[Correlation of Lipin gene expression with hepatic fat content in rats with intrauterine growth retardation]. / LipinåŸºå› è¡¨è¾¾ä¸Žå®«å† å‘è‚²è¿Ÿç¼“å¤§é¼ è‚è„è„‚è‚ªå«é‡çš„ç›¸å ³æ€§ç ”ç©¶.

OBJECTIVES: To study the correlation of the expression of Lipin1 in visceral adipose tissue and Lipin2 in liver tissue with hepatic fat content in rats with intrauterine growth retardation (IUGR). METHODS: Pregnant rats were given a low-protein (10% protein) diet during pregnancy to establish a model of IUGR in neonatal rats. The pregnant rats in the control group were given a normal-protein (21% protein) diet during pregnancy. The neonatal rats were weighed and liver tissue was collected on day 1 and at weeks 3, 8, and 12 after birth, and visceral adipose tissue was collected at weeks 3, 8, and 12 after birth. The 3.0T 1H-magnetic resonance spectroscopy was used to measure hepatic fat content at weeks 3, 8, and 12 after birth. Real-time PCR was used to measure mRNA expression levels of Lipin2 in liver tissue and Lipin1 in visceral adipose tissue. Western blot was used to measure protein levels of Lipin2 in liver tissue and Lipin1 in visceral adipose tissue. A Pearson correlation analysis was performed to investigate the correlation of mRNA and protein expression of Lipin with hepatic fat content. RESULTS: The IUGR group had significantly higher mRNA and protein expression levels of Lipin1 in visceral adipose tissue than the control group at weeks 3, 8, and 12 after birth (P<0.05). Compared with the control group, the IUGR group had significantly lower mRNA and protein expression levels of Lipin2 in liver tissue on day 1 after birth and significantly higher mRNA and protein expression levels of Lipin2 at weeks 1, 3, 8, and 12 after birth (P<0.05). At week 3 after birth, there was no significant difference in hepatic fat content between the IUGR and control groups (P>0.05), while at weeks 8 and 12 after birth, the IUGR group had a significantly higher hepatic fat content than the control group (P<0.05). The protein and mRNA expression levels of Lipin1 were positively correlated with hepatic fat content (r=0.628 and 0.521 respectively; P<0.05), and the protein and mRNA expression levels of Lipin2 were also positively correlated with hepatic fat content (r=0.601 and 0.524 respectively; P<0.05). CONCLUSIONS: Upregulation of the mRNA and protein expression levels of Lipin1 in visceral adipose tissue and Lipin2 in liver tissue can increase hepatic fat content in rats with IUGR and may be associated with obesity in adulthood.

Neoadjuvant intra-arterial versus intravenous chemotherapy in colorectal cancer.

ABSTRACT: To investigate the clinical benefits of transcatheter arterial infusion chemotherapy compared with intravenous chemotherapy in patients with colorectal cancer (CRC).From May 2013 to March 2018, 83 patients (50 men and 33 women) with surgically proven CRC were retrospectively included. Before surgery, 62 patients received conventional systemic chemotherapy, and 21 transcatheter arterial chemotherapy. Basic characteristics, disease control rate (DC), adverse reactions, postoperative complications, and toxicity profiles were collected and compared between the 2 groups.The sigmoid colon (43.37%) was the most common primary tumor location, and the least was the transverse colon (6.02%). Most lesions invaded the subserosa or other structures T3-4 (78.31%), and other lesions invaded the muscular layer T1-2 (21. 69%). The overall DC was 80.65% in the intravenous chemotherapy group and 90.48% in the arterial chemotherapy group (P < .05). Adverse events included myelosuppression and gastrointestinal reactions such as nausea, vomiting, diarrhea, abnormal liver function, and neurotoxicity, which were significantly less common in the intra-arterial group than in the intravenous group (P < .05). Postoperative complications included abdominal infection (11.29% vs 14.29%), intestinal obstruction (6.45% vs 4.76%), anastomotic bleeding (1.61% vs 0.00%), and anastomotic fistula (6.45% vs 4.76%) in the intravenous and intra-arterial groups, respectively (P > .05).Preoperative transcatheter arterial infusion chemotherapy is a safe and effective neoadjuvant chemotherapy measure for CRC with fewer adverse reactions and a higher overall DC.

Magnetic resonance spectroscopy on hepatocellular carcinoma after transcatheter arterial chemoembolization.

BACKGROUND AND OBJECTIVE: Proton magnetic resonance spectroscopy (MRS) of the liver in vivo is in experimental phase. MRS observation on liver cancer after transcatheter arterial chemoembolization (TACE) has seldom been reported. This study was to investigate the value of MRS in assessing the metabolic changes of hepatocellular carcinoma (HCC) after TACE. METHODS: Twenty-five consecutive patients with pathologically-confirmed HCC received 1H MRS of all hepatic lesions using 1.5T whole body MR scanner before TACE and at 3-10 days after TACE. Choline-to-lipid (Cho/Lip), glucogen/glucose-to-lipid (Glu/Lip), and glytamine/glutamate-to-lipid (Glx/Lip) ratios were measured and analyzed statistically. RESULTS: The Cho/Lip, Glu/Lip, and Glx/Lip ratios were 0.21 +/- 0.08, 0.11 +/- 0.05, 0.28 +/- 0.10 before TACE, respectively, and were 0.10 +/- 0.08, 0.07 +/- 0.07, 0.18 +/- 0.12 after TACE, respectively, with significant differences (P < 0.05). CONCLUSIONS: Using MRS can evaluate the early metabolic responses of HCC to TACE.

[Comparison between pathological findings and MR diffusion-weighted imaging in primary hepatocellular carcinoma after transcatheter arterial chemoembolization].

OBJECTIVE: To explore the pathological basis of diffusion-weighted imaging (DWI) findings in hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). METHODS: DWI was performed in 15 patients with HCC treated by TACE within 24 - 48 hours before II-phase operation. The DWI findings of the liver lesions were analyzed and correlated with pathological findings including macroscopic observation, HE staining and immunohistochemical staining for bFGF. RESULTS: (1) The viable tumor area showed mostly hypersignal intensity (12/15), whereas coagulative necrotic lesions showed hyposignal (8/15) or isosignal intensity (6/15). The ADC values of zones of viable tumor and necrosis in tumor were (1.42 +/- 0.16) x 10(-3) mm(2)/s and (1.58 +/- 0.18) x 10(-3) mm(2)/s, respectively. There was a significant difference of ADC values between the two zones (t = 2.618, P < 0.05). (2) There was a significant difference in ADC values of viable tumor between well and poorly differentiated tumors (t = -2.646, P < 0.05). The distinction of ADC values of the whole tumor was significant among tumors with different degree of necrosis (chi(2) = 7.236, P < 0.05). (3) A negative correlation was observed between bFGF protein expression index and ADC values of viable parts of the tumors in the study group (r = -0.552, P = 0.033). CONCLUSION: DWI shows certain characteristic features of the HCC after TACE, and can be used to distinguish viable and necrotic tumor tissues in HCC after TACE.

In vitro and in vivo magnetic resonance imaging with chlorotoxin-conjugated superparamagnetic nanoprobes for targeting hepatocarcinoma.

The present study aimed to assess the in vitro and in vivo magnetic resonance imaging (MRI) features of chlorotoxin (CTX)-conjugated superparamagnetic iron oxide (SPIO) nanoprobes. CTX-conjugated nanoprobes were composed of SPIO coated with polyethylene glycol (PEG) and conjugated with CTX. The nanoprobes were termed SPIO-PEG-CTX. MRI of the SPIO and SPIO-PEG-CTX solutions at a different concentration was performed with a 3.0-T MRI scanner (Philips Achieva 3.0T X Series; Phillips Healthcare, The Netherlands). Rabbit VX2 hepatocarcinoma was established by a traditional laparotomy method (injection of the tumor particles into the liver using a 15G syringe needle) following approval by the institutional animal care and use committee. Contrast-enhanced MRI of VX2 rabbits (n=8) was performed using the same MRI scanner with SPIO­PEG-CTX solutions as the contrast agent. Data were analyzed with calibration curve and a paired t-test. The SPIO-PEG-CTX nanoparticles were successfully prepared. With increasing concentrations of the solutions, the MRI signal intensity was increased at T1WI, but decreased at T2WI, which were the same as that for SPIO. Rabbit VX2 carcinoma appeared as a low MRI signal at T1WI, and high at T2WI. After injection of the contrast agent, the MRI signal of carcinoma was decreased relative to that before injection at T2WI (1,161±331.5 vs. 1,346±300.5; P=0.004<0.05), while the signal of the adjacent normal hepatic tissues was unchanged (480.6±165.1 vs. 563.4±67.8; P=0.202>0.05). The SPIO-PEG-CTX nanoparticles showed MRI negative enhancement at T2WI and a targeting effect in liver cancer, which provides the theoretical basis for further study of the early diagnosis of hepatocellular carcinoma.

VEGF(165) expressing bone marrow mesenchymal stem cells differentiate into hepatocytes under HGF and EGF induction in vitro.

A short half-life and low levels of growth factors in an injured microenvironment necessitates the sustainable delivery of growth factors and stem cells to augment the regeneration of injured tissues. Our aim was to investigate the ability of VEGF(165) expressing bone marrow mesenchymal stem cells (BMMSCs) to differentiate into hepatocytes when cultured with hepatocyte growth factor (HGF) and epidermal growth factor (EGF) in vitro. We isolated, cultured and identified rabbit BMMSCs, then electroporated the BMMSCs with VEGF(165)-pCMV6-AC-GFP plasmid. G418 was used to select transfected cells and the efficiency was up to 70%. The groups were then divided as follows: Group A was electroporated with pCMV6-AC-GFP plasmid + HGF + EGF and Group B was electroporated with VEGF(165)-pCMV6-AC-GFP plasmid +HGF + EGF. After 14 days, BMMSCs were induced into short spindle and polygonal cells. Alpha-fetoprotein (AFP) was positive and albumin (ALB) was negative in Group A, while both AFP and ALB were positive in group B on day 10. AFP and ALB in both groups were positive on day 20, but the quantity of AFP in group B decreased with prolonged time and was about 43.5% less than group A. The quantity of the ALB gene was increased with prolonged time in both groups. However, there was no significant difference between group A and B on day 10 and 20. Our results demonstrated that VEGF(165)-pCMV6-AC-GFP plasmid modified BMMSCs still had the ability to differentiate into hepatocytes. The VEGF(165) gene promoted BMMSCs to differentiate into hepatocyte-like cells under the induction of HGF and EGF, and reduced the differentiation time. These results have implications for cell therapies.

Effect of preoperative transcatheter arterial chemoembolization on angiogenesis of hepatocellular carcinoma cells.

AIM: To evaluate the effects of four types of preoperative transcatheter arterial chemoembolization (TACE) on angiogenesis of hepatocellular carcinoma (HCC) cells. METHODS: A total of 136 patients with HCC underwent liver resection. One to five courses of TACE prior to liver resection were performed in 79 patients (TACE group), in which one to four courses of chemotherapy alone were performed in 11 patients (group A); one to five courses of chemotherapy combined with iodized oil were performed in 33 patients (group B); one to three courses of chemotherapy combined with iodized oil and gelatin sponge were performed in 23 patients (group C); one to three courses of chemotherapy combined with iodized oil, ethanol and gelatin sponge were performed in 12 patients (group D). The other 57 patients only received liver resection (non-TACE group). The microvessels were marked by CD31. The expression of CD31 and vascular endothelial growth factor (VEGF) protein were detected by immunohistochemical methods. RESULTS: The mean microvessel density (MVD) in HCC cells was significantly higher in groups A, B, C and D than in the non-TACE group (P < 0.05). The expression of VEGF protein in HCC cells were significantly higher in groups A, B, C and D than in the non-TACE group (P < 0.05). MVD and the expression of VEGF protein were positively correlated. Mean MVD and the expression of VEGF protein were closely related to the number of courses of TACE and the interval of TACE. CONCLUSION: Four different types of preoperative TACE regimens enhanced angiogenesis in HCC cells by up-regulating the expression of VEGF protein. It is necessary to repress angiogenesis of liver cancer after TACE.