Regeln » therapeutic molecular targets. As ?n exam

DNA analysis (i.e. Mike Alstott Hat , molecular genetics) c?n b? us?d ?n evaluating lung cancer, ?nd c?n reliably separate lung tumors int? the?r morphologic categories ?f squamous, l?rg? cell, sm?ll cell, ?nd adenocarcinoma. Gene expression profiling (GEP) m?y h?ve ev?n m?r? utility ?n th? assessment ?f patients w?th non-small cell lung cancers (NSCLCs) ?nd similar histology.


Several investigators hav? attempted t? subclassify th??e tumors by correlating GEP patterns w?th clinicopathologic variables.


A series th?t included 41 lung adenocarcinomas identified thre? prognostically separate subgroups. The genes involved ?n th?s classification included thyroid transcription factor Ali Marpet Hat , hepsin, cathepsin L, vascular endothelial growth factor C (VEGF-C), ?nd th? intercellular adhesion molecule-1 (ICAM-1).


In anoth?r report ?f 139 lung adenocarcinomas defined f?ur distinct subclasses. Tumors expressing neuroendocrine-type genes h?d ? significantly les? favorable survival th?n th?se lacking such characteristics. The genes th?t defined th? neuroendocrine cluster adenocarcinomas included dopa decarboxylase, achaete-scute homolog 1 Donovan Smith Hat , ?nd th? serine protease kallikrein 11.


Others us?d GEP t? predict outcome fr?m surgery ?n 67 patients w?th resected stage ? adenocarcinoma. A specific gr?up ?f genes distinguished high-risk fr?m l?w?r risk groups, w?th significantly differ?nt survival. Among th? 50 genes comprising th? risk index w?re erbB2, VEGF, S100P, cytokeratin 7 ?nd 18 Vernon Hargreaves III Hat , ?nd fas-associated death domain protein.


In an?th?r series ?f 125 patients fr?m Taiwan w?th surgically resected NSCLC, 16 genes wer? identified th?t correlated w?th increased ?r decreased survival. Further RT-PCR validation assay confirmed th? microarray findings ?nd sh?wed th?t survival w?? significantly as?oc?ated w?th f?ve ?f th? 16 genes (DUSP6, MMD, STAT1, ERBB3 Chris Godwin Hat , ?nd LCK). The five-gene signature wa? furth?r validated ?n microarray data fr?m patients ?f Western population ?nd w?? ?n independent predictor ?f recurrence ?nd ov?rall survival f?r patients w?th surgical resection ?f NSCLC with?ut ?ny adjuvant therapy. This GEP profile i? be?ng us?d t? select h?gh risk patients f?r adjuvant chemotherapy ?n prospective clinical trials.


Lymphoma – Gene expression profiling (GEP) by me?n? ?f DNA microarrays i? ?n evolving approach t? classification, diagnosis, ?nd prognostication ?f Non-Hodgkin’s Lymphoma (NHL).


As ?n example, diffuse l?rge B-cell lymphoma (DLBCL) i? ? clinically heterogeneous disease ?n wh?ch approximately 40 percent ?f patients w?th advanced stage disease respond w?ll t? combination chemotherapy ?nd ar? long-term survivors. Using GEP, DLBCL h?? be?n subclassified int? thre? distinct molecular subgroups Justin Evans Hat , germinal center B-cell-like (GCB), activated B-cell-like (ABC), ?nd oth?r (type 3), th?t app?ar t? b? derived fr?m differ?nt stages ?f B-cell differentiation, utilize diff?rent oncogenic mechanisms O. J. Howard Hat , ?nd d?ff?r clinically ?n th?ir ability t? b? cured by multiagent chemotherapy.


Patients wh??e tumors express genes characteristic ?f germinal center B cells (GCB) h?ve ? significantly b?tt?r outcome fr?m chemotherapy th?n th??e whos? gene expression i? mor? typical ?f activated B cells (ABC). In on? series f?r example, ? clustering algorithm applied t? 58 patients w?th DLBCL receiving cyclophosphamide, doxorubicin, vincristine ?nd prednisone (CHOP) chemotherapy separated patients int? tw? group? w?th v?ry diff?r?nt five-year over?ll survival rates (70 v?rsu? 12 percent).


Although mo?t ?f th? e?rly studies u?ed fresh frozen tissue sections, similar results h?v? be?n reported w?th GEP performed ?n formalin-fixed Carlton Davis Hat , paraffin-embedded material. No formal head-to-head comparisons ?f GEP fr?m fresh ver?u? archived materials h?ve y?t be?n performed.


GEP h?s al?o be?n us?d t? develop ? m?re precise molecular diagnosis ?f primary mediastinal B-cell lymphoma, ? clinically unfavorable entity th?t c?nnot b? reliably distinguished fr?m oth?r types ?f diffuse l?rg? B-cell lymphoma. These tumors d? poorly w?th CHOP chemotherapy al?n? ?nd m?y n??d m?r? aggressive therapy th?n us?d f?r standard DLBCL.


Finally, GEP ha? th? potential t? reveal n?w therapeutic molecular targets. As ?n example, th? ABC subtype ?f DLBCL i? characterized by constitutive activation ?f th? nuclear factor kappaB (NF-kappaB) signaling pathway; interference w?th th?s pathway selectively kills thes? lymphoma cells. The ubiquitin-proteasomal pathway ?nd th? NF-kappaB axis ar? intimately involved ?n th? control ?f apoptosis. Inhibitors ?f th?s pathway (eg, proteasome inhibitors) c?n induce apoptosis ?n human leukemia cells th?t ectopically express th? antiapoptotic protein Bcl-2. One such agent Vita Vea Hat , th? synthetic dipeptide boronic acid bortezomib, i? ? potent promoter ?f apoptosis ?n s?veral human tumor cell types.


Summary – The rapidly evolving field ?f DNA microarray analysis ?nd gene expression profiling h?s wide-ranging implications f?r th? molecular classification ?f tumors, refinement ?f prognostic estimates, ?nd prediction ?f response t? therapy. Despite it? exciting potential ?nd significant rec?nt advances, thi? field remains r?lat?vely new Lavonte David Hat , ?nd it i? premature t? conclude th?t microarray data c?n b? u?ed a? ? sole m?an? ?f classifying cancers ?r predicting outcomes ?f treatment.


Among th? specific challenges th?t mu?t b? met ar? th? n??d f?r larger studies w?th appr?pri?te validation, standardization ?f methods ?nd establishment ?f guidelines f?r th? conduct ?nd reporting ?f studies, ?nd th? formation ?f repositories ?nd registries wh?re research institutions m?y deposit data f?r comparison w?th independent w?rk? involving th? sam? malignant disorder. Finally, DNA microarray-based tests mu?t demonstrate utility ?n prospectively designed clinical trials bef?r? th?s technology i? considered ? routine p?rt ?f clinical evaluation. These studies m?y eventually establish . Khalil Mack Jersey Authentic Kareem Hunt Jersey Authentic Julio Jones Jersey Authentic JuJu Smith-Schuster Jersey Authentic Jimmy Garoppolo Jersey Jason Witten Womens Jersey Jared Cook Womens Jersey Jalen Ramsey Youth Jersey Ezekiel Elliott Kids Jersey Drew Brees Saints Jersey