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BackgroundThe combination of phytochemicals with chemotherapy drugs is an emerging new strategy for cancer therapy to increase antitumor responses.MethodsThe present study investigates the effect of the combination of capsaicin (CAP) with cisplatin (DDP) and the potential underlying anticancer mechanisms in osteosarcoma (OS) cells in vitro and in vivo.ResultsCell viability assays and isobolographic analyses demonstrated that the combination of CAP and DDP showed synergistic cytotoxic effects on OS cells. We chose relatively low concentrations of CAP (100 μM) and DDP (16.7 μM) for subsequent experiments. Generally, the combination of CAP and DDP had significant effects on apoptosis induction, cell cycle arrest and cell invasion inhibition in OS cells compared with the individual-treatment groups and the control group. Moreover, cotreatment with CAP and DDP triggered prosurvival autophagy through reactive oxygen species (ROS)/JNK and p-AKT/mTOR signaling in OS cells. The combination regimen of CAP and DDP also inhibited tumor growth in an OS xenograft model.ConclusionThese results suggest that the combination of CAP and DDP has strong inhibitory effects on OS cells and identify CAP as a promising agent for supplementing standard chemotherapy and possible future targeted therapy in OS.

Objective-Susceptibility to atherosclerosis is genetically complex, and modifier genes that do not operate via traditional risk factors are largely unknown. A mouse genetics approach can simplify the genetic analysis and provide tools for mechanistic studies. Methods and Results-We previously identified atherosclerosis susceptibility QTL (Athsq1) on chromosome 4 acting independently of systemic risk factors. We now report confirmation of this locus in congenic strains carrying the MOLF-derived susceptibility allele in the C57BL/6J-Ldlr Ϫ/Ϫ genetic background. Homozygous congenic mice exhibited up to 4.5-fold greater lesion area compared to noncongenic littermates (PϽ0.0001). Analysis of extracellular matrix composition revealed prominent accumulation of versican, a presumed proatherogenic matrix component abundant in human lesions but almost absent in the widely-used C57BL/6 murine atherosclerosis model. The results of a bone marrow transplantation experiment suggested that both accelerated lesion development and versican accumulation are mediated, at least in part, by macrophages. Interestingly, comparative mapping revealed that the Athsq1 congenic interval contains the mouse region homologous to a widely-replicated CHD locus on human chromosome 9p21. Key Words: atherosclerosis Ⅲ congenic strain Ⅲ genetics Ⅲ extracellular matrix Ⅲ mapping S usceptibility to atherosclerosis is influenced by both genetic and environmental factors, with approximately 40% to 60% of interindividual variation attributed to genetic factors. 1 The complex etiology has hampered genetic studies of atherosclerosis in humans per se until recently. Early studies used the candidate gene approach to identify rare genetic variants contributing to traditional risk factors including plasma levels of LDL/VLDL, HDL, lipoprotein (a), homocysteine, and blood pressure. [2][3][4][5][6] Now many of the genes underlying Mendelian forms of dyslipidemia have been shown to contribute to population variation of plasma lipids using genome-wide association (GWA) studies. [7][8][9] Attempts to identify genes directly underlying coronary artery disease (CAD)/ myocardial infarct (MI) were first pursued through linkage studies of families enriched for disease 10 -14 and large-scale association studies. [15][16][17][18] However, the first locus to be widely-replicated for CHD was recently revealed through a series of GWA studies. 19 -22 A common variant was localized to chromosome (chr) 9p21, but the underlying gene and mechanism of action are unknown. Thus, while a number of genes contributing to traditional risk factors have been identified, few of the genes underlying nontraditional risk factors are known. Conclusion-These studies confirm the proatherogenic activity of a novel gene(s) in the MOLF-derivedAnimal models offer an alternative approach for the genetic analysis of complex diseases such as atherosclerosis. In early work, the existence of atherosclerosis susceptibility loci in the mouse model was suggested using recombinant inbred strains of mice. [23]...

BackgroundCervical lymph node metastasis of papillary thyroid carcinoma (PTC) is common. However, whether undergoing prophylactic central lymph node (CLN) dissection or lateral lymph node (LLN) dissections to prevent metastasis is still controversial. This study aimed to retrospectively investigate the risk factors of LLN metastasis in clinical lymph node-negative (cN0) PTC patients.MethodsWe retrospectively studied 783 lymph node-negative (cN0) PTC patients who underwent total thyroidectomy plus CLN dissection and LLN dissection.ResultsThe rates of CLN and LLN metastases were 68.2 and 47.4%, respectively. Large tumor size (> 20 mm) had a fourfold higher risk of LLN metastasis compared with small tumor size (≤ 20 mm; OR = 4.082, 95% CI 2.646–6.289; P = 0.001). Patients with tumor in the upper lobe had ~ 3-fold higher risk of LLN metastasis compared with patients with tumor in other locations (OR = 2.874, 95% CI 1.916–4.310; P = 0.001). Multifocality and extrathyroidal extension indicated a twofold higher risk of LLN metastasis. Having ≥ 2 CLN metastases dramatically increased the risk of LLN metastasis, compared with those with < 2 CLN metastases (OR = 6.536, 95% CI 4.630–9.259; P = 0.001).ConclusionsLarge tumor size (> 20 mm), tumor located in the upper lobe, multifocality, extrathyroidal extension, and ≥ 2 CLN metastases may increase the risk of LLN metastasis in cN0 PTC patients.

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