A myriad of medicinal effects has been attributed to Thymoquinone (TQ), the major biological-active component of Nigella sativa. TQ has been shown to exhibit potent anti-tumor activities. The present work was undertak...A myriad of medicinal effects has been attributed to Thymoquinone (TQ), the major biological-active component of Nigella sativa. TQ has been shown to exhibit potent anti-tumor activities. The present work was undertaken to further explore TQ’s chemopreventive efficacy against 1, 2-dimethylhydrazine (DMH)-induced colon carcinogenesis in the rat model through a two-phase study (initiation and post-initiation) and to evaluate its potential impact on tumor progression and invasion in vivo. TQ treatment in the initiation phase significantly reduced tumor incidence, multiplicity and mean tumor volume. However, although mean tumor volume and multiplicity were decreased upon TQ treatment in the post-initiation phase, TQ did not reduce incidence significantly. Cellular proliferation, as assessed by expression of colonic PCNA, was shown to be inhibited in consequence to TQ treatment in both phases, with a more pronounced reduction in the initiation phase. In addition, our results demonstrated an appreciable negative impact of TQ on vascular endothelial growth factor (VEGF) production in tumor-bearing rats. Furthermore, we provided evidence that TQ-treatment, in both phases, tended to considerably suppress tumor progression and invasion. Taken together, the present study demonstrated that TQ, at an orally daily dose of 10 mg/kg, has a chemopreventive effect in the initiation phase, and has the potential to attenuate tumor burden, suppress progression of pre-neoplastic lesions and to inhibit tumor growth in the post-initiation phase of DMH-induced colon carcinogenesis, We surmise that such effects of TQ may be due to suppression of cellular proliferation and inhibition of VEGF production. The results could provide an effective chemopreventive approach in the primary prevention of colon cancer in humans in the next future, and illuminate a promising horizon to combat progression of benign colonic pre-neoplastic lesions into malignant metastatic tumors and to manage colon cancer.展开更多
Background:In the early metastasis of colon cancer,cancer cells detach,migrate,and infiltrate surrounding tissues,including lymph vessels and blood vessels.Tumor heterogeneity arises from both tumor cells and distinct...Background:In the early metastasis of colon cancer,cancer cells detach,migrate,and infiltrate surrounding tissues,including lymph vessels and blood vessels.Tumor heterogeneity arises from both tumor cells and distinct microenvironments.Maldistribution of blood vessels,creates hypoxic regions within the tumors,fostering cancer stem cell-like properties due to reduced oxygen and nutrient supply.Under hypoxia,tumor cells shift to a glycolytic pathway,producing more lactic acid that acidifies the microenvironment and leads to unstable heart rate variability(HRV)factors,weight disparity,and a higher incidence of aberrant crypt foci(ACF).These hypoxic-induced parameters promote cancer cell invasion,increase radiation resistance,and facilitate cancer cell migration.Methods:In this study,we induced hypoxia-preneoplastic colon damage in albino Wister rats by administrating 1,2-dimethyl hydrazine(DMH).After successfully creating a hypoxic environment in albino Wister rats,resulting in preneoplastic colon damage,we randomly allocated Wistar albino rats into seven groups,each containing 8 animals,and conducted a 6-week study.Group 1-Normal control(administered 1 mM EDTA+saline,2 ml/kg/day,p.o.);group 2-Toxic control(administered DMH,30 mg/kg/week,s.c.);group 3-Standard treatment(DMH,30 mg/kg/week,s.c.for 6 weeks),followed by 5-fluorouracil and Leucovorin(25 mg/kg each on 1^(st),3^(rd),7^(th),and 10^(th) days,i.p.after 6 weeks administration of DMH);group 4-Low dose of P1(DMH,30 mg/kg/week,s.c.+P1,2 mg/kg,i.v.,weekly for 3 weeks);group 5-High dose P1(DMH,30 mg/kg/week,s.c.+P1,4 mg/kg,i.v.,weekly for 3 weeks),group 6-Low dose of P2(DMH,30 mg/kg/week,s.c.,+P2,2 mg/kg,i.v.,weekly for 3 weeks),group 7-High dose of P2(DMH,30 mg/kg/week,s.c.,+P2,4 mg/kg,i.v.weekly for 3 weeks).Results:DMH-treated rats exhibited alterations in HRV factors,weight disparity,elevated gastric pH,increased total acidity,a higher incidence of ACF,and changes in antioxidant markers(TBARs,SOD,catalase,GSH).Brightfield microscopy at 40x magnification revealed the presence of large crypts within aberrant crypt foci in the toxic control group.Conclusion:Treatment groups P1 and P2 containing triazine derivatives initiated proteasomal degradation of Hypoxia Inducible Factor-1α(HIF-1α)by activating Prolyl Hydroxylase(PHDs)pathways.HIF-1αunder a hypoxic environment is responsible for activating a multitude of genes involved in angiogenesis,metastasis,invasiveness,pH changes,metabolic reprogramming,stem cell maintenance,resistance to radiation,and downstream regulation of the immune system.Treatment with P1 and P2 groups helped minimize the ACF count and restored HRV factors,weight disparity,pH levels,total acidity,and oxidative balance.Our findings emphasize the potential role of 1,2,4-triazine derivatives in suppressing hypoxia-induced colon carcinogenesis.展开更多
Colorectal cancer is the second most common cause of cancer-related death in many industrialized countries and is characterized by a heterogenic pool of cells with distinct differentiation patterns. Recently, the conc...Colorectal cancer is the second most common cause of cancer-related death in many industrialized countries and is characterized by a heterogenic pool of cells with distinct differentiation patterns. Recently, the concept that cancer might arise from a rare population of cells with stem cell-like properties has received support with regard to several solid tumors, including colorectal cancer. According to the cancer stem cell hypothesis, cancer can be considered a disease in which mutations either convert normal stem cells into aberrant counterparts or cause a more differentiated cell to revert toward a stem cell-like behaviour; either way these cells are thought to be responsible for tumor generation and propagation. The statement that only a subset of cells drives tumor formation has major implications for the development of new targeted therapeutic strategies aimed at eradicating the tumor stem cell population. This review will focus on the biology of normal and malignant colonic stem cells, which might contribute to our understanding of the mechanisms responsible for tumor development and resistance to therapy.展开更多
AIM To critically evaluate previous scientific evidence on Fusobacterium's role in colorectal neoplasia development.METHODS Two independent investigators systematically reviewed all original scientific articles pu...AIM To critically evaluate previous scientific evidence on Fusobacterium's role in colorectal neoplasia development.METHODS Two independent investigators systematically reviewed all original scientific articles published between January,2000,and July,2017,using Pub Med,EMBASE,and MEDLINE. A total of 355 articles were screened at the abstract level. Of these,only original scientific human,animal,and in vitro studies investigating Fusobacterium and its relationship with colorectal cancer(CRC) were included in the analysis. Abstracts,review articles,studies investigating other colonic diseases,and studies written in other languages than English were excluded from our analysis. Ninety articles were included after removing duplicates,resolving disagreements between the two reviewers,and applying the above criteria.RESULTS Studies have consistently identified positive associations between Fusobacterium,especially Fusobacterium nucleatum(F. nucleatum),and CRC. Stronger associations were seen in CRCs proximal to the splenic flexure and Cp G island methylator phenotype(CIMP)-high CRCs. There was evidence of temporality and a biological gradient,with increased F. nucleatum DNA detection and quantity along the traditional adenoma-carcinoma sequence and in CIMP-high CRC precursors. Diet may have a differential impact on colonic F. nucleatum enrichment;evidence suggests that high fiber diet may reduce the risk of a subset of CRCs that are F. nucleatum DNA-positive. Data also suggest shorter CRC and disease-specific survival with increased amount of F. nucleatum DNA in CRC tissue. The pathophysiology of enrichment of F. nucleatum and other Fusobacterium species in colonic tissue is unclear;however,the virulence factors and changes to the local colonic environment with disruption of the protective mucus layer may contribute. The presence of a host lectin(Gal-Gal NAc) in the colonic epithelium may also mediate F. nucleatum attachment to CRC and precursors through interaction with an F. nucleatum protein,fibroblast activation protein 2(FAP2). The clinical significance of detection or enrichment of Fusobacterium in colorectal neoplasia is ambiguous,but data suggest a procarcinogenic effect of F. nucleatum,likely due to activation of oncogenic and inflammatory pathways and modulation of the tumor immune environment. This is hypothesized to be mediated by certain F. nucleatum strains carrying invasive properties and virulence factors such as Fad A and FAP.CONCLUSION Evidence suggests a potential active role of Fusobacterium,specifically F. nucleatum,in CRC. Future prospective and experimental human studies would fill an important gap in this literature.展开更多
A field defect is a field of pre-malignant tissue in which a new cancer is likely to arise. Field defects often appear to be histologically normal under the microscope. Recent research indicates that cells within a fi...A field defect is a field of pre-malignant tissue in which a new cancer is likely to arise. Field defects often appear to be histologically normal under the microscope. Recent research indicates that cells within a field defect characteristically have an increased frequency of epigenetic alterations and these may be fundamentally important as underlying factors in progression to cancer. However, understanding of epigenetic field defects is at an early stage, and the work of Katsurano et al published this year, is a key contribution to this field. One question examined by Katsurano et al was how early could the formation of an epigenetic field defect be de-tected in a mouse colitis model of tumorigenesis. They highlighted a number of measurable epigenetic altera-tions, detected very early in normal appearing tissue undergoing histologically invisible tumorigenesis. They also documented the increasing presence of the epigenetic alterations at successive times during progression to cancer. In this commentary, we offer a perspective on the changes they observed within a broader sequence of epigenetic events that occur in progressionto cancer. In particular, we highlight the likely central role of epigenetic deficiencies in DNA repair gene expression that arise during progression to cancer.展开更多
The multiple beneficial effects on human health of the short-chain fatty acid butyrate,synthesized from nonabsorbed carbohydrate by colonic microbiota,are well documented.At the intestinal level,butyrate plays a regul...The multiple beneficial effects on human health of the short-chain fatty acid butyrate,synthesized from nonabsorbed carbohydrate by colonic microbiota,are well documented.At the intestinal level,butyrate plays a regulatory role on the transepithelial fluid transport,ameliorates mucosal inflammation and oxidative status,reinforces the epithelial defense barrier,and modulates visceral sensitivity and intestinal motility.In addition,a growing number of studies have stressed the role of butyrate in the prevention and inhibition of colorectal cancer.At the extraintestinal level,butyrate exerts potentially useful effects on many conditions,including hemoglobinopathies,genetic metabolic diseases,hypercholesterolemia,insulin resistance,and ischemic stroke.The mechanisms of action of butyrate are different;many of these are related to its potent regulatory effects on gene expression.These data suggest a wide spectrum of positive effects exerted by butyrate,with a high potential for a therapeutic use in human medicine.展开更多
I read with great interest the recent article by Cordero et al in a recent issue of your esteemed journal.Interestingly,the past few years have seen the emergence of CD26 as an important diagnostic and prognostic mark...I read with great interest the recent article by Cordero et al in a recent issue of your esteemed journal.Interestingly,the past few years have seen the emergence of CD26 as an important diagnostic and prognostic marker for a number of systemic malignancies besides colo-rectal carcinomas.For instance,serum CD26 levels are an important emerging marker of B-cell chronic lymphocytic leukemia(B-CLL).In fact,Molica et al have recently reported shorter time to first treatment in B-CLL which exhibit higher serum CD26 levels and simultaneously demonstrate absence of mutation in Ig V(H).Similarly,CD26 serves as a marker of poor prognosis in T cell lymphomas.Simultaneously,a poor response to 2’-deoxycoformycin is seen T cell lymphomas expressing CD26.Similarly,breast carcinomas exhibit decreased CD26 mean fluorescence intensity and a decreased percentage of CD26 positive lymphocytes in comparison to benign breast tumors and healthy individuals.展开更多
Understanding of the mechanism of colorectal carcinogenesis has been gaining momentum for some years on account of its high incidence and impact on the lives of individuals affected. Different genetic abnormalities ha...Understanding of the mechanism of colorectal carcinogenesis has been gaining momentum for some years on account of its high incidence and impact on the lives of individuals affected. Different genetic abnormalities have been found in colorectal cancers from different sites. For example,proximal colon cancer is usually related to the nucleotide instability pathway,as microsatellite instability(MSI). However,distal colon cancer is usually associated with specific chromosomal instability(CIN). The development of cancer at the rectum,though similar to that at the colon,displays its own unique features. These differences might be partially attributed to different embryological development and physiological circumstances. Environmental factors such as diet and alcohol intake also differ in their role in the development of tumors in the three segments,proximal colon,distal colon,and rectum. "Proximal shift" of colon cancer has been known for some time,and survival rates of colorectal cancer are higher when rectal cancers are excluded,both of which emphasize the three different segments of colorectal cancer and their different properties. Meanwhile,colonic and rectal cancers are distinctive therapeutic entities. The concept of three entities of colorectal cancer may be important in designing clinical trails or therapeutic strategies. However,the dispute about the inconsistency of data concerning the site-specific mechanism of colorectal carcinoma does exist,and more evidence about molecular events of carcinogenesis and targeted therapy needs to be collected to definitely confirm the conception.展开更多
2011080 Annexin A2 expression in human esophagealsquamous cell carcinoma and its correlation withinvasion and metastasis. FENG Junguo (冯军国), etal. Med Res Center, 1st Affil Hosp, Xinjiang Med Univ,Urumqi 830054 . C...2011080 Annexin A2 expression in human esophagealsquamous cell carcinoma and its correlation withinvasion and metastasis. FENG Junguo (冯军国), etal. Med Res Center, 1st Affil Hosp, Xinjiang Med Univ,Urumqi 830054 . Chin J Dig 2010; 30 (11):798-802.展开更多
文摘A myriad of medicinal effects has been attributed to Thymoquinone (TQ), the major biological-active component of Nigella sativa. TQ has been shown to exhibit potent anti-tumor activities. The present work was undertaken to further explore TQ’s chemopreventive efficacy against 1, 2-dimethylhydrazine (DMH)-induced colon carcinogenesis in the rat model through a two-phase study (initiation and post-initiation) and to evaluate its potential impact on tumor progression and invasion in vivo. TQ treatment in the initiation phase significantly reduced tumor incidence, multiplicity and mean tumor volume. However, although mean tumor volume and multiplicity were decreased upon TQ treatment in the post-initiation phase, TQ did not reduce incidence significantly. Cellular proliferation, as assessed by expression of colonic PCNA, was shown to be inhibited in consequence to TQ treatment in both phases, with a more pronounced reduction in the initiation phase. In addition, our results demonstrated an appreciable negative impact of TQ on vascular endothelial growth factor (VEGF) production in tumor-bearing rats. Furthermore, we provided evidence that TQ-treatment, in both phases, tended to considerably suppress tumor progression and invasion. Taken together, the present study demonstrated that TQ, at an orally daily dose of 10 mg/kg, has a chemopreventive effect in the initiation phase, and has the potential to attenuate tumor burden, suppress progression of pre-neoplastic lesions and to inhibit tumor growth in the post-initiation phase of DMH-induced colon carcinogenesis, We surmise that such effects of TQ may be due to suppression of cellular proliferation and inhibition of VEGF production. The results could provide an effective chemopreventive approach in the primary prevention of colon cancer in humans in the next future, and illuminate a promising horizon to combat progression of benign colonic pre-neoplastic lesions into malignant metastatic tumors and to manage colon cancer.
基金C.Karthikeyan,Indira Gandhi National Tribal University,Lalpur,Amarkantak,Anuppur,Madhya Pradesh,484887,India,for providing the gift sample of 1,2,4-triazine derivatives used for the study.
文摘Background:In the early metastasis of colon cancer,cancer cells detach,migrate,and infiltrate surrounding tissues,including lymph vessels and blood vessels.Tumor heterogeneity arises from both tumor cells and distinct microenvironments.Maldistribution of blood vessels,creates hypoxic regions within the tumors,fostering cancer stem cell-like properties due to reduced oxygen and nutrient supply.Under hypoxia,tumor cells shift to a glycolytic pathway,producing more lactic acid that acidifies the microenvironment and leads to unstable heart rate variability(HRV)factors,weight disparity,and a higher incidence of aberrant crypt foci(ACF).These hypoxic-induced parameters promote cancer cell invasion,increase radiation resistance,and facilitate cancer cell migration.Methods:In this study,we induced hypoxia-preneoplastic colon damage in albino Wister rats by administrating 1,2-dimethyl hydrazine(DMH).After successfully creating a hypoxic environment in albino Wister rats,resulting in preneoplastic colon damage,we randomly allocated Wistar albino rats into seven groups,each containing 8 animals,and conducted a 6-week study.Group 1-Normal control(administered 1 mM EDTA+saline,2 ml/kg/day,p.o.);group 2-Toxic control(administered DMH,30 mg/kg/week,s.c.);group 3-Standard treatment(DMH,30 mg/kg/week,s.c.for 6 weeks),followed by 5-fluorouracil and Leucovorin(25 mg/kg each on 1^(st),3^(rd),7^(th),and 10^(th) days,i.p.after 6 weeks administration of DMH);group 4-Low dose of P1(DMH,30 mg/kg/week,s.c.+P1,2 mg/kg,i.v.,weekly for 3 weeks);group 5-High dose P1(DMH,30 mg/kg/week,s.c.+P1,4 mg/kg,i.v.,weekly for 3 weeks),group 6-Low dose of P2(DMH,30 mg/kg/week,s.c.,+P2,2 mg/kg,i.v.,weekly for 3 weeks),group 7-High dose of P2(DMH,30 mg/kg/week,s.c.,+P2,4 mg/kg,i.v.weekly for 3 weeks).Results:DMH-treated rats exhibited alterations in HRV factors,weight disparity,elevated gastric pH,increased total acidity,a higher incidence of ACF,and changes in antioxidant markers(TBARs,SOD,catalase,GSH).Brightfield microscopy at 40x magnification revealed the presence of large crypts within aberrant crypt foci in the toxic control group.Conclusion:Treatment groups P1 and P2 containing triazine derivatives initiated proteasomal degradation of Hypoxia Inducible Factor-1α(HIF-1α)by activating Prolyl Hydroxylase(PHDs)pathways.HIF-1αunder a hypoxic environment is responsible for activating a multitude of genes involved in angiogenesis,metastasis,invasiveness,pH changes,metabolic reprogramming,stem cell maintenance,resistance to radiation,and downstream regulation of the immune system.Treatment with P1 and P2 groups helped minimize the ACF count and restored HRV factors,weight disparity,pH levels,total acidity,and oxidative balance.Our findings emphasize the potential role of 1,2,4-triazine derivatives in suppressing hypoxia-induced colon carcinogenesis.
基金Supported by Italian Association for Cancer Research
文摘Colorectal cancer is the second most common cause of cancer-related death in many industrialized countries and is characterized by a heterogenic pool of cells with distinct differentiation patterns. Recently, the concept that cancer might arise from a rare population of cells with stem cell-like properties has received support with regard to several solid tumors, including colorectal cancer. According to the cancer stem cell hypothesis, cancer can be considered a disease in which mutations either convert normal stem cells into aberrant counterparts or cause a more differentiated cell to revert toward a stem cell-like behaviour; either way these cells are thought to be responsible for tumor generation and propagation. The statement that only a subset of cells drives tumor formation has major implications for the development of new targeted therapeutic strategies aimed at eradicating the tumor stem cell population. This review will focus on the biology of normal and malignant colonic stem cells, which might contribute to our understanding of the mechanisms responsible for tumor development and resistance to therapy.
文摘AIM To critically evaluate previous scientific evidence on Fusobacterium's role in colorectal neoplasia development.METHODS Two independent investigators systematically reviewed all original scientific articles published between January,2000,and July,2017,using Pub Med,EMBASE,and MEDLINE. A total of 355 articles were screened at the abstract level. Of these,only original scientific human,animal,and in vitro studies investigating Fusobacterium and its relationship with colorectal cancer(CRC) were included in the analysis. Abstracts,review articles,studies investigating other colonic diseases,and studies written in other languages than English were excluded from our analysis. Ninety articles were included after removing duplicates,resolving disagreements between the two reviewers,and applying the above criteria.RESULTS Studies have consistently identified positive associations between Fusobacterium,especially Fusobacterium nucleatum(F. nucleatum),and CRC. Stronger associations were seen in CRCs proximal to the splenic flexure and Cp G island methylator phenotype(CIMP)-high CRCs. There was evidence of temporality and a biological gradient,with increased F. nucleatum DNA detection and quantity along the traditional adenoma-carcinoma sequence and in CIMP-high CRC precursors. Diet may have a differential impact on colonic F. nucleatum enrichment;evidence suggests that high fiber diet may reduce the risk of a subset of CRCs that are F. nucleatum DNA-positive. Data also suggest shorter CRC and disease-specific survival with increased amount of F. nucleatum DNA in CRC tissue. The pathophysiology of enrichment of F. nucleatum and other Fusobacterium species in colonic tissue is unclear;however,the virulence factors and changes to the local colonic environment with disruption of the protective mucus layer may contribute. The presence of a host lectin(Gal-Gal NAc) in the colonic epithelium may also mediate F. nucleatum attachment to CRC and precursors through interaction with an F. nucleatum protein,fibroblast activation protein 2(FAP2). The clinical significance of detection or enrichment of Fusobacterium in colorectal neoplasia is ambiguous,but data suggest a procarcinogenic effect of F. nucleatum,likely due to activation of oncogenic and inflammatory pathways and modulation of the tumor immune environment. This is hypothesized to be mediated by certain F. nucleatum strains carrying invasive properties and virulence factors such as Fad A and FAP.CONCLUSION Evidence suggests a potential active role of Fusobacterium,specifically F. nucleatum,in CRC. Future prospective and experimental human studies would fill an important gap in this literature.
文摘A field defect is a field of pre-malignant tissue in which a new cancer is likely to arise. Field defects often appear to be histologically normal under the microscope. Recent research indicates that cells within a field defect characteristically have an increased frequency of epigenetic alterations and these may be fundamentally important as underlying factors in progression to cancer. However, understanding of epigenetic field defects is at an early stage, and the work of Katsurano et al published this year, is a key contribution to this field. One question examined by Katsurano et al was how early could the formation of an epigenetic field defect be de-tected in a mouse colitis model of tumorigenesis. They highlighted a number of measurable epigenetic altera-tions, detected very early in normal appearing tissue undergoing histologically invisible tumorigenesis. They also documented the increasing presence of the epigenetic alterations at successive times during progression to cancer. In this commentary, we offer a perspective on the changes they observed within a broader sequence of epigenetic events that occur in progressionto cancer. In particular, we highlight the likely central role of epigenetic deficiencies in DNA repair gene expression that arise during progression to cancer.
基金Supported by A Grant from Agenzia Italiana del Farmaco(AIFA) grant code FARM6FJ728
文摘The multiple beneficial effects on human health of the short-chain fatty acid butyrate,synthesized from nonabsorbed carbohydrate by colonic microbiota,are well documented.At the intestinal level,butyrate plays a regulatory role on the transepithelial fluid transport,ameliorates mucosal inflammation and oxidative status,reinforces the epithelial defense barrier,and modulates visceral sensitivity and intestinal motility.In addition,a growing number of studies have stressed the role of butyrate in the prevention and inhibition of colorectal cancer.At the extraintestinal level,butyrate exerts potentially useful effects on many conditions,including hemoglobinopathies,genetic metabolic diseases,hypercholesterolemia,insulin resistance,and ischemic stroke.The mechanisms of action of butyrate are different;many of these are related to its potent regulatory effects on gene expression.These data suggest a wide spectrum of positive effects exerted by butyrate,with a high potential for a therapeutic use in human medicine.
文摘I read with great interest the recent article by Cordero et al in a recent issue of your esteemed journal.Interestingly,the past few years have seen the emergence of CD26 as an important diagnostic and prognostic marker for a number of systemic malignancies besides colo-rectal carcinomas.For instance,serum CD26 levels are an important emerging marker of B-cell chronic lymphocytic leukemia(B-CLL).In fact,Molica et al have recently reported shorter time to first treatment in B-CLL which exhibit higher serum CD26 levels and simultaneously demonstrate absence of mutation in Ig V(H).Similarly,CD26 serves as a marker of poor prognosis in T cell lymphomas.Simultaneously,a poor response to 2’-deoxycoformycin is seen T cell lymphomas expressing CD26.Similarly,breast carcinomas exhibit decreased CD26 mean fluorescence intensity and a decreased percentage of CD26 positive lymphocytes in comparison to benign breast tumors and healthy individuals.
基金supported by the Program of Science and Technology in the National "Eleventh 5-year Plan" of China (No. 2006BAI0214)the Foundation of Science and Technology of Hangzhou City, China (No. 20061123B02)
文摘Understanding of the mechanism of colorectal carcinogenesis has been gaining momentum for some years on account of its high incidence and impact on the lives of individuals affected. Different genetic abnormalities have been found in colorectal cancers from different sites. For example,proximal colon cancer is usually related to the nucleotide instability pathway,as microsatellite instability(MSI). However,distal colon cancer is usually associated with specific chromosomal instability(CIN). The development of cancer at the rectum,though similar to that at the colon,displays its own unique features. These differences might be partially attributed to different embryological development and physiological circumstances. Environmental factors such as diet and alcohol intake also differ in their role in the development of tumors in the three segments,proximal colon,distal colon,and rectum. "Proximal shift" of colon cancer has been known for some time,and survival rates of colorectal cancer are higher when rectal cancers are excluded,both of which emphasize the three different segments of colorectal cancer and their different properties. Meanwhile,colonic and rectal cancers are distinctive therapeutic entities. The concept of three entities of colorectal cancer may be important in designing clinical trails or therapeutic strategies. However,the dispute about the inconsistency of data concerning the site-specific mechanism of colorectal carcinoma does exist,and more evidence about molecular events of carcinogenesis and targeted therapy needs to be collected to definitely confirm the conception.
文摘2011080 Annexin A2 expression in human esophagealsquamous cell carcinoma and its correlation withinvasion and metastasis. FENG Junguo (冯军国), etal. Med Res Center, 1st Affil Hosp, Xinjiang Med Univ,Urumqi 830054 . Chin J Dig 2010; 30 (11):798-802.