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Abstract Background Optimal management and outcome of primary gastric lymphoma (PGL) have not been well defined in the rituximab era. This study aimed to analyze the clinical characteristics, prognostic factors, and roles of different treatment modalities in Chinese patients with PGL. Methods The clinicopathological features of 83 Chinese patients with PGL were retrospectively reviewed. Staging was performed according to the Lugano staging system for gastrointestinal non-Hodgkin's lymphoma. Results The predominant pathologic subtype among Chinese patients with PGL in our study was diffuse large B cell lymphoma (DLBCL), followed by mucosa-associated lymphoid tissue (MALT) lymphoma. Among the 57 patients with gastric DLBCL, 20 patients (35.1%) were classified as the germinal center B cell-like (GCB) subtype and 37 patients (64.9%) as the non-GCB subtype. The 83 patients had a five-year overall survival (OS) and event-free survival (EFS) of 52% and 59%, respectively. Cox regression analysis showed that stage-modified international prognostic index (IPI) and performance status (PS) were independent predictors of survival. In the 67 B-cell lymphoma patients who received chemotherapy, 36 patients treated with rituximab (at least 3 cycles) had a mean OS of 72 months (95% CI 62-81) versus 62 months (95% CI 47-76) for patients without rituximab treatment (P = 0.021). Conclusion The proportion of Chinese gastric DLBCL cases with non-GCB subtype was higher than the GCB subtype. Stage-modified IPI and PS were effective prognostic factors in Chinese patients with PGL. Our data suggested that primary gastric B-cell lymphoma might have an improved outcome with rituximab in addition to chemotherapy. More studies are necessary, preferentially large prospective randomized clinical trials to obtain more information on the impact of the rituximab in the primary gastric B-cell lymphoma.

Abstract Background It is expected that prolonged circulation of anticancer drugs will increase their anticancer activity while decreasing their toxic side effects. The purpose of this study was to prepare 5-fluorouracil (5-FU) loaded block copolymers, with poly(γ-benzyl-L-glutamate) (PBLG) as the hydrophobic block and poly(ethylene glycol) (PEG) as the hydrophilic block, and then examine the 5-FU release characteristics, pharmacokinetics, and anticancer effects of this novel compound. Methods 5-FU loaded PEG-PBLG (5-FU/PEG-PBLG) nanoparticles were prepared by dialysis and then scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to observe the shape and size of the nanoparticles, and ultraviolet spectrophotometry was used to evaluate the 5-FU in vitro release characteristics. The pharmacokinetic parameters of 5-FU/PEG-PBLG nanoparticles in rabbit plasma were determined by measuring the 5-FUby high-performance liquid chromatography (HPLC). To study in vivo effects, LoVo cells (human colon cancer cell line) or Tca8113 cells (human oral squamous cell carcinoma cell line) were implanted in BALB/c nude mice that were subsequently treated with 5-FU or 5-FU/PEG-PBLG nanospheres. Results 5-FU/PEG-PBLG nanoparticles had a core-shell spherical structure with a diameter of 200 nm and a shell thickness of 30 nm. The drug loading capacity was 27.1% and the drug encapsulation was 61.5%. Compared with 5-FU, 5-FU/PEG-PBLG nanoparticles had a longer elimination half-life (t1/2, 33.3 h vs. 5 min), lower peak concentration (C, 4563.5 μg/L vs. 17047.3 μg/L), and greater distribution volume (VD, 0.114 L vs. 0.069 L). Compared with a blank control, LoVo cell xenografts and Tca8113 cell xenografts treated with 5-FU or 5-FU/PEG-PBLG nanoparticles grew slower and had prolonged tumor doubling times. 5-FU/PEG-PBLG nanoparticles showed greater inhibition of tumor growth than 5-FU (p < 0.01). In the PEG-PBLG nanoparticle control group, there was no tumor inhibition (p > 0.05). Conclusion In our model system, 5-FU/PEG-PBLG nanoparticles changed the pharmacokinetic behavior of 5-FU, thus increasing its anticancer activity. 5-Fluorouracil loaded nanoparticles have potential as a novel anticancer drug that may have useful clinical applications.

Background and Objective: The Expand Access Program (EAP) of Iressa(gefitinib, ZD1839) in China was initiated in 2001 with the aim of providing gefitinib to non-small cell lung cancer (NSCLC) patients who failed to respond to standard treatment or who could not tolerate chemotherapy. The primary objective was to describe the quality of life (QoL), tumor control status, drug safety, and clinical/genomic features of active long-term survivors enrolled in the EAP. The secondary objective was to determine the clinical characteristics of long-term survivors in the EAP program., Methods: In this descriptive observational study, data were collected based on epidemiological research methods. The data of patients who were actively participating in the EAP and still undergoing gefitinib treatment were collected in a cross-sectional manner to reflect the current status of each patient. Meanwhile, the data of patients who had been on gefitinib treatment for more than three years and had already been terminated from the EAP or those who were fast progressors were collected retrospectively., Results: A total of 934 patients were screened in the EAP database. Among these patients, 25 were active long-term survivors still enrolled in the EAP and 34 were long-term survivors who had been terminated from the program. These 59 patients were enrolled in 15 different centers in China, and the remaining 875 patients were fast progressors. The median scores for the Functional Assessment of Cancer Therapy-Lung (FACT-L), Trial Outcome Index (TOI), and Lung Cancer Subscale (LCS) of the 25 long-term survivors were 64.5, 37 and 12.5, respectively. The performance status 0-1 accounted for 91.6% of the data observed during the cross-sectional survey. For active long-term survivors, the objective response rate was 37.5%, the disease control rate was 87.5%, and the median duration of response time was almost 68 months. In the long-term survivor group, no serious and new adverse events were reported. Patients who were aged under 65 years (68.5%), affected with adenocarcinoma (81.4%), female (55.9%), or had never smoked (71%) accounted for majority of the long-term survivors. The percentage of females was significantly higher in the long-term survivor group than in the fast progressor group (P=0.02). Three tissue samples were collected from each of the 24 active long-term survivors, and one patient was found to be positive of EGFR mutation. Twenty-two blood samples were also collected, and one patient tested positive for EGFR mutation. The Ki67 protein expression was also tested in three tissue samples, and two of these were found positive for Ki67 protein expression, with a response duration time of over 73 months., Conclusions: A 250 mg dose of gefitinib offers good QoL and is safe for advanced NSCLC long-term survivors even after more than three years of treatment. According to the evaluation of the current tumor control statuses of patients, gefitinib demonstrates good efficacy in these active long-term survivors.

Lymphotoxin alpha (LTalpha) was first identified as a direct anti-tumor factor, whereas increasing evidence has recently shown that in most cases the growth inhibition mediated by LTalpha requires the synergistic action of other factors, such as RNA transcription or protein synthesis inhibitor. In this study, we evaluated the combined effects of LTalpha and ten chemotherapeutic drugs on cell growth in a panel of human epithelial tumor cells, and explored the molecular mechanism of their mutual action. The results showed that platinums (cisplatin, carboplatin, oxaliplatin) are more universally effective than other chemotherapeutic drugs (doxorubicin, epi-doxorubicin, 5-flourouracil, mitomycin, cyclophosphamide, vincristine and vinorelbine) to enhance the response of six human epithelial tumor cell lines (A375, Bcap37, NCI-H157, SW480, BGC-823 and HeLa) to LTalpha. A systemic treatment with a combination of LTalpha and cisplatin in a human Bcap37 breast cancer xenograft nude mice model dramatically improved the therapeutic efficacy of LTalpha. Further analysis revealed that the sensitization of platinums was associated with platinums-induced suppression of nuclear factor-kappaB (NFkappaB) and subsequent downregulation of X-linked inhibitor of apoptosis protein (XIAP), which rescued caspase-3 from inhibition. Our results suggested that a proper combination of bio-agents such as LTalpha and conventional chemotherapeutic drugs such as platinums may be an efficient treatment strategy for human epithelial cancers.

Background: Gefitinib, a selective inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, has been approved effective in local advanced or metastatic non-small cell lung cancer (NSCLC), with the equivalent response rate to that of chemotherapy in Asian patients. Asian ethnicity, gender, smoking history, adenocarcinoma histology were remarkably associated with gefitinib response and survival. However, predictive factors of gefitinib response and survival are still unclear in Asian population. In this study, we retrospectively reviewed the data of 153 Chinese NSCLC patients who received a single agent of gefitinib with the purpose of identifying the potential predictive factors of gefitinib response and survival., Methods: Tumor response, survival and the clinicopathologic factors of 153 NSCLC patients treated between November of 2003 and June of 2004 were collected retrospectively from the multicenter clinical trial in China. Pearson Chi-square test and Logistic regression test were performed respectively as univariate and multivariate analyses of gefitinib response. Overall survivals between groups with different predictive factors were compared by log-rank tests. Multivariate analysis was performed to identify factors that independently predict for survival., Results: A total of 153 patients were included in this analysis. Objective response rate was statistically significant higher in patients with younger age (≤65 years) and longer interval from diagnosis to gefitinib treatment (≥6 months) in multivariate analysis (P < 0.05). The median follow-up duration was 10.0 months (0.5-16.8). The median survival was 10.3 months (95% CI: 8.1-12.6) and 1-year survival was 44.1%. Significant independent predictive factors associated with longer survival in multivariate analysis were good performance status (score 0-1), controlled disease (CR+PR+SD) to most recent chemotherapy and controlled disease to gefitinib (P < 0.05)., Conclusions: Gefitinib is effective in local advanced or metastatic NSCLC patients who failed to chemotherapy in Chinese population. In Chinese NSCLC population, younger age (≤65 years) and longer interval from diagnosis to gefitinib treatment (≥6 months) were predictive factors in multivariate analysis for gefitinib response; good performance status (score 0-1), controlled disease to most recent chemotherapy and controlled disease to gefitinib were independent prognostic factors for survival.

Background: Endostar™ (rh-endostatin, YH-16) is a new recombinant human endostatin developed by Medgenn Bioengineering Co. Ltd., Yantai, Shandong, P.R.China. Pre-clinical study indicated that YH-16 could inhibit tumor endothelial cell proliferation, angiogenesis and tumor growth. Phase I and phase II studies revealed that YH-16 was effective as single agent with good tolerance in clinical use.The current study was to compare the response rate , median ti me to progression (TTP) ,clinical benefit andsafety in patients with advanced non-small cell lung cancer ( NSCLC) , who were treated with YH-16 plus vi-norelbine and cisplatin (NP) or placebo plus NP., Methods: Four hundred and ninety-three histologically or cy-tologically confirmed stage IIIB and IV NSCLC patients , withlife expectancy > 3 months and ECOG perform-ance status 0-2 , were enrolledin a randomized ,double-blind ,placebo-controlled , multicenter trial ,either trialgroup : NP plus YH-16 (vinorelbine 25 mg/m² on day 1 and day 5 ,cisplatin 30mg/m² on days 2 to 4 , YH-167.5mg/m² on days 1 to 14) or control group : NP plus placebo (vinorelbine 25 mg/m² on day 1 and day 5 ,cis-platin 30 mg/m² on days 2 to 4 ,0.9% sodium-chloride 3 .75 ml on days 1 to 14) every 3 weeks for 2-6 cycles .The trial endpoints included response rate ,clinical benefit rate ,time to progression,quality of life and safety ., Results: Of 486 assessable patients , overall response rate was 35.4% in trial group and 19.5% in controlgroup (P=0 .0003) . The median TTP was 6 .3 months and 3 .6 months for trial group and control group respectively (P < 0 .001) . The clinical benefit rate was 73 .3 %in trial group and 64.0% in control group (P=0 .035) .In untreated patients of trial group and control group ,the response rate was 40 .0% and 23.9%(P=0 .003) ,the clinical benefit rate was 76 .5 % and 65 .0 % (P=0 .023) ,the median TTP was 6 .6 and 3 .7months (P=0 .0000) ,respectively .In pretreated patients of trial group and control group ,the response ratewas 23.9% and 8.5%(P=0 .034) ,the clinical benefit rate was 65.2% and 61.7%(P=0 .68) ,the median TTP was 5 .7 and 3 .2 months (P=0 .0002) ,respectively . The relief rate of clinical symptoms in trial groupwas higher than that of those in control group ,but no significance existed (P > 0 .05) . The score of quality oflife in trial group was significantly higher than that in control group (P=0 .0155) after treatment . There were no significant differences in incidence of hematologic and non-hematologic toxicity , moderate and severe sideeffects betweentrial group and control group ., Conclusions: The addition of YH-16 to NP regimen results in significantly and clinically meaningful improvement in response rate , median time to tumor progression,and clinical benefit rate compared with NP alone in advanced NSCLC patients . YH-16 in combination with chemotherapy shows a synergic activity and a favorable toxic profile in advanced cancer patients .

Background: To study the expressions and its clinical significances of fas and P53 protein in human non-small cell lung cancer (NSCLC) after complete surgical resection., Methods: Immunohistochemical stain of fas and P53 was performed on paraffin-embedded sections from 269 NSCLC patients who underwent surgery and were followed up for 1.1 to 122.2 (median, 48.4) months postoperatively. Differences in survival rates and clinical characteristics were evaluated by SPSS10.0 statistical software packet., Results: The rate of fas and P53 expression in NSCLC cancer tissue was 43.1% and 49.4% respectively. Fas expressions were seen more frequently in female patients (59.3% vs 39.1%, P < 0.01). Univariate analysis showed that fas expression was a good factor for predicting prognosis. The 5-year survival rate of the patients whose tumors had positive fas expression was significantly better than those individuals whose tumors had negative fas expression (51.4% vs 42.4%, P=0.02), especially in patients in stage I and IIIA . The expression of P53 had no significant influence on the prognosis of these 269 NSCLC patients. Combined analysis of fas and P53 expression in NSCLC cancer tissues showed significant prognostic influence (P=0.01). The 5-year survival were 40.1% (fas+ and P53-), 45.4% (both positive or both negative) and 57.2% (fas- and P53+), respectively. COX multivariate analysis showed that reduced fas expression in 269 NSCLC is an independent risk factor, especially in stage IIIA NSCLC., Conclusions: Fas and P53 protein are indicators of NSCLC biological behavior. Reduced fas expression in NSCLC is an independent risk factor for early stage patients. Analysis of apoptosis related proteins expression in tumors might be helpful to predict the prognosis of patients with NSCLC.

Objective: To evaluate Amifostin's effect on protecting kidney from cisplatinum (DDP) injury and its adverse reactions and safety., Methods: 193 Patients were divided into two groups randomly: 102 in group A (treatment group) and 91 in group B (control group). Indexes such as blood routine, blood calcium, liver function, blood urea nitrogen (BUN), cretinine (C), and urinary N-acetyl-beta-D-glucosaminidase (NAG)/C and micro-albumin (MAB/C) were monitored at different intervals before or after treatment., Results: In the two courses of treatment in both groups, the deviation (D) values of MAB/C before treatment and on D2 in group A were lower than those in grop B (P < 0.05), so were those before treatment and on D4, D6, D10 and D14 (P < 0.01). The D-values of NAG/C before treatment and on D4, D6, D10 and D14 in the first course of group A were obviously lower than those on the corresponding days in group B (P < 0.01), so were those before treatment and on D2, D4, D6, D10 and D14 in the second course (P < 0.01)., Conclusion: The reduction of MAB/C and NAG/C by Amifostin in group A demonstrates that: Amifostin is able to effectively protect the renal function, regardless of the type of tumor. In contrast with group B, Amifostin in group A shows no protection for tumor in lung cancer and ovarian cancer. The main side effects of Amifostin are mild hypotension, nausea, vomiting and hypocalcemia in some patients.

Objective: To evaluate the response rate and adverse reactions of xeloda, an analogue of 5-fluorouracil, in the treatment of relapsed and metastatic breast cancer., Methods: Twenty-two breast cancer patients who had recurrent and metastatic measurable foci were treated from Dec. 1999 to Feb. 2000. Xeloda was given, as a single drug, at a dose of or 2,510 mg/m2/d, bid, for two weeks followed by one week rest as one cycle, at least for one cycle in each patient., Results: Among these 22 patients, there was no complete response. Rates of partial response 8(36.4%), stable disease 10(45.5%), progressive disease 4(18.2%), and clinical benefit response (CR + PR + SD) 18(81.8%). The response rate in patients who had failed in previous chemotherapy of taxanes and/or anthracycline was 30.0%-33.3%. The common adverse reactions were hand-foot syndrome, skin pigmentation, nausea, vomiting, anorexia and fatigue. Mild-moderate anemia and leukopenia were observed in 36.4% of patients. Stomatitis, dizziness, diarrhea and chest distress were present in some. One patient developed degree IV myelosuppression. Total bilirubin and alanine transaminase (ALAT) mild elevation occurred in a few patients., Conclusion: Xeloda is an effective drug in the treatment of patients with relapsed and metastatic breast cancer, especially for those who have failed in chemotherapy with taxanes and/or anthracycline. Xeloda is well tolerated but has mild adverse reactions.