Prognostic significance of CYFRA21-1, CEA and hemoglobin in patients with esophageal squamous cancer undergoing concurrent chemoradiotherapy.

PURPOSE: To evaluate the prognostic value of serum CYFRA21-1, CEA and hemoglobin levels regarding long-term survival of patients with esophageal squamous cell carcinoma (ESCC) treated with concurrent chemoradiotherapy (CRT). METHODS: Age, gender, Karnofsky Performance Status (KPS), tumor location, tumor length, T stage, N stage and serum hemoglobin, and CYFRA21-1 and CEA levels before concurrent CRT were retrospectively investigated and related to outcome in 113 patients receiving 5-fluorouracil and cisplatin combined with radiotherapy for ESCC. The Kaplan-Meier method was used to analyze prognosis, the log-rank to compare groups, the Cox proportional hazards model for multivariate analysis, and ROC curve analysis for assessment of predictive performance of biologic markers. RESULTS: The median survival time was 20.1 months and the 1-, 2-, 3-, 5- year overall survival rates were 66.4%, 43.4%, 31.9% and 15.0%, respectively. Univariate analysis showed that factors associated with prognosis were KPS, tumor length, T-stage, N-stage, hemoglobin, CYFRA21-1 and CEA level. Multivariate analysis showed T-stage, N-stage, hemoglobin, CYFRA21-1 and CEA level were independent predictors of prognosis. By ROC curve, CYFRA21-1 and hemoglobin showed better predictive performance for OS than CEA (AUC= 0.791, 0.704, 0.545; P=0.000, 0.000, 0.409). CONCLUSIONS: Of all clinicopathological and molecular factors, T stage, N stage, hemoglobin, CYFRA21-1 and CEA level were independent predictors of prognosis for patients with ESCC treated with concurrent CRT. Among biomarkers, CYFRA21-1 and hemoglobin may have a better predictive potential than CEA for long-term outcomes.

[Endostatin in different administration routes combined with adriamycin chemotherapy in the treatment of liver cancer xenograft in mice].

OBJECTIVE: To study the antiangiogenetic and tumor inhibitory effects of endostatin (Es) by intratumoral versus intravenous administration combined with adriamycin (Adm) for treatment of transplanted tumor in mice. METHODS: Forty mice were subjected to subcutaneous implantation of H22 cells and randomly divided into 4 groups by the body weight when the tumor diameter reached 1 cm, namely the control group (with intratumoral and intravenous injection of normal saline), Es intratumoral group (with intratumoral injection Es and intraperitoneal Adm injection), Es vein group (with intravenous Es injection and intraperitoneal Adm injection), and Adm group (with intratumoral saline injection and intraperitoneal Adm injection). The tumor volumes and tumor inhibition rates were calculated, and the expression of vascular endothelial growth factor (VEGF) and the microvessel density (MVD) of the tumors were examined, with the survival time of the mice also observed. RESULTS: The tumor volume was smaller in Es intratumoral group than in the other groups (P<0.05). The expression of VEGF and M VD in Es intratumoral group was significantly decreased as compared with that in the other groups (P<0.05). The survival time was significantly longer in Es intratumoral group and Es vein group than in the other groups (P<0.05), but showed no significant difference between Es intratumoral group and Es vein group (P>0.05). CONCLUSION: In combination with Adm regimen, Es given intratumoral injection produces better effect than intravenous Es injection against angiogenesis and tumor growth, no significant difference can be found in the survival time between them.

[Effect of sequential intratumoral injection of xenogeneic antigens for immunotherapy in immunized mice bearing S180 tumor].

OBJECTIVE: To investigate the therapeutic effect of sequential intratumoral injection of xenogeneic antigens in immunized tumor-bearing mice. METHODS: Sequential intratumoral injection of the xenoantigens was performed in immunized mice bearing S180 tumor. The tumor size changes were observed, and the tumor-infiltrating lymphocytes (TIL) including CD3+CD4+T, CD3+CD8+T, and CD3+CD4+CD25+T lymphocytes were counted with flow cytometry. The concentrations of IL-2 and TNF-alpha in the tumor was measured using ELISA. RESULTS: No significant difference was found in the number of CD3+T lymphocytes in the TILs between different groups. After the immunotherapy, the percentages of CD3+CD4+T, CD3+CD8+T and CD3+CD4+CD25+T lymphocytes were 54%, 22% and 2.91%, respectively, with the CD4+/CD8+ ratio of 2.49, significantly different from that in the control group (P<0.05). The concentrations of IL-2 and TNF-alpha were 100.61 pg/ml and 54.114 pg/ml, respectively, significantly different from those in the control group (P<0.05). CONCLUSION: Sequential intratumoral injection of heteragenetic antigena can significantly increase the amount of effector cells and cytokines in the micro-environment of the tumor, and decrease the expression of T regulatory.

[Synthesis and characterization of folic acid-conjugated chitosan nanoparticles as a tumor-targeted drug carrier].

OBJECTIVE: To synthesize and characterize paclitaxel (PTX)-loaded folate-conjugated chitosan (FA-CTS/PTX) nanoparticles and evaluate its cytotoxicity in vitro. METHODS: CTS/PTX and FA-CTS/PTX nanoparticles were prepared using reductive amidation and ionic gelation of chitosan with tripolyphosphate anions (TPP). The particle size was determined by laser scattering and the morphology observed using transmission electron microscopy, and the PTX content in the nanoparticles was determined using ultraviolet spectrophotometer at 227 nm. The in vitro cytotoxicity of the nanoparticles against HeLa cells was evaluated by MTT assay. Fluorescence microscopy was used to observe the HeLa cells incubated with FA-chitosan nanoparticles in the presence or absence of folic acid in the culture medium. RESULTS: PTX loading did not cause adhesion of the FA-CTS nanoparticles, which presented with uniform spherical morphology with an average diameter of 282.8 nm. The loading and encapsulation efficiencies of FA-CTS/PTX were 9.0% and 75.4%, respectively. The FA-CTS nanoparticles showed a greater extent of intracellular uptake in the absence of folic acid, indicating that the cellular uptake of the nanoparticles occurred through endocytosis mediated by the folate receptors. The PTX-loaded FA-CTS nanoparticles exhibited potent cytotoxicity against HeLa cells, an effect 2- to 3-fold stronger than that of PTX-loaded CTS nanoparticles. CONCLUSION: FA-CTS can be a promising drug carrier with high efficiency in condensing drug, good tumor-targeting ability and low cytotoxicity.

[Expression of DNA transcription- and repair-related genes in cisplatin-resistant human ovarian carcinoma cell line COC1/DDP].

OBJECTIVE: To study the molecular mechanism underlying cisplatin resistance in ovarian carcinoma by detecting the expressions of DNA transcription- and repair-related genes in cisplatin-resistant human ovarian carcinoma COC1 cell line. METHODS: The differential expression of DNA transcription- and repair-related genes between the parental COC1 and cisplatin-resistant COC1/DDP cell line was determined using cDNA microarray. RESULTS AND CONCLUSION: Compared with COC1 cells, 143 genes in COC1/DDP cells showed significant differential expression, among which 20 were DNA transcription- and repair-related genes including 13 significantly up-regulated genes and 7 down-regulated ones. Abnormality of DNA transcription and repair might be involved in the development of cisplatin resistance in COC1/DDP cells.

Synthesis of targeted drug delivery system for fluorouracil using sulfadiazine as the carrier.

OBJECTIVE: To synthesize a targeted drug delivery system for 5-fluorouracil (5Fu) using sulfadiazine (SF) as a carrier with reduced side-effects and strong antitumor activity. METHODS: SF-poly (ethylene glycol) (PEG) conjugate was initially synthesized. 5Fu was subjected to reaction with trichloromethyl chloroformate to prepare chloroformyl 5Fu, which was linked to a spacer hydroxyl group of PEG that served as a macromolecular linking arm between SF and 5Fu. The content of 5Fu in the conjugate was determined by ultraviolet spectrophotometry. Spectrum of ultraviolet and infrared along with differential scanning calorimetry were employed to identify the structure of the conjugate of SFPEG-end capped 5Fu. RESULTS: The drug loading content of the conjugate was 3.2 %, and structural analysis confirmed the linkage between 5Fu and SF via PEG. CONCLUSION: Targeted drug delivery system for 5Fu using SF as a carrier has been successfully synthesized by this means.