Objective To investigate the invasion ability of Panc-1 cells in vivo and in vitro af ter being t ransfected with tissue factor pathway inhibitor 2 gene ( TFPI-2) . Methods The expression vector pEGFP-C1-TFPI-2 was transfected into human pancreatic cancer line Panc-1 cells by using liposome. TFPI-2 mRNA and protein of transfected and nontransfected cells were detected by reverse t ranscription-polymerase chain reaction (RT-PCR) and Western blot respectively. The tumor cells invasive behavior of t ransfected ( Panc-1-TFPI-2) and nontransfected ( Panc-1-V and Panc-1-P) cells were assessed in vitro through Boyden Chamber method. The transfected and nontransfected cells were implanted into nude mice to observe it s growth and metastasis in vivo. Results Expressions of mRNA and protein of TFPI-2 were confirmed in transfected cells. Af ter TFPI-2 t ransfection , the number of Panc-1-TFPI-2 , Panc-1-V and Panc-1-P cells passing through membrane of Boyden Chamber were 24. 4 ±3. 5 ,61. 3 ±4. 1 and 60. 2 ±3. 9 , respectively. The number of TFPI-2-expressing cells to t raverse a Matrigel-coated membrane was obviously decreased compared with that of non-expressing cells , the invasion ability was lower than that before transfection in vitro. The subcutaneous tumor volume of the Panc-1-TFPI-2 group was (438. 0 ±69. 8) mm3 , the Panc-1-V group was (852. 0 ±102. 9) mm3 and the Panc-1-P group was (831. 0 ±78. 1) mm3 , P lt; 0. 05. The metastasis to liver and lung and muscular invasion occurred in the Panc-1-V group and the Panc-1-P group. There were no muscular invasion and metastatic lesions in the Panc-1-TFPI-2 group. Conclusion TFPI-2 gene expression may obviously inhibit the invasion ability of pancreatic cancer cells in vitro and in vivo , which provides an experimental basis for the treatment of human pancreatic cancer by gene therapy.
ObjectiveTo observe the effect of systemic chemotherapy on conditions of tumor infiltrating,metastasis and disease-specific survival (DSS) for advanced retinoblastoma (RB). MethodsForty-one patients with advanced RB who received enucleation were enrolled in this study. There were 26 males and 15 females, age at diagnosis was ranged from 2 to 72 months, with a mean of 23.08 months. There were 16 bilateral patients and 25 unilateral patients; 13 group D eyes and 28 group E eyes. 16 patients received enucleation as the primary treatment (operation group), 25 eyes received chemotherapy before enucleation (chemotherapy group). There was no significant statistical difference between two groups for the gender, unilateral and bilateral, international staging or diagnostic age (P>0.05). The histopathology report was performed to assess the risk of postoperative tumor-node-metastasis staging (pTNM) in each patient, and the extent of tumor invasion in the optic nerve, choroid and anterior chamber was divided into 3 levels of low risk, medium risk and high risk. Five deaths were all in the group E with chemotherapy before enucleation. Using R software survival analysis software package survfit function, the application of Kaplan-Meier estimation method, DSS of RB children was calculated from the time of diagnosis, up to the date of the death of patient. DSS differences between chemotherapy, operation group and eye removal time (more than 3 months, less than 3 months) in group E RB children were analyzed. ResultsThe proportion of high risk pTNM stage in chemotherapy group was significantly lower than the operation group. But there was no significant difference between the two groups in the overall risk classification (χ2=3.130,P=0.077). For group D eyes, the overall risk classification in chemotherapy group was significantly lower than the operation group (χ2=5.870,P=0.015). There was no significant difference between the two groups in the overall risk of group E eyes (χ2=0.020,P=0.889). The DSS in chemotherapy group and operation group were 0.71 and 1.00, respectively; the difference was significant (χ2=3.700,P=0.05). The DSS in children whose enucleation delayed for more than 3 months and children whose enucleation performed within 3 months were 0.64 and 1.00, respectively; the difference was significant (χ2=4.800,P=0.028). ConclusionSystemic chemotherapy did not reduce the risk of tumor invasion and metastasis in patients with advanced RB. Instead, it will reduce the DSS in group E eyes of RB.
ObjectiveTo evaluate the prognostic significance of metastatic lymph nodes ratio (MLNR) in patients with node-positive breast cancer. MethodsThe clinical data of 94 patients with nodepositive breast cancer underwent modified radical mastectomy were retrospectively analyzed. The survival rate and prognosis factors of patients with complete follow-up data were assessed by log-rank test and multivariate regression analysis. Results The survival time of 94 patients ranged from 12-75 months, with median 64 months. The 5-year overall survival rate was 72.34% (68/94). The total MLNR was 0.31 (486/1 553). Univariate analysis demonstrated that the survival was influenced significantly by tumor size, number of lymph node metastasis, MLNR, ER status, and radiotherapy or not (Plt;0.05), but not by patient’s age, menopause or not, PR status, endocrine therapy or not, and histological type (Pgt;0.05). Multivariate analysis showed that MLNR (OR=2.565, 95%CI=1.043-6.309， P=0.040) and tumor size (OR=2.220, 95%CI=1.045-4.716， P=0.038) were independent prognostic factors for the patients with node-positive breast cancer. Conclusion MLNR is a major independent prognostic factor for the patients with node-positive breast cancer, which is more accurate than the number of metastatic lymph nodes in predicting the survival of patients with node-positive breast cancer.
Objective To evaluate the characteristics of two angiographic manifestation of ocular fundus in choroidal metastatic carcinomas. Methods Fundus fluoresein angiography (FFA) and indocyanine green angiography (ICGA) were performed on 17 patients (24 eyes) with choroidal metastatic carcinomas, and the characteristics of these two kinds of angiograms were analyzed and compared each other. Results According to various clinical features, e.g., locations of metastatic tumor in ocular fundus, disease course, and different kinds of original malignancy, the findings of ocular fundus were divided into (1) Isolation type: FFA showed pinpoint and mottled leaks against hypofluorescence background, increased and confluent fluoresecence in later stage. ICGA showed the similar images as in FFA, except later appearance of leaks and the choroidal vesseles could be seen beneath the thin metastatic tumor mass.(2) Diffusion type: Tumors showed hypofluorescence in early stage and uneven ill-defined hyperfluorescence both in FFA and in ICGA. (3) Small metastatic carcinomas: Hypofluorescence in early stage and mild mottled hyperfluorescence were found in FFA as well as in ICGA. Conclusion Both FFA and ICGA are helpful in the diagnosis of choroidal metastatic tumors and ICGA may be conducive if there are some troubles in diagnosing the tumors with FFA. (Chin J Ocul Fundus Dis, 2002, 18: 92-95)
Objective To investigate the influence of different pressures and duration of CO2 pneumoperitoneum on the adhesive and invasive ability of gastric cancer cells based on the expressions of adhesive and invasive molecules. Methods With an artificial CO2 pneumoperitoneum model in vitro, human gastric cancer cell lines including MKN-45, SGC-7901, and MKN-28 were exposed to CO2 in different environments: 0 mm Hg （1 mm Hg=0.133 kPa）, 9 mm Hg （2 h, 4 h）, and 15 mm Hg （2 h, 4 h）. The expressions of mRNA of E-cadherin, intercellular adhesion molecule-1 (ICAM-1), matrix metalloproteinase-2 (MMP-2), and vascular endothelial growth factor-A (VEGF-A) in the different environments were measured by RT-PCR. The expressions of protein of E-cadherin and ICAM-1 in the environments of 0 mm Hg and 15 mm Hg （4 h） were measured by FCM. Results With the increase of duration or pressure, RT-PCR showed that there was a downward trend in the expression of E-cadherin mRNA as well as there were upward trends in the expressions of ICAM-1, MMP-2, and VEGF-A mRNA; FCM showed that there was a downward trend in the expression of E-cadherin protein while the expression of ICAM-1 protein showed the opposite change. But there were no obvious differences under different environment (P＞0.05). Conclusions Under low pressure (≤15 mm Hg) and short time (≤4 h) of CO2 pneumoperitoneum, the adhesive and invasive ability of gastric cancer cells could not be affected, which means that under this environment, CO2 pneumoperitoneum will not increase the possibility of neoplasm metastasis.
ObjectiveTo explore the clinical features, primary lesions and prognosis of optic nerve metastases.MethodsSeven patients (11 eyes) with optic nerve metastatic tumor diagnosed by the examinations of ophthalmology, laboratory and pathology in Chinese PLA General Hospital from April 2015 to September 2017 were included in this study. All patients underwent BCVA, flash VEP, OCT, orbital MRI, serum tumor marker, cerebral spinal fluid detection and PET-CT. Histopathological examination of primary or near superficial metastases was performed. The follow-up period was ranged from 16 to 44 months, with the mean of 23.0±10.9 months. The clinical characteristics, primary tumor, imaging features, treatment and clinical prognosis in the patients were analyzed.ResultsAmong 7 patients, there were 5 males and 2 females, with the mean age of 53.90±14.99 years; 3 patients with unilateral optic nerve involvement, 4 patients with bilateral optic nerve involvement; 5 patients (71.4%) first diagnosed in ophthalmology. Five patients (45.5%) were misdiagnosed as optic neuritis, optic disc edema in 6 eyes (54.5%). All of them appear loss of visual acuity, including 8 eyes (72.7%) with BCVA＜0.1, 2 eyes (18.2%) with BCVA 0.1-0.5, 1 eye (9.1%) with BCVA＞0.5. MRI results show that 1 patient with intraorbital segment, 1 patient with internal segment of optic canal, 4 patients with intracranial segment, 1 patient with intracranial segment and optic chiasma involved simultaneously, 4 patients involving surrounding tissue. There were 4 patients (57.1 %) with lung cancer, 2 patients (28.6%) with kidney cancer, 1 patient (14.3%) with gastric cance; 6 patients (85.7%) with metastasis from other sites, 2 patients with brain metastasis (1 patient with meningitis carcinomatosa). There were 2 patients (28.6%) with previous primary cancer surgery. After diagnosis, 1 patient received chemotherapy, 1 patient received radiotherapy, 5 patients gave up treatment. At the end of follow-up, 1 patient (1 eye) of chemotherapy with BCVA increased by 2 line; 1 patient (2 eyes) of radiotherapy with no change in BCVA; of the 5 patients who gave up treatment, 1 patient died of disease, 1 patient lost follow-up, and 3 patients (4 eyes) had no change in BCVA.ConclusionsWith atypically clinical manifestations, the optic nerve metastases easily misdiagnosed as optic neuritis, and with poor therapeutic effect. Primary lesions are mostly found in lung cancer.
ObjectiveTo explore the relation between vascular endothelial growth factor （VEGF） and the formation of tumor thrombosis in the main trunks of portal vein (PVTT). MethodsTumor specimens were collected from 36 patients (16 patients with PVTT, the other patients without PVTT and metastasis) undergoing resection of hepatocellular carcinoma (HCC) and portal thrombectemy, PVTT specimens of 16 patients named group A1, the same patients’ with HCC named group A2, tumor specimens of the other patients named group B. In situ hybridization and immunohistochemistry were used to investigate VEGF mRNA, protein and microvessel density (MVD) on surgical specimens. The intensity was evaluated using a computer image analyzercell analysis system.ResultsVEGF mRNA expression was detected in the tumor’ cell of the specimens. The expression rates of VEGF mRNA in the group B, A2, A1 were 30%, 100%, 100% respectively, and the expression rates of VEGF mRNA in group A2 and A1 were higher than that in group B （P＜0.01）. The intensity of VEGF mRNA in group A2 （0.078 5±0.019 6） were lower than in group A1 （0.194 4±0.059 0） （P＜0.01）. VEGF protein expression was often detected in the tumor cell, vascular endothelial cell and fibroblast cells. Invasion was detected in small vein in group A2, more tumor cell colony detected in group A1. The expression rates of VEGF protein in group B, A2, A1 were same as VEGF mRNA; the intensity of VEGF protein in A1 （0.165 6± 0.034 5） was higher than in group A2 （0.108 1±0.024 3） （P＜0.01）. MVD in group B, A2, A1 was 31.9±14.4, 63.3±15.1, 116±27.6/view of 200 microscopefield, MVD in group A1 was higher than group A2 （P＜0.01）, higher in group A2 than in group B. There was a statistically significant correlation between the intensity of VEGF expression and MVD in group B,A2 and A1. ConclusionVEGF could play an important role in the invasion, metastasis of HCC and the formation of PVTT. Angiogenesis in tumor is correlated well with the progression of HCC.
Objective To evaluate the therapeutic effects of percutaneous microwave ablation (MWA) for metastatic liver cancer. Methods Ultrasound-guided percutaneous MWA technique was used to treat 27 cases of hepatic metastases with 69 nodules 〔0.9-13.2 (3.0±2.0) cm in diameter〕. Local therapeutic effect, local and distant recurrence rate and survival rate were evaluated respectively. Results The complete ablation (CA) rate which was used to evaluate the local therapeutic effects was 92.8% (64/69), with 100% (34/34), 92.3%(24/26) and 66.7% (6/9) in a diameter of nodules lt;3.0 cm, 3.0-5.0 cm and ≥5.0 cm respectively. The CA rate was lower in the group of a diameter of nodules ≥5.0 cm as compared with other two groups (Plt;0.05). The local recurrence rate was 9.4% (6/64), with 2.9% (1/34), 16.7% (4/24) and 16.7% (1/6) in a diameter of nodules lt;3.0 cm, 3.0-5.0 cm and ≥5.0 cm respectively. The intrahepatic distant recurrence rate was 44.4% (12/27). The follow-up time after MWA was 3－34 (17.0±8.7) months. During the follow-up period, 6 months, 1 and 2-year cumulative survival rate was 88.9%, 63.0% and 34.4% respectively, with a mean survival time of 17.8 months, and with a median survival time of 19.0 months.Conclusion Percutaneous MWA treatment offers satisfactory local tumoricidal efficacy to metastatic liver cancer and the patients with recurrence and new metastases can be therapy repeatedly to improve long-term survival.
ObjectiveTo systematically review the efficacy and safety of 89SrCl2 for bone metastases.MethodsDatabases including PubMed, EMbase, The Cochrane Library (Issue 12, 2016), MEDLINE, CBM, VIP, CNKI and WanFang Data were electronically searched from inception to December 2016 to collect randomized controlled trials (RCT) about 89SrCl2 in the treatment of bone metastases. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Then meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 19 RCTs involving 1 899 patients were included. The results of meta-analysis showed that: compared to the group without 89SrCl2, group of 89SrCl2 combined with other treatments had benefits for complete relief of bone pain (RR=1.53, 95%CI 1.16 to 2.01, P=0.002), total relief of bone pain (RR=1.33, 95%CI 1.22 to 1.45, P<0.001), bone metastases complete response rate (RR=1.61, 95%CI 1.20 to 2.16, P=0.002), bone metastases total response rate (RR=1.61, 95%CI 1.26 to 2.08, P<0.001), improvement of quality of life (RR=1.44, 95%CI 1.06 to 1.97, P=0.02). The proportion of pain flare (RR=10.35, 95%CI 2.01 to 53.37, P=0.005), leucopenia (RR=2.49, 95%CI 1.84 to 3.37, P<0.001) and thrombocytopenia (RR=2.64, 95%CI 1.76 to 3.97, P<0.001) in the 89SrCl2 group were higher than that in the control group.Conclusion89SrCl2 combined with the other treatments is better for bone metastases than without 89SrCl2. Due to the limited quantity and quality of included studies, the above results should be verify by more high quality studies.
Objective To establish a new model of orthotopic-transplatation tumor of human malignant choroidal melanoma. Methods pEGFP-N1, the eukaryotic expressive plasmid of green fluorescent protein (GFP), was transfered into human malignant choroidal melanoma cell line (OCM-1) by liposome lipofectanine, then the cell clones with stable GFP expression were screened out by means of neomycin, fluorescence microscope, and flow cytometer. Two μl cell suspension of OCM-1 cells with GFP expression with the density of 4.5×107-5.5×107 cells/ml was injected into the subretinal space of right eyes of 40 nude mice (40 eyes) under binocular operating microscope with left eyes as the control ones. The growth of the transplanted malignant choroidal melanoma was observed in vivo using the fluorescence stereomicroscope. The mice were killed at different time after the operation to observe the metastasis of the tumor to optic nerve, brain and other organs including lung, liver, kidney and spleen. Moreover, pathological detection and immunohistochemical staining of GFP was carried out. Results At the postoperative 10th-12th days, the growths of the transplanted malignant choroidal melanoma with dilated and distorted blood vessels and neovascularization were observed; at the postope rative 20th-22nd days, the melanoma occupied the whole cavity of vitreous body; and at the postoperative 24th-26th days, the transplanted tumor grew out of the eye. Metastases of the carcinoma to olfactory bulb, kidney, lung and liver were seen at the failure phase soon after the extra-ocular phase. The histopathological characteristics of the transplanted tumor were similar to those of human, and the results of immunohistochemical staining showed positive expression of GFP in the tumor cells. Conclusion The orthotopic model of malignant choroidal melanoma set up via injection of human malignant choroidal melanoma cells labeled by GFP into the subretinal space of nude mice may provide a new approach to investigate the natural courses of growth and metastasis of malignant choroidal melanoma. (Chin J Ocul Fundus Dis，2004，20：245-248)