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
AIM to investigate the expression of proliferating cell nuclear antigen(p CNA)and E-cadherin in gastric carcinoma and to analyze their clinical significance.METHODS A total of 146 patients were selected for this study...AIM to investigate the expression of proliferating cell nuclear antigen(p CNA)and E-cadherin in gastric carcinoma and to analyze their clinical significance.METHODS A total of 146 patients were selected for this study,including 38 patients with intestinal metaplasia,42with dysplasia,and 66 with primary gastric cancer.In addition,40 patients with normal gastric tissues were selected as controls.the expression of p CNA and E-cadherin was detected by immunohistochemistry.Differences in p CNA and the E-cadherin labeling indexes among normal gastric mucosa,intestinal metaplasia,dysplasia,and gastric carcinoma were compared.Subjects with normal gastric tissues were assigned to a normal group,while gastric cancer patients were assigned to a gastric cancer group.the difference in p CNA and E-cadherin expression between these two groups was compared.the relationship between expression of p CNA and E-cadherin and clinicopathological features was also explored in gastric cancer patients.furthermore,prognosis-related factors,as well as the expression of p CNA and E-cadherin,were analyzed in patients with gastric cancer to determine the 3-year survival of these patients.RESULTS the difference in p CNA and the E-cadherin labeling indexes among normal gastric mucosa,intestinal metaplasia,dysplasia,and gastric carcinoma was statistically significant(p1),while the positive expression of E-cadherin was a protective factor(RR<1).the sensitivity,specificity,and accuracy of p CNA positivity in predicting the 3-year survival of patients with gastric cancer were 93.33%,38.89%,and0.64,respectively;while these values for E-cadherin negativity were 80.0%,41.67%,and 0.59,respectively.When p CNA positivity and E-cadherin negativity were combined,the sensitivity,specificity,and accuracy were66.67%,66.67%,and 0.67,respectively.CONCLUSION Combined detection of p CNA and E-cadherin can improve the accuracy of assessing the prognosis of patients with gastric cancer.展开更多
OBJECTIVE: To study the relationship between oval cells and primary hepatocarcinoma and the expression of c-kit and proliferating cell nuclear antigen (PCNA) in oval cells of rats with hepatocellular carcinoma. METHOD...OBJECTIVE: To study the relationship between oval cells and primary hepatocarcinoma and the expression of c-kit and proliferating cell nuclear antigen (PCNA) in oval cells of rats with hepatocellular carcinoma. METHODS: A hundred and twenty clean SD rats were divided into three groups: normal group, cancer-induction group and intervention group. The normal group was fed with standard forage while the rest two groups were fed with 3'-methyl-2-methylamino-azobenzene (DAB) to induce carcinoma for 14 weeks and then fed with standard forage and water. Uscharidin was injected abdominally to the intervention group from the first week to the 14th week. All rats were killed and biopsy specimens were taken from the left and right liver lobes for immunohistochemical staining of c-kit and PCNA on the 2nd, 4th, 6th, 8th, 10th, 12th, 14th, 16th, 18th, 20th, 22nd, and 24th week. RESULTS: From the 2nd to 14th week after liver infection, c-kit positive cells, mainly oval cells were found in the portal area in the carcinoma-induction group and dotted positive pigmentations in liver lobules. In the 22nd week, a large number of cancerous nodes occurred and nuclei heteromorphi-m was apparent; the number of positive cell decreased but positive cells could be sparsely observed in cancerous nodes. In the 2nd week of the carcinoma-induction process, PCNA positive cells were oval cells in the portal area. In the 4th week, a lot of hepatic cells were positively stained, especially in the central vein area. In the 6th week, PCNA positive cells could be seen in the lobules of the liver. In the 8th week, the number of PCNA cells decreased comparatively. From the 10th to 14th week, oval cells in the portal area were still over-expressed. From the 16th to 24th week, a large number of cancerous nodes occurred and PCNA was over-expressed in some of them. In necrotic cancerous nodes, the para-cancerous PCNA positive cells were sparsely distributed and their number was less than that of PCNA positive cells of cancerous tissues. CONCLUSIONS: Hepatic stem cells originating from the terminal biliary plexus of the portal area are involved in the development of hepatocarcinoma because c-kit positive cells expressed in cancerous nodes, accompany the whole process of the development. In the middle inflammatory period of carcinoma-induction, the expression of PCNA in hepatic cells peaked, but the index decreased in the late inflammatory period and in the proliferated fibrosis stage. The expression of PCNA is a tortuous process, going up, down, then up again from normal tissues to cancerous tissues. Combined with pathological findings, PCNA can be considered as a warning index for carcinomatous cells.展开更多
AIM: An increase in bile ductular structures is observed in diverse human liver diseases, especially in primary biliary cirrhosis (PBC). These structures harbor the progenitor cell component of the liver. Caveolins ar...AIM: An increase in bile ductular structures is observed in diverse human liver diseases, especially in primary biliary cirrhosis (PBC). These structures harbor the progenitor cell component of the liver. Caveolins are cholesterol-binding proteins involved in the regulation of several intracellular processes including cholesterol transport. This study aims to examine the role of caveolin in PBC.METHODS: Immunohistochemical and Western blottingstudies were performed on human liver specimens obtained from patients with PBC and normal liver samples. The expression of caveolin (CAV)-1 and -2 was determined using specific antibodies.RESULTS: In normal liver, scanty immunostaining for CAV1 and -2 was observed in bile ductules. In PBC liver samples, the expression levels of CAV-1 and -2 were increased on proliferating bile ductules especially in stage 3 cases, but was sparse on interlobular bile duct in stage 1 specimens. Especially, the regenerating bile ductules at the interface of portal tracts and necrotic areas were immunostained intensely for CAV-1 and -2. These phenomena were confirmed by Western blot.CONCLUSION: The present results demonstrate increased expression of caveolins in proliferating bile ductules in PBC, which may be related to the homeostasis of cholesterol transport in regenerating bile ductules in PBC liver.展开更多
OBJECTIVE:To study the effect of Lichong Decoction(Lichong Decoction for strengthening anti-pathogenic Qi and eliminating blood stasis) on the expression of insulin-like growth factor-I(IGF-I) and proliferating cell n...OBJECTIVE:To study the effect of Lichong Decoction(Lichong Decoction for strengthening anti-pathogenic Qi and eliminating blood stasis) on the expression of insulin-like growth factor-I(IGF-I) and proliferating cell nuclear antigen(PCNA) mRNA in a rat model of uterine leiomyoma.METHODS:Fifty female Wistar rats were randomized into a normal control group,model group,Lichong Decoction group,Guizhifuling Capsule(Capsule containing Cassia Twig and Poria) group,and Mifepristone group.The uterine leiomyoma model was established by peritoneal injections of exogenous estrogen and progesterone hormone.The ultrastructural changes in cells of rat uterine tissues were observed with transmission electron microscopy,and the expression of IGF-I and PCNA mRNA was detected by real-time fluorescent quantitative PCR.RESULTS:Following treatment,cells in the Lichong Decoction group appeared to be arranged normally,the cellular morphology were almost in a normal state,hyperplasia and hypertrophy of the chondriosome was reduced,collagen fibers were arranged in a regular manner,without obvious hyperplasia,and the expression of IGF-I and PCNA mRNA was significantly decreased compared with the model group(P<0.01).CONCLUSIONS:The effect of Lichong Decoction on uterine leiomyoma is related to its function in reducing the expression of IGF-I and PCNA mRNA.展开更多
To investigate the relationship of bcl-2, p53, proliferating cell nuclear antigen (PCNA) to cell proliferation, apoptosis and pathological parameters, the patterns of cell growth and turnover in renal cell carcinoma (...To investigate the relationship of bcl-2, p53, proliferating cell nuclear antigen (PCNA) to cell proliferation, apoptosis and pathological parameters, the patterns of cell growth and turnover in renal cell carcinoma (RCC), formalin-fixed and paraffin-embedded tissue blocks from 34 patients with RCC were examined. Cell proliferation activity was detected by PCNA immunostaining and the proliferation index (PI) was expressed as a percentage of the PCNA-positive cells in the tumor cells. Apoptosis was detected by terminal deoxy- nucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and the apoptotic index (AI) was expressed as a percentage of the TUNEL-positive cells in the tumor cells. Expressions of bcl-2 and p53 were assessed immunohistochemically. Our results showed that the PI ranged from 6.0 % to 24.0 % (median 12.3 %) and the AI from 2.0 % to 8.0 % (median 5.4 %) in RCC. The expression of the bcl-2 protein was demonstrated in 15 cases (44.1 %); the expression of the p53 protein, however, was seen in only 3 case. bcl-2 positivity was not associated with PI or AI or any pathological parameters. There were close associations between PI and tumor grade and stage, and a significant relationship between AI and the tumor grade of RCC. Our study suggests that bcl-2 positivity was not associated with PI or AI or any pathological parameters. There are close associations between PI and AI and tumor grade and stage of RCC. Active cell proliferation may be accompanied by frequent apoptosis in RCC.展开更多
Aim: To explore the usefulness of proliferating cell nuclear antigen proliferating index (PCNA PI) in the pathologicaldiagnosis and treatment of male infertility. Methods: Testicular biopsy specimen obtained from 48 c...Aim: To explore the usefulness of proliferating cell nuclear antigen proliferating index (PCNA PI) in the pathologicaldiagnosis and treatment of male infertility. Methods: Testicular biopsy specimen obtained from 48 cases of male in-fertility and 2 normal controls were fixed and embedded. The sections were stained with anti-PCNA monoclonal anti-bodies or haematoxylin/eosin. Proliferating index (PI), expressed as the percentage of germ-cell nuclei positivelystained with PCNA antibody, was assessed from more than 20 seminiferous tubules or 600 germ-cells. Results: Theinfertile patients were divided into 4 groups: Group 1, normal spermatogenesis (14 cases); Group 2, hypospermato-genesis (16 cases); Group 3, germinal arrest (10 cases); Group 4, Sertoli cell only syndrome (8 cases). The PCNAPI of normal control testis was 86.5 % (mean value). Group 3 had a significantly lower PCNA PI (29.8 %) than nor-mal testis; Group 1 and 2 had similar Pis (82.3% and 82.3%, respectively) as the control testis. PI of the negativecontrol (Group 4) was 0 as no germ-cells were found. Conclusion: PCNA PI is useful for assessing germ-cell ki-netics, especially for pathological diagnosis of germinal arrest which is difficult to differentiate by routine HE stainingtechnique. In germinal arrest, there is a significantly lowered PCNA PI, which is an indication of DNA synthesis dete-rioration, suggesting the use of therapies be different from those for hypospermatogenesis. (Asian J Androl 2001 Mar;3: 63-66)展开更多
The relationship between the apoptosis and the expression of proliferating cell nuclear antigen (PCNA) and the clinical stages in gastric cancers was studied. By using terminal deoxynucleotidyl transferase mediated ni...The relationship between the apoptosis and the expression of proliferating cell nuclear antigen (PCNA) and the clinical stages in gastric cancers was studied. By using terminal deoxynucleotidyl transferase mediated nick end labelling (TUNEL) technique and PCNA immunohistochemical staining, the apoptosis and the expression of PCNA in tissue of gastric carcinoma were assayed in situ, the index of apoptosis (AI), index of PCNA (PI) and the rate of AI/PI were calculated. AI and PI in gastric cancer tissues were (6.5±3.7) % and (49.8±15.9) % respectively, and the rate of AI/PI was 0.13±0.05, which were obviously different from those of normal gastric mucosa in paragastric cancer ( P <0.01). With the advanced TNM stages of gastric carcinoma, the AI was decreased, PI was increased and the rate of AI/PI decreased in gastric carcinoma. There was significant difference in them between the gastric cancer tissues and normal gastric mucosa in pericarcinoma in TNM stage Ⅱ to Ⅳ ( P <0.05). It was suggested that the decreased apoptotic cells and the increased proliferating cells were obviously related to the tumor genesis and tumor progression in gastric carcinoma. The AI, PI and the rate of AI/PI would become the prognostic factors in advanced gastric carcinoma.展开更多
To study the relationship between p53 protein, proliferating cell nuclear antigen (PCNA) expression and benign or malignant gestational trophoblastic disease (MGTD). Methods: The histotomic sections of 48 patients wit...To study the relationship between p53 protein, proliferating cell nuclear antigen (PCNA) expression and benign or malignant gestational trophoblastic disease (MGTD). Methods: The histotomic sections of 48 patients with gestational trophoblastic disease and 24 patients of normal chorionic villi were stained using immunohistochemistry. The monoclonal antibodies were used to determine p53 protein and PCNA. Results: The frequency of p53 and PCNA positive expression were significantly different among the chorionic villi of normal pregnancy, hydratidiform mole (HM) and MGTD. But neither p53 nor PCNA has any relation with the clinical staging or metastasis of MGTD. Conclusion: Both P53 and PCNA are valuable in diagnosis of human gestational trophoblastic disease.展开更多
Objective: To correlate the frequency of p53 mutations, bcl-2 expression and the proliferation status (proliferating cell nuclear antigen, PCNA) in patients with bladder cancer with cell proliferation, apoptosis and t...Objective: To correlate the frequency of p53 mutations, bcl-2 expression and the proliferation status (proliferating cell nuclear antigen, PCNA) in patients with bladder cancer with cell proliferation, apoptosis and their clinico-pathologic ?ndings. Methods: Para?n-embedded sections from 39 super?cial (T1G1-G3) and 23 invasive (T2-T4a G3 N0M0) primary transitional cell carcinomas (TCC) in the bladder were investigated immunohistochemically for p53, bcl-2 and PCNA. The median follow-up was 37 months; 24 had recurrences. The proliferation index (PI) was expressed as a percentage of the PCNA-positive cells in the tumor cells. Apoptosis was detected by terminal deoxy-nucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and the apoptotic index (AI) was expressed as a percentage of the TUNEL- positive tumor cells. Results: P53 mutation was identi?ed in 50 patients (80.6%). The mutation was most common in tumors of grade 3 (91.3%) as compared to grade 2 (78.5%) and grade 1 (72.7%, P0.05). The PI ranged from 17.2% to 41.8% (median 22.4%) and the AI from 1.9% to 3.5% (median 2.9%) in bladder cancer. Statistical analyses revealed a close associations between PI, AI and tumor grade and stage of bladder cancer. Conclusion: P53 mutation correlates with invasion. P53 and PCNA overexpression may o?er valuable additional prognostic information in bladder tumors. With the progression of the tumor grade, cell proliferation may be accompanied by frequent apoptosis in bladder cancer, but the PI increased much more than the AI.展开更多
After co-cultrured osteoblast with fl-TCP ceramics, the cellular proliferating, mineralization and osteocalcin expression were studied. MTT assay showed that fl-TCP ceramics had no affect on cellular proliferating. La...After co-cultrured osteoblast with fl-TCP ceramics, the cellular proliferating, mineralization and osteocalcin expression were studied. MTT assay showed that fl-TCP ceramics had no affect on cellular proliferating. Laser scanning confocal detection showed that fl-TCP ceramics could increase the mineralization level of osteoblast. Furthermore, RT-PCR showed that fl-TCP could increase the expression level of osteocalcin. Those results indicate β-TCP ceramics had perfect biocompatibility and increased the mineralization of osteoblast to accelerate osteogenesis by means of affecting the expression of genes involving in osteogeneticprocess.展开更多
PCNA has been considered as a useful marker for the estimation of growth rates of marine phytoplankton at the species level. Since dinoflagellates are noted for having many prokaryotic features in that they are the on...PCNA has been considered as a useful marker for the estimation of growth rates of marine phytoplankton at the species level. Since dinoflagellates are noted for having many prokaryotic features in that they are the only eukaryotes to have permanently condensed chromosomes as well as lacking histones and a nucleosome, the sensitivity to UVB radiation and the validity of PCNA as a maker of growth rate in dinoflagellate need to be evaluated. Prorocentrum donghaiense Lu was investigated to valuate the UVB sensitivity in relation to cellular and molecular aspects of PCNA as a growth indicator. The effects of UVB radiation on PCNA were studied using the methods of western blots technology and whole-cell immunoflurescence with one mono-antibody. UVB changed the cell morphology, halted the growth and increased the cell size, even caused cell death to a certain extent after treatment with UVB radiation in P. donghaiense. Compared with the control, treating the algal cultures in exponential phases with UVB radiation for 24 h caused chromatin release and increases in protein levels of PCNA.展开更多
To explore a novel strategy for antisense gene therapy of cancer,the coding sequence of hum an proliferating cell nuclear antigen(PCNA) c DNA was reversely inserted into the eukaryotic vector p L XSN by molecular clon...To explore a novel strategy for antisense gene therapy of cancer,the coding sequence of hum an proliferating cell nuclear antigen(PCNA) c DNA was reversely inserted into the eukaryotic vector p L XSN by molecular cloning techniques and transferred into bladder cancer EJcells with li- posome. The PCNA expression in transferred cells was dynamically detected by immunofluo- rescence and RT- PCR techniques. Changes of proliferation activities of cancer cells were assayed by MTT colorim etric and cloning formation m ethods.In the experiment,the antisense eukaryotic vector was successfully constructed and nam ed as p L APSN.After transfection with it for1- 7 days,PCNA protein and m RNA levels in cancer cells were blocked by16 .74 % - 84 .2 1% (P< 0 .0 5 ) and2 3.2 7% - 86 .15 % (P<0 .0 5 ) respectively.The proliferation activities of transferred cells were inhibited by 2 7.91% - 6 2 .0 7% (P<0 .0 1) ,with cloning formation abilities being de- creased by 5 0 .81% (P<0 .0 1) . Itwas concluded that the in vitro proliferation activities of cancer cells could be effectively inhibited by blocking PCNA expression with antisense technique,which could serve as an ideal strategy for gene therapy of bladder cancer.展开更多
In order to study the effect of and mechanism of lysophosphatidylcholine (LysoPC) on proliferation of the calf thoracic aorta smooth muscle cells (ASMCs), the ASMCs were used to observe the effects of LysoPC induced e...In order to study the effect of and mechanism of lysophosphatidylcholine (LysoPC) on proliferation of the calf thoracic aorta smooth muscle cells (ASMCs), the ASMCs were used to observe the effects of LysoPC induced endothelial cell conditioned medium on the DNA content and proliferating cell nuclear antigen (PCNA) expression in the calf thoracic ASMCs by flow cytometry and Western Blot technique. It was found that LysoPC induced endothelial cell conditioned medium could significantly promote PCNA expression of the calf ASMCs, induce the converting of ASMCs from G 0 /G 1 phase to S phase of DNA synthesis, and increase the tyrosine phosphorylation protein expression. Tyrosine protein kinase inhibitor (TPKi) RG50864 could obviously inhibit proliferation of LysoPC induced ASMCs in a dose dependence manner. The results indicated that the effect of LysoPC promoting the proliferation of ASMCs is partly evoked by endothelial cell derived growth factors such as PDGF and so on.展开更多
AIM:To investigate the relationship between the mast cell density(MCD)and the context of clinicopathological parameters and expression of p185,estrogen receptor(ER),and proliferating cell nuclear antigen(PCNA)in gastr...AIM:To investigate the relationship between the mast cell density(MCD)and the context of clinicopathological parameters and expression of p185,estrogen receptor(ER),and proliferating cell nuclear antigen(PCNA)in gastric carcinoma.METHODS:Mast cell,p185,ER,and PCNA were detected using immunohistochemical S-P labeling method.Mast cell was counted in tissue of gastric carcinoma and regional lymph nodes respectively,and involved lymph nodes(ILN)were examined as usual.RESULTS:MCD was significantly related to both age and depth of penetration(x2=4.688,P21/0.03 mm2and MCD≤21/0.03 mm2in 100 patients;MCD in 1-6 ILN group patients was significantly higher than that in 7-15 ILN or>15 ILN group patients(u=6.881,8.055,P21/0.03 mm2and MCD≤21/0.03 mm2in 100 patients.CONCLUSION:Mast cell may have effect on inhibiting invasive growth of tumor,especially in the aged patients;The number of mast cells,in certain degree,may predicate the number of involved lymph nodes,which is valuable for assessment of prognosis;MCD was related to the expression of p185,ER,and PCNA in gastric carcinoma.It suggests that mast cell accumulation may inhibit the proliferation and the dissemination of the gastric carcinoma.INTRODUCTION Recently,many studies have reported on the association of mast cell with various tumorst.In several malignancies,mast cell has been found to correlate with growth,penetration and prognosis of tumor.Therefore,our study was undertaken to investigate the relationship between the mast cell density(MCD)and the context of clinicopathological parameters and expression of p 185,estrogen receptor(ER),and proliferating cell nuclear antigen(PCNA)in gastric carcinoma.展开更多
Harmful algal blooms (HABs) have been affecting negatively the shellfish and aquaculture industries around the world. Though a lot of efforts have been made to disclose the changes of environmental factors involved ...Harmful algal blooms (HABs) have been affecting negatively the shellfish and aquaculture industries around the world. Though a lot of efforts have been made to disclose the changes of environmental factors involved and their effects on the HABs events, the molecular mechanism of this process remains unclear. To address this problem, proliferating cell nuclear antigen gene (pcna) was isolated and characterized from Alexandrium catenella. It showed high homology to those of other dinoflagellates (89% and 91% homology to Pfiesteria piscicid and Pyrocystis lunula, respectively), and also 42%–43% homology to those of plant and animals. The expression level of pcna revealed by quantitative real time PCR was the lowest at the late lagging cell growth phase, increased to the highest at the late exponential phase, and then decreased at the stationary phase. Though the cell growth rate was also changing, no positive correlation between pcna expression level and cell growth rate was displayed throughout the whole cell growth stages (r 2 =0.024 6). However, the pcna expression level had the similar trend with the change of cell growth rate throughout the whole growing process, e.g., from increasing at the earlier cell growth stage to decreasing at the following stages, though slightly lagging to the latter.展开更多
Non-proliferating cells efficiently generate adenosine 5’-triphosphate (ATP) through mitochondrial oxidative phosphorylation.By contrast, proliferating cells, including cancer cells, tend to rely on aerobic glycolysi...Non-proliferating cells efficiently generate adenosine 5’-triphosphate (ATP) through mitochondrial oxidative phosphorylation.By contrast, proliferating cells, including cancer cells, tend to rely on aerobic glycolysis, an inefficient way to generate energy, and this phenomenon is termed 'the Warburg effect'1,2.However, the advantage of the Warburg effect provided for proliferating cells has been unclear3.Here we propose that aerobic glycolysis may maintain proton homeostasis to benefit proliferating cells.展开更多
Ulva prolifera is the most common specie causative to green tide,and its growth is sensitive to temperature stress.However,the mechanisms of U.prolifera response to temperature stress remain elusive.In this study,high...Ulva prolifera is the most common specie causative to green tide,and its growth is sensitive to temperature stress.However,the mechanisms of U.prolifera response to temperature stress remain elusive.In this study,high temperature(36℃)stimulus promoted the death of unformed cell wall protoplasts and delayed the division of formed cell wall protoplasts,while low-temperature(4℃)stimulus did not,suggesting that the mechanisms of the response of U.prolifera to high and low temperature stresses are different.Transcriptome results show that proliferation-related genes were differentially expressed under high and low-temperature stresses,especially the proliferating cell nuclear antigen(PCNA)and cyclins(CYCs).Subsequently,the interaction between PCNA and Cyclin A was confirmed by Co-immunoprecipitation,yeast two-hybrid,and so on.Furthermore,high-and low temperature stresses induced the expression of PCNA and Cyclin A in varying of degrees,and activated extracellular signal-regulated kinase(ERK)signal pathway.These results suggest,PCNA,Cyclin A,and ERK signal pathway played important roles in the resistance of U.prolifera to temperature stress.Interestingly,high-temperature stress induced an increase of miR-2916 in abundance,and exhibiting reverse expression of PCNA;and PCNA was target gene of miR-2916,suggesting that miR-2916 protected U.prolifera from high-temperature stress via post-transcriptionally regulation of PCNA.This study laid a foundation for understanding the function of PCNA and Cyclin A,moreover,it has a guiding significance to explore the mechanisms of the response to temperature stress from proliferation-related genes regulatory networks in U.prolifera.展开更多
Objective: To study the relationship between proliferating cell nuclear antigen expression and its malignancy potential in colorectal carcinoma. Methods: Paraffin sections of 86 patients with advanced colorectal carci...Objective: To study the relationship between proliferating cell nuclear antigen expression and its malignancy potential in colorectal carcinoma. Methods: Paraffin sections of 86 patients with advanced colorectal carcinoma were assessed by immunohistochemical study, using a mouse monoclonal antibody (pc-10, DAKO Co. USA) to check proliferating cell nuclear antigen (PCNA). To compare PCNA with conventional clinicopathologic factor, including p53 overexpression, tissue carcinoembnyonic antigen immunoreactivity pattern and flow cytometric DNA ploidy for assessing tumor malignancy potential. In addition, recurrence and survival of patients with advanced colorectal carcinoma after curative resection were analyzed in accordance with degree of PCNA expression. Results: PCNA-labeling index (PCNA-LI) increased significantly as the tumor stage advanced (p=0.0001). Strong correlations were observed between PCNA-LI and various pathologic parameters, including histologic differentiation (P=0.0027), lymphatic invasion (P=0.0001), vascular invasion (P=0.0001), lymph node metastasis (P=0.0001), and liver metastasis (P=0.0036). Mean PCNA-LI was also significantly higher in tumor with DNA aneuploidy (P=0.0006) and negative (P=0.01). Linear relationships were demonstrated between PCNA-LI and clinical outcomes; Recurrence rate was significantly greater in the group with higher than the mean PCNA-LI, who underwent curative resection (P<0.01), and three-year survival rates for curative cases with higher than the mean PCNA-LI were significantly poorer than those with lower than mean PCNA-LI (P<0.005). Conclusion: There were correlations between PCNA-LI and various pathologic parameters, PCNA-LI increased significantly as the tumor stage advanced in colorectal carcinoma, the rates of recurrence and death got higher as PCNA-LI increased after curative resection for colorectal carcinoma.展开更多
AIM: To explore the feasibility of passage of bone- marrow-derived liver stem cells (BDLSCs) in culture systems that contain cholestatic serum.METHODS: Whole bone marrow cells of rats were purified with conditioni...AIM: To explore the feasibility of passage of bone- marrow-derived liver stem cells (BDLSCs) in culture systems that contain cholestatic serum.METHODS: Whole bone marrow cells of rats were purified with conditioning selection media that contained 50 mL/L cholestatic serum. The selected BDLSCs were grown in a proliferating culture system and a differentiating culture system. The culture systems contained factors that stimulated the proliferation and differentiation of BDLSCs. Each passage of the proliferated stem cells was subjected to flow cytometry to detect stem cell markers. The morphology and phenotypic markers of BDLSCs were characterized using immunohistochemistry, reverse transcription polymerase chain reaction (RT-PCR) and electron microscopy. The metabolic functions of differentiated cells were also determined by glycogen staining and urea assay.RESULTS: The conditioning selection medium isolated BDLSCs directly from cultured bone marrow cells. The selected BDLSCs could be proliferated for six passages and maintained stable markers in our proliferating system. When the culture system was changed to a differentiating system, hepatocyte-like colony-forming units (H-CFUs) were formed. H-CFUs expressed markers of embryonic hepatocytes (alpha-fetoprotein, albumin and cytokeratin 8/18), biliary cells (cytokeratin 19), hepatocyte functional proteins (transthyretin and cytochrome P450-261), and hepatocyte nuclear factors 1α and -3β). They also had glycogen storage and urea synthesis functions, two of the critical features of hepatocytes.CONCLUSION: BDLSCs can be selected directly from bone marrow cells, and pure BDLSCs can be proliferated for six passages. The differentiated cells have hepatocyte-like phenotypes and functions. BDLSCs represent a new method to provide a readily available alternate source of cells for clinical hepatocyte therapy.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.
摘要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.
基金the National Natural Science foundation of China,No.81360330
摘要AIM to investigate the expression of proliferating cell nuclear antigen(p CNA)and E-cadherin in gastric carcinoma and to analyze their clinical significance.METHODS A total of 146 patients were selected for this study,including 38 patients with intestinal metaplasia,42with dysplasia,and 66 with primary gastric cancer.In addition,40 patients with normal gastric tissues were selected as controls.the expression of p CNA and E-cadherin was detected by immunohistochemistry.Differences in p CNA and the E-cadherin labeling indexes among normal gastric mucosa,intestinal metaplasia,dysplasia,and gastric carcinoma were compared.Subjects with normal gastric tissues were assigned to a normal group,while gastric cancer patients were assigned to a gastric cancer group.the difference in p CNA and E-cadherin expression between these two groups was compared.the relationship between expression of p CNA and E-cadherin and clinicopathological features was also explored in gastric cancer patients.furthermore,prognosis-related factors,as well as the expression of p CNA and E-cadherin,were analyzed in patients with gastric cancer to determine the 3-year survival of these patients.RESULTS the difference in p CNA and the E-cadherin labeling indexes among normal gastric mucosa,intestinal metaplasia,dysplasia,and gastric carcinoma was statistically significant(p1),while the positive expression of E-cadherin was a protective factor(RR<1).the sensitivity,specificity,and accuracy of p CNA positivity in predicting the 3-year survival of patients with gastric cancer were 93.33%,38.89%,and0.64,respectively;while these values for E-cadherin negativity were 80.0%,41.67%,and 0.59,respectively.When p CNA positivity and E-cadherin negativity were combined,the sensitivity,specificity,and accuracy were66.67%,66.67%,and 0.67,respectively.CONCLUSION Combined detection of p CNA and E-cadherin can improve the accuracy of assessing the prognosis of patients with gastric cancer.
基金This work was supported by the grants from Science Foundation of Guangdong Province (No. 00593 and 01059. 2001).
摘要OBJECTIVE: To study the relationship between oval cells and primary hepatocarcinoma and the expression of c-kit and proliferating cell nuclear antigen (PCNA) in oval cells of rats with hepatocellular carcinoma. METHODS: A hundred and twenty clean SD rats were divided into three groups: normal group, cancer-induction group and intervention group. The normal group was fed with standard forage while the rest two groups were fed with 3'-methyl-2-methylamino-azobenzene (DAB) to induce carcinoma for 14 weeks and then fed with standard forage and water. Uscharidin was injected abdominally to the intervention group from the first week to the 14th week. All rats were killed and biopsy specimens were taken from the left and right liver lobes for immunohistochemical staining of c-kit and PCNA on the 2nd, 4th, 6th, 8th, 10th, 12th, 14th, 16th, 18th, 20th, 22nd, and 24th week. RESULTS: From the 2nd to 14th week after liver infection, c-kit positive cells, mainly oval cells were found in the portal area in the carcinoma-induction group and dotted positive pigmentations in liver lobules. In the 22nd week, a large number of cancerous nodes occurred and nuclei heteromorphi-m was apparent; the number of positive cell decreased but positive cells could be sparsely observed in cancerous nodes. In the 2nd week of the carcinoma-induction process, PCNA positive cells were oval cells in the portal area. In the 4th week, a lot of hepatic cells were positively stained, especially in the central vein area. In the 6th week, PCNA positive cells could be seen in the lobules of the liver. In the 8th week, the number of PCNA cells decreased comparatively. From the 10th to 14th week, oval cells in the portal area were still over-expressed. From the 16th to 24th week, a large number of cancerous nodes occurred and PCNA was over-expressed in some of them. In necrotic cancerous nodes, the para-cancerous PCNA positive cells were sparsely distributed and their number was less than that of PCNA positive cells of cancerous tissues. CONCLUSIONS: Hepatic stem cells originating from the terminal biliary plexus of the portal area are involved in the development of hepatocarcinoma because c-kit positive cells expressed in cancerous nodes, accompany the whole process of the development. In the middle inflammatory period of carcinoma-induction, the expression of PCNA in hepatic cells peaked, but the index decreased in the late inflammatory period and in the proliferated fibrosis stage. The expression of PCNA is a tortuous process, going up, down, then up again from normal tissues to cancerous tissues. Combined with pathological findings, PCNA can be considered as a warning index for carcinomatous cells.
摘要AIM: An increase in bile ductular structures is observed in diverse human liver diseases, especially in primary biliary cirrhosis (PBC). These structures harbor the progenitor cell component of the liver. Caveolins are cholesterol-binding proteins involved in the regulation of several intracellular processes including cholesterol transport. This study aims to examine the role of caveolin in PBC.METHODS: Immunohistochemical and Western blottingstudies were performed on human liver specimens obtained from patients with PBC and normal liver samples. The expression of caveolin (CAV)-1 and -2 was determined using specific antibodies.RESULTS: In normal liver, scanty immunostaining for CAV1 and -2 was observed in bile ductules. In PBC liver samples, the expression levels of CAV-1 and -2 were increased on proliferating bile ductules especially in stage 3 cases, but was sparse on interlobular bile duct in stage 1 specimens. Especially, the regenerating bile ductules at the interface of portal tracts and necrotic areas were immunostained intensely for CAV-1 and -2. These phenomena were confirmed by Western blot.CONCLUSION: The present results demonstrate increased expression of caveolins in proliferating bile ductules in PBC, which may be related to the homeostasis of cholesterol transport in regenerating bile ductules in PBC liver.
基金Supported by the National Natural Science Foundation of China(No.81073096)the Natural Science Foundation of Beijing City(No.7082015)the "Cultivation Plan for Youth Backbone Talents" Project(PHR 201008403) of Higher SchoolTalent Strong Education Plan
摘要OBJECTIVE:To study the effect of Lichong Decoction(Lichong Decoction for strengthening anti-pathogenic Qi and eliminating blood stasis) on the expression of insulin-like growth factor-I(IGF-I) and proliferating cell nuclear antigen(PCNA) mRNA in a rat model of uterine leiomyoma.METHODS:Fifty female Wistar rats were randomized into a normal control group,model group,Lichong Decoction group,Guizhifuling Capsule(Capsule containing Cassia Twig and Poria) group,and Mifepristone group.The uterine leiomyoma model was established by peritoneal injections of exogenous estrogen and progesterone hormone.The ultrastructural changes in cells of rat uterine tissues were observed with transmission electron microscopy,and the expression of IGF-I and PCNA mRNA was detected by real-time fluorescent quantitative PCR.RESULTS:Following treatment,cells in the Lichong Decoction group appeared to be arranged normally,the cellular morphology were almost in a normal state,hyperplasia and hypertrophy of the chondriosome was reduced,collagen fibers were arranged in a regular manner,without obvious hyperplasia,and the expression of IGF-I and PCNA mRNA was significantly decreased compared with the model group(P<0.01).CONCLUSIONS:The effect of Lichong Decoction on uterine leiomyoma is related to its function in reducing the expression of IGF-I and PCNA mRNA.
摘要To investigate the relationship of bcl-2, p53, proliferating cell nuclear antigen (PCNA) to cell proliferation, apoptosis and pathological parameters, the patterns of cell growth and turnover in renal cell carcinoma (RCC), formalin-fixed and paraffin-embedded tissue blocks from 34 patients with RCC were examined. Cell proliferation activity was detected by PCNA immunostaining and the proliferation index (PI) was expressed as a percentage of the PCNA-positive cells in the tumor cells. Apoptosis was detected by terminal deoxy- nucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and the apoptotic index (AI) was expressed as a percentage of the TUNEL-positive cells in the tumor cells. Expressions of bcl-2 and p53 were assessed immunohistochemically. Our results showed that the PI ranged from 6.0 % to 24.0 % (median 12.3 %) and the AI from 2.0 % to 8.0 % (median 5.4 %) in RCC. The expression of the bcl-2 protein was demonstrated in 15 cases (44.1 %); the expression of the p53 protein, however, was seen in only 3 case. bcl-2 positivity was not associated with PI or AI or any pathological parameters. There were close associations between PI and tumor grade and stage, and a significant relationship between AI and the tumor grade of RCC. Our study suggests that bcl-2 positivity was not associated with PI or AI or any pathological parameters. There are close associations between PI and AI and tumor grade and stage of RCC. Active cell proliferation may be accompanied by frequent apoptosis in RCC.
摘要Aim: To explore the usefulness of proliferating cell nuclear antigen proliferating index (PCNA PI) in the pathologicaldiagnosis and treatment of male infertility. Methods: Testicular biopsy specimen obtained from 48 cases of male in-fertility and 2 normal controls were fixed and embedded. The sections were stained with anti-PCNA monoclonal anti-bodies or haematoxylin/eosin. Proliferating index (PI), expressed as the percentage of germ-cell nuclei positivelystained with PCNA antibody, was assessed from more than 20 seminiferous tubules or 600 germ-cells. Results: Theinfertile patients were divided into 4 groups: Group 1, normal spermatogenesis (14 cases); Group 2, hypospermato-genesis (16 cases); Group 3, germinal arrest (10 cases); Group 4, Sertoli cell only syndrome (8 cases). The PCNAPI of normal control testis was 86.5 % (mean value). Group 3 had a significantly lower PCNA PI (29.8 %) than nor-mal testis; Group 1 and 2 had similar Pis (82.3% and 82.3%, respectively) as the control testis. PI of the negativecontrol (Group 4) was 0 as no germ-cells were found. Conclusion: PCNA PI is useful for assessing germ-cell ki-netics, especially for pathological diagnosis of germinal arrest which is difficult to differentiate by routine HE stainingtechnique. In germinal arrest, there is a significantly lowered PCNA PI, which is an indication of DNA synthesis dete-rioration, suggesting the use of therapies be different from those for hypospermatogenesis. (Asian J Androl 2001 Mar;3: 63-66)
基金This project was supported by the special constructing project of m edical clinical subject from Health Ministry(No.6 716 8)
摘要The relationship between the apoptosis and the expression of proliferating cell nuclear antigen (PCNA) and the clinical stages in gastric cancers was studied. By using terminal deoxynucleotidyl transferase mediated nick end labelling (TUNEL) technique and PCNA immunohistochemical staining, the apoptosis and the expression of PCNA in tissue of gastric carcinoma were assayed in situ, the index of apoptosis (AI), index of PCNA (PI) and the rate of AI/PI were calculated. AI and PI in gastric cancer tissues were (6.5±3.7) % and (49.8±15.9) % respectively, and the rate of AI/PI was 0.13±0.05, which were obviously different from those of normal gastric mucosa in paragastric cancer ( P <0.01). With the advanced TNM stages of gastric carcinoma, the AI was decreased, PI was increased and the rate of AI/PI decreased in gastric carcinoma. There was significant difference in them between the gastric cancer tissues and normal gastric mucosa in pericarcinoma in TNM stage Ⅱ to Ⅳ ( P <0.05). It was suggested that the decreased apoptotic cells and the increased proliferating cells were obviously related to the tumor genesis and tumor progression in gastric carcinoma. The AI, PI and the rate of AI/PI would become the prognostic factors in advanced gastric carcinoma.
摘要To study the relationship between p53 protein, proliferating cell nuclear antigen (PCNA) expression and benign or malignant gestational trophoblastic disease (MGTD). Methods: The histotomic sections of 48 patients with gestational trophoblastic disease and 24 patients of normal chorionic villi were stained using immunohistochemistry. The monoclonal antibodies were used to determine p53 protein and PCNA. Results: The frequency of p53 and PCNA positive expression were significantly different among the chorionic villi of normal pregnancy, hydratidiform mole (HM) and MGTD. But neither p53 nor PCNA has any relation with the clinical staging or metastasis of MGTD. Conclusion: Both P53 and PCNA are valuable in diagnosis of human gestational trophoblastic disease.
摘要Objective: To correlate the frequency of p53 mutations, bcl-2 expression and the proliferation status (proliferating cell nuclear antigen, PCNA) in patients with bladder cancer with cell proliferation, apoptosis and their clinico-pathologic ?ndings. Methods: Para?n-embedded sections from 39 super?cial (T1G1-G3) and 23 invasive (T2-T4a G3 N0M0) primary transitional cell carcinomas (TCC) in the bladder were investigated immunohistochemically for p53, bcl-2 and PCNA. The median follow-up was 37 months; 24 had recurrences. The proliferation index (PI) was expressed as a percentage of the PCNA-positive cells in the tumor cells. Apoptosis was detected by terminal deoxy-nucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and the apoptotic index (AI) was expressed as a percentage of the TUNEL- positive tumor cells. Results: P53 mutation was identi?ed in 50 patients (80.6%). The mutation was most common in tumors of grade 3 (91.3%) as compared to grade 2 (78.5%) and grade 1 (72.7%, P0.05). The PI ranged from 17.2% to 41.8% (median 22.4%) and the AI from 1.9% to 3.5% (median 2.9%) in bladder cancer. Statistical analyses revealed a close associations between PI, AI and tumor grade and stage of bladder cancer. Conclusion: P53 mutation correlates with invasion. P53 and PCNA overexpression may o?er valuable additional prognostic information in bladder tumors. With the progression of the tumor grade, cell proliferation may be accompanied by frequent apoptosis in bladder cancer, but the PI increased much more than the AI.
基金the Research Fund of Key Labortary for Advanced Technology in Environmental Protection of Jiangsu Province (No. AE201037)the Foundation for Talent Recruitment of Yancheng Institute of Technology (No. XKR2011007)the "973" Chinese National Key Fundamental Research and Development Program (No. G1999064701)
摘要After co-cultrured osteoblast with fl-TCP ceramics, the cellular proliferating, mineralization and osteocalcin expression were studied. MTT assay showed that fl-TCP ceramics had no affect on cellular proliferating. Laser scanning confocal detection showed that fl-TCP ceramics could increase the mineralization level of osteoblast. Furthermore, RT-PCR showed that fl-TCP could increase the expression level of osteocalcin. Those results indicate β-TCP ceramics had perfect biocompatibility and increased the mineralization of osteoblast to accelerate osteogenesis by means of affecting the expression of genes involving in osteogeneticprocess.
基金the National Key Basic Research and Development Program (red tide "973"program) of China under contract No. 2301CB409700 the National Natural Science Foundation of China under contract Nos 40232021,405211303 Ministry of Science and Technology of China under contract Nos 2005AA635240 and MEL0608.
摘要PCNA has been considered as a useful marker for the estimation of growth rates of marine phytoplankton at the species level. Since dinoflagellates are noted for having many prokaryotic features in that they are the only eukaryotes to have permanently condensed chromosomes as well as lacking histones and a nucleosome, the sensitivity to UVB radiation and the validity of PCNA as a maker of growth rate in dinoflagellate need to be evaluated. Prorocentrum donghaiense Lu was investigated to valuate the UVB sensitivity in relation to cellular and molecular aspects of PCNA as a growth indicator. The effects of UVB radiation on PCNA were studied using the methods of western blots technology and whole-cell immunoflurescence with one mono-antibody. UVB changed the cell morphology, halted the growth and increased the cell size, even caused cell death to a certain extent after treatment with UVB radiation in P. donghaiense. Compared with the control, treating the algal cultures in exponential phases with UVB radiation for 24 h caused chromatin release and increases in protein levels of PCNA.
基金This studywassupported by a grant from the NationalNatural Sciences Foundation ofChina(No. 39770 739)
摘要To explore a novel strategy for antisense gene therapy of cancer,the coding sequence of hum an proliferating cell nuclear antigen(PCNA) c DNA was reversely inserted into the eukaryotic vector p L XSN by molecular cloning techniques and transferred into bladder cancer EJcells with li- posome. The PCNA expression in transferred cells was dynamically detected by immunofluo- rescence and RT- PCR techniques. Changes of proliferation activities of cancer cells were assayed by MTT colorim etric and cloning formation m ethods.In the experiment,the antisense eukaryotic vector was successfully constructed and nam ed as p L APSN.After transfection with it for1- 7 days,PCNA protein and m RNA levels in cancer cells were blocked by16 .74 % - 84 .2 1% (P< 0 .0 5 ) and2 3.2 7% - 86 .15 % (P<0 .0 5 ) respectively.The proliferation activities of transferred cells were inhibited by 2 7.91% - 6 2 .0 7% (P<0 .0 1) ,with cloning formation abilities being de- creased by 5 0 .81% (P<0 .0 1) . Itwas concluded that the in vitro proliferation activities of cancer cells could be effectively inhibited by blocking PCNA expression with antisense technique,which could serve as an ideal strategy for gene therapy of bladder cancer.
基金This project was supported by a grant from Hubei Scien-tific and Technological Comm ittee (No. 96 2 9110 1)
摘要In order to study the effect of and mechanism of lysophosphatidylcholine (LysoPC) on proliferation of the calf thoracic aorta smooth muscle cells (ASMCs), the ASMCs were used to observe the effects of LysoPC induced endothelial cell conditioned medium on the DNA content and proliferating cell nuclear antigen (PCNA) expression in the calf thoracic ASMCs by flow cytometry and Western Blot technique. It was found that LysoPC induced endothelial cell conditioned medium could significantly promote PCNA expression of the calf ASMCs, induce the converting of ASMCs from G 0 /G 1 phase to S phase of DNA synthesis, and increase the tyrosine phosphorylation protein expression. Tyrosine protein kinase inhibitor (TPKi) RG50864 could obviously inhibit proliferation of LysoPC induced ASMCs in a dose dependence manner. The results indicated that the effect of LysoPC promoting the proliferation of ASMCs is partly evoked by endothelial cell derived growth factors such as PDGF and so on.
摘要AIM:To investigate the relationship between the mast cell density(MCD)and the context of clinicopathological parameters and expression of p185,estrogen receptor(ER),and proliferating cell nuclear antigen(PCNA)in gastric carcinoma.METHODS:Mast cell,p185,ER,and PCNA were detected using immunohistochemical S-P labeling method.Mast cell was counted in tissue of gastric carcinoma and regional lymph nodes respectively,and involved lymph nodes(ILN)were examined as usual.RESULTS:MCD was significantly related to both age and depth of penetration(x2=4.688,P21/0.03 mm2and MCD≤21/0.03 mm2in 100 patients;MCD in 1-6 ILN group patients was significantly higher than that in 7-15 ILN or>15 ILN group patients(u=6.881,8.055,P21/0.03 mm2and MCD≤21/0.03 mm2in 100 patients.CONCLUSION:Mast cell may have effect on inhibiting invasive growth of tumor,especially in the aged patients;The number of mast cells,in certain degree,may predicate the number of involved lymph nodes,which is valuable for assessment of prognosis;MCD was related to the expression of p185,ER,and PCNA in gastric carcinoma.It suggests that mast cell accumulation may inhibit the proliferation and the dissemination of the gastric carcinoma.INTRODUCTION Recently,many studies have reported on the association of mast cell with various tumorst.In several malignancies,mast cell has been found to correlate with growth,penetration and prognosis of tumor.Therefore,our study was undertaken to investigate the relationship between the mast cell density(MCD)and the context of clinicopathological parameters and expression of p 185,estrogen receptor(ER),and proliferating cell nuclear antigen(PCNA)in gastric carcinoma.
基金The Nature Science Foundation of Qingdao, China under contract No. 05-1-JC-87International Foundation for Science under contract No.AA/16180 awarded to Sui Zhenghong
摘要Harmful algal blooms (HABs) have been affecting negatively the shellfish and aquaculture industries around the world. Though a lot of efforts have been made to disclose the changes of environmental factors involved and their effects on the HABs events, the molecular mechanism of this process remains unclear. To address this problem, proliferating cell nuclear antigen gene (pcna) was isolated and characterized from Alexandrium catenella. It showed high homology to those of other dinoflagellates (89% and 91% homology to Pfiesteria piscicid and Pyrocystis lunula, respectively), and also 42%–43% homology to those of plant and animals. The expression level of pcna revealed by quantitative real time PCR was the lowest at the late lagging cell growth phase, increased to the highest at the late exponential phase, and then decreased at the stationary phase. Though the cell growth rate was also changing, no positive correlation between pcna expression level and cell growth rate was displayed throughout the whole cell growth stages (r 2 =0.024 6). However, the pcna expression level had the similar trend with the change of cell growth rate throughout the whole growing process, e.g., from increasing at the earlier cell growth stage to decreasing at the following stages, though slightly lagging to the latter.
基金supported by National Natural Science Foundation of China (Grant No.81622037 and 81672762)Beijing Municipal Natural Science Foundation (Grant No.5194023)Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five–year Plan (Grant No.CIT&TCD20190333)
摘要Non-proliferating cells efficiently generate adenosine 5’-triphosphate (ATP) through mitochondrial oxidative phosphorylation.By contrast, proliferating cells, including cancer cells, tend to rely on aerobic glycolysis, an inefficient way to generate energy, and this phenomenon is termed 'the Warburg effect'1,2.However, the advantage of the Warburg effect provided for proliferating cells has been unclear3.Here we propose that aerobic glycolysis may maintain proton homeostasis to benefit proliferating cells.
基金Supported by the National Natural Science Foundation of China(Nos.41976109,42276100)the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)。
摘要Ulva prolifera is the most common specie causative to green tide,and its growth is sensitive to temperature stress.However,the mechanisms of U.prolifera response to temperature stress remain elusive.In this study,high temperature(36℃)stimulus promoted the death of unformed cell wall protoplasts and delayed the division of formed cell wall protoplasts,while low-temperature(4℃)stimulus did not,suggesting that the mechanisms of the response of U.prolifera to high and low temperature stresses are different.Transcriptome results show that proliferation-related genes were differentially expressed under high and low-temperature stresses,especially the proliferating cell nuclear antigen(PCNA)and cyclins(CYCs).Subsequently,the interaction between PCNA and Cyclin A was confirmed by Co-immunoprecipitation,yeast two-hybrid,and so on.Furthermore,high-and low temperature stresses induced the expression of PCNA and Cyclin A in varying of degrees,and activated extracellular signal-regulated kinase(ERK)signal pathway.These results suggest,PCNA,Cyclin A,and ERK signal pathway played important roles in the resistance of U.prolifera to temperature stress.Interestingly,high-temperature stress induced an increase of miR-2916 in abundance,and exhibiting reverse expression of PCNA;and PCNA was target gene of miR-2916,suggesting that miR-2916 protected U.prolifera from high-temperature stress via post-transcriptionally regulation of PCNA.This study laid a foundation for understanding the function of PCNA and Cyclin A,moreover,it has a guiding significance to explore the mechanisms of the response to temperature stress from proliferation-related genes regulatory networks in U.prolifera.
摘要Objective: To study the relationship between proliferating cell nuclear antigen expression and its malignancy potential in colorectal carcinoma. Methods: Paraffin sections of 86 patients with advanced colorectal carcinoma were assessed by immunohistochemical study, using a mouse monoclonal antibody (pc-10, DAKO Co. USA) to check proliferating cell nuclear antigen (PCNA). To compare PCNA with conventional clinicopathologic factor, including p53 overexpression, tissue carcinoembnyonic antigen immunoreactivity pattern and flow cytometric DNA ploidy for assessing tumor malignancy potential. In addition, recurrence and survival of patients with advanced colorectal carcinoma after curative resection were analyzed in accordance with degree of PCNA expression. Results: PCNA-labeling index (PCNA-LI) increased significantly as the tumor stage advanced (p=0.0001). Strong correlations were observed between PCNA-LI and various pathologic parameters, including histologic differentiation (P=0.0027), lymphatic invasion (P=0.0001), vascular invasion (P=0.0001), lymph node metastasis (P=0.0001), and liver metastasis (P=0.0036). Mean PCNA-LI was also significantly higher in tumor with DNA aneuploidy (P=0.0006) and negative (P=0.01). Linear relationships were demonstrated between PCNA-LI and clinical outcomes; Recurrence rate was significantly greater in the group with higher than the mean PCNA-LI, who underwent curative resection (P<0.01), and three-year survival rates for curative cases with higher than the mean PCNA-LI were significantly poorer than those with lower than mean PCNA-LI (P<0.005). Conclusion: There were correlations between PCNA-LI and various pathologic parameters, PCNA-LI increased significantly as the tumor stage advanced in colorectal carcinoma, the rates of recurrence and death got higher as PCNA-LI increased after curative resection for colorectal carcinoma.
摘要AIM: To explore the feasibility of passage of bone- marrow-derived liver stem cells (BDLSCs) in culture systems that contain cholestatic serum.METHODS: Whole bone marrow cells of rats were purified with conditioning selection media that contained 50 mL/L cholestatic serum. The selected BDLSCs were grown in a proliferating culture system and a differentiating culture system. The culture systems contained factors that stimulated the proliferation and differentiation of BDLSCs. Each passage of the proliferated stem cells was subjected to flow cytometry to detect stem cell markers. The morphology and phenotypic markers of BDLSCs were characterized using immunohistochemistry, reverse transcription polymerase chain reaction (RT-PCR) and electron microscopy. The metabolic functions of differentiated cells were also determined by glycogen staining and urea assay.RESULTS: The conditioning selection medium isolated BDLSCs directly from cultured bone marrow cells. The selected BDLSCs could be proliferated for six passages and maintained stable markers in our proliferating system. When the culture system was changed to a differentiating system, hepatocyte-like colony-forming units (H-CFUs) were formed. H-CFUs expressed markers of embryonic hepatocytes (alpha-fetoprotein, albumin and cytokeratin 8/18), biliary cells (cytokeratin 19), hepatocyte functional proteins (transthyretin and cytochrome P450-261), and hepatocyte nuclear factors 1α and -3β). They also had glycogen storage and urea synthesis functions, two of the critical features of hepatocytes.CONCLUSION: BDLSCs can be selected directly from bone marrow cells, and pure BDLSCs can be proliferated for six passages. The differentiated cells have hepatocyte-like phenotypes and functions. BDLSCs represent a new method to provide a readily available alternate source of cells for clinical hepatocyte therapy.