Study of the development of thermoresistance in human pancreatic carcinoma cell lines using proteome analysis

In order to find candidate proteins that are potentially associated with the thermoresistant phenotype in combination with drug resistance, we analyzed the differential protein expression in vitro in the human pancreatic cancer cell line EPP85-181-P and classical and atypical multidrug-resistant variants and their thermoresistant counterparts using proteomics. This study identifies sets of proteins that may lead to the development of thermoresistance. These results provide a fundamental basis to elucidate the molecular mechanism of thermoresistance and chemoresistance phenomena that may assist the therapy of inoperable cancers.     

Binding evaluation of isoform 1 fromCratylia mollis lectin to human mammary tissues

The phenomenon of altered carbohydrates in transformed cell surfaces has been studied through histochemical techniques using lectins. Specific binding patterns to normal and transformed mammary tissues were evaluated by Isoform 1 fromCratylia mollis lectin (Cra Iso 1). Protocols using a direct method, incubation of Cra Iso I conjugated to peroxidase (Cra Iso 1-Per) with mammary tissues, followed by diaminobenzidine and hydrogen peroxidase interaction, were performed. Neoplastic tissues, marked by Cra Iso 1, showed a higher intensity of staining than normal ones, in comparison withCanavalia ensiformis lectin, Concanavalin A (Con A), conjugated to peroxidase (Con A-Per). The assay with Cra Iso 1 also indicated a possible utilization of this lectin to characterize normal and transformed mammary cells.     

Alkaloids from Juglans Mandshurica maxim induce distinctive cell death in hepatocellular carcinoma cells

The aim of this work was to further investigate the anticancer potential of Juglans mandshurica Maxim, including the separation of active constituents and their anti-proliferative effects with underlying mechanism of action. Five alkaloids (1–5) were isolated from the bark of J. mandshurica. Among them, 1 showed the highest cytotoxic activities against Hep3B and HepG2 cells with an IC50 values of 61.80 and 56.24 μM, respectively. Therefore, the cellular mechanism involved 1 was subsequently studied. Our results showed that 1 markedly caused apoptosis and autophagy, but without cell cycle arrest in HepG2 cells. Interestingly, only autophagic cell death was induced in 1-treated Hep3B cells. It is concluded that the isolated alkaloids exerted a certain anti-hepatoma potential, and our results may provide a basis for the further investigation of the alkaloids extracted from J. mandshurica.     

Destabilizing the interplay between miR-1275 and IGF2BPs by Tamarix articulata and quercetin in hepatocellular carcinoma

Insulin-like growth factor-2 binding proteins (IGF2BPs) are oncogenic RNA-binding proteins, highly up-regulated in HCC, and were recently validated as direct targets of the tumour suppressor miR-1275. It is worth noting that around 47% of FDA approved anticancer drugs are derived from plants. Modulation by miRNAs and their cellular signalling cascades could constitute new pathways by which these phytochemicals exert their effects. This study aimed to investigate the potential use of Tamarix articulata, quercetin and epigallocatechin gallate (EGCG) in HCC and how these phytochemicals could epigenetically modulate the IGF axis using their impact on miR-1275. T. articulata ethyl acetate fraction significantly reduced the viability of Huh-7 cells compared to control cells. Treatment with T. articulata ethyl acetate fraction, quercetin and EGCG significantly enhanced miR-1275, while suppressed IGF2BP1 and IGF2BP3 mRNA expression levels. In summary, T. articulata, quercetin and EGCG have important implications for HCC molecular-targeted therapy through destabilizing the interplay between miR-1275 and the IGF axis.     

后腹腔镜下肾部分切除术后发生尿瘘的危险因素分析

目的 分析和探讨后腹腔镜下肾部分切除术后发生尿瘘的危险因素。方法统计和分析2004-10-2013-06 行腹 腔镜下经后腹膜路径肾部分切除术后发生尿瘘的128 例肾肿瘤患者的临床资料,尿瘘严格定义为手术2d 后仍从后腹膜引流管持续引流出尿液。结果术后有14 例（10.9%）患者发生尿瘘。发生尿瘘的患者中10 例（71.4%）未行CTA 检查,术中平均出血量（232.3±86.7）ml,平均肾动脉阻断时间（28.2±7.5）min,平均住院时间（13.1±2.1）d,9 例（64.3%）术中发现集合系统破损。单因素分析提示年龄（P =0.1102）、糖尿病（P =0.0445）、肿瘤内生型生长（P =0.0835）、术前是否行CTA 检查（P=0.0137）、集合系统损伤（P=0.0935）、肾动脉阻断时间（P =0.1225）及术中出血量（P=0.0045）是发生尿瘘的危险因素;多因素分析提示糖尿病（P =0.0381）、术前是否行CTA 检查（P =0.0433）及术中出血量（P =0.0155）是术后发生尿瘘的独立危险因素。结论糖尿病、术中出血 量及术前是否行肾脏CTA 检查是后腹腔镜下肾部分切除术后发生尿瘘的独立危险因素。减少术中出血有利于术者获得清晰的操作视野,有效缝合破损的集合系统,从而防止尿瘘的发生。     

Simultaneous determination of mitotane,its metabolite,and five steroid hormones in urine samples by capillary electrophoresis using β-CD2SDS1 complexes as hydrophobic compounds solubilizers

Mitotane is a cytotoxic drug used in the treatment of inoperable adrenocortical carcinoma, it inhibits steroidogenesis as well, and therefore monitoring the level of steroid hormones in patients treated with mitotane is a crucial point of therapy. Hence, we have developed a simple, fast, and efficient electrophoretic method combined with reverse polarity sweeping as online preconcentration technique and dispersive liquid–liquid microextraction for the simultaneous determination of mitotane, its main metabolite DDA, and five steroid hormones (progesterone, testosterone, epitestosterone, cortisol, and corticosterone) in urine samples. In addition, a new sample matrix consisting of β-CD₂SDS₁ complexes for a high hydrophobic compounds solubilization was developed. Approach based on the application of β-cyclodextrin and SDS complex of a ratio 2:1 allowed for hydrodynamic injection into the capillary of a solution containing both mitotane and other analytes. The detection limits of the analytes for the reverse polarity sweeping-dispersive liquid–liquid microextraction method were found to be in the range of 1.5–3 ng/mL, which were approximately 1000 times lower than in the conventional hydrodynamic injection (5 s, 0.5 psi) without any preconcentration procedure. All analytes were completely resolved in less than 13 min by uncoated silica capillary with an inner diameter of 75 μm (ID) × 60 cm. Electrophoretic separation was performed in reverse polarity with a voltage of –25 kV with a background electrolyte (BGE) consisting of 100 mM SDS, 25% ACN, 25 mM phosphate buffer (pH 2.5), and 7 mM β-cyclodextrin.     

New Insights on Potentiometric Immunosensor at Carbon Fiber Microelectrode for Alpha-Fetoprotein in Hepatocellular Carcinoma

Herein, we investigated the analytical features of potentiometric immunosensors for detection of alpha-fetoprotein (AFP) in hepatocellular carcinoma at different electrodes, such as carbon fiber microelectrode (CFME) and carbon-disk electrode (CDE), respectively. To construct such an immunosensor, anti-AFP capture antibodies were first conjugated covalently onto the activated electrodes through typical carbodiimide coupling. Thereafter, one-step immunoreaction protocol was successfully introduced to develop a new potentiometric immunoassay upon addition of AFP. Accompanying the antigen-antibody reaction, the surface charges of the modified electrodes were changed for the readout of electric potential. Results indicated that the linear range of CDE-based immunosensor was 0.1–100 ng mL⁻¹ AFP, whereas the assay sensitivity by using CFME could be further increased to 3.2 pg mL⁻¹ with the linear range from 0.01 to 500 ng mL⁻¹ AFP. Meanwhile, CFME-based immunosensor showed high sensitivity, good reproducibility and specificity, and could be utilized for the analysis of human serum specimens with consistent results relative to commercialized ELISA kit.     

Decorated CuO nanoparticles over chitosan-functionalized magnetic nanoparticles: Investigation of its anti-colon carcinoma and anti-gastric cancer effects

In this study, a green protocol for supporting CuO nanoparticles over chitosan-modified amino-magnetic nanoparticles is described. The physicochemical and morphological properties of the desired nanocomposite assessed by various techniques like ICP, FT-IR, FE-SEM, EDX, TEM, XRD and VSM. In the oncological part of the recent study, the Cu(NO₃)₂, Fe₃O₄, and Fe₃O₄-NH₂@CS/CuO nanocomposite cell viability was very low against human gastric cancer cell lines i.e. MKN45, AGS, and KATO III and human colorectal carcinoma cell lines i.e. HT-29, HCT 116, HCT-8 [HRT-18], and Ramos.2G6.4C10. The IC50 of Fe₃O₄-NH₂@CS/CuO nanocomposite against MKN45, AGS, KATO III, HT-29, HCT 116, HCT-8 [HRT-18], and Ramos.2G6.4C10 cell lines were 517, 525, 544, 282, 214, 420, and 477 µg/mL, respectively. Thereby, the best anti-gastro-duodenal cancers findings of our Fe₃O₄-NH₂@CS/CuO nanocomposite was seen in the HCT 116 cell line case.     

磁共振扩散加权成像联合血清AFP对小肝癌临床诊断及疗效评估的价值

将194例小肝癌患者纳入小肝癌组,185例肝细胞结节患者纳入结节组,所有患者均行MRI扩散加权成像(DWI-MRI),评估患者在DWI-MRI上的形态学表现及ADC值,检测患者血清AFP水平,比较不同检测方法诊断小肝癌的准确度、灵敏度、特异度。结果显示,应用DWI-MRI联合血清AFP诊断小肝癌的特异度、灵敏度和准确度均显著高于单独应用DWI-MRI,或血清AFP(P<0.05)。表明DWI-MRI联合血清AFP对小肝癌的诊断价值显著,可为病情评估提供切实可行的参考。     

The Effect of Hispidulin,a Flavonoid from Salvia plebeia,on Human Nasopharyngeal Carcinoma CNE-2Z Cell Proliferation,Migration, Invasion,and Apoptosis

Nasopharyngeal carcinoma (NPC) is a common malignant head and neck tumor. Drug resistance and distant metastasis are the predominant cause of treatment failure in NPC patients. Hispidulin is a flavonoid extracted from the bioassay-guided separation of the EtOH extract of Salvia plebeia with strong anti-proliferative activity in nasopharyngeal carcinoma cells (CNE-2Z). In this study, the effects of hispidulin on proliferation, invasion, migration, and apoptosis were investigated in CNE-2Z cells. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay and the colony formation assay revealed that hispidulin could inhibit CNE-2Z cell proliferation. Hispidulin (25, 50, 100 μM) also induced apoptosis in a dose-dependent manner in CNE-2Z cells. The expression of Akt was reduced, and the expression of the ratio of Bax/Bcl-2 was increased. In addition, scratch wound and transwell assays proved that hispidulin (6.25, 12.5, 25 μM) could inhibited the migration and invasion in CNE-2Z cells. The expressions of HIF-1α, MMP-9, and MMP-2 were decreased, while the MMPs inhibitor TIMP1 was enhanced by hispidulin. Moreover, hispidulin exhibited potent suppression tumor growth and low toxicity in CNE-2Z cancer-bearing mice at a dosage of 20 mg/kg/day. Thus, hispidulin appears to be a potentially effective agent for NPC treatment.