Gastrointestinal(GI)cancers,including malignancies in the gastrointestinal tract and accessory organs of digestion,represent the leading cause of death worldwide due to the poor prognosis of most GI cancers.An investi...Gastrointestinal(GI)cancers,including malignancies in the gastrointestinal tract and accessory organs of digestion,represent the leading cause of death worldwide due to the poor prognosis of most GI cancers.An investigation into the potential molecular targets of prediction,diagnosis,prognosis,and therapy in GI cancers is urgently required.Proliferating cell nuclear antigen(PCNA)clamp associated factor(PCLAF),which plays an essential role in cell proliferation,apoptosis,and cell cycle regulation by binding to PCNA,is a potential molecular target of GI cancers as it contributes to a series of malignant properties,including tumorigenesis,epithelial-mesenchymal transition,migration,and invasion.Furthermore,PCLAF is an underlying plasma prediction target in colorectal cancer and liver cancer.In addition to GI cancers,PCLAF is also involved in other types of cancers and autoimmune diseases.Several pivotal pathways,including the Rb/E2F pathway,NF-κB pathway,and p53-p21 cascade,are implicated in PCLAF-mediated diseases.PCLAF also contributes to some diseases through dysregulation of the p53 pathway,WNT signal pathway,MEK/ERK pathway,and PI3K/AKT/mTOR signal cascade.This review mainly describes in detail the role of PCLAF in physiological status and GI cancers.The signaling pathways involved in PCLAF are also summarized.Suppression of the interaction of PCLAF/PCNA or the expression of PCLAF might be potential biological therapeutic strategies for GI cancers.展开更多
Objective To study the effects of P53, PCNA, Bc1-2 protein and their relationship in salivary adenoid cystic carclnoma(SACC). Methods These protelns were examlned by lmmunohistochemistry. Results overexpressions of Ps...Objective To study the effects of P53, PCNA, Bc1-2 protein and their relationship in salivary adenoid cystic carclnoma(SACC). Methods These protelns were examlned by lmmunohistochemistry. Results overexpressions of Ps, and PCNA were revealed in ACC samples, they were higher than those in (polymorphous adenomas) PA, but expression of Bc1-2 protein was not different between ACC and PA. In 3 subtypes of ACC, expressions of 3 proteins were different. Conciusion Mutations of P53, Bc1-2 may be involed in the occurrence of SACC, expression of PCNA and mutation of P53 may coexist in the development of the SACC.展开更多
AIM To explore the anti-tumor effects of esophageal cancerrelated gene 2(ECRG2) in combination with cisplatin(DDP) in DDP-resistant esophageal cancer cells(EC9706/DDP).METHODS A drug-resistant cell model was establish...AIM To explore the anti-tumor effects of esophageal cancerrelated gene 2(ECRG2) in combination with cisplatin(DDP) in DDP-resistant esophageal cancer cells(EC9706/DDP).METHODS A drug-resistant cell model was established, with EC9706/DDP cells being treated with ECRG2 and/or DDP. Cell viability was examined by MTT assay. The rate of cell apoptosis was determined by flow cytometry. The mR NA expression levels of proliferating cell nuclear antigen(PCNA), metallothionein(MT), and p53 were determined by RT-PCR and PCNA, while MT and p53 protein expression levels were determined by western blotting.RESULTS The anti-proliferative effect of ECRG2 in combination with DDP was superior when compared to ECRG2 or DDP alone. The inhibition rate for the combination reached its peak(51.33%) at 96 h. The early apoptotic rates of the control, ECRG2 alone, DDP alone, and ECRG2 plus DDP groups were 5.71% ± 0.27%, 12.68% ± 0.61%, 14.15% ± 0.87%, and 27.96% ±0.36%, respectively. Although all treatment groups were significantly different from the control group(P < 0.05), the combination treatment of ECRG2 plus DDP performed significantly better when compared to either ECRG2 or DDP alone(P < 0.05). The combination of ECRG2 and DDP significantly upregulated p53 m RNA and protein levels and downregulated PCNA m RNA and protein levels compared to ECRG2 or DDP alone(P < 0.05). However, no changes were seen in the expression of MT mR NA or protein.CONCLUSION ECRG2 in combination with DDP can inhibit viability and induce apoptosis in esophageal cancer DDP-resistant cells, possibly via upregulation of p53 expression and downregulation of PCNA expression. These findings suggest that the combination of ECRG2 and DDP may be a promising strategy for the clinical treatment of esophageal cancers that are resistant to DDP.展开更多
AIM: To evaluate the inhibitive effect of olmesartan to fibroblast proliferation and the anti-scarring effect in Tenon's capsule, both in vitro and in vivo.· METHODS: Human primary Tenon's capsule fibrobl...AIM: To evaluate the inhibitive effect of olmesartan to fibroblast proliferation and the anti-scarring effect in Tenon's capsule, both in vitro and in vivo.· METHODS: Human primary Tenon's capsule fibroblasts were cultured in vitro, treated with up titrating concentrations of olmesartan. The rate of inhibition was tested with methyl thiazol tetrazolium(MTT) method.Real-time PCR was performed to analyze changes in m RNA expressions of the fibrosis-related factors: matrix metalloproteinase-2(MMP-2), tissue inhibitor of metalloproteinase(TIMP-1,2) and proliferating cell nuclear antigen(PCNA). Thirty rabbits were divided into5 groups(3, 7, 14, 21, and 28d). A rabbit conjunctiva flap model was created in each eye. Olmesartan solution was injected subconjunctivally and then evaluated its anti-proliferation and anti-fibrosis effects through the histological morphology and immunohistochemistry of MMP-2 and PCNA in each group. Only the 7d group was treated with Masson's trichrome to compare the neovascularization in the subconjunctiva area.·RESULTS: In vitro, cultured Tenon's capsule human fibroblasts showed a dose dependent inhibition by olmesartan in MTT. Olmesartan reduced m RNA expressions of MMP-2 and PCNA but increased m RNA expressions of TIMP-1 and TIMP-2. In vivo, the rabbit eyes treated with olmesartan at 3rd, 7th, 14 thand 21stdays demonstrated a significant reduced expressions of MMP-2 and PCNA compared with control eye, no significant difference observed in 28 thday group. The cellular proliferation and neovascularization was suppressed by olmesartan in Masson's trichrome observation.·CONCLUSION: By inhibiting fibroblasts in vitro and in vivo, olmesartan prevents the proliferation and activity of fibroblasts in scar tissue formation, which might benefit glaucoma filtering surgery.展开更多
In order to investigate the expression of androgen receptor in meningiomas and its relation to tumor proliferative potential, we examined the expression of AR and proliferating cell nuclear antigen by avidine biotin c...In order to investigate the expression of androgen receptor in meningiomas and its relation to tumor proliferative potential, we examined the expression of AR and proliferating cell nuclear antigen by avidine biotin complex immunohistochemistry in 39 cases of meningiomas. Of the 39 cases of meningiomas, 20 showed positive AR immunoreactivity. The AR expression positivity rates were 31 % in benign meningiomas, 58 % in atypical meningiomas, 87.5 % in malignant meningiomas, respectively. In addition to the tumor cells, cells of microvascular endothelial proliferation were frequently AR positive. Malignant meningiomas had a significantly higher percentage of AR positive cells compared with atypical and benign meningiomas . The mean proliferating cell nuclear antigen labeling index was significantly higher in the malignant meningiomas when compared with atypical meningiomas and benign meningiomas . AR positive meningiomas had higher PCNA LI than AR negative meningiomas . The expression of AR in tumor tissues was significantly related with PCNA LI. These data indicated that AR in the meningiomas was correlated with histological grade and AR might participate in the growth of these tumors and tumor angiogenesis. The measurement of AR in these tumors may indirectly represent tumor growth potential.展开更多
Cells in mammalian cochleae virtually stop proliferation and exit cellular circle before birth. Consequently, hair cells and spiral ganglion neurons destroyed by ototoxic factors cannot be replaced through proliferati...Cells in mammalian cochleae virtually stop proliferation and exit cellular circle before birth. Consequently, hair cells and spiral ganglion neurons destroyed by ototoxic factors cannot be replaced through proliferative regeneration. However, substantial proliferation occurs in organotypic cultures of cochleae from postnatal mice. In the present study, we studied the time course of proliferative growth in cultures of mouse cochlea explants obtained from up to 12 postnatal days. The mitotic nature of this growth was confirmed by bromodeoxyuridine (BrdU) staining and expression of proliferation cell nuclear antigen (PCNA) evaluated with real-time quantitative poly-merase chain reaction(RT-PCR). Similar growth time course was found in the cochlear explants of different postnatal ages. The new growth reached its maximum at around 2 days in culture followed by a slow-down, and virtually stopped after 5 days of culture. The possible mechanisms and the significance of this proliferation are discussed.展开更多
To evaluate apoptosis in lupus nephritis and the relationship between the existence of apoptotic cells in renal tissue and histopathological or clinical changes Methods Apoptosis was detected by in situ nick end label...To evaluate apoptosis in lupus nephritis and the relationship between the existence of apoptotic cells in renal tissue and histopathological or clinical changes Methods Apoptosis was detected by in situ nick end labeling techniques (TUNEL) in renal biopsies from 25 patients with type Ⅳ lupus nephritis (LN), 12 patients with IgA nephropathy IgAN, 4 patients with idiopathic mesangioproliferative glomerulonephritis (MsPGN) and 3 patients with acute poststreptococcal glomerulonephritis (APGN) Normal renal tissue obtained at nephrectomy for hypernephroma in 4 adults was used as control Proliferating cells were identified by proliferating cell nuclear antigen (PCNA) in these patients Results Compared to other proliferative glomerulo^nephritis and controls, the patients with lupus nephritis had less apoptotic cells, a higher ratio of PCNA+ cells/TdT+ cells (P/T) in renal tissues; and their P/T ratio in glomeruli and tubulointerstitium correlated with the chronicity index, r =0 4983 ( P =0 0132), r =0 8399 ( P <0 001), r =0 6614 ( P =0 0033), respectively P/T ratios in the glomerulus and tubule had a positive correlation with 24 hour urinary protein, r =0 8554 ( P <0 001) and r =0 7134 ( P =0 001); and a negative correlation with creatinine clearance (Ccr), r =-0 4880 ( P =0 0133) and r =-0 7229 ( P =0 001), which in tubules positively correlated with serum creatinine (Scr), r =0 4107 ( P =0 0414) Conclusions Apoptosis is reduced in proliferative lupus nephritis Intense proliferation without a commensurate increase in apoptosis is a possible mechanism that leads to chronic progressive renal histopathological展开更多
基金the National Natural Science Foundation of China,No.81971943 and No.81772196and the Hubei Provincial Natural Science Foundation of China,No.2020CFB656.
文摘Gastrointestinal(GI)cancers,including malignancies in the gastrointestinal tract and accessory organs of digestion,represent the leading cause of death worldwide due to the poor prognosis of most GI cancers.An investigation into the potential molecular targets of prediction,diagnosis,prognosis,and therapy in GI cancers is urgently required.Proliferating cell nuclear antigen(PCNA)clamp associated factor(PCLAF),which plays an essential role in cell proliferation,apoptosis,and cell cycle regulation by binding to PCNA,is a potential molecular target of GI cancers as it contributes to a series of malignant properties,including tumorigenesis,epithelial-mesenchymal transition,migration,and invasion.Furthermore,PCLAF is an underlying plasma prediction target in colorectal cancer and liver cancer.In addition to GI cancers,PCLAF is also involved in other types of cancers and autoimmune diseases.Several pivotal pathways,including the Rb/E2F pathway,NF-κB pathway,and p53-p21 cascade,are implicated in PCLAF-mediated diseases.PCLAF also contributes to some diseases through dysregulation of the p53 pathway,WNT signal pathway,MEK/ERK pathway,and PI3K/AKT/mTOR signal cascade.This review mainly describes in detail the role of PCLAF in physiological status and GI cancers.The signaling pathways involved in PCLAF are also summarized.Suppression of the interaction of PCLAF/PCNA or the expression of PCLAF might be potential biological therapeutic strategies for GI cancers.
文摘Objective To study the effects of P53, PCNA, Bc1-2 protein and their relationship in salivary adenoid cystic carclnoma(SACC). Methods These protelns were examlned by lmmunohistochemistry. Results overexpressions of Ps, and PCNA were revealed in ACC samples, they were higher than those in (polymorphous adenomas) PA, but expression of Bc1-2 protein was not different between ACC and PA. In 3 subtypes of ACC, expressions of 3 proteins were different. Conciusion Mutations of P53, Bc1-2 may be involed in the occurrence of SACC, expression of PCNA and mutation of P53 may coexist in the development of the SACC.
基金Supported by the Public Welfare Project Foundation of Henan Province,No.20130010
文摘AIM To explore the anti-tumor effects of esophageal cancerrelated gene 2(ECRG2) in combination with cisplatin(DDP) in DDP-resistant esophageal cancer cells(EC9706/DDP).METHODS A drug-resistant cell model was established, with EC9706/DDP cells being treated with ECRG2 and/or DDP. Cell viability was examined by MTT assay. The rate of cell apoptosis was determined by flow cytometry. The mR NA expression levels of proliferating cell nuclear antigen(PCNA), metallothionein(MT), and p53 were determined by RT-PCR and PCNA, while MT and p53 protein expression levels were determined by western blotting.RESULTS The anti-proliferative effect of ECRG2 in combination with DDP was superior when compared to ECRG2 or DDP alone. The inhibition rate for the combination reached its peak(51.33%) at 96 h. The early apoptotic rates of the control, ECRG2 alone, DDP alone, and ECRG2 plus DDP groups were 5.71% ± 0.27%, 12.68% ± 0.61%, 14.15% ± 0.87%, and 27.96% ±0.36%, respectively. Although all treatment groups were significantly different from the control group(P < 0.05), the combination treatment of ECRG2 plus DDP performed significantly better when compared to either ECRG2 or DDP alone(P < 0.05). The combination of ECRG2 and DDP significantly upregulated p53 m RNA and protein levels and downregulated PCNA m RNA and protein levels compared to ECRG2 or DDP alone(P < 0.05). However, no changes were seen in the expression of MT mR NA or protein.CONCLUSION ECRG2 in combination with DDP can inhibit viability and induce apoptosis in esophageal cancer DDP-resistant cells, possibly via upregulation of p53 expression and downregulation of PCNA expression. These findings suggest that the combination of ECRG2 and DDP may be a promising strategy for the clinical treatment of esophageal cancers that are resistant to DDP.
基金the Scientific Research and Laboratory Center of the Second Affiliated Hospital of Xi'an Jiaotong University for the technical support
文摘AIM: To evaluate the inhibitive effect of olmesartan to fibroblast proliferation and the anti-scarring effect in Tenon's capsule, both in vitro and in vivo.· METHODS: Human primary Tenon's capsule fibroblasts were cultured in vitro, treated with up titrating concentrations of olmesartan. The rate of inhibition was tested with methyl thiazol tetrazolium(MTT) method.Real-time PCR was performed to analyze changes in m RNA expressions of the fibrosis-related factors: matrix metalloproteinase-2(MMP-2), tissue inhibitor of metalloproteinase(TIMP-1,2) and proliferating cell nuclear antigen(PCNA). Thirty rabbits were divided into5 groups(3, 7, 14, 21, and 28d). A rabbit conjunctiva flap model was created in each eye. Olmesartan solution was injected subconjunctivally and then evaluated its anti-proliferation and anti-fibrosis effects through the histological morphology and immunohistochemistry of MMP-2 and PCNA in each group. Only the 7d group was treated with Masson's trichrome to compare the neovascularization in the subconjunctiva area.·RESULTS: In vitro, cultured Tenon's capsule human fibroblasts showed a dose dependent inhibition by olmesartan in MTT. Olmesartan reduced m RNA expressions of MMP-2 and PCNA but increased m RNA expressions of TIMP-1 and TIMP-2. In vivo, the rabbit eyes treated with olmesartan at 3rd, 7th, 14 thand 21stdays demonstrated a significant reduced expressions of MMP-2 and PCNA compared with control eye, no significant difference observed in 28 thday group. The cellular proliferation and neovascularization was suppressed by olmesartan in Masson's trichrome observation.·CONCLUSION: By inhibiting fibroblasts in vitro and in vivo, olmesartan prevents the proliferation and activity of fibroblasts in scar tissue formation, which might benefit glaucoma filtering surgery.
文摘In order to investigate the expression of androgen receptor in meningiomas and its relation to tumor proliferative potential, we examined the expression of AR and proliferating cell nuclear antigen by avidine biotin complex immunohistochemistry in 39 cases of meningiomas. Of the 39 cases of meningiomas, 20 showed positive AR immunoreactivity. The AR expression positivity rates were 31 % in benign meningiomas, 58 % in atypical meningiomas, 87.5 % in malignant meningiomas, respectively. In addition to the tumor cells, cells of microvascular endothelial proliferation were frequently AR positive. Malignant meningiomas had a significantly higher percentage of AR positive cells compared with atypical and benign meningiomas . The mean proliferating cell nuclear antigen labeling index was significantly higher in the malignant meningiomas when compared with atypical meningiomas and benign meningiomas . AR positive meningiomas had higher PCNA LI than AR negative meningiomas . The expression of AR in tumor tissues was significantly related with PCNA LI. These data indicated that AR in the meningiomas was correlated with histological grade and AR might participate in the growth of these tumors and tumor angiogenesis. The measurement of AR in these tumors may indirectly represent tumor growth potential.
文摘Cells in mammalian cochleae virtually stop proliferation and exit cellular circle before birth. Consequently, hair cells and spiral ganglion neurons destroyed by ototoxic factors cannot be replaced through proliferative regeneration. However, substantial proliferation occurs in organotypic cultures of cochleae from postnatal mice. In the present study, we studied the time course of proliferative growth in cultures of mouse cochlea explants obtained from up to 12 postnatal days. The mitotic nature of this growth was confirmed by bromodeoxyuridine (BrdU) staining and expression of proliferation cell nuclear antigen (PCNA) evaluated with real-time quantitative poly-merase chain reaction(RT-PCR). Similar growth time course was found in the cochlear explants of different postnatal ages. The new growth reached its maximum at around 2 days in culture followed by a slow-down, and virtually stopped after 5 days of culture. The possible mechanisms and the significance of this proliferation are discussed.
基金This work was supported by a grant from Shanghai Scientific Technologi cal Committee(No 954119005).
文摘To evaluate apoptosis in lupus nephritis and the relationship between the existence of apoptotic cells in renal tissue and histopathological or clinical changes Methods Apoptosis was detected by in situ nick end labeling techniques (TUNEL) in renal biopsies from 25 patients with type Ⅳ lupus nephritis (LN), 12 patients with IgA nephropathy IgAN, 4 patients with idiopathic mesangioproliferative glomerulonephritis (MsPGN) and 3 patients with acute poststreptococcal glomerulonephritis (APGN) Normal renal tissue obtained at nephrectomy for hypernephroma in 4 adults was used as control Proliferating cells were identified by proliferating cell nuclear antigen (PCNA) in these patients Results Compared to other proliferative glomerulo^nephritis and controls, the patients with lupus nephritis had less apoptotic cells, a higher ratio of PCNA+ cells/TdT+ cells (P/T) in renal tissues; and their P/T ratio in glomeruli and tubulointerstitium correlated with the chronicity index, r =0 4983 ( P =0 0132), r =0 8399 ( P <0 001), r =0 6614 ( P =0 0033), respectively P/T ratios in the glomerulus and tubule had a positive correlation with 24 hour urinary protein, r =0 8554 ( P <0 001) and r =0 7134 ( P =0 001); and a negative correlation with creatinine clearance (Ccr), r =-0 4880 ( P =0 0133) and r =-0 7229 ( P =0 001), which in tubules positively correlated with serum creatinine (Scr), r =0 4107 ( P =0 0414) Conclusions Apoptosis is reduced in proliferative lupus nephritis Intense proliferation without a commensurate increase in apoptosis is a possible mechanism that leads to chronic progressive renal histopathological
