AIM: To evaluate the significance of transforming growth factor beta (TGF β) expression, in correlation with histopathological parameters, at the front of invasion in T1 colorectal cancer (CRC) and presence of metast...AIM: To evaluate the significance of transforming growth factor beta (TGF β) expression, in correlation with histopathological parameters, at the front of invasion in T1 colorectal cancer (CRC) and presence of metastases. METHODS: TGF p immunohistochemical expression was studied in 34 specimens of colorectal adenocarcinomas (pT1). A three-step avidin-biotinylated immuno-peroxidase (ABCu-NCL) staining technique was performed on 4-μm paraffin-embedded tissue sections with a monoclonal antibody to TGF β (Novocastra, NCL-TGFB, clone TGFB 17, dilution 1:40). RESULTS: Seventeen (50%) out of 34 lesions were positive for TGF p expression. The TGF β-positive rate in patients with vascular invasion was significantly higher than in those without vascular invasion (11/14 cases, P<0.01, P= 0.005). The TGF p-positive rate was observed in 91.7% of patients with presence of tumor budding at the front of invasion (11/12 cases, P<0.01, P= 0.0003). A statistically significant correlation was found between the presence of lymph node metastases and positive expression of TGF β (14/16 cases, P<0.01, P= 0.0001). We also observed that the TGF β-positive rates in groups with distant and non-distant metastases were 92.8% and 20% respectively, and a significant correlation between TGF β expression and distant metastasis was shown (P<0.01, P= 0.00003). CONCLUSION: The evaluation of TGF β expression of protein in association with histological parameters can be used as a parameter of the aggressiveness of pT1 CRC.展开更多
Epithelial-to-mesenchymal transition(EMT) is defined as the transformation of an epithelial cell into a spindle cell with the loss of membrane E-cadherin expression and the gain of mesenchymal markers positivity. In t...Epithelial-to-mesenchymal transition(EMT) is defined as the transformation of an epithelial cell into a spindle cell with the loss of membrane E-cadherin expression and the gain of mesenchymal markers positivity. In the field of colorectal cancer(CRC), first data about EMT was published in 1995 and more than 400 papers had been written up to March 2016. Most of them are focused on the molecular pathways and experimentally-proved chemoresistance. In the present article, an update in the field of EMT in CRC based on the review of the literature and personal experience of the authors is presented. The information about the molecular and immunohistochemical(IHC) particularities of these processes and their possible role in the prognosis of CRC were also up-dated. This article focuses on the IHC quantification of the EMT, the immunoprofile of tumor buds and on the relation between EMT, angiogenesis, and stem cells activation. The EMT-induced chemoresistance vs chemotherapyor radiotherapy-induced EMT and cellular senescence was also synthesized for both conventional and targeted therapy. As a future perspective, the EMTangiogenesis-stemness link could be used as a possible valuable parameter for clinical follow-up and targeted therapeutic oncologic management of patients with CRC. Association of dexamethasone and angiotensin converting enzyme inhibitors combined with conventional chemotherapies could have clinical benefits in patients with CRC. The main conclusion is that, although many studies have been published, the EMT features are still incompletely elucidated and newly discovered EMT markers provide confusing data in understanding this complicated process, which might have significant clinical impact.展开更多
Objective： To investigate the frequency of parasympathetic neurogenesis and determine its association with tumor budding and prognosis in pancreatic ductal adenocarcinoma （PDAC）. Methods： Parasympathetic neurogene...Objective： To investigate the frequency of parasympathetic neurogenesis and determine its association with tumor budding and prognosis in pancreatic ductal adenocarcinoma （PDAC）. Methods： Parasympathetic neurogenesis was defined as the distribution of abnormal parasympathetic nerves in the stroma tissue. Staining of vesicular acetylcholine transporter （VAChT）, as a marker for parasympathetic neurogenesis, was performed on a representative specimen of the tumor for 59 PDAC patients with available clinical, pathologic, and follow-up information. Three specimens containing normal pancreatic tissues were stained in parallel. The number of parasympathetic nerve fibers was counted in five high-power microscopic fields （5×0.785 mm2）. Cut-offvalues were calculated by receiver operating characteristic curve analysis. Results： VAChT-positive parasympathetic nerve fibers were not seen in the stroma of 3 cases of normal pancreatic tissues. In 59 PDAC cases, the range of parasympathetic neurogenesis was 4-38 fibers/（5×0.785） mm2, with a median of 18 fibers/（5×0.785） mm2. Patients with parasympathetic neurogenesis 〉 15 fibers/（5×0.785） mm2 were defined as the high-density group （39 patients, 66.1%）, and those with parasympathetic neurogenesis 〈15 fibers/（5×0.785） mm2 as the low-density group （20 patients, 33.9%）. The high-density group had a higher occurrence of tumor budding （P=0.001） and a higher rate of early recurrence （P=0.035）. Parasympathetic neurogenesis appeared to be an independent adverse prognostic factor [hazard ratio （HR）=2.45, 95% confidence interval （95% CI）： 1.25-4.81, P=0.009], in addition to American Joint Committee on Cancer （AJCC） stage （P=0.010） and tumor budding （P=0.009）. Conclusions： Parasympathetic neurogenesis is strongly associated with tumor budding and correlates with an adverse prognosis in PDAC.展开更多
The drought resistances of 44 maize germplasms at budding stage were studied with 19.2% polyethylene glycol(PEG-6000)in order to provide new germplasm resource for drought resistance breeding of maize.The results show...The drought resistances of 44 maize germplasms at budding stage were studied with 19.2% polyethylene glycol(PEG-6000)in order to provide new germplasm resource for drought resistance breeding of maize.The results showed there were five extremely high drought resistance germplasms,20 germplasms with high drought resistance,and 19 germplasms with medium drought resistance.The significance testing was also used to demonstrate that the germination index(GI)and germination of drought resistance index(GDRI)of N4,N54-1 and Wuming No.1 were dramatically remarkable than others.The conclusion was that the 44 maize germplasm had good drought resistance and could be used as germplasm resource of the drought resistance breeding of maize,which had a great value of development and utilization.展开更多
Colorectal cancer （CRC）, the third most commonly di- agnosed type of cancer in men and women worldwide is recognized as a complex multi-pathway disease, an observation sustained by the fact that histologically ident...Colorectal cancer （CRC）, the third most commonly di- agnosed type of cancer in men and women worldwide is recognized as a complex multi-pathway disease, an observation sustained by the fact that histologically identical tumors may have different outcome, including various response to therapy. Therefore, particularly in early and intermediate stage （stages Ⅱ and Ⅲ, respec- tively） CRC, there is a compelling need for biomarkers helpful of selecting patients with aggressive disease that might benefit from adjuvant and targeted therapy. Histopathological examination shows that likely other solid tumors the development and progression of hu- man CRC is not only determined by genetically abnor- mal cells, but also by intricate interactions between malignant cells and the surrounding microenvironment. This has led to reconsider the features of tumor mi- croenvironment as potential predictive and prognostic biomarkers. Among the histopathological biomarkers, tumor budding （i.e., the presence of individual cells and small clusters of tumor cells at the tumor invasive front）has received much recent attention, particularly in the setting of CRC. Although its acceptance as a reportable factor has been held back by a lack of uniformity with respect to qualitative and quantitative aspects, tumor budding is now considered as an independent adverse prognostic factor in CRC that may allow for stratifica- tion of patients into risk categories more meaningful than those defined by tumor-node-metastasis staging alone, and also potentially guide treatment decisions, especially in T2-T3 NO （stage Ⅱ） CRCs.展开更多
Tumor-host interaction at the invasive front of colorectal cancer represents a critical interface encompassing a dynamic process of de-differentiation of colorectal carci-noma cells known as epithelial mesenchymal tra...Tumor-host interaction at the invasive front of colorectal cancer represents a critical interface encompassing a dynamic process of de-differentiation of colorectal carci-noma cells known as epithelial mesenchymal transition (EMT). EMT can be identified histologically by the presence of "tumor budding" ,a feature which can be highly specific for tumors showing an inf iltrating tumor growth pattern. Importantly,tumor budding and tumor border configuration have generated considerable interest as additional prognostic factors and are also recognized as such by the International Union Against Cancer. Evidence seems to suggest that the presence of tumor budding or an infiltrating growth pattern is inversely correlated with the presence of immune and inflammatory responses at the invasive tumor front. In fact,several tumor-associated antigens such as CD3,CD4,CD8,CD20,Granzyme B,FOXP3 and other immunological or inflammatory cell types have been identified as poten-tially prognostic in patients with this disease. Evidence seems to suggest that the balance between protumor (including budding and inf iltrating growth pattern) and anti-tumor (immune response or certain inflammatory cell types) factors at the invasive front of colorectal cancer may be decisive in determining tumor progression and the clinical outcome of patients with colorectal cancer. On one hand,the inf iltrating tumor border configuration and tumor budding promote progression and dissemination of tumor cells by penetrating the vascular and lymphatic vessels. On the other,the host attempts to fend off this attack by mounting an immune response to protect vascular and lymphatic channels from invasion by tumor buds. Whereas standard pathology reporting of breast and prostate cancer involves additional prognostic features,such as the BRE and Gleason scores,the ratio of pro-and anti-tumor factors could be a promising approach for the future development of a prognostic score for patients with colorectal cancer which could complement tumor node metastasis stagin展开更多
文摘AIM: To evaluate the significance of transforming growth factor beta (TGF β) expression, in correlation with histopathological parameters, at the front of invasion in T1 colorectal cancer (CRC) and presence of metastases. METHODS: TGF p immunohistochemical expression was studied in 34 specimens of colorectal adenocarcinomas (pT1). A three-step avidin-biotinylated immuno-peroxidase (ABCu-NCL) staining technique was performed on 4-μm paraffin-embedded tissue sections with a monoclonal antibody to TGF β (Novocastra, NCL-TGFB, clone TGFB 17, dilution 1:40). RESULTS: Seventeen (50%) out of 34 lesions were positive for TGF p expression. The TGF β-positive rate in patients with vascular invasion was significantly higher than in those without vascular invasion (11/14 cases, P<0.01, P= 0.005). The TGF p-positive rate was observed in 91.7% of patients with presence of tumor budding at the front of invasion (11/12 cases, P<0.01, P= 0.0003). A statistically significant correlation was found between the presence of lymph node metastases and positive expression of TGF β (14/16 cases, P<0.01, P= 0.0001). We also observed that the TGF β-positive rates in groups with distant and non-distant metastases were 92.8% and 20% respectively, and a significant correlation between TGF β expression and distant metastasis was shown (P<0.01, P= 0.00003). CONCLUSION: The evaluation of TGF β expression of protein in association with histological parameters can be used as a parameter of the aggressiveness of pT1 CRC.
基金Supported by University of Medicine and Pharmacy of TirguMures,Romania,Team Research Projects Frame:UMFTGMPO-CC-02-F01,No.19/2014
文摘Epithelial-to-mesenchymal transition(EMT) is defined as the transformation of an epithelial cell into a spindle cell with the loss of membrane E-cadherin expression and the gain of mesenchymal markers positivity. In the field of colorectal cancer(CRC), first data about EMT was published in 1995 and more than 400 papers had been written up to March 2016. Most of them are focused on the molecular pathways and experimentally-proved chemoresistance. In the present article, an update in the field of EMT in CRC based on the review of the literature and personal experience of the authors is presented. The information about the molecular and immunohistochemical(IHC) particularities of these processes and their possible role in the prognosis of CRC were also up-dated. This article focuses on the IHC quantification of the EMT, the immunoprofile of tumor buds and on the relation between EMT, angiogenesis, and stem cells activation. The EMT-induced chemoresistance vs chemotherapyor radiotherapy-induced EMT and cellular senescence was also synthesized for both conventional and targeted therapy. As a future perspective, the EMTangiogenesis-stemness link could be used as a possible valuable parameter for clinical follow-up and targeted therapeutic oncologic management of patients with CRC. Association of dexamethasone and angiotensin converting enzyme inhibitors combined with conventional chemotherapies could have clinical benefits in patients with CRC. The main conclusion is that, although many studies have been published, the EMT features are still incompletely elucidated and newly discovered EMT markers provide confusing data in understanding this complicated process, which might have significant clinical impact.
基金supported by grants from China Cancer Research Foundation Y-N2013-008the Doctoral Program of the Ministry of Education 20130001110089 to DR Xiu+1 种基金the National Natural Science Foundation of China 81272709 to W FuPeking University Third Hospital Grant Y81524-01 to LF Zhang
文摘Objective： To investigate the frequency of parasympathetic neurogenesis and determine its association with tumor budding and prognosis in pancreatic ductal adenocarcinoma （PDAC）. Methods： Parasympathetic neurogenesis was defined as the distribution of abnormal parasympathetic nerves in the stroma tissue. Staining of vesicular acetylcholine transporter （VAChT）, as a marker for parasympathetic neurogenesis, was performed on a representative specimen of the tumor for 59 PDAC patients with available clinical, pathologic, and follow-up information. Three specimens containing normal pancreatic tissues were stained in parallel. The number of parasympathetic nerve fibers was counted in five high-power microscopic fields （5×0.785 mm2）. Cut-offvalues were calculated by receiver operating characteristic curve analysis. Results： VAChT-positive parasympathetic nerve fibers were not seen in the stroma of 3 cases of normal pancreatic tissues. In 59 PDAC cases, the range of parasympathetic neurogenesis was 4-38 fibers/（5×0.785） mm2, with a median of 18 fibers/（5×0.785） mm2. Patients with parasympathetic neurogenesis 〉 15 fibers/（5×0.785） mm2 were defined as the high-density group （39 patients, 66.1%）, and those with parasympathetic neurogenesis 〈15 fibers/（5×0.785） mm2 as the low-density group （20 patients, 33.9%）. The high-density group had a higher occurrence of tumor budding （P=0.001） and a higher rate of early recurrence （P=0.035）. Parasympathetic neurogenesis appeared to be an independent adverse prognostic factor [hazard ratio （HR）=2.45, 95% confidence interval （95% CI）： 1.25-4.81, P=0.009], in addition to American Joint Committee on Cancer （AJCC） stage （P=0.010） and tumor budding （P=0.009）. Conclusions： Parasympathetic neurogenesis is strongly associated with tumor budding and correlates with an adverse prognosis in PDAC.
基金Supported by the Subproject of National Science Foundation Platform Project(2005DKA21000-5-49)~~
文摘The drought resistances of 44 maize germplasms at budding stage were studied with 19.2% polyethylene glycol(PEG-6000)in order to provide new germplasm resource for drought resistance breeding of maize.The results showed there were five extremely high drought resistance germplasms,20 germplasms with high drought resistance,and 19 germplasms with medium drought resistance.The significance testing was also used to demonstrate that the germination index(GI)and germination of drought resistance index(GDRI)of N4,N54-1 and Wuming No.1 were dramatically remarkable than others.The conclusion was that the 44 maize germplasm had good drought resistance and could be used as germplasm resource of the drought resistance breeding of maize,which had a great value of development and utilization.
基金Supported by Ministero dell'Istruzione,dell'Università e della Ricerca,Target Project Oncologia 2006Alleanza Contro il Cancrothe Italian Association for Cancer Research,grant project No.IG5256
文摘Colorectal cancer （CRC）, the third most commonly di- agnosed type of cancer in men and women worldwide is recognized as a complex multi-pathway disease, an observation sustained by the fact that histologically identical tumors may have different outcome, including various response to therapy. Therefore, particularly in early and intermediate stage （stages Ⅱ and Ⅲ, respec- tively） CRC, there is a compelling need for biomarkers helpful of selecting patients with aggressive disease that might benefit from adjuvant and targeted therapy. Histopathological examination shows that likely other solid tumors the development and progression of hu- man CRC is not only determined by genetically abnor- mal cells, but also by intricate interactions between malignant cells and the surrounding microenvironment. This has led to reconsider the features of tumor mi- croenvironment as potential predictive and prognostic biomarkers. Among the histopathological biomarkers, tumor budding （i.e., the presence of individual cells and small clusters of tumor cells at the tumor invasive front）has received much recent attention, particularly in the setting of CRC. Although its acceptance as a reportable factor has been held back by a lack of uniformity with respect to qualitative and quantitative aspects, tumor budding is now considered as an independent adverse prognostic factor in CRC that may allow for stratifica- tion of patients into risk categories more meaningful than those defined by tumor-node-metastasis staging alone, and also potentially guide treatment decisions, especially in T2-T3 NO （stage Ⅱ） CRCs.
文摘Tumor-host interaction at the invasive front of colorectal cancer represents a critical interface encompassing a dynamic process of de-differentiation of colorectal carci-noma cells known as epithelial mesenchymal transition (EMT). EMT can be identified histologically by the presence of "tumor budding" ,a feature which can be highly specific for tumors showing an inf iltrating tumor growth pattern. Importantly,tumor budding and tumor border configuration have generated considerable interest as additional prognostic factors and are also recognized as such by the International Union Against Cancer. Evidence seems to suggest that the presence of tumor budding or an infiltrating growth pattern is inversely correlated with the presence of immune and inflammatory responses at the invasive tumor front. In fact,several tumor-associated antigens such as CD3,CD4,CD8,CD20,Granzyme B,FOXP3 and other immunological or inflammatory cell types have been identified as poten-tially prognostic in patients with this disease. Evidence seems to suggest that the balance between protumor (including budding and inf iltrating growth pattern) and anti-tumor (immune response or certain inflammatory cell types) factors at the invasive front of colorectal cancer may be decisive in determining tumor progression and the clinical outcome of patients with colorectal cancer. On one hand,the inf iltrating tumor border configuration and tumor budding promote progression and dissemination of tumor cells by penetrating the vascular and lymphatic vessels. On the other,the host attempts to fend off this attack by mounting an immune response to protect vascular and lymphatic channels from invasion by tumor buds. Whereas standard pathology reporting of breast and prostate cancer involves additional prognostic features,such as the BRE and Gleason scores,the ratio of pro-and anti-tumor factors could be a promising approach for the future development of a prognostic score for patients with colorectal cancer which could complement tumor node metastasis stagin
