A Preliminary Study on the Establishment of the PDTX Model.

OBJECTIVE: The current study aims to explore the establishment of the patient-derived tumor xenograft (PDTX) model. MATERIALS AND METHODS: Twenty patients with gastric cancer, 10 males and 10 females, were enrolled in the current study. Firstly, the volume, invasion and metastasis of the xenografts were observed. Subsequently, the correlation between tumor tissues of the PDTX mouse model and the patients' primary tumor tissues was evaluated by pathological H&E staining and immunohistochemistry. RESULTS: The results showed that the PDTX models corresponding to 15 of the 20 patients were successfully established, and the success rate of PDTX model establishment was 75%. Furthermore, the PDTX models maintained the differentiation degree, morphological characteristics and structural characteristics of tumor cells. CONCLUSION: A PDTX model can be used as a substitute for cancer patients in clinical practice and may be suitable for clinical pharmacodynamic screening and new drug development.

[Interim report of prospective clinical study of two different digestive tract reconstruction after total gastrectomy].

OBJECTIVE: To compare post-operative long-term complications and quality of life of two digestive reconstruction procedures after total gastrectomy. METHODS: A total of 109 gastric cancer patients in Tianjin Medical University Cancer Hospital from March 2012 to February 2013 were prospectively enrolled and randomly divided into functional jejunal interposition (FJI) group (52 cases) and Roux-en-Y (R-Y) group (57 cases). The post-operative complications, nutritional status, and the quality of life were compared between two groups. RESULTS: One, 3 and 6 months after operation, the incidence of R-S syndrome in FJI group was lower as compared to R-Y group[13% (6/45) vs. 37% (18/49), 3% (1/30) vs. 42% (14/33), 5% (1/21) vs. 48% (11/23), all P<0.01], while 3 months after operation, the incidence of reflux and heartburn in FJI group was higher[53% (16/30) vs. 21% (7/33), P<0.01; 37% (11/30) vs. 12% (4/33), P<0.05]. There were no significant differences in quality of life questionnaire QLQ-C30 between R-Y and FJI groups. QLQ-STO22 stomach module revealed in FJI group, the eating score was better, but reflux score was worse as compared to R-Y group 3 months after operation (all P<0.01). CONCLUSIONS: Functional jejunal interposition keeps intestinal continuity preserving and food duodenal passing, which is a reasonable digestive reconstruction procedure.

The most appropriate category of metastatic lymph nodes to evaluate overall survival of gastric cancer following curative resection.

AIMS: The purpose of this study was to provide a nodal grouping category based on metastatic lymph nodes to evaluate overall survival in gastric cancer patients following curative resection (R0). PATIENTS AND METHODS: We reviewed data of 308 gastric cancer patients following curative resection to evaluate significantly survival differences in different categories of the number of metastatic lymph nodes. RESULTS: In 308 evaluable patients, 5-year survival rate (YSR) was 52.9% (median follow-up, 84 months; range, 6-144 months). A total of 6309 lymph nodes were harvested and examined from all 308 patients, and the average number of lymph nodes harvested for per patient was 20.5 (range, 15-49). The average number of metastatic lymph nodes was 5.4 (range, 0-37) per patient. The initial metastatic node cutoffs were designed as 0, 1-4, 5-8, 9-11, 12-16, and >or=17. According to this new category of the number of metastatic lymph nodes, the 5-YSR of various patient groups were 85.7%, 62.8%, 34.3%, 0%, 0%, and 3.4%, respectively. However, we found that there were not significant prognostic differences between patients with 9 metastatic lymph nodes and patients with more than 9 metastatic lymph nodes (P > 0.05). So we redesigned the later cutoffs of number of metastatic lymph nodes. They were as follows: 0, 1-4, 5-8, and >or=9 of metastatic lymph nodes. We demonstrated this new category of the number of metastatic lymph nodes was more appropriate to evaluate overall survival of gastric cancer patients following curative resection than anyone of the current metastatic lymph nodal stagings (such as N stag in UICC, location of metastatic lymph nodes in JCGC, or ratio of metastatic lymph nodes) by using the case-control matched fashion. CONCLUSIONS: Our new category of the number of metastatic lymph nodes was an important prognostic factor of gastric cancer patients following curative resection. There were significant overall survival differences in gastric cancer patient groups with various numbers of metastatic lymph nodes following curative resection.

[Expression change of apoptosis-associated genes after hyperthermia, chemotherapy and radiotherapy in human colon cancer-transplanted nude mice].

OBJECTIVE: To investigate the expression change of apoptosis-associated genes in human colon cancer cells transplanted into nude mice after hyperthermia, chemotherapy and radiotherapy. METHODS: Human colon cancer cell line HT29 was transplanted into the hind limbs of nude mice. Under the laboratory-simulated condition of hyperthermia(43 degree centigrade, 60 min), actual radiation doses and MMC doses were calculated in reference to the clinical practice. The mice were divided into 6 groups according to the treatment approaches: hyperthermia (group A), chemotherapy (group B), radiotherapy (group D), thermochemotherapy (group C), thermoradiotherapy (group E) and thermochemoradiotherapy (group F). The mice were sacrificed at different time points and the tumor tissues were taken for further procedures. The morphologic changes of P53, Bcl-2 and Bax expression in membrane, cytoplasm and nucleus of tumor cell after treatment were observed by immunohistochemistry stain (SP method). RESULTS: All of the six approaches of treatment could down-regulate the expression of P53 and Bcl-2, and up-regulate the expression of Bax in different levels. There was no significant difference in the amount of reduction of P53 expression among group A, C and E. The extent of reduction in the above mentioned groups was significantly different as compared to group B and D. By comparing to group D, the extent of reduction of P53 expression was greater in group B. Down-regulation of Bcl-2 could be enhanced when hyperthermia was combined with chemotherapy (group C) or radiation (group E), but more obvious down-regulation was found in group E as compared to group C. Hyperthermia itself could not obviously up-regulate Bax expression, and it occurred at last. Bax expression increased more by chemotherapy treatment (group B) than that by radiation (group D). By comparing to group C, the greater increase occurred in group E. CONCLUSIONS: Hyperthermia enhances the effects of radiosensitivity and chemosensitivity on tumors by changing the expression of apoptosis-associated genes P53, Bcl-2 and Bax. Hyperthermia combined with chemotherapy and/or radiation has a greater effect on down-regulation of P53 and Bcl-2 expression and up-regulation of Bax expression than any single therapy.

Analysis of risk factors for the interval time, number and pattern of hepatic metastases from gastric cancer after radical gastrectomy.

AIM: To analyze the risk factors for interval time, number and pattern of hepatic metastases from gastric cancer after radical gastrectomy, and provide evidence for predicting and preventing hepatic metastasis from gastric cancer after radical gastrectomy. METHODS: A retrospective study of 87 patients with hepatic metastasis who underwent radical gastrectomy for gastric cancer from 1996 to 2001. The data was analyzed to evaluate significant risk factors for interval time, number and pattern of hepatic metastases originating from gastric cancer after radical gastrectomy. RESULTS: The size of gastric cancer and lymph node metastases were independently correlated with the interval time of hepatic metastases; the depth of invasion was independently correlated with the number of hepatic metastases; while the depth of invasion and Lauren classification were independently correlated with the pattern of hepatic metastases. CONCLUSION: We evaluated the interval time of hepatic metastases with the size of gastric cancer and lymph node metastases. The depth of invasion could be used to evaluate the number of hepatic metastases, while the depth of invasion and the Lauren classification could be used to evaluate the pattern of hepatic metastases in patients who underwent radical gastrectomy.

[Prognostic analysis of liver metastasis in gastric cancer patients with radical gastrectomy].

OBJECTIVE: To elucidate the prognostic factors of liver metastasis in gastric cancer patients with radical gastrectomy. METHODS: Clinicopathological data of 87 liver metastasis patients, undergone radical gastrectomy for gastric cancer from 1996 to 2001, were retrospectively analyzed. RESULTS: Of these 87 patients, the 1-, 3- and 5-year survival rates were 28.8%, 3.6% and 0 respectively and the average survival time after gastrectomy was (11.3+/-1.1) months. By univariate analysis, tumor location, tumor size, histologic differentiation, invasive depth, Lauren classification, metastasis of lymph nodes from lymphadenectomy, vascular invasion, nervous invasion, peritoneal metastasis, number of liver metastasis, liver metastatic distribution and resection of liver metastasis were found to be significant factors associated with the prognosis of liver metastatic patients after radical gastrectomy. By multivariate analysis, location, the Lauren classification, liver metastatic distribution and resection of liver metastasis were found to be independent factors associated with hepatic metastasis after radical gastrectomy. CONCLUSION: Location of gastric cancer, Lauren classification, liver metastatic distribution and resection of liver metastasis are important factors to evaluate the prognosis of liver metastasis in gastric cancer patients with radical gastrectomy.

Change in expression of apoptosis genes after hyperthermia, chemotherapy and radiotherapy in human colon cancer transplanted into nude mice.

AIM: To investigate the change in expression of p53, Bcl-2, and Bax genes in human colon cancer cells transplanted into nude mice after hyperthermia, chemotherapy, radiotherapy, thermochemotherapy, thermoradiotherapy and thermochemoradiotherapy. METHODS: Human colon cancer cell line (HT29) was transplanted into the hind limbs of nude mice. Under laboratory simulated conditions of hyperthermia (43 centigrade, 60 min), the actual radiation doses and doses of mitomycin C (MMC) were calculated in reference to the clinical radiotherapy for human rectal cancer and chemotherapy prescription for colon cancer. The mice were divided into 6 groups according to the treatment approaches: hyperthermia, chemotherapy, radiotherapy, thermochemotherapy, thermoradiotherapy, and thermochemoradiotherapy. The mice were sacrificed at different time points and the tumor tissue was taken for further procedures. The morphologic changes in membrane, cytoplasm and nuclei of tumor cells of p53, Bcl-2, and Bax after treatment, were observed by immunohistochemistry staining. RESULTS: All of the six treatment modalities down-regulated the expression of p53, Bcl-2 and up-regulated the expression of Bax at different levels. The combined therapy of hyperthermia, with chemotherapy, and/or irradiation showed a greater effect on down-regulating the expression of p53 (0.208 +/- 0.009 vs 0.155 +/- 0.0115, P < 0.01) and Bcl-2 (0.086 +/- 0.010 vs 0.026 +/- 0.0170, P < 0.01) and up-regulating Bax expression (0.091 +/- 0.0013 vs 0.207 +/- 0.027, P < 0.01) compared with any single therapy. CONCLUSION: Hyperthermia enhances the effect of radio- and chemotherapy on tumors by changing the expression of apoptosis genes, such as p53, Bcl-2 and Bax.

Non-taxane compounds from the bark of Taxus yunnanensis.

From the bark of Taxus yunnanensis, 15 non-taxane compounds were isolated. Through spectroscopic methods such as ID and 2D NMR and MS experiments, one of them was determined as a new abietane-type diterpenoid named taxayunnin (1). The other 14 known compounds were identified as taxamairin C (2), taxamairin A (3), 3beta-hydroxy-sandaracopimaric acid (4), (+)-3-hydroxy-isodrimenin (5), rubrosterone (6), ponasterone A (7), ecdysterone (8), 20-hydroxy-echysone-20,22-monoacetonide (9), 7-oxositosterol (10), stigmast-4-en-6beta-ol-3-one (11), 5alpha,6beta-dihydroxy-daucosterol (12), beta-sitosterol (13), daucosterol (14), 1-O-beta-D-glucopyranosyl-(2S, 3R, 4E, 8Z)-2-N-(2'-hydroxypalmitoy])-octadeca-sphinga-4,8-dienine (15), respectively. Compounds 4-6, 9-12 and 15 were isolated from Taxus plants for the first time.