the acquired immune response targeting the CNS in MS originates from the periphery. Both T and B cells undergo activation and maturation in the lymphoid system allowing them to cross the blood brain barrier and infiltrate CNS tissue. Within the CNS, they require a local proinflammatory milieu contributed by macrophages and microglia to mediate their effector function which ultimately leads to damage of myelin sheath, oligodendrocytes, and neurons. In the current review, we elucidate the role of the immune system in MS with particular emphasis on activation and migration of immune cells to the CNS, the role of CNS cells in the inflammatory process and the contribution of the immune system to damage and repair. Based on these considerations we discuss new strategies to investigate pathogenetic pathways in multiple sclerosis.