Vai ai contenuti. | Spostati sulla navigazione | Spostati sulla ricerca | Vai al menu | Contatti | Accessibilità

| Crea un account

Enzo, Maria Vittoria (2013) Analysis of blood-based markers as predicting tools of pathologic tumour response in rectal cancer patients receiving neo-adjuvant chemoradiotherapy. [Tesi di dottorato]

Full text disponibile come:

[img]
Anteprima
Documento PDF
12Mb

Abstract (inglese)

Neo-adjuvant chemo-radio therapy (pCRT) has been accepted as a standard care in the treatment of patients with locally advanced rectal cancer. The multimodality treatment has been established to improve tumour downstaging, pathological complete response, and local disease control. However, the response of individual tumors to the treament is not uniform and ranges from complete response to complete resistance. The discovery of new molecular markers that predict the tumour response is surely of wide interest for personalizing the therapy and reducing time, costs and side effects in the patients with resistant tumours. Many potential biomarkers have been evaluated in order to predict the response to pCRT, and to implement targeted therapeutics. However, single-marker or multi-markers analyses, based on pre-treatment tissue biopsies, often obtained conflicting results demonstrating the heterogeneity of the individual tumour response. Moreover, the prediction of histopathological response to neo-adjuvant treatment is complicated by the interaction and the involvement of the microenvironment in modulating the sensitivity to pCRT. In this study, we developed blood-based methods of biomarker analysis in order to evaluate the histopathological response to treatment in a broad contest that can take into account not only the signalling pathway of tumour cells but also the microenvironment as a part of a unique system. Indeed, the non-invasive nature and the dynamism for which different molecules could be detected according with physiological and pathological states has given us the possibility to monitor the response along the administration of the treatment. In particular, we focused on two different kind of circulating molecules: the cell-free DNA (cfDNA) and the circulating low molecular weight (LMW) peptides. In particular, we investigated the presence, the quantity of cfDNA and its integrity (cfDNA integrity = non apototic cfDNA / total cfDNA) along the chemo-radio treatment. For this purpose we measured the cfDNA concentration and cfDNA integrity in a prospective study of locally advanced rectal cancer patients plasma collected before the pCRT, after two weeks from initiation of the pCRT and after the pCRT. We evaluated the association of these markers with the histological response to the chemo-radio therapy, demonstrating a different kinetic of cfDNA integrity in association with the tumour response.
Then we studied the LMW peptidome circulating in plasma, in order to find evidences of possible differences in the peptide profile that could reflect the tumour response. To overcome the technical difficulties in harvesting LMW species, we have employed the mesoporous chip-based technology, developed by the Nanomedicine Department of The Methodist Hospital Research Institute in Houston, Texas. This mesoporous device, in combination with matrix-assisted laser desorption/ionization - time of flight mass spectrometry (MALDI-TOF MS), allows the isolation and the detection of small peptides from the large proteins. We analyzed plasma of rectal cancer patients, with positive or negative response to the therapy, at the same time points as the cfDNA: before, during, after the chemo-radio therapy. Multivariate analyses of the LMW peptide profile at different time points identified combinations of peptides that revealed high discriminating capacity of the different tumour responses. In particular, before the pCRT, a pattern of five ionic species showed a sensitivity and a specificity of 80% and after the pCRT, a pattern of other five specific ionic species showed a sensitivity of 80% and a specificity of 85% to cluster patients on the basis of histopathologic response to pCRT. Moreover the identification of the amino acids sequences of the response-specific ionic species revealed the presence of protein fragments that could be directly or indirectly valuable for further investigation on the resistance mechanisms of the rectal tumour to the neo-adjuvant chemo-radio therapy

Abstract (italiano)

La radiochemioterapia neoadiuvante (pCRT) è un protocollo standard accettato per il trattamento di pazienti con cancro rettale localmente avanzato. Il trattamento preoperatorio multimodale è stato introdotto per la riduzione dello stadio del tumore, per l’aumento della risposta completa patologica e per il controllo locale della malattia. Tuttavia la risposta patologica al trattamento non è uniforme e varia da una risposta completa alla resistenza totale. La scoperta di nuovi marcatori molecolari in grado di predire la risposta del tumore è sicuramente di grande interesse al fine di personalizzare la terapia, riducendo così i tempi, i costi e gli effetti collaterali nei pazienti con tumori resistenti. Molti potenziali biomarcatori sono stati valutati con l’obiettivo di prevedere la risposta alla pCRT, e di attuare terapie mirate. Finora molti studi su singolo o multi-marcatore sono stati eseguiti prevalentemente su biopsie di tessuto pre-trattamento. I risultati ottenuti, tuttavia, erano spesso contrastanti dimostrando l'eterogeneità individuale della risposta tumorale al trattamento. Inoltre, la predizione della risposta istopatologica alla pCRT è complicata dall’interazione e dal coinvolgimento del microambiente che può modulare la sensibilità del tumore al trattamento. In questo studio, abbiamo sviluppato metodi di analisi di biomarcatori su sangue, al fine di valutare la risposta del tumore al trattamento in un contesto più ampio, che rende conto non solo dell’ambiente strettamente tumorale, ma che prende in considerazione anche il microambiente come parte di un sistema unico. Infatti, la natura non invasiva del materiale biologico analizzato e il dinamismo per cui molecole differenti possono essere rilevate secondo lo stato fisiologico e patologico dell’organismo, ci hanno permesso di monitorare la risposta lungo il tempo di somministrazione del trattamento. In particolare, ci siamo concentrati su due diversi tipi di molecole circolanti: il DNA libero da cellule (cfDNA) e i peptidi a basso peso molecolare (Low Molecular Weight, LMW). In particolare, abbiamo studiato la presenza, la quantità e l’integrità del cfDNA durante il trattamento radio-chemioterapico. A questo scopo abbiamo misurato la concentrazione e l'integrità del cfDNA (cfDNA integrity=cfDNA apoptotico/cfDNA totale) in uno studio prospettico di plasma di pazienti con carcinoma rettale localmente avanzato, raccolto prima della pCRT, dopo due settimane dall'inizio del trattamento e dopo la pCRT. Abbiamo valutato l'associazione di questi marcatori con la risposta istologica alla chemio-radio terapia, dimostrando la presenza di diversa cinetica nell’integrità del cfDNA, in associazione con la risposta tumorale.
Nel plasma, abbiamo quindi studiato il peptidoma circolante a basso peso molecolare, al fine di trovare potenziali differenze nel profilo peptidico che potessero riflettere la risposta tumorale. Per superare le difficoltà tecniche nella rilevazione dei peptidi circolanti a basso peso molecolare, abbiamo utilizzato una strategia basata sull’esclusione dimensionale di un chip di silice mesoporosa (MSC), sviluppato dal Dipartimento Nanomedicina del The Methodist Hospital Research Institute di Houston, Texas. Questo dispositivo mesoporoso, in combinazione con l’utilizzo dello spettrometro di massa MALDI-TOF MS (Matrix-Assisted Laser Desorption/Ionization-Time Of Flight Mass Spectrometry), consente l'efficiente rimozione di grandi proteine e l'isolamento del peptidoma circolante da campioni di fluidi corporei. Abbiamo analizzato il plasma di pazienti con cancro rettale, prelevato in diversi tempi (prima, durante, dopo la chemio-radio terapia) e stratificati secondo la risposta positiva o negativa alla pCRT. L'analisi multivariata del profilo peptidico nei diversi tempi di analisi ha identificato combinazioni di peptidi che evidenziavano un’elevata capacità discriminante della risposta tumorale. In particolare, il modello di regressione logistica ha evidenziato, prima della pCRT, una combinazione di cinque specie ioniche capace di identificare i pazienti che non rispondono al trattamento, con una sensibilità e una specificità del 80%; mentre la stessa analisi con i campioni raccolti dopo la pCRT, ha identificato un'altra combinazione di cinque specie ioniche che evidenziano una sensibilità del 80% e una specificità del 85%. Inoltre, l'identificazione delle sequenze amminoacidiche di alcune tra le specie ioniche discriminanti la risposta alla pCRT, hanno rivelato la presenza di frammenti proteici che possono essere direttamente o indirettamente utili per ulteriori indagini sui meccanismi di resistenza del tumore rettale alla radio-chemio terapia neo-adiuvante

Statistiche Download - Aggiungi a RefWorks
Tipo di EPrint:Tesi di dottorato
Relatore:Agostini, Marco
Dottorato (corsi e scuole):Ciclo 25 > Scuole 25 > ONCOLOGIA E ONCOLOGIA CHIRURGICA
Data di deposito della tesi:29 Gennaio 2013
Anno di Pubblicazione:29 Gennaio 2013
Parole chiave (italiano / inglese): locally advanced rectal cancer treated with chemo-radio therapy, markers predictive of preoperative chemo-radio therapy tumour response, cell free DNA, circulating Low molecular weight peptidome
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/06 Oncologia medica
Area 05 - Scienze biologiche > BIO/11 Biologia molecolare
Struttura di riferimento:Dipartimenti > Dipartimento di Scienze Chirurgiche Oncologiche e Gastroenterologiche
Codice ID:5600
Depositato il:14 Ott 2013 11:37
Simple Metadata
Full Metadata
EndNote Format

Bibliografia

I riferimenti della bibliografia possono essere cercati con Cerca la citazione di AIRE, copiando il titolo dell'articolo (o del libro) e la rivista (se presente) nei campi appositi di "Cerca la Citazione di AIRE".
Le url contenute in alcuni riferimenti sono raggiungibili cliccando sul link alla fine della citazione (Vai!) e tramite Google (Ricerca con Google). Il risultato dipende dalla formattazione della citazione.

• Aebersold R. et al., Mass spectrometry-based proteomics, (2003) Nature 422(13) 198-207. Cerca con Google

• Albrethsen J., Reproducibility in Protein Profiling by MALDI-TOF Mass Spectrometry, (2007) Clinical Chemistry 53:5 852–858 Cerca con Google

• Andersen C.L. et al, Clusterin expression in normal mucosa and colorectal cancer, molecular and cellular proteomics, (2007) 6.6 1039-1048 Cerca con Google

• Andrew D. et al., The Genomics of Colorectal Cancer: State of the Art, (2008) Current Genomics 9:1-10 Cerca con Google

• Barcellos-Hoff M.H. et al., A systems biology approach to multicellular and multi-generational radiation responses, (2006) Mutat Res 2:32–38 Cerca con Google

• Bateson H. et al., Use of matrix-assisted laser desorption/ionisation mass spectrometry in cancer research, (2011) Journal of Pharmacological and Toxicological Methods, 64:197–206 Cerca con Google

• Beggs A.D. et al., The genomics of colorectal cancer: state of the art, (2008) Curr Genomics 9(1):1-10. Cerca con Google

• Bertolini F. et al., Prognostic and predictive value of baseline and posttreatment molecular marker expression in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy, (2007) Int. J. Radiation Oncology Biol. Phys. 68(5): 1455-1461 Cerca con Google

• Bouamrani A. et al, Mesoporous silica chips for selective enrichment and stabilization of low molecular weight proteome, (2010) Proteomics 10(3): p. 496-505. Cerca con Google

• Brettingham-Moore K.H. et al, Using gene expression profiling to predict response and prognosis in gastrointestinal cancers—the promise and the perils, (2011) Ann Surg Oncol 18(5): 1484-1491 Cerca con Google

• Buczacki S. et al., Stem cells, quiescence and rectal carcinoma: an unexplored relationship and potential therapeutic target, (2011) British Journal of Cancer 105: 1253-1259 Cerca con Google

• Burnett-Hartman A.N. et al., Colorectal polyp type and the association with charred meat consumption, smoking, and microsomal epoxide hydrolase polymorphisms, (2011) Nutr Cancer Cerca con Google

• Chan K.C.A. et al., Persistent Aberrations in Circulating DNA Integrity after Radiotherapy Are Associated with Poor Prognosis in Nasopharyngeal Carcinoma Patients, (2008) Clin Cancer Res 14(13): 4141–4145. Cerca con Google

• Cho K.R. et al., Genetic Alterations in the Adenoma-Carcinoma Sequence, (1992) Cancer 70:1727-1731. Cerca con Google

• Choi J. J. Et al., The role of macrophages in the in vitro generation of extracellular DNA from apoptotic and necrotic cells, (2005) Immunology 115, 55–62. Cerca con Google

• Cunningham D. et al., Colorectal cancer, (2010) Lancet 375(9719): 1030– 1047 Cerca con Google

• Curtin K. et al., Somatic alterations, metabolizing genes, and smoking in rectal Cancer, (2009) Int J Cancer. 125(1): 158–164 Cerca con Google

• De Bruin E.C., Prognostic Value of Apoptosis in Rectal Cancer Patients of the Dutch Tota lMesorectal Excision Trial: Radiotherapy Is Redundant in Intrinsically High-Apoptotic Tumors, (2006) Clin Cancer Res 12(21) Cerca con Google

• Deligezer U. et al., Effect of Adjuvant Chemotherapy on Integrity of Free Serum DNA in Patients with Breast Cancer, (2008) Ann NY Acad Sci 1137:175-179 Cerca con Google

• Eischeid A.C. et al., SYTO dyes and EvaGreen outperform SYBR Green in real-time PCR, (2011) BMC Research Notes 4:263. Cerca con Google

• Fearon E.R., Molecular Genetics of Colorectal Cancer, (2011) Annu. Rev. Pathol. Mech. Dis 6:479-507. Cerca con Google

• Ferlay J. et al., Estimates of the cancer incidence and mortality in Europe in 2006. (2007) Ann Oncol. 18: 581-592 Cerca con Google

• Ferrari M., Cancer nanotechnology: opportunities and challenges, (2005) Nat Rev Cancer 5(3): p. 161-71. Cerca con Google

• Ferrari M., Nanotechnology-enabled medicine, (2005) Discov Med. 5(28):363-366. Cerca con Google

• Findeisen P. et al., Functional protease profiling with reporter peptides in serum specimens of colorectal cancer patients: demonstration of its routine diagnostic applicability, (2012) Journal of Experimental & Clinical Cancer Research 31:56 Cerca con Google

• Findeisen P. et al., Functional protease profiling for diagnosis of malignant disease, (2012) Proteomics Clin. Appl. 6, 60-78 Cerca con Google

• Findeisen P. et al., Preanalytical impact of sample handling on proteome profiling experiments with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, (2005) Clin. Chem. 51:2409–2411. Cerca con Google

• Fleischhacker M. et al, Methods for isolation of cell-free plasma DNA strongly affect DNA yield, (2011) Clin Chim Acta 20;412(23-24):2085-2088. Cerca con Google

• Fleischhacker M. et al., Circulating nucleic acids (CNAs) and cancer–a survey, (2007) Biochim Biophys Acta 1775: 181–232. Cerca con Google

• Fodde R. et al., Mutations in the APC tumor suppressor gene cause chromosomal instability. (2001) Nature 3:433-438. Cerca con Google

• Fodde R. et al., Wnt/beta-catenin signaling in cancer stemness and malignant behavior, (2007) Curr Opin Cell Biol 19(2):150-158. Cerca con Google

• Frattini M. et al., Different Genetic Features Associated with Colon and Rectal Carcinogenesis, (2004) Clinical Cancer Research 10: 4015–4021. Cerca con Google

• Freitas P.P. et al., Optimization and integration of magnetoresistive sensors, (2011) Journal of SPIN, (1):71-91 Cerca con Google

• Ghadimi B.M. et al., Effectiveness of gene expression profiling for response prediction of rectal adenocarcinomas to preoperative chemoradiotherapy, (2005) J Clin Oncol 23(9): 1826-1838 Cerca con Google

• Giacona M.B. et al., Cell-free DNA in human blood plasma: length measurements in patients with pancreatic cancer and healty controls, (1998) Pancreas 17:89-97. Cerca con Google

• Godin B, et al, Multistage nanovectors: from concept to novel imaging contrast agents and therapeutics, (2011) Acc Chem Res, 44(10): 979-89. Cerca con Google

• Goetz E.M. et al., ATM-dependent IGF-1 induction regulates secretory clusterin expression after DNA damage and in genetic instability, (2011) Oncogene 30: 3745–3754 Cerca con Google

• Gormally E. et al., Circulating free DNA in plasma or serum as biomarker of carcinogenesis: Practical aspects and biological significance, (2007) Mutation Research 635:105–117. Cerca con Google

• Grade M. et al., The molecular basis of chemoradiosensitivity in rectal cancer: implications for personalized therapy, (2012) Langenbecks Arch Surg 397: 543–555. Cerca con Google

• Gudnason H. et al., Comparison of multiple DNA dyes for real-time PCR: effects of dye concentration and sequence composition on DNA amplification and melting temperature, (2007) Nucleic Acids Res. 35(19): e127. Cerca con Google

• Harrington K. et al., Molecular Biology for the Radiation Oncologist: the 5Rs of Radiobiology meet the Hallmarks of Cancer, (2007) Clinical Oncology 19: 561-571 Cerca con Google

• Hilario M. et al., Processing and classification of protein mass spectra, (2006) Mass Spectrometry Reviews, 25: 409– 449 Cerca con Google

• Holdenrieder S. et al., DNA Integrity in Plasma and Serum of Patients with Malignant and Benign Diseases, (2008) Ann N Y Acad Sci 1137(1):162–170. Cerca con Google

• Hooker C.M. et al, A prospective cohort study of rectal cancer risk in relation to active cigarette smoking and passive smoke exposure, (2008) Ann Epidemiol. 18:28–35. Cerca con Google

• Hortin G.L., The MALDI-TOF Mass Spectrometric View of the Plasma Proteome and Peptidome, (2006) Clinical Chemistry 52:7 1223–1237 Cerca con Google

• Hu Y, et al., Nanodevices in diagnostics, (2011) Wiley Interdiscip Rev Nanomed Nanobiotechnol. 3(1): 11-32. Cerca con Google

• Hu Y, et al., Nanotexture Optimization by Oxygen Plasma of Mesoporous Silica Thin Film for Enrichment of Low Molecular Weight Peptides Captured from Human Serum, Sci China Chem, 2010. 53(11): 2257-2264. Cerca con Google

• Hu Y, et al., Tailoring of the nanotexture of mesoporous silica films and their functionalized derivatives for selectively harvesting low molecular weight protein, ACS Nano, 2010. 4(1): 439-51 Cerca con Google

• Introduction to Fourier Transform Infrared Spectrometry, 2001 Thermo Nicolet Corporation Cerca con Google

• Jahr S. et al., DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells, (2001) Cancer Res 61:1659-65 Cerca con Google

• Jass J.R., Classification of colorectal cancer based on correlation of clinical, morphological and molecular features, (2007) Histopathology 50(1): 113-130. Cerca con Google

• Jemal A. et al, Global cancer statistics, (2011) Cancer J. Clin. 61(2):69 Cerca con Google

• Jiang W. W. et al., Increased plasma DNA integrity index in head and neck cancer patients, (2006) Int J Cancer, 119: 2673-2676 Cerca con Google

• Jimenez C.R. et al., Proteomics of colorectal cancer: Overview of discovery studies and identification of commonly identified cancer-associated proteins and candidate CRC serum markers, (2010) Journal of proteomics 73: 1873-1895 Cerca con Google

• Julien L.A. et al., Current Neoadjuvant Strategies in Rectal Cancer, (2010) Journal of Surgical Oncology 101:321–326 Cerca con Google

• Jung K. et al., Cell-free DNA in the blood as a solid tumor biomarker—A critical appraisal of the literature, (2010) Clin. Chim. Acta 411:1611–1624. Cerca con Google

• Kapiteijn E. et al., Mechanisms of oncogenesis in colon versus rectal cancer, (2001) Journal of Pathology 195: 171-178. Cerca con Google

• Karas M. et al., Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons, (1988) Analytical Chemistry 60: 2299–2301. Cerca con Google

• Karpova M.A. et al., Cancer-specific MALDI-TOF profiles of blood serum and plasma: Biological meaning and perspectives, (2010) Journal of proteomics 73: 537-551 Cerca con Google

• Kauh J. et al., Colorectal cancer prevention, (2004) Curr Probl Cancer 28: 240-264. Cerca con Google

• Kim I.J. et al., Microarray gene expression profiling for predicting complete response to preoperative chemoradiotherapy in patients with advanced rectal cancer, (2007) Dis Colon Rectum 50 (9): 1342-1353 Cerca con Google

• Kinzler K.W. et al., Lessons from Hereditary Colorectal Cancer, (1996) Ceel 87:159-170 Cerca con Google

• Klokov D, et al, IR-inducible clusterin gene expression: a protein with potential roles in ionizing radiation-induced adaptive responses, genomic instability, and bystander effects, (2004) Mutation Research 568: 97-110 Cerca con Google

• Kohler C. et al., Cell-free DNA in the Circulation as a Potential Cancer Biomarker, Anticancer Research (2011) 31: 2623-2628 Cerca con Google

• Kulasingam V. et al., Strategies for discovering novel cancer biomarkers through utilization of emerging technologies, (2008) Nature clinical practice oncology 5(10) Cerca con Google

• Kulikova, GA, et al., In vitro studies of interaction of modified silica nanoparticles with different types of immunocompetent cells. J Biomed Mater Res A, 2010. 95(2): p. 434-9. Cerca con Google

• Kumar V. et al., Robbins and Cotran’s pathologic basis of disease 8th edition, 2009 Cerca con Google

• Kuremsky J.G., Biomarkers for response to neoadjuvant chemoradiation for rectal cancer, (2009) Int. J. Radiation Oncology Biol. Phys., 74(3): 673–688 Cerca con Google

• Larsson S.C. et al, Diabetes mellitus and risk of colorectal cancer: a meta-analysis, (2005) J Natl Cancer Inst. 97(22):1679 Cerca con Google

• Lee H.J. et al., Biomarker discovery from the plasma proteome using multidimensional fractionation proteomics, (2006) Current Opinion in Chemical Biology 10:42–49 Cerca con Google

• Lewis J.K. et al., Matrix-assisted Laser Desorption/Ionization Mass Spectrometry in Peptide and Protein Analysis, (2000) Encyclopedia of Analytical Chemistry, R.A. Meyers (Ed.) pp. 5880–5894, John Wiley & Sons Ltd, Chichester Cerca con Google

• Li F.Y. et al., Colorectal cancer, one entity or three, (2009) J Zhejiang Univ Sci B 10(3): 219-29 Cerca con Google

• Li J.N. et al., Differences in gene expression profiles and carcinogenesis pathways between colon and rectal cancer, (2012) Journal of Digestive Diseases 13: 24–32 Cerca con Google

• Li M. et al., Colorectal Cancer or Colon and Rectal Cancer? Clinicopathological Comparison between Colonic and Rectal Carcinomas, (2007) Oncology 73:52–57 Cerca con Google

• Longley D.B. et al., 5-Fluorouracil: mechanisms of action and clinical strategies , (2003) Nature review 3:330-338 (2003) Cerca con Google

• López-Otín C. et al., Proteases: Multifunctional Enzymes in Life and Disease, (2008) The Journal of Biological Chemistry, 283: 30433-30437. Cerca con Google

• Martin K. J. et al., A need for basic research on fluid-based early detection biomarkers. Cancer Res, 70: 5203-5206. Cerca con Google

• Mazzarelli P. et al., The dual face of CLU: from normal to malignant phenotype, (2009) Adv Cancer Res. 105:45-61. Cerca con Google

• Menard C. et al., Exposure with Serum Proteomic Analysis Discovering Clinical Biomarkers of Ionizing Radiation, (2006) Cancer Res 66:1844-1850 Cerca con Google

• Mothersill C. et al., Radiation-induced bystander effects- implications for cancer, (2004) Nature Review cancer 4: 158-164 Cerca con Google

• Nannini M. et al., Gene expression profiling in colorectal cancer using microarray technologies: results and perspectives, (2009) Cancer Treat Rev 35(3): 201–209 Cerca con Google

• Norris J.L. et al., Processing MALDI Mass Spectra to Improve Mass Spectral Direct Tissue Analysis, (2007) Int J Mass Spectrom. 260(2-3): 212–221. Cerca con Google

• Pajonk F. et al., Radiation Resistance of Cancer Stem Cells: The 4 R’s of Radiobiology Revisited, (2010) Stem Cells 28(4): 639–648. Cerca con Google

• Petricoin E.F., The blood peptidome: a higher dimension of information content for cancer biomarker discovery, (2006) Nature review 6: 961:966 Cerca con Google

• Pietrowska M. et al., MALDI-MS-Based Profiling of Serum Proteome: Detection of Changes Related to Progression of Cancer and Response to Anticancer Treatment, (2012) International Journal of Proteomics, ID 926427, 10 pages Cerca con Google

• Push W. et al., Mass spectrometry-based clinical proteomics, (2003) Pharmacogenomics 4(4): 463-476. Cerca con Google

• Quesada V. et al., The Degradome database: mammalian proteases and diseases of proteolysis, Nucleic Acids Research, (2009) 37, Database issue D239–D243 Cerca con Google

• Rawlings N.D. et al, MEROPS: the peptidase database. (2008) Nucleic Acids Res. 36 Database issue, D320-325. Cerca con Google

• Reerink O. et al., Molecular prognostic factors in locally irresectable rectal cancer treated preoperatively by chemoradiotherapy, (2004) Anticancer Res. 24:1217–1221. Cerca con Google

• Ren X.R. et al., Focal adhesion kinase in netrin-1 signaling, (2004) Nat. Neurosci. Nat 7(11): 1204-1212. Cerca con Google

• Ricci-Vitiani L. et al., Colon cancer stem cells, (2008) Gut 57;538-548. Cerca con Google

• Riehemann K, et al, Nanomedicine--challenge and perspectives, (2009) Angew Chem Int Ed Engl, 48(5): 872-97. Cerca con Google

• Rodel C. et al., Rectal cancer: state of the art in 2012, (2012) current opinion oncology 24(4). Cerca con Google

• Roy S, et al., Novel multiparametric approach to elucidate the surface amine-silanization reaction profile on fluorescent silica nanoparticles, (2010) Langmuir, 26(23): 18125-18134. Cerca con Google

• Sakamoto J.H. et al, Enabling individualized therapy through nanotechnology, Pharmacol Res, 2010. 62(2): p. 57-89. Cerca con Google

• Sanz-Pamplona R. et al., Gene Expression Differences between Colon and Rectum Tumors, (2011) Clin Cancer Res 17:7303-7312. Cerca con Google

• Sauer R. et al., German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer, (2004) N Engl J Med 351:1731–1740. Cerca con Google

• Savino R. et al., Mesopore-assisted profiling strategies in clinical proteomics for drug/target discovery, (2012) Drug Discovery Today 17 (3/4) Cerca con Google

• Schmidt B. et al., Integrity of Cell-Free Plasma DNA in Patients with Lung Cancer and Nonmalignant Lung Disease, (2008) Ann N Y Acad Sci 1137(1):207–213. Cerca con Google

• Schwarzenbach H. et al., Cell-free nucleic acids as biomarkers in cancer patients, (2011) Nat Rev Cancer, 11(6): 426-437 Cerca con Google

• Selzer E. et al., Basic principles of molecular effects of irradiation, (2012) Wien Med Wochenschr 162/3–4: 47–54 Cerca con Google

• Shannan B. et al., Challenge and promise: roles for clusterin in pathogenesis, progression and therapy of cancer, (2006) Cell Death and Differentiation 13: 12–19. Cerca con Google

• Smith F.M. et al., Pathological and molecular predictors of the response of rectal cancer to neoadjuvant radiochemotherapy, (2006) EJSO 32: 55–64 Cerca con Google

• Smith F.M. et al., Combination of SELDI-TOF-MS and Data Mining Provides Early-stage Response Prediction for Rectal Tumors Undergoing Multimodal Neoadjuvant Therapy, (2007) Annals of Surgery 245(2): 259-266 Cerca con Google

• Sorenson, G. D. et al. Soluble normal and mutated DNA sequences from single-copy genes in human blood, Cancer Epidemiol. Biomarkers Prev. 3, 67–71 (1994). Cerca con Google

• Sriram K.B. et al., Pleural fluid cell-free DNA integrity index to identify cytologically negative malignant pleural effusions including mesotheliomas, (2012) BMC Cancer, 12:428. Cerca con Google

• Stewart B.W., Kleihus P., Editors. World Cancer Report. Lyon: IARC Press, (2003). Cerca con Google

• Taback B. et al., Quantification of Circulating DNA in the Plasma and Serum of Cancer Patients, (2004) Ann N Y Acad Sci 1022(1):17–24. Cerca con Google

• Taguchi A. et al., Unleashing the Power of Proteomics to Develop Blood-Based Cancer Markers, (2013) Clinical Chemistry 59:1000–000 Cerca con Google

• Terracciano R. et al., Selective binding and enrichment for low-molecular weight biomarker molecules in human plasma after exposure to nanoporous silica particles, (2006) Proteomics, 6(11): 3243-50. Cerca con Google

• The rectum, chapter 71, Bailey & Love's Short Practice of Surgery, 25th edition, 2012). Cerca con Google

• Tirumalai R.S. et al., Characterization of the Low Molecular Weight Human Serum Proteome, (2003) Molecular & Cellular Proteomics 2.10 1096:1103 Cerca con Google

• Tsang J. C. H. et al., Circulating nucleic acids in plasma/serum, (2007) Pathology 39(2):197-207 Cerca con Google

• Umetani N. et al., Increased integrity of free circulating DNA in sera of patients with colorectal or periampullary cancer: direct quantitative PCR for ALU repeats, (2006) Clin Chem 52: 1062-1069 Cerca con Google

• Umetani N. et al., Prediction of breast tumor progression by integrity of free circulating DNA in serum, (2006) J Clin Oncol 24: 4270-4276, Cerca con Google

• Vainio H. et al., Fruit and vegetables in cancer prevention, (2006) Nutr. Cancer 54(1): 111-142. Cerca con Google

• Valentini V. et al., Evidence and research in rectal cancer, (2008) Radiotherapy and Oncology 87: 449–474. Cerca con Google

• Villanueva J et al, Differential eoprotease activities confer tumor-specific serum peptidome patterns, the journal of clinical investigation, 2006. 116(1):271-284 Cerca con Google

• Villanueva J. et al., Monitoring Peptidase Activities in Complex Proteomes by MALDITOF Mass Spectrometry, (2009) Nat Protoc. 4(8): 1167–1183 Cerca con Google

• Vogelstein B. et al., Surfing the p53 network, (2000) Nature, 408: 307-310. Cerca con Google

• Wang B.G. et al., Increased Plasma DNA Integrity in Cancer Patients, (2003) Cancer Res 63(14): 3966–3968. Cerca con Google

• Wang J. et al., Carcinogen metabolism genes, red meat and poultry intake, and colorectal cancer risk, (2012) Int J Cancer. 130(8):1898-907. Cerca con Google

• Watanabe T. et al., Prediction of sensitivity of rectal cancer cells in response to preoperative radiotherapy by DNA microarray analysis of gene expression profiles, (2006) Cancer Res 66(7): 3370–3374 Cerca con Google

• Wong J.W.H. et al., SpecAlign—processing and alignment of mass spectra datasets, (2005) Bioinformatics application notes, 21( 9):2088–2090 Cerca con Google

• Wong, J.W.H. et al., Application of Fast Fourier Transform Cross-Correlation for the Alignment of Large Chromatographic and Spectral Datasets., (2005) Anal. Chem., 77: 5655-5661 Cerca con Google

• Woodward W.A. et al., Molecular basis of radiation therapy, chapter 50 of the textbook “The molecular basis of cancer” by Mendelsohn J., Howley P.M., Israel M.A., Gray J.W., Thompson C.B., third edition, 2008 Cerca con Google

• Worthley D. L. et al., Colorectal carcinogenesis: road maps to cancer, (2007) World Journal of Gastroenterology, 13(28): 3784-3791 Cerca con Google

• Yi J. et al., Inhibition of intrinsic protelytic activities moderates preanalytical variability and instability of human plasma, (2006) Journal of proteome research, 6:1768-1781. Cerca con Google

• Yang Y. ET AL., Integrative Genomic Data Mining for Discovery of Potential Blood-Borne Biomarkers for Early Diagnosis of Cancer, (2008) PLosONE 3(11). Cerca con Google

• Zampino M.G. et al., Rectal cancer, (2004) Critical Reviews in Oncology/Hematology 51:121–143 Cerca con Google

• Zampino M.G. et al., Rectal cancer, (2009) Critical Reviews in Oncology / Hematology 70(2): 160-182 Cerca con Google

• Zavoral M. et al., Colorectal cancer screening in Europe, (2009) World J Gastroenterol 15(47): 5907-5915 Cerca con Google

• Zhang, Y. et al., Enrichment of low-abundance peptides and proteins on zeolite nanocrystals for direct MALDI-TOF MS analysis, (2005) Angew. Chem. Int. Ed. 44: 615–617 Cerca con Google

• Zhang H. et al, Clusterin inhibits apoptosis by interacting with activated Bax, (2005) Nature Cell Biology 7(9): 909-915 Cerca con Google

• Zitt M. et al., Circulating cell-free DNA in plasma of locally advanced rectal cancer patients undergoing preoperative chemoradiation: a potential diagnostic tool for therapy monitoring, (2008) Dis. Markers, 25: 159-165 Cerca con Google

Download statistics

Solo per lo Staff dell Archivio: Modifica questo record