RRM1 gene expression in peripheral blood is predictive of shorter survival in Chinese patients with advanced non-small-cell lung cancer treated by gemcitabine and platinum

Objective  

To evaluate the predictive values of gene expressions of ribonucleotide reductase M1 (RRM1) and breast cancer susceptibility gene 1 (BRCA1) in peripheral blood from Chinese patients with non-small-cell lung cancer (NSCLC) treated with gemcitabine plus platinum.     

Prognostic value of serum soluble Fas in patients with locally advanced unresectable rectal cancer receiving concurrent chemoradiotherapy

Objective: This study was designed to detect the changes of serum soluble Fas (sFas) levels in patients with locally advanced unresectable rectal cancer (LAURC),and to explore its prognostic value of response.Methods: Soluble samples were obtained from LAURC subjects,treated by concurrent chemoradiotherapy,before treatment and one month after treatment.Healthy donor serum samples were used as controls.sFas concentration was measured by enzyme-linked immunosorbent assay (ELISA).Results: The sFas levels before treatment and one month after treatment were both significantly higher in LAURC subjects than in healthy controls [(8.79±1.39) and (7.74±1.32) vs.(5.53±1.13) ng/L,P0.01].The sFas levels before treatment and one month after treatment were significantly lower in the response group (complete and partial responses) than in the non-response group (stable and progressive diseases) [(8.50±1.25) vs.(10.17±1.26) ng/L,P0.01 and (7.50±1.24) vs.(8.90±1.13) ng/L,P0.01,respectively].The one-year survival rate was 54.2% and 82.6% in those with sFas levels 8.79 ng/L and 8.79 ng/L before treatment (P0.02),respectively,50.0% and 87.0% in those with sFas levels 7.74 ng/L and 7.74 ng/L one month after treatment (P0.01),respectively.Conclusions: The sFas level is higher in LAURC subjects than in healthy controls.Concurrent chemoradiotherapy can reduce sFas levels in LAURC patients.The monitoring of sFas may provide prognostic information for LAURC patients.     

Increasing the immune activity of exosomes: the effect of miRNA-depleted exosome proteins on activating dendritic cell/cytokine-induced killer cells against pancreatic cancer

Background

Tumor-derived exosomes were considered to be potential candidates for tumor vaccines because they are abundant in immune-regulating proteins, whereas tumor exosomal miRNAs may induce immune tolerance, thereby having an opposite immune function.

Objective

This study was designed to separate exosomal protein and depleted exosomal microRNAs (miRNAs), increasing the immune activity of exosomes for activating dendritic cell/cytokine-induced killer cells (DC/CIKs) against pancreatic cancer (PC).

Methods

PC-derived exosomes (PEs) were extracted from cultured PANC-1 cell supernatants and then ruptured; this was followed by ultrafiltered exosome lysates (UELs). DCs were stimulated with lipopolysaccharide (LPS), PE, and UEL, followed by co-culture with CIKs. The anti-tumor effects of DC/CIKs against PC were evaluated by proliferation and killing rates, tumor necrosis factor-α (TNF-α) and perforin secretion. Exosomal miRNAs were depleted after lysis and ultrafiltration, while 128 proteins were retained, including several immune-activating proteins.

Results

UEL-stimulated DC/CIKs showed a higher killing rate than LPS- and PE-stimulated DC/CIKs.

Conclusions

miRNA-depleted exosome proteins may be promising agonists for specifically activating DC/CIKs against PC.

     

Induced pluripotent stem cell-related genes influence biological behavior and 5-fluorouracil sensitivity of colorectal cancer cells

Objective  

We aimed to perform a preliminary study of the association between induced pluripotent stem cell (iPS)-related genes and biological behavior of human colorectal cancer (CRC) cells, and the potential for developing anti-cancer drugs targeting these genes.     

HER-2 overexpression and survival in colorectal cancer: a meta-analysis

Objective

Numerous studies examining the relationship between human epidermal growth factor receptor 2 (HER-2) overexpression and survival in patients with colorectal cancer (CRC) have yielded controversial results. We therefore performed a meta-analysis more precisely to estimate its prognostic value.

Methods

Published studies investigating the effect of HER-2 overexpression on CRC survival were identified; the hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CIs) were pooled in terms of disease-specific or overall survival.

Results

Eleven studies were included in the meta-analysis. The pooled data showed that HER-2 overexpression was negatively related to CRC survival (HR=1.10, 95% CI: 0.77–1.44). Subgroup analyses regarding test method and study quality also demonstrated little association between HER-2 overexpression and CRC survival (HR=0.89, 95% CI: 0.50–1.29; HR=0.90, 95% CI: 0.43–1.37, respectively).

Conclusions

Regardless of several limitations, our study suggested that HER-2 overexpression probably had little impact on CRC survival.     

早期经尿道前列腺隧道式电切治疗前列腺癌近距离照射治疗术后尿潴留(英文)

研究目的:探讨早期经尿道前列腺隧道式电切治疗前列腺癌近距离照射治疗术后尿潴留的适应症及其对近距离照射治疗疗效的影响。创新要点:前列腺癌近距离照射治疗已经成为75岁以上患者的首选,前列腺癌近距离照射治疗术后尿潴留发生率为1.5%~22.0%。经尿道前列腺电切常用于药物治疗无效的反复尿潴留患者,且手术时机多在近距离照射治疗术后6个月以后。经尿道前列腺隧道式电切治疗前列腺癌近距离照射治疗术后尿潴留可在6个月内进行,患者尿道症状从IV(出现尿潴留,需要导尿)下降为0级(没有症状)或I级(轻度,中度尿频,2~3次/晚),较术前改善明显,且对近距离照射治疗疗效无明显影响。研究方法:浙江大学医学院附属邵逸夫医院2009年2月至2013年7月间所有接受前列腺癌近距离照射治疗的病例共190例,其中9例(4.7%)患者术后出现反复尿潴留,且早期行经尿道前列腺隧道式电切术治疗,回顾分析其临床资料。重要结论:前列腺癌近距离照射治疗术后反复尿潴留,在严格防护下早期行经尿道前列腺隧道式电切是安全有效的,且电切后对近距离照射治疗疗效无明显影响。     

Cordycepin induces apoptosis by enhancing JNK and p38 kinase activity and increasing the protein expression of Bcl-2 pro-apoptotic molecules

Objective  

To explore the molecular mechanism by which cordycepin inhibits cell proliferation and induces apoptosis of human colorectal cancer cells.     

Proteomic analysis of primary colon cancer-associated fibroblasts using the SELDI-ProteinChip platform

Objective: Cancer-associated fibroblasts (CAFs) are one of the hallmarks of the cancer microenvironment. Recent evidence has indicated that CAFs are more competent in enhancing cancer cell growth and migration than normal fibroblasts. However, the unique protein expression of CAFs has not been fully elucidated. This study aims to investigate the characterizations of colon CAFs by comparing the differential protein expression between CAFs and normal fibroblasts. Methods: Primary fibroblasts were isolated from surgical specimen of human colon cancer and matched normal colonic tissue. Purity of the cell population was verified through immunostain analysis. Total cell lysates and conditioned media from each group of cells were extracted, and protein expression analysis was conducted using the surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) ProteinChip platform. Results: Most primary cells showed typical fibroblast-like features after two weeks. Increased proportion of α-smooth muscle actin-positive myofibroblasts was detected within the CAFs in four of the six pairs of primary cells. Fibroblast activation protein was weakly expressed in most cells without differences. Using SELDI-TOF-MS ProteinChip platform, four protein peaks mass over charge ratio (m/z) 1142, 3011, 4035, and 4945 were detected in the total cell lysates, and two protein peaks m/z 1368 and 1389 were detected in the conditioned media. The potential candidate proteins found in the Swiss-Prot database include morphogenetic neuropeptides, FMRFamide-related peptides, insulin-like growth factor II, thymosin β-4-like protein 3, and tight junction-associated protein 1. Conclusions: Using the SELDI-ProteinChip platform, differential protein expressions were identified in colon CAFs compared with normal colonic stromal fibroblasts. The complex proteomic alternations in colon CAFs may play important roles related to the colon cancer microenvironment.     

Systematic review of laparoscopy-assisted versus open gastrectomy for advanced gastric cancer

Objective

The study compared laparoscopy-assisted gastrectomy (LAG) with open gastrectomy (OG) in the management of advanced gastric cancer (AGC).

Methods

Literature search was performed in the Medline, Embase, and Cochrane Library databases to identify control studies that compared LAG and OG for AGC. A meta-analysis was conducted to examine the surgical safety and oncologic adequacy, using the random-effect model.

Results

Seven eligible studies including 815 patients were analyzed. LAG was associated with less blood loss, less use of analgesics, shorter time of flatus and periods of hospital stay, but longer time of operation. The incidence of most complications was similar between the two groups. However, LAG was associated with a lower rate of pulmonary infection (odds ratio (OR) 0.19; 95% confidence interval (CI) 0.05 to 0.68; P<0.05). No significant differences were noted in terms of the number of harvested lymph nodes (weighted mean difference (WMD) 1.165; 95% CI–2.000 to 4.311; P>0.05), overall mortality (OR 0.65; 95% CI 0.39 to 1.10; P>0.05), cancer-related mortality (OR 0.64; 95% CI 0.32 to 1.25; P>0.05), or recurrence (OR 0.62; 95% CI 0.33 to 1.16; P>0.05).

Conclusions

LAG could be performed safely for AGC with adequate lymphadenectomy and has several short-term advantages compared with conventional OG. No differences were found in long-term outcomes. However, these results should be validated in large randomized controlled studies (RCTs) with sufficient follow-up.     

Methylenetetrahydrofolate reductase C677T polymorphism predicts response and time to progression to gemcitabine-based chemotherapy for advanced non-small cell lung cancer in a Chinese Han population

Objective:The aim of this study was to evaluate the association between the methylenetetrahydrofolate reductase(MTHFR) C677T excision repair cross-complementation group 1(ERCC1) genetic polymorphisms and the clinical efficacy of gemcitabine-based chemotherapy in advanced non-small cell lung cancer(NSCLC).Methods:A total of 135 chemonaive patients with unresectable advanced NSCLC were treated with gemcitabine/platinum regimens.The polymorphisms of MTHFR C677T,ERCC1 C8092A,and ERCC1 C118T were genotyped using the TaqMan methods.Results:The overall response rate was 28.9%.Patients with MTHFR CC genotype had a higher rate of objective response than patients with variant genotype(TT or CT)(41.2% versus 19.1%,P=0.01).Median time to progression(TTP) of patients with MTHFR CC genotype was longer than that of patients with variant genotype(7.6 months versus 5.0 months,P=0.003).No significant associations were obtained between ERCC1 C118T and C8092A polymorphisms and both response and survival.Conclusions:Our data suggest the value of MTHFR C677T polymorphism as a possible predictive marker of response and TTP in advanced NSCLC patients treated with gemcitabine/platinum.     

Expression of three essential antioxidants of Helicobacter pylori in clinical isolates

Objective

Helicobacter pylori maintains long-term persistence in the host and combats oxidative stress via many antioxidant proteins, which are expected to be relevant to bacterial-associated gastric diseases. We aimed to investigate the expression of three essential antioxidants in H. pylori strains isolated from patients with different clinical outcomes. Methods: Forty H. pylori strains were isolated from endoscopic biopsy specimens of gastric mucosa from 13 patients with gastric cancer, 13 with peptic ulcer, and 14 with gastritis. The expression of thioredoxin 1 (Trx1), arginase (RocF), and alkyl hydroperoxide reductase (AhpC) in H. pylori was measured by real-time PCR. Comparisons among multiple sample sets were analyzed using a one-way ANOVA test. Pearson’s correlation test was used to assess relationships among multiple continuous variables.

Results

Trx1 expression of H. pylori in gastric cancer and peptic ulcer tissues was higher than that in tissues with gastritis. RocF expression of H. pylori in gastric cancer tissues was higher than that in tissues exhibiting peptic ulcer and gastritis. However, we did not find any differences in AhpC expression in samples from patients with different clinical outcomes. The expression of Trx1 and RocF had a positive, linear correlation. The expression of Trx1 and AhpC had a positive correlation without a linear trend. We found no correlation between the expression of RocF and AhpC.

Conclusions

Our observations indicate that the expression of Trx1 and RocF in H. pylori might be related to gastric carcinogenesis. In H. pylori, the expression of members of the antioxidant system may be correlated and relevant to gastric cancer.     

舒尼替尼对结肠成纤维细胞体内外抑制机制研究(英文)

研究目的:探索小分子酪氨酸激酶抑制剂舒尼替尼(sunitinib)对结肠肿瘤微环境中的肿瘤相关成纤维细胞的作用及其机制。创新要点:舒尼替尼通过抑制肿瘤间质成纤维细胞的生长,间接发挥抗肿瘤效应,为结肠癌综合治疗的提供新途径。研究方法:通过细胞周期分析和细胞增殖测定进行舒尼替尼体外抑制肿瘤细胞的研究。采用Western-blot检测磷酸化血小板衍生生长因子β受体(PDGFR-β)、蛋白激酶B(Akt)及细胞外信号调节蛋白激酶(ERK)的蛋白水平。通过注射肠腺癌细胞株SW620和结肠成纤维细胞构建的裸鼠移植瘤模型来研究舒尼替尼的体内抑瘤效果。重要结论:舒尼替尼可有效抑制结肠癌来源的原代结肠成纤维细胞生长,该抑制作用主要通过抑制血小板衍生生长因子(PDGF)信号通路得以实现。     

Up-regulation of mitochondrial antioxidation signals in ovarian cancer cells with aggressive biologic behavior

Objective  

Recently, a high frequency of mutations in mitochondrial DNA (mtDNA) has been detected in ovarian cancer. To explore the alterations of proteins in mitochondria in ovarian cancer, a pair of human ovarian carcinoma cell lines (SKOV3/SKOV3.ip1) with different metastatic potentials was examined.     

泰国南邦省陶瓷厂细颗粒物对大鼠肺部的影响(英文)简

Background： Lung cancer ranks as the fifth largest of all cancer cases in Thailand. However, it is the first leading cancer in the northern part of Thailand （data from 2003-2007）. There are several predisposing causes that lead to lung cancer and one important inducement is particulate matters （PMs）. Lampang Province in Thailand is famous for the ceramic industry, where there are over 200 ceramic industrial factories. PMs are produced during the ceramic manufacturing process and spread throughout all of the working areas. It is very possible that workers could directly inhale PM-contaminated air during working hours. Objective： This study focuses on the toxic effects of PMs collected from ceramic factories on genes and lungs of rats. Methods： PMs collected from six ceramic factories in Lampang Province were extracted using dimethyl sulfoxide （DMSO）. The inductively coupled plasma mass spec- trometry （ICP-MS） and inductively coupled plasma optical emission spectrometry （ICP-OES） were used to analyze the chemical elements at lower and higher concentrations, respectively. Then, the toxicity of PMs on the genes was ex- amined by the Ames test, and subsequently, the effect of PMs on DNA was examined by quantifying the amount of 8-hydroxy-2＇-deoxyguanosine （8-OHdG）. Finally, the toxicity of the PMs on rat＇s lungs was examined by histology. Results： As chemical elements of lower concentrations, cadmium, chromium, nickel, copper, and lead were detected by ICP-MS. As chemical elements of higher concentrations, manganese, magnesium, zinc, iron, potassium, calcium, and sodium were detected by ICP-OES. No mutagenicity in Salmone/la typhimurium was found in the PM extracts from all six factories by utilizing the Ames test. In the histological study, the reduction in spaces of alveolar ducts and sacs, and terminal bronchioles, the thickening of interstitial connective tissues were noted by PM extracts in high amounts （100 and 350 pg）. Female rats were more sensitive to PM extracts than males in terms of their pulmonary damages. Conclusions： PMs were not mutagenic to S. typhimurium but can damage the lung tissue of rats.     

Down-regulation of eIF5A-2 prevents epithelial-mesenchymal transition in non-small-cell lung cancer cells

Background

Epithelial-mesenchymal transition (EMT) is believed to be the critical process in malignant tumor invasion and metastases, and has a great influence on improving the survival rate in non-small-cell lung cancer (NSCLC) patients. Recent studies suggested that eukaryotic initiation factor 5A-2 (eIF5A-2) might serve as an adverse prognostic marker of survival. We detected eIF5A-2 in NSCLC A549 cells, and found that the invasive capability correlates with the eIF5A-2 expression.

Methods

Transforming growth factor (TGF)-β1 was used to induce EMT in A549 cells. Western blotting, immunofluorescence, wound healing assay, and transwell-matrigel invasion chambers were used to identify phenotype changes. Western blotting was also used to observe changes of the expression of eIF5A-2. We down-regulated the eIF5A-2 expression using an eIF5A-2 siRNA and identified the phenotype changes by western blotting and immunofluorescence. We tested the change of migration and invasion capabilities of A549 cells by the wound healing assay and transwell-matrigel invasion chambers.

Results

After stimulating with TGF-β1, almost all A549 cells changed to the mesenchymal phenotype and acquired more migration and invasion capabilities. These cells also had higher eIF5A-2 protein expression. Down-regulation of eIF5A-2 expression with eIF5A-2 siRNA transfection could change the cells from mesenchymal to epithelial phenotype and decrease tumor cell migration and invasive capabilities significantly.

Conclusions

The expression of eIF5A-2 was up-regulated following EMT phenotype changes in A549 cells, which correlated with enhanced tumor invasion and metastatic capabilities. Furthermore, in the A549 cell line, the process of EMT phenotype change could be reversed by eIF5A-2 siRNA, with a consequent weakening of both invasive and metastatic capabilities.     

Clinical characteristics and treatment of thyroid cancer in children and adolescents: a retrospective analysis of 83 patients

Objective

To study the clinical characteristics, treatment, and prognosis of thyroid cancer in children and adolescents.

Methods

We performed a retrospective analysis of clinical data from 83 cases of thyroid cancer in children and adolescents from January 1990 to December 2010. We compared extra-thyroid extension, lymph node metastasis, distant metastasis, and prognosis between pediatric patients ≤12 years of age (27 cases) and those >12 years of age (56 cases). All the patients agreed to undergo thyroidectomy and endocrine therapy, and the consent was obtained from parents or guardians.

Results

Histopathology included papillary carcinoma in 67 cases, papillary carcinoma with partial follicular growth pattern in 1 case, papillary carcinoma with squamous metaplasia in 4 cases, follicular carcinoma in 7 cases, medullary carcinoma in 3 cases, and poorly differentiated carcinoma in 1 case. The total lymph node metastasis rate was 78.31%. Patients ≤12 years of age showed a higher rate of lymph node metastasis than the older group (92.59% vs. 71.43%, P=0.028). The incidence rate in females in the older group was higher than that in the younger group (80.36% vs. 59.26%, P=0.041). There were no significant differences in extra-thyroid extension, distant metastasis, survival rate, or recurrent disease between the two groups.

Conclusions

The lymph node metastasis of thyroid cancer is higher in patients ≤12 years of age than in those >12 years of age; the incidence rate is higher in females than in males. Childhood thyroid cancer has a good prognosis, surgery being the most effective treatment. Choosing a reasonable surgery method and comprehensive postoperative treatment can achieve a cure and satisfactory survival rate.