Metastasis associated genomic aberrations in stage II rectal cancer

Hong Zhao,Zhi-Zhou Shi,Rui Jiang,Dong-Bing Zhao,Hai-Tao Zhou,Jian-Wei Liang,Xin-Yu Bi,Jian-Jun Zhao,Zhi-Yu Li,Jian-Guo Zhou,Zhen Huang,Ye-Fan Zhang,Jian Wang,Xin Xu,Yan Cai,Ming-Rong Wang,Yu Zhang 한국유전학회 2016 Genes & Genomics Vol.38 No.11

Genomic aberrations of rectal carcinoma, especially DNA copy number changes associated with metastasis were largely unclear. We aim to identify the metastasis associated biomarkers in stage II rectal cancer. Formalin-fixed, paraffin-embedded primary tumor tissues of stage II rectal carcinoma were analyzed by array-based comparative genomic hybridization, and genomic aberrations were identified by Genomic Workbench and SAM software. Copy number changes and mRNA expressions were validated by Real-time PCR in an independent rectal cancer samples. The results showed that the most frequent gains in stage II rectal cancer were at 1q21.2-q23.1, 3p21.31, 11q12.2-q23.3, 12q24.11-q24.31, 12q13.11-q14.1 and losses in 18q11.2-q23, 17q21.33-q22, 13q31.1-q31.3, 21q21.1-q21.3, 8p23.3-p23.1 and 4q22.1-q23. Twenty-two amplifications and five homozygous deletions were also identified. We further found that S100A1 (1q21.3-q23.1), MCM7 (7q22.1) and JUND (19p13.11) were amplified and overexpressed in stage II rectal cancer. Interestingly, the genomic aberrations affected 14 signaling pathways including VEGF signaling pathway and fatty acid metabolism. Most importantly, loss of 13q31.1-q34 and gain of 1q44 were associated with distant metastasis. Our results indicated that these metastasis associated genomic changes may be useful to reveal the pathogenesis of rectal cancer metastasis and identify candidate biomarkers.

Outcome after Simultaneous Resection of Gastric Primary Tumour and Synchronous Liver Metastases: Survival Analysis of a Single-center Experience in China

Liu, Qian,Bi, Jian-Jun,Tian, Yan-Tao,Feng, Qiang,Zheng, Zhao-Xu,Wang, Zheng Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.4

Background: The optimal surgical strategy for the treatment of synchronous resectable gastric cancer liver metastases remains controversial. The aims of this study were to analyze the outcome and overall survival of patients presenting with gastric cancer and liver metastases treated by simultaneous resection. Materials and Methods: Between January 1990 and June 2009, 35 patients diagnosed with synchronous hepatic metastases from gastric carcinoma received simultaneous resection of both primary gastric cancer and synchronous hepatic metastases. The clinicopathologic features and the surgical results of the 35 patients were retrospectively analyzed. Results: The 5-year overall survival rate after surgery was 14.3%. Five patients survived for more than 5 years after surgery. No mortality has occurred within 30 days after resection, although two patients (5.7%) developed complications during the peri-operative course. Univariate analysis revealed that patients with the presence of lymphovascular invasion of the primary tumor, bilateral liver metastasis and multiple liver metastases suffered poor survival. Lymphovascular invasion by the primary lesion and multiple liver metastases were significant prognostic factors that influenced survival in the multivariate analysis (p=0.02, p=0.001, respectively). Conclusions: The presence of lymphovascular invasion of the primary tumor and multiple liver metastases are significant prognostic determinants of survival. Gastric cancer patients without lymphovascular invasion and with a solitary synchronous liver metastasis may be good candidates for hepatic resection. Simultaneous resection of both primary gastric cancer and synchronous hepatic metastases may effectively prolong survival in strictly selected patients.

Experimental Study on Sustained-release 5-Fluorouracil Implantation in Canine Peritoneum and Para-aortic Abdominalis

Wei, Guo,Nie, Ming-Ming,Shen, Xiao-Jun,Xue, Xu-Chao,Ma, Li-Ye,Du, Cheng-Hui,Wang, Shi-Liang,Bi, Jian-Wei Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1

Objective: To observe local and systemic toxicity after sustained-release 5-fluorouracil (5-Fu) implantation in canine peritoneum and para-aortic abdominalis and the changes of drug concentration in the local implanted tissue with time. Methods: 300 mg sustained-release 5-Fu was implanted into canine peritoneum and para-aorta abdominalis. Samples were taken 3, 5, 7 and 10 days after implantation for assessment of changes and systemic reactions. High performance liquid chromatography was applied to detect the drug concentrations of peritoneal tissue at different distances from the implanted site, lymphatic tissue of para-aortic abdominalis, peripheral blood and portal venous blood. Results: 10 days after implantation, the drug concentrations in the peritoneum, lymphatic tissue and portal vein remained relatively high within 5 cm of the implanted site. There appeared inflammatory reaction in the local implanted tissue, but no visible pathological changes such as cell degeneration and necrosis, and systemic reaction like anorexia, nausea, vomiting and fever. Conclusions: Sustained-release 5-Fu implantation in canine peritoneum and para-aortic abdominalis can maintain a relatively high tumour-inhibiting concentration for a longer time in the local implanted area and portal vein, and has mild local and systemic reactions. Besides, it is safe and effective to prevent or treat recurrence of gastrointestinal tumours and liver metastasis.

Intravenous Flurbiprofen Axetil Enhances Analgesic Effect of Opioids in Patients with Refractory Cancer Pain by Increasing Plasma β-Endorphin

Wu, Ting-Ting,Wang, Zhi-Gang,Ou, Wu-Ling,Wang, Jun,Yao, Guo-Qing,Yang, Bo,Rao, Zhi-Guo,Gao, Jian-Fei,Zhang, Bi-Cheng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.24

Background: The study aimed to investigate the analgesic effect of a combination of intravenous flurbiprofen axetil and opioids, and evaluate the relationship between refractory pain relief and plasma ${\beta}$-endorphin levels in cancer patients. Materials and Methods: A total of 120 cancer patients was randomly divided into two groups, 60 patients took orally morphine sulfate sustained-release tablets in group A, and another 60 patients receiving the combination treatment of intravenous flurbiprofen axetil and opioid drugs in group B. After 7 days, pain relief, quality of life improvement and side effects were evaluated. Furthermore, plasma ${\beta}$-endorphin levels were measured by radioimmunoassay. Results: With the combination treatment of intravenous intravenous flurbiprofen axetil and opioids, the total effective rate of pain relief rose to 91.4%, as compared to 82.1% when morphine sulfate sustained-release tablet was used alone. Compared with that of group A, the analgesic effect increased in group B (p=0.031). Moreover, satisfactory pain relief was associated with a significant increase in plasma ${\beta}$-endorphin levels. After the treatment, plasma ${\beta}$-endorphin level in group B was $62.4{\pm}13.5pg/ml$, which was higher than that in group A ($45.8{\pm}11.2pg/ml$) (p<0.05). Conclusions: Our results suggest the combination of intravenous flurbiprofen axetil and opioids can enhance the analgesic effect of opioid drugs by increasing plasma ${\beta}$-endorphin levels, which would offer a selected and reliable strategy for refractory cancer pain treatment.

Optimization of Reference Genes for Normalization of the Quantitative Polymerase Chain Reaction in Tissue Samples of Gastric Cancer

Zhao, Lian-Mei,Zheng, Zhao-Xu,Zhao, Xiwa,Shi, Juan,Bi, Jian-Jun,Pei, Wei,Feng, Qiang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.14

For an exact comparison of mRNA transcription in different samples or tissues with real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), it is crucial to select a suitable internal reference gene. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and beta-actin (ACTB) have been frequently considered as house-keeping genes to normalize for changes in specific gene expression. However, it has been reported that these genes are unsuitable references in some cases, because their transcription is significantly variable under particular experimental conditions and among tissues. The present study was aimed to investigate which reference genes are most suitable for the study of gastric cancer tissues using qRT-PCR. 50 pairs of gastric cancer and corresponding peritumoral tissues were obtained from patients with gastric cancer. Absolute qRT-PCR was employed to detect the expression of GAPDH, ACTB, RPII and 18sRNA in the gastric cancer samples. Comparing gastric cancer with corresponding peritumoral tissues, GAPDH, ACTB and RPII were obviously upregulated 6.49, 5.0 and 3.68 fold, respectively. Yet 18sRNA had no obvious expression change in gastric cancer tissues and the corresponding peritumoral tissues. The expression of GAPDH, ${\beta}$-actin, RPII and 18sRNA showed no obvious changes in normal gastric epithelial cells compared with gastric cancer cell lines. The carcinoembryonic antigen (CEA), a widely used clinical tumor marker, was used as a validation gene. Only when 18sRNA was used as the normalizing gene was CEA obviously elevated in gastric cancer tissues compared with peritumoral tissues. Our data show that 18sRNA is stably expressed in gastric cancer samples and corresponding peritumoral tissues. These observations confirm that there is no universal reference gene and underline the importance of specific optimization of potential reference genes for any experimental condition.