AIM： Nitrative and oxidative DNA damage such as 8-nitroguanine and 8-oxo-7,8-dihydro-2＇-deoxyguanosine （8-oxodG） formation has been implicated in initiation and/ or promotion of inflammation-mediated carcinogenesi...AIM： Nitrative and oxidative DNA damage such as 8-nitroguanine and 8-oxo-7,8-dihydro-2＇-deoxyguanosine （8-oxodG） formation has been implicated in initiation and/ or promotion of inflammation-mediated carcinogenesis. The aim of this study is to clarify whether these DNA lesions participate in the progression of intrahepatic cholangiocarcinoma. METHODS： We investigated the relation of the formation of 8-nitroguanine and 8-oxodG and the expression of hypoxia-inducible factor-1α （HIF-1α） with tumor invasion in 37 patients with intra-hepatic cholangiocarcinoma. RESULTS： Immunohistochemical analyses revealed that 8-nitroguanine and 8-oxodG formation occurred to a much greater extent in cancerous tissues than in non-cancerous tissues. HIF-1α could be detected in cancerous tissues in all patients, suggesting low oxygen tension in the tumors. HIF-1α expression was correlated with inducible niltric oxide synthase （iNOS） expression （r = 0.369 and P = 0.025） and 8-oxodG formation （r = 0.398 and P = 0.015）. Double immunofluorescence study revealed that iNOS and HIF-1α co-localized in cancerous tissues. Notably, the formation of 8-oxodG was correlated significantly with lymphatic invasion （r = 0.386 and P = 0.018）. Moreover, 8- nitroguanine and 8-oxodG in non-cancerous tissues were associated significantly with neural invasion （P = 0.042 and P = 0.026, respectively）. These results suggest that reciprocal activation between HIF-1α and iNOS mediates persistent DNA damage, which induces tumor invasiveness via mutations, resulting in poor prognosis. CONCLUSION： The formation of 8-nitroguanine and 8-oxodG plays an important role in multiple steps of genetic changes leading to tumor progression, including invasiveness.展开更多
Tumorigenesis involves metabolic reprogramming and abnormal lipid metabolism,which is manifested by increased endogenous fat mobilization,hypertriglyceridemia,and increased fatty acid synthesis.Fatty acid synthase(FAS...Tumorigenesis involves metabolic reprogramming and abnormal lipid metabolism,which is manifested by increased endogenous fat mobilization,hypertriglyceridemia,and increased fatty acid synthesis.Fatty acid synthase(FASN)is a key enzyme for the de novo synthesis of fatty acids,and monoacylglycerol esterase(MGLL)is an important metabolic enzyme that converts triglycerides into free fatty acids.Both enzymes play an important role in lipid metabolism and are associated with tumor-related signaling pathways,the most common of which is the PI3K–AKT signaling pathway.They can also regulate the immune microenvironment,participate in epithelial–mesenchymal transition,and then regulate tumor invasion and metastasis.Current literature have shown that these two genes are abnormally expressed in many types of tumors and are highly correlated with tumor migration and invasion.This article introduces the structures and functions of FASN and MGLL,their relationship with abnormal lipid metabolism,and the mechanism of the regulation of tumor invasion and metastasis and reviews the research progress of the relationship of FASN and MGLL with tumor invasion and metastasis.展开更多
This paper is concerned with the parabolic-parabolic-elliptic system■in a bounded domainΩ?Rnwith a smooth boundary,where the parametersχ,ζ1,ζ2are positive constants and m≥1.Based on the coupled energy estimates,...This paper is concerned with the parabolic-parabolic-elliptic system■in a bounded domainΩ?Rnwith a smooth boundary,where the parametersχ,ζ1,ζ2are positive constants and m≥1.Based on the coupled energy estimates,the boundedness of the global classical solution is established in any dimensions(n≥1)provided that m>1.展开更多
BACKGROUND： Four tumor markers for hepatocellular carcinoma（HCC）, alpha-fetoprotein（AFP）, glypican-3（GPC3）, vascular endothelial growth factor（VEGF） and des-gammacarboxy prothrombin（DCP）, are closely associ...BACKGROUND： Four tumor markers for hepatocellular carcinoma（HCC）, alpha-fetoprotein（AFP）, glypican-3（GPC3）, vascular endothelial growth factor（VEGF） and des-gammacarboxy prothrombin（DCP）, are closely associated with tumor invasion and patient＇s survival. This study estimated the predictability of preoperative tumor marker levels along with pathological parameters on HCC recurrence after hepatectomy.METHODS： A total of 140 patients with HCC who underwent hepatectomy between January 2012 and August 2012 were enrolled. The demographics, clinical and follow-up data were collected and analyzed. The patients were divided into two groups： patients with macroscopic vascular invasion（Ma VI ＋） and those without Ma VI（Ma VI-）. The predictive value of tumor markers and clinical parameters were evaluated by univariate and multivariate analysis.RESULTS： In all patients, tumor size（〉8 cm） and Ma VI were closely related to HCC recurrence after hepatectomy. For Ma VI＋ patients, VEGF（〉900 pg/m L） was a significant predictor for recurrence（RR=2.421; 95% CI： 1.272-4.606; P=0.007）. The 1- and 2-year tumor-free survival rates for Ma VI＋ patients with VEGF ≤900 pg/m L versus for those with VEGF 〉900 pg/m L were 51.5% and 17.6% versus 19.0% and 4.8%（P〈0.001）. For Ma VI- patients, DCP 〉445 m Au/m L and tumor size 〉8 cm were two independent risk factors for tumor recurrence（RR=2.307, 95% CI： 1.132-4.703, P=0.021; RR=3.150, 95% CI： 1.392-7.127, P=0.006; respectively）. The 1- and 2-year tumor-free survival rates for the patients with DCP ≤445 m Au/m L and those with DCP 〉445 m Au/m L were 90.4% and 70.7% versus 73.2% and 50.5% respectively（P=0.048）. The 1-and 2-year tumor-free survival rates for the patients with tumor size ≤8 cm and 〉8 cm were 83.2% and 62.1% versus 50.0% and 30.0%, respectively（P=0.003）.CONCLUSIONS： The Ma VI＋ patients with VEGF ≤900 pg/m L had a relatively high tumor-free survival than those with VEGF 〉900 pg/m L. In the Ma VI- patients, DCP 〉445 m Au/m L and tumor size 〉8 cm were predictive factors for postoperative recurrence.展开更多
To observe the process of invasion, retina of rat was used as a model to substitute the inner limiting membrane of retina for the basement membrane. Retina invaded by esophageal carcinoma cells and B16 melanoma cells ...To observe the process of invasion, retina of rat was used as a model to substitute the inner limiting membrane of retina for the basement membrane. Retina invaded by esophageal carcinoma cells and B16 melanoma cells upon the inner limiting membrane was studied by scanning and transmission electron microscopy. The results showed that the inner limiting membrane was destroyed by both kinds of tumor cells. The process of destruction was followed by a series of transformations in the inner limiting membrane, i.e. folding, swelling, thickening, and granular change. The inner limiting membrane was dissolved focally as a result of transformation, and then tumor cells invaded the retina through these dissolved regions. It seems that, as a barrier, the inner limiting membrane plays a similar role as the basement membrane.展开更多
AIM： To investigate the influence of CO2-insufflation pressure on adhesion, invasion and metastatic potential of colon cancer cells based on adhesion molecules expression. METHODS： With an/n vitro artificial pneumop...AIM： To investigate the influence of CO2-insufflation pressure on adhesion, invasion and metastatic potential of colon cancer cells based on adhesion molecules expression. METHODS： With an/n vitro artificial pneumoperitoneum model, SW1116 human colon carcinoma cells were exposed to CO2-insufflation in 5 different pressure groups： 6 mmHg, 9 mmHg, 12 mmHg, 15 mmHg and control group, respectively for 1 h. Expression of E-cadherin, ICAM-I, CD44 and E-selectin was meas- ured at 0, 12, 24, 48 and 72 h after CO2-insufflation using flow cytometry. The adhesion and invasion capacity of SW1116 cells before and after exposure to CO2-insufflation was detected by cell adhesion/invasion assay in vitro. Each group of cells was injected intraperitoneally into 16 BALB/C mice. The number of visible abdominal cavity tumor nodules, visceral metas-tases and survival of the mice were recorded in each group. RESULTS： The expression of E-cadherin, ICAM-1, CD44 and E-selectin in SWl116 cells were changed significantly following exposure to CO2 insufflation at different pressures （P 〈 0.05）. The expression of E-cadherin, CD44 and ICAM-1 decreased with increasing CO2-insufflation pressure. The adhesive/ invasive cells also decreased gradually with increasing pressure as determined by the adhesion/invasion assay. In animal experiments, the number of abdominal cavity tumor nodules in the 15 mmHg group was also significantly lower than that in the 6 mmHg group （29.7± 9.91 vs 41.7±14.90, P = 0.046）. However, the survival in each group was not statistically different. CONCLUSION： CO2-insufflation induced a temporary change in the adhesion and invasion capacity of cancer cells in vitro. Higher CO2-insufflation pressure inhibited adhesion, invasion and metastatic potential in vitro and in vivo, which was associated with reduced expression of adhesion molecules.展开更多
In order to investigate the relationship between the extent of tumor invasion and the tumor size, axillary lymph nodes metastasis, Her-2 gene overexpression, and histologic grading in breast invasive ductal carcinoma ...In order to investigate the relationship between the extent of tumor invasion and the tumor size, axillary lymph nodes metastasis, Her-2 gene overexpression, and histologic grading in breast invasive ductal carcinoma as well as the optimal extent of excision during the breast-serving surgery, the clinical data of 104 patients with breast invasive ductal carcinoma who had received modified radical mastectomy were analyzed. The correlation analysis on invasive extent, which was evaluated by serial sections at an interval of 0.5 cm from 4 different directions taking the focus as the centre, and the tumor size, axillary lymph nodes metastasis, Her-2 gene overexpression, and his- tologic grading was processed. There was a significant correlation between invasive extent and tumor size （r=-0.766, P〈0.01）, and lymph nodes metastases 0=0.574, P〈0.01）, but there was no significant correlation between invasive extent and Her-2 expression （r=-0.106, P〉0.05）, and histologic grading （r=-0.228, P〉0.05）. The 100% negative rate of infiltration in patients without nipple discharge with tumor size 〈2, 2-3 and 〉3 cm was obtained at 1.5, 2.0 and 2.5 cm away from the tumor respectively. It is concluded that the performance of breast-serving surgery in patients with breast invasive ductal carcinoma should be evaluated by tumor size in combination with axillary lymph nodes involvement to decide the possibility of breast-serving and the secure excision extent.展开更多
To observe the inhibitory effects of an antisense u-PAR vector on invasion of highly invasive PC-3M cell subclones, the effects of the antisense u-PAR on activity of MMP-9 in those highly invasive cell subclones were ...To observe the inhibitory effects of an antisense u-PAR vector on invasion of highly invasive PC-3M cell subclones, the effects of the antisense u-PAR on activity of MMP-9 in those highly invasive cell subclones were detected by a quantitative RT-PCR and zymography. The monolayer invasion assay and colony formation assay in soft agar were used. And tumorigenesis rate and invasions by the cell subclones with or without the antisense u-PAR were observed in nude mice. It was found that in vitro growth of highly invasive PC-3M cell subclones transfected with the antisense u-PAR was declined, and the ability of anchorage-independent growth of those cell subclones was found decreased sharply, with the inhibiting rate becoming 79%and 60% , respectively. Although the anti-sense u-PAR didn't change MMP-9 gene transcription, they could inhibit the activation of MMP-9 of highly invasive PC-3M cell subclones. Moreover, the tumorigenesis rate of the cell subclones with the antisense u-PAR decreased and the growth of a neoplasm also slowed down. The t tests showed the difference between experimental and control groups was statistically significant (P<0.01). The anti-sense u-PAR vector could not only inhibit the invasion ability of highly invasive PC-3M cell subclones in vitro but also restrain the growth of those cell subclones in vivo.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 staging to improve the clinical management of patients with this disease.展开更多
Glioma is one of the lethal central nervous system tumors.The infiltrative and invasive growth nature makes it difficult to identify the boundary between glioma and the normal tissues,resulting in inevitable recurrenc...Glioma is one of the lethal central nervous system tumors.The infiltrative and invasive growth nature makes it difficult to identify the boundary between glioma and the normal tissues,resulting in inevitable recurrence after surgery operation.Gliomas do not metastasize,so to prevent the residual tumor from proliferating or invading is a key challenge.Previous report indicated that hypotaurine could facilitate glioma invasion and suppress demethylases’activities.Using a hypotaurine synthesis deficient U251 cell line,we proved that the cells invasion ability was impaired.Gene expression profile analysis exhibited that knocking down one of the key enzymes of hypotaurine synthesis,2-aminoethanethiol dioxygenase(ADO),significantly affected the extracellular matrix-receptor process.Of that process,Wnt5a expression was severely upregulated by decreased intracellular ADO expression.Cells cultured at the presence of hypotaurine showed a decrease in intracellular Wnt5a protein and mRNA levels.This phenotype was due to hypermethylation of Wnt5a promoter,which was most likely the result of hypotaurine’s inhibiting demethylases activities.Collectively,this study demonstrated that hypotaurine synthesis deficient U251 cells were prone to epigenetic modification and Wnt5a seemed to be a tumor suppressor under that circumstance.This tumor suppression effect is warranted to be reevaluated in real tumor samples and the relevant evidence might contribute to develop new glioma interference strategies.展开更多
Cancer is a predominant culprit behind worldwide death and accounts for up to 10 million deaths every year.Chemotherapy is the primary therapeutic method employed for cancer in clinical settings and is essential in co...Cancer is a predominant culprit behind worldwide death and accounts for up to 10 million deaths every year.Chemotherapy is the primary therapeutic method employed for cancer in clinical settings and is essential in controlling tumor progression.Despite the advances in this field,tumor invasion and metastasis during treatment remain a significant cause of treatment failure.Nevertheless,the underlying mechanisms involving such a disappointing phenomenon are still not fully elucidated.Vinorelbine(VNB)extends the lifespan of many cancer patients in the clinic as an emerging chemotherapy drug approved by Food and Drug Administration(FDA).However,VNB-induced tumor metastasis is still an intractable problem,which may be closely related to the abnormal oxidative stress generated during VNB-mediated treatment.Hence,the study aims to construct a reductive nanosystem loaded with VNB,called VNB-VNP,to improve cancer cure rates and reduce tumor metastasis.With the reductive component vitamin E,VNB-VNP can effectively reduce oxidative stress and significantly outperform free VNB in preventing tumor progression.The transcriptome analysis shows that VNB-VNP can alleviate the over-expression of ectonucleotide pyrophosphatase/phosphodiesterase 2(ENPP2),which may be the main reason why VNB-VNP can inhibit tumor invasion and metastasis.Overall,the research designs a new platform for VNB treatment,which demonstrates promising efficacy in inhibiting neoplastic progression and identifies a new mechanism associated with VNB-induced tumor metastasis,which may offer several valuable references for enhancing chemotherapy efficacy in clinical anti-tumor therapy.展开更多
OBJECTIVE To investigate the expression of the high mobility group boxl（HMGB1） in human cervical squamous epithelial carcinoma （CSEC） and to explore the relationship of HMGB1 expression to the differentiation degr...OBJECTIVE To investigate the expression of the high mobility group boxl（HMGB1） in human cervical squamous epithelial carcinoma （CSEC） and to explore the relationship of HMGB1 expression to the differentiation degree, size, invasion and metastasis of CSEC. METHODS Immunohistochemical staining of tissue microarrays and Western blot analysis were conducted to detect the expression of HMGB1 in the following tissue samples： 30 carcinoma in situ, 90 invasive CSEC without metastasis, 30 invasive CSEC with metastasis, 30 cases of normal cervical squamous epithelia. RESULTS The positive-expression rate of HMGB1 was 58.7% （88/150） in CSEC, showing a significant difference compared to normal cervical squamous epithelia. The expression of HMGB1 was correlated with tumor size, invasion and metastasis of CSEC （respectively, P〈0.01）, but had no relationship with the degree of differentiation （P〉0.05）. CONCLUSION The over-expression of HMGB1 in CSEC might be a useful parameter as an indication of tumor invasion, metastasis, prognosis and overall biological behavior of human CSEC, as well as a noval target site for gene therapy.展开更多
Objective: To select a target molecule associated with invasive potential in PC-3M cell. Methods: Cell subclones were isolated from PC-3M cell line with the method of limited dilution and their invasive ability charac...Objective: To select a target molecule associated with invasive potential in PC-3M cell. Methods: Cell subclones were isolated from PC-3M cell line with the method of limited dilution and their invasive ability characterized by monolayer invasion assay. The expression of u-PAR in the cell subclones at mRNA and protein levels was assayed respectively by non-competitive quantitative RT-PCR and immunohistochemical assay. Results: The expression level of u-PAR in highly invasive cell subclones was higher than that of lower invasive subclones. Conclusion: The higher expression level of u-PAR is associated with the relative strong invasive ability of PC-3M subclones. It is indicated that the u-PAR might be a promising target molecule for inhibiting invasion of highly invasive PC-3M cell subclones.展开更多
It is essential in treating rectal cancer to have adequate preoperative imaging,as accurate staging can influence the management strategy,type of resection,and candidacy for neoadjuvant therapy.In the last twenty year...It is essential in treating rectal cancer to have adequate preoperative imaging,as accurate staging can influence the management strategy,type of resection,and candidacy for neoadjuvant therapy.In the last twenty years,endorectal ultrasound(ERUS) has become the primary method for locoregional staging of rectal cancer.ERUS is the most accurate modality for assessing local depth of invasion of rectal carcinoma into the rectal wall layers(T stage) .Lower accuracy for T2 tumors is commonly reported,which could lead to sonographic overstaging of T3 tumors following preoperative therapy.Unfortunately,ERUS is not as good for predicting nodal metastases as it is for tumor depth,which could be related to the unclear definition of nodal metastases.The use of multiple criteria might improve accuracy.Failure to evaluate nodal status could lead to inadequate surgical resection.ERUS can accurately distinguish early cancers from advanced ones,with a high detection rate of residual carcinoma in the rectal wall.ERUS is also useful for detection of local recurrence at the anastomosis site,which might require fine-needle aspiration of the tissue.Overstaging is more frequent than understaging,mostly due to inflammatory changes.Limitations of ERUS are operator and experiencedependency,limited tolerance of patients,and limited range of depth of the transducer.The ERUS technique requires a learning curve for orientation and identification of images and planes.With sufficient time and effort,quality and accuracy of the ERUS procedure could be improved.展开更多
AIM:To investigate the expression profile of miRNA in esophageal squamous cell carcinoma(ESCC).METHODS:The expression profile of miRNA in ESCC tissues was analyzed by miRNA microarray.The expression levels of miR-143 ...AIM:To investigate the expression profile of miRNA in esophageal squamous cell carcinoma(ESCC).METHODS:The expression profile of miRNA in ESCC tissues was analyzed by miRNA microarray.The expression levels of miR-143 and miR-145 in 86 ESCC patients were determined by real-time polymerase chain reaction(PCR) using TaqMan assay.The mobility effect was estimated by wound-healing using esophageal carcinoma cells transfected with miRNA expression plasmids.RESULTS:A set of miRNAs was found to be deregulated in the ESCC tissues,and the expression levels of miR-143 and-145 were significantly decreased in most of the ESCC tissues examined.Both miR-143 and miR-145 expression correlated with tumor invasion depth.The transfection of human esophageal carcinoma cells with miR-143 and miR-145 expression plasmids resulted in a greater inhibition of cell mobility,however,the protein level of the previously reported target of miR-145,FSCN1,did not show any significant downregulation.CONCLUSION:These findings suggest that the deregulation of miRNAs plays an important role in the progression of ESCC.Both miR-143 and miR-145 might act as anti-oncomirs common to ESCC.展开更多
AIM: To analyze the predictive factors for lymph node metastasis (LNM) in early gastric cancer (EGC). METHODS: Data from patients surgically treated for gastric cancers between January 1994 and December 2007 were retr...AIM: To analyze the predictive factors for lymph node metastasis (LNM) in early gastric cancer (EGC). METHODS: Data from patients surgically treated for gastric cancers between January 1994 and December 2007 were retrospectively collected. Clinicopathological factors were analyzed to identify predictive factors for LNM. RESULTS: Of the 2936 patients who underwent gas-trectomy and lymph node dissection, 556 were diag-nosed with EGC and included in this study. Among these, 4.1% of patients had mucosal tumors (T1a) with LNM while 24.3% of patients had submucosal tumorswith LNM. Univariate analysis found that female gen-der, tumors ≥ 2 cm, tumor invasion to the submucosa, vascular and lymphatic involvement were significantly associated with a higher rate of LNM. On multivariate analysis, tumor size, lymphatic involvement, and tumor with submucosal invasion were associated with LNM. CONCLUSION: Tumor with submucosal invasion, size ≥ 2 cm, and presence of lymphatic involvement are predictive factors for LNM in EGC.展开更多
Summary： This study aimed to establish a new in vitro three-dimensional （3D） cell culture and use quantum dots （QDs） molecular imaging to examine the invasive behaviors of hepatocellular carcinoma （HCC） cells. ...Summary： This study aimed to establish a new in vitro three-dimensional （3D） cell culture and use quantum dots （QDs） molecular imaging to examine the invasive behaviors of hepatocellular carcinoma （HCC） cells. Each well of the 24-well cell culture plate was cover-slipped. Matrigel diluted with se- rum-free DMEM was added and HCCLM9 cells were cultured on the Matrigel. The cell morphological and cell growth characteristics were observed by inverted microscopy and laser confocal microscopy at different culture time. Cell invasive features were monitored by QDs-based real-time molecular imaging techniques. The results showed that on this 3D cell culture platform, HCCLM9 cells exhibited typical multi-step invasive behaviors, including reversion of cell senescence, active focal proliferation and dominant clones invasion. During the process, cells under 3D cell culture showed biological behaviors of spatio-temporal characteristics. Cells first merged on the surface of matrix, then gradually infiltrated and migrated into deep part of matrix, presenting polygonal morphology with stretched protrusions, forming tubular, annular and even network structure, which suggested that HCC cells have the morpho- logical basis for vasculogenic mimicry. In addition, small cell clones with their edges well-circumscribed in early stage, progressed into a large irregular clone with ill-defined edge, while the other cells developed invadopodia. And QDs probing showed MT1-MMP was strongly expressed in the invadopodia. These findings indicate that a novel 3D cell culture platform has been successfully estab- lished, which can mimic the in vivo tumor microenvironment, and when combined with QDs-based mo- lecular imaging, it can help to better investigate the invasive behaviors of HCC cells.展开更多
BACKGROUND: Hilar cholangiocarcinoma is associated with low resectability and poor survival. The aim of this study was to evaluate the roles of matrix metalloproteinases- 2 (MMP-2 ) and its tissue inhibitor of metallo...BACKGROUND: Hilar cholangiocarcinoma is associated with low resectability and poor survival. The aim of this study was to evaluate the roles of matrix metalloproteinases- 2 (MMP-2 ) and its tissue inhibitor of metalloproteinase-2 (TIMP-2) in tumor invasion or as a prognostic factor in patients with human hilar cholangiocarcinoma. METHODS: The expressions of MMP-2 and TIMP-2 were investigated in patients. Paraffinized tissue sections ob- tained from 50 patients with human hilar cholangiocarcino- ma were analysed. The expressions of MMP-2 and TIMP-2 were examined immunohistochemically. Image analysis with image-pro plus analysis software was used to semi- quantitatively determine the ratio of MMP-2 to TIMP-2. RESULTS: The expression levels of MMP-2 and TIMP-2 were strongly associated with tumor hepatic invasion in pa- tients with hilar cholangiocarcinoma. Significant diffe- rences in the ratio of MMP-2 to TIMP-2 between some pathologic factors were observed in patients with hilar cholangiocarcinoma. CONCLUSIONS: MMP-2 plays an essential role in tumor invasion and metastasis,while TIMP-2 is shown to strongly inhibit cancer invasion and metastasis. The ratio of MMP-2 to TIMP-2 may be a prognostic indicator for patients with hilar cholangiocarcinoma.展开更多
To evaluate the specific inhibition of antisense u PAR on the u PAR expressions in highly invasive cell subclones and to determine its blocking function in the invasion by those cells, a cDNA fragment of u PAR ob...To evaluate the specific inhibition of antisense u PAR on the u PAR expressions in highly invasive cell subclones and to determine its blocking function in the invasion by those cells, a cDNA fragment of u PAR obtained by RT PCR was inserted into a plasmid vector named pcDNA3 in antisense orientation. Then the antisense u PAR recombinant was transfected into highly invasive cell subclones. The u PAR expression in neo resistant cells was examined by RT PCR and immunohistochemical assay. Compared to the control cells, the content of mRNA and protein of u PAR in transfected cells decreased sharply, and the rate of inhibition was 53 % and 73 %, respectively, indicating that an antisense u PAR might have played a specific inhibitory role in its expression in the cells, which may provide a good cell model for making further investigation of the inhibitory effects of the antisense u PAR on invasion in highly invasive cell subclones of human prostate carcinoma.展开更多
Background: Recurrence after resection of hepatocellu-lar carcinoma(HCC) is a major obstacle to improveprognosis. Therefore, further improvement of long-term survival may depend on prevention and treat-ment of the rec...Background: Recurrence after resection of hepatocellu-lar carcinoma(HCC) is a major obstacle to improveprognosis. Therefore, further improvement of long-term survival may depend on prevention and treat-ment of the recurrent tumor.Objective: To evaluate the progress of surgery forHCC, the risk factors for recurrence, and clinical andbasic studies on the prevention and management of re-currence and metastasis after resection of HCC.Data sources: A review of currently available data inthe mentioned areas.Data synthesis: Encouraging changes in the prognosticpattern were observed when the primary liver cancer(PLC) data of 1958-1967 (n=118), 1968-1977 (n=356), 1978-1987(n=715) and 1988-1997 (n=2038)were compared. The 5-year survival was 2.8%, 7.3%,27.1% and 52.5%, respectively, and the 10-yearsurvival 2.8%, 4.3%, 19.8% and 39.9%, respective-ly. Risk factors for recurrence included symptomaticpatient, high γ-glutamyl-peptidase (γ-PGT), largetumor size, portal vein embolus, advanced tumorstage, etc. Active hepatitis activity in the nontumorousliver and perioperative transfusion enhanced the re-currence. Molecular research into the invasiveness ofHCC identified some factors positively related to inva-siveness: p16 and p53 mutation, H-ras, c-cerbB2,mdm2, transforming growth factor (TGF), epidermalgrowth factor receptor (EGF-R), matrix metallopro-teinase-2 (MMP-2), urokinasetype plasminogen acti-vator (uPA), its receptor (uPA-R) and inhibitor(PAI-1), intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF),platelet-derived endothelial cell growth factor (PD-ECGF), and basic fibroblast growth factor (bFGF).In contrast, some factors were negatively related toHCC invasiveness: nm23-H1, Kai-1, tissue inhibitor ofmetalloproteinase-2 (TIMP-2), integrin 5, and E-cadherin. Re-resection of subclinical recurrence yield-ed a 5-year survival of 56.0% calculated from the firstresection (n=202) .Postoperative transarterialchemoembolization (TACE, n=103), hepatic arterycannulation during operation (n=105), postoperativebiotherapy (n=49), and cryohepatectomy (cryosurgeryfollowed by immediate resection of the frozen tumor,n=84) might decrease the recurrence rate, and the3-year recurrence rate was 7.6%, 18.0%, 11.1%, and30.1%, respectively. Minimal intraoperative blood lossand transfusion could reduce postoperative recurrence,although the exact mechanism remains to be elucidat-ed.Conlusions: HCC invasiveness is the major topic to bestudied, particularly in the molecular level. Anti-an-giogenesis, biotherapy, novel approach based on molec-ular findings, and multidisciplinary interventions mightalso be important for HCC.展开更多
基金Supported by the Khon Kaen University Research Fund in Thailand Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan
文摘AIM： Nitrative and oxidative DNA damage such as 8-nitroguanine and 8-oxo-7,8-dihydro-2＇-deoxyguanosine （8-oxodG） formation has been implicated in initiation and/ or promotion of inflammation-mediated carcinogenesis. The aim of this study is to clarify whether these DNA lesions participate in the progression of intrahepatic cholangiocarcinoma. METHODS： We investigated the relation of the formation of 8-nitroguanine and 8-oxodG and the expression of hypoxia-inducible factor-1α （HIF-1α） with tumor invasion in 37 patients with intra-hepatic cholangiocarcinoma. RESULTS： Immunohistochemical analyses revealed that 8-nitroguanine and 8-oxodG formation occurred to a much greater extent in cancerous tissues than in non-cancerous tissues. HIF-1α could be detected in cancerous tissues in all patients, suggesting low oxygen tension in the tumors. HIF-1α expression was correlated with inducible niltric oxide synthase （iNOS） expression （r = 0.369 and P = 0.025） and 8-oxodG formation （r = 0.398 and P = 0.015）. Double immunofluorescence study revealed that iNOS and HIF-1α co-localized in cancerous tissues. Notably, the formation of 8-oxodG was correlated significantly with lymphatic invasion （r = 0.386 and P = 0.018）. Moreover, 8- nitroguanine and 8-oxodG in non-cancerous tissues were associated significantly with neural invasion （P = 0.042 and P = 0.026, respectively）. These results suggest that reciprocal activation between HIF-1α and iNOS mediates persistent DNA damage, which induces tumor invasiveness via mutations, resulting in poor prognosis. CONCLUSION： The formation of 8-nitroguanine and 8-oxodG plays an important role in multiple steps of genetic changes leading to tumor progression, including invasiveness.
基金This work was supported by grants from the National Natural Science Foundation of China(Nos.81672637 and 81872164).
文摘Tumorigenesis involves metabolic reprogramming and abnormal lipid metabolism,which is manifested by increased endogenous fat mobilization,hypertriglyceridemia,and increased fatty acid synthesis.Fatty acid synthase(FASN)is a key enzyme for the de novo synthesis of fatty acids,and monoacylglycerol esterase(MGLL)is an important metabolic enzyme that converts triglycerides into free fatty acids.Both enzymes play an important role in lipid metabolism and are associated with tumor-related signaling pathways,the most common of which is the PI3K–AKT signaling pathway.They can also regulate the immune microenvironment,participate in epithelial–mesenchymal transition,and then regulate tumor invasion and metastasis.Current literature have shown that these two genes are abnormally expressed in many types of tumors and are highly correlated with tumor migration and invasion.This article introduces the structures and functions of FASN and MGLL,their relationship with abnormal lipid metabolism,and the mechanism of the regulation of tumor invasion and metastasis and reviews the research progress of the relationship of FASN and MGLL with tumor invasion and metastasis.
基金supported by the NSF of China(11871226)Guangdong Basic and Applied Basic Research Foundation(2020A1515010140 and 2022B1515020032)Guangzhou Science and Technology Program(202002030363)。
文摘This paper is concerned with the parabolic-parabolic-elliptic system■in a bounded domainΩ?Rnwith a smooth boundary,where the parametersχ,ζ1,ζ2are positive constants and m≥1.Based on the coupled energy estimates,the boundedness of the global classical solution is established in any dimensions(n≥1)provided that m>1.
基金supported by grants from the National High Technology Research and Development Program of China(863 Program 2012AA020204)the"New-Century 151 Talent Program"of Zhejiang Province(the 1st level)+1 种基金Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health TalentsPublic Technology Research Projects of Science and Technology Department of Zhejiang,China(2014C37061)
文摘BACKGROUND： Four tumor markers for hepatocellular carcinoma（HCC）, alpha-fetoprotein（AFP）, glypican-3（GPC3）, vascular endothelial growth factor（VEGF） and des-gammacarboxy prothrombin（DCP）, are closely associated with tumor invasion and patient＇s survival. This study estimated the predictability of preoperative tumor marker levels along with pathological parameters on HCC recurrence after hepatectomy.METHODS： A total of 140 patients with HCC who underwent hepatectomy between January 2012 and August 2012 were enrolled. The demographics, clinical and follow-up data were collected and analyzed. The patients were divided into two groups： patients with macroscopic vascular invasion（Ma VI ＋） and those without Ma VI（Ma VI-）. The predictive value of tumor markers and clinical parameters were evaluated by univariate and multivariate analysis.RESULTS： In all patients, tumor size（〉8 cm） and Ma VI were closely related to HCC recurrence after hepatectomy. For Ma VI＋ patients, VEGF（〉900 pg/m L） was a significant predictor for recurrence（RR=2.421; 95% CI： 1.272-4.606; P=0.007）. The 1- and 2-year tumor-free survival rates for Ma VI＋ patients with VEGF ≤900 pg/m L versus for those with VEGF 〉900 pg/m L were 51.5% and 17.6% versus 19.0% and 4.8%（P〈0.001）. For Ma VI- patients, DCP 〉445 m Au/m L and tumor size 〉8 cm were two independent risk factors for tumor recurrence（RR=2.307, 95% CI： 1.132-4.703, P=0.021; RR=3.150, 95% CI： 1.392-7.127, P=0.006; respectively）. The 1- and 2-year tumor-free survival rates for the patients with DCP ≤445 m Au/m L and those with DCP 〉445 m Au/m L were 90.4% and 70.7% versus 73.2% and 50.5% respectively（P=0.048）. The 1-and 2-year tumor-free survival rates for the patients with tumor size ≤8 cm and 〉8 cm were 83.2% and 62.1% versus 50.0% and 30.0%, respectively（P=0.003）.CONCLUSIONS： The Ma VI＋ patients with VEGF ≤900 pg/m L had a relatively high tumor-free survival than those with VEGF 〉900 pg/m L. In the Ma VI- patients, DCP 〉445 m Au/m L and tumor size 〉8 cm were predictive factors for postoperative recurrence.
文摘To observe the process of invasion, retina of rat was used as a model to substitute the inner limiting membrane of retina for the basement membrane. Retina invaded by esophageal carcinoma cells and B16 melanoma cells upon the inner limiting membrane was studied by scanning and transmission electron microscopy. The results showed that the inner limiting membrane was destroyed by both kinds of tumor cells. The process of destruction was followed by a series of transformations in the inner limiting membrane, i.e. folding, swelling, thickening, and granular change. The inner limiting membrane was dissolved focally as a result of transformation, and then tumor cells invaded the retina through these dissolved regions. It seems that, as a barrier, the inner limiting membrane plays a similar role as the basement membrane.
文摘AIM： To investigate the influence of CO2-insufflation pressure on adhesion, invasion and metastatic potential of colon cancer cells based on adhesion molecules expression. METHODS： With an/n vitro artificial pneumoperitoneum model, SW1116 human colon carcinoma cells were exposed to CO2-insufflation in 5 different pressure groups： 6 mmHg, 9 mmHg, 12 mmHg, 15 mmHg and control group, respectively for 1 h. Expression of E-cadherin, ICAM-I, CD44 and E-selectin was meas- ured at 0, 12, 24, 48 and 72 h after CO2-insufflation using flow cytometry. The adhesion and invasion capacity of SW1116 cells before and after exposure to CO2-insufflation was detected by cell adhesion/invasion assay in vitro. Each group of cells was injected intraperitoneally into 16 BALB/C mice. The number of visible abdominal cavity tumor nodules, visceral metas-tases and survival of the mice were recorded in each group. RESULTS： The expression of E-cadherin, ICAM-1, CD44 and E-selectin in SWl116 cells were changed significantly following exposure to CO2 insufflation at different pressures （P 〈 0.05）. The expression of E-cadherin, CD44 and ICAM-1 decreased with increasing CO2-insufflation pressure. The adhesive/ invasive cells also decreased gradually with increasing pressure as determined by the adhesion/invasion assay. In animal experiments, the number of abdominal cavity tumor nodules in the 15 mmHg group was also significantly lower than that in the 6 mmHg group （29.7± 9.91 vs 41.7±14.90, P = 0.046）. However, the survival in each group was not statistically different. CONCLUSION： CO2-insufflation induced a temporary change in the adhesion and invasion capacity of cancer cells in vitro. Higher CO2-insufflation pressure inhibited adhesion, invasion and metastatic potential in vitro and in vivo, which was associated with reduced expression of adhesion molecules.
文摘In order to investigate the relationship between the extent of tumor invasion and the tumor size, axillary lymph nodes metastasis, Her-2 gene overexpression, and histologic grading in breast invasive ductal carcinoma as well as the optimal extent of excision during the breast-serving surgery, the clinical data of 104 patients with breast invasive ductal carcinoma who had received modified radical mastectomy were analyzed. The correlation analysis on invasive extent, which was evaluated by serial sections at an interval of 0.5 cm from 4 different directions taking the focus as the centre, and the tumor size, axillary lymph nodes metastasis, Her-2 gene overexpression, and his- tologic grading was processed. There was a significant correlation between invasive extent and tumor size （r=-0.766, P〈0.01）, and lymph nodes metastases 0=0.574, P〈0.01）, but there was no significant correlation between invasive extent and Her-2 expression （r=-0.106, P〉0.05）, and histologic grading （r=-0.228, P〉0.05）. The 100% negative rate of infiltration in patients without nipple discharge with tumor size 〈2, 2-3 and 〉3 cm was obtained at 1.5, 2.0 and 2.5 cm away from the tumor respectively. It is concluded that the performance of breast-serving surgery in patients with breast invasive ductal carcinoma should be evaluated by tumor size in combination with axillary lymph nodes involvement to decide the possibility of breast-serving and the secure excision extent.
文摘To observe the inhibitory effects of an antisense u-PAR vector on invasion of highly invasive PC-3M cell subclones, the effects of the antisense u-PAR on activity of MMP-9 in those highly invasive cell subclones were detected by a quantitative RT-PCR and zymography. The monolayer invasion assay and colony formation assay in soft agar were used. And tumorigenesis rate and invasions by the cell subclones with or without the antisense u-PAR were observed in nude mice. It was found that in vitro growth of highly invasive PC-3M cell subclones transfected with the antisense u-PAR was declined, and the ability of anchorage-independent growth of those cell subclones was found decreased sharply, with the inhibiting rate becoming 79%and 60% , respectively. Although the anti-sense u-PAR didn't change MMP-9 gene transcription, they could inhibit the activation of MMP-9 of highly invasive PC-3M cell subclones. Moreover, the tumorigenesis rate of the cell subclones with the antisense u-PAR decreased and the growth of a neoplasm also slowed down. The t tests showed the difference between experimental and control groups was statistically significant (P<0.01). The anti-sense u-PAR vector could not only inhibit the invasion ability of highly invasive PC-3M cell subclones in vitro but also restrain the growth of those cell subclones in vivo.
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 staging to improve the clinical management of patients with this disease.
基金supported by New and Old Energy Conversion Project of Jining City(2017ZDGH031)Guiding funds for the development of local science and technology by the Central government(2017106014)Natural Science Foundation of Liaoning Province(L2015317).
文摘Glioma is one of the lethal central nervous system tumors.The infiltrative and invasive growth nature makes it difficult to identify the boundary between glioma and the normal tissues,resulting in inevitable recurrence after surgery operation.Gliomas do not metastasize,so to prevent the residual tumor from proliferating or invading is a key challenge.Previous report indicated that hypotaurine could facilitate glioma invasion and suppress demethylases’activities.Using a hypotaurine synthesis deficient U251 cell line,we proved that the cells invasion ability was impaired.Gene expression profile analysis exhibited that knocking down one of the key enzymes of hypotaurine synthesis,2-aminoethanethiol dioxygenase(ADO),significantly affected the extracellular matrix-receptor process.Of that process,Wnt5a expression was severely upregulated by decreased intracellular ADO expression.Cells cultured at the presence of hypotaurine showed a decrease in intracellular Wnt5a protein and mRNA levels.This phenotype was due to hypermethylation of Wnt5a promoter,which was most likely the result of hypotaurine’s inhibiting demethylases activities.Collectively,this study demonstrated that hypotaurine synthesis deficient U251 cells were prone to epigenetic modification and Wnt5a seemed to be a tumor suppressor under that circumstance.This tumor suppression effect is warranted to be reevaluated in real tumor samples and the relevant evidence might contribute to develop new glioma interference strategies.
基金supported by the National Natural Science Foundation of China(No.81973246)Public Welfare Project of Zhejiang Natural Science Foundation(No.GF22H308848).
文摘Cancer is a predominant culprit behind worldwide death and accounts for up to 10 million deaths every year.Chemotherapy is the primary therapeutic method employed for cancer in clinical settings and is essential in controlling tumor progression.Despite the advances in this field,tumor invasion and metastasis during treatment remain a significant cause of treatment failure.Nevertheless,the underlying mechanisms involving such a disappointing phenomenon are still not fully elucidated.Vinorelbine(VNB)extends the lifespan of many cancer patients in the clinic as an emerging chemotherapy drug approved by Food and Drug Administration(FDA).However,VNB-induced tumor metastasis is still an intractable problem,which may be closely related to the abnormal oxidative stress generated during VNB-mediated treatment.Hence,the study aims to construct a reductive nanosystem loaded with VNB,called VNB-VNP,to improve cancer cure rates and reduce tumor metastasis.With the reductive component vitamin E,VNB-VNP can effectively reduce oxidative stress and significantly outperform free VNB in preventing tumor progression.The transcriptome analysis shows that VNB-VNP can alleviate the over-expression of ectonucleotide pyrophosphatase/phosphodiesterase 2(ENPP2),which may be the main reason why VNB-VNP can inhibit tumor invasion and metastasis.Overall,the research designs a new platform for VNB treatment,which demonstrates promising efficacy in inhibiting neoplastic progression and identifies a new mechanism associated with VNB-induced tumor metastasis,which may offer several valuable references for enhancing chemotherapy efficacy in clinical anti-tumor therapy.
文摘OBJECTIVE To investigate the expression of the high mobility group boxl（HMGB1） in human cervical squamous epithelial carcinoma （CSEC） and to explore the relationship of HMGB1 expression to the differentiation degree, size, invasion and metastasis of CSEC. METHODS Immunohistochemical staining of tissue microarrays and Western blot analysis were conducted to detect the expression of HMGB1 in the following tissue samples： 30 carcinoma in situ, 90 invasive CSEC without metastasis, 30 invasive CSEC with metastasis, 30 cases of normal cervical squamous epithelia. RESULTS The positive-expression rate of HMGB1 was 58.7% （88/150） in CSEC, showing a significant difference compared to normal cervical squamous epithelia. The expression of HMGB1 was correlated with tumor size, invasion and metastasis of CSEC （respectively, P〈0.01）, but had no relationship with the degree of differentiation （P〉0.05）. CONCLUSION The over-expression of HMGB1 in CSEC might be a useful parameter as an indication of tumor invasion, metastasis, prognosis and overall biological behavior of human CSEC, as well as a noval target site for gene therapy.
文摘Objective: To select a target molecule associated with invasive potential in PC-3M cell. Methods: Cell subclones were isolated from PC-3M cell line with the method of limited dilution and their invasive ability characterized by monolayer invasion assay. The expression of u-PAR in the cell subclones at mRNA and protein levels was assayed respectively by non-competitive quantitative RT-PCR and immunohistochemical assay. Results: The expression level of u-PAR in highly invasive cell subclones was higher than that of lower invasive subclones. Conclusion: The higher expression level of u-PAR is associated with the relative strong invasive ability of PC-3M subclones. It is indicated that the u-PAR might be a promising target molecule for inhibiting invasion of highly invasive PC-3M cell subclones.
文摘It is essential in treating rectal cancer to have adequate preoperative imaging,as accurate staging can influence the management strategy,type of resection,and candidacy for neoadjuvant therapy.In the last twenty years,endorectal ultrasound(ERUS) has become the primary method for locoregional staging of rectal cancer.ERUS is the most accurate modality for assessing local depth of invasion of rectal carcinoma into the rectal wall layers(T stage) .Lower accuracy for T2 tumors is commonly reported,which could lead to sonographic overstaging of T3 tumors following preoperative therapy.Unfortunately,ERUS is not as good for predicting nodal metastases as it is for tumor depth,which could be related to the unclear definition of nodal metastases.The use of multiple criteria might improve accuracy.Failure to evaluate nodal status could lead to inadequate surgical resection.ERUS can accurately distinguish early cancers from advanced ones,with a high detection rate of residual carcinoma in the rectal wall.ERUS is also useful for detection of local recurrence at the anastomosis site,which might require fine-needle aspiration of the tissue.Overstaging is more frequent than understaging,mostly due to inflammatory changes.Limitations of ERUS are operator and experiencedependency,limited tolerance of patients,and limited range of depth of the transducer.The ERUS technique requires a learning curve for orientation and identification of images and planes.With sufficient time and effort,quality and accuracy of the ERUS procedure could be improved.
基金Supported by Grants from the NSFC-Guangdong Joint Fund,No.U0932001the National Natural Science Foundation of China,No.30900560
文摘AIM:To investigate the expression profile of miRNA in esophageal squamous cell carcinoma(ESCC).METHODS:The expression profile of miRNA in ESCC tissues was analyzed by miRNA microarray.The expression levels of miR-143 and miR-145 in 86 ESCC patients were determined by real-time polymerase chain reaction(PCR) using TaqMan assay.The mobility effect was estimated by wound-healing using esophageal carcinoma cells transfected with miRNA expression plasmids.RESULTS:A set of miRNAs was found to be deregulated in the ESCC tissues,and the expression levels of miR-143 and-145 were significantly decreased in most of the ESCC tissues examined.Both miR-143 and miR-145 expression correlated with tumor invasion depth.The transfection of human esophageal carcinoma cells with miR-143 and miR-145 expression plasmids resulted in a greater inhibition of cell mobility,however,the protein level of the previously reported target of miR-145,FSCN1,did not show any significant downregulation.CONCLUSION:These findings suggest that the deregulation of miRNAs plays an important role in the progression of ESCC.Both miR-143 and miR-145 might act as anti-oncomirs common to ESCC.
文摘AIM: To analyze the predictive factors for lymph node metastasis (LNM) in early gastric cancer (EGC). METHODS: Data from patients surgically treated for gastric cancers between January 1994 and December 2007 were retrospectively collected. Clinicopathological factors were analyzed to identify predictive factors for LNM. RESULTS: Of the 2936 patients who underwent gas-trectomy and lymph node dissection, 556 were diag-nosed with EGC and included in this study. Among these, 4.1% of patients had mucosal tumors (T1a) with LNM while 24.3% of patients had submucosal tumorswith LNM. Univariate analysis found that female gen-der, tumors ≥ 2 cm, tumor invasion to the submucosa, vascular and lymphatic involvement were significantly associated with a higher rate of LNM. On multivariate analysis, tumor size, lymphatic involvement, and tumor with submucosal invasion were associated with LNM. CONCLUSION: Tumor with submucosal invasion, size ≥ 2 cm, and presence of lymphatic involvement are predictive factors for LNM in EGC.
基金supported by grants from National Natural Science Foundation of China(No.81171396)Creative Research Groups of the National Natural Science Foundation of China(No.20921062)+1 种基金National Science and Technology Major Project(No.2012ZX10002012-12)National University Students Innovation Training Project of China(No.111048673)
文摘Summary： This study aimed to establish a new in vitro three-dimensional （3D） cell culture and use quantum dots （QDs） molecular imaging to examine the invasive behaviors of hepatocellular carcinoma （HCC） cells. Each well of the 24-well cell culture plate was cover-slipped. Matrigel diluted with se- rum-free DMEM was added and HCCLM9 cells were cultured on the Matrigel. The cell morphological and cell growth characteristics were observed by inverted microscopy and laser confocal microscopy at different culture time. Cell invasive features were monitored by QDs-based real-time molecular imaging techniques. The results showed that on this 3D cell culture platform, HCCLM9 cells exhibited typical multi-step invasive behaviors, including reversion of cell senescence, active focal proliferation and dominant clones invasion. During the process, cells under 3D cell culture showed biological behaviors of spatio-temporal characteristics. Cells first merged on the surface of matrix, then gradually infiltrated and migrated into deep part of matrix, presenting polygonal morphology with stretched protrusions, forming tubular, annular and even network structure, which suggested that HCC cells have the morpho- logical basis for vasculogenic mimicry. In addition, small cell clones with their edges well-circumscribed in early stage, progressed into a large irregular clone with ill-defined edge, while the other cells developed invadopodia. And QDs probing showed MT1-MMP was strongly expressed in the invadopodia. These findings indicate that a novel 3D cell culture platform has been successfully estab- lished, which can mimic the in vivo tumor microenvironment, and when combined with QDs-based mo- lecular imaging, it can help to better investigate the invasive behaviors of HCC cells.
文摘BACKGROUND: Hilar cholangiocarcinoma is associated with low resectability and poor survival. The aim of this study was to evaluate the roles of matrix metalloproteinases- 2 (MMP-2 ) and its tissue inhibitor of metalloproteinase-2 (TIMP-2) in tumor invasion or as a prognostic factor in patients with human hilar cholangiocarcinoma. METHODS: The expressions of MMP-2 and TIMP-2 were investigated in patients. Paraffinized tissue sections ob- tained from 50 patients with human hilar cholangiocarcino- ma were analysed. The expressions of MMP-2 and TIMP-2 were examined immunohistochemically. Image analysis with image-pro plus analysis software was used to semi- quantitatively determine the ratio of MMP-2 to TIMP-2. RESULTS: The expression levels of MMP-2 and TIMP-2 were strongly associated with tumor hepatic invasion in pa- tients with hilar cholangiocarcinoma. Significant diffe- rences in the ratio of MMP-2 to TIMP-2 between some pathologic factors were observed in patients with hilar cholangiocarcinoma. CONCLUSIONS: MMP-2 plays an essential role in tumor invasion and metastasis,while TIMP-2 is shown to strongly inhibit cancer invasion and metastasis. The ratio of MMP-2 to TIMP-2 may be a prognostic indicator for patients with hilar cholangiocarcinoma.
基金ThisworkprojectsupportedbyagrantfromNaturalSciencesFoundationofHubeiProvince (No .2 0 0 0J0 77)
文摘To evaluate the specific inhibition of antisense u PAR on the u PAR expressions in highly invasive cell subclones and to determine its blocking function in the invasion by those cells, a cDNA fragment of u PAR obtained by RT PCR was inserted into a plasmid vector named pcDNA3 in antisense orientation. Then the antisense u PAR recombinant was transfected into highly invasive cell subclones. The u PAR expression in neo resistant cells was examined by RT PCR and immunohistochemical assay. Compared to the control cells, the content of mRNA and protein of u PAR in transfected cells decreased sharply, and the rate of inhibition was 53 % and 73 %, respectively, indicating that an antisense u PAR might have played a specific inhibitory role in its expression in the cells, which may provide a good cell model for making further investigation of the inhibitory effects of the antisense u PAR on invasion in highly invasive cell subclones of human prostate carcinoma.
文摘Background: Recurrence after resection of hepatocellu-lar carcinoma(HCC) is a major obstacle to improveprognosis. Therefore, further improvement of long-term survival may depend on prevention and treat-ment of the recurrent tumor.Objective: To evaluate the progress of surgery forHCC, the risk factors for recurrence, and clinical andbasic studies on the prevention and management of re-currence and metastasis after resection of HCC.Data sources: A review of currently available data inthe mentioned areas.Data synthesis: Encouraging changes in the prognosticpattern were observed when the primary liver cancer(PLC) data of 1958-1967 (n=118), 1968-1977 (n=356), 1978-1987(n=715) and 1988-1997 (n=2038)were compared. The 5-year survival was 2.8%, 7.3%,27.1% and 52.5%, respectively, and the 10-yearsurvival 2.8%, 4.3%, 19.8% and 39.9%, respective-ly. Risk factors for recurrence included symptomaticpatient, high γ-glutamyl-peptidase (γ-PGT), largetumor size, portal vein embolus, advanced tumorstage, etc. Active hepatitis activity in the nontumorousliver and perioperative transfusion enhanced the re-currence. Molecular research into the invasiveness ofHCC identified some factors positively related to inva-siveness: p16 and p53 mutation, H-ras, c-cerbB2,mdm2, transforming growth factor (TGF), epidermalgrowth factor receptor (EGF-R), matrix metallopro-teinase-2 (MMP-2), urokinasetype plasminogen acti-vator (uPA), its receptor (uPA-R) and inhibitor(PAI-1), intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF),platelet-derived endothelial cell growth factor (PD-ECGF), and basic fibroblast growth factor (bFGF).In contrast, some factors were negatively related toHCC invasiveness: nm23-H1, Kai-1, tissue inhibitor ofmetalloproteinase-2 (TIMP-2), integrin 5, and E-cadherin. Re-resection of subclinical recurrence yield-ed a 5-year survival of 56.0% calculated from the firstresection (n=202) .Postoperative transarterialchemoembolization (TACE, n=103), hepatic arterycannulation during operation (n=105), postoperativebiotherapy (n=49), and cryohepatectomy (cryosurgeryfollowed by immediate resection of the frozen tumor,n=84) might decrease the recurrence rate, and the3-year recurrence rate was 7.6%, 18.0%, 11.1%, and30.1%, respectively. Minimal intraoperative blood lossand transfusion could reduce postoperative recurrence,although the exact mechanism remains to be elucidat-ed.Conlusions: HCC invasiveness is the major topic to bestudied, particularly in the molecular level. Anti-an-giogenesis, biotherapy, novel approach based on molec-ular findings, and multidisciplinary interventions mightalso be important for HCC.
