Methylation of the RASSFIA promoter in breast cancer.

Tumor suppressor genes are the key targets of hypermethylation in breast cancer and may therefore lead to malignancy by deregulation of cell growth and division. Our previous pilot study with pairs of malignant and normal breast tissues identified a correlation between RASSFIA gene methylation and breast cancer. To determine the relationship between RASSFIA methylation and breast cancer, we conducted a larger study. We took samples from 108 patients with breast cancer, 28 patients with benign breast tumors, and 33 subjects with normal breast tissues at the Second Affiliated Hospital of Nanjing Medical University at Wuxi between July 2013 and September 2015. We used the samples to investigate methylation levels of the RASSF1A gene for associations with breast cancer. Quantitative real-time polymerase chain reaction (PCR) and methylation-specific PCR were used to investigate the levels of RASSF1A mRNA expression and RASSF1A methylation, respectively. RASSFIA was not expressed in 22 of the 108 breast cancer tissue samples (20.37%), and there was no statistically significant difference (P > 0.05); however, RASSFIA expression was significantly lower than that in the normal breast tissue samples (P < 0.05). Moreover, the methylation rate of the RASSFIA gene promoter was significantly higher in the breast cancer tissues (64.81%) than in the normal breast tissues (18.18%) and benign breast tumors (17.86%) (P < 0.05). High methylation of the RASSF1A gene promoter was an important reason for its downregulation, and the gene played a critical regulated role in the incidence and development of breast cancer.

Retraction RETRACTION of "Methylation of the RASSFIA promoter in breast cancer" by Y. Ji, H.H. Jin, M.D. Wang, W.X. Cao, J.L. Bao - Genet. Mol. Res. 15 (2): gmr.15028261 (2016) - DOI: 10.4238/gmr.15028261.

The retracted article is: Ji Y, Jin HH, Wang MD, Cao WX, et al. (2016). Methylation of the RASSFIA promoter in breast cancer. Genet. Mol. Res. 15: gmr.15028261. There are significant parts of this article (particularly, in the discussion section) that are copied from "Methylation of HIN-1, RASSF1A, RIL and CDH13 in breast cancer is associated with clinical characteristics, but only RASSF1A methylation is associated with outcome", by Jia Xu, Priya B Shetty, Weiwei Feng, Carol Chenault, Robert C Bast Jr, Jean-Pierre J Issa, Susan G Hilsenbeck and Yinhua Yu, published in BMC Cancer 2012; 12: 243. DOI: 10.1186/1471-2407-12-243. The first paragraphs of both discussions are identical. This is concerning. The abstract and introduction sections have much of their text plagiarized. Overall, there is high plagiarism detected. The GMR editorial staff was alerted and after a thorough investigation, we have strong reason to believe that the peer review process was failure and, after review and contacting the authors, the editors of Genetics and Molecular Research decided to retract the article in accordance with the recommendations of the Committee on Publication Ethics (COPE). The authors and their institutions were advised of this serious breach of ethics.

SPE-UPLC-MS/MS for the determination of phthalate monoesters in rats urine and its application to study the effects of food emulsifier on the bioavailability of priority controlling PAEs.

This research was mainly focused on the effects of food emulsifier on the bioavailability of six priority controlling phthalate acid esters (PAEs) for the further accurate assessment of their toxic effects, using the corresponding phthalate acid monoesters (PAMEs) in rats urine as biomarkers. Glycerin monostearate was chosen as typical food emulsifier. A method was established to determine PAMEs in urine from rats either in experimental group (integrated gavaged with glycerin monostearate and PAEs) or in control group (gavaged with PAEs only), by using solid-phase extraction (SPE) coupled with ultra performance liquid chromatography tandem mass spectrometry (SPE-UPLC-MS/MS). Extraction recoveries were more than 75% for all the PAMEs; the calibration curve was linear in the range of 1.0-1000.0ng/mL with R(2)>0.995; the limits of detection (LOD) were 0.30ng/mL-0.50ng/mL. In addition, by analysing quality control (QC) urine samples in 3 days, it showed that the method was precise and accurate, for the intra-day and inter-day RSD within 16%, and the accuracy more than 82%. Internal exposure amount of all PAEs in experimental group was significantly higher than that in control group with p values of less than 0.05 except for butyl benzyl phthalates (BBP) (P=0.07). The bioavailability of all PAEs ranged from 5.03% to 109.35% with the presence of food emulsifiers glycerin monostearate, observably higher than that without glycerin monostearate (1.12% to 54.39%). It indicated that food emulsifiers increased the bioavailability of PAEs and may lead to potential food safety risk, which should bring awareness and be further studied.

Influence of L-methionine-deprived total parenteral nutrition with 5-fluorouracil on gastric cancer and host metabolism.

AIM: To investigate the influence of L-methionine-deprived total parenteral nutrition with 5-FU on gastric cancer and host metabolism. METHODS: N-methyl-N'-nitro-nitrosoguanidine (MNNG) induced gastric cancer rats were randomly divided into four groups: Met-containing TPN group (n=11), Met-deprived TPN group (n =12), Met-containing TPN+5-FU group (n=11) and Met-deprived TPN+5-FU group (n=12). Five rats in each group were sacrificed after 7 days of treatment and the samples were taken for examination. The remaining rats in each group were then fed separately with normal diet after the treatment until death, the life span was noted. RESULTS: The tumors were enlarged in Met-containing group and shrank in Met-deprived group markedly after the treatment. The DNA index (DI) of tumor cells and the body weight (BW) of rats had no significant change in the two groups, however, the ratio of tumor cells'S phase was increased. The ratio of G2M phase went up in Met-containing group, but down in Met-deprived group. In the other two groups that 5-FU was added, the BW of rats, and the diameter of tumors, the DI of tumor cells, the S and G2M phase ratio of tumor cells were all decreased, particularly in Met-deprived plus 5-FU group. Pathological examination revealed that the necrotic foci of the tumor tissue increased after Met-deprived TPN treatment, and the nucleoli of tumor cells enlarged. In MetTPN+5-FU group, severe nuclear damage was also found by karyopyknosis and karyorrhexis, meanwhile there was slight degeneration in some liver and kidney cells. The serum free Met and Cysteine decreased markedly (P<0.001), while other amino acids, such as serum free serine and glutamine increased significantly (P<0.005). All the rats died of multiple organ failure caused by cancer metastasis. The average survival time was 18.6 days in Met-containing TPN group, 31 days in Met-deprived TPN group, 27.5 days in Met-containing TPN+5-FU group, and 43 days in Met-deprived TPN+5-FU group (P<0.05). CONCLUSION: Met-deprived TPN causes methionine starvation of tumor cells, and can enhance the anti-tumor effect of 5-FU and prolong the life span of gastric cancer bearing rats.

[Effects of parenteral nutrition on cell cycle kinetics in gastric cancer patients].

Studies were made on tumor growth changes by 1-week supplementary parenteral nutrition in undernourished advanced gastric cancer patients. Biopsy of the normal mucosa and cancerous tissue were taken through endoscope before and one week after parenteral nutrition and at the time of operation. Percentage of cells in various phases were analyzed by flow cytometry. The frequency of S and proliferative phases were markedly increased (P < 0.05) in cancerous tissue but not in the normal mucosa. These results demonstrate that a stimulating effect may be present in tumor cell kinetics and hence, the use of a cycle-specific chemotherapeutic agent is indicated.

[Effects of preoperative parenteral nutritional support with chemotherapy on tumor cell kinetics in gastric cancer patients].

The purpose of this study is to elucidate the effect of preoperative parenteral nutritional support (PNS) plus chemotherapy on tumor cell kinetics. 19 advanced gastric cancer (AGC) patients were divided into the following groups: group A (n = 7): in addition to their oral intake, received a PNS for 5 days, which yielded 117 Kj.kg-1.d-1 of non-protein calories and 0.15g.kg-1.d-1 of nitrogen. Group B(n = 6): were infused with 5-Fu at 8-10mg.kg-1.d-1 for 5 days and mitomycin C at 6-8mg.d-1 on the first and fifth day. Group C (n = 6): received a PNS plus 5-Fu with MMC as group A and B did. Specimens of gastric cancer and normal gastric mucosa were taken endoscopically before and after PNS. All specimens were studied by flow cytometry for cell cycle analysis. The results showed that the frequency of cells in S and proliferative phases were significantly increased after PNS (P < 0.01, P < 0.001), but decreased after PNS+chemotherapy (P < 0.05, P < 0.025). No significant change after single chemotherapy was observed. In conclusion, PNS might enhance the effect of chemotherapy in AGC patients, probably, by stimulation of tumor cell kinetics.

[Effects of parenteral nutrition on protein metabolism in patients with gastric cancer].

UNLABELLED: In this study, the changes of protein kinetics in patients with gastric cancer were determined using by 15N-glycine tracer assay before and after parenteral nutrition. The results showed that the protein turnover especially anabolic rate may be enhanced by parenteral nutritional support. The pre- and post operative increase of protein anabolic rate was more than that of the catabolic rate, about 10% and 88% respectively. This phenomenon could be explained as following, (1). the abnormal metabolism in cancer patients was extinguished after the tumor resection; (2). the supplementation of the nitrogen was increased; (3). branched chain amino acids could be used as energy resource for muscle metabolism and to improve protein synthesis while its breakdown was inhibited. CONCLUSION: It is necessary to administer the parenteral nutritional support to patients with malnutrition before operation. With adequate nitrogen and calorie supply, negative nitrogen balance could be improved.