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Lymphatic reprogramming of blood vascular endothelium by Kaposi sarcoma-associated herpesvirus
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Hong YK, Foreman K, Shin JW, et al. Lymphatic reprogramming of blood vascular endothelium by Kaposi sarcoma-associated herpesvirus. Nat Genet 2004; 36:683-685.
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Hong, Y.K.1
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Kaposi sarcoma herpesvirus-induced cellular reprogramming contributes to the lymphatic endothelial gene expression in Kaposi sarcoma
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Engels EA, Pfeiffer RM, Goedert JJ, et al. Trends in cancer risk among people with AIDS in the United States 1980-2002. AIDS 2006; 20:1645-1654. • A comparison of risks for cancer in the pre and post-HAART eras in the US using AIDS and cancer registries, demonstrating a declining risk for Kaposi's sarcoma and non-Hodgkin's lymphoma, but an increased risk for Hodgkin's disease.
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Engels EA, Pfeiffer RM, Goedert JJ, et al. Trends in cancer risk among people with AIDS in the United States 1980-2002. AIDS 2006; 20:1645-1654. • A comparison of risks for cancer in the pre and post-HAART eras in the US using AIDS and cancer registries, demonstrating a declining risk for Kaposi's sarcoma and non-Hodgkin's lymphoma, but an increased risk for Hodgkin's disease.
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4
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33646413672
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Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J Cancer 2006; 118:3030-3044. • An interesting statistical analysis of the worldwide burden of cancers attributable to infectious agents, which estimates that 17.8% (1.9 million cases) of the worldwide incidence of cancer in 2002 can be attributed to infection.
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Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J Cancer 2006; 118:3030-3044. • An interesting statistical analysis of the worldwide burden of cancers attributable to infectious agents, which estimates that 17.8% (1.9 million cases) of the worldwide incidence of cancer in 2002 can be attributed to infection.
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5
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33845603155
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Whitby D, Marshall VA, Bagni RK, et al. Reactivation of Kaposi's sarcoma-associated herpesvirus by natural products from Kaposi's sarcoma endemic regions. Int J Cancer 2007; 120:321-328. • An unorthodox approach that attempts to explain the high prevalence (above 90%) of KSHV in hyperendemic regions by identifying natural products present in the environment that can increase viral reactivation.
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Whitby D, Marshall VA, Bagni RK, et al. Reactivation of Kaposi's sarcoma-associated herpesvirus by natural products from Kaposi's sarcoma endemic regions. Int J Cancer 2007; 120:321-328. • An unorthodox approach that attempts to explain the high prevalence (above 90%) of KSHV in hyperendemic regions by identifying natural products present in the environment that can increase viral reactivation.
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6
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33746832011
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The TSC2/mTOR pathway drives endothelial cell transformation induced by the Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor
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• A very thorough study showing that the KSHV vGPCR protein can activate the mTOR pathway and that mTOR may be required for KSHV-associated tumorigenesis
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Sodhi A, Chaisuparat R, Hu J, et al. The TSC2/mTOR pathway drives endothelial cell transformation induced by the Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor. Cancer Cell 2006; 10:133-143. • A very thorough study showing that the KSHV vGPCR protein can activate the mTOR pathway and that mTOR may be required for KSHV-associated tumorigenesis.
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Sodhi, A.1
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33645741486
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•] showing the KSHV K1 protein can activate the Akt/mTOR pathway and that this contributes to Kaposi's sarcoma tumorigenesis.
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•] showing the KSHV K1 protein can activate the Akt/mTOR pathway and that this contributes to Kaposi's sarcoma tumorigenesis.
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8
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33845566461
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Pantanowitz L, Dezube BJ, Hernandez-Barrantes S, et al. Matrix metalloproteinases in the progression and regression of Kaposi's sarcoma. J Cutan Pathol 2006; 33:793-798. • An immunohistochemical study showing that Kaposi's sarcoma lesional cells express MMPs, and that there is continued overexpression in partially regressed lesional tumor cells and infiltrating macrophages after treatment.
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Pantanowitz L, Dezube BJ, Hernandez-Barrantes S, et al. Matrix metalloproteinases in the progression and regression of Kaposi's sarcoma. J Cutan Pathol 2006; 33:793-798. • An immunohistochemical study showing that Kaposi's sarcoma lesional cells express MMPs, and that there is continued overexpression in partially regressed lesional tumor cells and infiltrating macrophages after treatment.
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9
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20144367584
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Sirolimus for Kaposi's sarcoma in renal-transplant recipients
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Stallone G, Schena A, Infante B, et al. Sirolimus for Kaposi's sarcoma in renal-transplant recipients. N Engl J Med 2005; 352:1317-1323.
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Sin SH, Roy D, Wang L, et al. Rapamycin is efficacious against primary effusion lymphoma (PEL) cell lines in vivo by inhibiting autocrine signaling. Blood 2007; 109:2165-2173. • Laboratory and animal study which shows that the mTOR pathway is essential for KSHV-associated PEL and that a mechanism of PEL inhibition by the mTOR inhibitor rapamycin is to inhibit autocrine growth factors such as interleukin-6 and -10.
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Sin SH, Roy D, Wang L, et al. Rapamycin is efficacious against primary effusion lymphoma (PEL) cell lines in vivo by inhibiting autocrine signaling. Blood 2007; 109:2165-2173. • Laboratory and animal study which shows that the mTOR pathway is essential for KSHV-associated PEL and that a mechanism of PEL inhibition by the mTOR inhibitor rapamycin is to inhibit autocrine growth factors such as interleukin-6 and -10.
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11
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0035892769
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Expression of p53 and human herpesvirus-8 (HHV-8)-encoded latency-associated nuclear antigen with inhibition of apoptosis in HHV-8-associated malignancies
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Katano H, Sato Y, Sata T. Expression of p53 and human herpesvirus-8 (HHV-8)-encoded latency-associated nuclear antigen with inhibition of apoptosis in HHV-8-associated malignancies. Cancer 2001; 92:3076-3084.
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Katano, H.1
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Use of liposomal anthracyclines in Kaposi's sarcoma
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Krown SE, Northfelt DW, Osoba J, Stewart JS. Use of liposomal anthracyclines in Kaposi's sarcoma. Semin Oncol 2004; 31 (Suppl 13):36-52.
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Petre CE, Sin SH, Dittmer DP. Functional p53 signaling in Kaposi's sarcoma-associated herpesvirus lymphomas: implications for therapy. J Virol 2007; 81:1912-1922. • A report which demonstrates that Nutlin-3, a p53 activator, is efficacious in PEL cell lines.
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Petre CE, Sin SH, Dittmer DP. Functional p53 signaling in Kaposi's sarcoma-associated herpesvirus lymphomas: implications for therapy. J Virol 2007; 81:1912-1922. • A report which demonstrates that Nutlin-3, a p53 activator, is efficacious in PEL cell lines.
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14
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Modeling the therapeutic efficacy of p53 restoration in tumors
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Martins CP, Brown-Swigart L, Evan GI. Modeling the therapeutic efficacy of p53 restoration in tumors. Cell 2006; 127:1323-1334.
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Restoration of p53 function leads to tumour regression in vivo
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Ventura, A.1
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Xue W, Zender L, Miething C, et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 2007; 445:656-660. •• Three reports (including [14,15]) that show that restoration and activation of wild-type p53 in established murine cancers leads to tumor regression. Provides the rationale for exploring the therapeutic potential of p53-activating agents such as Nutlin-3.
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Xue W, Zender L, Miething C, et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 2007; 445:656-660. •• Three reports (including [14,15]) that show that restoration and activation of wild-type p53 in established murine cancers leads to tumor regression. Provides the rationale for exploring the therapeutic potential of p53-activating agents such as Nutlin-3.
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17
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Herpes viral cyclin/Cdk6 complexes evade inhibition by CDK inhibitor proteins
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Cyclin-dependent kinase activity is required for efficient expression and posttranslational modification of human cytomegalovirus proteins and for production of extracellular particles
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Sanchez V, Spector DH. Cyclin-dependent kinase activity is required for efficient expression and posttranslational modification of human cytomegalovirus proteins and for production of extracellular particles. J Virol 2006; 80:5886-5896.
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Taylor SL, Kinchington PR, Brooks A, Moffat JF. Roscovitine, a cyclin-dependent kinase inhibitor, prevents replication of varicella-zoster virus. J Virol 2004; 78:2853-2862.
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Taylor SL, Kinchington PR, Brooks A, Moffat JF. Roscovitine, a cyclin-dependent kinase inhibitor, prevents replication of varicella-zoster virus. J Virol 2004; 78:2853-2862.
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0036310685
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Pharmacological cyclin-dependent kinase inhibitors inhibit replication of wild-type and drug-resistant strains of herpes simplex virus and human immunodeficiency virus type 1 by targeting cellular, not viral, proteins
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Schang LM, Bantly A, Knockaert M, et al. Pharmacological cyclin-dependent kinase inhibitors inhibit replication of wild-type and drug-resistant strains of herpes simplex virus and human immunodeficiency virus type 1 by targeting cellular, not viral, proteins. J Virol 2002; 76:7874-7882.
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Inhibition of cellular Cdk2 activity blocks human cytomegalovirus replication
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Bresnahan WA, Boldogh I, Chi P, et al. Inhibition of cellular Cdk2 activity blocks human cytomegalovirus replication. Virology 1997; 231:239-247.
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Viral cyclin-cyclin-dependent kinase 6 complexes initiate nuclear DNA replication
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Cannon M, Cesarman E, Boshoff C. KSHV G protein-coupled receptor inhibits lytic gene transcription in primary-effusion lymphoma cells via p21-mediated inhibition of Cdk2. Blood 2006; 107:277-284. • A report that further underscores the multiple roles that the KSHV vGPCR plays in KSHV pathogenesis.
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Cannon M, Cesarman E, Boshoff C. KSHV G protein-coupled receptor inhibits lytic gene transcription in primary-effusion lymphoma cells via p21-mediated inhibition of Cdk2. Blood 2006; 107:277-284. • A report that further underscores the multiple roles that the KSHV vGPCR plays in KSHV pathogenesis.
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Upton JW, Speck SH. Evidence for CDK-dependent and CDK-independent functions of the murine gammaherpesvirus 68 v-cyclin. J Virol 2006; 80:11946-11959. • Provides experimental evidence that viral cyclins have functions that are not dependent on associated kinase activity.
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Upton JW, Speck SH. Evidence for CDK-dependent and CDK-independent functions of the murine gammaherpesvirus 68 v-cyclin. J Virol 2006; 80:11946-11959. • Provides experimental evidence that viral cyclins have functions that are not dependent on associated kinase activity.
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Krug LT, Moser JM, Dickerson SM, Speck SH. Inhibition of NF-kappaB activation in vivo impairs establishment of gammaherpesvirus latency. PLoS Pathog 2007; 3:e11. • An in-vivo demonstration that underscores the importance of NF-kappa B in KSHV/γ herpesvirus pathogenesis.
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Krug LT, Moser JM, Dickerson SM, Speck SH. Inhibition of NF-kappaB activation in vivo impairs establishment of gammaherpesvirus latency. PLoS Pathog 2007; 3:e11. • An in-vivo demonstration that underscores the importance of NF-kappa B in KSHV/γ herpesvirus pathogenesis.
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Antitumor effects of bortezomib (PS-341) on primary effusion lymphomas
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Angiogenesis inhibitor IM862 is ineffective against AIDS-Kaposi's sarcoma in a phase III trial, but demonstrates sustained, potent effect of highly active antiretroviral therapy: From the AIDS Malignancy Consortium and IM862 Study Team
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Loss of p53 impedes the antileukemic response to BCR-ABL inhibition
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Dezube BJ, Krown SE, Lee JY, et al. Matrix metalloproteinase inhibitor COL-3 in the treatment of AIDS-related Kaposi's sarcoma: A phase II AIDS Malignancy Consortium Study. J Clin Oncol 2006; 24:1389-1394. • A randomized phase II trial of the matrix metalloproteinase inhibitor, COL-3, demonstrating activity of this agent in AIDS-associated Kaposi's sarcoma, with superior activity and better tolerance at the lower of two doses.
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Dezube BJ, Krown SE, Lee JY, et al. Matrix metalloproteinase inhibitor COL-3 in the treatment of AIDS-related Kaposi's sarcoma: A phase II AIDS Malignancy Consortium Study. J Clin Oncol 2006; 24:1389-1394. • A randomized phase II trial of the matrix metalloproteinase inhibitor, COL-3, demonstrating activity of this agent in AIDS-associated Kaposi's sarcoma, with superior activity and better tolerance at the lower of two doses.
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Little RF, Pluda JM, Wyvill KM, et al. Activity of subcutaneous interleukin-12 in AIDS-related Kaposi sarcoma. Blood 2006; 107:4650-4657. • An escalating dose phase I/II clinical trial of interleukin-12, demonstrating substantial antitumor activity in patients with AIDS-associated Kaposi's sarcoma.
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Little RF, Pluda JM, Wyvill KM, et al. Activity of subcutaneous interleukin-12 in AIDS-related Kaposi sarcoma. Blood 2006; 107:4650-4657. • An escalating dose phase I/II clinical trial of interleukin-12, demonstrating substantial antitumor activity in patients with AIDS-associated Kaposi's sarcoma.
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A phase I trial of protease inhibitor-based antiretroviral therapy with recombinant interferon alfa-2b in patients with HIV-related Kaposi's sarcoma
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• A phase I trial of the combination of recombinant IFN-α with protease inhibitor-based antiretroviral therapy that established the maximum tolerated dose of IFN as part of this combination, but showed no effect on clearance of KSHV
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Krown SE, Lee JY, Lin L, et al. A phase I trial of protease inhibitor-based antiretroviral therapy with recombinant interferon alfa-2b in patients with HIV-related Kaposi's sarcoma. J Aquired Immun Defic Syndr 2006; 41:149-153. • A phase I trial of the combination of recombinant IFN-α with protease inhibitor-based antiretroviral therapy that established the maximum tolerated dose of IFN as part of this combination, but showed no effect on clearance of KSHV.
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J Aquired Immun Defic Syndr
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Lebbe C, Euvrard S, Barrou B, et al. Sirolimus conversion for patients with posttransplant Kaposi's sarcoma. Am J Transplant 2006; 6:2164-2168. • A retrospective study of 14 cases of posttransplant Kaposi's sarcoma, showing two complete responses, eight partial responses and five nonresponses after switching from a calcineurin inhibitor to sirolimus. Three partial responders relapsed after 5-9 months while still on sirolimus therapy. The authors stress the need for prospective studies with pharmacodynamic evaluation to better assess the mechanisms of primary and acquired drug resistance.
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Lebbe C, Euvrard S, Barrou B, et al. Sirolimus conversion for patients with posttransplant Kaposi's sarcoma. Am J Transplant 2006; 6:2164-2168. • A retrospective study of 14 cases of posttransplant Kaposi's sarcoma, showing two complete responses, eight partial responses and five nonresponses after switching from a calcineurin inhibitor to sirolimus. Three partial responders relapsed after 5-9 months while still on sirolimus therapy. The authors stress the need for prospective studies with pharmacodynamic evaluation to better assess the mechanisms of primary and acquired drug resistance.
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Kauffman HM, Cherikh WS, McBride MA, et al. Posttransplant de novo malignancies in renal transplant recipients: the past and present. Transpl Int 2006; 19:607-620. • A review of posttransplant malignancies from transplant registries and transplant center reports, documenting the incidence of cancers in different eras according to the type of posttransplant immunosuppression.
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Kauffman HM, Cherikh WS, McBride MA, et al. Posttransplant de novo malignancies in renal transplant recipients: the past and present. Transpl Int 2006; 19:607-620. • A review of posttransplant malignancies from transplant registries and transplant center reports, documenting the incidence of cancers in different eras according to the type of posttransplant immunosuppression.
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Campistol JM, Eris J, Oberbauer R, et al. Sirolimus therapy after early cyclosporine withdrawal reduces the risk for cancer in adult renal transplantation. J Am Soc Nephrol 2006; 17:581-589. • Report of a trial in renal allograft recipients randomized to either continue on cyclosporine with sirolimus and corticosteroids or to have cyclosporine withdrawn and sirolimus levels increased. Risks of skin and nonskin cancers were decreased in the group in which cyclosporine was discontinued.
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Campistol JM, Eris J, Oberbauer R, et al. Sirolimus therapy after early cyclosporine withdrawal reduces the risk for cancer in adult renal transplantation. J Am Soc Nephrol 2006; 17:581-589. • Report of a trial in renal allograft recipients randomized to either continue on cyclosporine with sirolimus and corticosteroids or to have cyclosporine withdrawn and sirolimus levels increased. Risks of skin and nonskin cancers were decreased in the group in which cyclosporine was discontinued.
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32944457518
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O'Reilly KE, Rojo F, She QB, et al. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 2006; 66:1500-1508. •• An interesting study with potentially important clinical implications that explores the mechanisms of resistance of tumor cells to mTOR inhibitors. The authors demonstrate that feedback downregulation of receptor tyrosine kinase signaling is a frequent event in tumor cells with constitutive mTOR activation. Reversal of this feedback loop by rapamycin may attenuate its therapeutic effects, whereas combination therapy that ablates mTOR function and prevents Akt activation may result in improved antitumor activity.
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O'Reilly KE, Rojo F, She QB, et al. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 2006; 66:1500-1508. •• An interesting study with potentially important clinical implications that explores the mechanisms of resistance of tumor cells to mTOR inhibitors. The authors demonstrate that feedback downregulation of receptor tyrosine kinase signaling is a frequent event in tumor cells with constitutive mTOR activation. Reversal of this feedback loop by rapamycin may attenuate its therapeutic effects, whereas combination therapy that ablates mTOR function and prevents Akt activation may result in improved antitumor activity.
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Akt plays a central role in sarcomagenesis induced by Kaposi's sarcoma herpesvirus-encoded G protein-coupled receptor
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Evaluation of antitumoral properties of the protease inhibitor indinavir in a murine model of hepatocarcinoma
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Srirangam A, Mitra R, Wang M, et al. Effects of HIV protease inhibitor ritonavir on Akt-regulated cell proliferation in breast cancer. Clin Cancer Res 2006; 12:1883-1896. • Three reports (including [41,42]) that explore the mechanisms by which HIV protease inhibitors can inhibit cancer cell growth and which are independent of their effects on the viral protease target.
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Srirangam A, Mitra R, Wang M, et al. Effects of HIV protease inhibitor ritonavir on Akt-regulated cell proliferation in breast cancer. Clin Cancer Res 2006; 12:1883-1896. • Three reports (including [41,42]) that explore the mechanisms by which HIV protease inhibitors can inhibit cancer cell growth and which are independent of their effects on the viral protease target.
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