assay-to-measure-nucleocytoplasmic-transport-real-time-within-motor

Assay to Measure Nucleocytoplasmic Transport in Real Time within Motor Neuron-like NSC-34 Cells

Nucleocytoplasmic transport refers to the import and export of large molecules from the cell nucleus. Recently, a number of studies have shown a ...

Ben-Gurion University of the Negev

&quot;&#x540C;&#x79CD;&#x5F02;&#x4F53;&#x6548;&#x5E94;&quot;&#x662F;&#x6307;&#x8BF1;&#x5BFC; B &#x7EC6;&#x80DE;&#x7684;&#x6297;&#x4F53;&#x5408;&#x6210;&#x4E3B;&#x673A;&#x6216;&#x4E3B;&#x673A; T &#x7EC6;&#x80DE;&#x7684;&#x7EC6;&#x80DE;&#x6BD2;&#x6027;&#x4F5C;&#x7528;&#xFF0C;&#x5305;&#x62EC;&#x540C;&#x79CD;&#x5F02;&#x4F53;&#x6DCB;&#x5DF4;&#x7EC6;&#x80DE;&#x8F93;&#x6CE8;&#x7684;&#x6297;&#x80BF;&#x7624;&#x6D3B;&#x6027;&#x3002;&#x6211;&#x4EEC;&#x663E;&#x793A;&#x6CBB;&#x7597;&#x5C0F;&#x9F20;&#x73AF;&#x78F7;&#x9170;&#x80FA; &#xFF08;Cy&#xFF09; &#x8DDF; CD8(+) &#x8017;&#x7AED; T &#x7EC6;&#x80DE;&#x540C;&#x79CD;&#x5F02;&#x4F53;&#x8005;&#x6DCB;&#x5DF4;&#x7EC6;&#x80DE;&#x8F93;&#x6CE8; (Cy + CD8(-) DLI) &#x4E0E;&#x8840;&#x6DB2;&#x548C;&#x56FA;&#x4F53;&#x764C;&#x75C7;&#x6A21;&#x578B;&#x4E2D;&#x7684;&#x6700;&#x5C0F;&#x6BD2;&#x6027;&#x8BF1;&#x5BFC;&#x56DE;&#x5F52;&#x7684;&#x65E2;&#x5B9A;&#x80BF;&#x7624;&#x5373;&#x4F7F;&#x6350;&#x52A9;&#x7EC6;&#x80DE;&#x6700;&#x7EC8;&#x88AB;&#x5BBF;&#x4E3B;&#x514D;&#x75AB;&#x7CFB;&#x7EDF;&#x62D2;&#x7EDD;&#x3002;Cy + CD8(-) DLI &#x7406;&#x60F3;&#x7684;&#x6297;&#x80BF;&#x7624;&#x6548;&#x679C;&#x6240;&#x9700;&#x7684;&#x6350;&#x52A9; CD4(+) T &#x7EC6;&#x80DE;&#x3001; &#x4E3B;&#x673A; CD8(+) T &#x7EC6;&#x80DE;&#x548C;&#x6297;&#x539F;&#x8868;&#x8FBE;&#x6B63;&#x5E38;&#x4E3B;&#x673A;&#x4F46;&#x4E0D;&#x662F;&#x80BF;&#x7624;&#x7EC4;&#x7EC7;&#x7684;&#x5B58;&#x5728;&#x3002;&#x7ED3;&#x679C;&#x652F;&#x6301;&#x7684;&#x6350;&#x52A9; CD4(+) T &#x7EC6;&#x80DE;&#x4ECB;&#x5BFC;&#x79FB;&#x690D;&#x7269;&#x6297;&#x5BBF;&#x4E3B; (&#x5308;&#x7259;&#x5229;) &#x53CD;&#x5E94;&#x6709;&#x6548;&#x5524;&#x9192; Cy &#x8010;&#x4E3B;&#x673A; CD8(+) T &#x7EC6;&#x80DE;&#x6297;&#x80BF;&#x7624;&#x514D;&#x75AB;&#x80FD;&#x529B;&#x6A21;&#x578B;&#x3002;&#x8FD9;&#x4E9B;&#x4E8B;&#x4EF6;&#x63D0;&#x4F9B;&#x7684;&#x6297;&#x80BF;&#x7624;&#x514D;&#x75AB;&#x7EC6;&#x80DE;&#x673A;&#x7406;&quot;&#x540C;&#x79CD;&#x5F02;&#x4F53;&#x6548;&#x5E94;&quot;&#x3002;Cy + CD8(-) DLI &#x53EF;&#x80FD;&#x89C9;&#x9192;&#x5230;&#x665A;&#x671F;&#x764C;&#x75C7;&#x7684;&#x5BBF;&#x4E3B;&#x514D;&#x75AB;&#x53CD;&#x5E94;&#x7684;&#x6709;&#x6548;&#x548C;&#x5FAE;&#x6709;&#x6BD2;&#x7684;&#x6218;&#x7565;&#x3002;

&#x91CD;&#x65B0;&#x5BA1;&#x67E5;&#x7684;&#x540C;&#x79CD;&#x5F02;&#x4F53;&#x6548;&#x5E94;&#xFF1A; &#x5185;&#x6E90;&#x6027;&#x3001; &#x80BF;&#x7624;&#x7279;&#x5F02;&#x6027; T &#x7EC6;&#x80DE;&#x7684;&#x5916;&#x6E90;&#x5E2E;&#x52A9;&#x3002;

The "allogeneic effect" refers to the induction of host B cell antibody synthesis or host T cell cytotoxicity, including tumoricidal activity, by an infusion of allogeneic lymphocytes. We show that treatment of mice with cyclophosphamide (Cy) followed by CD8(+) T cell-depleted allogeneic donor lymphocyte infusion (Cy + CD8(-) DLI) induces regression of established tumors with minimal toxicity in models of both hematologic and solid cancers, even though the donor cells are eventually rejected by the host immune system. The optimal antitumor effect of Cy + CD8(-) DLI required the presence of donor CD4(+) T cells, host CD8(+) T cells, and alloantigen expression by normal host but not tumor tissue. The results support a model in which a donor CD4(+) T cell-mediated graft-versus-host (GVH) reaction effectively awakens antitumor immunity among Cy-resistant host CD8(+) T cells. These events provide the cellular mechanism of the "allogeneic effect" in antitumor immunity. Cy + CD8(-) DLI may be an effective and minimally toxic strategy for awakening the host immune response to advanced cancers.

The allogeneic effect revisited: exogenous help for endogenous, tumor-specific T cells.

L&#39;effet &laquo; allog&egrave;ne &raquo; se r&eacute;f&egrave;re &agrave; l&#39;induction de l&#39;h&ocirc;te B cellule synth&egrave;se d&#39;anticorps ou l&#39;h&ocirc;te cytotoxicit&eacute; des lymphocytes T, y compris l&#39;activit&eacute; d&#39;effets, par une injection de lymphocytes allog&eacute;niques. Nous montrons que traitement des souris avec cyclophosphamide (Cy), suivi de CD8 infusion de lymphocyte de donneurs allog&eacute;niques d&eacute;pl&eacute;tion des lymphocytes T (Cy + appel&eacute;s IDD) induit une r&eacute;gression des tumeurs &eacute;tablies avec une toxicit&eacute; minimale dans les mod&egrave;les de cancers h&eacute;matologiques et de solides, m&ecirc;me si les cellules du donneur sont finalement rejet&eacute;s par le syst&egrave;me immunitaire. L&#39;effet antitumoral optimale de Cy + appel&eacute;s IDD exigeait la pr&eacute;sence de cellules T CD4 +, cellules T CD8 h&ocirc;tes et expression alloantig&egrave;ne par h&ocirc;te normal mais pas les tissus tumoraux. Les r&eacute;sultats supportent un mod&egrave;le dans lequel des r&eacute;actions donneur CD4 + T cell-mediated greffon contre h&ocirc;te (GVH) r&eacute;veille efficacement immunit&eacute; antitumorale chez les cellules T CD8 h&ocirc;te Cy-r&eacute;sistant. Ces &eacute;v&eacute;nements fournissent le m&eacute;canisme cellulaire de l&#39;effet &laquo; allog&egrave;ne &raquo; dans l&#39;immunit&eacute; anti-tumorale. CY + appel&eacute;s IDD peut &ecirc;tre une strat&eacute;gie efficace et tr&egrave;s peu toxique pour l&#39;&eacute;veil de la r&eacute;ponse immunitaire h&ocirc;te &agrave; cancers avanc&eacute;s.

L&#39;effet allog&eacute;nique revisit&eacute; : aide exog&egrave;ne pour endog&egrave;nes, sp&eacute;cifique des lymphocytes T.

Der &quot;allogene-Effekt&quot; bezieht sich auf die Induktion von Host B-Zell-Antik&ouml;rper-Synthese oder Host T-Zell-Zytotoxizit&auml;t, einschlie&szlig;lich der Tumoricidal-Aktivit&auml;t, durch eine Infusion von allogenen Lymphozyten. Wir zeigen, dass die Behandlung von M&auml;usen mit Cyclophosphamid (Cy), gefolgt von CD8(+) T-Zell-abgereichertem allogene Spender-Lymphozyten-Infusion (Cy + CD8(-) DLI) mit minimaler Toxizit&auml;t in Modellen sowohl feste als auch h&auml;matologische Krebserkrankungen R&uuml;ckbildung der etablierten Tumoren induziert, obwohl die Spenderzellen schlie&szlig;lich durch das Immunsystem abgelehnt werden. Der optimale antitumor-Effekt von Cy + CD8(-) DLI ben&ouml;tigt die Anwesenheit von Spenderzellen CD4(+) T, CD8(+) T Wirtszellen und Alloantigen Ausdruck von normalen Host aber nicht Tumorgewebe. Die Ergebnisse unterst&uuml;tzen ein Modell in dem Spender CD4(+) T-Zell-vermittelten Graft-versus-Host (GVH) Reaktion effektiv antitumor Immunit&auml;t unter Cy-resistente CD8(+) T Wirtszellen erwacht. Diese Ereignisse stellen den zellul&auml;ren Mechanismus des &quot;allogene Effekts&quot; antitumor-Festigkeit. CY + CD8(-) DLI m&ouml;glicherweise eine wirksame und minimal toxischen Strategie zum erwecken der Host Immunantwort zu fortgeschrittenen Tumorerkrankungen.

Die allogene Wirkung revisited: exogene Hilfe f&uuml;r endogene, Tumor-spezifischer T-Zellen.

L&#39;effetto&quot;allogenica&quot; si riferisce all&#39;induzione di sintesi anticorpale B cell host o host citotossicit&agrave; delle cellule T, compresa l&#39;attivit&agrave; tumoricidal, da un&#39;infusione di linfociti allogenici. Mostriamo che trattamento di topi con ciclofosfamide (Cy) seguito da infusione di linfociti T cell-impoverito donatore allogenico (Cy + CD8(-) DLI) cellule induce la regressione dei tumori stabiliti con tossicit&agrave; minima in modelli di tumori ematologici e solidi, anche se le cellule del donatore sono infine respinto dal sistema immunitario ospite. L&#39;effetto antitumorale ottima di Cy + DLI CD8(-) necessaria la presenza di cellule T CD4(+) donatore, host cellule T ed espressione alloantigen dalla normale host, ma non il tessuto tumorale. I risultati supportano un modello in cui una reazione mediata da cellule T graft-versus-host (GVH) di donatore CD4(+) risveglia efficacemente l&#39;immunit&agrave; antitumorale tra cellule cellule T Cy-resistente. Questi eventi forniscono il meccanismo cellulare il &laquo;effetto allogenico&raquo; nell&#39;immunit&agrave; antitumorale. CY + DLI CD8(-) pu&ograve; essere una strategia efficacia e minimamente tossica per risveglio la risposta immunitaria ai tumori avanzati.

L&#39;effetto allogenico rivisitato: aiuto esogeno endogeno, tumore-specifiche cellule T.

&#x300C;&#x540C;&#x7A2E;&#x52B9;&#x679C;&#x300D;&#x30DB;&#x30B9;&#x30C8; B &#x7D30;&#x80DE;&#x6297;&#x4F53;&#x306E;&#x5408;&#x6210;&#x306E;&#x8A98;&#x5C0E;&#x307E;&#x305F;&#x306F;&#x30DB;&#x30B9;&#x30C8; T &#x7D30;&#x80DE;&#x6BD2;&#x6027;&#x3001;&#x540C;&#x7A2E;&#x306E;&#x30EA;&#x30F3;&#x30D1;&#x7403;&#x306E;&#x6CE8;&#x5165;&#x306B;&#x3088;&#x308B;&#x6297;&#x816B;&#x760D;&#x6D3B;&#x6027;&#x3092;&#x542B;&#x3080;&#x3092;&#x6307;&#x3057;&#x307E;&#x3059;&#x3002;&#x306B;&#x3082;&#x304B;&#x304B;&#x308F;&#x3089;&#x305A;&#x3001;&#x30C9;&#x30CA;&#x30FC;&#x7D30;&#x80DE;&#x306F;&#x3001;&#x6700;&#x7D42;&#x7684;&#x306B;&#x3001;&#x30DB;&#x30B9;&#x30C8;&#x514D;&#x75AB;&#x30B7;&#x30B9;&#x30C6;&#x30E0;&#x306B;&#x3088;&#x3063;&#x3066;&#x62D2;&#x5426;&#x3055;&#x308C;&#x307E;&#x3059;&#x6CBB;&#x7642;&#x3060;&#x308D;&#x3046;&#x3053;&#x306B;&#x3088;&#x3063;&#x3066; T &#x7D30;&#x80DE;&#x67AF;&#x6E07;&#x30C9;&#x30CA;&#x30FC; &#x30EA;&#x30F3;&#x30D1;&#x7403;&#x6CE8;&#x5165; (Cy + CD8(-) DLI) &#x30B7;&#x30AF;&#x30ED;&#x30DB;&#x30B9;&#x30D5;&#x30A1;&#x30DF;&#x30C9; (Cy) &#x3092;&#x6301;&#x3064;&#x30DE;&#x30A6;&#x30B9;&#x306E;&#x304C;&#x3093;&#x306F;&#x3001;&#x8840;&#x6DB2;&#x3068;&#x56FA;&#x4F53;&#x306E;&#x4E21;&#x65B9;&#x306E;&#x30E2;&#x30C7;&#x30EB;&#x3067;&#x6700;&#x5C0F;&#x9650;&#x306E;&#x6BD2;&#x6027;&#x304C;&#x78BA;&#x7ACB;&#x3055;&#x308C;&#x305F;&#x816B;&#x760D;&#x306E;&#x56DE;&#x5E30;&#x3092;&#x8A98;&#x5C0E;&#x3059;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x3057;&#x307E;&#x3059;&#x3002;&#x6700;&#x9069;&#x306A;&#x6297;&#x816B;&#x760D;&#x52B9;&#x679C;&#x306E; Cy + CD8(-) DLI &#x30C9;&#x30CA;&#x30FC; CD4(+) T &#x7D30;&#x80DE;&#x3001;&#x30DB;&#x30B9;&#x30C8;&#x3060;&#x308D;&#x3046;&#x3053;&#x306E; T &#x7D30;&#x80DE;&#x3001;&#x30A2;&#x30ED;&#x5F0F;&#x306B;&#x3088;&#x3063;&#x3066;&#x901A;&#x5E38;&#x306E;&#x30DB;&#x30B9;&#x30C8;&#x304C;&#x306A;&#x3044;&#x816B;&#x760D;&#x7D44;&#x7E54;&#x306E;&#x5B58;&#x5728;&#x304C;&#x5FC5;&#x8981;&#x3002;&#x7D50;&#x679C;&#x3067;&#x30C9;&#x30CA;&#x30FC; CD4(+) T &#x7D30;&#x80DE;&#x306B;&#x3088;&#x308B;&#x79FB;&#x690D;&#x7247;&#x5BFE;&#x5BBF;&#x4E3B; (GVH&#xFF09; &#x53CD;&#x5FDC;&#x304C; Cy &#x8010;&#x6027;&#x30DB;&#x30B9;&#x30C8;&#x3060;&#x308D;&#x3046;&#x3053;&#x306E; T &#x7D30;&#x80DE;&#x9593;&#x306E;&#x6297;&#x816B;&#x760D;&#x514D;&#x75AB;&#x3092;&#x52B9;&#x679C;&#x7684;&#x306B;&#x76EE;&#x899A;&#x3081;&#x308B;&#x30E2;&#x30C7;&#x30EB;&#x3092;&#x30B5;&#x30DD;&#x30FC;&#x30C8;&#x3057;&#x307E;&#x3059;&#x3002;&#x3053;&#x308C;&#x3089;&#x306E;&#x30A4;&#x30D9;&#x30F3;&#x30C8;&#x300C;&#x540C;&#x7A2E;&#x306E;&#x52B9;&#x679C;&#x300D;&#x306E;&#x7D30;&#x80DE;&#x30E1;&#x30AB;&#x30CB;&#x30BA;&#x30E0;&#x306B;&#x304A;&#x3051;&#x308B;&#x6297;&#x816B;&#x760D;&#x514D;&#x75AB;&#x3092;&#x63D0;&#x4F9B;&#x3057;&#x307E;&#x3059;&#x3002;Cy + CD8(-) DLI &#x9032;&#x884C;&#x764C;&#x306B;&#x5BBF;&#x4E3B;&#x514D;&#x75AB;&#x5FDC;&#x7B54;&#x3092;&#x76EE;&#x899A;&#x3081;&#x306E;&#x52B9;&#x679C;&#x7684;&#x3067;&#x6700;&#x5C0F;&#x6709;&#x6BD2;&#x306A;&#x6226;&#x7565;&#x304C;&#x3042;&#x308A;&#x307E;&#x3059;&#x3002;

&#x540C;&#x7A2E;&#x306E;&#x52B9;&#x679C;&#x518D;&#x8003;:&#x3001;&#x816B;&#x760D;&#x56FA;&#x6709;&#x306E;&#x5185;&#x56E0;&#x6027; T &#x7D30;&#x80DE;&#x306E;&#x5916;&#x56E0;&#x6027;&#x30D8;&#x30EB;&#x30D7;&#x3002;

&quot;&#xD6A8;&#xACFC;&quot; allogeneic &#xD638;&#xC2A4;&#xD2B8; B &#xC138;&#xD3EC; &#xD56D; &#xCCB4; &#xD569;&#xC131; &#xC720;&#xB3C4; &#xB610;&#xB294; &#xD638;&#xC2A4;&#xD2B8; allogeneic &#xC138;&#xD3EC;&#xC758; &#xC8FC;&#xC785;&#xC5D0; &#xC758;&#xD574; &#xCCAD;&#xC18C;&#xB144; &#xD65C;&#xB3D9;&#xC744; &#xD3EC;&#xD568; &#xD55C; T&#xC758; &#xC138;&#xD3EC; &#xC138;&#xD3EC; &#xB3C5;&#xC131;&#xC744; &#xB9D0;&#xD569;&#xB2C8;&#xB2E4;. &#xC6B0;&#xB9AC;&#xB294; &#xAE30;&#xC99D;&#xC790; &#xC138;&#xD3EC; &#xACB0;&#xAD6D; &#xC219;&#xC8FC; &#xBA74;&#xC5ED; &#xCCB4;&#xACC4;&#xC5D0; &#xC758;&#xD574; &#xAC70;&#xBD80; &#xD558;&#xB294; &#xACBD;&#xC6B0;&#xC5D0; CD8(+) T &#xC138;&#xD3EC; &#xACE0;&#xAC08; allogeneic &#xAE30;&#xC99D;&#xC790; &#xB9BC;&#xD504; &#xAD6C; &#xC8FC;&#xC785; (&#xC2F8;&#xC774; + CD8(-) DLI) &#xC774;&#xC5B4;&#xC11C; cyclophosphamide (Cy)&#xC640; &#xC950;&#xC758; &#xCE58;&#xB8CC; &#xD608;&#xC561;&#xD559; &#xBC0F; &#xACE0;&#xCCB4; &#xC554;&#xC758; &#xBAA8;&#xB378;&#xC5D0; &#xCD5C;&#xC18C;&#xD55C;&#xC758; &#xB3C5;&#xC131;&#xC73C;&#xB85C; &#xC124;&#xB9BD;&#xB41C; &#xC885;&#xC591;&#xC758; &#xC7AC;&#xBC1C;&#xC744; &#xC720;&#xB3C4; &#xBCF4;&#xC5EC;&#xC90D;&#xB2C8;&#xB2E4;. &#xC2F8;&#xC774; + CD8(-) DLI &#xCD5C;&#xC801;&#xC758; antitumor &#xD6A8;&#xACFC; &#xAE30;&#xC99D;&#xC790; CD4(+) T &#xC138;&#xD3EC;, &#xD638;&#xC2A4;&#xD2B8; CD8(+) T &#xC138;&#xD3EC;&#xC640; &#xC77C;&#xBC18; &#xD638;&#xC2A4;&#xD2B8; &#xD558;&#xC9C0; &#xC885;&#xC591; &#xC870;&#xC9C1;&#xC5D0; &#xC758;&#xD574; alloantigen &#xC2DD;&#xC758; &#xC874;&#xC7AC;&#xB97C; &#xD544;&#xC694;&#xD569;&#xB2C8;&#xB2E4;. &#xACB0;&#xACFC;&#xB294; &#xAE30;&#xC99D;&#xC790; CD4(+) T &#xC138;&#xD3EC; &#xC911;&#xC7AC; &#xC774;&#xC2DD;-&#xB300;-&#xD638;&#xC2A4;&#xD2B8; (GVH) &#xBC18;&#xC751;&#xC744; &#xD6A8;&#xACFC;&#xC801;&#xC73C;&#xB85C; Cy &#xB0B4; &#xD638;&#xC2A4;&#xD2B8; CD8(+) T &#xC138;&#xD3EC; &#xAC04;&#xC758; antitumor &#xBA74;&#xC5ED; &#xAE68;&#xC5B4;&#xB09C;&#xB2E4; &#xBAA8;&#xB378;&#xC744; &#xC9C0;&#xC6D0; &#xD569;&#xB2C8;&#xB2E4;. &#xC774;&#xB7EC;&#xD55C; &#xC774;&#xBCA4;&#xD2B8;&#xB294; antitumor &#xB0B4;&#xC131;&#xC744; &quot;allogeneic &#xD6A8;&#xACFC;&quot;&#xC758; &#xC138;&#xD3EC; &#xBA54;&#xCEE4;&#xB2C8;&#xC998;&#xC744; &#xC81C;&#xACF5;&#xD569;&#xB2C8;&#xB2E4;. &#xC2F8;&#xC774; + CD8(-) DLI &#xACE0;&#xAE09; &#xC554;&#xC5D0; &#xD638;&#xC2A4;&#xD2B8; &#xBA74;&#xC5ED; &#xC751;&#xB2F5;&#xC744; &#xAC01; &#xC131;&#xC744; &#xC704;&#xD55C; &#xD6A8;&#xACFC;&#xC801;&#xC774; &#xACE0; &#xCD5C;&#xC18C; &#xB3C5;&#xC131; &#xC804;&#xB7B5;&#xC744; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;.

&#xC7AC;&#xAC80;&#xD1A0; allogeneic &#xD6A8;&#xACFC;: &#xC0DD;, &#xC885;&#xC591; &#xAD00;&#xB828; T cells exogenous &#xB3C4;&#xC6C0;&#xB9D0;.

El &quot;efecto alog&eacute;nico&quot; se refiere a la inducci&oacute;n de host s&iacute;ntesis de anticuerpo de c&eacute;lulas B o host Citotoxicidad celular T, incluyendo actividad tumoricida, por una infusi&oacute;n de linfocitos alog&eacute;nicos. Mostramos que tratamiento de ratones con ciclofosfamida (Cy) seguido por CD8 infusi&oacute;n de linfocitos de donantes alog&eacute;nicos T c&eacute;lula-agotado (Cy + CD8(-) DLI) induce la regresi&oacute;n de tumores establecidos con toxicidad m&iacute;nima en modelos de c&aacute;nceres hematol&oacute;gicos tanto s&oacute;lidos, a pesar de que las c&eacute;lulas del donante son finalmente rechazadas por el sistema inmunol&oacute;gico de su hu&eacute;sped. El efecto antitumoral &oacute;ptimo de Cy + DLI CD8(-) necesaria la presencia de c&eacute;lulas CD4 T del donante, las c&eacute;lulas CD8 T del hu&eacute;sped y expresi&oacute;n aloant&iacute;geno por host normal pero no tejido del tumor. Los resultados apoyan un modelo en el que una reacci&oacute;n de donantes CD4 mediada por c&eacute;lulas T graft-versus-host (GVH) efectivamente despierta inmunidad antitumoral entre las de c&eacute;lulas T CD8 anfitri&oacute;n de Cy-resistente. Estos eventos proporcionan el mecanismo celular del &quot;efecto alog&eacute;nico&quot; en inmunidad antitumoral. CY + CD8(-) DLI puede ser una estrategia efectiva y m&iacute;nimamente t&oacute;xica para despertar la inmunorespuesta del anfitri&oacute;n a c&aacute;nceres avanzados.

El efecto allogeneic revisitado: ayuda ex&oacute;gena para c&eacute;lulas T end&oacute;genas, tumorales.

Cryoablation of a solitary tumor mass releases intact tumor antigens and can induce protective antitumor immunity but has limited efficacy in the treatment of established metastatic cancer. Cyclophosphamide (Cy), an anticancer drug, selectively depletes regulatory T cells (T(reg)s) and attenuates suppression of antitumor immunity. We used a BALB/c mouse model of metastatic colon cancer to investigate the systemic antitumor effects of in situ cryotherapy alone or in combination with 200 mg/kg i.p. Cy. When combined with Cy, cryoablation was significantly more effective than either surgical excision or cautery at inducing systemic antitumor immunity, resulting in the cure of a fraction of animals with established metastatic disease and resistance to tumor rechallenge. Lymphocytes from cured animals contained an expanded population of tumor-specific, interferon-gamma producing T cells and transferred antitumor immunity to naive recipients. Depletion of CD8(+) cells significantly impaired the adoptive transfer of antitumor immunity. Furthermore, treatment with Cy and cryoablation was associated with a significant decrease in the ratio of regulatory to effector CD4(+) T cells. The combination of tumor cryoablation and Cy induces potent, systemic antitumor immunity in animals with established metastatic disease.

Cyclophosphamide unmasks an antimetastatic effect of local tumor cryoablation.

MoS2 hybrid nanostructures: from octahedral to quasi-spherical shells within individual nanoparticles.

Tradeoffs between health and wealth are among the most important decisions individuals make, and are central to social and economic policy. Yet, only a few studies have investigated the utility of health and wealth empirically. This paper investigates this utility function both theoretically and empirically. We conduct detailed personal interviews with 180 cancer patients, and also obtain questionnaires from 132 diabetes patients. We find strong support for the utility function U(h, w)=h·log(w), where h denotes health and w denotes wealth.

The utility of health and wealth.

A new procedure for the synthesis of MoS(2) nanotubes is reported, and additionally demonstrated for MoSe(2), WS(2), and WSe(2). Highly concentrated sunlight creates continuous high temperatures, strong temperature gradients, and extended hot annealing regions, which, together with a metallic (Pb) catalyst, are conducive to the formation of different inorganic nanotubes. Structural characterization (including atomic resolution images) reveals a three-step reaction mechanism. In the first step, MoS(2) platelets react with water-air residues, decompose by intense solar irradiation, and are converted to molybdenum oxide. Subsequently, the hot annealing environment leads to the growth of Pb-stabilized MoO(3-x) nanowhiskers. Shortly afterward, the surface of the MoO(3-x) starts to react with the sulfur vapor supplied by the decomposition of nearby MoS(2) platelets and becomes enveloped by MoS(2) layers. Finally, the molybdenum oxide core is gradually transformed into MoS(2) nanotubes. These findings augur well for similar syntheses of as yet unattained nanotubes from other metal chalcogenides.

New high-temperature Pb-catalyzed synthesis of inorganic nanotubes.

Allowing patients to take part in the initial investment for the development of cures for their illnesses can, under certain conditions, lead to the development of drugs that would have otherwise not been developed and to a dramatic welfare increase. We theoretically analyze these conditions. The suggested patient investment mechanism, which we call CureShare, does not involve any philanthropy or government subsidies. It is simply a way to overcome market failure. Based on empirical data, we estimate that applying this mechanism may save thousands of lives annually and may dramatically improve the quality of many others.

Market failure in the pharmaceutical industry and how it can be overcome: the CureShare mechanism.

We report a reasonably high yield (~50%) synthesis of silicon carbide (SiC) nanowires from silicon oxides and carbon in vacuum, by novel solar and lamp photothermal ablation methods that obviate the need for catalysis, and allow relatively short reaction times (~10 min) in a nominally one-step process that does not involve toxic reagents. The one-dimensional core/shell β-SiC/SiOx nanostructures-characterized by SEM, TEM, HRTEM, SAED, XRD and EDS-are typically several microns long, with core and outer diameters of about 10 and 30 nm, respectively. HRTEM revealed additional distinctive nanoscale structures that also shed light on the formation pathways.

High-yield synthesis of silicon carbide nanowires by solar and lamp ablation.

Pharmaceutical sales exceed $850 billion a year, of which 84% are accounted for by brand drugs. Drug prices are the focus of an ongoing heated debate. While some argue that pharmaceutical companies exploit monopolistic power granted by patent protection to set prices that are "too high", others claim that these prices are necessary to motivate the high R&D investments required in the pharmaceutical industry. This paper employs a recently documented utility function of health and wealth to derive the theoretically optimal pricing of monopolistic breakthrough drugs. This model provides a framework for a quantitative discussion of drug price regulation. We show that mild price regulation can substantially increase consumer surplus and the number of patients who purchase the drug, while having only a marginal effect on the revenues of the pharmaceutical company.

The pricing of breakthrough drugs: theory and policy implications.

We report the synthesis and supporting density-functional-theory computations for a closed-cage, misfit layered-compound superstructure from PbS-SnS2, generated by highly concentrated sunlight from a precursor mixture of Pb, SnS2, and graphite. The unique reactor conditions created in our solar furnace are found to be particularly conducive to the formation of these nanomaterials. Detailed structural and chemical characterization revealed a spontaneous inside-out formation mechanism, with a broad range of nonhollow fullerene-like structures starting at a diameter of ∼20 nm and a wall thickness of ∼5 layers. The computations also reveal a counterintuitive charge transfer pathway from the SnS2 layers to the PbS layers, which indicates that, in contrast to binary-layered compounds where it is principally van der Waals forces that hold the layers together, polar forces appear to be as important in stabilizing superstructures of misfit layered compounds.

Article	Year
The allogeneic effect revisited: exogenous help for endogenous, tumor-specific T cells. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation\| PubMed ID: 18410892	2008
Cyclophosphamide unmasks an antimetastatic effect of local tumor cryoablation. The Journal of pharmacology and experimental therapeutics\| PubMed ID: 19407102	2009
MoS2 hybrid nanostructures: from octahedral to quasi-spherical shells within individual nanoparticles. Angewandte Chemie (International ed. in English)\| PubMed ID: 21328645	2011
The utility of health and wealth. Journal of health economics\| PubMed ID: 22459500	2012
New high-temperature Pb-catalyzed synthesis of inorganic nanotubes. Journal of the American Chemical Society\| PubMed ID: 22966874	2012
Market failure in the pharmaceutical industry and how it can be overcome: the CureShare mechanism. The European journal of health economics : HEPAC : health economics in prevention and care\| PubMed ID: 23417217	2014
High-yield synthesis of silicon carbide nanowires by solar and lamp ablation. Nanotechnology\| PubMed ID: 23881269	2013
The pricing of breakthrough drugs: theory and policy implications. PloS one\| PubMed ID: 25422889	2014
Solar Synthesis of PbS-SnS2 Superstructure Nanoparticles. ACS nano\| PubMed ID: 26154896	2015

Moshe Levy

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