Anticarcinogenic effects of halofuginone on lung‐derived cancer cells

Malignant mesothelioma is a rare but aggressive form of malignancy, which is difficult to diagnose and is resistant to current chemotherapeutic treatment options. Molecular techniques have been used to investigate the mechanisms of action and the beneficial therapeutic effects of halofuginone (HF) in several cancers but not malignant mesotheliomas. In this study, the antiproliferative and apoptotic effects of HF were investigated through its ability to deregulate EGFR downstream signalling cascade proteins in the pathologically aggressive malignant mesothelioma and non‐small‐cell lung cancer cells. We showed that administration of HF at nanomolar concentrations induced a dose‐dependent reduction in the viability of cancer cells, made cell cycle arrest, inhibited proliferation of cancer cells via STAT3 and ERK1/2 pathways and triggered the apoptotic cascade via p38MAPK. We demonstrated that the apoptotic cell death mechanism was mediated by enhanced activation of caspase‐3 and concomitant PARP cleavage, downregulation of Bcl‐2 and upregulation of Bax in both malignant mesothelioma and lung cancer cells. In particular, we demonstrated that cancer cells were more sensitive to HF treatment than normal mesothelial cells. Taken together, this study suggests that HF exerts its anticancer effects in lung‐derived cancers by targeting signal transduction pathways mainly through deregulation of ERK1/2, STAT3 and p38MAPK to reduce cancer cell viability, induce cell cycle arrest and apoptotic cell death. Thus, HF might be considered as a potential agent against malignant mesothelioma and/or lung cancer cells.     

Improved nitrogen nutrition enhances root uptake, root-to-shoot translocation and remobilization of zinc ((65) Zn) in wheat

This study focussed on the effect of increasing nitrogen (N) supply on root uptake and root-to-shoot translocation of zinc (Zn) as well as retranslocation of foliar-applied Zn in durum wheat (Triticum durum). Nutrient solution experiments were conducted to examine the root uptake and root-to-shoot translocation of (65) Zn in seedlings precultured with different N supplies. In additional experiments, the effect of varied N nutrition on retranslocation of foliar-applied (65) Zn was tested at both the vegetative and generative stages. When N supply was increased, the (65) Zn uptake by roots was enhanced by up to threefold and the (65) Zn translocation from roots to shoots increased by up to eightfold, while plant growth was affected to a much smaller degree. Retranslocation of (65) Zn from old into young leaves and from flag leaves to grains also showed marked positive responses to increasing N supply. The results demonstrate that the N-nutritional status of wheat affects major steps in the route of Zn from the growth medium to the grain, including its uptake, xylem transport and remobilization via phloem. Thus, N is a critical player in the uptake and accumulation of Zn in plants, which deserves special attention in biofortification of food crops with Zn.     

Studies on the antioxidant activities of some new chromone compounds

Recent reviews evidence that the naturally occurring compounds containing the chromone skeleton exhibit antiradical activities, providing protection against oxidative stress. The antioxidant activities of 13 new synthesized chromonyl‐2,4‐thiazolidinediones, chromonyl‐2,4‐imidazolidinediones and chromonyl‐2‐thioxoimidzolidine‐4‐ones were evaluated using in vitro antioxidant assays, including superoxide anion radical (), hydroxyl radical (), 2,2‐diphenyl‐1‐picryl‐hydrazyl free radical (DPPH^?) scavenging capacity and total antioxidant capacity ferric ion reducing activity. Superoxide anion radical was produced using potassium superoxide/18‐crown‐6‐ether dissolved in dimethylsulfoxide, and the Fenton‐like reaction (Fe(II) + H₂O₂) was a generator of hydroxyl radicals. Chemiluminescence, spectrophotometry, electron paramagnetic resonance (EPR) and 5,5‐dimethyl‐1‐pyrroline‐N‐oxide (DMPO) as the spin trap were the measurement techniques. The results showed that the majority of the chromone derivatives tested showed a strong scavenging effect towards free radicals, similar to the chemiluminescence reaction with superoxide anion radical with a high activity, inhibition of the DMPO‐OOH radical EPR signal (24–58%), the DMPO‐OH radical EPR signal (4–75%) and DPPH radical EPR signal (6–100%) at 1 mmol/L. Several of the examined compounds exhibited the high reduction potentials. The results obtained show that the new synthesized chromone derivatives may directly scavenger reactive oxygen species and thus may play a protective role against oxidative damage. Copyright © 2014 John Wiley & Sons, Ltd.     

Lysostaphin-Coated Titan-Implants Preventing Localized Osteitis by Staphylococcus aureus in a Mouse Model

The increasing incidence of implant-associated infections induced by Staphylococcus aureus (SA) in combination with growing resistance to conventional antibiotics requires novel therapeutic strategies. In the current study we present the first application of the biofilm-penetrating antimicrobial peptide lysostaphin in the context of bone infections. In a standardized implant-associated bone infection model in mice beta-irradiated lysostaphin-coated titanium plates were compared with uncoated plates. Coating of the implant was established with a poly(D,L)-lactide matrix (PDLLA) comprising lysostaphin formulated in a stabilizing and protecting solution (SPS). All mice were osteotomized and infected with a defined count of SA. Fractures were fixed with lysostaphin-coated locking plates. Plates uncoated or PDLLA-coated served as controls. All mice underwent debridement and lavage on Days 7, 14, 28 to determine the bacterial load and local immune reaction. Fracture healing was quantified by conventional radiography. On Day 7 bacterial growth in the lavages of mice with lysostaphin-coated plates showed a significantly lower count to the control groups. Moreover, in the lysostaphin-coated plate groups complete fracture healing were observed on Day 28. The fracture consolidation was accompanied by a diminished local immune reaction. However, control groups developed an osteitis with lysis or destruction of the bone and an evident local immune response. The presented approach of terminally sterilized lysostaphin-coated implants appears to be a promising therapeutic approach for low grade infection or as prophylactic strategy in high risk fracture care e.g. after severe open fractures.     

A Laboratory Prognostic Index Model for Patients with Advanced Non-Small Cell Lung Cancer

Purpose

We aimed to establish a laboratory prognostic index (LPI) in advanced non-small cell lung cancer (NSCLC) patients based on hematologic and biochemical parameters and to analyze the predictive value of LPI on NSCLC survival.

Patients and Methods

The study retrospectively reviewed 462 patients with advanced NSCLC diagnosed between 2000 and 2010 in a single institution. We developed an LPI that included serum levels of white blood cells (WBC), lactate dehydrogenase (LDH), albumin, calcium, and alkaline phosphatase (ALP), based on the results of a Cox regression analysis. The patients were classified into 3 LPI groups as follows: LPI 0: normal; LPI 1: one abnormal laboratory finding; and LPI 2: at least 2 abnormal laboratory findings.

Results

The median follow up period was 44 months; the median overall survival (OS) and median progression-free survival (PFS) were 11 and 6 months, respectively. A multivariate analysis revealed that the following could be used as independent prognostic factors: an Eastern Cooperative Oncology Group performance status score (ECOG PS) ≥2, a high LDH level, serum albumin <3 g/dL, serum calcium>10.5 g/dL, number of metastases>2, presence of liver metastases, malignant pleural effusion, or receiving chemotherapy ≥4 cycles. The 1-year OS rates according to LPI 0, LPI 1, and LPI 2 were 54%, 34%, and 17% (p<0.001), respectively and 6-month PFS rates were 44%, 27%, and 15% (p<0.001), respectively. The LPI was a significant predictor for OS (Hazard Ratio (HR): 1.41; 1.05–1.88, p<0.001) and PFS (HR: 1.48; 1.14–1.93, p<0.001).

Conclusion

An LPI is an inexpensive, easily accessible and independent prognostic index for advanced NSCLC and may be helpful in making individualized treatment plans and predicting survival rates when combined with clinical parameters.     

Localization of pan-cadherin immunoreactivity in adult rat tissues

Cadherins, being responsible for selective cell recognition and normal tissue integrity in adults, regulate morphogenesis in a variety of organs during development. In this study, anti-rat pan-cadherin antibody, specific to all subgroups of the cadherin family, was used to map the distribution of the pan-cadherin immunoreactivity in adult rat organs. Pan-cadherin immunoreactivity positive tissues were: secretory cells of the adenohypophysis, autonomic nerve, corneal epithelium, oesophageal nerve plexus, stomach and pyloric glandular cells, epithelium of the ileum and its nerve plexus, alveolar cells of the lung, proximal convoluted tubules of the kidney, islet cells of Langerhans, and the acinar cells of the exocrine pancreas. For the first time, positive pan-cadherin immunoreactivity was demonstrated in the epithelial cells of the corpus ciliaris and in the nerve plexus of corpus cavernosum of the penis. In conclusion, our results suggest that cells in many tissues and organs of the adult rat synthesize cadherins.     

Marker utility of miniature inverted-repeat transposable elements for wheat biodiversity and evolution

Transposable elements (TEs) account for up to 80% of the wheat genome and are considered one of the main drivers of wheat genome evolution. However, the contribution of TEs to the divergence and evolution of wheat genomes is not fully understood. In this study, we have developed 55 miniature inverted-repeat transposable element (MITE) markers that are based on the presence/absence of an element, with over 60% of these 55 MITE insertions associated with wheat genes. We then applied these markers to assess genetic diversity among Triticum and Aegilops species, including diploid (AA, BB and DD genomes), tetraploid (BBAA genome) and hexaploid (BBAADD genome) species. While 18.2% of the MITE markers showed similar insertions in all species indicating that those are fossil insertions, 81.8% of the markers showed polymorphic insertions among species, subspecies, and accessions. Furthermore, a phylogenetic analysis based on MITE markers revealed that species were clustered based on genus, genome composition, and ploidy level, while 47.13% genetic divergence was observed between the two main clusters, diploids versus polyploids. In addition, we provide evidence for MITE dynamics in wild emmer populations. The use of MITEs as evolutionary markers might shed more light on the origin of the B-genome of polyploid wheat.     

Immunohistochemical characterization of perineal melanoma in Kilis goats

We describe the clinical, histopathological and immunohistochemical features of the malignant melanomas in the perineal regions of Kilis goats from Sanliurfa province in Turkey. We studied 13 female Kilis goats between 3 and 8 years old that were brought to Harran University Veterinary School, Department of Surgery, between 2002 and 2010. By macroscopic examination, the masses were determined to have elastic consistency, dark brown-black color, necrotic surfaces and ulceration. Microscopically, pleomorphic cells were observed under the basal layer and these advanced toward the dermis. These cells were polyhedral, round or spindle-shaped, anaplastic, and their cytoplasm contained varying amounts of dark brown-black pigments. Immunohistochemical staining was obtained with anti-melan A, vimentin and S100 antibodies.     

The outcome of twin pregnancies complicated by single fetal death after 20 weeks of gestation.

A retrospective study involving 972 twin births was conducted to evaluate the maternal and fetal outcomes of twin pregnancies complicated by single fetal death. The incidence of single fetal death in twin pregnancies after 20 weeks was 3.3%. Preterm birth rates for 37 and 32 gestational weeks were 81.3% and 41.6% respectively. The median interval between the diagnosis of fetal death and the delivery was 11 days (range 1-27 days). Eighteen (56%) infants were delivered by cesarean and 14 (43%) vaginally. Twin-twin transfusion syndrome (TTTS) was the cause of single fetal death in 8 of 32 twin pregnancies (25%). Ten of the surviving co-twins were lost in the neonatal period (31.3%) and half of those neonatal deaths were due to TTTS. TTTS is the major contributor for perinatal mortality in same-sex twins complicated by single fetal death. The death of one twin in utero should not be the only indication for preterm delivery, and in case of severe prematurity with a stable intrauterine environment; expectant management may be advisable until fetal lung maturation ensues.     

Natural history of 11 cases of twin-twin transfusion syndrome without intervention.

The natural history of 11 cases of twin-twin transfusion syndrome (TTTS) in monochorionic diamniotic (MCDA) twin pregnancies has been reviewed. Seven cases before 28 weeks and four pregnancies after 28 weeks had been followed up without intervention. Eight cases had premature uterine contractions. All seven pregnancies before 28 weeks aborted, leading to a 100% mortality rate. After 28 weeks all mothers delivered live births. The diagnosis of TTTS before 28 weeks, and with premature uterine contraction, seems to be a poor prognostic sign.