Proteomics,and Metabolomics: Magnetic Resonance Spectroscopy for the Presurgical Screening of Thyroid Nodules

We review the progress and state-of-the-art applications of studies in Magnetic Resonance Spectroscopy (MRS) and Imaging as an aid for diagnosis of thyroid lesions of different nature, especially focusing our attention to those lesions that are cytologically undetermined. It appears that the high-resolution of High-Resolution Magic-Angle-Spinning (HRMAS) MRS improves the overall accuracy of the analysis of thyroid lesions to a point that a significant improvement in the diagnosis of cytologically undetermined lesions can be expected. This analysis, in the meantime, allows a more precise comprehension of the alterations in the metabolic pathways induced by the development of the different tumors. Although these results are promising, at the moment, a clinical application of the method to the common workup of thyroid nodules cannot be used, due to both the limitation in the availability of this technology and the wide range of techniques, that are not uniformly used. The coming future will certainly see a wider application of these methods to the clinical practice in patients affected with thyroid nodules and various other neoplastic diseases.     

甲状腺良、恶性结节的临床、超声及细胞学特征分析

目的:研究良、恶性甲状腺结节的相关临床因素、超声特征与甲状腺细针穿刺细胞学检查结果之间的关系。方法:收集2010年1月至2013年12月在上海市第一人民医院因甲状腺结节就诊,并进行超声引导下FNAB检查患者的临床资料,以FNAB细胞学诊断结果为诊断标准,分析和比较不同性质甲状腺结节患者的年龄、性别、甲状腺疾病家族史、临床症状、血清甲状腺激素、甲状腺自身抗体(TPOAb和TRAb)水平,超声检查所发现的结节数量、性状、前后径与横径比(AP/TR)、回声类型、钙化类型、边界状态、血流情况等因素,采用Logistic多因素回归,探讨这些临床和超声特征与甲状腺良、恶性结节之间的关系。结果:根据FNAB结果,1592例患者中,良性结节者1492例,恶性结节者77例,结果不确定者23例。以良性组作为对照,年龄40岁、TPOAb(+)是恶性甲状腺结节的独立危险因素(P0.05);出现钙化点、细小钙化斑、边界不规整的超声表现的恶性甲状腺的风险显著升高(P0.05)。结论:超声检查甲状腺结节出现钙化点、细小钙化斑或边界不规整等与FNAB诊断的甲状腺恶性结节之间存在明显的关联。     

US-FNAB 在甲状腺良恶性结节鉴别诊断中的应用价值

目的:探讨超声引导下甲状腺穿刺活检(US-FNAB)对甲状腺良恶性结节的诊断价值。方法:本研究选取了60例已做过甲状腺结节手术的患者,入院后先行常规超声(US)检查后行超声引导下甲状腺穿刺活检(US-FNAB)通过观察并记录良恶性结节诊断结果:,诊断结果:符合率及诊断结果:符合率与结节大小的关系,评价US-FNAB对甲状腺良恶性结节的诊断价值。结果:常规超声诊断出恶性结节4例,良性结节33例;超声引导下细针穿刺活检诊断出恶性结节8例,良性结节40例。US组中,15例误诊,8例漏诊中,诊断符合率为61.7%。US-FNAB组中,4例误诊,漏诊2例,诊断符合率80.0%。经统计学分析,US-FNAB组诊断符合率明显高于US组(P0.05),US组与US-FNAB组在各结节直径的患者分布上相比差异无统计学意义(P0.05)。两组组内各结节直径的患者分布上相比差异也无统计学意义(P0.05)。US-FNAB组中,随着结节直径增大,诊断符合率略有降低。对直径10mm的甲状腺结节诊断率达100%。结论:US-FNBA对甲状腺良恶性结节具有较高的诊断准确性,诊断准确性受结节大小影响较小,对直径较小的甲状腺结节检出率较高。     

Application of Molecular Diagnostics to the Evaluation of the Surgical Approach to Thyroid Cancer

Recent important studies that include long-term follow-up have shown that BRAF and RAS mutations can have negative implications for disease recurrence and survival. BRAF positivity has been shown to be associated with decreased survival and is an independent predictor of poor prognosis. Reliable pre-operative identification of high-risk papillary thyroid cancer (PTC) patients may productively guide initial surgical management since reoperative neck surgery is associated with increased morbidity. However, it is probably too early to conclude that at present it is possible to tailor surgical therapy patient by patient only on the basis of their mutational status. Other important parameters, not including molecular testing, represented by some specific morphological aspects, still play an important role, probably still more significant than molecular diagnostics, such as neck ultrasonography. Pre-operative knowledge of BRAF-positive PTC could alter the initial surgical treatment for at least 20% of patients and can potentially prevent the increased morbidity associated with reoperative neck exploration. However, additional multi-institutional and randomized studies will be needed to further define the role of the pre-operative identification of BRAF positivity to guide not only the initial extent of total thyroidectomy (TT) but also the need for and extent of lymphadenectomy.     

Molecular docking analysis of bioactive compounds from Cissampelos pareira with PPAR gamma

We document the Molecular docking analysis of bioactive compounds from Cissampelos pareira with PPAR gamma for further consideration in drug discovery for T2DM.     

New targeted therapies for thyroid cancer

The increasing incidence of thyroid cancer is associated with a higher number of advanced disease characterized by the loss of cancer differentiation and metastatic spread. The knowledge of the molecular pathways involved in the pathogenesis of thyroid cancer has made possible the development of new therapeutic drugs able to blockade the oncogenic kinases (BRAF V600E, RET/PTC) or signaling kinases [vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptors (PDGFR)] involved in cellular growth and proliferation. Some clinical trials have been conducted showing the ability of targeted therapies (sorafenib, sunitinib, axitinib, imanitib, vandetanib, pazopanib, gefitinib) in stabilizing the course of the disease. Until now, however, no consensus guidelines have been established for patient selection and more data on toxicities and side effects are needed to be collected.     

Berberine modulates deacetylation of PPARγ to promote adipose tissue remodeling and thermogenesis via AMPK/SIRT1 pathway

Pharmacological stimulation of adipose tissue remodeling and thermogenesis to increase energy expenditure is expected to be a viable therapeutic strategy for obesity. Berberine has been reported to have pharmacological activity in adipose tissue to anti-obesity, while the mechanism remains unclear. Here, we observed that berberine significantly reduced the body weight and insulin resistance of high-fat diet mice by promoting the distribution of brown adipose tissue and thermogenesis. We have further demonstrated that berberine activated energy metabolic sensing pathway AMPK/SIRT1 axis to increase the level of PPARγ deacetylation, which leads to promoting adipose tissue remodeling and increasing the expression of the thermogenic protein UCP-1. These findings suggest that berberine that enhances the AMPK/SIRT1 pathway can act as a selective PPARγ activator to promote adipose tissue remodeling and thermogenesis. This study proposes a new mechanism for the regulation of berberine in adipose tissue and offers a great prospect for berberine in obesity treatment     

Optimization of methods for peripheral blood mononuclear cells isolation and expansion of human gamma delta T cells

Human Vg9/Vδ2 T cells (γδ T cells) are immune surveillance cells both in innate and adaptive immunity and are a possible target for anticancer therapies, which can induce immune responses in a variety of cancers. Small non-peptide antigens such as zoledronate can do activation and expansion of T cells in vitro. It is evident that for adoptive cancer therapies, large numbers of functional cells are needed into cancer patients. Hence, optimization of methods needs to be carried out for the efficient expansion of these T cells. Standardization of peripheral blood mononuclear cells (PBMCs) isolation was devised. Cytokines (interleukin 2 (IL-2) and interleukin 15 (IL-15)) and zoledronate were also standardized for different concentrations. It was found that an increased number of PBMCs were recovered when washing was done at 1100 revolution per minute (rpm). Significantly high expansion fold was (2524 ± 787 expansion fold) achieved when stimulation of PBMCs was done with 1 µM of zoledronate and both cytokines IL-2 and IL-15 supported the expansion and survival of cells at the concentrations of 100 IU/ml and 10 ng/ml respectively. 14-day cultures showed highly pure (91.6 ± 5.1%) and live (96.5 ± 2.5%) expanded γδ T cells. This study aimed to standardize an easy to manipulate technique for the expansion of γδ T cells, giving a higher yield.     

A disintegrin and metalloproteinase 8 induced epithelial‐mesenchymal transition to promote the invasion of colon cancer cells via TGF‐β/Smad2/3 signalling pathway

A disintegrin and metalloproteinase 8 (ADAM8) protein is a multi‐domain transmembrane glycoprotein which involves in extracellular matrix remodelling, cell adhesion, invasion and migration. ADAM8 and epithelial‐mesenchymal transition (EMT) play an important role in tumour invasion has been well established. However, the interaction between ADAM8 and EMT has remained unclear. The data of colon cancer patients obtained from TCGA (The Cancer Genome Atlas) and GTEx (Genotype‐Tissue Expression Project) were analysed by the bioinformatics research method. The expression of ADAM8 in colon cancer cells was up‐regulated and down‐regulated by transfecting with the expression plasmid and small interfering RNA, respectively. Transwell invasion assay, immunohistochemistry, immunocytochemistry, Western blotting and qRT‐PCR were utilized to study the effect of ADAM8 on colon cancer cell''s EMT and its related mechanisms. Analysis of TCGA and GTEx data revealed that ADAM8 was linked to poor overall survival in colon cancer patients. Besides, ADAM8 was correlated with multiple EMT biomarkers (E‐cadherin, N‐cadherin, Vimentin, Snail2 and ZEB2). In vitro, we also proved that the up‐regulation of ADAM8 could promote EMT effect and enhance the invasive ability of colon cancer cells. On the contrary, the down‐regulation of ADAM8 in colon cancer cells attenuated these effects above. Further studies suggested that ADAM8 modulated EMT on colon cancer cells through TGF‐β/Smad2/3 signalling pathway. Our research suggested that ADAM8 could be a potential biomarker for the prognosis of colon cancer and induced EMT to promote the invasion of colon cancer cells via activating TGF‐β/Smad2/3 signalling pathway.     

API-2-Induced Cell Migration Is Overcome by Small Molecular Approaches Inhibiting β-Catenin

Frequent mutation of APC (90%) in advanced colorectal cancer (CRC) results in the simultaneous activation of Wnt/β-catenin and AKT signaling pathways, and the current therapeutic limitations of the AKT inhibitors for treating CRC patients are nuclear β-catenin-induced EMT and bypassing apoptosis. In this study, we discover that the combinatorial treatment of an AKT inhibitor and KY1022, a β-catenin destabilizer, effectively overcomes the current limitations of API-2, an AKT inhibitor, by reducing nuclear β-catenin. Taken together, we demonstrate that the simultaneous suppression of Wnt/β-catenin with the AKT signaling pathways is an ideal strategy for suppressing the AKT-inhibitor-mediated metastasis and for maximizing the therapeutic effects of AKT inhibitors.