1,265 research outputs found
Binding of TGF- ?1 latency-associated peptide (LAP) to ???6 integrin modulates behaviour of squamous carcinoma cells
No full textThe integrin ?v?6 is not detectable on normal keratinocytes in vivo but expression is increased significantly in oral squamous cell carcinoma where this heterodimer has been shown to play a role in cell migration, invasion and protease expression. Although regarded initially as a fibronectin receptor, ?v?6 may bind to arginine-glycine-aspartic acid sequences in other matrix molecules including tenascin and vitronectin. Interestingly, ?v?6 has also been shown to have high affinity for the TGF-1 latency associated peptide and to participate in the activation of the TGF-1 latent complex. Since TGF-1 is present in squamous carcinomas, it is possible that latency associated peptide may modulate malignant keratinocyte behaviour independently from the classical TGF- signalling pathways through its interaction with integrins. We show here that when latency associated peptide is immobilised onto a surface, it acts as an ?v?6-specific ligand for oral squamous carcinoma cells promoting adhesion and haptotactic migration in addition to ?v?6-dependent increase in pro-MMP-9 expression. In contrast, even very low concentrations of soluble latency associated peptide (0.1 g ml-1) inhibited ?v?6-dependent adhesion, migration and invasion. Thus ?v?6-dependent processes of oral squamous cell carcinoma, is likely to be modulated, not only by the local concentration of latency associated peptide in the stroma, but also whether it is immobilised in the matrix or released as a soluble protein
Still waiting for the smoke to clear - lasers in the treatment of onychomycosis
No full textIn 2009, the first lasers indicated in the treatment of onychomycosis reached the shores of the United Kingdom with the aspirations of being a revolution in the treatment of this common, stubborn nail infection. It has now been five years since their arrival and we have witnessed the emergence of specialist nail clinics offering laser treatments to patients across the country. Despite the revolution on the high street, with large sums of money changing hands for both the purchase of these devices and for treatment, the flow of evidence assessing the lasers real effectiveness has been rather slower to follow. In this article the author discusses the current issues and evidence on lasers in onychomycosis, from a UK perspective
Development of a quantitative method to analyse tumour cell invasion in organotypic culture
No full textTumour invasion is a dynamic process occurring in three dimensions and involving interactions between both tumour and stromal cells. Experimental analysis of squamous carcinoma cell invasion has often used the organotypic gel culture system, which is generated by plating tumour cells on to a synthetic stroma composed of a collagen gel embedded with fibroblasts. Unfortunately, quantitation of invasion in these organotypic gels has relied largely on subjective pathological opinion, which may be influenced by different patterns of tumour cell infiltration. Therefore a computer-assisted digital image analysis system that assesses invasion objectively and provides a numerical 'Invasion Index' was developed. The Invasion Index, by combining depth and pattern of invasion in a single value, establishes a quantitative value that allows assessment of the influences of positive and negative regulation of tumour invasion. These data demonstrate that the organotypic gel system is a robust, accurate, and reproducible method for measuring tumour cell invasion. They also show that the Invasion Index can be used after organotypic gels have been implanted in mice for up to 6 weeks. Illustrative examples of how various factors influence the invasion of squamous carcinoma cells in three dimensions both in vitro and in vivo are provided
High resolution in vivo imaging of breast cancer by targeting the pro-invasive integrin alphabeta6.
No full textTinea pedis: diagnosis and management
No full textDermatophyte onychomycosis is a common condition, particularly in the elderly and immunosuppressed. As these sections of the population are set to increase, it is likely that the prevalence of dermatophytic nail infection will also increase. Advances in antifungal therapy, with the introduction of newer and safer drugs such as terbinafine and itraconazole, have improved out-comes significantly. However, around a quarter of patients will suffer reinfection or recurrence in the subsequent months. The possible reasons for this are considered. Data from recently published studies have demonstrated an increased mycological and clinical cure rate using a combination of topical and oral antifungal agents. This approach may be a cost-effective means of improving outcomes for patients with more resistant nail disease
POLARIZATION BEHAVIOR OF I.R. DIFFRACTION GRATINGS
No full textAuthor Institution: Bausch and Lomb Inc.Interaction between incident electromagnetic radiation and the regular groove structure of a diffraction grating gives rise to polarization phenomena whenever the groove spacing is less than about 5 times the wave-length. Theory predicts the general behavior but fails to account for some of the details observed experimentally. For many problems in I.R. spectroscopy and T.R. lasers, it is important to be aware of what actually takes place. Special equipment for obtaining data on diffracted energy in both planes of polarization will be described and results typical of commonly used gratings will be compared with theory
A tropism-modified, CAR-detargeted Ad5 vector which displays reduced hepatotropism and an optimal profile has an improved therapeutic index compared with Ad5
No full textPsoriasin (S100A7) associates with integrin ?6 subunit and is required for ?v?6-dependent carcinoma cell invasion
No full textExpression of the integrin ?v?6 is upregulated in a variety of carcinomas where it appears to be involved in malignant progression, although the biology of this integrin is not fully explored. We have generated oral carcinoma cells that express ?v?6 composed of wild-type ?v and a mutant ?6 that lacks the unique C-terminal 11 amino acids (aa). We found that these residues, although not required for ?v?6-dependent adhesion or migration, are essential for ?v?6-dependent invasive activity. We have used a proteomic approach to identify novel binding partners for the ?6 subunit cytoplasmic tail and report that psoriasin (Psor) (S100A7) bound preferentially to the recombinant ?6 cytoplasmic domain, though not in the absence of the unique C-terminal 11aa. Endogenous cellular Psor co-precipitated with endogenous ?6 and colocalised with ?v?6 at the cell membrane and intracellular vesicles. Knockdown of Psor, with small interfering RNA, had no effect on ?v?6-dependent adhesion or migration but abrogated ?v?6-mediated oral carcinoma cell invasion both in Transwell and, the more physiologically relevant, organotypic invasion assays, recapitulating the behaviour of the ?6-mutant cell line. Membrane-permeant Tat-peptides encoding the unique C-terminal residues of ?6, bound directly to recombinant Psor and inhibited cellular Psor binding to ?6; this blocked ?v?6-dependent, but not ?v?6-independent, invasion. These data identify a novel interaction between Psor and ?6 and demonstrate that it is required for ?v?6-dependent invasion by carcinoma cells. Inhibition of this interaction may represent a novel therapeutic strategy to target carcinoma invasion
BAG-1 expression in human breast cancer: interrelationship between BAG-1 RNA, protein, HSC70 expression and clinico-pathological data
No full textBAG-1 (BCL-2 athanogene-1), a multifunctional protein which associates with steroid hormone receptors (including the oestrogen receptor) and the anti-apoptotic BCL-2 protein, regulates steroid hormone-dependent transcription and apoptosis. Direct interaction with 70 kD heat-shock proteins, HSC70 and HSP70, may mediate the diverse functions of BAG-1. Immunohistochemistry was used to examine the expression of BAG-1 and HSC70 in 160 cases of invasive breast cancer. BAG-1 was expressed in 92% of cases; most tumours exhibited cytoplasmic BAG-1, while a smaller proportion also had nuclear immunostaining. There was a significant inverse correlation between histological grade and nuclear BAG-1 expression, with higher-grade tumours tending to have reduced nuclear BAG-1 expression, but there was no association with cytoplasmic BAG-1. There was also no significant correlation between nuclear or cytoplasmic BAG-1 expression and oestrogen receptor positivity. Since BAG-1 may be influenced by hormonal background, the relationship between grade and oestrogen receptor was examined separately in pre-menopausal and post-menopausal women. The statistically significant correlation between nuclear BAG-1 expression and low tumour grade was strong in pre-menopausal, but not apparent in post-menopausal women. A statistically significant correlation was observed between cytoplasmic, but not nuclear, BAG-1 expression and oestrogen receptor status in pre-menopausal, but not post-menopausal, women. There was no correlation between BAG-1 protein expression and RNA, suggesting that important post-transcriptional mechanisms control BAG-1 expression in vivo. HSC70 was also detected in the majority (97%) of cases, although expression was not correlated with BAG-1 levels, oestrogen receptor status or tumour grade. Overall survival in cases with high levels of nuclear BAG-1 expression was improved, though not significantly. These results are consistent with the hypothesis that BAG-1 plays an important but variable role in breast cancers developing in pre-menopausal and post-menopausal women
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