Liu W.-N.,Fujian Medical University |
Lin J.-H.,Fujian Medical University |
Cheng Y.-R.,Fujian Institute of Microbiology |
Zhang L.,Fujian University of Traditional Chinese Medicine |
And 8 more authors.
Oncology Research | Year: 2013
The mTOR pathway is a central control of cell growth, proliferation, metabolism, and survival, and is deregulated in most cancers. Cancer cells are addicted to increased activity of mTOR kinase-mediated signaling pathways, leading to numerous inhibitors of mTOR signaling in preclinic and clinical trials for cancer therapy. Phosphorus-containing sirolimus (FIM-A), which targets mTOR signaling, inhibits cancer cell growth in vitro. Here we report that FIM-A reduces the angiogenesis and proliferation of osteosarcoma both in vitro and in vivo. In cultured osteosarcoma cell lines, FIM-A inhibited cell proliferation and arrested cells in the G1 phase of the cell cycle, accompanied with reduction of VEGF and HIF-1α. With in vivo mouse osteosarcoma xenografts, FIM-A treatment resulted in the inhibition of mTORC1 signaling as demonstrated by the decreased phosphorylation of p70S6K1 and 4E-BP1. Consistent with this finding, FIM-A significantly decreased the average tumor volume, nuclei staining of PCNA, and the number of intratumoral microvessels. Our data demonstrated that targeting mTORC1 by FIM-A inhibited the growth of osteosarcoma in vitro and in vivo, providing the basis for further development of FIM-A as a therapy for osteosarcoma patients. Copyright © 2013 Cognizant Comm. Corp. All rights reserved.
Lin D.-X.,Wenzhou Medical College |
Zhang Q.-Y.,Wenzhou Medical College |
Li X.,Mindong Hospital of Ningde |
Ye Q.-W.,Mindong Hospital of Ningde |
And 2 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2011
Purpose: Many physicians express a relatively nihilistic approach to the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Consensus among surgeons regarding the indications for an aggressive approach has not been reached. Current study was aimed to determine whether an aggressive approach, with an extended resection with thrombectomy and adjuvant therapy, would lead to an improved survival for HCC patients with PVTT. Methods: A retrospective review of 116 HCC patients with PVTT admitted from 1996 to 2006 was conducted. Patients were divided into 2 time-period (TP) cohorts, of them, 51 cases in the first 5 years (TP1) and 65 in the last 5 years (TP2). Results: Surgical operations were performed on 68 patients. Twenty-one surgical resections were performed in TP1 and forty-seven in TP2. The extent of liver resections, as well as the frequency of thrombectomy, was greater in TP2 (P = 0.039). During both time-periods, an aggressive therapy was associated with improved survival (P < 0.02 TP1, P < 0.001 TP2). Overall survival of all patients in TP2 was significantly greater than in TP1 (P < 0.001), with a median survival of 15 months in TP2, whereas in TP1, the survival was only 9 months. The median 1-, 3-year survivals in TP2 (54 and 34%, respectively) were also greater than that in TP1 (31 and 7%, respectively). A multiple logistic regression analysis revealed that radical resection and adjuvant therapy were the independent predictors of overall survival. Conclusions: An aggressive approach, combining extended liver resection with thrombectomy and adjuvant therapy, leads to an improved survival in the HCC patients with PVTT. © 2010 The Author(s).
Wang Z.-Y.,Mindong Hospital of Ningde |
Shi A.-Y.,Mindong Hospital of Ningde |
Liu Y.,Mindong Hospital of Ningde
International Journal of Ophthalmology | Year: 2011
AIM: To investigate the interference effect of Danshen injection on apoptosis of retinal cells in experimental retinal contusion. METHODS: Forty-two pigmented rabbits were selected, and the left and right eyes were in the experimental control group and Danshen injection group, respectively. The retinal contusion model was set up by Allen's reformative hitting method. The eyeballs of the 42 pigmented rabbits were enucleated 1 hour, 3 hours, 1 day, 3, 7, 14 and 28 days after the retinal contusion model was established. Another 2 pigmented rabbits were selected as the normal control, which underwent none of the contusion but eyeball extraction at the end of the observation period. TUNEL and transmission electron microscopy were used to detect the apoptosis of the retinal cells. Cell counts and statistical analysis were used to assess results. RESULTS: There was cell apoptosis in sensory layer after contusion of retina, but almost not observed in retinas from normal control, 14, 28 days group. They were abundant in 3 hours, 1 day, 3 days group, with morphological and biochemical changes of apoptosis features of apoptotic cells, in which sensory layer of the retina in the 3 days group the number of apoptotic cells reached its peak. It was also found that apoptosis cells in Danshen injection group were less than that in the experimental control group(P<0.01). CONCLUSION: Danshen injection may inhibit the apoptosis of retinal cells in experimental retinal contusion.
Wang Z.-Y.,Mindong Hospital of Ningde |
Shi A.-Y.,Mindong Hospital of Ningde
Chinese Journal of Tissue Engineering Research | Year: 2014
BACKGROUND: Retinal contusion injury is one of the leading causes for vision impairment, and clinical treatment is difficult. Although fundus change after retinal contusion injury has been fully understood, the pathogenesis and drug treatment still remain controversial. OBJECTIVE: To explore the apoptosis and related mechanism of optic nerve cells in rabbit model of retinal contusion injury. METHODS: Forty-eight healthy adult rabbits without oculopathy were divided into eight groups: 1 hour, 3 hours, 1 day, 3 days, 7 days, 14 days, 28 days after contusion and normal control, with six rabbits in each group. Right eye of each rabbit was treated with Allen's reformative hitting method as contusive retinopathy model. The eyeballs were enucleated at different time points after injury in rabbit retina. The pathological section of optic nerve 5 mm posterior to sieve plate was harvested. The morphologic changes of optic nerve were observed and number of glial cells was measured using hematoxylin-eosin staining. Electron microscope and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling technique were used to assess apoptosis. RESULTS AND CONCLUSION: In the normal control group, glial cells presented cylinder shapes and neural fibers arranged neatly. The trend of the glial cells was as the same as the neural fibers. But the optic nerve fibers arranged in disorder and the glial cells lost polarity in the groups of 1 hour, 3 hours, 1 day, 3 days, 7 days after retinal contusion injury. The number of glial cells in 1 hour, 3 hours, 1 day, 3 days, 7 days, 14 days, and 28 days was extremely significantly reduced compared with normal control group (P < 0. 01). There was cell apoptosis in optic nerve after retinal contusion injury, but almost not observed in optic nerve from normal control group, 1 hour and 28 days after injury. The apoptotic cells were abundant at 3 hours, 1 day, 3 days, 7 days, 14 days after injury, and peaked at 3 days, showing extremely significant differences compared with normal control group (P < 0. 01). Apoptosis occurs in optic nerve after contusion of retina, which may be one of the reasons for incomplete recovery of retinal function.