colorectal cancer, represents a major cause of morbidity and mortality from cancer in all Western countries and high technology development. Surgery, yet today, is the most effective means of therapy in the treatment of rectal cancer, where, in most cases, the actions of amputation adddomino-perineal resection and anterior apply. Transformation adenoma-carcinoma is considered the main mechanism for the development of 
el colorectal cancer, and this model has been described for the first time in 1975. The various phases of this process, which involves the transition from normal mucosa to adenoma and then to carcinoma in situ and finally to the spread of disease to other districts, are characterized by mutational events that occur in the genome against oncogenes and tumor suppressor genes responsible transformation and tumor progression. The molecular characterization was performed for the first time in the early '90s, by a research team led by Bert Vogelstein, and therefore the development of colorectal molecular model is also known as the "model of Vogelstein. According to that report, mutations in specific genes lead to specific developmental stages colorectal cancer: mutations in the APC gene cause an overgrowth, which becomes adenoma after inactivation by promoter hypermethylation of several genes (such as p16INK4a) and the gene mutations iperattivanti K -Ras. Following alterations inactivating TP53 gene leads to the stage of carcinoma in situ and, therefore, with the loss of expression of altri geni oncosoppressori, principalmente localizzati sul braccio lungo del cromosoma 18, come DCC, SMAD2 e SMAD4, la malattia è in grado di metastatizzare in altri distretti corporei, tipicamente il fegato e, in minor misura, il polmone.Il gran numero di studi che ha portato alla formulazione di tale modello ha fatto sì che il tumore colorettale venga considerato ancora oggi come paradigma di modello molecolare della crescita tumorale. Quantunque il modello di Vogelstein sia supportato da un'ampia gamma di studi epidemiologici, clinici, istopatologici e genetici, non è mai stato dimostrato direttamente. Risultati recentemente pubblicati sembrano porre in discussione tale modello. Infatti, emerge che solo in rare occasioni, circa il 10% dei casi, il tumore colorettale si sia sviluppato seguendo tale modello e che invece esistano numerose altre vie che portano ugualmente alla formazione del tumore colorettale, tutte accomunate da un'alterazione iniziale a carico del gene APC o dei prodotti genici con cui la proteina APC interagisce, come la proteina b-catenina. Un ulteriore elemento di critica al modello di Vogelstein è rappresentato dal fatto che i tumori del colon e quelli del retto sembra possano seguire vie di sviluppo differenti. Gli studi finora condotti hanno avuto il pregio di individuare una serie di marcatori molecolari, le cui alterazioni determinano l'insorgenza della neoplasia. Lo scopo delle ricerche attuali è quello di individuare, attraverso analisi molecolari, marcatori sensibili e specifici that can be used to detect early disease onset. Molecular analysis on body fluids such as feces and plasma, may provide high sensitivity with reduced invasiveness. In particular, the influx of exfoliated cells in the colon of feces, in an amount equal to about 1010 cells per day, suggests the use of fecal material to obtain DNA suitable for the determination of molecular alterations and the detection of cancerous lesions at the level intestinal epithelium. The search for molecular markers in DNA extracted from feces of patients operated on for colorectal cancer revealed conflicting aspects. The analysis of the APC gene, mutated in more than 80% of cases and involved in fasi precoci dello sviluppo tumorale, dovrebbe rappresentare un marcatore ideale. Tuttavia la sequenza di tale gene è molto ampia (2843 aminoacidi) e le mutazioni inattivanti possono insorgere ovunque. Le 5-6 mutazioni più frequenti (hot-spot mutations) non arrivano a coprire il 20% di tutte le mutazioni. Per questi motivi, la ricerca di mutazioni nel gene APC nelle feci, che recentemente è stata condotta grazie a metodiche molto sensibili, è molto laboriosa, costosa e potrebbe quindi essere indicata per predire la ripresa di malattia, ma non per la diagnosi precoce. Lo stesso discorso può valere per il gene TP53. Alterazioni a carico del gene K-Ras, invece, derivano da mutazioni in soltanto tre posizioni della sequenza nucleotidica del gene, two of which cover more than 98% of the mutations. In this relative ease of analysis, however, is matched by a low sensitivity: the K-Ras gene is mutated in only 50% of cases and it is possible to identify the mutation in fecal samples only if the primary tumor is located in the descending colon, sigmoid colon or in rectum. A recent study seems to offer significant prospects for a new molecular approach, less laborious and expensive. This approach stems from the observation of a correlation between the conservation of the DNA extracted from feces and presence of tumor cells in the colon. The ability to amplify DNA stool seems to be higher, thus allowing a greater level of amplification in DNA extracted from feces of patients with colorectal cancer or adenoma, compared to that obtained from healthy individuals. With the simple analysis of the amplified levels of fecal DNA (L-DNA: Long DNA) could be identified more than half of patients with cancer or precancerous lesions, with high specificity. In addition to good sensitivity and specificity, this technique of investigation has the advantage of being relatively simple and require shorter time and lower cost than the traditional analysis mutazionale.I reasons for the increased efficiency of amplification of DNA extracted from feces of patients with colorectal cancer are not known with accuracy. The hypothesis is that in healthy cells that exfoliate siano spesso necrotiche o apoptotiche e quindi con un DNA genomico degradato, frammentato e, conseguentemente, difficile da amplificare, mentre nei pazienti, le cellule tumorali esfoliate nel lume intestinale sarebbero prevalentemente integre e vitali e quindi con un DNA genomico ben conservato e più facilmente amplificabile.Le stesse considerazioni possono essere formulate anche per le analisi sul plasma, in cui tuttavia un nuovo marcatore sembra ricoprire un ruolo molto importante: il DNA liberamente circolante nel plasma non associato a cellule (cell-free DNA), di origine tumorale. Recentemente è emerso infatti che livelli abnormemente elevati di DNA liberamente circolante nel plasma sono correlati alla presenza di tumore colorettale primario. Dato che in altre malignancies such as non-small cell lung cancer, it was demonstrated that the level of free circulating DNA in plasma is predictive of disease recurrence or onset of metastases in specific body areas, such as the liver, in the follow-up patients, it is desirable that a similar correspondence is shown to be valid also for colorectal cancer, so you can have an additional and more efficient method of analysis of serological tests in addition to the CEA and CA19.9. In addition, a qualitative analysis of this DNA could provide a tool for early detection of malattia.Poiché analysis of individual molecular markers have not been successful, the future goal of research is to identify a battery of molecular markers that, together, are able to identify all the primary tumors and predict the recovery in the spot or in other districts. Such analysis, based on highly specific molecular alterations in the quality of their cancer may be associated, as mentioned above, the quantitative analysis is currently being studied in plasma. With the development of ever more sophisticated and sensitive, you may also be measured simultaneously in the same tumor gene expression of many thousands of genes is the case of the technique of cDNA microarray. Using this method will also be possible to analyze colorectal cancer mutational patterns that are different and therefore have followed different paths of transformation and tumor progression. The search and identification of new molecular markers with the technique of cDNA microarray, could lead to the identification of new therapeutic strategies to decrease the risk of developing cancers of the colon and rectum. It 's the case of studies involving the protein cyclooxygenase-2 (COX-2). COX-2 is a protein whose expression is induced as a result of many types of stress. E 'was shown that all of colon cancer, has greatly elevated levels of COX-2. Overexpression of this protein is present instead in at least 50% of adenomas. E 'was evaluated with RT-PCR, the expression of mRNA for COX-2 in 63 sporadic colorectal adenomas, generally higher in all lesions compared to that observed in the corresponding normal mucosa, the levels of mRNA for COX-2 correlated with the size but not with dell'adenoma headquarters, the macroscopic shape or degree of dysplasia. This increase in expression inhibits apoptosis and / or increase angiogenesis. This protein could then be linked to the risk or even result in the development of colorectal tumors. Therefore, drugs that inhibit the production of COX-2, such as anti-inflammatory drugs (NSAIDs), could play an important role in the prophylactic prevention of neoplastic transformation of mucosa del colon-retto, ripristinando i meccanismi favorenti l'apoptosi e regolando l'angiogenesi. In particolare, potrebbero beneficiare dell'assunzione di tali farmaci gli individui affetti da FAP; peraltro, sono disponibili dati che documentano un effetto protettivo di questa classe di farmaci anche per quanto riguarda i carcinomi sporadici. In particolare, in soggetti consumatori cronici di acido acetilsalicilico o di altri FANS è stata stimata una riduzione del rischio relativo di sviluppare carcinomi del colon-retto pari al 40-50%. Questi farmaci hanno dimostrato di possedere un effetto positivo prevenendo l'insorgenza di neoplasie (adenomi e carcinomi), determinando la regressione degli adenomi, inibendo la crescita dei carcinomi. La loro efficacia, which is also expressed in terms of reduction in tumor-associated mortality, has no correlation with age, sex, with the head concerned or with other risk factors coexist. However, NSAIDs also inhibit trade in the other proteins belonging to the family of cyclooxygenase, cyclooxygenase-1 (COX-1), which is vital in maintaining gastric homeostasis. Therefore, the possible benefits are largely canceled by the onset of side effects, particularly frequent and often important, especially when you consider that the effectiveness is closely related to dose (ineffective low dose acetylsalicylic acid) and recruitment of the drug, ceasing with the interruption administration. More recently, they were marketed, and are currently under investigation in oncology, NSAIDs selective cyclooxygenase-2. In particular, celecoxib and rofecoxib are at an advanced stage of evaluation, the results are currently available to lay a protective effect as the other non-selective NSAIDs, with fewer adverse side effects.
el colorectal cancer, and this model has been described for the first time in 1975. The various phases of this process, which involves the transition from normal mucosa to adenoma and then to carcinoma in situ and finally to the spread of disease to other districts, are characterized by mutational events that occur in the genome against oncogenes and tumor suppressor genes responsible transformation and tumor progression. The molecular characterization was performed for the first time in the early '90s, by a research team led by Bert Vogelstein, and therefore the development of colorectal molecular model is also known as the "model of Vogelstein. According to that report, mutations in specific genes lead to specific developmental stages colorectal cancer: mutations in the APC gene cause an overgrowth, which becomes adenoma after inactivation by promoter hypermethylation of several genes (such as p16INK4a) and the gene mutations iperattivanti K -Ras. Following alterations inactivating TP53 gene leads to the stage of carcinoma in situ and, therefore, with the loss of expression of altri geni oncosoppressori, principalmente localizzati sul braccio lungo del cromosoma 18, come DCC, SMAD2 e SMAD4, la malattia è in grado di metastatizzare in altri distretti corporei, tipicamente il fegato e, in minor misura, il polmone.Il gran numero di studi che ha portato alla formulazione di tale modello ha fatto sì che il tumore colorettale venga considerato ancora oggi come paradigma di modello molecolare della crescita tumorale. Quantunque il modello di Vogelstein sia supportato da un'ampia gamma di studi epidemiologici, clinici, istopatologici e genetici, non è mai stato dimostrato direttamente. Risultati recentemente pubblicati sembrano porre in discussione tale modello. Infatti, emerge che solo in rare occasioni, circa il 10% dei casi, il tumore colorettale si sia sviluppato seguendo tale modello e che invece esistano numerose altre vie che portano ugualmente alla formazione del tumore colorettale, tutte accomunate da un'alterazione iniziale a carico del gene APC o dei prodotti genici con cui la proteina APC interagisce, come la proteina b-catenina. Un ulteriore elemento di critica al modello di Vogelstein è rappresentato dal fatto che i tumori del colon e quelli del retto sembra possano seguire vie di sviluppo differenti. Gli studi finora condotti hanno avuto il pregio di individuare una serie di marcatori molecolari, le cui alterazioni determinano l'insorgenza della neoplasia. Lo scopo delle ricerche attuali è quello di individuare, attraverso analisi molecolari, marcatori sensibili e specifici that can be used to detect early disease onset. Molecular analysis on body fluids such as feces and plasma, may provide high sensitivity with reduced invasiveness. In particular, the influx of exfoliated cells in the colon of feces, in an amount equal to about 1010 cells per day, suggests the use of fecal material to obtain DNA suitable for the determination of molecular alterations and the detection of cancerous lesions at the level intestinal epithelium. The search for molecular markers in DNA extracted from feces of patients operated on for colorectal cancer revealed conflicting aspects. The analysis of the APC gene, mutated in more than 80% of cases and involved in fasi precoci dello sviluppo tumorale, dovrebbe rappresentare un marcatore ideale. Tuttavia la sequenza di tale gene è molto ampia (2843 aminoacidi) e le mutazioni inattivanti possono insorgere ovunque. Le 5-6 mutazioni più frequenti (hot-spot mutations) non arrivano a coprire il 20% di tutte le mutazioni. Per questi motivi, la ricerca di mutazioni nel gene APC nelle feci, che recentemente è stata condotta grazie a metodiche molto sensibili, è molto laboriosa, costosa e potrebbe quindi essere indicata per predire la ripresa di malattia, ma non per la diagnosi precoce. Lo stesso discorso può valere per il gene TP53. Alterazioni a carico del gene K-Ras, invece, derivano da mutazioni in soltanto tre posizioni della sequenza nucleotidica del gene, two of which cover more than 98% of the mutations. In this relative ease of analysis, however, is matched by a low sensitivity: the K-Ras gene is mutated in only 50% of cases and it is possible to identify the mutation in fecal samples only if the primary tumor is located in the descending colon, sigmoid colon or in rectum. A recent study seems to offer significant prospects for a new molecular approach, less laborious and expensive. This approach stems from the observation of a correlation between the conservation of the DNA extracted from feces and presence of tumor cells in the colon. The ability to amplify DNA stool seems to be higher, thus allowing a greater level of amplification in DNA extracted from feces of patients with colorectal cancer or adenoma, compared to that obtained from healthy individuals. With the simple analysis of the amplified levels of fecal DNA (L-DNA: Long DNA) could be identified more than half of patients with cancer or precancerous lesions, with high specificity. In addition to good sensitivity and specificity, this technique of investigation has the advantage of being relatively simple and require shorter time and lower cost than the traditional analysis mutazionale.I reasons for the increased efficiency of amplification of DNA extracted from feces of patients with colorectal cancer are not known with accuracy. The hypothesis is that in healthy cells that exfoliate siano spesso necrotiche o apoptotiche e quindi con un DNA genomico degradato, frammentato e, conseguentemente, difficile da amplificare, mentre nei pazienti, le cellule tumorali esfoliate nel lume intestinale sarebbero prevalentemente integre e vitali e quindi con un DNA genomico ben conservato e più facilmente amplificabile.Le stesse considerazioni possono essere formulate anche per le analisi sul plasma, in cui tuttavia un nuovo marcatore sembra ricoprire un ruolo molto importante: il DNA liberamente circolante nel plasma non associato a cellule (cell-free DNA), di origine tumorale. Recentemente è emerso infatti che livelli abnormemente elevati di DNA liberamente circolante nel plasma sono correlati alla presenza di tumore colorettale primario. Dato che in altre malignancies such as non-small cell lung cancer, it was demonstrated that the level of free circulating DNA in plasma is predictive of disease recurrence or onset of metastases in specific body areas, such as the liver, in the follow-up patients, it is desirable that a similar correspondence is shown to be valid also for colorectal cancer, so you can have an additional and more efficient method of analysis of serological tests in addition to the CEA and CA19.9. In addition, a qualitative analysis of this DNA could provide a tool for early detection of malattia.Poiché analysis of individual molecular markers have not been successful, the future goal of research is to identify a battery of molecular markers that, together, are able to identify all the primary tumors and predict the recovery in the spot or in other districts. Such analysis, based on highly specific molecular alterations in the quality of their cancer may be associated, as mentioned above, the quantitative analysis is currently being studied in plasma. With the development of ever more sophisticated and sensitive, you may also be measured simultaneously in the same tumor gene expression of many thousands of genes is the case of the technique of cDNA microarray. Using this method will also be possible to analyze colorectal cancer mutational patterns that are different and therefore have followed different paths of transformation and tumor progression. The search and identification of new molecular markers with the technique of cDNA microarray, could lead to the identification of new therapeutic strategies to decrease the risk of developing cancers of the colon and rectum. It 's the case of studies involving the protein cyclooxygenase-2 (COX-2). COX-2 is a protein whose expression is induced as a result of many types of stress. E 'was shown that all of colon cancer, has greatly elevated levels of COX-2. Overexpression of this protein is present instead in at least 50% of adenomas. E 'was evaluated with RT-PCR, the expression of mRNA for COX-2 in 63 sporadic colorectal adenomas, generally higher in all lesions compared to that observed in the corresponding normal mucosa, the levels of mRNA for COX-2 correlated with the size but not with dell'adenoma headquarters, the macroscopic shape or degree of dysplasia. This increase in expression inhibits apoptosis and / or increase angiogenesis. This protein could then be linked to the risk or even result in the development of colorectal tumors. Therefore, drugs that inhibit the production of COX-2, such as anti-inflammatory drugs (NSAIDs), could play an important role in the prophylactic prevention of neoplastic transformation of mucosa del colon-retto, ripristinando i meccanismi favorenti l'apoptosi e regolando l'angiogenesi. In particolare, potrebbero beneficiare dell'assunzione di tali farmaci gli individui affetti da FAP; peraltro, sono disponibili dati che documentano un effetto protettivo di questa classe di farmaci anche per quanto riguarda i carcinomi sporadici. In particolare, in soggetti consumatori cronici di acido acetilsalicilico o di altri FANS è stata stimata una riduzione del rischio relativo di sviluppare carcinomi del colon-retto pari al 40-50%. Questi farmaci hanno dimostrato di possedere un effetto positivo prevenendo l'insorgenza di neoplasie (adenomi e carcinomi), determinando la regressione degli adenomi, inibendo la crescita dei carcinomi. La loro efficacia, which is also expressed in terms of reduction in tumor-associated mortality, has no correlation with age, sex, with the head concerned or with other risk factors coexist. However, NSAIDs also inhibit trade in the other proteins belonging to the family of cyclooxygenase, cyclooxygenase-1 (COX-1), which is vital in maintaining gastric homeostasis. Therefore, the possible benefits are largely canceled by the onset of side effects, particularly frequent and often important, especially when you consider that the effectiveness is closely related to dose (ineffective low dose acetylsalicylic acid) and recruitment of the drug, ceasing with the interruption administration. More recently, they were marketed, and are currently under investigation in oncology, NSAIDs selective cyclooxygenase-2. In particular, celecoxib and rofecoxib are at an advanced stage of evaluation, the results are currently available to lay a protective effect as the other non-selective NSAIDs, with fewer adverse side effects. 
