Advanced therapeutic modalities in hepatocellular carcinoma: Novel insights

Hepatocellular carcinoma (HCC), the most common type of liver cancer, is usually a latent and asymptomatic malignancy caused by different aetiologies, which is a result of various aberrant molecular heterogeneity and often diagnosed at advanced stages. The incidence and prevalence have significantly increased because of sedentary lifestyle, diabetes, chronic infection with hepatotropic viruses and exposure to aflatoxins. Due to advanced intra- or extrahepatic metastasis, recurrence is very common even after radical resection. In this paper, we highlighted novel therapeutic modalities, such as molecular-targeted therapies, targeted radionuclide therapies and epigenetic modification-based therapies. These topics are trending headlines and their combination with cell-based immunotherapies, and gene therapy has provided promising prospects for the future of HCC treatment. Moreover, a comprehensive overview of current and advanced therapeutic approaches is discussed and the advantages and limitations of each strategy are described. Finally, very recent and approved novel combined therapies and their promising results in HCC treatment have been introduced.     

Cadmium Tolerance and Accumulation in Indian Mustard Is Enhanced by Overexpressing γ-Glutamylcysteine Synthetase

To investigate rate-limiting factors for glutathione and phytochelatin (PC) production and the importance of these compounds for heavy metal tolerance, Indian mustard (Brassica juncea) was genetically engineered to overexpress the Escherichia coli gshI gene encoding γ-glutamylcysteine synthetase (γ-ECS), targeted to the plastids. The γ-ECS transgenic seedlings showed increased tolerance to Cd and had higher concentrations of PCs, γ-GluCys, glutathione, and total non-protein thiols compared with wild-type (WT) seedlings. When tested in a hydroponic system, γ-ECS mature plants accumulated more Cd than WT plants: shoot Cd concentrations were 40% to 90% higher. In spite of their higher tissue Cd concentration, the γ-ECS plants grew better in the presence of Cd than WT. We conclude that overexpression of γ-ECS increases biosynthesis of glutathione and PCs, which in turn enhances Cd tolerance and accumulation. Thus, overexpression of γ-ECS appears to be a promising strategy for the production of plants with superior heavy metal phytoremediation capacity.     

Polyamine deficiency alters EGF receptor distribution and signaling effectiveness in IEC-6 cells

Cell growth andmigration are essential processes for the differentiation, maintenance,and repair of the intestinal epithelium. Epidermal growth factor (EGF)is an important factor in the reorganization of the cytoskeletonrequired for both processes. Because we had previously foundsignificant changes in the cytoskeleton during polyamine deficiency, itwas of interest to know whether those changes could prevent EGF fromstimulating growth and migration. Polyamine biosynthesis in IEC-6 cellswas interrupted by treatment with -difluoromethylornithine (DFMO), aspecific inhibitor of ornithine decarboxylase, the primaryrate-limiting enzyme of polyamine biosynthesis. DFMO halted cellproliferation and inhibited cell migration, and neither function couldbe normally stimulated by EGF. Immunocytochemistry of the transferrinreceptor (used as a marker for the endocytic pathway) revealed anabnormal distribution of the EGF receptor (EGFR) 10 min after bindingEGF. Polyamine deficiency depleted the cells of interiormicrofilaments, thickened the actin cortex, and prevented the promptassociation of EGF-bound EGFR with actin. EGF-stimulated 170-kDaprotein tyrosine phosphorylation and the kinase activity of purifiedmembrane EGFR were reduced by 50%. Immunoprecipatated EGFR proteinconcentration, however, was not reduced by polyamine deficiency. All ofthese changes could be prevented by supplementation with putrescine.Cytoskeletal disruption, reduced EGFR phosphorylation and kinaseactivity, aberrant intracellular EGFR distribution, and delayedassociation with actin filaments suggest a partial explanation for thedependence of epithelial cell growth and migration on polyamines.

     

A survey of scale insects in soil samples from Europe (Hemiptera,Coccomorpha)

In the last decades, several expeditions were organized in Europe by the researchers of the Hungarian Natural History Museum to collect snails, aquatic insects and soil animals (mites, springtails, nematodes, and earthworms). In this study, scale insect (Hemiptera: Coccomorpha) specimens extracted from Hungarian Natural History Museum soil samples (2970 samples in total), all of which were collected using soil and litter sampling devices, and extracted by Berlese funnel, were examined. From these samples, 43 scale insect species (Acanthococcidae 4, Coccidae 2, Micrococcidae 1, Ortheziidae 7, Pseudococcidae 21, Putoidae 1 and Rhizoecidae 7) were found in 16 European countries. In addition, a new species belonging to the family Pseudococcidae, Brevennia larvalis Kaydan, sp. n. and a new species of Ortheziidae, Ortheziola editae Szita & Konczné Benedicty, sp. n. are described and illustrated based on the adult female stage. Revised keys to the adult females of Brevennia and Ortheziola are presented.