Colorectal cancer is one of the commonest of solid malignancy in the world. Activating transcription factor 3 (ATF3), a homolog of the mouse TI-241 and rat LFR-1, is a stress responsive gene that has been widely indicated in different malignancies. However, the role of ATF3 in colon cancer is paradoxical with both a suggested pro- and anti-tumorigenic role. The objective of the current study was to investigate the role of ATF3 in colon cancer metastasis using HT29 and CaCO2 colon cancer cell lines. Expression of ATF3 was initially evaluated in five pairs of colon cancer and matched noncancerous colon tissues. The role of ATF3 in promoting in vitro migration and invasion were evaluated by siRNA-mediated knockdown and adenovirus-mediated overexpression of ATF3. In addition, the role of ATF3 in promoting in vivo tumor growth and hepatic metastasis was investigated by shRNA-mediated knockdown of ATF3. Expression of ATF3 was more in the colon cancer tissues as compared with the pooled noncancerous control colon tissue. Our results showed that in both HT29 and CaCO2 cells, ATF3 promoted in vitro motility and invasion. Furthermore, knockdown of ATF3 attenuated subcutaneous tumor growth and CD31(+) neovasculature in xenograft assays with HT29 and CaCO2 cells and inhibited hepatic metastasis. Cumulatively, our results unequivocally show that ATF3 promotes colon cancer metastasis.
Complete spontaneous thrombosis followed by recanalization of non-giant aneurysms is a rare event that can be discovered incidentally on advanced neural images. In this case report, the authors described a woman who presented with subarachnoid hemorrhage (SAH) and left posterior cerebral artery (PCA) territory ischemic stroke. Cerebral angiography revealed a left PCA aneurysm at the P1-P2 junction. The patient received conservative treatment and repeated cerebral angiography 4 weeks later demonstrated the disappeared aneurysm. Subsequent magnetic resonance imaging (MRI) and contrast-enhanced computed tomography (CT) demonstrated the totally thrombosed aneurysm with hydrocephalus. Ventriculo-peritoneal shunt surgery for hydrocephalus was performed and the patient noted a great improvement of the neurological deficit. Follow-up contrast-enhanced CT after 10 weeks revealed recurrence of the aneurysm. This case provides insight into the natural dynamic process of intracranial aneurysm, and a complete thrombosed aneurysm has the potential for recanalization. KEywoRds: Intracranial aneurysm, Subarachnoid hemorrhage, Spontaneous thrombosis, Recanalization ÖZDev olmayan anevrizmalarda rekanalizasyonla birlikte tam spontan tromboz nadirdir ve gelişmiş nöral görüntülerde tesadüfen bulunabilir. Bu olgu raporunda yazarlar subaraknoid kanama (SAK) ve sol posterior serebral arter (PSA) bölgesinde iskemik inmeyle gelen bir hastayı sunmaktadır. Serebral anjiyografi P1-P2 bileşkesinde bir sol PSA anevrizması göstermiştir. Hastaya konservatif tedavi verilmiş ve 4 hafta sonra tekrarlanan serebral anjiyografi anevrizmanın kaybolduğunu ortaya koymuştur. Daha sonraki manyetik rezonans görüntüleme (MRG) ve kontrastlı bilgisayarlı tomografi (BT) total tromboze olmuş anevrizma ve hidrosefali göstermiştir. Hidrosefali için ventriküloperitoneal şant cerrahisi yapılmış ve hastanın nörolojik defisinde büyük bir düzelme görmüştür. 10 hafta sonra takip kontrastlı BT anevrizmanın tekrarladığını göstermiştir. Bu olgu bir intrakraniyal anevrizmanın doğal dinamik süreci konusunda bilgi sağlamaktadır ve tam trombozlu bir anevrizmada rekanalizasyon potansiyeli mevcuttur.
BackgroundThere are two completely contradictory views regarding the impact of human bone-marrow-derived mesenchymal stem cells (hMSCs) on hepatocellular carcinomas (HCCs). The aim of this study was to investigate the effect of hMSC engraftment on HCC tissues in nude mouse models, and assess the effect on metastatic potential of HCC.MethodshMSCs were engrafted into the nude mouse models of high metastatic HCC via the tail vein. The mice in the experimental group were engrafted with hMSCs (5 × 105 cells per mouse) via the tail vein 15 days after inoculation of tumor cells, twice a week, while the animals in the control group were injected with hMSC culture medium (0.2 mL per mouse) via the tail vein. The subcutaneous tumor size was measured using an electronic digital caliper once every 4 days after hMSC engraftment. After 2, 3, 4, 5 and 6 weeks of tumor cell inoculation, the mice were killed and the tumors were collected in their entirety. The tumor weights and body weights of mice were measured, and the tumor inhibition rate was calculated. Quantitative real-time polymerase chain reaction (RT-PCR) was used to determine the expression of metastasis-related genes including osteopontin (OPN), bone sialoprotein (BSP) and integrin α5 subunit (α-V) in the mouse models of high-metastatic HCC, and the expression of apoptosis-related genes including B cell lymphoma/leukemia-2 (Bcl2), Bcl-2 associated X protein (Bax) and caspase 3 in tumor samples.ResultsThe tumor weight inhibition rate was 26.62% at 2 weeks, 52.00% at 3 weeks, 38.20% at 4 weeks, 31.98% at 5 weeks, and 30.23% at 6 weeks. Tumor tissue weight comparison results were significantly lower in the hMSC engraftment groups than in the control group at the second and third weeks. The expression of metastasis-related factors OPN, BSP and α-V gene was downregulated with time. The expression of antiapoptotic gene Bcl2 exhibited an obvious declining tendency, while the expression of apoptotic genes Bax and caspase 3 showed an obvious rising tendency. The expression of α-V and BSP significantly correlated positively with the expression of Bcl2, and negatively correlated with the expression of Bax and caspase 3. The tumor inhibition rate was not significantly correlated with the expression of antiapoptotic and apoptotic factors, and α-V and BSP factors, though it exhibited a significantly negative correlation with the expression of OPN.ConclusionsThe highest tumor inhibition rate was observed 3 weeks after hMSCs engraftment, and the tumor inhibition rate gradually reduced with the progression of time. The metastatic potential of tumor cells was downregulated after hMSC engraftment and hMSCs induce further tumor cells apoptosis. The decrease in the proliferation ability of tumor cells may induce a decline in metastatic potential in tumor cells.
BackgroundThis study investigates the effects of human bone marrow-derived mesenchymal stem cell (hMSC) on migration and proliferation ability of hepatocellular carcinoma (HCC) with high- and low-metastatic potential.MethodsThe hMSC and transforming growth factor-β1 (TGFβ-1) gene infected hMSC were co-cultured with hepatoma cells. The ability of cells migration was assessed by Transwell assay. The ability of cells proliferation was detected using CCK-8 assay. The mice were engrafted with hMSC and TGFβ-1 gene infected hMSC, respectively, after hepatoma cells inoculation 15 days, twice a week for 6 weeks successively. The tumor inhibition rate was calculated. TGFβ-1, osteopontin (OPN), and programmed cell death protein 4 (PDCD4) genes expression of hepatoma cells were detected by quantitative real-time polymerase chain reaction (qPCR) before and after co-cultured experiments.ResultsTGFβ-1 infected hMSC or hMSC co-culture with hepatoma cells groups can significantly promote hepatoma cells proliferation (P < 0.05). The migration numbers of hepatoma cells with TGFβ-1 infected hMSC co-culture groups were significantly reduced compared with the other two groups (P < 0.05). The tumors weight inhibition rates of MHCC97-H and MHCC97-L animal models were the highest in the third week by hMSC engraftment. But the highest tumor inhibition rate of MHCC97-H animal models was observed in the fourth week and MHCC97-L animal models in the fifth week after TGFβ-1 infected hMSC engraftment. OPN gene relative quantitative expression of hepatoma cells was significantly down-regulated after co-cultured with hMSC and TGFβ-1 gene infected hMSC groups (P < 0.05). TGFβ-1 gene relative quantitative expression of MHCC97-H and MHCC97-L cells was significantly up-regulated after co-cultured with TGFβ-1 gene infected hMSC groups (P < 0.05). PDCD4 expression had no statistical differences among groups.ConclusionshMSC and TGFβ-1 gene infected hMSC can promote hepatoma cells proliferation and inhibit hepatoma cells migration. hMSC and TGFβ-1 gene infected hMSC exhibit anti-tumor activity in a time-dependent manner. TGFβ-1 cytokine may be the main factor in HCC proliferation. OPN makes a significant contribution to the changes of hepatoma cells metastasis.
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