Activation of MAPK signaling pathway is essential for Id-1 induced serum independent prostate cancer cell growth

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Essential Role of NK Cells in IgG Therapy for Experimental Autoimmune Encephalomyelitis

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Classification between normal and tumor tissues based on the pair-wise gene expression ratio

BACKGROUND: Precise classification of cancer types is critically important for early cancer diagnosis and treatment. Numerous efforts have been made to use gene expression profiles to improve precision of tumor classification. However, reliable cancer-related signals are generally lacking. METHOD: Using recent datasets on colon and prostate cancer, a data transformation procedure from single gene expression to pair-wise gene expression ratio is proposed. Making use of the internal consistency of each expression profiling dataset this transformation improves the signal to noise ratio of the dataset and uncovers new relevant cancer-related signals (features). The efficiency in using the transformed dataset to perform normal/tumor classification was investigated using feature partitioning with informative features (gene annotation) as discriminating axes (single gene expression or pair-wise gene expression ratio). Classification results were compared to the original datasets for up to 10-feature model classifiers. RESULTS: 82 and 262 genes that have high correlation to tissue phenotype were selected from the colon and prostate datasets respectively. Remarkably, data transformation of the highly noisy expression data successfully led to lower the coefficient of variation (CV) for the within-class samples as well as improved the correlation with tissue phenotypes. The transformed dataset exhibited lower CV when compared to that of single gene expression. In the colon cancer set, the minimum CV decreased from 45.3% to 16.5%. In prostate cancer, comparable CV was achieved with and without transformation. This improvement in CV, coupled with the improved correlation between the pair-wise gene expression ratio and tissue phenotypes, yielded higher classification efficiency, especially with the colon dataset – from 87.1% to 93.5%. Over 90% of the top ten discriminating axes in both datasets showed significant improvement after data transformation. The high classification efficiency achieved suggested that there exist some cancer-related signals in the form of pair-wise gene expression ratio. CONCLUSION: The results from this study indicated that: 1) in the case when the pair-wise expression ratio transformation achieves lower CV and higher correlation to tissue phenotypes, a better classification of tissue type will follow. 2) the comparable classification accuracy achieved after data transformation suggested that pair-wise gene expression ratio between some pairs of genes can identify reliable markers for cancer

Structural evolution in synthetic, Ca-based sorbents for carbon capture

The carbonation of CaO-based materials at high temperatures (e.g. > 600°C) is a promising method of capturing CO₂ emitted from, e.g. the combustion of carbonaceous fuels. The resulting CaCO₃ can be regenerated by calcination at a temperature at which the equilibrium partial pressure exceeds that of the local partial pressure of CO₂ (e.g. 950°C). A process involving repeated cycles of carbonation and calcination of a calcareous material is called calcium looping. The capacity of a CaO-based sorbent to accept and reject CO₂ over many cycles is governed by a number of factors, such as chemical composition, surface morphology and pore structure, all of which often evolve with cycling. The present paper investigates the underlying mechanisms controlling the evolution of the micro-structures of a series of synthetic sorbents consisting of CaO mixed with the inert supports Ca₁₂Al₁₄O₃₃ and MgO. These sorbents were subjected to cycles of calcination and carbonation and were characterised using a variety of in situ and ex situ techniques. It was found that the balance between the degree of surface cracking during calcination and the extent of sintering during carbonation was responsible for changes in uptake during cycling, giving an increase in uptake for the supported CaO and a decrease for the unsupported CaO.The authors would like to thank the Australian Synchtrotron for the award of beamtime, and Justin Kimpton and Qinfen Gu for their help with the design and operation of the in situ gas flow capillary XRD cell. Mr Zlatko Zaracevic is acknowledged for the BET measurements. W.L acknowledges funding from the National Research Foundation (NRF), Prime Minister’s Office, Singapore under its Campus for Research Excellence and Technological Enterprise (CREATE) programme. B.G acknowledges the EU Research Fund for Coal and Steel (project number RFCR-CT-2012-00008). M.T.D acknowledges funding from the Cambridge Commonwealth Trusts and Trinity College, Cambridge and the EU ERC for an advanced fellowship for CPG. D.S.S acknowledges financial support by Engineering and Physical Sciences Research Council (EPSRC). C.D.L acknowledges funding by the Australian Research Council (Discovery Projects).This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.ces.2015.09.01

Polysaccharopeptide enhanced the anti-cancer effect of gamma-tocotrienol through activation of AMPK

BACKGROUND: Prostate cancer (PCa) frequently relapses after hormone ablation therapy. Unfortunately, once progressed to the castration resistant stage, the disease is regarded as incurable as prostate cancer cells are highly resistant to conventional chemotherapy. METHOD: We recently reported that the two natural compounds polysaccharopeptide (PSP) and Gamma-tocotrienols (gamma-T3) possessed potent anti-cancer activities through targeting of CSCs. In the present study, using both prostate cancer cell line and xenograft models, we seek to investigate the therapeutic potential of combining gamma-T3 and PSP in the treatment of prostate cancer. RESULT: We showed that in the presence of PSP, gamma-T3 treatment induce a drastic activation of AMP-activated protein kinase (AMPK). This was accompanied with inactivation of acetyl-CoA carboxylase (ACC), as evidenced by the increased phosphorylation levels at Ser 79. In addition, PSP treatment also sensitized cancer cells toward gamma-T3-induced cytotoxicity. Furthermore, we demonstrated for the first time that combination of PSP and gamma-T3 treaments significantly reduced the growth of prostate tumor in vivo. CONCLUSION: Our results indicate that PSP and gamma-T3 treaments may have synergistic anti-cancer effect in vitro and in vivo, which warrants further investigation as a potential combination therapy for the treatment of cancer.published_or_final_versio

Influenza Virus-Induced Lung Inflammation Was Modulated by Cigarette Smoke Exposure in Mice

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Id-1 stimulates cell proliferation through activation of EGFR in ovarian cancer cells

Increased EGFR (epidermal growth factor receptor) expression has been reported in many types of human cancer and its levels are positively associated with advanced cancers. Recently, upregulation of Id-1 (inhibitor of differentiation or DNA binding) protein was found in over 70% of ovarian cancer samples and correlated with poor survival of ovarian cancer patients. However, the molecular mechanisms responsible for the role of Id-1 in ovarian cancer are not clear. The aim of this study was to investigate the effect of Id-1 on ovarian cancer proliferation and its association with the EGFR pathway. To achieve this, we transfected an Id-1 expression vector into three ovarian cancer cell lines and examined cell proliferation rate by flow cytometry and bromodeoxyuridine staining. We found that ectopic Id-1 expression led to increased cell proliferation demonstrated by increased BrdU incorporation rate and S-phase fraction. The Id-1-induced cell growth was associated with upregulation of EGFR at both transcriptional and protein levels. In contrast, inactivation of Id-1 through transfection of an Id-1 antisense vector resulted in downregulation of EGFR. Our results indicate that increased Id-1 in ovarian cancer cells may promote cancer cell proliferation through upregulation of EGFR. Our findings also implicate that Id-1 may be a potential target for the development of novel strategies in the treatment of ovarian cancer. © 2004 Cancer Research UK.link_to_OA_fulltex

Tie-2 regulates the stemness and metastatic properties of prostate cancer cells.

Ample evidence supports that prostate tumor metastasis originates from a rare population of cancer cells, known as cancer stem cells (CSCs). Unfortunately, little is known about the identity of these cells, making it difficult to target the metastatic prostate tumor. Here, for the first time, we report the identification of a rare population of prostate cancer cells that express the Tie-2 protein. We found that this Tie-2High population exists mainly in prostate cancer cell lines that are capable of metastasizing to the bone. These cells not only express a higher level of CSC markers but also demonstrate enhanced resistance to the chemotherapeutic drug Cabazitaxel. In addition, knockdown of the expression of the Tie-2 ligand angiopoietin (Ang-1) led to suppression of CSC markers, suggesting that the Ang-1/Tie-2 signaling pathway functions as an autocrine loop for the maintenance of prostate CSCs. More importantly, we found that Tie-2High prostate cancer cells are more adhesive than the Tie-2Low population to both osteoblasts and endothelial cells. Moreover, only the Tie-2High, but not the Tie-2Low cells developed tumor metastasis in vivo when injected at a low number. Taken together, our data suggest that Tie-2 may play an important role during the development of prostate tumor metastasis.published_or_final_versio