Immunoglobulin free light chains are biomarkers of poor prognosis in basal-like breast cancer and are potential targets in tumor-associated inflammation

Inflammation is an important component of various cancers and its inflammatory cells and mediators have been shown to have prognostic potential. Tumor-infiltrating mast cells can promote tumor growth and angiogenesis, but the mechanism of mast cell activation is unclear. In earlier studies, we demonstrated that immunoglobulin free light chains (FLC) can trigger mast cells in an antigen-specific manner. Increased expression of FLC was observed within stroma of various human cancers including those of breast, colon, lung, pancreas, kidney and skin, and FLC expression co-localized with areas of mast cell infiltration. In a large cohort of breast cancer patients, FLC expression was shown associated with basal-like cancers with an aggressive phenotype. Moreover, lambda FLC was found expressed in areas of inflammatory infiltration and its expression was significantly associated with poor clinical outcome. Functional importance of FLCs was shown in a murine B16F10 melanoma model, where inhibition of FLC-mediated mast cell activation strongly reduced tumor growth. Collectively, this study identifies FLCs as a ligand in the pro-tumorigenic activation of mast cells. Blocking this pathway may open new avenues for the inhibition of tumor growth, while immunohistochemical staining of FLC may be helpful in the diagnosis and prognosis of cancer

Overexpression of Cystathionine gamma-Lyase Suppresses Detrimental Effects of Spinocerebellar Ataxia Type 3

Spinocerebellar ataxia type 3 (SCA3) is a polyglutamine (polyQ) disorder caused by a CAG repeat expansion in the ataxin-3 (ATXN3) gene resulting in toxic protein aggregation. Inflammation and oxidative stress are considered secondary factors contributing to the progression of this neurodegenerative disease. There is no cure that halts or reverses the progressive neurodegeneration of SCA3. Here we show that overexpression of cystathionine.-lyase, a central enzyme in cysteine metabolism, is protective in a Drosophila model for SCA3. SCA3 flies show eye degeneration, increased oxidative stress, insoluble protein aggregates, reduced levels of protein persulfidation and increased activation of the innate immune response. Overexpression of Drosophila cystathionine.-lyase restores protein persulfidation, decreases oxidative stress, dampens the immune response and improves SCA3-associated tissue degeneration. Levels of insoluble protein aggregates are not altered; therefore, the data implicate a modifying role of cystathionine.-lyase in ameliorating the downstream consequence of protein aggregation leading to protection against SCA3-induced tissue degeneration. The cystathionine.-lyase expression is decreased in affected brain tissue of SCA3 patients, suggesting that enhancers of cystathionine.-lyase expression or activity are attractive candidates for future therapies

Non-AIDS defining cancers in the D:A:D Study-time trends and predictors of survival : a cohort study

BACKGROUND:Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.METHODS:Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.RESULTS:Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.CONCLUSIONS:The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC

RCo5-H and related systems

Applied Science

Integration of digital dental casts in cone-beam computed tomography scans

Contains fulltext : 108380.pdf (publisher's version ) (Open Access)Cone-beam computed tomography (CBCT) is widely used in maxillofacial surgery. The CBCT image of the dental arches, however, is of insufficient quality to use in digital planning of orthognathic surgery. Several authors have described methods to integrate digital dental casts into CBCT scans, but all reported methods have drawbacks. The aim of this feasibility study is to present a new simplified method to integrate digital dental casts into CBCT scans. In a patient scheduled for orthognathic surgery, titanium markers were glued to the gingiva. Next, a CBCT scan and dental impressions were made. During the impression-taking procedure, the titanium markers were transferred to the impression. The impressions were scanned, and all CBCT datasets were exported in DICOM format. The two datasets were matched, and the dentition derived from the scanned impressions was transferred to the CBCT of the patient. After matching the two datasets, the average distance between the corresponding markers was 0.1 mm. This novel method allows for the integration of digital dental casts into CBCT scans, overcoming problems such as unwanted extra radiation exposure, distortion of soft tissues due to the use of bite jigs, and time-consuming digital data handling

Integration of digital dental casts in cone beam computed tomography scans-a clinical validation study

Contains fulltext : 190129.pdf (publisher's version ) (Open Access

Mucoraceous moulds involved in the commercial fermentation of Sufu Pehtze

Sufu is a fermented cheese-like soybean product in China and Vietnam, obtained by fungal solid-state fermentation of soybean curd (tofu), which results in moulded tofu or 'pehtze'. The final product sufu is obtained by maturing pehtze in a brine containing alcohol and salt during a period of several months. The present report deals with the identity and phylogenetic relationships of mould starter cultures used for the preparation of pehtze. Starter cultures used in commercial pehtze fermentation were obtained from factories located in several provinces of China and Vietnam, isolated from their pehtze and some were obtained from culture collections. They were identified as Actinomucor repens, Actinomucor taiwanensis, Mucor circinelloides, Mocur hiemalis, Mocur racemosus, and Rhizopus microsporus var. microsporus. Phylogenetic relations based on sequencing of genomic DNA of these starters and of relevant control strains from collections indicate that the genera Mucor, Actinomucor and Rhizopus form distinct and homogenous clusters, with Mucor and Actinomucor showing a slightly closer relationship with each other than with Rhizopus