Structural micro-fat graft is one of the surgical techniques for facial rejuvenation, and it is reliable for correction of sunken upper eyelids especially. However, several factors may influence surgical outcomes substancially. The author introduces the modified micro-fat graft to correct sunken eyelids and multiple eyelid folds to make better results. A series of 162 patients who underwent the refined structural micro-fat graft were included in this study. The purified fat was injected into the subcutaneous and sub-orbicularis oculi muscle layer of the upper eyelids through the 19-gauge cannula with 1 ml syringe. After the operation, all patients were followed up on 2 weeks, 1 month, 3 months, 6months, and 1 year. Clinical photographs were taken every visit and the author evaluated the volume and symmetry of the eyelids and checked the satisfaction of each patient and any complications. Among the 162 patients, 156 patients were satisfied with the upper eyelid volume after primary fat graft and other 6 patients were performed secondary fat graft. Even though the volume of the fat was sufficient, 4 patients showed palpable fat nodule during the follow-up period. Modified micro-fat graft is a simple, safe, and alternative method to correct sunken eyelids and multiple eyelid folds.
Blepharoplasty ; Catheters ; Eyelids ; Follow-Up Studies ; Humans ; Muscles ; Rejuvenation ; Syringes ; Transplants

Metformin is an anti-diabetic drug and has anticancer effects on various cancers. Several studies have suggested that metformin reduces cell proliferation and stimulates cell-cycle arrest and apoptosis. However, the definitive molecular mechanism of metformin in the pathophysiological signaling in endometrial tumorigenesis and metastasis is not clearly understood. In this study, we examined the effects of metformin on the cell viability and apoptosis of human cervical HeLa and endometrial HEC-1-A and KLE cancer cells. Metformin suppressed cell growth in a dose-dependent manner and dramatically evoked apoptosis in HeLa cervical cancer cells, while apoptotic cell death and growth inhibition were not observed in endometrial (HEC-1-A, KLE) cell lines. Accordingly, the p27 and p21 promoter activities were enhanced while Bcl-2 and IL-6 activities were significantly reduced by metformin treatment. Metformin diminished the phosphorylation of mTOR, p70S6K and 4E-BP1 by accelerating adenosine monophosphateactivated kinase (AMPK) in HeLa cancer cells, but it did not affect other cell lines. To determine why the anti-proliferative effects are observed only in HeLa cells, we examined the expression level of liver kinase B1 (LKB1) since metformin and LKB1 share the same signalling system, and we found that the LKB1 gene is not expressed only in HeLa cancer cells. Consistently, the overexpression of LKB1 in HeLa cancer cells prevented metformin-triggered apoptosis while LKB1 knockdown significantly increased apoptosis in HEC-1-A and KLE cancer cells. Taken together, these findings indicate an underlying biological/physiological molecular function specifically for metformin-triggered apoptosis dependent on the presence of the LKB1 gene in tumorigenesis.

The imprinted tumour suppressor NOEY2 is downregulated in various cancer types, including ovarian cancers. Recent data suggest that NOEY2 plays an essential role in regulating the cell cycle, angiogenesis and autophagy in tumorigenesis. However, its detailed molecular function and mechanisms in ovarian tumours remain unclear. In this report, we initially demonstrated the inhibitory effect of NOEY2 on tumour growth by utilising a xenograft tumour model. NOEY2 attenuated the cell growth approximately fourfold and significantly reduced tumour vascularity. NOEY2 inhibited the phosphorylation of the signalling components downstream of phosphatidylinositol-3’-kinase (PI3K), including phosphoinositide-dependent protein kinase 1 (PDK-1), tuberous sclerosis complex 2 (TSC-2) and p70 ribosomal protein S6 kinase (p70S6K), during ovarian tumour progression via direct binding to vascular endothelial growth factor receptor-2 (VEGFR-2). Particularly, the N-terminal domain of NOEY2 (NOEY2-N) had a potent anti-angiogenic activity and dramatically downregulated VEGF and hypoxia-inducible factor-1α (HIF-1α), key regulators of angiogenesis. Since no X-ray or nuclear magnetic resonance structures is available for NOEY2, we constructed the threedimensional structure of this protein via molecular modelling methods, such as homology modelling and molecular dynamic simulations. Thereby, Lys15 and Arg16 appeared as key residues in the N-terminal domain. We also found that NOEY2-N acts as a potent inhibitor of tumorigenesis and angiogenesis. These findings provide convincing evidence that NOEY2-N regulates endothelial cell function and angiogenesis by interrupting the VEGFR-2/PDK-1/GSK-3β signal transduction and thus strongly suggest that NOEY2-N might serve as a novel anti-tumour and anti-angiogenic agent against many diseases, including ovarian cancer.

The imprinted tumour suppressor NOEY2 is downregulated in various cancer types, including ovarian cancers. Recent data suggest that NOEY2 plays an essential role in regulating the cell cycle, angiogenesis and autophagy in tumorigenesis. However, its detailed molecular function and mechanisms in ovarian tumours remain unclear. In this report, we initially demonstrated the inhibitory effect of NOEY2 on tumour growth by utilising a xenograft tumour model. NOEY2 attenuated the cell growth approximately fourfold and significantly reduced tumour vascularity. NOEY2 inhibited the phosphorylation of the signalling components downstream of phosphatidylinositol-3’-kinase (PI3K), including phosphoinositide-dependent protein kinase 1 (PDK-1), tuberous sclerosis complex 2 (TSC-2) and p70 ribosomal protein S6 kinase (p70S6K), during ovarian tumour progression via direct binding to vascular endothelial growth factor receptor-2 (VEGFR-2). Particularly, the N-terminal domain of NOEY2 (NOEY2-N) had a potent anti-angiogenic activity and dramatically downregulated VEGF and hypoxia-inducible factor-1α (HIF-1α), key regulators of angiogenesis. Since no X-ray or nuclear magnetic resonance structures is available for NOEY2, we constructed the threedimensional structure of this protein via molecular modelling methods, such as homology modelling and molecular dynamic simulations. Thereby, Lys15 and Arg16 appeared as key residues in the N-terminal domain. We also found that NOEY2-N acts as a potent inhibitor of tumorigenesis and angiogenesis. These findings provide convincing evidence that NOEY2-N regulates endothelial cell function and angiogenesis by interrupting the VEGFR-2/PDK-1/GSK-3β signal transduction and thus strongly suggest that NOEY2-N might serve as a novel anti-tumour and anti-angiogenic agent against many diseases, including ovarian cancer.

Snail is implicated in tumour growth and metastasis and is up-regulated in various human tumours. Although the role of Snails in epithelial-mesenchymal transition, which is particularly important in cancer metastasis, is well known, how they regulate tumour growth is poorly described. In this study, the possible molecular mechanisms of Snail in tumour growth were explored. Baculoviral inhibitor of apoptosis protein (IAP) repeat-containing protein 3 (BIRC3), a co-activator of cell proliferation during tumourigenesis, was identified as a Snail-binding protein via a yeast two-hybrid system. Since BIRC3 is important for cell survival, the effect of BIRC3 binding partner Snail on cell survival was investigated in ovarian cancer cell lines. Results revealed that Bax expression was activated, while the expression levels of anti-apoptotic proteins were markedly decreased by small interfering RNA (siRNA) specific for Snail (siSnail). siSnail, the binding partner of siBIRC3, activated the tumour suppressor function of p53 by promoting p53 protein stability. Conversely, BIRC3 could interact with Snail, for this reason, the possibility of BIRC3 involvement in EMT was investigated. BIRC3 overexpression resulted in a decreased expression of the epithelial marker and an increased expression of the mesenchymal markers. siSnail or siBIRC3 reduced the mRNA levels of matrix metalloproteinase (MMP)-2 and MMP-9. These results provide evidence that Snail promotes cell proliferation by interacting with BIRC3 and that BIRC3 might be involved in EMT via binding to Snail in ovarian cancer cells. Therefore, our results suggested the novel relevance of BIRC3, the binding partner of Snail, in ovarian cancer development.

Cervical tumors represent a prevalent form of cancer affecting women worldwide; current treatment options involve surgery, radiotherapy, and chemotherapy. Angiogenesis, the process of new blood vessel formation, is a crucial factor in cervical tumor growth. The molecular mechanisms underlying the effects of the liver kinase B1 (LKB1/STK11) tumor suppressor protein on tumor angiogenesis have not been elucidated. Therefore, we investigated the role of LKB1 in cervical tumor angiogenesis both in vitro and in vivo in this study. Our results demonstrated that LKB1 inhibited cervical tumor angiogenesis by suppressing the expression of angiogenesis-related factors such as vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1α. LKB1 directly affected both carcinoma and vascular endothelial cells, resulting in a significant reduction in tumor growth and angiogenesis. Furthermore, LKB1 was found to bind to VEGF receptor 2 (VEGFR-2) and target the VEGFR-2-mediated protein kinase B/ mechanistic target of rapamycin signaling pathway in endothelial cells, thereby reducing cervical tumor growth and angiogenesis.Our study provides new insights into the molecular mechanisms underlying the anti-tumor and anti-angiogenic effects of LKB1 in cervical cancer. These findings will help develop new therapeutic strategies for cervical cancer.

Liver kinase B1 (LKB1) is a crucial tumor suppressor involved in various cellular processes, including embryonic development, tumor initiation and progression, cell adhesion, apoptosis, and metabolism. However, the precise mechanisms underlying its functions remain elusive. In this study, we demonstrate that LKB1 interacts directly with malic enzyme 3 (ME3) through the N-terminus of the enzyme and identified the binding regions necessary for this interaction. The binding activity was confirmed to promote the expression of ME3 in an LKB1-dependent manner and was also shown to induce apoptosis activity. Furthermore, LKB1 and ME3 overexpression upregulated the expression of tumour suppressor proteins (p53 and p21) and downregulated the expression of antiapoptotic proteins (nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and B-cell lymphoma 2 (Bcl-2)). Additionally, LKB1 and ME3 enhanced the transcription of p21 and p53 and inhibited the transcription of NF-κB. Moreover, LKB1 and ME3 suppressed the phosphorylation of various components of the phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B signaling pathway. Overall, these results suggest that LKB1 promotes pro-apoptotic activities by inducing ME3 expression.

Glycoproteins isolated from fruit bodies and mycelial cultures of mushrooms exhibit anti-carcinogenic actions in human cancer cells and animal tumor cells by induction of apoptosis. Here, we report that isoflavone-conjugated glycoproteins (designate Gluvone), exhibit strong anti-carcinogenic effects on human breast cancer MCF-7 cells by induction of apoptosis. Gluvone with 9.4 kDa of molecular weight was isolated from submerged-liquid culture of Agaricus blazei mycelia (ABM) in soy flake-containing liquid medium. MCF-7 cells were incubated with various amounts of Gluvone (0~250 microM) for a period of 6 days. Gluvone exhibited anti-proliferative actions in a dose-dependent manner and 62% growth inhibition at 200 microM for 4 days relative to control. Hoechst 33258 staining analysis revealed that Gluvone induced formation of apoptotic bodies. Gluvone was associated with down-regulation of anti-apoptotic Bcl-2 protein expression as well as up-regulation of pro-apoptotic Bax protein expression. Gluvone treatment induced proteolytic activation of caspase-9 and caspase-3 through cytochrome c release from mitochondria to cytosol as well as concomitant degradation of poly (ADP-ribose) polymerase (PARP). In addition, Gluvone induced activation of caspase-8. Taken all together, these results indicate that the anti-proliferative effect of Gluvone is associated with induction of apoptotic cell death through the mitochondrial dysfunction pathway mediated by enhancement of Bax protein expression and suppression of Bcl-2 protein expression.
Agaricales ; Agaricus* ; Animals ; Anticarcinogenic Agents ; Apoptosis ; bcl-2-Associated X Protein* ; Bisbenzimidazole ; Breast Neoplasms ; Caspase 3 ; Caspase 8 ; Caspase 9 ; Cell Death ; Cytochromes c ; Cytosol ; Down-Regulation ; Fruit ; Glycoproteins* ; Humans ; Isoflavones* ; MCF-7 Cells ; Mitochondria ; Molecular Weight ; Up-Regulation

The anti-proliferative efficacy of t,t-conjugated linoleic acid (t,t-CLA), c9,t11-CLA, and t10,c12-CLA was compared in several human cancer cell lines. Gastric NCI-N87, liver Hep3B, pancreas Capan-2, and lung NCI-H522 cancer cells were incubated with 50 microM CLA isomers over a period of 6 days. The t,t-CLA inhibited the growth of all cancer cell lines to different extents, but c9,t11-CLA and t10,c12-CLA inhibited or stimulated the growth of the cancer cell lines. NCI-N87 cells were the most sensitive to growth inhibition and apoptosis from all CLA isomers tested. In NCI-N87 cells, CLA isomers reduced the release of arachidonic acid (AA) via the inhibition of cytosolic phospholipase A2 (cPLA2) activity, consequently reducing the production of PGE2 through the inhibition of cyclooxygenase-2 (COX-2). The efficacies of CLA isomers were in the following order (from most to least effective): t,t-CLA, t10,c12-CLA and c9,t11-CLA. Overall, these results imply that the anti-proliferative efficacy of t,t-CLA on cancer cells, especially NCI-N87 cells, was greater than other CLA isomers due to its induction of apoptosis through the inhibition of cPLA2 and COX-2 activities.
Apoptosis ; Arachidonic Acid ; Cell Line* ; Cyclooxygenase 2 ; Cytosol ; Dinoprostone ; Humans* ; Linoleic Acid* ; Liver ; Lung ; Pancreas ; Phospholipases A2

PURPOSE: The purpose of this study was to evaluate the factors that are associated with the accuracy of magnetic resonance (MR) imaging for predicting myometrial invasion and lymph node metastasis in women with endometrial carcinoma. MATERIALS AND METHODS: We retrospectively reviewed the medical records and preoperative MR imaging reports of 128 women who had pathologically proven endometrial carcinoma. We compared the MR imaging and the histopathology findings. RESULTS: The sensitivity, specificity and accuracy for identifing any myometrial invasion (superficial or deep) were 0.81, 0.61 and 0.74, respectively; these values for deep myometrial invasion were 0.60, 0.94 and 0.86, respectively. The sensitivity, specificity and accuracy of MR imaging for detecting lymph node metastasis were 50.0%, 96.6% and 93.0%, respectively. The patients who were older, had more deliveries and a larger tumor size more frequently had incorrect prediction of deep myometrial invasion (p=0.034, p=0.044, p=0.061, respectively). A higher tumor grade, a histology other than the endometrioid type, myometrial invasion on MR findings and a larger tumor size were associated with a more frequent false-negative prediction of lymph node metastasis (p=0.018, p=0.017, p=0.002, p=0.047, respectively). A larger tumor size was also associated with more frequent false-positive results (p=0.009). CONCLUSIONS: There are several factors that make accurate assessment of myometrial invasion or lymph node metastasis difficult with using MRI; therefore, the patients with these factors should have their MR findings cautiously interpreted.
Endometrial Neoplasms* ; Female ; Humans ; Lymph Nodes* ; Magnetic Resonance Imaging* ; Medical Records ; Neoplasm Metastasis* ; Retrospective Studies ; Sensitivity and Specificity