15 research outputs found
A network data-based survey and analysis of attention towards breast reconstruction after breast cancer surgery in Chinese and American populations
Background: Breast reconstruction is an effective technique to rebuild the appearance of the breasts in patients after mastectomy and improves the prognosis. The current study aimed to compare and analyze willingness for breast reconstruction after breast cancer between populations in China and the United States, from the perspective of social concern, using big data analysis. We also aimed to explore factors affecting surgical selection and to identify methods that can improve social cognition and acceptance of breast reconstruction. Methods: Using Baidu and Google, two representative Internet search engines in China and the United States as research tools, and using big data search volume as the benchmark, we compared and analyzed breast reconstruction willingness and attention characteristics between Chinese and American people, based on search heat, geographical distribution, age and sex, keyword distribution, ethnic group, and social development degree. Results: In both the long-term and short-term, Chinese people paid more attention towards searching about breast cancer, but less attention to breast reconstruction after breast cancer surgery. However, in both the short-term and long-term, people from the United States paid more attention towards breast cancer and breast reconstruction with the help of the Internet, showing a synchronous change relationship. There was a large regional difference in the search volume for breast cancer among the Chinese population, while no significant regional differences were noted in the search volume for breast cancer in the United States. However, a large regional difference was observed in the search volume for breast reconstruction between the two countries; people in the coastal and economically developed areas paid more attention to it. Most people who paid attention to breast reconstruction in China were women aged 20–39 years, while the attention among men was low. Search keywords were also limited to breast cancer-related information. However, between Asians and European Americans, Americans paid more attention to breast cancer and were affected by regional development, religious beliefs, and health facilities. Conclusion: Attention towards breast reconstruction after breast cancer was lower in the Chinese population than in the American population, and this difference was closely related to the level of regional development. There is insufficient information on breast reconstruction after breast cancer in recent Internet media. In addition to strengthening communication in clinics, media education is important to improve the cognitive level and social awareness of patients and their families, which is conducive to breast reconstruction
Liposomal C6 Ceramide Activates Protein Phosphatase 1 to Inhibit Melanoma Cells.
Melanoma is one common skin cancer. In the present study, the potential anti-melanoma activity by a liposomal C6 ceramide was tested in vitro. We showed that the liposomal C6 (ceramide) was cytotoxic and anti-proliferative against a panel of human melanoma cell lines (SK-Mel2, WM-266.4 and A-375 and WM-115). In addition, liposomal C6 induced caspase-dependent apoptotic death in the melanoma cells. Reversely, its cytotoxicity was attenuated by several caspase inhibitors. Intriguingly, liposomal C6 was non-cytotoxic to B10BR mouse melanocytes and primary human melanocytes. Molecularly, liposomal C6 activated protein phosphatase 1 (PP1) to inactivate Akt-mammalian target of rapamycin (mTOR) signaling in melanoma cells. On the other hand, PP1 shRNA knockdown or exogenous expression of constitutively activate Akt1 (CA-Akt1) restored Akt-mTOR activation and significantly attenuated liposomal C6-mediated cytotoxicity and apoptosis in melanoma cells. Our results suggest that liposomal C6 activates PP1 to inhibit melanoma cells
VS-5584 and ABT-737 synergistically inhibits A375 xenograft growth <i>in vivo</i>-A375 bearing nude mice (n = 10 for each group) were treated with vehicle control (SX-1292, “C”), VS-5584 (“VS”, oral, 25 mg/kg/d for 21 days), ABT-737 (“ABT”, oral, 25 mg/kg/d for 21 days), or VS-5584 plus ABT-737 combo (“Com”), tumor volumes (A and B) and mice body weights (C) were recorded.
<p>Two weeks after initial drug administration, xenografted tumors of two mice per group were isolated, expressions of listed proteins in the tumor lysates were tested and quantified (D). Data were expressed as mean ± SD, experiments were repeated twice. *<i>p</i><0.05 vs group “C”. **<i>p</i><0.05 vs “VS-5584” only group. ***<i>p</i><0.05 vs “ABT-737” only group.</p
VS-5584 inhibits melanoma cell survival and proliferation-Established melanoma cell lines (A375, A-2058 and SK-MEL-3), patient-derived primary melanoma cells, B10BR melanocytes and primary human keratinocytes (“Kera”) were treated with applied concentration of VS-5585 (“VS”) or vehicle control (“C”, 0.1% of DMSO), cell survival was tested by MTT assay (A, E and F) and trypan blue exclusion assay (B, for A375 cells); Cell proliferation was analyzed by through [H<sup>3</sup>] Thymidine incorporation assay (C, for A375 cells) and clonogenicity assay (D, for A375 cells).
<p>Data were expressed as mean ± SD, experiments were repeated three times. *<i>p</i><0.05 vs group “C”.</p
VS-5584, a Novel PI3K-mTOR Dual Inhibitor, Inhibits Melanoma Cell Growth <i>In Vitro</i> and <i>In Vivo</i>
<div><p>Melanomas cause over 76% of skin cancer deaths annually. Phosphatidylinositol 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) signaling pathway is important for melanoma initiation and progression. In the current study, we evaluated the potential anti-melanoma effect of VS-5584, a novel and highly potent PI3K-mTOR dual inhibitor. We demonstrated that VS-5584 potently inhibited survival and proliferation of established (A375, A-2058 and SK-MEL-3 lines) and primary human melanoma cells, but was non-cytotoxic to non-cancerous human skin keratinocytes and B10BR murine melanocytes. At the meantime, VS-5584 induced caspase-dependent apoptotic death in melanoma cells, and its cytotoxicity was alleviated by the caspase inhibitors. At the molecular level, VS-5584 blocked AKT-mTOR activation and downregulated cyclin D1 expression in melanoma cells, while the expressions of Bcl-xL and Bcl-2 were not affected by VS-5584 treatment. On the other hand, a BH-3 mimetic Bcl-xL/Bcl-2 inhibitor ABT-737, as well as siRNA-mediated knockdown of Bcl-xL or Bcl-2, enhanced the activity of VS-5584 in melanoma cells. <i>In vivo</i>, oral administration of VS-5584 suppressed A375 melanoma xenograft growth in nude mice, and its activity was further enhanced by co-administration of ABT-737. These results provide the rationale for the clinical assessment of VS-5584 in melanoma patients and development of ABT-737 and other Bcl-xL/Bcl-2 inhibitors as the possible adjuvants.</p></div
Bcl-xL/Bcl-2 inhibition sensitizes VS-5584-mediated activity in melanoma cells-A375 cells (A and B), primary human melanoma cells (F), B10BR murine melanocytes (G) or primary human keratinocytes (“Kera”) (G) were treated with VS-5584 (“VS”, 10 nM) or plus ABT-737 (“ABT”, 25 nM) for 72 hours, cell viability (MTT assay) and apoptosis (ELISA assay, for A375 cells) were tested.
<p>A375 cells, transfected with scramble control siRNA (sc-RNAi), Bcl-2 siRNA or Bcl-xL siRNA, were treated with VS-5584 (VS, 10 nM) for 72 hours, expression of Bcl-2, Bcl-xL and GAPDH was tested by Western blots (C, their expressions were quantified), cell survival (D) and apoptosis (E) were also tested. Data were expressed as mean ± SD, experiments were repeated three times. “C” stands for vehicle control (0.1% of DMSO). *<i>p</i><0.05 vs group “C”. **<i>p</i><0.05 vs “VS” only group (A, B and F). **<i>p</i><0.05 vs sc-RNAi group (D and E).</p
VS-5584 induces melanoma cell apoptosis-A375 cells, pre-treated with the caspase-3 inhibitor z-DVED-fmk (“dved”, 60 μM), the pan caspase inhibitor z-VAD-fmk (“vad”, 60 μM), were treated with applied concentration of VS-5584 (“VS”) for indicated time, caspase-3/-9 activity was analyzed as described (A), cell apoptosis was tested by Histone-DNA ELISA assay (B) and Annexin V FACS assay (C), cell survival and proliferation were tested by MTT assay (D) and clonogenicity assay (E), respectively.
<p>Patient-derived primary melanoma cells were treated with VS-5584 (“VS”, 25 nM) or vehicle control (“C”, 0.1% of DMSO) for 48 hours, cell apoptosis was assayed by Histone-DNA ELISA assay (F). Data were expressed as mean ± SD, experiments were repeated three times. *<i>p</i><0.05 vs group “C”. **<i>p</i><0.05 vs “VS” (25 nM) only group (B-E).</p
Signaling changes by VS-5584 in melanoma cells-A375 and A-2058 cells were treated with VS-5584 (“VS”, 25 nM) or the vehicle control (1% DMSO, “C”) for 6 hours (for A and B) or 24 hours (for C), expression of listed proteins was tested by Western blots.
<p>Relative intensity of kinase phosphorylations (vs. non-phosphorylated kinases) as well as cyclin D1 and Bcl-2 expression (vs. GAPDH) of three independent experiments were shown (A-C, lower panels). Data were expressed as mean ± SD, experiments were repeated three times. *<i>p</i><0.05 vs group “C”.</p
Liposomal C6 activates protein phosphatase, and inhibits Akt-mTOR signaling in melanoma cells.
<p>Cultured melanoma cell lines (WM-115 and A-375) were either left untreated (“Ctrl”), treated with applied concentration of liposomal C6 ceramide (“Lipo C6”) or liposomal ghost (“Lipo”), cells were further cultured for applied time, protein phosphatase activity (A and B) and expression of listed kinases (C and E) were tested. Akt and P70S6K1 phosphorylations were quantified (D and F). Experiments were repeated three times, and similar results were obtained. Data were presented as mean ± SD. * p<0.05 vs. “Ctrl” group.</p
Activation of PP1 is required for liposomal C6-induced anti-melanoma cell activity <i>in vitro</i>.
<p>Stable WM-115 cells expressing the pan PP1 shRNA, constitutively-activate mutant Akt1 (“CA-Akt1”), or empty vector (“pSuper-puro”) were treated with or without applied concentration of liposomal C6 ceramide (“Lipo C6”), expression of listed proteins was tested by Western blots (A); Relative protein phosphatase activity was shown (B); Cell survival (C), and cell apoptosis (D) were tested by MTT assay and Annexin V assay, respectively. Experiments were repeated three times, and similar results were obtained. Data were presented as mean ± SD. *p<0.05 vs. untreated “Ctrl” group. <sup>#</sup> p<0.05 vs. “Lipo C6” of Vector group.</p