Mouse cancer models have consistently been used to qualify new anticancer drugs in the development of human clinical trials. Rodent tumour models currently being used and which include transgenic tumour models, and those generated by planting human tumour cell lines subcutaneously in immunodeficient mice, do not sufficiently represent clinical cancer characteristics, especially with regard to metastasis and drug sensitivity. The increasingly used patient-derived human tumour tissue (PDTT) xenografts models implanted subcutaneously or in subrenal capsule in immunodeficient mice, such as athymic nude mice or severe combined immunedeficient (SCID) mice, may provide a more accurate reflection of human tumour biological characteristics than tumour cell lines. The ability to passage patients' fresh tumour tissues into large numbers of immunodeficient mice provides possibilities for better preclinical testing of new therapies for the treatment and better outcome for cancer. In this review, we outline the methods of establishing xenograft models, discuss the biological stability of PDTT xenograft models and demonstrate their roles in developing new anticancer drugs and testing therapeutic regimens in cancer patients.

Melatonin, a multiple signal molecule, plays important roles in delaying senescence during the development of plants. Because few species have been studied for the effect of exogenous melatonin on anti-aging, the plausible mechanism of melatonin of anti-aging effects on other plant species has remained largely unknown. In the present study, the effects of exogenous melatonin on leaf senescence in kiwifruit were examined during natural aging after melatonin (200 μM) or water (Control) pretreatment. The decreased membrane damage and lower hydrogen peroxide (H2O2) content due to the enhanced scavenging activity of antioxidant enzymes peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) demonstrated that melatonin effectively delayed the aging of kiwifruit leaves. Likewise, owing to up-regulated expression of chlorophyll a/b-binding protein (CAB) gene in the sampled leaves pretreated with melatonin, chlorophyll degradation decreased. Therefore, osmoregulatory substances in sampled leaves accumulated (e.g., soluble sugar and soluble protein) and seedling cell environment stability was maintained. Simultaneously, melatonin decreased H2O2 concentration owing to increased glutathione (GSH) and ascorbate (AsA) content, and the expression levels of glutathione reductase (GR), ascorbate peroxidase (APX), monodehydroascorbate reductase (MDAR), dehydroascorbate reductase (DHAR) were up-regulated by melatonin application, indicating that the increase of GSH and AsA was attributed to the expression of these genes. In addition, a large amount of flavonoids accumulated in seedlings pretreated with melatonin, and transcript levels of eight genes involved in flavonoid synthesis, including phenylalanine ammonia-lyase (PAL), cinnamate-4-hydroxymate (C4H), chalcone synthase (CHS), flavanone 3-hydroxylase (F3H), flavonol synthase (FNS), leucoanthocyanin reductase (LAR), anthocyanin reductase (ANR), flavonoid 3-O-glucosyltransferase (UFGT) were enhanced in response to melatonin application. These results indicated that melatonin delayed aging of kiwifruit leaves by activating the antioxidant capacity and enhancing flavonoid biosynthesis. All of these results can provide clear proof that melatonin plays a key roles in delaying leaf senescence.

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BackgroundGrape buds exhibit non-uniform, or delayed, break in early spring in subtropical regions because the accumulation of chilling is insufficient. Hydrogen cyanamide (H2CN2, HC) can partially replace chilling to effectively promote bud sprouting and is used widely in warm winter areas. However, the exact underlying mechanism of grape bud release from endodormancy induced by HC remains elusive.ResultsIn this study, the transcriptome of grape winter buds under in vitro conditions following HC and water treatment (control) was analyzed using RNA-seq technology. A total of 6772 differentially expressed genes (DEGs) were identified. Furthermore, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that starch and sucrose metabolism and plant hormone signaling transduction were most enriched out of the 50 total pathways. HC treatment induced the upregulated expression of sucrose synthase (SUS), sucrose phosphate synthase (SPS), α-amylase (AM), and β-amylase (BM) and downregulated expression of sucrose invertase (INV), hexokinase (HK), fructokinase (FK), soluble starch synthase (SS), and granule-bound starch synthase (GBSS). Hence, the starch concentration in the HC-treated group was significantly lower than that in control, whereas soluble sugar content in the HC-treated group increased quickly and was higher than that in control between 0 and 8 d. The concentration of indoleacetic acid (IAA) and zeatin (ZT) increased, whereas that of abscisic acid (ABA) and gibberellin (GA) decreased in HC treated group, which coincided with the expression level of genes involved in above hormone signals. The content of hydrogen peroxide (H2O2) and enzyme activity of superoxide dismutase (SOD) and peroxidase (POD) were increased in grape buds with HC treatment, whereas catalase (CAT) activity was decreased. HC treatment increased the expression of POD, SOD, primary amine oxidase (PAO), polyamine oxidase (PAOX), and glutathione peroxidase (GSH-Px).ConclusionBased on these results, it is possible to propose a mechanistic model that underlies the regulation of endodormancy release in grapevine buds by exogenous HC application.

Phosphoprotein-binding domains (PPBDs) mediate many important cellular and molecular processes. Ten PPBDs have been known to exist in the human proteome, namely, 14-3-3, BRCT, C2, FHA, MH2, PBD, PTB, SH2, WD-40 and WW. PepCyber:P∼PEP is a newly constructed database specialized in documenting human PPBD-containing proteins and PPBD-mediated interactions. Our motivation is to provide the research community with a rich information source emphasizing the reported, experimentally validated data for specific PPBD–PPEP interactions. This information is not only useful for designing, comparing and validating the relevant experiments, but it also serves as a knowledge-base for computationally constructing systems signaling pathways and networks. PepCyber:P∼PEP is accessible through the URL, http://www.pepcyber.org/PPEP/. The current release of the database contains 7044 PPBD-mediated interactions involving 337 PPBD-containing proteins and 1123 substrate proteins.