Loss of heterozygosity in colorectal cancer

Colorectal cancer (CRC) is one of the most common malignancies in the world. The development and progression of CRC is a multistep process, which involves many dietary and environmental factors. A great number of oncogenes, tumour suppressor genes and DNA repair genes contribute to molecular and biological features of CRC, providing us much essential information about the pathogenesis of this disease. Loss of heterozygosity (LOH) of tumour suppressor genes was observed at various loci ondifferent chromosomes like 1p, 1q, 4q, 5q, 8p, 9q, 11q, 12p, 14q, 15q, 17p, 17q, 18p, 18q and 22q in CRCs. In this review, the loss of heterozygosity in patients with colorectal cancer and the interrelationship between tumour suppressor genes and colorectal cancer initiation and progression are discussed

Production of recombinant human dipeptidyl peptidase IV from SF9 cells in microbial fermenters

The human dipeptidyl peptidase IV (hDPPIV/CD26) is expressed as an immune response in some cancer cells as well as intestine and incretin metabolism, and deficiency of the enzyme leads to metabolic disorders. In the present study, recombinant hDPPIV/CD26 genes were expressed in baculovirus–insect cell systems in a 5-L stirred-tank fermenter. Because of the shear sensitivity of the insect cell line, production from insect cells should be performed in new-generation type bioreactors, which are commonly more expensive than microbial fermenters. To optimize the process, hydrodynamic parameters and oxygen consumption of Sf9 cells at 1.5 L and 3 L were monitored, and a certain amount of serum was added to the production medium to decrease shear and stabilize the growth of insect cells that normally do not need serum addition. In this study, dimensionless numbers and some hydrodynamic parameters were calculated in 1.5 L, and predictions were made for 3 L fermenter volumes. Agitation rates of 60 rpm were determined to protect insect cells against damaging shear stress. Regarding the agitation rate, oxygen mass transfer coefficient (k L a) was 0.0129 min –1 for 1.5 L and was kept constant for 3 L (0.0133 min –1 ). The maximum enzyme activity from microbial fermenters was 2.37-fold higher than activity from T-flask in our previous work. The infection efficiency of transfected cells was 78%–81% in the 1.5-L and 3-L fermenters. © TÜBİTAK

The effect of supersymmetric CP phases on Chargino-Pair Production via Drell-Yan Process at the LHC

We compute the rates for pp annihilation into chargino-pairs via Drell-Yan process taking into account the effects of supersymmetric soft phases, at proton-proton collider. In particular, the phase of the mu parameter gains direct accessibility via the production of dissimilar charginos. The phases of the trilinear soft masses do not have a significant effect on the cross sections.Comment: 24 pages, 7 figure

Improving emerging European NMIs’ capabilities in humidity measurement

The control and measurement of humidity is important for many industrial applications and to ensure the appropriate storage of materials and products. Humidity measurement techniques are diverse and each presents different challenges for use and calibration for a range of pressures and gases. Over the past few years, the development of humidity sensors and apparatus has matured to a level where traceable calibration is beneficial to all industries in which humidity and moisture measurement and control are important. This paper deals with a European project in which the overall objective is to develop or extend the measurement and research capabilities of the participating emerging NMI/DIs’ countries in the field of humidity measurements, where access to these types of facilities is currently limited

Levels of selected minerals, nitric oxide, and vitamins in aborted Sakis sheep raised under semitropical conditions

The serum levels of calcium, phosphorus, magnesium, copper, zinc and iron and of nitric oxide, retinol, and β-carotene were determined in Sakiz ewes that had experienced an abortion and in healthy controls. Ten healthy and 25 aborted Sakiz sheep were selected from Afyon zone in western Turkey. Their ages ranged between 2 and 4 years weighing between 40 and 60 kg at the time of experiment. All of the abortions occurred in October. The concentrations of retinol, β-carotene, phosphorus, and zinc were significantly lower and those of calcium and nitric oxide were increased in aborted ewes relative to healthy controls. The serum levels of iron, copper, and magnesium were not significantly different among the two groups. In conclusion, abortion is an important problem in commercially important species of ruminants in many regions in the tropics including of western Turkey. Deficiencies of retinol, β-carotene, phosphorus and zinc, and the increase of calcium and nitric oxide concentration may play an important role in the etiology of abortion in ewes. Prophylactic measures such as vitamin and mineral supplementation may be of help to prevent or reduce the incidence of abortion in sheep

Can computer-aided diagnosis assist in the identification of prostate cancer on prostate MRI? a multi-center, multi-reader investigation.

For prostate cancer detection on prostate multiparametric MRI (mpMRI), the Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2) and computer-aided diagnosis (CAD) systems aim to widely improve standardization across radiologists and centers. Our goal was to evaluate CAD assistance in prostate cancer detection compared with conventional mpMRI interpretation in a diverse dataset acquired from five institutions tested by nine readers of varying experience levels, in total representing 14 globally spread institutions. Index lesion sensitivities of mpMRI-alone were 79% (whole prostate (WP)), 84% (peripheral zone (PZ)), 71% (transition zone (TZ)), similar to CAD at 76% (WP, p=0.39), 77% (PZ, p=0.07), 79% (TZ, p=0.15). Greatest CAD benefit was in TZ for moderately-experienced readers at PI-RADSv2 <3 (84% vs mpMRI-alone 67%, p=0.055). Detection agreement was unchanged but CAD-assisted read times improved (4.6 vs 3.4 minutes, p<0.001). At PI-RADSv2 ≥ 3, CAD improved patient-level specificity (72%) compared to mpMRI-alone (45%, p<0.001). PI-RADSv2 and CAD-assisted mpMRI interpretations have similar sensitivities across multiple sites and readers while CAD has potential to improve specificity and moderately-experienced radiologists' detection of more difficult tumors in the center of the gland. The multi-institutional evidence provided is essential to future prostate MRI and CAD development

Spermatogonial stem cell sensitivity to capsaicin: An in vitro study

<p>Abstract</p> <p>Background</p> <p>Conflicting reports have been published on the sensitivity of spermatogenesis to capsaicin (CAP), the pungent ingredient of hot chili peppers. Here, the effect of CAP on germ cell survival was investigated by using two testis germ cell lines as a model. As CAP is a potent agonist of the transient receptor potential vanilloid receptor 1 (TRPV1) and no information was available of its expression in germ cells, we also studied the presence of TRPV1 in the cultured cells and in germ cells in situ.</p> <p>Methods</p> <p>The rat spermatogonial stem cell lines Gc-5spg and Gc-6spg were used to study the effects of different concentrations of CAP during 24 and 48 h. The response to CAP was first monitored by phase-contrast microscopy. As germ cells appear to undergo apoptosis in the presence of CAP, the activation of caspase 3 was studied using an anti activated caspase 3 antibody or by quantifying the amount of cells with DNA fragmentation using flow cytometry. Immunolocalization was done with an anti-TRPV1 antibody either with the use of confocal microscopy to follow live cell labeling (germ cells) or on Bouin fixed paraffin embedded testicular tissues. The expression of TRPV1 by the cell lines and germ cells was confirmed by Western blots.</p> <p>Results</p> <p>Initial morphological observations indicated that CAP at concentrations ranging from 150 uM to 250 uM and after 24 and 48 h of exposure, had deleterious apoptotic-like effects on both cell lines: A large population of the CAP treated cell cultures showed signs of DNA fragmentation and caspase 3 activation. Quantification of the effect demonstrated a significant effect of CAP with doses of 150 uM in the Gc-5spg cell line and 200 uM in the Gc-6spg cell line, after 24 h of exposure. The effect was dose and time dependent in both cell lines. TRPV1, the receptor for CAP, was found to be expressed by the spermatogonial stem cells in vitro and also by premeiotic germ cells in situ.</p> <p>Conclusion</p> <p>CAP adversely affects spermatogonial survival in vitro by inducing apoptosis to those cells and TRPV-1, a CAP receptor, may be involved in this effect as this receptor is expressed by mitotic germ cells.</p

The exchangeability of shape

<p>Abstract</p> <p>Background</p> <p>Landmark based geometric morphometrics (GM) allows the quantitative comparison of organismal shapes. When applied to systematics, it is able to score shape changes which often are undetectable by traditional morphological studies and even by classical morphometric approaches. It has thus become a fast and low cost candidate to identify cryptic species. Due to inherent mathematical properties, shape variables derived from one set of coordinates cannot be compared with shape variables derived from another set. Raw coordinates which produce these shape variables could be used for data exchange, however they contain measurement error. The latter may represent a significant obstacle when the objective is to distinguish very similar species.</p> <p>Results</p> <p>We show here that a single user derived dataset produces much less classification error than a multiple one. The question then becomes how to circumvent the lack of exchangeability of shape variables while preserving a single user dataset. A solution to this question could lead to the creation of a relatively fast and inexpensive systematic tool adapted for the recognition of cryptic species.</p> <p>Conclusions</p> <p>To preserve both exchangeability of shape and a single user derived dataset, our suggestion is to create a free access bank of reference images from which one can produce raw coordinates and use them for comparison with external specimens. Thus, we propose an alternative geometric descriptive system that separates 2-D data gathering and analyzes.</p

Radiogenomics of clear cell renal cell carcinoma: preliminary findings of The Cancer Genome Atlas–Renal Cell Carcinoma (TCGA–RCC) Imaging Research Group

Purpose: To investigate associations between imaging features and mutational status of clear cell renal cell carcinoma (ccRCC). Materials and methods: This multi-institutional, multi-reader study included 103 patients (77 men; median age 59 years, range 34–79) with ccRCC examined with CT in 81 patients, MRI in 19, and both CT and MRI in three; images were downloaded from The Cancer Imaging Archive, an NCI-funded project for genome-mapping and analyses. Imaging features [size (mm), margin (well-defined or ill-defined), composition (solid or cystic), necrosis (for solid tumors: 0%, 1%–33%, 34%–66% or >66%), growth pattern (endophytic, <50% exophytic, or ≥50% exophytic), and calcification (present, absent, or indeterminate)] were reviewed independently by three readers blinded to mutational data. The association of imaging features with mutational status (VHL, BAP1, PBRM1, SETD2, KDM5C, and MUC4) was assessed. Results: Median tumor size was 49 mm (range 14–162 mm), 73 (71%) tumors had well-defined margins, 98 (95%) tumors were solid, 95 (92%) showed presence of necrosis, 46 (45%) had ≥50% exophytic component, and 18 (19.8%) had calcification. VHL (n = 52) and PBRM1 (n = 24) were the most common mutations. BAP1 mutation was associated with ill-defined margin and presence of calcification (p = 0.02 and 0.002, respectively, Pearson’s χ2 test); MUC4 mutation was associated with an exophytic growth pattern (p = 0.002, Mann–Whitney U test). Conclusions: BAP1 mutation was associated with ill-defined tumor margins and presence of calcification; MUC4 mutation was associated with exophytic growth. Given the known prognostic implications of BAP1 and MUC4 mutations, these results support using radiogenomics to aid in prognostication and management