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Background and Objective: Adjuvant chemotherapy has become a standard postoperative treatment for stage III and high risk stage II colorectal carcinoma patients. However, only a few patients can finish 6-month adjuvant chemotherapy. This study was to find out whether the duration of adjuvant chemotherapy would affect the 3-year disease-free survival., Methods: Clinical data of 276 colorectal carcinoma patients, receiving at least two cycles of adjuvant chemotherapy including xeloda, 5-fluorouracil/calcium folinate (5-FU/CF) or Tegafur with or without oxaliplatin after radical operation in Sun Yat-sen University Cancer Center from April, 2003 to December, 2007, were analyzed for the impact of adjuvant chemotherapy duration on the 3-year disease-free survival., Results: Of the 276 patients, 216 received chemotherapy including oxaliplatin, 60 received xeloda, 5-FU/CF or tegafur as adjuvant chemotherapy. Of the 216 patients, only 49 finished the 6-month adjuvant chemotherapy. Both univariate and multivariate analyses showed that chemotherapy duration (P=0.032), sex (P=0.001), N stage (P=0.002), and pathologic differentiation (P=0.043) were independent prognosis factors for 3-year disease-free survival., Conclusion: Duration of adjuvant chemotherapy is an independent prognosis factor for 3-year disease-free survival of colorectal carcinoma patients.

Background and Objective: The incidence of intrahepatic cholangiocarcinoma (ICC) is low. Current treatment for ICC is unsatisfied. This study was to investigate the prognosis of patients with resectable or unresectable ICC., Methods: Clinical data of 84 patients with pathologically confirmed ICC treated at Cancer Center, Sun Yat-sen University from January 1997 to December 2007 were reviewed. Survival and prognosis were analyzed by Kaplan-Meier method and Cox regression model., Results: Of the 84 patients, 56 (66.7%) had resectable ICC, and 28 (33.3%) had unresectable ICC. Among the 56 patients with resectable ICC, 27 (48.2%) underwent radical resection, and 29 (51.8%) underwent palliative resection. The 2-year overall survival rate was 3.1% in unresectable ICC group; it was significantly higher in radical resection group than in palliative resection group (P<0.01). For the patients with resectable ICC, univariate analysis revealed that operation pattern, histological type, tumor size and number, lymph node metastasis, intrahepatic metastasis, portal vein thrombus, postoperative serum level of albumin, preoperative serum levels of CEA, CA199, TBIL, ALT and AST were related to the prognosis; multivariate analysis found that operation pattern, histological type, tumor number, preoperative serum levels of CEA, CA199 and TBIL were independent prognostic factors. For the patients with unresectable ICC, univariate analysis found that histological type and preoperative serum level of CA199 were related to the prognosis; whereas multivariate analysis found that histological type was the only independent prognostic factor. Chemotherapy showed no survival benefit in both resectable and unresectable ICC groups (P=0.30, P=0.78)., Conclusions: Radical resection is the main effective treatment for ICC patients to achieve long-term survival. Preoperative serum levels of CEA, CA199 and TBIL are significant prognostic factor for patients with resectable ICC.

Erythropoietin (EPO) has firstly known to regulate cell proliferation and differentiation along the erythroid lineage. Recent studies have shown that EPO, a pleiotropic cytokine, is proangiogenic and exerts broad tissue-protective effects in diverse nonhematopoietic organs. A series of studies have documented the expression of EPO and EPO receptor (EPO-R) in various cancer cells. The presence of an autocrine-paracrine EPO/EPO-R system may associate with the potential for stimulation of tumor neoangiogenesis and tumor proliferation, inhibition of apoptosis, or modulation of sensitivity to chemoradiotherapy. The complex mechanism needs further research. Recombinant human erythropoietin (rh-EPO) has been widely used in clinic to treat malignancy-associated anemia. Clinical trials have documented the efficacy of rh-EPO in increasing hemoglobin levels, reducing red blood cell (RBC) transfusion requirements and improving quality of life in cancer patients. However, three randomized trials reported negative outcomes with rh-EPO, as patients in the rh-EPO arm fared worse than their placebo-treated counterparts with progression-free survival. This review described EPO and EPO-R biology, focusing on the expression, pleiotropic function and mechanism on nonhematopoietic tissues especially on cancer cells.

Background & Objective: We have constructed plasmid "pTre-IFN-gamma" and proved that the Tet-off system could regulate the expression of human interferon-gamma (IFN-gamma) gene in murine marrow stromal cells in vitro. This study was to investigate the regulatory reversibility of Tet-off system and its effect on the expression of human IFN-gamma gene in murine marrow stromal cells in mice., Methods: Plasmids pTet-off and pTre-IFN-gamma were co-transfected into murine marrow stromal cells. The expression of IFN-gamma in marrow stromal cells was detected with ELISA. The marrow stromal cells were transfused into BABL/c naked mice after co-transfection. The expression of IFN-gamma mRNA in the spleen was detected by real-time fluorescent quantitative reverse transcription-polymerase chain reaction (RT-PCR)., Results: IFN-gamma protein was detected in the culture solution of marrow stromal cells after co-transfection. The secretion peak appeared within the first 72 h. The protein level of IFN-gamma was significantly lower in 300 ng/ml tetracycline hydrochloride-treated marrow stroma cells than in untreated cells [(67.11+/-22.14) pg/1 x 10(7) cells vs. (319.96+/-29.04) pg/1 x 10(7) cells, P<0.001]; its expression was increased when removed tetracycline hydrochloride (P=0.032). The expression of human IFN-gamma mRNA was detected in the spleen. The mRNA level of IFN-gamma was significantly higher in untreated group than in continuous tetracycline hydrochloride-treated group [(1.5+/-0.7)x10(5) copies . (100 mg)(-1) vs. (6.9+/-5.3)x10(2) copies . (100 mg)(-1), P<0.001]; its expression in the mice received tetracycline hydrochloride for one single time lay between the above two groups with significant difference., Conclusion: In mice, Tet-off system could rapidly, efficiently and reversibly regulate the expression of human IFN-gamma gene in marrow stromal cells in vitro and in vivo.

Background & Objective: Erythropoietin receptor (EPO-R) is expressed in many kinds of tumors. The EPO/EPO-R signaling is involved in tumor cell proliferation, angiogenesis, and invasion. This study was to detect the expression of EPO-R in esophageal carcinoma, and explore its correlation to angiogenesis., Methods: The expression of EPO-R protein in 110 specimens of primary esophageal carcinoma was assessed by immunohistochemistry. The microvessels were immunohistochemically labeled with factor VIII-related antigen (FVIII-R Ag) to assess microvessel density (MVD)., Results: EPO-R was detected in all tumor tissues. It was expressed in cytoplasm and/or on cell membrane. Up-regulated EPO-R expression was correlated to poor differentiation (P<0.001) and lymph node metastasis (P=0.006). Increased MVD was correlated to poor differentiation (P<0.001), lymph node metastasis (P<0.001), advanced stage (III/IVA/IVB) (P=0.022), and smoking (P=0.029). The expression of EPO-R was positively correlated to MVD (r=0.618, P<0.01)., Conclusions: EPO-R expressed generally in esophageal carcinoma. The level of EPO-R positively correlates to angiogenesis and progression of esophageal carcinoma. EPO might be an endogenous stimulant of angiogenesis during the progression of esophageal carcinoma.

Background & Objective: Burkitt's lymphoma is an aggressive non-Hodgkin's lymphoma (NHL) and often involves bone marrow and central nerve system. The efficacy of CHOP regimen on Burkitt's lymphoma is poor. The optimal chemotherapy regimen needs to be investigated. This study was to evaluate the efficacy of modified B-NHL-BFM-90 protocol on Burkitt's lymphoma in children and adolescents, and observe the survival status., Methods: From Oct. 1999 to Nov. 2006, 31 untreated Burkitt's lymphoma patients aged less than 20 were enrolled. The median age of these patients was 5 (range, 1.5-20 years old). Of the 31 patients, 20 (64.5%) were male, 11 (35.5%) were female. According to St Jude staging system, 1 (3.2%) was at stage I, 6 (19.4%) at stage II, 8 (25.8%) at stage III, 16 (51.6%) at stage IV; 24 (77.4%) were at stage III/IV. According to clinical stage, lactate dehydrogenase (LDH) level and treatment response, these patients were divided into low, moderate and high risk groups. They received modified B-NHL-BFM-90 protocol: cytotoxic drugs such as cyclophosphamide, vincristine, ifosfamide, etoposide, adriamycin, HD-methotrexate, vindesin, dexamethasone, cytarabinec/HD-cytarabine and intrathecal injection., Results: One patient died of tumor lysis syndrome during prophase. The efficacy was evaluable in 30 patients. Of the 30 patients, 25 (83.3%) achieved complete remission (CR), 3 (10.0%) achieved partial remission (PR), 2 (6.7%) had progressive disease (PD)û 1 had tumor relapse. Grade 3-4 myelosuppression occurred in most patients and were recovered by active support care and did not affect next course of chemotherapy. At a median follow-up of 33 months (range, 3-98 months), the 3-year event-free survival (EFS) rate was 86.0% for all patients, with 100% for stage I/II patients and 82.1% for stage III/IV patients, 100% for low risk group, 92.0% for moderate risk group, and 70.0% for high risk group., Conclusions: Modified B-NHL-BFM-90 protocol can improve the responses and survival of Burkitt's lymphoma in Chinese children and adolescents, with tolerable toxicity. It should be used in the experienced cancer center and hematological unit.

Background & Objective: No more survival improvement could be obtained in advanced non-small cell lung cancer (NSCLC) today with chemotherapy or radiotherapy. Clinical trails showed the antitumor effect of gefitinib on NSCLC with individual differences. This study was to select NSCLC patients of suitable type by comparing the efficacy of gefitinib on advanced NSCLC of bilateral diffuse type and unilateral giant mass type., Methods: Fifty advanced NSCLC patients of bilateral diffuse type (20 cases) and unilateral mass type (30 cases) received treatment of gefitinib. The efficacy of gefitinib on advanced NSCLC between the 2 groups was compared., Results: The median time to symptom improvement was significantly shorter in bilateral diffuse group than in unilateral mass group (4 days vs. 7 days, P<0.01). The disease control rate was significantly higher in bilateral diffuse group than in unilateral mass group (75% vs. 20%, P<0.01). The median progression-free time was significantly longer in bilateral diffuse group than in unilateral mass group (9.5 months vs. 3.6 months, P<0.01). Drug-related adverse events were similar in the 2 groups., Conclusions: Gefitinib is more effective to bilateral diffuse type NSCLC than to unilateral giant mass type NSCLC. It can be considered as the second-line medicine for bilateral diffuse type NSCLC.

Background & Objective: Previous studies showed that the infection rate of hepatitis B virus (HBV) is higher in non-Hodgkin's lymphoma (NHL) patients than in non-primary liver cancer solid tumor patients and general population in the same region, but the correlation of HBV infection to NHL is inconclusive. This study was to compare HBV infection rate of NHL patients with that of non-primary liver cancer solid tumor patients, and explore the correlation of HBV infection to NHL., Methods: The infection of hepatitis B virus surface antigen (HBsAg) in 109 NHL patients and 128 colorectal carcinoma patients was detected. The positive rates of HBsAg in the patients and general population were compared by Chi-square test., Results: The positive rate of HBsAg was significantly higher in NHL patients than in colorectal carcinoma patients and general population (40.4% vs. 14.1% and 17.3%, P<0.01). Regarding colorectal carcinoma patients as a reference group, odds ratio (OR) of NHL in HbsAg-positive population was 2.87, and the 95% confidence interval (95% CI) was 1.830-4.502., Conclusion: The positive rate of HBsAg is higher in NHL patients than in colorectal carcinoma patients and general population.

Background & Objective: The Tet-off system is a gene expression regulating system, which has high efficiency, low toxicity and strict turning-off function. This study was to investigate the regulatory expression of human interferon-gamma (IFNgamma) gene in murine bone marrow stromal cells (BMSCs) by Tet-off system., Methods: Plasmid pTre and human IFNgamma gene were digested using Sac II and Xba I, purified, and ligated by T4 ligase. The recombinant pTre-IFNgamma was identified by restriction analysis and sequencing. pTet-off and pTre-IFNgamma were co-transfected into murine BMSCs. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect IFNgamma mRNA 48 h after transfection. ELISA was used to detect IFNgamma protein in the cell culture medium everyday to analyze the secretary mode of IFNgamma. Then, Tetracycline was added to the culture medium immediately after co-transfection in gradient concentration and 48 h after co-transfection to observe its effect on IFNgamma secretion., Results: Restriction analysis and sequencing confirmed the orientation and sequence of the recombinant plasmid pTre-IFNgamma were correct. RT-PCR detected IFNgamma mRNA in BMSCs 48 h after co-transfection. ELISA showed the secretion of IFNgamma lasted 6 days and a peak appeared in the third 24 h, which was (720.09+/-241.51) pg per 1 x10(6) cells. Increasing tetracycline decreased the secretion of IFNgamma in the first 48 h: 10-100 ng/ml tetracycline decreased the secretion to nearly 0. When tetracycline was added 48 h after co-transfection, the secretion was obviously suppressed 8 h later, and the suppression was strengthened as time went by., Conclusion: The Tet-off system can efficiently and rapidly down-regulate the expression of human IFNgamma gene in murine BMSCs.

Background & Objectives: B cell non-Hodgkin's lymphoma (B-NHL) in childhood and adolescence is aggressive. Routine CHOP regimen can improve the survival rate of patients with early-stage disease, but its effect on patients with advanced disease was poor. Therefore, it is worthwhile to further investigate how to treat patients with B-NHL at different stages. This study was designed to retrospectively analyze and compare CHOP, CHOP+HD-MTX, and BFM-90 regimens in the survival rate of children and adolescents with B-NHL,and explore the optimal therapeutic strategy and protocols., Methods: Thirty cases of 3- to 17-year-old untreated patients with B-NHL were enrolled in CHOP group, with 13 in Stage I/II, and 17 in stage III/IV (St Jude staging), all patients received standard CHOP for 2 to 8 cycles, the regimen was repeated every 3 weeks. Eighteen cases of 3- to 14-year-old untreated patients with B-NHL were enrolled in CHOP+HD-MTX group, with 6 in Stage I/II, and 12 in stage III/IV (St Jude staging), all patients received CHOP+HD-MTX and intrathecal injection for 2 to 8 cycles, the regimen was repeated every 4 weeks. Twenty-five cases of 1.5- to 15-year-old untreated patients with B-NHL were enrolled in BFM-90 group, with 7 in Stage I/II,and 18 in stage III/IV (St Jude staging). The patients with stage I/II disease received A schema alteration with B schema of BFM-90 regimen for 4 to 6 cycles, while the patients with stage III/IV disease received AA schema alteration with BB schema of BFM-90 regimen for 6 cycles, the interval of cycles was 18-21 days. The survival rates were evaluated by Kaplan-Meier method., Results: In CHOP group,complete response (CR) rate was 70% (21/30), and partial response (PR) rate was 13% (4/30). In CHOP+HD-MTX group, CR rate was 83%, PR rate was 16%. In BFM-90 group, CR rate was 96% (24/25), and PR rate was 4% (1/25). The hematologic toxicity incidence was higher in BFM-90 group than in the other 2 groups. In CHOP group, the overall 2-year survival rate was 52.79% (72.73% for Stage I/II, and 37.82% for stage III/IV). In CHOP+HD-MTX group, the overall 2-year survival rate was 55.56 % (83.33 % for Stage I/II, and 41.67 % for stage III/IV). There was no significant difference between CHOP group and CHOP+HD-MTX group in survival rate (P=0.78). In BFM-90 group,2-year event-free survival rate (EFS) was 84.01 % (100% for Stage I/II, and 77.04 % for stage III/IV). The differences in survival rate between BFM-90 group and CHOP group, CHOP+HD-MTX group were both significant (P=0.013, and P=0.034)., Conclusion: BFM-90 regimen can greatly improve the survival rate of children and adolescents with B-NHL, especially of patients with advanced NHL. CHOP, and CHOP+HD-MTX regimens work better for the early stage patients, but produce low survival rate for patients with advanced NHL. A high intensive chemotherapy like BFM-90 regimen is necessary for children and adolescents with advanced B-NHL.

Background & Objective: Neuroblastoma is one of common solid tumors in children. The major treatment modality for neuroblastoma (NB) is chemotherapy combined with operation or irradiation. But the survival rate is still low for advanced patients. Further study is needed for improving cure rate of neuroblastoma. This study was designed to evaluate the efficacy of children with neuroblastoma treated in Cancer Center, Sun Yat-sen University, and to explore reasonable therapy strategy., Methods: The clinical data of 30 children with NB aged from 7 months to 13 years were analyzed retrospectively. These patients were treated with chemotherapy plus operation or radiation. The stages were as follow: II, n=2; III, n=12; IV, n=15; IVS, n=1. Chemotherapy regimen was CAV (cyclophosphamide 750 mg/m(2) d1, vincristine 1.5 mg/m(2), d1, Adriamycin 50 mg/m(2) d1) alternated with EP (teniposide or etoposide 60 mg/m(2) d1-d5, cisplatin 20 mg/m(2) d1-d5). The resection would be done after 4 to 6 cycles of chemotherapy if possible. The chemotherapy or radiation would be done after resection. If operation was not available, the patients continued to receive the chemotherapy. The patients with stage IVS only received cyclophosphamide plus vincristine., Results: Among 30 patients, 2 cases achieved complete remission (CR 6.7%) by chemotherapy alone; 21 cases achieved partial remission (PR 70%); 6 cases showed no change (NC 20%); 1 cases showed progressive diseases (3.3%). Overall response rate (CR+PR) were 76.7% by chemotherapy alone. Of 21 PR patients, 9 cases could be resected;4 cases achieved CR after operation; 1 case achieved CR after radiation. The 2-year overall survival rate was 47.8% for all patients; 100% for Stage II/IVS, 34% for stage III, 22% for stage IV, respectively. Grade III/IV hematological toxicity occurred in 41.2% of the CAV regimen and 26.6% of the EP regimen., Conclusion: Chemotherapy plus operation or radiation is the major treatment for neuroblastoma. CAV/EP alternative chemotherapy is the active regimen for NB. The toxicity is tolerable. Advance stage NB needs further study for improving the prognosis.

Background & Objective: For newly diagnosed non-Hodgkin's lymphoma (NHL), CHOP regimen shows good response, but quite a few patients belong to intrinsic drug resistance, or relapse after complete remission (CR). Clinical study has been focused on screening them out and improving the therapeutic response. The purpose of this study was to explore the predictive value of serum 90K/Mac-2BP on chemotherapy response in newly diagnosed NHLs, and to analyze the potential significance of serum 90K/Mac-2BP as a tumor marker in NHLs., Methods: Thirty healthy donors and 100 newly diagnosed patients were included in this study. Serum 90K/Mac-2BP level was measured with the quantitative sandwich enzyme linked immunosorbent assay (ELISA), and the relationship between serum 90K/Mac-2BP level and the therapeutic response as well as clinicopathological features was analyzed., Results: The level of serum 90K/Mac-2BP was associated with the response of the initial treatment in patients who received CHOP (CTX, ADM, VCR, Pred) chemotherapy. The response rate in patients with higher level (mean serum level >13.62 microg/ml) of 90K/Mac-2BP was 47.6% (20/42). The response rate in patients with lower level (mean serum level 0.05)., Conclusion: The level of serum 90K/Mac-2BP might predict the response of CHOP chemotherapy in NHLs, and is hopeful to be a new tumor marker.