9,012 research outputs found
The Akt inhibitor MK-2206 enhances the cytotoxicity of paclitaxel (Taxol) and cisplatin in ovarian cancer cells
No full textAbnormalities in the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway are commonly observed in human cancers and contribute to chemotherapy resistance. Combination therapy, involving the use of molecular targeted agents and traditional cytotoxic drugs, may represent a promising strategy to lower resistance and enhance cytotoxicity. Here, we demonstrate the efficacy of an Akt inhibitor, MK-2206, in increasing the cytotoxic effect of either paclitaxel (Taxol) or cisplatin against the ovarian cancer cell lines SKOV3 (with constitutively active Akt) and ES2 (with inactive Akt). Sequential treatment of Taxol or cisplatin, followed by MK-2206, induced a synergistic inhibition of cell proliferation and effectively promoted cell death, either by inhibiting the phosphorylation of Akt and its downstream effectors 4E-BP1 and p70S6K in SKOV3 cells or by restoring p53 levels, which were downregulated after Taxol or cisplatin treatment, in ES2 cells. Combination treatment also downregulated the pro-survival protein Bcl-2 in both SKOV3 and ES2 cells, which may have contributed to cell death. In addition, we discovered that Taxol/MK-2206 or cisplatin/MK-2206 combination treatment resulted in significant enhancement of intracellular reactive oxygen species (ROS) induced by MK-2206, in both SKOV3 and ES2 cells; however, MK-2206-induced growth inhibition was reversed by a ROS scavenger only in ES2 cells. MK-2206 also suppressed DNA repair, particularly in SKOV3 cells. Taken together, our results demonstrate that the Akt inhibitor MK-2206 enhances the efficacy of cytotoxic agents in both Akt-active and Akt-inactive ovarian cancer cells but through different mechanisms
nfluence of vibrational excitation on the nonadiabatic reactions of metal atoms with H-2
No full textThe role of Umkhonto we Sizwe (MK) in the national liberation struggle in South Africa with reference to the rural far northern Transvaal, 1976-1990
No full textIncludes bibliographical references (leaves 250-275)
Better prediction of prognosis for patients with nasopharyngeal carcinoma using primary tumor volume
No full textExperiencing the armed struggle : the Soweto generation and after
No full textIncludes bibliographical references (p. 354-369).This study explores the experiences of the rank-and-file soldiers of Umkhonto we Sizwe and the Azanian People's Liberation Anny. Extensive interviews by the author and other researchers reveal the voices of the soldiers themselves. The African National Congress and Pan African Congress archives at the University of the Western Cape and the University of Fort Hare supplement and verify these oral testimonies, as do some published sources. Most previously published materials about the armed struggle against apartheid have already focused on diplomacy, strategy and tactics, operations, leadership, and human rights abuses to the neglect of the soldiers' actual experiences. This study complements these with significant new oral history materials from the Soweto generation of soldiers and their successors. When dealing with MK, many authors have documented issues of the camp structure in Angola, and operations inside South Africa, so much of this detail is only addressed briefly, leaving space to explore the soldiers' experiences. In the case of APLA, very little has been written on its history, and more detail is provided on these subjects. This study therefore deals with the soldiers' politicisation and motivation for joining the armed struggle, their experiences in leaving South Africa and training in exile, the crises in exile which limited their effectiveness for a time, their return to fight in South Africa, and their difficulties in the "new" South Africa. These materials reveal that vast problems remain facing these veterans of the struggle against apartheid, and that they have the potential, if properly supported and employed, to contribute substantially to the development of present day South Africa. Conversely, if their neglect continues, they also have the potential to bring vast harm to the country. Further use of the investigative tools of oral history, especially if extended to the former soldiers' vernacular languages, is necessary to augment the history of South Africa, and these soldiers' contributions
Mitigating the autogenous shrinkage of alkali-activated slag by metakaolin
No full textThis study investigates the effectiveness of metakaolin (MK)in mitigating the autogenous shrinkage of alkali-activated slag (AAS). It is found that the autogenous shrinkage of AAS paste can be reduced by 40% and 50% when replacing 10% and 20% slag with MK, respectively. By providing additional Si and Al, and decreasing the pH of the pore solution, the incorporation of MK retards the formation of aluminium-modified calcium silicate hydrate (CASH)gels, the main reaction products in the studied pastes. The chemical shrinkage and pore refinement are consequently mitigated, resulting in a substantial reduction in the pore pressure. Meanwhile, the elastic modulus of AAS paste is only slightly influenced after MK addition. As a result, the autogenous shrinkage of AAS is significantly mitigated by incorporating MK. In addition, the introduction of MK would extend the setting time, slightly decrease the compressive strength, but greatly increase the flexural strength of AAS.Accepted Author ManuscriptMaterials and Environmen
TRITERPENOID SAPONINS FROM ANEMONE-HUPEHENSIS
No full textFour triterpenoid saponins were isolated from Anemone hupehensis. On the basis of chemical and spectroscopic evidence, two new saponins, hupehensis saponins D and E, were elucidated as 3-O-beta-D-glucopyranosyl (1-->3)-beta-D-ribopyranosyl (1-->3)-alpha-L-rhamnopyranosyl (1-->2)-alpha-L-arabinopyranosyl oleanolic acid-28-O-alpha-L-rhamnopyranosyl (1-->4)-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranoside and 3-O-beta-D-glucopyransoyl (1-->3-beta-D-ribopyranosyl (1-->3)-alpha-L-rhamnopyranosyl (1-->2)-alpha-L-arabinopyranosyl hederagenin-28-O-alpha-L-rhamnopyranosyl (1-->4)-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranoside. The two known saponins were identified as huzhangosides B and D
Reaction Dynamics of Ca(4s3d1D2)+CH4 -> CaH(X2U+)+CH3: Reaction Pathway and Energy Disposal for the CaH Product
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