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ABSTRACT: Cholangiocarcinoma (CCA) is a rare but lethal malignancy arising from the biliary tract epithelium. It has a poor prognosis largely due to the difficulties of early diagnosis and the lack of effective therapies. It is thus imperative to develop new and effective treatments for CCA, which depends heavily on the mechanistic understanding of the disease. Previous studies have suggested that somatic mutations in KRAS, BRAF, and PIK3CA genes are frequently found in several types of human cancers including colon, breast, and lung carcinomas as well as CCA. Yet, the frequency and the involvement of these oncogenic mutations in CCA in Chinese population have not been investigated. In this study, we evaluated the hotspot mutations of KRAS, BRAF, and PIK3CA genes in 34 Chinese CCA patients. Sequencing analysis revealed 13 (38.2%) and 11 (32.4%) patients bearing KRAS and PIK3CA mutations, in which two (5.9%) of them harbored both KRAS and PIK3CA mutations. Surprisingly, no BRAF mutation was detected in all 34 CCA samples. Our findings indicate that somatic mutations in KRAS and PIK3CA but not BRAF oncogenes are closely associated with the development of CCA in Chinese population and provide new potential targets for future therapeutic treatments of the disease.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 11/2010; 65(1):22-6. · 2.24 Impact Factor
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ABSTRACT: To compare the short-term curative effect of photodynamic therapy (PDT), PDT combined with chemotherapy and chemotherapy alone on the advanced esophageal cancer patients.
Retrospective analysis of 90 patients of esophageal cancer underwent PDT, PDT combined with chemotherapy and chemotherapy alone from 2004 to 2007 (stages III-IV), including 27 cases received PDT alone, 33 cases received PDT combined with chemotherapy and 30 cases chemotherapy alone. The enrolled patients were treated with intravenous administration of Photofrin as the photosensitizer at a dose of 2mg/kg. 630 nm laser irradiation was performed through optical fiber that passed through the biopsy channel of a flexible endoscope after 48 h. Two days later, the necrotic tissue was removed, and the primary sites and other newly identified lesions were subjected to a second irradiation and then the residual necrotic tissue was removed according to the patients' condition. Electronic endoscopy was performed to observe the effectiveness on tumor after 1 month. In PDT combined with chemotherapy group, chemotherapy regimen was 5-FU and DDP, administered 4 cycles after PDT and chemotherapy alone group only chemotherapy regimen 5-FU and DDP for four cycles. All the 90 patients were followed up for 2 years.
Symptomatic palliation rate of the PDT alone group, the complex treatment group and chemotherapy alone group was 85.2%, 93.9% and 60.0%, respectively, and effective rate under endoscopy was 85.2%, 90.9% and 63.3%, respectively, there is no statistically significant difference; the survival rate of 2 years was 29.6%, 54.5% and 16.7%, respectively, and medium survival time is longer (III stages 13 m, 22 m, 10 m; IV stages 7 m, 5m, 4m), there is statistically significant difference (p=0.046).
PDT combined with chemotherapy for the advanced esophageal cancer is superior to PDT alone and chemotherapy alone.
Photodiagnosis and photodynamic therapy 09/2010; 7(3):139-43.
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ABSTRACT: To investigate the inhibitory effect of photodynamic therapy (PDT) in combination with paclitaxel (PCT) on proliferation in esophageal carcinoma Eca-109 cells line.
Eca-109 cells were treated with PCT alone, HPD alone at different doses, or their combinations. For the combined treatments, the cells were exposed to PCT for 12 h followed by incubation with HPD at high, middle or low concentrations for 4 h. PDT was then performed on these treated cells and fluorescence microscopic observation was made before and after PDT. The cell survival was measured by MTT assay, and the cell apoptosis rate analyzed by flow cytometry after a 24-h cell incubation following PDT.
The fluorescence excitation of the cells was weakened after PDT. Combined treatments resulted in significantly lowered cell survival rate and increased cell apoptosis rates as compared to those of the control cells and the cells treated with PCT alone and low-dose HPD (P<0.01). Significant differences were also noted among the cells exposed to HPD at different concentrations (P<0.05).
PDT combined with PCT have significant synergetic effects in inhibiting the proliferation of human esophageal carcinoma cells and inducing their apoptosis in vitro.
Nan fang yi ke da xue xue bao = Journal of Southern Medical University 06/2010; 30(6):1310-2, 1315.
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ABSTRACT: To investigate the mechanism of photodynamic therapy (PDT) in nude mice bearing human esophageal cancer cell line Eca-109 xenografts.
A nude mouse model bearing human esophageal carcinoma was established by subcutaneous transplantation of Eca-109 cells. The mice were then randomized into 4 groups, namely hematoporphyrin derivative (HpD)-PDT group (given HpD and laser irradiation), exclusive laser irradiation group, exclusive HpD group and blank control group. In HpD-PDT group, the mice were exposed to irradiation at the light energy density of 120 Jsol;cm(2) delivered via a DIOMED 630 PDT system 24 h after intraperitoneal HpD injection, and the mice in exclusive laser irradiation group received only laser irradiation. Three days later, all the nude mice were sacrificed for determination of malondialdehyde (MDA) production, immunohistochemistry for caspase-3 protein and HE staining of the tumor tissue.
The MDA level was significantly higher in HpD-PDT group than in the other 3 groups (P<0.01), and comparable between the latter 3 groups. Expression of caspase-3 protein was similar between HpD-PDT group and the blank control group (P>0.05). Under light microscope, HE staining visualized massive tissue necrosis in HpD-PDT group with homogeneous red staining.
In human esophageal carcinoma xenografts in nude mice, HpD-PDT generates singlet oxygen to result in direct tumor cell damage and cause MDA production. Caspase-3 may not be activated in the apoptotic pathway, suggesting that this pathway may not be caspase-3-dependent.
Nan fang yi ke da xue xue bao = Journal of Southern Medical University 11/2009; 29(11):2222-4.
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ABSTRACT: Differential diagnosis for epithelial tissues of normal human gastric, undifferentiation gastric adenocarcinoma, gastric squamous cell carcinomas, and poorly differentiated gastric adenocarcinoma were studied using the Kubelka-Munk spectral function of the DNA and protein absorption bands at 260 and 280 nm in vitro. Diffuse reflectance spectra of tissue were measured using a spectrophotometer with an integrating sphere attachment. The results of measurement showed that for the spectral range from 250 to 650 nm, pathological changes of gastric epithelial tissues induced that there were significant differences in the averaged value of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log[f(r infinity)] of the DNA absorption bands at 260 nm between epithelial tissues of normal human stomach and human undifferentiation gastric cancer, between epithelial tissues of normal human stomach and human gastric squamous cell carcinomas, and between epithelial tissues of normal human stomach and human poorly differentiated cancer. Their differences were 68.5% (p < 0.05), 146.5% (p < 0.05), 282.4% (p < 0.05), 32.4% (p < 0.05), 56.00 (p < 0.05) and 83.0% (p < 0.05) respectively. And pathological changes of gastric epithelial tissues induced that there were significant differences in the averaged value of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log[f(r infinity)] of the protein absorption bands at 280 nm between epithelial tissues of normal human stomach and human undifferentiation gastric cancer, between epithelial tissues of normal human stomach and human gastric squamous cell carcinomas, and between epithelial tissues of normal human stomach and human poorly differentiated cancer. Their differences were 86.8% (p < 0.05), 262.9% (p < 0.05), 660.1% (p < 0.05) and 34% (p < 0.05), 72. 2% (p < 0.05), 113.5% (p < 0.05) respectively. And pathological changes of gastric epithelial tissues induced that there were significant differences in the averaged value of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log[f(r infinity)] of the carotene absorption bands at 480 nm between epithelial tissues of normal human stomach and human undifferentiation gastric cancer, between epithelial tissues of normal human stomach and human gastric squamous cell carcinomas, and between epithelial tissues of normal human stomach and human poorly differentiated cancer. Their differences were 59.5% (p < 0.05), 73% (p < 0.05), 258.9% (p < 0.05), 118.7% (p < 0.05), 139.2% (p < 0.05), and 324. 6% (p < 0.05) respectively. It is obvious that pathological changes of gastric epithelial tissues induced that there were significant changes in the contents of the DNA, protein and beta-carotene of gastric epithelial tissues. The conclusion can be applied to rapid, low-cost and noninvasive the optical biopsy for gastric cancer and provides a useful reference.
Guang pu xue yu guang pu fen xi = Guang pu 09/2009; 29(9):2499-504. · 0.84 Impact Factor
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ABSTRACT: Differential diagnosis of human colon adenoma was studied using the Kubelka-Munk spectral function of the DNA and protein absorption bands at 260 and 280 nm in vitro. Diffuse reflectance spectra of tissue were measured using a spectrophotometer with an integrating sphere attachment. The results of measurement showed that for the spectral range from 590 to 1 064 nm pathological changes of colon epithelial tissues were induced so that there were significant differences in the averaged values of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log [f(r infinity)] of the DNA absorption bands at 260 nm between normal and adenomatous colon epithelial tissues, and the differences were 218% (p < 0.05) and 68.5% (p < 0.05) respectively. Pathological changes of colon epithelial tissues were induced so that there were significant differences in the averaged values of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log [f(r infinity)] of the protein absorption bands at 280 nm between normal and adenomatous colon epithelial tissues, and the differences were 208% (p < 0.05) and 59.0% (p < 0.05) respectively. Pathological changes of colon epithelial tissues were induced so that there were significant differences in the averaged values of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log [f(r infinity)] of the beta-carotene absorption bands at 480 nm between normal and adenomatous colon epithelial tissues, and the differences were 41.7% (p < 0.05) and 32.9% (p < 0.05) respectively. Obviously, pathological changes of colon epithelial tissues were induced so that there were significant changes in the contents of the DNA, protein and beta-carotene of colon epithelial tissues. The conclusion can be applied to rapid, low-cost and noninvasive optical biopsy of colon adenoma, and provides a useful reference.
Guang pu xue yu guang pu fen xi = Guang pu 06/2009; 29(6):1473-7. · 0.84 Impact Factor
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ABSTRACT: Our objective was to examine the effect of time intervals between Photofrin injection and laser irradiation [i.e., drug-light interval (DLI)] on the mode of action of Photofrin photodynamic therapy (PDT). Kunming mice transplanted with sarcoma-180 cells were used as an animal model. The tumor-bearing mice in the control group were given neither photosensitizer nor laser irradiation. PDT groups were given intravenous (i.v.) injection of Photofrin (7.5 mg/kg) prior to being irradiated with a 630 nm laser at 120 J/cm(2) at different DLIs (1 min-48 h). Tumors and overlying skin were visually examined daily. Histopathological and electron microscopic examinations were carried out 48 h after PDT. Survival rates were recorded. The mice in the groups that had experienced short DLIs (<60 min) showed stronger skin reactions than the groups subjected to long DLIs (>6 h). Histological examination showed that antitumor effects were achieved mainly by the destruction of tumor blood vessels and the formation of thrombosis at short DLIs, whereas, at long DLIs, the tumor cells were killed directly by PDT-mediated cytotoxicity. Electron microscopy revealed various degrees of mitochondrial swelling. The survival rate of the mice subjected to long DLIs was slightly higher than that of the mice subjected to short DLIs. Both vascular (e.g., tumor vessel destruction) and cellular (e.g., cytotoxicity) effects contributed to Photofrin PDT-induced tumor ablation.
Lasers in Medical Science 10/2008; 24(4):597-603. · 2.00 Impact Factor
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ABSTRACT: To evaluate the tumor cell-killing effect of photodynamic therapy against human esophageal cancer cells in vitro and identify the main factors affecting the effect.
Human esophageal cancer Eca-109 cells were incubated for 24 h in vitro with hematoporphyrin derivative (HpD) and Photofrin at different concentrations prior to exposure to a light energy density of 15 J/cm(2) delivered from a DIOMED 630 PDT system. The cell killing effect was also evaluated for different HpD concentrations combined with 3 light energy densities (10, 30, and 50 J/cm(2)), respectively. The cell survival rate was measured using MTT assay, and fluorescence spectrometry was used to detect the intracellular photosensitizer fluorescence of the tumor cells after incubation with HpD for 4 h.
The cell survival rate after incubation with the two photosensitizers at different concentrations were significantly different, and under the 3 different light energy densities, incubation of the cells with different HpD concentrations also resulted in significantly different cell survival rates (P<0.05). At the 4 low photosensitizer concentrations and with different light energy densities, the cell survival rates were similar (P>0.05), but the 4 higher photosensitizer concentrations resulted in significant difference in the cells survival (P<0.05). Correlation analysis showed that the intracellular photosensitizer concentration was positively correlated to the photosensitizer concentrations in cell incubation (r=0.997).
When the light source remains constant, the light energy density, the kinds of photosensitizers and their concentrations are the main factors affecting the Eca-109 cell-killing effect of PDT.
Nan fang yi ke da xue xue bao = Journal of Southern Medical University 01/2008; 27(12):1817-20.
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ABSTRACT: To investigate biological effect of hematoporphyrin derivative (HpD) photodynamic therapy (PDT) on in vitro cultured nasopharyngeal carcinoma (NPC) cell lines CNE2 and C666-1.
CNE2 and C666-1 cells cultured in vitro were incubated in a medium containing HpD at different concentrations (0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, and 4.0 microg/ml) for 4 h followed by exposure to different light doses (2, 5, 10, and 20 J/cm2) using a diode laser at 630 nm with power density of 20 mW/cm2. After 24 h of incubation with HpD-PDT, the survival rate of CNE2 and C666-1 cells were analyzed by MTT assay.
HpD-PDT produced effective killing of CNE2 and C666-1 cells cultured in vitro, and the killing effects were positively correlated with HpD concentration and the irradiation dose. Exposure of CNE2 and C666-1 cells to irradiation dose of 20 J/cm2 resulted in the IC50 of 0.7 and 1.2 microg/ml, respectively (P<0.01). With the same HpD concentration and irradiation dose, the survival rate of C666-1 cells, however, was significantly higher than that of CNE2 cells (P<0.05).
HpD-PDT may result in effective killing of CNE2 and C666-1 cells cultured in vitro, although C666-1 cells are less sensitive to HpD-PDT than CNE2 cells.
Nan fang yi ke da xue xue bao = Journal of Southern Medical University 02/2007; 27(2):165-7.
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ABSTRACT: To prepare photoimmunoconjugate of hematoporphyrin (HP) and herceptin, and study its killing and apoptosis-inducing effect on tumor cells BT-474.
HP-herceptin photoimmunoconjugate was synthesized with EDCI as the condensator. After exposure of the cells to 630 nm laser, the killing effect of the conjugate and cell apoptosis were evaluated by MTT assay and flow cytometry.
Compared with free HP at equivalent dose, the immune reactivity, killing effect and the apoptosis-inducing effect of HP-herceptin immunoconjugate on BT-474 cells was enhanced (P<0.05).
The killing effect of HP-herceptin immunoconjugate is stronger than free HP on BT-474 cells.
Nan fang yi ke da xue xue bao = Journal of Southern Medical University 03/2006; 26(3):355-7.
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ABSTRACT: To study the specific killing effect of the Photofrin-Herceptin immunoconjugate on the tumor cells expressing HER-2.
Photofrin (porfimer sodium) was covalently coupled to Herceptin (trastuzumab) via [1-ethyl-3-(3-dimethyl-aminopropyl)carbodiimide hydrochloride](EDCI) , and the killing effect of this conjugate was evaluated by means of MTT assay on SK-BR-3, MCF-7 and A549 cell lines expressing HER-2 at different levels.
The conjugate had weaker immunoactivity than Herceptin, but possessed stronger killing effect on the cell lines expressing HER-2 than Photofrin, Herceptin, as well as the mixture of Photofrin and Herceptin (P<0.05). In the cell lines negative for HER-2 expression, the killing effect of the conjugate was similar to that of Photofrin, Herceptin, and their mixture.
Photofrin-Herceptin immunoconjugate can specifically kill HER-positive cells in vitro.
Di 1 jun yi da xue xue bao = Academic journal of the first medical college of PLA 08/2005; 25(8):975-8.
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ABSTRACT: To investigate the expressions of recombinant green fluorescent protein (GFP) in 293 cells (human embryonic kidney cells) and CD34(+) cells transfected with adeno-associated virus carrying the gene encoding the recombinant GFP.
Mononuclear cells from the bone marrow were collected on cell separator CS-3000, and CD34(+) cells were separated on immunomagnetic MiniMACS columns. CD34(+) cells and 293 cells were transfected with recombined adeno-associated virus respectively, and the expressions of the GFP were detected by flow cytometry and fluorescence microscopy.
GFP expression was observed in the two cells under fluorescent microscope. The highest transfection efficiency of the recombined adeno-associated virus was about 32.8% in 293 cells and 25% in CD34(+) cells, and decreased with the prolongation of transfection time.
Adeno-associated viral vector encoding recombinant GFP can be transfected into human 293 cells and CD34(+) cells, which provides a basis for future gene therapy.
Di 1 jun yi da xue xue bao = Academic journal of the first medical college of PLA 02/2005; 25(1):26-9.
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Di 1 jun yi da xue xue bao = Academic journal of the first medical college of PLA 04/2004; 24(3):268.
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ABSTRACT: To evaluate the clinical efficacy and adverse effects of Photofrin photodynamic therapy (PDT) in patients with advanced cancers.
Forty patients with advanced cancers in stage IV with lumen obstruction, who failed to respond positively to other treatment regimens, received intravenous administration of Photofrin as the photosensitizer at the dose of 2 mg/kg.b.w. 48 h before PDT by 630 nm light (DIOMED) delivered through cylinder diffusing tip quartz fibers that passed through the biopsy channel of a flexible endoscope. PDT endoscopy was repeated, the necrotic tissue removed and, if necessary, the primary sites and other newly identified sites were subjected to a second exposure 8 h later. Two days after the second exposure, endoscopy was again performed and the necrotic tissue removed. Endoscopy was repeated one month after PDT and periodically thereafter as needed to treat symptomatic residual tumor.
The total rate of response to the treatment was 74% in these patients, and the rate of lumen obstruction due to the tumors decreased from 90% to 10% after PDT, with significantly improved Karnofsky performance score.
Photofrin PDT is effective and safe in the treatment of advanced cancer, which may relieve lumen obstruction and improve patient quality of life.
Di 1 jun yi da xue xue bao = Academic journal of the first medical college of PLA 01/2004; 23(12):1341-3.
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ABSTRACT: To explore the clinical significance of serum erythropoietin (EPO) detection in patients with cancer-related anemia for improving the life quality of the cancer patients in advanced stage with repeated chemotherapy.
The serum EPO levels were determined in 38 cases of cancer-related anemia with enzyme-linked immunosorbent assay (ELISA).
In 24 patients, the serum EPO level was elevated above the normal range, and lowered EPO level was detected in only 1 cases.
Normal or elevated serum EPO level in patients with cancer-related anemia indicates strong abilities of the patients in self regulation, having important clinical implications for the use of EPO.
Di 1 jun yi da xue xue bao = Academic journal of the first medical college of PLA 10/2003; 23(9):954-5.
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ABSTRACT: The aim of this study was to construct recombinant mDHFR-GFP/AAV vector containing mutated dihydrofolate reductase (mDHFR) and green fluorescent protein (GFP) fusion genes and its expression in NIH3T3 cells, to investigate the resistance of the cells to methotrexate. Amplified cDNA of mDHFR and GFP segmented from their plasmid separately were linked by PCR with the aminoacetic acid linker. The fusion gene was inserted into T vector, and after enzyme cutting the fusion gene fragment was inserted into AAV vector, then packaging the vector into recombined AAV and infected NIH3T3 cells. Expression of gene fusion was observed by PCR, fluorescent microscopy and flow cytometry. mDHFR and GFP cDNA were found in NIH3T3 genomic DNA, the GFP expression rate was about 25%, and resistance of the transferred cells to MTX was increased markedly. The results showed that AAV vector can transfer mDHFR and GFP fusion gene into NIH3T3 cells and increase resistance to MTX in gene modified cells. This data provided a basis for application of mDHFR and AAV vector in gene therapy.
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 07/2002; 10(3):212-7.
