Objective： As an important regulator of embryonic morphogenesis, homeodomain-containing gene 10 （HOXC10） has been found to promote progression of human cancers and its expression indicates poor survival outcome. Ho...Objective： As an important regulator of embryonic morphogenesis, homeodomain-containing gene 10 （HOXC10） has been found to promote progression of human cancers and its expression indicates poor survival outcome. However, very few studies are available on the role of HOXC10 in gastric carcinoma. Therefore, the aim of this study was to determine the role of HOXC10 in gastric cancer and the potential mechanism underlying its function for cancer biology. Methods： A primary gastric cancer mouse model was obtained via intra-gastric wall injection of gastric cancer cells and was used to evaluate the function of HOXC10 during gastric cancer progression in vivo. Immunohistochemistry was performed to visualize and measure HOXC10 protein expression in gastric cancer tissue. Cells were transfected with plasmids to increase the expression of HOXCIO, and siRNA transfection was performed to suppress HOXC10 expression. Reverse transcription polymerase chain reaction （RT-PCR） and western blotting were utilized to measure mRNA and protein expression, respectively. Proliferation, migration, and invasion were investigated using 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay, wound healing assay, and matrigel invasion assay in vitro, respectively. Results： HOXC10 expression was significantly increased in gastric cancer tissues compared to matched normal tissues. HOXC10 up-regulation significantly increased tumor volumes in nude mice. Plasmid transfection significantly increased HOXC10 protein and mRNA expressions and effectively promoted cell proliferation. Moreover, HOXC10 up-regulation significantly promoted migration and invasion of gastric cancer cells. Mechanistic investigation showed that HOXC10 up-regulation significantly increased mRNA and protein expression of mitogen-activated protein kinase （MAPK） signaling related genes, including c-myc, c-jun and p53, while also modulating the phosphorylation of c-Jun N-terminal kinase （JNK）, extracellular signal-regulated kinase （ERK） and P38 but not their total protein levels. Conclusions： This study demonstrated the tight link between HOXC10 and gastric cancer cell proliferation and metastasis via involvement of the MAPK pathway.展开更多
Gastrointestinal(GI) cancer is one of the most common causes of cancer-related deaths worldwide.Tumor markers are valuable in detecting post-surgical recurrence or in monitoring response to chemotherapy.Pyruvate kinas...Gastrointestinal(GI) cancer is one of the most common causes of cancer-related deaths worldwide.Tumor markers are valuable in detecting post-surgical recurrence or in monitoring response to chemotherapy.Pyruvate kinase isoform M2(PKM2),a glycolytic enzyme catalyzing conversion of phosphoenolpyruvate(PEP) to pyruvate,confers a growth advantage to the tumor cells and enables them to adapt to the tumor microenvironment.In this review,we have summarized current research on the expression and regulation of PKM2 in tumor cells,and its potential role in GI carcinogenesis and progression.Furthermore,we have also discussed the potential of PKM2 as a diagnostic and screening marker,and a therapeutic target in GI cancer.展开更多
Accumulating evidence suggests that periostin is frequently upregulated in tissue injury, inflammation,fibrosis and tumor progression. Periostin expression in cancer cells can promote metastatic potential of colorecta...Accumulating evidence suggests that periostin is frequently upregulated in tissue injury, inflammation,fibrosis and tumor progression. Periostin expression in cancer cells can promote metastatic potential of colorectal cancer(CRC)via activating PI3 K/Akt signaling pathway. Moreover, periostin is observed mainly in tumor stroma and cytoplasm of cancer cells, which may facilitate aggressiveness of CRC. In this review, we summarize information regarding periostin to emphasize its role as a prognostic marker of CRC.展开更多
Gastric cancer,with high morbidity and mortality rates,is one of the most heterogeneous tumors.Radical gastrectomy and postoperative chemotherapy are the standard treatments.However,the safety and efficacy of neoadjuv...Gastric cancer,with high morbidity and mortality rates,is one of the most heterogeneous tumors.Radical gastrectomy and postoperative chemotherapy are the standard treatments.However,the safety and efficacy of neoadjuvant therapy(NAT)need to be confirmed by many trials before implementation,creating a bottleneck in development.Although clinical benefits of NAT have been observed,a series of problems remain to be solved.Before therapy,more contributing factors should be offered for choice in the intended population and ideal regimens.Enhanced computed tomography(CT)scanning is usually applied to evaluate effectiveness according to Response Evaluation Criteria in Solid Tumors(RECIST),yet CT scanning results sometimes differ from pathological responses.After NAT,the appropriate time for surgery is still empirically defined.Our review aims to discuss the abovementioned issues regarding NAT for GC,including indications,selection of regimens,lesion assessment and NAT-surgery interval time.展开更多
Objective:To reveal the distribution signature of cancer susceptibility genes in patients with gastric adenocarcinoma,offering a diagnostic and prognostic surrogate for disease risk management and therapeutic decision...Objective:To reveal the distribution signature of cancer susceptibility genes in patients with gastric adenocarcinoma,offering a diagnostic and prognostic surrogate for disease risk management and therapeutic decisions.Methods:A total of 282 patients with gastric adenocarcinoma(182 males and 100 females)were enrolled in this study,with peripheral blood genomic DNA extracted.Mutations of 69 canonical cancer susceptibility genes or presumably tumor-related genes were analyzed by targeted capture-based high-throughput sequencing.Candidate mutations were particularly selected for discussion on tumor pathogenesis according to the American College of Medical Genetics and Genomics(ACMG)guidelines.Results:In this study,7.1%(20/282)of patients with gastric adenocarcinoma were found to harbor mutations of canonical or presumable cancer susceptibility genes.The detection rate in male patients(3.8%,7/182)was significantly lower than that in female patients(13%,13/100)(P=0.004).The most recurrent mutations were in AT mutated(ATM)(1.1%,3/282),followed by BRCA1,BRIP1 and RAD51D,all showed a detection rate of 0.7%(2/282).Mutations in three genes associated with hereditary gastric cancer syndromes were detected,namely,PMS2 and EP CAM associated with Lynch syndrome and CDH1 associated with hereditary di ffuse gastric cancer.The detection frequencies were all 0.4%(1/282).Notwithstanding no significant difference observed,the age of patients with pathogenic mutations or likely pathogenic mutations is slightly younger than that of non-carriers(median age:58.5 vs.60.5 years old),while the age of patients with ATM mutations was the youngest overall(median age:49.3 years old).Conclusions:Our study shed more light on the distribution signature and pathogenesis of mutations in gastric cancer susceptibility genes,and found the detection rate of pathogenic and likely pathogenic mutations in male patients was significandy lower than that in female patients.Some known and unidentified mutations were found in gastric cancer,which allowed us to gain more insight into the hereditary gastric cancer syndromes from the molecular perspective.展开更多
基金supported by the grants from‘San Ming’Project of Shenzhen city,ChinaMunicipal Health planning Commission Fund of Shenzhen city,China(No.201601004 and No.201704260051)
文摘Objective： As an important regulator of embryonic morphogenesis, homeodomain-containing gene 10 （HOXC10） has been found to promote progression of human cancers and its expression indicates poor survival outcome. However, very few studies are available on the role of HOXC10 in gastric carcinoma. Therefore, the aim of this study was to determine the role of HOXC10 in gastric cancer and the potential mechanism underlying its function for cancer biology. Methods： A primary gastric cancer mouse model was obtained via intra-gastric wall injection of gastric cancer cells and was used to evaluate the function of HOXC10 during gastric cancer progression in vivo. Immunohistochemistry was performed to visualize and measure HOXC10 protein expression in gastric cancer tissue. Cells were transfected with plasmids to increase the expression of HOXCIO, and siRNA transfection was performed to suppress HOXC10 expression. Reverse transcription polymerase chain reaction （RT-PCR） and western blotting were utilized to measure mRNA and protein expression, respectively. Proliferation, migration, and invasion were investigated using 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay, wound healing assay, and matrigel invasion assay in vitro, respectively. Results： HOXC10 expression was significantly increased in gastric cancer tissues compared to matched normal tissues. HOXC10 up-regulation significantly increased tumor volumes in nude mice. Plasmid transfection significantly increased HOXC10 protein and mRNA expressions and effectively promoted cell proliferation. Moreover, HOXC10 up-regulation significantly promoted migration and invasion of gastric cancer cells. Mechanistic investigation showed that HOXC10 up-regulation significantly increased mRNA and protein expression of mitogen-activated protein kinase （MAPK） signaling related genes, including c-myc, c-jun and p53, while also modulating the phosphorylation of c-Jun N-terminal kinase （JNK）, extracellular signal-regulated kinase （ERK） and P38 but not their total protein levels. Conclusions： This study demonstrated the tight link between HOXC10 and gastric cancer cell proliferation and metastasis via involvement of the MAPK pathway.
基金supported by the grants from ‘San Ming’ Project of Shenzhen city,China(No.SZSM201612051)Municipal Health Planning Commission Fund of Shenzhen city,China(No.201601004,No.SZXJ2017078 and No.SXZJ2018084)
文摘Gastrointestinal(GI) cancer is one of the most common causes of cancer-related deaths worldwide.Tumor markers are valuable in detecting post-surgical recurrence or in monitoring response to chemotherapy.Pyruvate kinase isoform M2(PKM2),a glycolytic enzyme catalyzing conversion of phosphoenolpyruvate(PEP) to pyruvate,confers a growth advantage to the tumor cells and enables them to adapt to the tumor microenvironment.In this review,we have summarized current research on the expression and regulation of PKM2 in tumor cells,and its potential role in GI carcinogenesis and progression.Furthermore,we have also discussed the potential of PKM2 as a diagnostic and screening marker,and a therapeutic target in GI cancer.
基金supported by grants from “San Ming” Project of Shenzhen city, China (No. SZSM201612051)Municipal Health Planning Commission Fund of Shenzhen city, China (No. 201601004, No. SZXJ2017078 and No. SXZJ2018084)
文摘Accumulating evidence suggests that periostin is frequently upregulated in tissue injury, inflammation,fibrosis and tumor progression. Periostin expression in cancer cells can promote metastatic potential of colorectal cancer(CRC)via activating PI3 K/Akt signaling pathway. Moreover, periostin is observed mainly in tumor stroma and cytoplasm of cancer cells, which may facilitate aggressiveness of CRC. In this review, we summarize information regarding periostin to emphasize its role as a prognostic marker of CRC.
基金supported by Shenzhen Sanming Project(No.SZSM201612051)。
文摘Gastric cancer,with high morbidity and mortality rates,is one of the most heterogeneous tumors.Radical gastrectomy and postoperative chemotherapy are the standard treatments.However,the safety and efficacy of neoadjuvant therapy(NAT)need to be confirmed by many trials before implementation,creating a bottleneck in development.Although clinical benefits of NAT have been observed,a series of problems remain to be solved.Before therapy,more contributing factors should be offered for choice in the intended population and ideal regimens.Enhanced computed tomography(CT)scanning is usually applied to evaluate effectiveness according to Response Evaluation Criteria in Solid Tumors(RECIST),yet CT scanning results sometimes differ from pathological responses.After NAT,the appropriate time for surgery is still empirically defined.Our review aims to discuss the abovementioned issues regarding NAT for GC,including indications,selection of regimens,lesion assessment and NAT-surgery interval time.
基金This study was supported by Shenzhen Sanming Project(No.SZSM201612051)Shenzhen Science and Technology Innovation Commission Project(No.ZDSYS 20190902092855097,No.GJHZ20180420180754917).
文摘Objective:To reveal the distribution signature of cancer susceptibility genes in patients with gastric adenocarcinoma,offering a diagnostic and prognostic surrogate for disease risk management and therapeutic decisions.Methods:A total of 282 patients with gastric adenocarcinoma(182 males and 100 females)were enrolled in this study,with peripheral blood genomic DNA extracted.Mutations of 69 canonical cancer susceptibility genes or presumably tumor-related genes were analyzed by targeted capture-based high-throughput sequencing.Candidate mutations were particularly selected for discussion on tumor pathogenesis according to the American College of Medical Genetics and Genomics(ACMG)guidelines.Results:In this study,7.1%(20/282)of patients with gastric adenocarcinoma were found to harbor mutations of canonical or presumable cancer susceptibility genes.The detection rate in male patients(3.8%,7/182)was significantly lower than that in female patients(13%,13/100)(P=0.004).The most recurrent mutations were in AT mutated(ATM)(1.1%,3/282),followed by BRCA1,BRIP1 and RAD51D,all showed a detection rate of 0.7%(2/282).Mutations in three genes associated with hereditary gastric cancer syndromes were detected,namely,PMS2 and EP CAM associated with Lynch syndrome and CDH1 associated with hereditary di ffuse gastric cancer.The detection frequencies were all 0.4%(1/282).Notwithstanding no significant difference observed,the age of patients with pathogenic mutations or likely pathogenic mutations is slightly younger than that of non-carriers(median age:58.5 vs.60.5 years old),while the age of patients with ATM mutations was the youngest overall(median age:49.3 years old).Conclusions:Our study shed more light on the distribution signature and pathogenesis of mutations in gastric cancer susceptibility genes,and found the detection rate of pathogenic and likely pathogenic mutations in male patients was significandy lower than that in female patients.Some known and unidentified mutations were found in gastric cancer,which allowed us to gain more insight into the hereditary gastric cancer syndromes from the molecular perspective.
