Synthesis, G-Quadruplex DNA binding and cytotoxic properties of naphthalimide substituted styryl dyes.

G-Quadruplex DNAs, formed by G-rich DNA sequences in human genes, are promising targets for design of cancer drugs. In this study, two naphthalimide substituted styryl dyes with different sizes of aromatic groups were synthesized. The spectral analysis showed that the dye X-2 with a large aromatic group formed aggregates in buffer solution displaying very weak fluorescence intensity, and disaggregated in the presence of G-Quadruplex DNAs with large intensity enhancements (up to ~1800 fold). Moreover, X-2 displayed good selectivity to G-Quadruplex DNAs. In contrast, dye X-3 with the smaller aromatic group had much lower fluorescence enhancements and poor selectivity to G-Quadruplex DNAs, suggesting that the suitably sized aromatic ring was essential for the interaction with G-Quadruplex. Further binding studies suggested that X-2 mainly bound on G-quartet surface through end-stacking mode. Cytotoxicity assay showed that both of the two dyes showed good anti-proliferative activities against the cancer cell lines and less cytotoxicity in non-malignant cell lines, which were better than a standard drug 5-fluorouracil. In addition, living cell imaging was also studied and demonstrated the potential applications of the new dye X-2 in bioassays and cell imaging.

[Simultaneous determination of four anthraquinones in rat plasma by HPLC-FLD method and its pharmacokinetic study].

This paper aims to develop a method for the determination of aloe-emodin, rhein, chrysophanol and physcion and study the pharmacokinetic properties of four anthraquinones in rat plasma after oral administration of gardenia and rhubarb decoction. The plasma concentrations at different time points of four anthraquinones were determined by HPLC-FLD method. Plasma samples were extracted with liquid-liquid extraction procedure. Plasma samples were separated on a C18 column (4.6 mm x 150 mm, 5 µm), using 0.2% acetic acid and methanol as mobile phase at a flow rate of 1.0 mL min(-1) with gradient elution. The excitation and emission wavelengths were set at 430, 525 nm, respectively. DAS 2.0 software was applied to calculate the pharmacokinetic parameters. The results showed four anthraquinones can be absorbed. The main parameters of aloe-emodin, rhein, chrysophanol and physcion were as follows: C(max) for aloe-emodin was (0.085 ± 0.058), (3.772 ± 1.152), (0.464 ± 0.267), (0.028 ± 0.008) mg x L(-1) respectively; t(max) for rhein was (1.042 ± 0.510), (0.805 ± 0.307), (1.167 ± 0.283), (0.616 ± 0.162) h respectively; t½ for chrysophanol was (3.557 ± 1.250), (6.879 ± 1.126), (5.196 ± 2.032), (4.337 ± 1.816) h; AUC(0-t) for physcion was (0.504 ± 0.130), (9.558 ± 1.106), (2.545 ± 1.554), (0.052 ± 0.018) mg x h x L(-1). This paper developed a selective, accurate and sensitive HPLC-FLD method for the simultaneous determination of four anthraquiones in rat plasma.

[Clinical study of lymph node metastatic pattern of thoracic esophageal squamous carcinoma].

OBJECTIVE: To analyze the patterns of lymph node metastases of thoracic esophageal carcinoma and define the adequate range of lymph node dissection. METHODS: The clinical data of 217 patients with esophageal carcinoma undergoing radical surgical resection of the lymph nodes in three regions were retrospectively analyzed. RESULTS: Lymph node metastases were found in 136 of the 217 patients (62.6%) and skip metastases of the lymph nodes in 12 patients (5.5%). In 3 989 lymph nodes desected, metastases were identified in 454 lymph nodes (11.38%). The rates of lymph node metastasis were 31.7%, 21.2% and 12.1% in the neck, thoracic mediastinum and abdominal cavity, respectively, in upper thoracic esophageal carcinoma, 21.9%, 30.5% and 15.6% in middle thoracic carcinoma, and 9.75%, 12.7% and 34.5% in lower thoracic carcinoma. The degree of tumor differentiation, depth of tumor invasion and lymphatic vessel invasion were factors influencing lymph node metastases (P<0.05). CONCLUSION: Because of the upward, downward and skip metastasis of esophageal carcinoma cells to the lymph nodes, the operable patients with thoracic esophagus carcinoma should receive radical desection of the lymph nodes in the 3 regions to promote the patients' survival.

[Analysis of lymph node metastases of 217 cases of thoracic esophageal carcinoma and its impact on prognosis].

BACKGROUND & OBJECTIVE: At present, the range of lymph node dissection in treatment of thoracic esophageal cancer is still controversial. This study was designed to explore the status of lymph node metastases of thoracic esophageal carcinoma and its influence on the prognosis and to seek reasonable dissecting range of lymph nodes. METHODS: A retrospective study was performed on the clinical data of 217 patients who had underwent radical operation through three-field lymphadenectomy. Nine distinguishing clinicopathological factors possibly influencing survival rate were chosen. A multivariate analysis of these factors was performed by the computerized Cox proportional hazards model. RESULTS: The 1-, 3-, and 5-year survival rates of all patients were 82.6%, 59.8%, and 48.8%, respectively. The lymph node metastasis rate was 62.6% and the leaping metastasis rate of lymph nodes was 5.5%. In 3989 lymph nodes dissected, metastases were detected in 454 (11.38%). The lymph node metastasis rates present in neck, thoracic mediastinum, and abdominal cavity were 31.7%, 21.2%, and 12.1% in upper-thoracic esophageal carcinoma, 21.9%, 30.5%, and 15.6% in middle-thoracic carcinoma, 9.75%, 12.7%, and 34.5% in lower-thoracic carcinoma, respectively. Degree of tumor differentiation, depth of tumor invasion, and lymphatic vessels invasion were the factors influencing lymph nodes metastases, but the length of tumor was not. According to multivariate analysis, depth of tumor invasion, tumor differentiation, the number of lymph nodes metastatic field, and tumor location were of prognostic significance. With the increasing of the number of lymph nodes metastatic field, the survival rate of the patients dropped gradually(P = 0.0284). CONCLUSION: Lymph node metastasis especially the number of lymph node metastatic field is one of key factors affecting the prognosis of patients. Because of the upward, downward, and leaping spreading of esophageal carcinoma cells to the lymph nodes, the patients with thoracic esophageal carcinoma should be given radical operation through three-field lymphadenectomy to promote the 5-years survival rate.

[A prospective study of combined chemoradiotherapy followed by surgery in the treatment of esophageal carcinoma].

OBJECTIVE: To evaluate the effect of combined chemoradiotherapy followed by surgery for patients with esophageal carcinoma. METHODS: Ninety-seven patients with stage II or III esophageal carcinoma without contraindication against operation and chemoradiotherapy, were randomly divided into two groups: combined group (Group A) 48 and control group (Group B) 49. Patients in group A were given neoadjuvant treatment consisted of chemotherapy with 5-fluorouracil and cisplatin for 2 cycles and radiotherapy of DT36 Gy/12 f/17 d. Three weeks later, operation was performed. Patients in group B were given operation alone. Survival rate was calculated with Kaplan-Meier method. Chi and Log-rank test was used to assess the difference between the two groups. RESULTS: The radical resectability of group A and group B were 85.4% and 65.3% (P = 0.018 1). The lymph node metastasis rate of the two groups were 21.7% and 45.7% (P = 0.019 4). The T stage of group A was significantly lowered (P = 0.003 6). The local and regional recurrence rate of two groups were 34.8% and 58.7% (P = 0.023 6), while there was no significant difference in operative complications between the two groups. Significant improvement in the long-term survival rate was observed in group A, especially in patients who achieved partial and complete response with high 5-year survival rate of 56.5%. CONCLUSION: Preoperative neoadjuvant chemoradiotherapy is able to reduce the tumor and tumor stage, lower the lymph node metastasis rate and local or regional recurrence rate, also it can improve radical resectability and long-term survival without increasing the operative complications.