精制胸腺活性肽药效学研究

目的 考察精制胸腺活性肽免疫学活性。方法 建立BALB/c小鼠肝细胞肿瘤(腹水型)模型,经腹腔连续注射肝肿瘤细胞15d,检测各种生命指标,以观察抗肿瘤效果。同时用E-玫瑰花环实验及淋巴细胞转化实验评价其生物学活性。结果 抗肿瘤实验表明,生命各项指标均优于盐水对照组,用药组10d、15d的存活率明显高于对照组;E-玫瑰花环及淋巴细胞转化实验均显示精制胸腺活性肽组明显高于对照组。结论 精制胸腺活性肽具有明显的免疫增强作用。     

纳米羟基磷灰石的表征及其对肝癌抑制作用的研究

利用化学方法辅助超声制备出稳定单分散的羟基磷灰石(HAP)纳米粒子体系.应用原子力显微镜(AFM)、粒径电位仪对HAP纳米粒子进行表征;采用形态学观察和MTT比色法研究HAP纳米粒子对细胞系Bel-7402人肝癌细胞的作用;从单细胞荧光元素微区分析、超微结构及细胞周期的改变研究其作用机理.实验结果表明:HAP纳米粒子在体外对Bel-7402人肝癌细胞具有明显的抑制作用,通过进入到癌细胞内,阻滞细胞周期的进展,使细胞在G1期堆积,导致癌细胞胀亡.     

Role of Cyclooxygenase-2 in Head and Neck Tumorigenesis

The cyclooxygenase-2 (COX-2) is a potent enzyme that converts arachidonic acid to prostaglandins (PG), including PGE2, a key mediator of inflammation and angiogenesis. Importantly, COX-2 is activated in response to inflammatory stimuli, where it is also believed to promote the development and progression of head and neck cancers (HNC). COX-2 can mediate its protumorigenic effect through various mechanisms, such as inducing cell proliferation, inhibition of apoptosis, and suppressing the host’s immune response. Furthermore, COX-2 can induce the production of vascular endothelial growth factors, hence, promoting angiogenesis. Indeed, the ability of COX-2 inhibitors to selectively restrict the proliferation of tumor cells and mediating apoptosis provides promising therapeutic targets for cancer patients. Thus, in this comprehensive review, we summarized the reported differential expression patterns of COX-2 in different stages of head and neck carcinogenesis—from potentially premalignant lesions to invasive carcinomas. Furthermore, we examined the available meta-analysis evidence for COX-2 role in the carcinogenesis of HNC. Finally, further understanding of the biological processes of COX-2 and its role in orchestrating cell proliferation, apoptosis, and angiogenesis may give therapeutically beneficial insight to develop the management plan of HNC patients and improve their clinical outcomes.     

Inhibition of the FGF/FGFR System Induces Apoptosis in Lung Cancer Cells via c-Myc Downregulation and Oxidative Stress

Lung cancer represents an extremely diffused neoplastic disorder with different histological/molecular features. Among the different lung tumors, non-small-cell lung cancer (NSCLC) is the most represented histotype, characterized by various molecular markers, including the expression/overexpression of the fibroblast growth factor receptor-1 (FGFR1). Thus, FGF/FGFR blockade by tyrosine kinase inhibitors (TKi) or FGF-ligand inhibitors may represent a promising therapeutic approach in lung cancers. In this study we demonstrate the potential therapeutic benefit of targeting the FGF/FGFR system in FGF-dependent lung tumor cells using FGF trapping (NSC12) or TKi (erdafitinib) approaches. The results show that inhibition of FGF/FGFR by NSC12 or erdafitinib induces apoptosis in FGF-dependent human squamous cell carcinoma NCI-H1581 and NCI-H520 cells. Induction of oxidative stress is the main mechanism responsible for the therapeutic/pro-apoptotic effect exerted by both NSC12 and erdafitinib, with apoptosis being abolished by antioxidant treatments. Finally, reduction of c-Myc protein levels appears to strictly determine the onset of oxidative stress and the therapeutic response to FGF/FGFR inhibition, indicating c-Myc as a key downstream effector of FGF/FGFR signaling in FGF-dependent lung cancers.     

Significant Roles of Regulatory T Cells and Myeloid Derived Suppressor Cells in Hepatitis B Virus Persistent Infection and Hepatitis B Virus-Related HCCs

The adaptive immune system, including type1 helper T cells (Th1 cells), cytotoxic T lymphocytes (CTLs), and dendritic cells (DCs), plays an important role in the control of hepatitis B virus (HBV). On the other hand, regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs) suppress the immune reaction in HBV and hepatocellular carcinoma (HCC). Excessive activation of immune suppressive cells could contribute to the persistent infection of HBV and the progression of HCC. The frequency and/or function of Tregs could affect the natural course in chronic hepatitis B patients and the treatment response. In addition to the suppressive function of MDSCs, MDSCs could affect the induction and function of Tregs. Therefore, we should understand in detail the mechanism by which Tregs and MDSCs are induced to control HBV persistent infection and HBV-related HCC. Immune suppressive cells, including Tregs and MDSCs, contribute to the difficulty in inducing an effective immune response for HBV persistent infection and HBV-related HCC. In this review, we focus on the Tregs and MDSCs that could be potential targets for immune therapy of chronic hepatitis B and HBV-related HCC.     

Crossing Paths in Human Renal Cell Carcinoma (hRCC)

Historically, cell-signaling pathways have been studied as the compilation of isolated elements into a unique cascade that transmits extracellular stimuli to the tumor cell nucleus. Today, growing evidence supports the fact that intracellular drivers of tumor progression do not flow in a single linear pathway, but disseminate into multiple intracellular pathways. An improved understanding of the complexity of cancer depends on the elucidation of the underlying regulatory networks at the cellular and intercellular levels and in their temporal dimension. The high complexity of the intracellular cascades causes the complete inhibition of the growth of one tumor cell to be very unlikely, except in cases in which the so-called “oncogene addiction” is known to be a clear trigger for tumor catastrophe, such as in the case of gastrointestinal stromal tumors or chronic myeloid leukemia. In other words, the separation and isolation of the driver from the passengers is required to improve accuracy in cancer treatment. This review will summarize the signaling pathway crossroads that govern renal cell carcinoma proliferation and the emerging understanding of how these pathways facilitate tumor escape. We outline the available evidence supporting the putative links between different signaling pathways and how they may influence tumor proliferation, differentiation, apoptosis, angiogenesis, metabolism and invasiveness. The conclusion is that tumor cells may generate their own crossroads/crosstalk among signaling pathways, thereby reducing their dependence on stimulation of their physiologic pathways.     

胰岛素受体底物1低表达促进头颈部鳞状细胞癌的侵袭转移

目的: 研究胰岛素受体底物1(insulin receptor substrate 1, IRS-1)在头颈部鳞状细胞癌(head and neck squamous cell carcinoma, HNSCC)侵袭转移中的作用及其可能的机制。 方法: 应用定量RT-PCR法检测HNSCC患者淋巴结转移灶和原发灶癌组织中IRS-1 mRNA的表达,以及不同转移能力头颈部肿瘤细胞株上IRS-1 mRNA的表达。用Taqman探针法检测miR-9及U6的相对表达量。利用小干扰RNA技术阻抑IRS-1表达,肿瘤细胞侵袭实验检测IRS-1干扰前后对细胞侵袭能力的影响。用定量RT-PCR和Western blot检测上皮-间叶转化(epithelial-mesenchymal transition, EMT)的标志物E-cadherin及vimentin mRNA和蛋白的表达;用SRB法检测细胞存活率。 结果: (1)HNSCC患者淋巴结转移灶中IRS-1 mRNA的表达低于原发灶(P<0.05);高转移性HNSCC细胞株中IRS-1 mRNA的表达低于低转移性细胞株(P<0.05)。(2)下调IRS-1表达,肿瘤细胞的侵袭能力增强,上皮-间叶转化标志物E-cadherin表达下降,同时伴有miR-9表达的升高。 结论: IRS-1低表达可能通过上皮-间叶转化和上调miR-9而增强细胞的侵袭能力,促进HNSCC的转移。     

Synergistic Effect of Functionalized Nickel Nanoparticles and Quercetin on Inhibition of the SMMC-7721 Cells Proliferation

The effect of functionalized nickel (Ni) nanoparticles capped with positively charged tetraheptylammonium on cellular uptake of drug quercetin into hepatocellular carcinoma cells (SMMC-7721) has been explored in this study via microscopy and electrochemical characterization as well as MTT assay. Meanwhile, the influence of Ni nanoparticles and/or quercetin on cell proliferation has been further evaluated by the real-time cell electronic sensing (RT-CES) study. Our observations indicate that Ni nanoparticles could efficiently improve the permeability of cancer cell membrane, and remarkably enhance the accumulation of quercetin in SMMC-7721 cells, suggesting that Ni nanoparticles and quercetin would facilitate the synergistic effect on inhibiting proliferation of cancer cells.