Contrast-enhanced ultrasound for evaluating response to pulsed-wave high-intensity focused ultrasound therapy in advanced pancreatic cancer.

OBJECTIVE: To examine whether contrast-enhanced ultrasound (CEUS) parameters in patients with advanced pancreatic cancer could be used to assess response to treatment with pulsed-wave high intensity focused ultrasound (PW-HIFU). METHODS: We prospectively recorded the pretreatment and posttreatment CEUS related parameters, CA19-9, pain scores of 30 patients with advanced pancreatic cancer treated with PW-HIFU treatment. Correlation of clinical parameters, tumor characteristics, and PW-HIFU treatment energy with CEUS parameters were analyzed. RESULTS: Pain score decreased after treatment (from 4.80±2.14 to 3.28±1.93, p = 0.001). CA19-9 dropped in RT decreased group, 4 weeks after one session PW-HIFU, compared with prolonged group (p = 0.013). According to the display of blood vessels in the mass by CEUS, tumors were classified by vessel grade (VG), VG1: no vessel can be seen; VG 2: vessels diameter < 5 mm; VG 3: vessels diameter > 5 mm. VGs were different between increased and decreased relative rise intensity (rRI) groups (p = 0.008). VG1 group shown a decreased rRI after treatment, while VG3 group showed the opposite trend (p = 0.006). CONCLUSIONS: CEUS can evaluating response to PW-HIFU in advanced pancreatic cancer. Quantitative analysis may help to assess the short-term efficacy of patients and help for individualized treatment.

LMO4 promotes the invasion and proliferation of gastric cancer by activating PI3K-Akt-mTOR signaling.

This study assessed the biological functions of LIM-domain-only 4 (LMO4) in gastric cancer (GC) and investigated the underlying molecular mechanisms. It was found that the expression of LMO4 was significantly upregulated in GC tissues and closely associated with clinicopathological factors, overall survival and disease-free survival of patients. After knockdown of LMO4 in MGC-803 and SGC-7901 cells, invasion and proliferation were obviously suppressed. Furthermore, LMO4 knockdown suppressed the phosphorylation of phosphatidylinositol 3-kinase (PI3K), Akt and mammalian target of rapamycin (mTOR). Miltefosine, the inhibitor of PI3K/Akt, and dactolisib, the inhibitor of mTOR, abrogated recombinant LMO4-induced GC cell invasion and proliferation. These results suggest that LMO4 promotes GC cell invasion and proliferation mainly through PI3K-Akt-mTOR signaling. LMO4 may serve as a potential therapeutic target for GC in the future.

Knockdown of Decoy Receptor 3 Impairs Growth and Invasiveness of Hepatocellular Carcinoma Cell Line of HepG2.

BACKGROUND: Decoy receptor 3 (DcR3) binds to Fas ligand (FasL) and inhibits FasL-induced apoptosis. The receptor is overexpressed in hepatocellular carcinoma (HCC), and it is associated with the growth and metastatic spread of tumors. DcR3 holds promises as a new target for the treatment of HCC, but little is known regarding the molecular mechanisms underlying the oncogenic properties of DcR3. The present work, therefore, examined the role of DcR3 in regulating the growth and invasive property of liver cancer cell HepG2. METHODS: HepG2 cells were stably transfected with lentivirus-based short hairpin RNA vector targeting DcR3. After the knockdown of DcR3 was confirmed, cell proliferation, clone formation, ability of migrating across transwell membrane, and wound healing were assessed in vitro. Matrix metalloproteinase-9 (MMP 9) and vascular epithelial growth factor (VEGF)-C and D expressions of the DcR3 knockdown were also studied. Comparisons between multiple groups were done using one-way analysis of variance (ANOVA), while pairwise comparisons were performed using Student's t test. P< 0.05 was regarded statistically significant. RESULTS: DcR3 was overexpressed in HepG2 compared to other HCC cell lines and normal hepatocyte Lo-2. Stable knockdown of DcR3 slowed down the growth of HepG2 (P < 0.05) and reduced the number of clones formed by 50% compared to those without DcR3 knockdown (P < 0.05). The knockdown also reduced the migration of HepG2 across transwell matrix membrane by five folds compared to the control (P < 0.05) and suppressed the closure of scratch wound (P < 0.05). In addition, the messenger RNA levels of MMP 9, VEGF-C, and VEGF-D were significantly suppressed by DcR3 knockdown by 90% when compared with the mock control (P < 0.05). CONCLUSIONS: Loss of DcR3 impaired the growth and invasive property of HCC cell line of HepG2. Targeting DcR3 may be a potential therapeutic approach for the treatment of HCC.