| Colorectal cancer (CRC) is the third most common malignancy in the western world. In the world,500 000 new cases are diagnosed annually,of which approximately 10% die from this disease,making it the second most common malignant cause of death .In China,incidence rates stabilized among men and female from 1973 through 1993,but continued to increase and have been the 4th most common tumor. Unfortunately,despite improvements colorectal carcinoma in surgical technique,molecular biology,radiological imaging and adjuvant therapy, there has been comparatively little change in mortality from colorectal cancer during the past 40 years,and the overall five years survival is only around 50%,and mortality increased from 2.37/100,000 to 8.61/100,000 in recent years. The prognosis for patients with hepatic metastasis is bleak. The median survival is 6-9 months and may increase to 12 months with 5-fluorouracil chemotherapy. Although newer agents such as irinotecan and oxaliplatin may improve survival slightly,chemotherapy remains a palliative treatment. Surgical resection offers the only hope of a cure although the proportion of patients with resectable disease is 10%. The presence of diffuse disease or tumor that invades vital structures such as the portal hepatis is a contraindication to surgery. Although, chemotherapy and radiotherapy have been used in colorectal cancer to reduce local recurrence,improve operability and allow anal sphincter preservation,but it does not seem to improve long-term survival and is associated with more complications, particularly small-bowel obstruction and late-onset diarrhoea due to radiation enteritis. Although studies on gene therapy have been carried out after 1990,it is impossible that gene therapy is applied to clinical treatment in large scale for the problem of vector technology. At present,differentiation therapy for tumors has become the hot point of anti-cancer research,which regulates the expression of oncogenes and tumor suppressed genes in tumors cells. It has been known for many decades that certain murine and human cancers can spontaneously mature to benign tissue. These observations have stimulated investigators to attempt to induce a state of more normal or benign differentiation in cancer cells using biologic substances or chemicals.With the advent of new genetic and molecular pathology techniques,many authors have come to consider the causes and pathogenesis of colon carcinoma as multifactorial with the relationship between each factor not fully understood. All of these factors seem to cooperate in stimulating a disturbance of genes that regulate cell proliferation and programmed cell death. Carcinogenesis and tumor progression are,therefore,thought to be the result of a series of progressive gene alterations,including the activation of oncogenes and the inactivation of tumor suppressor genes.In the recently years,research has suggested that the differentiation agents can induce tumor cells to high differentiation and inhibit the invasion and recurrence of tumor cells to some extent. Furthermore,the combination use of different types of differentiation agents, which could gather the anticancer ability of differentiation agents by synergistic or complementary function,has become a new research tendency. Obviously,understanding the exact mechanism of each differentiation agents is the base of the combination use of them.The search for PA that can reverse the characteristic cellular dedifferentiation of neoplasms, inhibit their growth, and hence be added to the therapeutic armamentarium has led to the identification of aromatic fatty acids as a promising new class of antitumor agents. Phenylacetate has recently been shown to suppress tumor growth and promote differentiation in experimental models. A phase I trial of phenylacetate was conducted in patients with advanced solid tumors. phenylacetate elimination was accounted for by conversion to phenylacetylglutamine, which was excreted in the urine. Sodium phenylacetat... |
PDF Full Text Request