【Abstract】Objective To introduce the progress on clinic trial of antiangiogenic breast cancer therapy. Methods The current literatures on progress on clinic trial of antiangiogenic breast cancer therapy were reviewed. ResultsPathological angiogenesis is a hallmark of cancer. Concentrated efforts in this area of research are leading to the discovery of a growing number of antiangiogenic molecules, more than 30 of which are already on clinical trial. About 10 of angiogenic inhibitors are already on clinical trial of antiangiogenic breast cancer therapy. Most of them are in clinical phase Ⅰ or Ⅱ studies and a few, however, have progressed to phase III evaluation. Some results show that angiogenic inhibitors can reduce the toxicity and be less likely to generate drug resistance than conventional cytotoxic drugs. Conclusion Pathological angiogenesis is indeed essential for breast cancer metastasis and recurrence. Antiangiogenesis can cause regression of the breast cancer and provide a optimum stragy to treat the breast cancer.
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 understand the latest research progress of long noncoding RNAs (lncRNAs) in occurrence and development mechanisms of common digestive system neoplasms.
MethodLiteratures about regulated occurrence and development mechanisms of digestive system neoplasms by lncRNA were reviewed according to the results searched from PubMed.
ResultsThere were three main function modes (decoy, guide, and scaffold) of the lncRNAs, which could regulate proliferation, apoptosis, invasion, and metastasis of the digestive system neoplasms, such as gastrointestinal cancer, liver cancer, and pancreatic cancer through the mechanisms of the epigenetic regulation, transcription regulation, and posttranscription regulation.
ConclusionsThe functions and tumorigenic mechanisms of the most lncRNAs are not entirely clear. The functions of lncRNAs played in the digestive system neoplasms needs to be understood, which might contribute to new tumor biomarker detection and effective treatment strategies.
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.
Objective To explore the values of telomerase in the diagnosis, therapy and prognostic parameter of colorectal cancer. Methods Telomerase activity in colorectal cancer, peri-cancerous and normal mucosa was detected by PCRTRAP-ELISA assay. Results The positive rates of telomerase in colorectal cancer, peri-cancerous and normal mucosa were 84.8%, 20.0% and 0% respectively. 66.7% of the early stage colorectal cancer expressed telomerase. Telomerase activity was reversely correlated with tumor differentiation.Conclusion Telomerase may be an earlier event of malignant progression in colorectal cancer. It might be a parameter for diagnosis of colorectal cancer.
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.
PURPOSE:Studying the multidrug resistance(MDR) phenotype occurring in retinoblastoma and its mechanism.
METHODS:Using the procedure of stepwise increase in drug concentrations to obtain a retinoblastoma subline which resistant to 600ng/ml vincristine (HXO-RB/VCR). Characteristics of this drug-resistant cell line were investigated by cell
counting,drugcontents determinatin,drug sensitivity evaluation and radiation sensitivity test. RESULTS:This cell line was cross-resistant to VDS,MMC VP16，ADM ,DDP,CBP,but not resistant to BCNU and 5-Fu. It was proved to be collaterally sensitive to MTX,and the response to 60Co gamma;-ray was modified slightly in HXO-RB/VCR cell line. Intracellular levels of VCR was much higher in HXO-RB44 cells than in the resistant subline. Those cross-resistances can be reversed by verapamil partly.
CONCLUSIONS:MDR and radiation resistance of retinoblastoma can be induced by exposing to VCR and reversed by verapamil partly.
（Chin J Ocul Fundus Dis,1997,13: 6-9）
Objective To investigate the influence of CO2-insufflation pressure on invasion potential of the colon cancer cells. Methods With an in vitro artificial pneumoperitoneum model, SW1116 human colon cancer cells were exposed to CO2-insufflation of 5 different pressure groups: 6, 9, 12, 15 mm Hg and control group, respectively for 1 h. The invasion capacities of SW1116 cells exposed to CO2-insufflation of 5 different pressure groups were detected by cell adhesion/invasion assay in vitro. Results Immediately following exposure to 15 mm Hg CO2 insufflation, the invasion of SW1116 cells decreased significantly compared to the cells before exposure. At the 0 h time point, the cells exposed to 15 mm Hg were significantly less invasive than those exposed to the other insufflation pressure (P＜0.05), and the cells exposed to 6 mm Hg were more invasive than cells exposed to the other insufflation pressure (P＜0.05). And 72 h after exposed to CO2-insufflation, the differences between the pressure groups were not significant. Conclusion CO2-insufflation induced a temporary change in the invasion capacity of cancer cells in vitro, higher pressure of CO2-insufflation inhibits the invasion potential.
