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Accurately delineating tumor boundaries is key to predicting survival rates of cancer patients and assessing response of tumor microenvironment to various therapeutic techniques such as chemotherapy and radiotherapy. This review discusses various strategies that have been deployed to accurately delineate tumor boundaries with particular emphasis on the potential of chemotherapeutic nanomaterials in tumor boundary delineation. It also compiles the types of tumors that have been successfully delineated by currently available strategies. Finally, the challenges that still abound in accurate tumor boundary delineation are presented alongside possible perspective strategies to either ameliorate or solve the problems. It is expected that the information communicated herein will form the first compendious baseline information on tumor boundary delineation with chemotherapeutic nanomaterials and provide useful insights into future possible paths to advancing current available tumor boundary delineation approaches to achieve efficacious tumor therapy.
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Background: Pancreatic cancer is among the most lethal malignancies worldwide. In this study, we aimed to determine whether miR-573 could suppress pancreatic cancer cell proliferation, migration, and invasion by targeting E2F3. Materials and Methods: MiR-573 expression in pancreatic cancer tissues and cell lines was measured using real-time PCR. Target genes of miR-573 were screened using bioinformatics tools and confirmed using dual-luciferase reporter assay and real-time PCR. Pancreatic cancer cells were transfected using an miR-573 mimic or siRNA E2F3. Furthermore, cell proliferation, migration, and invasion were assessed using CCK-8, Edu staining, colony-forming assay, wound healing assay, and transwell assay in vitro. The in vivo effects of miR-573 were verified using tumor xenografts. Differential expression and prognostic analyses of miR-573 and E2F3 were visualized using the KaplanMeier plotter and GEPIA. Results: We found that the expression of miR-573 was significantly reduced in pancreatic cancer tissues and cell lines. Overexpression of miR-573 obviously suppressed the proliferation, migration, and invasion of pancreatic cancer cells. The Dual-luciferase assay showed that miR-573 could specifically target E2F3. Furthermore, E2F3 was up-regulated in pancreatic cancer tissues and cell lines and E2F3 down-regulation inhibited the proliferation, migration, and invasion of pancreatic cancer cells. The ectopic expression of miR-573 inhibited xenograft tumor growth in vivo. Results from the Kaplan-Meier analysis and GEPIA showed that patients with a high level of miR-573 had a significantly reduced risk of death while those with a high level of E2F3 displayed significant correlation with the tumor stage and suffered worse prognosis. Conclusions: MiR-573 could suppress the proliferation, migration, and invasion of pancreatic cancer cells by targeting E2F3, thereby establishing miR-573 as a novel regulator of E2F3 and indicating its critical role in tumorigenesis, especially in pancreatic cancer.
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<p><b>OBJECTIVE</b>To investigate the expression of miR-29b in cholangiocarcinoma and explore its effects on cell proliferation and apoptosis of cholangiocarcinoma cells.</p><p><b>METHODS</b>Real-time PCR was used to detect the expression of miR-29b in cholangiocarcinoma cells line QBC939 and cholangiocarcinoma tissues. The lentiviral vector LV-hsa-miR-29b and blank vector were constructed to infect QBC939 cells. MTT assay and cell clone formation assay were performed to assess the changes in the cell proliferation and clone formation, respectively; flow cytometry was employed to evaluate the effect of miR-29b overexpression on cell cycle and apoptosis.</p><p><b>RESULTS</b>The expression of miR-29b was significantly down-regulated in QBC939 cells and cholangiocarcinoma tissues as compared with H-69 cells and normal tissues ( < 0.01). Compared with the blank vector, the lentiviral vector LV-hsa-miR-29b caused significantly increased expression of miR-29b in QBC939 cells ( < 0.01), which exhibited suppressed cell proliferation and clone formation ( < 0.01 or 0.05), cell cycle arrest at the S phase ( < 0.05), and significantly increased cell apoptosis ( < 0.01).</p><p><b>CONCLUSIONS</b>As a tumor-suppressing miRNA, miR-29b is down-regulated in cholangiocarcinoma, and its overexpression can suppress the proliferation and induce apoptosis of cholangiocarcinoma cells.</p>
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Objective To investigate the expression of interleukin-33(IL-33)and vascular endothelial growth factor C(VEGF-C)in gastric cancer tissues and serum,and to explore the relationship between these two indicators and gastric cancer lymph node metastasis.Methods The levels of IL-33 and VEGF-C in the tissues of gastric mucosa and serum were detected by immunohistochemical SP method and enzyme-linked immunosorbent assay(ELISA)in 98 patients with gastric cancer and 36 healthy subjects.Results The expression rates of IL-33 and VEGF-C in gastric cancer were 67.35％and 74.49％,which were significantly higher than the rates in normal gastric tissue(47.22％and 61.11％).The difference was statistically significant(P<0.01).The expression of IL-33 and VEGF-C was correlated with the degree of tumor differentiation,tissue infiltration,lymph node metastasis,distant metastasis and clinical stage(P<0.05).The positive rates of IL-33 and VEGF-C in gastric cancer lymph node metastasis group were higher than those in non-lymph node metastasis group(P<0.05).The serum concentrations of IL-33 and VEGF-C in patients with gastric cancer were(50.24±13.08)pg/mL and(210.73±58.35)pg/mL,respectively,which were higher than those in healthy control group(P<0.05);the expressions of serum concentration of IL-33 and VEGF-C in the cases with lymph node metastasis were higher than those without lymph node metastasis and the difference was statistically significant(P<0.05).Conclusion High levels of IL-33 in gastric carcinoma patients might induce the secretion of VEGF-C,promote lymph node metastasis,and be applied as an important index of the appraisal to the prognosis of gastric cancer.
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ObjectiveTo study the expressions of CD90 and hTERT in hepatocellular carcinoma (HCC),and their relationships to progression of tumor.MethodsThe expressions of CD90 and hTERT in hepatocellular carcinoma were detected by S-P immunohistochemical staining.Twenty patients with hemangiomas of liver were used as control.ResultsCompared with the control group,the positive rates of CD90 and hTERT in HCC were significantly higher (63.9％ and 47.2％ vs 0％ and 0％).The positive rates of CD90 and hTERT were significantly higher in patients with tumors at UICC Ⅲ-Ⅳ stage than at UICC stage Ⅰ -Ⅱ (79.1％ and 62.5％ vs 33.3％ and 16.6％).The CD90 expression correlated with hTERT positively.There were significant differences in survival between patients with CD90+ and CD90- or hTERT+ and hTERT-.The median postoperative survivals for patients with CD90+ and hTERT+,CD90- and hTERT- were 85 d and 76 d,505 d and 463 d,respectively.ConclusionsCD90 expression correlated positively with progression of HCC.It has the potential to serve as a prognostic marker for HCC.
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ObjectiveTo investigate the targeting infection of single chain antibody againstAFP (scFv anti-AFP) directed lentivirus and the inhibitory effects of a dual-growth inhibition systemon hepatocarcinoma cells.MethodsPlasmids WtP53-pPRIME-miR30-shRNA-IGF1R,pMD2G-Anti-AFP,and psPAX2 have previously been constructed to cotransfect to the packaging cell line 293Tusing Lipofectamine2000.The infection results were observed through fluorescence microscopy.PCRand Western blotting were used to demonstrate the successful transduction and transcription of theWtP53-pPRIME-miR30-shRNA-IGF1R gene.The effects of reconstructed lentivirus infected liver cellgrowth were assessed by the cell growth curve of CCK8 cells. Apoptosis was evaluated by theTUNEL assay.ResultsRecombined lentivirus was successfully constructed with the functional PFUtiters of recombined lentivirus at 4.58× 109PFU/ml.This positive result was confirmed by PCR andWestern blotting.ConclusionsThe targeted therapy mediated by anti-AFP scFv could significantlyinhibit the proliferation of HEP3B cells and promote the apoptosis.
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Objective To investigate the expression of CD90,IGF1R in hepatocellular carcinoma.Methods CD90,IGF1R expression were detected by SP immunohistochemical staining in 36 cases of hepatocellular carcinoma,20 cases of normal liver tissue biopsied from patients of chronic cholecystitis undergoing cholecystectomy. Results The positive rate of CD90 (63.89％,23/36),IGF1R (52.78％,19/36) in hepatocellular carcinoma significantly increased (P ＜ 0.05 ); The positive rate of CD90 was higher in UICC Ⅲ - Ⅳ stage group (79.17％ ) than in UICC stage Ⅰ - Ⅱ group (33.33％,P ＜0.05) ;The positive rate of CD90 was higher in low differentiated group (76.92％ ) than in well-differentiated group (56.52％,P ＜0.05).The positive rate of IGF1R was higher in UICC Ⅲ - Ⅳ stage group (70.83％ ) than in UICC stage Ⅰ - Ⅱ group ( 16.67％,P ＜ 0.05 ). The positive rate of IGF1R was higher in low differentiated group (84.62％) than in well-differentiated group (37.38％,P ＜ 0.05 ).The expression of IGF1R was positively correlated with that of CD90 (P ＜ 0.05 ).The median survival of CD90+ patients (85 days) was shorter than CD90- patients ( 505 days ) ( P ＜ 0.05 ).The median survival of IGF1 R + patients (100 days) was shorter than IGF1 R- patients (408 days,P ＜ 0.05). Conclusions CD90 or IGF1R expression correlates positively with the progression of HCC.
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Objective To observe the effects of hIL-10-MSCs on heterologous T cell prolifera-tion. Methods hlL-10 was cloned by RT-PCR and then hIL-10/pLOX-cwGFPs was construct. The lentivirus was transfected into cavy MSCs and cell culture supernatant was tested for IL-10 protein by ELISA assay. The effects of hIL-10-MSCs on heterologous T cell proliferation were determined by CCK-8. The effect of peripheral blood mononuclearcell secretion IFN-γ was tested by EIASA. Results hIL-10/pLOX-cwGFP were constructed successfully and hIL-10-MSCs cell culture supernatant of IL-10 protein were increased obviously, hIL-10-MSCs could inhibit heterologous T cell proliferation sig-nificantly(P<0.05) but could not induce T cell proliferation (P<0.05). Adding IL-2 could reverse this inhibition(P<0.05), hIL-10-MSCs cell culture supernatant could inhibit peripheral blood mono-nuclearcell secretion IFN-γ. Conclusion hIL-10-MSCs may play an important role in significant im-munosuppression of heterologous T cell proliferation and suppression of secretion IFN-γ by peripheral blood mononuclear cells.
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Objective To observe the influence of hIL-10-MSCs on apoptosis of rats subject to discordant liver xenotransplantation. Methods The model of guinea pig to rat discordant liver xenotransplantation was set up. The orthotopic liver transplantation model was established by using modified two-cuff technique. Following groups were designed: control group, MSCs group and hIL-10MSCs group. Before and after operation, the recipients in control group were injected with normal sodium (2 ml) and decaesadril (0.5 ml) ;Those in MSCs group were injected with MSCs (4.0× 106/ml)and decaesadril (0.5 ml); Those in hIL-10-MSCs group were injected with hIL-10-MSCs (4.0 × 106/ ml)and decaesadril (0.5 ml). Twelve h after operation, the livers of recipient were observed by HE staining and electron microscope, and apoptosis of the livers was detected by using TUNEL. The expression levels of hIL-10, caspase-3, Fas and FasL were assayed by Western blot or immunohistochemistry. Results As compared with control group and MSCs group, the pathological changes was alleviated, the expression of IL-10 was significantly increased, the expression of FasL was significantly reduced in hIL-10-MSCs group. The positive area size of Fas and Caspase-3 in hIL-10MSCs group was 11.5 % and 25.1 %, respectively, significantly smaller than those in control group (35.3 % and 70.8 % respectively, P＜0.05. Apoptosis index in hIL-10-MSCs group was 32.5 %,which was significantly lower than in control group (74.1%) and MSCs group (50. 3 % ). ConclusionhIL-10-MSCs can notably decrease apoptosis of the transplanted liver probably by inhibiting theexpression of Fas/FasL.
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Objective To observe the influence of hIL-10-MSCs on rejection of rat discordant liver xenotransplantation. Methods The model of cavia to rat discordant liver xenotransplantation was established. The rats were randomized into the control group, MSCs group, and hIL-10-MSCs group.The survival time and liver function of each recipient were observed and expression levels of E-Selectin, LFA-1, VCAM-1, and NF-κB determined by RT-PCR and ELISA 24 h after transplantation.Results The survival time was prolonged, liver function improved, and expressions levels of E-Selectin, LFA-1, VCAM-1 and NF-κB were significantly decreased in the hIL-10-MSCs group (P＜0.05).Conclusion hIL-10-MSCs are able to protect transplanted liver and decrease the expression of E-Selectin, LFA-1, VCAM-1, and NF-κB in the liver.
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Objective To explore the application value of superior mesenteric vein-caval-right atrium Y shape shunt (abbr.SMV-CV-RA Y shape shunt) as a new approach for treatment of mixed pattern Budd-Chiari syndrome (B-CS).Methods The clinical data of 101 cases of mixed pattern B-CS patients were evaluated for the curative effect.Of the 101 patients,62 were treated with superior ruesenteric vein-caval-right atrium Y shape shunt,26 with splenic vein-caval shunt and 13 with superior mesenteric vein-caval shunt using artificial vascular graft.Results Compared with the plastocyte count of patients receiving splenic vein-caval shunt and superior mesenteric vein-caval shunt,the plastocyte count of 62 cases undergoing SMV-CV-RA shunt increased obviously after operation (P＜0.05).The portal vein pressure of patients with SMV-CV-RA shunt decreased significantly (P＜0.05),but the pressure of patients in splenic vein-caval shunt group and superior mesenteric vein-caval shunt group deceased slightly (P＞0.05).The incidence of hepatic encephalopathy in one year after operation was not significantly different among the 3 groups (P＞0.05).The incidence was 3.2%(2/62),0% (0/26),0% (0/13),respectively.The recanalization rate of artificial vascular graft was 95.2%(59/62),69.2%(18/25),38.4%(5/13),respectively in SMV-CV-RA shunt group,splenic vein-caval shunt group and superior mesenteric vein-caval shunt group.The recanalization rate of artificial vascular graft in SMV-CV-RA shunt group was increased significantly (P＜0.05).Conclusion Compared with splenic vein-caval shunt and superior mesenteric vein-caval shunt,the SMV-CV-RA Y shape shunt can get satisfactory effeet in curing massive hemorrhage of gastrointestinal tract for cutting down the pressure of portal vein and inferior vena.Otherwise,the shunt could eliminate hypersplenia of patients.The splenic vein-caval shunt and superior mesenteric vein-caval shunt are not effective in curing the mixed pattern B-CS.
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Objective To investigate the protective effect of peroxisome proliferator-activated receptor ?(PPAR?) activator 15-deoxyprostaglandin J2(15d-PGJ2) in rat hepatic ischemia-reperfusion injury and its mechanism.Methods The models of 70% warm ischemia-reperfusion injury were established in SD rats,rats were randomly divided into 4 groups: sham operation group,ischemia-reperfusion group,15d-PGJ2 group and 15d-PGJ2+GW9662 group.After reperfusion,serum AST and ALT levels were determined;the liver tissues were removed for measurement of activity of NF-?B and myeloperoxidase(MPO),TNF-? content and expression of ICAM-1.Results Compared with sham operation group,the serum levels of ALT and AST,and the activities of MPO and NF-?B,TNF-? content and expression of ICAM-1 in ischemia-reperfusion group,15d-PGJ2 group and 15d-PGJ2+GW9662 group were greatly improved(P
