The published article titled“Procaine inhibits the proliferation and migration of colon cancer cells through inactivation of the ERK/MAPK/FAK pathways by regulation of RhoA”has been retracted from Oncology Research,...The published article titled“Procaine inhibits the proliferation and migration of colon cancer cells through inactivation of the ERK/MAPK/FAK pathways by regulation of RhoA”has been retracted from Oncology Research,Vol.26,No.2,2018,pp.209–217.展开更多
AIM To investigate the role of calmodulin-dependent protein kinase Ⅱ(Ca MKⅡ) in colon cancer growth,migration and invasion.METHODS Ca MKⅡ expression in colon cancer and paracancerous tissues was evaluated via immun...AIM To investigate the role of calmodulin-dependent protein kinase Ⅱ(Ca MKⅡ) in colon cancer growth,migration and invasion.METHODS Ca MKⅡ expression in colon cancer and paracancerous tissues was evaluated via immunochemistry. Transcriptional and posttranscriptional levels of Ca MKⅡin tissue samples and MMP2,MMP9 and TIMP-1 expression in the human colon cancer cell line HCT116 were assessed by q RTPCR and western blot. Cell proliferation was detected with the MTT assay. Cancer cell migration and invasion were investigated with the Transwell culture system and woundhealing assay.RESULTS We first demonstrated that CaMK Ⅱ was ove rexpressed in human colon cancers and was associated with cancer differentiation. In the human colon cancer cell line HCT116,the Ca MKII-specific inhibitor KN93,but not its inactive analogue KN92,decreased cancer cell proliferation. Furthermore,KN93 also significantly prohibited HCT116 cell migration and invasion. The specific inhibition of ERK1/2 or p38 decreased the proliferation and migration of colon cancer cells.CONCLUSION Our findings highlight Ca MKⅡ as a potential critical mediator in human colon tumor development and metastasis.展开更多
Lymph node staging is of crucial importance for the therapy stratification and prognosis estimation in colon cancer. Beside the detection of metastases,the number of harvested lymph nodes itself has prognostic relevan...Lymph node staging is of crucial importance for the therapy stratification and prognosis estimation in colon cancer. Beside the detection of metastases,the number of harvested lymph nodes itself has prognostic relevance in stage Ⅱ/Ⅲ cancers. A stage migration effect caused by missed lymph node metastases has been postulated as most likely explanation for that. In order to avoid false negative node staging reporting of at least 12 lymph nodes is recommended. However,this threshold is met only in a minority of cases in daily practice. Due to quality initiatives the situation has improved in the past. This,however,had no influence on staging in several studies. While the numbers of evaluated lymph nodes increased continuously during the last decades the rate of node positive cases remained relatively constant. This fact together with other indications raised doubts that understaging is indeed the correct explanation for the prognostic impact of lymph node harvest. Several authors assume that immune response could play a major role in this context influencing both the lymph node detectability and the tumor's behavior. Further studies addressing this issue are need. Based on the findings the recommendations concerning minimal lymph node numbers and adjuvant chemotherapy should be reconsidered.展开更多
Verticillin A is a diketopiperazine compound which was previously isolated from Amanita flavorubescens Aik(containing parasitic fungi Hypomyces hyalines(Schw.)Tul.).Here,we initially found,by wound healing assay and T...Verticillin A is a diketopiperazine compound which was previously isolated from Amanita flavorubescens Aik(containing parasitic fungi Hypomyces hyalines(Schw.)Tul.).Here,we initially found,by wound healing assay and Tran swell assay in vitro,that verticilli n A possesses an inhibitory effect agai nst the migrati on and in vasion of the human colon cancer cell.Subsequently,c-mesenchymal,epithelial transition factor(c-Met)was identified as a molecular target of verticillin A by screening key genes related to cell migration.Verticillin A-mediated c-Met suppress!on is at the transcriptio nal level.Further study dem on strated that verticilli n A suppressed c-MET phosphorylation and decreased c-MET protein level.In addition,verticillin A inhibited the phosphorylation of c-MET downstream molecules including rat sarcoma(Ras)-associated factor(Raf),extracellular signal-regulated kinase(ERK),and protein kinase B(AKT).Overexpression of Erk partially reversed the verticillin A-mediated anti-metastasis action in the human colon cancer cell.More importantly,verticillin A also inhibited cancer cell metastasis in vivo.Thus,verticillin A can significantly inhibit the migration and invasion of colon cancer cells by targeting c-Met and inhibiting Ras/Raf/mitogen-activated extracellular signal-regulated kinase(MEK)/ERK signaling pathways.Therefore,we determined that verticillin A is a natural compound that can be further developed as an anti-metastatic drug in human cancers.展开更多
Objective This study aimed to investigate how macrophage migration inhibitory factor(MIF)regulates the interaction of signal transducer and activator of transcription 1(STAT1)with CD74,and affects colon cancer prolife...Objective This study aimed to investigate how macrophage migration inhibitory factor(MIF)regulates the interaction of signal transducer and activator of transcription 1(STAT1)with CD74,and affects colon cancer proliferation and invasion.Methods After transfecting MIF small interfering RNA into the SW480 cell line,the expression of STAT1 and CD74 mRNA was detected by qRT-PCR and western blotting.Transwell and MTT assays were performed to detect the colon cancer cell invasion and proliferation ability.Co-immunoprecipitation was used to detect the interaction between CD74 and STAT1 proteins in the treated and control groups.Results The cellular biological assays(MTT and Transwell)showed that the proliferation and invasion ability of colon cancer cells decreased after MIF knockdown;the results showed significant statistical difference(P<0.05).The results of the co-immunoprecipitation assay suggested that MIF knockdown in colon cancer cells could inhibit the binding of CD74 and STAT1 proteins;statistical difference was observed between the two groups(P<0.05).Conclusion MIF can increase the proliferation and invasion of colon cancer cells by promoting the combination of CD74 and STAT1.展开更多
Objective: To study the regulating effect of luteolin on colon cancer HT-29 cell proliferation, migration and epithelial-mesenchymal transition. Methods: Colon cancer HT-29 cells were cultured and randomly divided int...Objective: To study the regulating effect of luteolin on colon cancer HT-29 cell proliferation, migration and epithelial-mesenchymal transition. Methods: Colon cancer HT-29 cells were cultured and randomly divided into two groups, control group were treated with serum-free medium without drugs and LUT group were treated with serum-free medium containing luteolin. After 24 h of treatment, cells were collected to extract RNA, and then fluorescent quantitative PCR method was used to determine the mRNA expression of proliferation genes, migration genes and epithelial-mesenchymal transition genes. Results: After 24 h of luteolin treatment, Lrig1, TSPYL5, Bim, SOX15 and DLC1 mRNA expression in LUT group were significantly higher than those in control group while RPS15a, Bad, TRPV5, TRPV6, PLD2, IBP, SphK1, FAK, Vimentin and N-cadherin mRNA expression were significantly lower than those in control group. Conclusion: Luteolin has inhibiting effect on colon cancer HT-29 cell proliferation, migration and epithelial-mesenchymal transition.展开更多
BACKGROUND Circular RNAs (circRNAs) are considered to be highly stable due to the closed structure, which are predominately correlated with the development and progression of a wide variety of cancers. Colon cancer is...BACKGROUND Circular RNAs (circRNAs) are considered to be highly stable due to the closed structure, which are predominately correlated with the development and progression of a wide variety of cancers. Colon cancer is one of the most common malignancies worldwide. A recent study demonstrated the upregulated expression of circPIP5K1A in non-small cell lung cancer. However, few studies have investigated the relationship between circ_0014130 level and colon cancer. Therefore, elucidating the underlying mechanisms of circPIP5K1A’s role may help with the identification of novel diagnostic and therapeutic targets for colon cancer. AIM To investigate the status of circPIP5K1A in colon cancers and its effects on the modulation of cancer development. METHODS The expression level of circPIP5K1A in tissue and serum samples from colon cancer patients, as well as human colonic cancer cell lines was detected by realtime quantitative reverse transcription-polymerase chain reaction. Following the transfection of specifically synthesized small interfering RNA (siRNA) into colon cell lines, we used Hoechst staining assay to measure the ratio of cell death in the absence of circPIP5K1A. Moreover, we also used the Transwell assay to assess the migratory function of colon cells overexpressing circPIP5K1A. Additionally, we employed a series of bioinformatics prediction programs to predict the potential of circPIP5K1A-targeted miRNAs and mRNAs. The miR-1273a vector was constructed, and then transfected with or without circPIP5K1A vector into colon cancer cells. Afterwards, the expression of activator protein 1 (AP-1), interferon regulating factor 4 (IRF-4), caudal type homeobox 2 (CDX-2), and zinc finger of the cerebellum 1 (Zic-1) was detected by western blotting. RESULTS CircPIP5K1A was significantly upregulated in colon cancer tissue relative to their adjacent normal tissues. Knockdown of circPIP5K1A in colon cancer cells impaired cell viability and suppressed cell invasion and migration, while enforced expression of circPIP5K1A exhibited the opposite effects on cell migration. Bioinformatics prediction program predicted that the association of circPIP5K1A with miR-1273a, as well as AP-1, IRF-4, CDX-2, and Zic-1. Subsequent studies showed that overexpression of circPIP5K1A augmented the expression of AP-1 but attenuated the expression of IRF-4, CDX-2, and Zic-1. Reciprocally, overexpression of miR-1273a abrogated the oncogenic function of circPIP5K1A in colon cancers. CONCLUSION Overall, our data demonstrate the oncogenic role of circPIP5K1A-miR-1273a axis in regulation of colon cancer development, which provides a novel insights into colon cancer pathogenesis.展开更多
AIM： To study the effects of lysophosphatidic acid （LPA） on proliferation, adhesion, migration, and apoptosis in the human colon cancer cell line, SW480, and its mechanisms of action. METHODS： Methyl tetrazolium a...AIM： To study the effects of lysophosphatidic acid （LPA） on proliferation, adhesion, migration, and apoptosis in the human colon cancer cell line, SW480, and its mechanisms of action. METHODS： Methyl tetrazolium assay was used to assess cell proliferation. Flow cytometry was employed to detect cell apoptosis. Cell migration was measured by using a Boyden transweU migration chamber. Cell adhesion assay was performed in 96-well plates according to protocol. RESULTS： LPA significantly stimulated SW480 cell proliferation in a dose-dependent and timeependent manner compared with the control group （P 〈 0.05） while the mitogen-activated protein kinase （MAPK） inhibitor, PD98059, significantly blocked the LPA stimulation effect on proliferation. LPA also significantly stimulated adhesion and migration of SW480 cells in a dosedependent manner （P 〈 0.05）. Rho kinase inhibitor, Y-27632, significantly inhibited the upegulatory effect of LPA on adhesion and migration （P 〈 0.05）. LPA significantly protected cells from apoptosis induced by the chemotherapeutic drugs, cisplatin and 5-FU （P 〈 0.05）, but the phosphoinositide 3-kinase （PI3K） inhibitor, LY294002, significantly blocked the protective effect of LPA on apoptosis. CONCLUSION： LPA stimulated proliferation, adhesion,migration of 5W480 cells, and protected from apoptosis. The Ras/Raf-MAPK, G12/13-Rho-RhoA and PI3K- AKT/PKB signal pathways may be involved.展开更多
Estrogens play important roles in the development and progression of multiple tumor types.Accumulating evidence points to the significance of estrogen action not only in tumors of hormonally regulated tissues such as ...Estrogens play important roles in the development and progression of multiple tumor types.Accumulating evidence points to the significance of estrogen action not only in tumors of hormonally regulated tissues such as the breast,endometrium and ovary,but also in the development of colorectal cancer(CRC).The effects of estrogens in physiological and pathophysiological conditions are mediated by the nuclear estrogen receptorsαandβ,as well as the membranebound G protein-coupled estrogen receptor(GPER).The roles of GPER in CRC development and progression,however,remain poorly understood.Studies on the functions of GPER in the colon have shown that this estrogen receptor regulates colonic motility as well as immune responses in CRC-associated diseases,such as Crohn’s disease and ulcerative colitis.GPER is also involved in cell cycle regulation,endoplasmic reticulum stress,proliferation,apoptosis,vascularization,cell migration,and the regulation of fatty acid and estrogen metabolism in CRC cells.Thus,multiple lines of evidence suggest that GPER may play an important role in colorectal carcinogenesis.In this review,we present the current state of knowledge regarding the contribution of GPER to colon function and CRC.展开更多
BACKGROUND Endoscopic placement of a self-expandable metal stent(SEMS)is a minimally invasive treatment for use in malignant and benign colonic obstruction.However,their widespread use is still limited with a nationwi...BACKGROUND Endoscopic placement of a self-expandable metal stent(SEMS)is a minimally invasive treatment for use in malignant and benign colonic obstruction.However,their widespread use is still limited with a nationwide analysis showing only 5.4%of patients with colon obstruction undergoing stent placement.This underutilization could be due to perceived increase risk of complications with stent placement.AIM To review long-and short-term clinical success of SEMS use for colonic obstruction at our center.METHODS We retrospectively reviewed all the patients who underwent colonic SEMS placement over aeighteen year period (August 2004 through August 2022) at our academic center. Demographicsincluding age, gender, indication (malignant and benign), technical success, clinical success,complications (perforation, stent migration), mortality, and outcomes were recorded.RESULTSSixty three patients underwent colon SEMS over an 18-year period. Fifty-five cases were formalignant indications, 8 were for benign conditions. The benign strictures included diverticulardisease stricturing (n = 4), fistula closure (n = 2), extrinsic fibroid compression (n = 1), and ischemicstricture (n = 1). Forty-three of the malignant cases were due to intrinsic obstruction from primaryor recurrent colon cancer;12 were from extrinsic compression. Fifty-four strictures occurred on theleft side, 3 occurred on the right and the rest in transverse colon. The total malignant case (n = 55)procedural success rate was 95% vs 100% for benign cases (P = 1.0, NS). Overall complication ratewas significantly higher for benign group: Four complications were observed in the malignantgroup (stent migration, restenosis) vs 2 of 8 (25%) for benign obstruction (1-perforation, 1-stentmigration) (P = 0.02). When stratifying complications of perforation and stent migration there wasno significant difference between the two groups (P = 0.14, NS).CONCLUSIONColon SEMS remains a worthwhile option for colonic obstruction related to malignancy and has ahigh procedural and clinical success rate. Benign indications for SEMS placement appear to havesimilar success to malignant. While there appears to be a higher overall complication rate inbenign cases, our study is limited by sample size. When evaluating for perforation alone theredoes not appear to be any significant difference between the two groups. SEMS placement may bea practical option for indications other that malignant obstruction. Interventional endoscopistsshould be aware and discuss the risk for complications in setting of benign conditions. Indicationsin these cases should be discussed in a multi-disciplinary fashion with colorectal surgery.展开更多
文摘The published article titled“Procaine inhibits the proliferation and migration of colon cancer cells through inactivation of the ERK/MAPK/FAK pathways by regulation of RhoA”has been retracted from Oncology Research,Vol.26,No.2,2018,pp.209–217.
基金Supported by the National Natural Science Foundation of China,No.81302131
文摘AIM To investigate the role of calmodulin-dependent protein kinase Ⅱ(Ca MKⅡ) in colon cancer growth,migration and invasion.METHODS Ca MKⅡ expression in colon cancer and paracancerous tissues was evaluated via immunochemistry. Transcriptional and posttranscriptional levels of Ca MKⅡin tissue samples and MMP2,MMP9 and TIMP-1 expression in the human colon cancer cell line HCT116 were assessed by q RTPCR and western blot. Cell proliferation was detected with the MTT assay. Cancer cell migration and invasion were investigated with the Transwell culture system and woundhealing assay.RESULTS We first demonstrated that CaMK Ⅱ was ove rexpressed in human colon cancers and was associated with cancer differentiation. In the human colon cancer cell line HCT116,the Ca MKII-specific inhibitor KN93,but not its inactive analogue KN92,decreased cancer cell proliferation. Furthermore,KN93 also significantly prohibited HCT116 cell migration and invasion. The specific inhibition of ERK1/2 or p38 decreased the proliferation and migration of colon cancer cells.CONCLUSION Our findings highlight Ca MKⅡ as a potential critical mediator in human colon tumor development and metastasis.
文摘Lymph node staging is of crucial importance for the therapy stratification and prognosis estimation in colon cancer. Beside the detection of metastases,the number of harvested lymph nodes itself has prognostic relevance in stage Ⅱ/Ⅲ cancers. A stage migration effect caused by missed lymph node metastases has been postulated as most likely explanation for that. In order to avoid false negative node staging reporting of at least 12 lymph nodes is recommended. However,this threshold is met only in a minority of cases in daily practice. Due to quality initiatives the situation has improved in the past. This,however,had no influence on staging in several studies. While the numbers of evaluated lymph nodes increased continuously during the last decades the rate of node positive cases remained relatively constant. This fact together with other indications raised doubts that understaging is indeed the correct explanation for the prognostic impact of lymph node harvest. Several authors assume that immune response could play a major role in this context influencing both the lymph node detectability and the tumor's behavior. Further studies addressing this issue are need. Based on the findings the recommendations concerning minimal lymph node numbers and adjuvant chemotherapy should be reconsidered.
基金Zhejiang Provincial Natural Science Foundation of China(No.LY20H160039)the National Natural Science Foundation of China(No.31570811)Siyuan Foundation,Hongkong,China。
文摘Verticillin A is a diketopiperazine compound which was previously isolated from Amanita flavorubescens Aik(containing parasitic fungi Hypomyces hyalines(Schw.)Tul.).Here,we initially found,by wound healing assay and Tran swell assay in vitro,that verticilli n A possesses an inhibitory effect agai nst the migrati on and in vasion of the human colon cancer cell.Subsequently,c-mesenchymal,epithelial transition factor(c-Met)was identified as a molecular target of verticillin A by screening key genes related to cell migration.Verticillin A-mediated c-Met suppress!on is at the transcriptio nal level.Further study dem on strated that verticilli n A suppressed c-MET phosphorylation and decreased c-MET protein level.In addition,verticillin A inhibited the phosphorylation of c-MET downstream molecules including rat sarcoma(Ras)-associated factor(Raf),extracellular signal-regulated kinase(ERK),and protein kinase B(AKT).Overexpression of Erk partially reversed the verticillin A-mediated anti-metastasis action in the human colon cancer cell.More importantly,verticillin A also inhibited cancer cell metastasis in vivo.Thus,verticillin A can significantly inhibit the migration and invasion of colon cancer cells by targeting c-Met and inhibiting Ras/Raf/mitogen-activated extracellular signal-regulated kinase(MEK)/ERK signaling pathways.Therefore,we determined that verticillin A is a natural compound that can be further developed as an anti-metastatic drug in human cancers.
文摘Objective This study aimed to investigate how macrophage migration inhibitory factor(MIF)regulates the interaction of signal transducer and activator of transcription 1(STAT1)with CD74,and affects colon cancer proliferation and invasion.Methods After transfecting MIF small interfering RNA into the SW480 cell line,the expression of STAT1 and CD74 mRNA was detected by qRT-PCR and western blotting.Transwell and MTT assays were performed to detect the colon cancer cell invasion and proliferation ability.Co-immunoprecipitation was used to detect the interaction between CD74 and STAT1 proteins in the treated and control groups.Results The cellular biological assays(MTT and Transwell)showed that the proliferation and invasion ability of colon cancer cells decreased after MIF knockdown;the results showed significant statistical difference(P<0.05).The results of the co-immunoprecipitation assay suggested that MIF knockdown in colon cancer cells could inhibit the binding of CD74 and STAT1 proteins;statistical difference was observed between the two groups(P<0.05).Conclusion MIF can increase the proliferation and invasion of colon cancer cells by promoting the combination of CD74 and STAT1.
基金National Natural Science Foundation of China No:21273283.
文摘Objective: To study the regulating effect of luteolin on colon cancer HT-29 cell proliferation, migration and epithelial-mesenchymal transition. Methods: Colon cancer HT-29 cells were cultured and randomly divided into two groups, control group were treated with serum-free medium without drugs and LUT group were treated with serum-free medium containing luteolin. After 24 h of treatment, cells were collected to extract RNA, and then fluorescent quantitative PCR method was used to determine the mRNA expression of proliferation genes, migration genes and epithelial-mesenchymal transition genes. Results: After 24 h of luteolin treatment, Lrig1, TSPYL5, Bim, SOX15 and DLC1 mRNA expression in LUT group were significantly higher than those in control group while RPS15a, Bad, TRPV5, TRPV6, PLD2, IBP, SphK1, FAK, Vimentin and N-cadherin mRNA expression were significantly lower than those in control group. Conclusion: Luteolin has inhibiting effect on colon cancer HT-29 cell proliferation, migration and epithelial-mesenchymal transition.
基金Supported by the National Natural Science Foundation of China,No.81703028and Hubei Cancer Hospital,No.20162017B01
文摘BACKGROUND Circular RNAs (circRNAs) are considered to be highly stable due to the closed structure, which are predominately correlated with the development and progression of a wide variety of cancers. Colon cancer is one of the most common malignancies worldwide. A recent study demonstrated the upregulated expression of circPIP5K1A in non-small cell lung cancer. However, few studies have investigated the relationship between circ_0014130 level and colon cancer. Therefore, elucidating the underlying mechanisms of circPIP5K1A’s role may help with the identification of novel diagnostic and therapeutic targets for colon cancer. AIM To investigate the status of circPIP5K1A in colon cancers and its effects on the modulation of cancer development. METHODS The expression level of circPIP5K1A in tissue and serum samples from colon cancer patients, as well as human colonic cancer cell lines was detected by realtime quantitative reverse transcription-polymerase chain reaction. Following the transfection of specifically synthesized small interfering RNA (siRNA) into colon cell lines, we used Hoechst staining assay to measure the ratio of cell death in the absence of circPIP5K1A. Moreover, we also used the Transwell assay to assess the migratory function of colon cells overexpressing circPIP5K1A. Additionally, we employed a series of bioinformatics prediction programs to predict the potential of circPIP5K1A-targeted miRNAs and mRNAs. The miR-1273a vector was constructed, and then transfected with or without circPIP5K1A vector into colon cancer cells. Afterwards, the expression of activator protein 1 (AP-1), interferon regulating factor 4 (IRF-4), caudal type homeobox 2 (CDX-2), and zinc finger of the cerebellum 1 (Zic-1) was detected by western blotting. RESULTS CircPIP5K1A was significantly upregulated in colon cancer tissue relative to their adjacent normal tissues. Knockdown of circPIP5K1A in colon cancer cells impaired cell viability and suppressed cell invasion and migration, while enforced expression of circPIP5K1A exhibited the opposite effects on cell migration. Bioinformatics prediction program predicted that the association of circPIP5K1A with miR-1273a, as well as AP-1, IRF-4, CDX-2, and Zic-1. Subsequent studies showed that overexpression of circPIP5K1A augmented the expression of AP-1 but attenuated the expression of IRF-4, CDX-2, and Zic-1. Reciprocally, overexpression of miR-1273a abrogated the oncogenic function of circPIP5K1A in colon cancers. CONCLUSION Overall, our data demonstrate the oncogenic role of circPIP5K1A-miR-1273a axis in regulation of colon cancer development, which provides a novel insights into colon cancer pathogenesis.
文摘AIM： To study the effects of lysophosphatidic acid （LPA） on proliferation, adhesion, migration, and apoptosis in the human colon cancer cell line, SW480, and its mechanisms of action. METHODS： Methyl tetrazolium assay was used to assess cell proliferation. Flow cytometry was employed to detect cell apoptosis. Cell migration was measured by using a Boyden transweU migration chamber. Cell adhesion assay was performed in 96-well plates according to protocol. RESULTS： LPA significantly stimulated SW480 cell proliferation in a dose-dependent and timeependent manner compared with the control group （P 〈 0.05） while the mitogen-activated protein kinase （MAPK） inhibitor, PD98059, significantly blocked the LPA stimulation effect on proliferation. LPA also significantly stimulated adhesion and migration of SW480 cells in a dosedependent manner （P 〈 0.05）. Rho kinase inhibitor, Y-27632, significantly inhibited the upegulatory effect of LPA on adhesion and migration （P 〈 0.05）. LPA significantly protected cells from apoptosis induced by the chemotherapeutic drugs, cisplatin and 5-FU （P 〈 0.05）, but the phosphoinositide 3-kinase （PI3K） inhibitor, LY294002, significantly blocked the protective effect of LPA on apoptosis. CONCLUSION： LPA stimulated proliferation, adhesion,migration of 5W480 cells, and protected from apoptosis. The Ras/Raf-MAPK, G12/13-Rho-RhoA and PI3K- AKT/PKB signal pathways may be involved.
基金Supported by grants from the National Science Centre,Poland(2017/24/T/NZ5/00045 and2015/17/N/NZ5/00336 to Damian Jacenik)the U.S.National Institutes of Health(NIH R01CA163890 and CA194496 to Eric R.Prossnitz+3 种基金 R01 CA207051 to Ellen J.Beswick)the UNM Comprehensive Cancer Center(P30 CA118100)the Autophagy,Inflammation and Metabolism Center of Biomedical Research Excellence(P20 GM121176)Dialysis Clinic,Inc.(to Eric R.Prossnitz)
文摘Estrogens play important roles in the development and progression of multiple tumor types.Accumulating evidence points to the significance of estrogen action not only in tumors of hormonally regulated tissues such as the breast,endometrium and ovary,but also in the development of colorectal cancer(CRC).The effects of estrogens in physiological and pathophysiological conditions are mediated by the nuclear estrogen receptorsαandβ,as well as the membranebound G protein-coupled estrogen receptor(GPER).The roles of GPER in CRC development and progression,however,remain poorly understood.Studies on the functions of GPER in the colon have shown that this estrogen receptor regulates colonic motility as well as immune responses in CRC-associated diseases,such as Crohn’s disease and ulcerative colitis.GPER is also involved in cell cycle regulation,endoplasmic reticulum stress,proliferation,apoptosis,vascularization,cell migration,and the regulation of fatty acid and estrogen metabolism in CRC cells.Thus,multiple lines of evidence suggest that GPER may play an important role in colorectal carcinogenesis.In this review,we present the current state of knowledge regarding the contribution of GPER to colon function and CRC.
文摘BACKGROUND Endoscopic placement of a self-expandable metal stent(SEMS)is a minimally invasive treatment for use in malignant and benign colonic obstruction.However,their widespread use is still limited with a nationwide analysis showing only 5.4%of patients with colon obstruction undergoing stent placement.This underutilization could be due to perceived increase risk of complications with stent placement.AIM To review long-and short-term clinical success of SEMS use for colonic obstruction at our center.METHODS We retrospectively reviewed all the patients who underwent colonic SEMS placement over aeighteen year period (August 2004 through August 2022) at our academic center. Demographicsincluding age, gender, indication (malignant and benign), technical success, clinical success,complications (perforation, stent migration), mortality, and outcomes were recorded.RESULTSSixty three patients underwent colon SEMS over an 18-year period. Fifty-five cases were formalignant indications, 8 were for benign conditions. The benign strictures included diverticulardisease stricturing (n = 4), fistula closure (n = 2), extrinsic fibroid compression (n = 1), and ischemicstricture (n = 1). Forty-three of the malignant cases were due to intrinsic obstruction from primaryor recurrent colon cancer;12 were from extrinsic compression. Fifty-four strictures occurred on theleft side, 3 occurred on the right and the rest in transverse colon. The total malignant case (n = 55)procedural success rate was 95% vs 100% for benign cases (P = 1.0, NS). Overall complication ratewas significantly higher for benign group: Four complications were observed in the malignantgroup (stent migration, restenosis) vs 2 of 8 (25%) for benign obstruction (1-perforation, 1-stentmigration) (P = 0.02). When stratifying complications of perforation and stent migration there wasno significant difference between the two groups (P = 0.14, NS).CONCLUSIONColon SEMS remains a worthwhile option for colonic obstruction related to malignancy and has ahigh procedural and clinical success rate. Benign indications for SEMS placement appear to havesimilar success to malignant. While there appears to be a higher overall complication rate inbenign cases, our study is limited by sample size. When evaluating for perforation alone theredoes not appear to be any significant difference between the two groups. SEMS placement may bea practical option for indications other that malignant obstruction. Interventional endoscopistsshould be aware and discuss the risk for complications in setting of benign conditions. Indicationsin these cases should be discussed in a multi-disciplinary fashion with colorectal surgery.
