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Lahiri V. L. Srivastava R. K. Hazra D. K. Gupta A. K. Painuly N. K. Sharma S. K. Khanna-Hazra P. Khanna P. Gupta R. K. Pathak Manish 《Cell biochemistry and biophysics》1994,24(1-3):9-14
Cell Biochemistry and Biophysics - Despite attempts to maintain asepsis, good manufacturing practices, and the use of terminal sterilization by millipore filtration, the nuclear practitioner is... 相似文献
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Vijay Ramakrishnan Teresa Kimlinger Jessica Haug Utkarsh Painuly Linda Wellik Timothy Halling S. Vincent Rajkumar Shaji Kumar 《PloS one》2012,7(11)
The PI3K/Akt/mTOR signal transduction pathway plays a central role in multiple myeloma (MM) disease progression and development of therapeutic resistance. mTORC1 inhibitors have shown limited efficacy in the clinic, largely attributed to the reactivation of Akt due to rapamycin induced mTORC2 activity. Here, we present promising anti-myeloma activity of MK-2206, a novel allosteric pan-Akt inhibitor, in MM cell lines and patient cells. MK-2206 was able to induce cytotoxicity and inhibit proliferation in all MM cell lines tested, albeit with significant heterogeneity that was highly dependent on basal pAkt levels. MK-2206 was able to inhibit proliferation of MM cells even when cultured with marrow stromal cells or tumor promoting cytokines. The induction of cytotoxicity was due to apoptosis, which at least partially was mediated by caspases. MK-2206 inhibited pAkt and its down-stream targets and up-regulated pErk in MM cells. Using MK-2206 in combination with rapamycin (mTORC1 inhibitor), (PI3K inhibitor), or U0126 (MEK1/2 inhibitor), we show that Erk- mediated downstream activation of PI3K/Akt pathway results in resistance to Akt inhibition. These provide the basis for clinical evaluation of MK-2206 alone or in combination in MM and potential use of baseline pAkt and pErk as biomarkers for patient selection. LY294002相似文献
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Hazra D. K. Lahiri V. L. Gupta A. K. Painuly N. K. Pathak Manish Khanna Pankaj Gupta R. K. Khanna-Hazra P. Saran Shabd 《Cell biochemistry and biophysics》1994,24(1-3):1-7
Radiosilver-111 and Radiogold-199 were proposed by us (1) as suitable isotopes for radioimmunotherapy in areas such as India by reason of their suitable half-lives and B-emissions
(Ag-111T
1/2=7.45 d and Au-199T
1/2=3.15 d). Since silver is monovalent, it is difficult to link to conventional bifunctional chelates. We therefore explored
the use of sulfur-based linkers (2). Encouraged by the Thakur and De Fulvio Technique (3) of linking technetium to disulfide
groups in antibodies reduced by ascorbic acid that is eminently biocompatible, we have explored the linkage of silver to immunoglobulin
reduced by ascorbic acid. The linkage of silver was assessed with stable Ag-108 using dialysis to quantify the free silver
after the reaction of silver and reduced immunoglobulins in various molar ratios (1∶1, 1∶2, 1∶5, 1∶10). The silver quantity
was estimated gravimetrically after precipitation as chloride. It was observed that using these molar ratios there was negligible
silver efflux into the dialysate, suggesting stable linkage. We also assessed the linkage using Ag-110M as radiotracer. The
comparative results with the two techniques are described. 相似文献
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