Trastuzumab in combination with chemotherapy versus chemotherapy alone for first-line treatment of HER2-positive advanced gastric or gastroesophageal junction cancer: a Phase III, multi-center, randomized controlled trial, Chinese subreport / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of trastuzumab in combination with chemotherapy versus chemotherapy alone in the first-line treatment of HER-2-positive advanced gastric or gastro-oesophageal junction cancer.</p><p><b>METHODS</b>Fifteen Chinese research centers are involved in the BO18255 (ToGA) study. Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumor showed overexpression of HER-2 protein by immunohistochemistry +++ or FISH-positive. Patients were randomly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine or 5-FU plus cisplatin or chemotherapy in combination with intravenous trastuzumab. The primary endpoint was overall survival.</p><p><b>RESULTS</b>Eighty-five Chinese patients were enrolled in this study, of whom 84 were included in the primary analysis: trastuzumab plus chemotherapy (FP/H) (n = 36) and chemotherapy alone (FP)(n = 48). The median follow-up was 15.2 months in the FP/H group and 14.2 months in the FP group. The median survival time was 12.6 months in the FP/H group compared with 9.7 months in the FP group [hazard ratio 0.72, 95%CI (0.40; 1.29)]. Grade 3/4 adverse events were higher in the FP/H(63.9%)than FP (47.9%) groups, including neutropenia, vomiting and nausea. Two mild cardiac adverse events occurred in the FP/H group. Severe adverse events occurred in 3 cases of both two groups, respectively.</p><p><b>CONCLUSIONS</b>Addition of trastuzumab to chemotherapy is well tolerated and shows improved survival in Chinese patients with advanced gastric or gastro-oesophageal junction cancer. These results are consistent with the results of ToGA whole population trial. Trastuzumab in combination with chemotherapy can be considered as a new option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer.</p>

Safety and efficacy of first-line bevacizumab combined with taxane therapy in Chinese patients with HER2-negative locally recurrent or metastatic breast cancer: findings from the ATHENA study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Three randomised trials have demonstrated that combining bevacizumab with first-line chemotherapy significantly improves progression-free survival versus chemotherapy alone in HER2-negative locally recurrent/metastatic breast cancer (LR/mBC). However, data from Chinese populations are limited and possible differences between ethnic and geographic populations are unknown. This study was conducted to determine whether there are differences in safety and efficacy in patients with HER2-negative LR/mRC between Chinese and Western populations after they receive first-line bevacizumab combined with taxane-based therapy.</p><p><b>METHODS</b>In the single-arm, open-label, Avastin Therapy for Advanced Breast Cancer (ATHENA) study (NCT00448591), patients with HER2-negative LR/mBC received first-line bevacizumab (investigator's choice of 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) combined with taxane-based therapy. The primary endpoint was safety profile and the secondary is time to progression (TTP). A subpopulation analysis was conducted to assess safety and efficacy in Chinese patients.</p><p><b>RESULTS</b>Of 2264 patients treated in ATHENA, 202 were enrolled in China. Bevacizumab was combined with docetaxel in 90% of Chinese patients and paclitaxel in 10%. The most common grade 3/4 adverse events were diarrhoea (in 5.0% of patients) and hypertension (in 2.5% of patients). Grade 3/4 proteinuria occurred in 0.5%. After median follow-up of 17.6 months and events in 56% of patients, median TTP was 9.0 months (95%CI, 8.4-11.1). Overall survival data were immature.</p><p><b>CONCLUSIONS</b>We found no evidence of increased bevacizumab-related toxicity or reduced efficacy in Chinese LR/mBC patients receiving first-line bevacizumab-taxane therapy compared with predominantly Western populations. The safety profile was generally similar to previously reported LR/mBC trials. Subtle differences may be attributable to different lifestyle and cardiovascular risk factors in Chinese patients compared with the overall population. It appears reasonable to extrapolate findings from bevacizumab-based randomised trials to Chinese populations.</p>

Efficacy and safety of bevacizumab plus chemotherapy in Chinese patients with metastatic colorectal cancer: a randomized phase III ARTIST trial / 癌症

The efficacy and safety of bevacizumab with modified irinotecan, leucovorin bolus, and 5-fluorouracil intravenous infusion (mIFL) in the first-line treatment of metastatic colorectal cancer (mCRC) has not been well evaluated in randomized clinical trials in Chinese patients. We conducted a phrase III trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL [irinotecan (125 mg/m(2)), leucovorin (20 mg/m(2)) bolus, and 5-fluorouracil intravenous infusion (500 mg/m(2)) weekly for four weeks every six weeks] plus bevacizumab (5 mg/kg every two weeks) group and the mIFL group, respectively. Co-primary objectives were progression-free survival (PFS) and 6-month PFS rate. In total, 214 patients were enrolled. Our results showed that addition of bevacizumab to mIFL significantly improved median PFS (4.2 months in the mIFL group vs. 8.3 months in the bevacizumab plus mIFL group, P < 0.001), 6-month PFS rate (25.0% vs. 62.6%, P < 0.001), median overall survival (13.4 months vs. 18.7 months, P = 0.014), and response rate (17% vs. 35%, P = 0.013). Grades 3 and 4 adverse events included diarrhea (21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia (19% in the mIFL group and 33% in the bevacizumab plus mIFL group). No wound-healing complications or congestive heart failure occurred. Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first-line treatment for Chinese patients with mCRC. Clinical benefit and safety profiles were consistent with those observed in pivotal phase III trials with mainly Caucasian patients.

One patient with metastastic colorectal cancer successfully treated by combination of targeted agents after failure of chemotherapy / 癌症

Either cetuximab or bevacizumab can improve the survival of patients with metastastic colorectal cancer (mCRC) if administered combided with cytotoxic agents. However, the effect of two or more target agents in combination is uncertain in these patients. Here, we reported a patient with mCRC successfully treated by a combination of target agents after the failure of chemotherapy. The patient received palliative resection of primary tumor followed by 9 cycles of postoperative XELOX regimen, cytokine-induced killer cell (CIK)-based biotherapy, traditional Chinese medicine, particle implantation in the lung metastatic lesions. The tumor progressed 20 months after the standard treatments. Then, the regimen cetuximab, bevacizumab and cefitinib was applied. During the treatment with targeted agents, grade IV acne-like rash and relatively severe parionychia of the toes occurred. Both of them recovered smoothly. The PET-CT reexamination at 40 days after the target treatment showed that the metabolism of mediastinal lymph nodes basically recovered to a normal level. The combination of multiple targeted agents obtained a progression-free survival(PFS) of 11 months and the patient with a good quality of life during this period.

Preclinical study of apoptosis of B-NHL cell lines induced by anti-CD20 monoclonal antibody / 中国实验血液学杂志

The aim of this study was to investigate the effect of anti-CD20 monoclonal antibody (McAb) on induction of apoptosis in malignant B cell lines in vitro and to explore its possible mechanism. The human Burkitt's lymphoma cell lines (Daudi, Namalwa, Raji and Ramos cells) were cultured in vitro. The inhibitory rate of cell proliferation was detected by XTT assay, the apoptosis of cells was determined by flow cytometry. The expression of BCL-2 in human Burkitt's lymphoma cell lines (Daudi, Namalwa, Raji and Ramos cells) treated with rituximab (20 microg/ml) for 24 hours was analyzed by Western blot. The results showed that the anti-CD20 McAb had a slight anti-proliferation effect on the Daudi, Namalwa, Raji cell lines and no effect on the Ramos cell line. There is no correlation between the effect and the concentration of anti-CD20 McAb. Anti-CD20 McAb as a single agent could weakly induce the apoptosis of four cell lines. The inhibitory rate of cell proliferation ranged from 3% to 10%. Expression of BCL-2 protein was down-regulated after treated by anti-CD20 McAb for 24 hours in Raji and Namalwa cell lines. It is concluded that the anti-CD20 McAb as a monomer can slightly inhibit the proliferation of Daudi, Namalwa and Raji cell lines, the inhibition does not dependent on the treating time and the concentrations of anti-CD20 McAb. Anti-CD20 McAb as a monomer can weakly induce the apoptosis of four cell lines. Expression of BCL-2 in Raji and Namalwa cell lines is down-regulated after the cells were treated by anti-CD20 McAb for 24 hours. Down-regulation of BCL-2 expression may be one of the mechanisms enhancing the cytotoxicity of cytotoxic drugs.

Analysis of the efficacy and safety of gefitinib in the treatment of recurrent advanced non-small cell lung cancer in an expanded access program (EAP) / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study is to evaluate the efficacy and safety of Gefitinib in the treatment of Chinese patients with recurrent advanced non-small-cell lung cancer (NSCLC).</p><p><b>METHODS</b>120 patients were enrolled in this trial from September 2002 to March 2005, and 103 patients were evaluable. All patients were histologically or/and cytologically confirmed to have a locally advanced or metastatic NSCLC, and failed to previous standard treatments. The patients received orally 250 mg of Gefitinib once daily until the disease progression or intolerance to toxicity. First evaluation of response was undertaken one month after drug initiation, then every 2 or 3 months till disease progression. Each patient was followed up every 6 months untill death or end of follow-up.</p><p><b>RESULTS</b>Among the 103 evaluable patients, the objective response rate was 18.4% (19/103), and the disease control rate was 51.5% (53/103). The median time to progression (mTTP) was 3 months (range: 0.2 approximately 40), the median survival time (MST) was 9.8 months (range: 0.5 approximately 51), the 1-, 2-, 3-year survival rates were 44.7%, 26.4% and 13.2%, respectively. The TTP of 41 patients was longer than 6 months with a MST of 25.5 months. The results of COX model analysis suggested that the patients with adenocarcinoma, rash and favourable performance status (PS) had longer TTP. The patients with favourable PS and well controlled disease had longer survival time. Adverse events included skin rash, dry skin, diarrhea and elevation of serum glutamate pyruvate transaminase (SGPT), and were usually mild.</p><p><b>CONCLUSION</b>Gefitinib is effective in treatment of patient with recurrent advanced NSCLC. The patients with controlled disease may achieve a long survival, and the adverse reactions are mild and tolerable.</p>

Preliminary result of multi-center clinical trial on the docetaxel, 5-Fu and DDP in the treatment of advanced, recurrent or metastatic nasopharyngeal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>This clinical study was designed to evaluate the efficacy and toxicity of the combined regimen of docetaxel, 5-Fu and DDP (TPF) in the treatment of advanced or relapsed nasopharyngeal carcinoma (NPC).</p><p><b>METHODS</b>Fifty-six patients with newly diagnosed or recurrent/metastatic NPC following chemotherapy or radiotherapy were enrolled. Both docetaxel and DDP were administered intravenously for 6 hours at the dose of 70 mg/m2 on D1. 5-Fu was given at a dose of 400-500 mg/m2 for 6 hours from D1 to D5. Dexamethasone was routinely administered before injection of docetaxel. This combination was repeated every 3 to 4 weeks, and continued for 4-6 cycles or until PD for the responders.</p><p><b>RESULTS</b>Fifty-one (91.1%) patients were evaluable for response assessment. The response rate for whole group was 72.5% (37/51) with a CR rate of 9.8% (5/51). The stable disease accounted for 17.6% (9/51). There were 17(30.4%) chemotherapy-naïve patients. The overall response rate in those was 82.4% with a CR rate of 29.4%. However, the response rate for previously treated patients was 64.7% without CR. Twelve patients had progressed disease, including 5 (8.9%) died of disease progression with a median follow-up of 11 month (ranged from 1 to 19 months). Totally, 196 courses of chemotherapy were administered. The major toxicity was myelosupression, nausea/vomiting. The incidence of leucopenia was 48% with 22.2% of these in NCI grade II or IV. But only 2 patients (3.6%) experienced leucopenia with a fever. Other mild toxicities including alopecia, asthenia, mucositis and diarrhea were also observed.</p><p><b>CONCLUSION</b>Our preliminary outcome shows docetaxel, 5-Fu and DDP combination is effective and safe for the patients with advanced or relapsed nasopharyngeal carcinoma. But further clinical study is warranted.</p>

Relationship between clinopathological features and outcome of rituximab treatment for diffuse large B-cell lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the relationship of clinopathological features and outcome of rituximab treatment for diffuse large B-cell lymphoma (DLBCL).</p><p><b>METHODS</b>Sixty-nine patients with DLBCL received intravenous infusion of rituximab in combination with different chemotherapy regimens have been retrospectively analyzed. The influencing factors such as age, stage, serum level of lactate dehydrogenase (LDH) and bulky disease were analyzed retrospectively in terms of the response. The anti-/ pro-apoptosis proteins were detected by immunohistochemistry (SP methods). The correlation of protein expression with efficacy of rituximab treatment was also analyzed.</p><p><b>RESULTS</b>In the patients with previously untreated aggressive B-NHL, the combination of rituximab with chemotherapy achieved an overall response rate (ORR) of 90.7% and CR of 69.8%, while in the patients with relapsed disease, that was 80.8% (ORR) and 30.8% (CR). The disease stage (P = 0.046), serum lactate dehydrogenase (LDH) (P = 0.024), physical status (P = 0.009) and bulky disease (P = 0.013) were found to be unfavorable factors for the immunochemotherapy. The treatment efficacy in the patients with Bcl-2 overexpression was better than that in cases with negative one. No correlation of the bax and survivin expression with immunochemotherapy efficacy was observed.</p><p><b>CONCLUSION</b>The immunochemotherapy regimen (rituximab plus chemotherapy) can improve the response rate and CR rate without significant increase in toxicity in patients with diffuse large B-cell lymphoma. The advanced stage, high serum LDH level, relapsed disease, bulky disease and negative Bcl-2 expression are unfavorable factors affecting the therapeutic efficacy.</p>

Clinical characteristics and prognosis of different subtypes of breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics and prognosis of patients with different subtypes of breast cancer: basaloid, HER-2 and luminal types, and try to find the evidence of individualized treatment for the patients.</p><p><b>METHODS</b>1280 histologically and immunohistochemically proven patients with resectable breast cancer were treated, and the clinical data including characteristics, relapse and survival of the patients with different subtypes of breast cancer were analyzed retrospectively.</p><p><b>RESULTS</b>Of the 1280 breast cancer patients, basaloid, HER-2 and luminal types accounted for 20.9%, 23.2% and 55.9%, respectively. Basaloid type was more likely to be found in younger patients frequently with a family history of breast cancer. HER-2 type usually had a tumor of larger size with more advanced stage disease and more metastatic lymph nodes. Luminal type was likely to occur in aged patients with an earlier stage disease. The recurrence rates in basaloid, HER-2 and luminal types were 25.0%, 27.9% and 11.7%, respectively. Patients with basaloid or HER-2 type were found to have a significantly higher recurrence rate than the patients with luminal type breast cancer (P < 0.001), but no significant difference was observed between the basaloid and HER-2 types. However, patients with basaloid type breast cancer were more likely to develop lung metastasis than HER-2 type (13.4% vs. 7.1%, P = 0.017). Up to December 2006, the 5-year disease-free survival (DFS) rates for patients with basaloid, HER-2 and luminal types were 72.2%, 68.2% and 86.2% (P < 0.001), respectively. The overall 5-yr survival (OS) rates of the three groups were 88.6%, 83.8% and 95.8% (P < 0.001) , respectively. Of the patients with luminal type breast cancer, HER2-negative patients had a higher DFS (86.2% vs 57.0%, P < 0.001) and OS (95.8% vs 87.7%, P = 0.0001) compared with those with HER2-positive. The results of Multivariate Cox Regression showed that tumor size and lymph node state were the most important factors influencing the prognosis.</p><p><b>CONCLUSION</b>Each subtype of breast cancer has somewhat its own specific clinical features in terms of recurrence pattern and prognosis, therefore, individualized treatment regimen may be required.</p>

Nadaplatin or cisplatin combined with paclitaxol in treatment for non-small cell lung cancer: a randomized controlled study / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the therapeutic effect, long term survival and side effect on NSCLC patients treated with nadaplatin combined with paclitaxol and cisplatin combined with paclitaxol.</p><p><b>METHODS</b>NSCLC patients with stage IIIB or IV were randomized into two groups in this prospective clinical study. TN group: nadaplatin 30 mg/m2 dl-3, paclitaxol 175 mg/m2 dl, repeated every 4 weeks. TP group: DDP 30 mg/m2 dl-3, paclitaxol 175 mg/m2 dl, repeated every 4 weeks.</p><p><b>RESULTS</b>Sixty patients were enrolled and 57 were evaluable with 30 in TN group and 27 in TP group. The overall response rate were 43.3% vs. 48.1% (P = 0.716), and the disease control rate were 86.7% vs. 88.8% in TN and TP group (P = 0.799), respectively. The median survival time was 14.3 vs. 13.0 months, and the 1- and 2-year survival rate was 62.5% vs. 59.1%, 0% vs. 5.8% in TN and TP group (P = 0.839), respectively. The rates of neutropenia and thrombocytopenia were similar in TN and TP groups whereas more patients in TP group than in TN group suffered from anemia (38.5% vs. 17.5%, P = 0.001), nausea and vomiting (82.6% vs. 35.6%, P = 0.000), fatigue (35.9% vs. 14.1%, P = 0.000) and peripheral neurotoxicity (50.0% vs. 21.9%, calculated by case, P = 0.023).</p><p><b>CONCLUSION</b>Nadaplatin combined with paclitaxol is an effective treatment regimen for NSCLC patients. When compared with similar regimen with cisplatin, the response rate and survival were similar; however, nadaplatin regimen shows some superiority as regards some treatment side effect.</p>

Antitumor immune responses induced by idiotype-pulsed dendritic cells with cell-penetrating peptide vaccination in vivo / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To confirm the therapeutic effect of dendritic cell (DC) vaccine on treatment for mice with lymphoma and the protective effect of DC vaccine loaded with different antigens on the tumor-bearing BAL B/c mice.</p><p><b>METHODS</b>Firstly, a mouse tumor model was set up by s. c. inoculation of 1 x 10(6)/mouse A20 tumor cells. Then different DC vaccines were injected, respectively, and the tumor size and survival time were observed. Secondly, the immunized mice with DC vaccines were challenged with A20 tumor cells, and observed whether a new tumor occurred in the mice and the time of survival.</p><p><b>RESULTS</b>The tumor of mice immunized with Id-DC vaccines grew slower than the controls (mean time of survival was 40.4 days vs. 33.4 days), but statistically not significantly different. The tumor of mice injected with CPP-Id-DC vaccines grew slower than that injected with Id-DC vaccines and controls, and one of 5 mice got CR and the tumor in another one mouse became stable. The median survival time was 70.8 days during a 90-days observation period. The difference was significant (P<0.01). The mice injected with Id-DC vaccines were challenged with A20 tumor cells showed new tumor occurred at 7 - 12 days, and 1 of the 5 mice survived for 60 days. The mice injected with CPP-Id-DC vaccines had no tumor.</p><p><b>CONCLUSION</b>The DC loaded with CPP-Id was better than that loaded with Id alone in treating B cell lymphoma, and It can enhance their antitumor responses and prolong the survival time of the A20 tumor animal models. The vaccine of DC loaded with CPP-Id can protect mice from A20 tumor cell challenge.</p>

Modified BFM-90 regimen greatly improves treatment outcomes of chinese childhood and adolescent lymphoblastic lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>This study was designed to evaluate the efficacy and toxicity of modified BFM-90 regimen originated from Germany authors in the treatment of Chinese childhood and adolescent lymphoblastic lymphoma.</p><p><b>METHODS</b>Thirty-six untreated lymphoblastic lymphoma patients aged from 3 to 18 years were included, with 1 patient in stage II , 9 in stage III and 26 in stage IV. Of these 36 patients, 28 (77.7%) were diagnosed as T cell phenotype, 26 (72. 2%) were found to have mediastinal mass, 21 (58. 3%) had bone marrow involvement. All patients received chemotherapy of modified BFM-90 regimen consisting of induction remission, central nerve system prophylaxis, re-induction remission and maintenance therapy. Total treatment duration was two years. The difference from standard BFM-90 is that we omitted cranial radiotherapy but gave regular high dose methotrexate (MTX) iv infusion and intrathecal MTX therapy during maintenance therapy period. Kaplan-Meier method was used to evaluate survival rate.</p><p><b>RESULTS</b>Of 36 patients, 32 (88%) achieved complete remission (CR) , 1 (2. 7%) partial remission (PR) with an overall response rate of 90.7%. One patient had disease progression ( DP). Two patients received autologous stem cell transplantation at CR1, and two patients received radiotherapy to mediastinum. Totally, 5 patients relapsed, while 2 of them were still alive after salvage chemotherapy. The other 3 died of tumor progression. Two patients died during induction remission, 1 of fungal septicemia, the other of cerebral hemorrhage; one PR and one DP patient died of disease, therefore, totally 7 patients died at last. Median follow-up time was 28 months. Overall three-year survival rate was 78. 3%. The major toxicity was myelosuppression.</p><p><b>CONCLUSION</b>Modified BFM-90 protocol can improve the efficacy and survival of Chinese childhood and adolescent lymphoblastic lymphoma with tolerable toxicity. However, this modified protocol should only be used in experienced cancer center or hematological unit.</p>

CEOP regimen in the treatment for non-Hodgkin's lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study is to analyse the efficacy and toxicity of CEOP regimen in the treatment of non-Hodgkin's lymphoma (NHL).</p><p><b>METHODS</b>From January 1995 to December 2000, 121 patients with NHL were treated by CEOP regimen with or without radiotherapy for the involved field. The clinical characteristics, response, toxicity and long-term survival results were analysed retrospectively.</p><p><b>RESULTS</b>Of these 121 patients, 83 (68.6%) had B-cell NHL and 38(31.4%) peripheral T or NK-cell NHL; 55. 4% (67/121) had early disease (stage I or II), and 89.3% (108/121) had IPI score 0-2. The median age was 53 years (range: 7-79 yr). All patients were treated by CEOP regimen (totally, 471 cycles) with or without radiotherapy. The overall response (OR) rate in this series was 90.9% (110/121) with a complete remission (CR) rate of 71.9% (87/121); whereas the response rate of chemotherapy alone was 88.4% (107/121) with a CR rate of 67.8% (82/121). Major toxicity consisted of grade III-IV myelosuppression (11.9%), neutropenia (1.9%) and thrombocytopenia and anemia (1.1%). Alopecia was observed in 46.3%. However, cardiotoxicity was mild and reversible. Median follow-up duration in this series was 63 months (range: 2-116 months). The overall 1-, 3- and 5-year survival rate was 84.8%, 62.7% and 55.9%, respectively, with a median survival time of 85 months (2-118 months).</p><p><b>CONCLUSION</b>Our data show that CEOP regimen combined with or without radiotherapy for the involved field is effective and well tolerated by the patients with non-Hodgkin's lymphoma.</p>

Significance of EGFR and p-ERK expression in nasopharyngeal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To detect the expression of EGFR and p-ERK in nasopharyngeal carcinoma (NPC) and investigate their clinical significance.</p><p><b>METHODS</b>Immunohistochemistry LSAB method was adopted to detect the expression of EGFR and p-ERK. Statistical analysis was performed using SPSS statistical software package (10.0) to correlate their expression with clinical characteristics and prognosis.</p><p><b>RESULTS</b>Positive staining for EGFR was observed in 39 of 55 cases (70.9%). The EGFR expression was correlated with clinical stage and gender. EGFR expression was correlated with poorer overall survival (OS) and shorter time to progression (TTP). Positive staining for p-ERK was observed in 29 of 55 cases (52.7%). There was a statistically significant association between positive p-ERK expression and advanced clinical stage. Positive p-ERK expression was correlated with poorer OS, disease-free survival (DFS) and TTP. EGFR expression was correlated with the expression of p-ERK. On multivariate analysis, age over 50 years was an independent poor prognostic factor for NPC. Both EGFR and p-ERK were not independent prognostic factors for NPC.</p><p><b>CONCLUSION</b>Expressions of EGFR and p-ERK are detected in NPC. Their abnormally high expression signifies poor prognosis in NPC patients.</p>

Apoptosis induced by DNA primase inhibitor 3,3'-diethyl-9-methylthia-carbocyanine iodide in human leukemia HL-60 cells / 药学学报

<p><b>AIM</b>To investigate apoptosis induced by 3,3'-diethyl-9-methylthia-carbocyanine iodide (DMTCCI), an inhibitor of DNA primase found in our previous study, and the mechanism of DMTCCI in human myelogenous leukemia HL-60 cells.</p><p><b>METHODS</b>HL-60 cells were cultured in RPMI-1640 medium and treated with different concentrations of DMTCCI. MTT assay was used to detect growth inhibition. Flow cytometry and DNA ladders were used to detect apoptosis. Western blotting was used to observe the expression of survivin, Bcl-xL, Bad, Bax, Bcl-2, caspase-9, caspase-3, caspase-6, PARP, DFF45 and lamin B protein. Caspase-3 activity was measured by ApoAlert Caspase-3 Assay Kit.</p><p><b>RESULTS</b>DMTCCI inhibited proliferation of human leukemia HL-60 cells with IC50 value of 0.24 micromol x L(-1). The results of flow cytometry and DNA ladders showed that DMTCCI could induce apoptosis of HL-60 cells. The expression levels of protein survivin and Bcl-xL were down-regulated, Bad and Bax were up-regulated, while Bcl-2 protein had no change in response to DMTCCI treatment in HL-60 cells. Treatment of HL-60 cells with DMTCCI induced the proteolytic cleavage of caspase-9, caspase-3, caspase-6, PARP, DFF45 and lamin B protein. Caspase-3 activity apparently increased at 3 h and reached a peak at 12 h after exposure to 1 micromol x L(-1) of DMTCCI in HL-60 cells.</p><p><b>CONCLUSION</b>DMTCCI inhibited proliferation and induced apoptosis of human leukemia HL-60 cells. Bcl-2 family proteins, survivin and caspases family proteins might play a role in the apoptosis process induced by DMTCCI.</p>

Clinical and pathological reassessment of 493 cases of non-Hodgkin's lymphomas according to current WHO classification of lymphoid neoplasms / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinical and pathological features of non-Hodgkin's lymphoma (NHL) and to evaluate the applicability of the new WHO classification of lymphoid neoplasms.</p><p><b>METHODS</b>According to the new WHO classification, a total of 500 cases of non-Hodgkin's lymphoma diagnosed during the period 1992 - 2003 were reviewed and reappraised with their morphological, immunological and clinical characteristics. Clinical survival analysis was performed in 156 cases that accompanied with follow-up data.</p><p><b>RESULTS</b>Among 500 cases previously diagnosed as lymphomas, 493 cases (98.6%) were confirmed to be NHL, of which B-cell neoplasms was 69.0% and T/NK-cell neoplasms 29.8%. Overall, 6 subtypes including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), unspecified peripheral T-cell lymphoma (PT-un), precursor T-lymphoblastic lymphoma (T-LBL), extranodal marginal zone B-cell lymphoma of MALT type (MALT) and B-small lymphocytic lymphoma (B-SLL) were among the most common subtypes. In pediatric and young patient populations, the most common subtypes were LBL, DLBCL and Burkitt's lymphoma. The frequency of LBL in all patients, especially in the juniors, was much higher than those reported outside Mainland China, and the frequency of FL was much higher than the reported in Mainland China. The frequency of FL was much higher than the reported in Mainland China. Clinical survivals among different histological subtypes of NHL varied considerably with statistic significance (P < 0.001). Marginal zone B-cell lymphoma and SLL demonstrated the best prognosis, LBL and PT-un both the worst, whereas DLBCL and FL had an intermediate prognosis, however, subgrouping of FL according to WHO classification did not reveal a significant survival difference (P > 0.05).</p><p><b>CONCLUSIONS</b>Basing upon the results of a comprehensive survey on the morphologic features, immunophenotyping and clinical data of the above cases, the new WHO classification of lymphoid neoplasms is practical and easily applicable for routine pathological evaluation of lymphoproliferaive disorders and in guiding the clinical management. It appears that the diagnostic and grading criteria for FL in Mainland China need to be re-evaluated.</p>

Long-term outcomes of 392 non-Hodgkin's lymphoma patients treated with pirarubicin based regimens / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyse the effectiveness and toxicity of combined chemotherapy regimen containing pirarubicin (THP) in the treatment of non-Hodgkin's lymphoma (NHL).</p><p><b>METHODS</b>Three hundred and ninety two patients with NHL were treated by THP containing regimen with or without involved field radiotherapy. The clinical characteristics, response, toxicity and long-term survival rates were analysed.</p><p><b>RESULTS</b>The median age of the patients was 47 (5 - 87) years and 26.0% aged more than 60 years. 61.0% of the patients were males and 39.0% females. B-cell and T/NK cell NHL accounted for 68.4% and 23.2% respectively with 56.9% of diffuse large B cell lymphoma and 12.5% of peripheral T cell lymphoma. 92.6% of the patients were ECOG < 1, 63.2% in stage I + II, 84.7% with IPI score 0 - 2 and 25% with B symptoms, 93.9% (368/392) of the patients received CTOP (containing THP) regimen chemotherapy and among them 28.5% (112/392) plus involved field radiotherapy. Altogether 1598 courses were administered on 368 patients. The overall response rate was 88.5% (341/385) with a complete remission (CR) rate of 63.6%, major toxicity was myelosuppression with 12.8%, 1.0% and 1.5% of grade III - IV neutropenia, thrombocytopenia and anemia, respectively. G-CSF support was given for 553 courses (34.6%). Alopecia account for 19.8%. The incidence of mild cardiotoxicity was 5.8%. Treatment-related mortality was 1.6% (6/368). Median follow-up was 24 months. The 1, 3 and 5 year actuarial survival rates were 86.4% , 66.5% and 59.2%, respectively. Median survival time has not been achieved.</p><p><b>CONCLUSION</b>The efficacy of THP based regimen CTOP for the treatment of aggressive NHL is promising. Further clinical trial is warranted.</p>

First-line Xeloda (Capecitabine) treatment for advanced and recurrent colorectal cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of capecitabine as first-line therapy in patients with advanced and recurrent colorectal cancer.</p><p><b>METHODS</b>From December 2000 to November 2001, sixty patients with advanced and recurrent colorectal cancer received first-line capecitabine treatment given at a dose of 1250 mg/m(2) twice daily, on days 1 - 14 every 21 days. At least 2 cycles were administered.</p><p><b>RESULTS</b>The overall response rate was 23.3% with 14 PR, 24 SD (40.0%) and 15 PD. The median survival time was 14.7 months. The survival rate was 63.9% at 12-months and 33.4% at 24-months. Grade III-IV adverse effects were diarrhea in 4 patients (6.6%), anemia in 2 (3.3%) and hand-foot syndrome (HFS) in 1 (1.7%); Grade I-II adverse effects were hyperpigmentation in 20 (33.3%), HFS in 18 (30.0%) and diarrhea in 10 (16.7%).</p><p><b>CONCLUSION</b>Capecitabine is an efficacious and better-tolerated alternative treatment for the patients with advanced and recurrent colorectal cancer.</p>