AIM:To investigate the ezrin expression in normal colorectal mucosa and colorectal cancer tissues, and study the correlation between ezrin expression in colorectal cancer tissues and tumor invasion and metastasis.METH...AIM:To investigate the ezrin expression in normal colorectal mucosa and colorectal cancer tissues, and study the correlation between ezrin expression in colorectal cancer tissues and tumor invasion and metastasis.METHODS: Eighty paraffin-embedded cancer tissue samples were selected from primary colorectal adenocarcinoma. Twenty-eight patients had well-differentiated, 22 had moderately differentiated and 30 had poorly differentiated adenocarcinoma. Forty-five patients and 35 patients had lymph node metastasis. Forty-five patients were of Dukes A to B stage, and 35 were of C to D stage. Another 22 paraffi n-embedded tissue blocks of normal colorectal epithelium (>5 cm away from the edge of the tumor) were selected as the control group. All patients with colorectal cancer were treated surgically and diagnosed histologically, without preoperative chemotherapy or radiotherapy. The immunohistochemistry was used to detect the ezrin expression in paraffin-embedded normal colorectal mucosa tissues and colorectal cancer tissue samples.RESULTS: Ezrin expression in colorectal cancer was significantly higher than in normal colorectal mucosa (75.00% vs 9.09%, P<0.01), and there was a close relationship between ezrin expression and the degree of tumor differentiation, lymph node metastasis and Dukes stage (88.46% vs 50.00%, P<0.01; 94.28% vs 51.11%, P<0.01; 94.28% vs 51.11%, P<0.01).CONCLUSION: Ezrin expression is obviously higher in colorectal cancer tissues than in normal colorectal mucosa tissues, and the high level of ezrin expression is closely related to the colorectal cancer invasion and metastasis process.展开更多
AIM: To study the clinicopathological significance of p53 and mdm2 protein expression in human pancreatic cancer. METHODS: To investigate the expression of p53 and mdm2 in pancreatic cancer by immunohistochemistry, an...AIM: To study the clinicopathological significance of p53 and mdm2 protein expression in human pancreatic cancer. METHODS: To investigate the expression of p53 and mdm2 in pancreatic cancer by immunohistochemistry, and the relationships between the p53 and mdm2 protein expression and clinicopathological parameters in pancreatic cancer.RESULTS: The positive expression of p53 protein was found in 40 of 59 patients (67.8%) and that of mdm2 protein in 17 of 59 patients (28.8%). No obvious relationships were found between p53 as well as mdm2 expression and sex, tumor site, TNM staging and histological differentiation. p53 expression was increased in patients younger than 65 years old, while mdm2 had no relationship with age. The survival time of the patients with the positive expression of p53 and mdm2 proteins was obviously shorter than the other groups. CONCLUSION: Both p53 and mdm2 presented relatively high expression in human pancreatic cancer. The overexpression of p53 and mdm2 might reflect the malignant proliferation of pancreatic cancer and their co-expression might be helpful to evaluate the prognosis of the patients with pancreatic cancer.展开更多
Understanding the cell-of-origin of ovarian high grade serous cancer(HGSC)is the prerequisite for efficient prevention and early diagnosis of this most lethal gynecological cancer.Recently,a mesenchymal type of ovaria...Understanding the cell-of-origin of ovarian high grade serous cancer(HGSC)is the prerequisite for efficient prevention and early diagnosis of this most lethal gynecological cancer.Recently,a mesenchymal type of ovarian HGSC with the poorest prognosis among ovarian cancers was identified by both TCGA and AOCS studies.The cell-of-origin of this subtype of ovarian cancer is unknown.While pursuing studies to understand the role of the Hippo pathway in ovarian granulosa cell physiology and pathology,we unexpectedly found that the Yes-associated protein 1(YAP1),the major effector of the Hippo signaling pathway,induced dedifferentiation and reprogramming of the ovarian granulosa cells,a unique type of ovarian follicular cells with mesenchymal lineage and high plasticity,leading to the development of high grade ovarian cancer with serous features.Our research results unveil a potential cell-of-origin for a subtype of HGSC with mesenchymal features.展开更多
Pancreatic cancer is a devastating malignant disease with 5-year survival rate less than 8%.The impenetrable desmoplastic stroma of pancreatic tissue and serious side-effects of existing drugs hinder the effective tre...Pancreatic cancer is a devastating malignant disease with 5-year survival rate less than 8%.The impenetrable desmoplastic stroma of pancreatic tissue and serious side-effects of existing drugs hinder the effective treatment for pancreatic carcinoma.Thus,it is imperative to exploit much more safe and efficient methods to prolong the survival of pancreatic cancer patients.In this study,we explored a superior anti-pancreatic cancer strategy based on gadofullerene nanoparticles(GFNPs)using an orthotopic human pancreatic carcinoma(PANC-1)tumor model.It was demonstrated that GFNPs could efficiently suppress orthotopic pancreatic cancer in a dose manner,and significantly extend the survival rate of tumor-bearing mice.Of note,the proteomic profiling of tumor tissues revealed that GFNPs ameliorated the coagulation cascade dysfunction and downregulated the thrombin expression in pancreatic tumor tissues.The regulation of abnormal thrombin by GFNPs was validated in vitro and in vivo.More importantly,GFNPs suppressed orthotopic pancreatic cancer with negligible adverse effects,superior to the widely recognized clinical antipancreatic cancer drug,gemcitabine.Together,this study provides a promising therapeutic for intractable pancreatic cancer as well as a potential to alleviate the cancer-associated thromboembolic diseases.展开更多
基金Supported by Natural Science Foundation of Shanghai,No.04ZB14072
文摘AIM:To investigate the ezrin expression in normal colorectal mucosa and colorectal cancer tissues, and study the correlation between ezrin expression in colorectal cancer tissues and tumor invasion and metastasis.METHODS: Eighty paraffin-embedded cancer tissue samples were selected from primary colorectal adenocarcinoma. Twenty-eight patients had well-differentiated, 22 had moderately differentiated and 30 had poorly differentiated adenocarcinoma. Forty-five patients and 35 patients had lymph node metastasis. Forty-five patients were of Dukes A to B stage, and 35 were of C to D stage. Another 22 paraffi n-embedded tissue blocks of normal colorectal epithelium (>5 cm away from the edge of the tumor) were selected as the control group. All patients with colorectal cancer were treated surgically and diagnosed histologically, without preoperative chemotherapy or radiotherapy. The immunohistochemistry was used to detect the ezrin expression in paraffin-embedded normal colorectal mucosa tissues and colorectal cancer tissue samples.RESULTS: Ezrin expression in colorectal cancer was significantly higher than in normal colorectal mucosa (75.00% vs 9.09%, P<0.01), and there was a close relationship between ezrin expression and the degree of tumor differentiation, lymph node metastasis and Dukes stage (88.46% vs 50.00%, P<0.01; 94.28% vs 51.11%, P<0.01; 94.28% vs 51.11%, P<0.01).CONCLUSION: Ezrin expression is obviously higher in colorectal cancer tissues than in normal colorectal mucosa tissues, and the high level of ezrin expression is closely related to the colorectal cancer invasion and metastasis process.
文摘AIM: To study the clinicopathological significance of p53 and mdm2 protein expression in human pancreatic cancer. METHODS: To investigate the expression of p53 and mdm2 in pancreatic cancer by immunohistochemistry, and the relationships between the p53 and mdm2 protein expression and clinicopathological parameters in pancreatic cancer.RESULTS: The positive expression of p53 protein was found in 40 of 59 patients (67.8%) and that of mdm2 protein in 17 of 59 patients (28.8%). No obvious relationships were found between p53 as well as mdm2 expression and sex, tumor site, TNM staging and histological differentiation. p53 expression was increased in patients younger than 65 years old, while mdm2 had no relationship with age. The survival time of the patients with the positive expression of p53 and mdm2 proteins was obviously shorter than the other groups. CONCLUSION: Both p53 and mdm2 presented relatively high expression in human pancreatic cancer. The overexpression of p53 and mdm2 might reflect the malignant proliferation of pancreatic cancer and their co-expression might be helpful to evaluate the prognosis of the patients with pancreatic cancer.
基金supported by the National Cancer Institute/the National Institute of Health(1R01CA197976,1R01CA201500)Vincent Memorial Hospital Foundation+6 种基金the Vincent Center for Reproductive Biologythe Olson Center for Women’s HealthUniversity of Nebraska Medical Center Graduate Studies Fellowshipthe Fred&Pamela Buffett Cancer Center(LB595)Colleen’s Dream FoundationMarsha Rivkin Center for Ovarian Cancer Research(the Barbara Learned Bridge Funding Award)the Co BRE grant from the Nebraska Center for Cellular Signaling/the National Institute of General Medical Science/the National Institute of Health(5P30GM106397)。
文摘Understanding the cell-of-origin of ovarian high grade serous cancer(HGSC)is the prerequisite for efficient prevention and early diagnosis of this most lethal gynecological cancer.Recently,a mesenchymal type of ovarian HGSC with the poorest prognosis among ovarian cancers was identified by both TCGA and AOCS studies.The cell-of-origin of this subtype of ovarian cancer is unknown.While pursuing studies to understand the role of the Hippo pathway in ovarian granulosa cell physiology and pathology,we unexpectedly found that the Yes-associated protein 1(YAP1),the major effector of the Hippo signaling pathway,induced dedifferentiation and reprogramming of the ovarian granulosa cells,a unique type of ovarian follicular cells with mesenchymal lineage and high plasticity,leading to the development of high grade ovarian cancer with serous features.Our research results unveil a potential cell-of-origin for a subtype of HGSC with mesenchymal features.
基金supported by the National Major Scientific Instruments and Equipments Development Project(ZDYZ2015-2)the Key Research Program of the Chinese Academy of Sciences(QYZDJSSW-SLH025)the National Natural Science Foundation of China(51902313)。
文摘Pancreatic cancer is a devastating malignant disease with 5-year survival rate less than 8%.The impenetrable desmoplastic stroma of pancreatic tissue and serious side-effects of existing drugs hinder the effective treatment for pancreatic carcinoma.Thus,it is imperative to exploit much more safe and efficient methods to prolong the survival of pancreatic cancer patients.In this study,we explored a superior anti-pancreatic cancer strategy based on gadofullerene nanoparticles(GFNPs)using an orthotopic human pancreatic carcinoma(PANC-1)tumor model.It was demonstrated that GFNPs could efficiently suppress orthotopic pancreatic cancer in a dose manner,and significantly extend the survival rate of tumor-bearing mice.Of note,the proteomic profiling of tumor tissues revealed that GFNPs ameliorated the coagulation cascade dysfunction and downregulated the thrombin expression in pancreatic tumor tissues.The regulation of abnormal thrombin by GFNPs was validated in vitro and in vivo.More importantly,GFNPs suppressed orthotopic pancreatic cancer with negligible adverse effects,superior to the widely recognized clinical antipancreatic cancer drug,gemcitabine.Together,this study provides a promising therapeutic for intractable pancreatic cancer as well as a potential to alleviate the cancer-associated thromboembolic diseases.
