Characteristics, Prognostic Factors, and Survival of Patients with NK/T-Cell Lymphoma of Non-upper Aerodigestive Tract: A 17-Year Single-Center Experience / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The extranodal natural killer (NK)/T-cell lymphoma (NKTCL) of non-upper aerodigestive tract (NUAT) was found to have clinical heterogeneity compared with NKTCL of the upper aerodigestive tract (UAT) in small scale studies. We conducted this study in a much larger cohort to analyze the clinical characteristics, prognostic factors, treatment modality, and clinical outcomes of patients with NUAT-NKTCL. MATERIALS AND METHODS: From January 2001 to December 2017, a total of 757 NKTCL patients were identified and included in this study, including 92 NUAT-NKTCL patients (12.2%) and 665 UAT-NKTCLpatients (87.8%). RESULTS: NUAT-NKTCL patients had relatively poorer performance status, more unfavorable prognostic factors, and more advanced stage, compared with UAT-NKTCL patients. The 5-year overall survival (OS) was 34.7% for NUAT-NKTCL, which was significantly worse than UAT-NKTCL (64.2%, p<0.001). The median OS duration was 30.9 months for NUAT-NKTCL. Multivariate analysis showed that presence with B symptoms and elevated serum lactate dehydrogenase independently predicted worse OS. International prognostic index score and prognostic index of natural killer lymphoma score still had prognostic values in NUAT-NKTCL, while the Ann Arbor system could not accurately predict the OS. CONCLUSION: NUAT-NKTCL is a distinctive subtype of NKTCL in many aspects. Patients with NUAT-NKTCL have relatively poorer performance status, more unfavorable prognostic factors, more advanced stage, and poorer prognosis.

Hepatitis B virus reactivation and hepatitis in diffuse large B-cell lymphoma patients with resolved hepatitis B receiving rituximab-containing chemotherapy: risk factors and survival / 癌症

<p><b>INTRODUCTION</b>Hepatitis B virus (HBV) reactivation has been reported in B-cell lymphoma patients with resolved hepatitis B (hepatitis B surface antigen [HBsAg]-negative and hepatitis B core antibody [HBcAb]-positive). This study aimed to assess HBV reactivation and hepatitis occurrence in diffuse large B-cell lymphoma (DLBCL) patients with resolved hepatitis B receiving rituximab-containing chemotherapy compared with HBsAg-negative/HBcAb-negative patients to identify risk factors for HBV reactivation and hepatitis occurrence and to analyze whether HBV reactivation and hepatitis affect the survival of DLBCL patients with resolved hepatitis B.</p><p><b>METHODS</b>We reviewed the clinical data of 278 patients with DLBCL treated with rituximab-containing therapy between January 2004 and May 2008 at Sun Yat-sen University Cancer Center, China. Predictive factors for HBV reactivation, hepatitis development, and survival were examined by univariate analysis using the chi-square or Fisher's exact test and by multivariate analysis using the Cox regression model.</p><p><b>RESULTS</b>Among the 278 patients, 165 were HBsAg-negative. Among these 165 patients, 6 (10.9%) of 55 HBcAb-positive (resolved HBV infection) patients experienced HBV reactivation compared with none (0%) of 110 HBcAb-negative patients (P = 0.001). Patients with resolved hepatitis B had a higher hepatitis occurrence rate than HBsAg-negative/HBcAb-negative patients (21.8% vs. 8.2%, P = 0.013). HBcAb positivity and elevated baseline alanine aminotransferase (ALT) levels were independent risk factors for hepatitis. Among the 55 patients with resolved hepatitis B, patients with elevated baseline serum ALT or aspartate aminotransferase (AST) levels were more likely to develop hepatitis than those with normal serum ALT or AST levels (P = 0.037, P = 0.005, respectively). An elevated baseline AST level was an independent risk factor for hepatitis in these patients. Six patients with HBV reactivation recovered after immediate antiviral therapy, and chemotherapy was continued. HBcAb positivity, HBV reactivation, or hepatitis did not negatively affect the survival of DLBCL patients.</p><p><b>CONCLUSIONS</b>DLBCL patients with resolved hepatitis B may have a higher risk of developing HBV reactivation and hepatitis than HBsAg-negative/HBcAb-negative patients. Close monitoring and prompt antiviral therapy are required in these patients.</p>

The prognostic value of Tiam1 protein expression in head and neck squamous cell carcinoma: a retrospective study / 癌症

<p><b>INTRODUCTION</b>Head and neck squamous cell carcinoma (HNSCC) is a common cancer worldwide and has a poor prognosis. A biomarker predicting the clinical outcome of HNSCC patients could be useful in guiding treatment planning. Overexpression of the T lymphoma invasion and metastasis 1 (Tiam1) protein has been implicated in the migration and invasion of neoplasms. However, its role in HNSCC progression needs to be further validated. We detected the expression of Tiam1 in normal and tumor tissues and determined its association with clinical outcomes in patients with HNSCC.</p><p><b>METHODS</b>We measured the expression of Tiam1 in normal and cancerous tissue samples from the patients with HNSCC treated at Sun Yat-sen University Cancer Center between 2001 and 2008. The Tiam1 expression was scored from 0 to 12 based on the percentage of positively stained cells and the staining intensity. We then determined the diagnostic performance of this score in predicting overall survival (OS) and disease-free survival (DFS).</p><p><b>RESULTS</b>Of the 194 evaluable patients, those with advanced disease, lymph node metastasis at diagnosis, and recurrence or metastasis during follow-up had a higher tendency of having high Tiam1 expression as compared with their counterparts (P < 0.05). The proportion of samples with high Tiam1 expression was also higher in cancerous tissues than in non-cancerous tissues (57.7% vs. 13.9%, P < 0.001). Cox proportional hazards regression analysis revealed that Tiam1 expression scores of 5 and greater independently predicted short OS and DFS.</p><p><b>CONCLUSION</b>The Tiam1 expression is shown as a promising biomarker of clinical outcomes in patients with HNSCC and should be evaluated in prospective trials.</p>

Prognostic values of interim and post-therapy 18F-FDG PET/CT scanning in adult patients with Burkitt's lymphoma / 癌症

<p><b>BACKGROUND</b>The prognostic values of interim and post-therapy fluorine-18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (CT) scanning have been confirmed in several subtypes of lymphoma. However, its prognostic value in Burkitt's lymphoma has not been clearly defined. The aim of the present study was to assess the prognostic value of PET/CT scanning during different treatment processes of Burkitt's lymphoma.</p><p><b>METHODS</b>A total of 29 adult patients with newly diagnosed Burkitt's lymphoma were retrospectively involved in this study; of them, 23 patients underwent baseline PET/CT, 15 patients underwent mid-therapy PET/CT after 1-4 cycles of chemotherapy, and 17 patients underwent post-therapy PET/CT after all planned first-line chemotherapy cycles. Mid-therapy and post-therapy PET/CT results (positive vs. negative) were visually interpreted according to the criteria of the International Harmonization Project. The reduction in the maximum standardizes uptake values (∆SUVmax) of 25%, 50%, and 75% were regarded as cutoff points. Overall survival (OS) and progression-free survival (PFS) were regarded as the major endpoints.</p><p><b>RESULTS</b>The median OS and PFS were 27.6 months (range 6.5-78.3 months) and 27.2 months (range 3.0-78.3 months), respectively. The median SUVmax of the baseline PET/CT was 18.3 (range 1.6-35.9), whereas the median SUVmax of the mid-therapy and post-therapy PET/CT decreased to 4.0 (range 0-17.6) and 3.0 (range 0-14.5), respectively. The patients' Eastern Cooperative Oncology Group (ECOG) scores (<2 vs. ≥2) were significantly associated with the baseline PET/CT SUVmax. The mid-therapy and post-therapy PET/CT results (positive vs. negative) showed no significant association with OS or PFS. The optimal cutoff ∆SUVmax from the baseline to the post-therapy PET/CT that could predict a change in OS in patients with Burkitt's lymphoma was 50% (P = 0.019).</p><p><b>CONCLUSIONS</b>(18)F-FDG uptake was intense in Burkitt's lymphoma, and there was a significant reduction in SUVmax during the interim and post-therapy PET/CT procedures. A ∆SUVmax of greater than 50% was a favorable cutoff point to predict the OS of Burkitt's lymphoma patients.</p>

Clinical characteristics of the patients with Hodgkin's lymphoma involving extranodal sites / 癌症

Differences between Hodgkin's lymphoma (HL) patients in China and Western countries are known to exist, but data on Chinese patients with HL are limited. It is not clear whether there are clinical and histological differences in patients with HL involving different extranodal sites. This is the first study to analyze Chinese patients with HL involving different extranodal sites. We selected 22 HL patients with extranodal involvement from more than 250 previously untreated HL patients. Most patients were young males, and 20 of the 22 patients had stage IV disease. The major pathologic types were nodular sclerosis classical HL (NSCHL) and mixed cellularity classical HL(MCCHL). At diagnosis, the most commonly involved extranodal sites were the liver and lung, followed by the bones. There was no significant association between the international prognostic score(IPS) and survival in patients with different extranodal sites. Our data showed the overall survival (OS) and disease-free survival (DFS) rates of low-risk group (IPS = 0-2) were relatively higher than those of high-risk group (IPS ≥ 3), but the IPS did not show predictive power for survival. Although HL with extranodal involvement is rare, it should be considered as a unique form of HL.

Neuroendocrine tumors of the kidney: report of 3 cases and review of the literature / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the biological and clinicopathological characteristics of neuroendocrine tumors of the kidney (KNETs) for improving the diagnosis and treatment of this diseases.</p><p><b>METHODS</b>The pathological and clinical features of 3 KNET cases treated in Sun Yat-sen University Cancer Center between 1999 and 2010 were summarized, and the the histogenesis, pathological and immunohistochemical characteristics, diagnosis and prognosis of KNETs were analyzed with review of all reported cases worldwide.</p><p><b>RESULTS</b>All the 3 patients had waist masses but without clinical manifestations of carcinoid syndrome, and underwent resection of the tumors. The postoperative pathological diagnosis was carcinoid carcinoma in 2 patients and Wilms tumor with neuroendocrine differentiation in 1 patient. Immunohistochemical examination showed that the tumors were positively stained for cytokeratin and vimentin; positivity for neuron-specific enolase and synaptophysin was found in 2 cases, and chromogranin positivity in 1 case. After the operation, 1 patient received chemotherapy, 1 had biotherapy and radiotherapy, and 1 received no further treatment. During the follow-up from 6 months to 6 years, 1 patient died of tumor metastasis, 1 was lost to follow-up, and 1 showed no recurrence until now.</p><p><b>CONCLUSIONS</b>KNETs has specific pathological characteristics. Abdominal masses, acute loin pain and hematuria are the most common symptoms. A definite diagnosis relies on pathology and immunohistochemistry. For early carcinoid carcinoma, surgical resection is curable, but in advanced cases, the prognosis is poor and comprehensive therapy is recommended.</p>

Clinicopathological characteristics of male breast cancer: analysis of 25 cases at a single institution / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate general and clinicopathological characteristics of male breast cancer and analyzed the factors affecting the outcomes of the patients based on the data from a single institution.</p><p><b>METHODS</b>Twenty-five male breast cancer patients treated at Sun Yet-sen University Cancer Center between January 1, 2000 and April 30, 2011 were included into the study. The patients were followed up for 1 to 90 months with a median follow-up of 51 months. The general and clinicopathological characteristics including family history, age, smoking, alcohol drinking, site of tumor, location of tumor, histological type, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), Ki-67, vascular endothelial growth factor (VEGF), P53 expression, neoadjuvant chemotherapy, surgery, adjuvant chemotherapy, adjuvant radiotherapy, adjuvant endocrine therapy, tumor size, lymph node status, distant metastasis and TNM stage were investigated by univariate analysis to evaluate the impact of these factors on patient survival.</p><p><b>RESULTS</b>The 5-year survival rate was 66.5% in these patients. Neoadjuvant chemotherapy, tumor size, lymph node status, distant metastasis and TNM stage were significant predictors for the overall survival. Patients receiving adjuvant endocrine therapy tended to have a better overall survival, though this was not supported statistically (P=0.086). However, patients with neoadjuvant chemotherapy had a poorer overall survival than those without it (P=0.000). Patients in stages I and II had better overall survival than those in stages III and IV (P=0.000).</p><p><b>CONCLUSION</b>The 5-year survival rate was 66.5% in these male breast cancer patients. Neoadjuvant chemotherapy, tumor size, lymph node status, distant metastasis and TNM stage are significant predictors of the overall patient survival.</p>

Efficacy of cetuximab combined with chemotherapy for patients with advanced colorectal cancer and unclear K-ras status / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the efficacy and safety of cetuximab combined with chemotherapy for patients with advanced colorectal cancer (ACRC) and unclear K-ras status.</p><p><b>METHODS</b>Clinical data of 102 ACRC patients, treated by cetuximab combined with chemotherapy in Sun Yat-sen Cancer Center from March 2005 to December 2008, were collected. The cumulative survival rate, objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) of the cases were calculated. The difference in ORR, DCR, PFS and oval survival (OS) between the regimens used as first-line and non-first-line treatment, and between the regimens including oxaliplatin and irinotecan were compared.</p><p><b>RESULTS</b>The overall ORR of cetuximab plus chemotherapy was 43.1%, DCR 73.5%, median PFS 4.0 months, OS 28.5 months, and the 1-year, 3-year, and 5-year survival rate was 89.2%, 50.9% and 27.5%, respectively. The differences in ORR (50.0% vs. 40.0%, P = 0.344), DCR (78.1% vs. 72.9%, P = 0.571) and OS (51.0 months vs. 35.0 months, P = 0.396) between the regimens as first line and as non-first line treatment were not statistically significant. However, the PFS of the regimen as first-line was longer than that as non-first-line treatment (PFS 5.5 months vs. 3.0 months, P = 0.001). The differences in ORR (54.2% vs. 40.0%, P = 0.223), DCR (79.2% vs. 74.7%, P = 0.654), PFS (5.0 months vs. 3.0 months, P = 0.726) and OS (36.0 months vs. 40.0 months, P = 0.759) between cetuximab plus oxliplatin and irinotecan were not statistically significant. The most common side effects of cetuximab plus chemotherapy were acneiform eruption (80.4%, grade 3-4 in 9.8%), neutropenia (66.7%, grade 3-4 in 18.6%), and diarrhea (19.6%, grade 3-4 in 5.9%). No treatment-related death was recorded.</p><p><b>CONCLUSION</b>Patients with advanced colorectal cancer and unclear K-ras treated by cetuximab combined with chemotherapy have good ORR and OS, and the regimen is safe with less adverse events for them. There is no significant difference between the efficacies of regimens as first line and as non-first line treatment, and between cetuximab plus oxliplatin and cetuximab plus irinotecan regimens.</p>

Expression and clinical significance of androgen receptor in triple negative breast cancer / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Androgen receptor (AR) is involved in the pathogenesis of breast cancer, but its role is not clearly defined. This study was to explore the expression of AR and its relationship with clinicopathologic parameters in triple negative breast cancer (negative estrogen receptor, negative progesterone receptor, and negative Her-2).</p><p><b>METHODS</b>Immunohistochemical assays were performed to determine the expression of AR in 137 cases of triple negative breast cancer and 132 cases of non-triple negative breast cancer. The relationships between AR expression and clinicopathologic data and prognosis were analyzed.</p><p><b>RESULTS</b>The positive rate of AR was significantly lower in triple negative breast cancer than in non-triple negative breast (27.7% vs. 83.3%, Chi2=83.963, P<0.001). AR expression was correlated with menorrheal status (Chi2=6.803, P=0.009), tumor grade (Chi2=5.173, P=0.023), node status (Chi2=7.787, P=0.005), 5-year disease-free survival (Chi2=5.012, P=0.025) and 5-year overall survival (Chi2=5.552, P=0.018) in triple negative breast cancer, but was not correlated with clinicopathologic parameters and survival in non-triple negative breast cancer. The 5-year overall survival rate was 78.8% in triple negative breast cancer and 83.3% in non-triple negative breast cancer.</p><p><b>CONCLUSIONS</b>The expression of AR is related to biological behaviors of triple negative breast cancer, and plays a role in endocrinotherapy and prognostic prediction.</p>

The expression of hepatitis B virus surface antigen in 120 Hodgkin's lymphoma patients / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Little is known about the incidence of hepatitis B virus (HBV) infection in Hodgkin's lymphoma patients. This study was to evaluate the impact of HBV infection on the survival of Hodgkin's lymphoma patient.</p><p><b>METHODS</b>Clinical data of 120 Hodgkin's lymphoma patients treated at the Sun Yat-sen University Cancer Center between January 2004 and October 2007 were collected. The impact of prognostic factors including HBV infection on survival was examined by univariate and multivariate analyses. A log-rank test was used for univariate analysis and the Cox proportional hazards regression model was used for multivariate analysis.</p><p><b>RESULTS</b>Of the 120 patients, 18 (15.0%) were hepatitis B virus surface antigen HBsAg-positive. The HBsAg-positive patients had lower 5-year survival rate than did the HBsAg-negative ones (66.9% vs. 91.3%, P = 0.006). When the patients were divided into early-stage (I + II) and advanced-stage (III + IV) groups, the 5-year survival rate was significantly different between the HBsAg-positive and -negative patients in early-stage group (64.8% vs. 96.0%, P < 0.001), while not significantly different in advanced-stage group (75.0% vs. 84.8%, P = 0.667). Both univariate and multivariate analyses showed that radiotherapy and HBV infection were independent prognosis factors for the patients with early-stage Hodgkin's lymphoma (P = 0.006 and 0.014, respectively).</p><p><b>CONCLUSIONS</b>The incidence of HBV infection is similar between Hodgkin's lymphoma patients and normal population. HBV infection is an independent prognosis factor for survival in the patients with early-stage Hodgkin's lymphoma.</p>

Long-term results of rituximab-based salvage chemotherapy for relapsed or refractory diffuse large B-cell lymphoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the efficacy and toxicity of rituximab-based salvage chemotherapy in the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL).</p><p><b>METHODS</b>Sixty-nine patients with relapsed or refractory DLBCL were treated by rituximab-based salvage chemotherapy, including 40 male and 29 female patients with a median age of 51.5 years (range 17 to 82 years). All the patients had prior treatments including of EPOCH, ICE, DHAP, GEMOX, and GDP. Twenty-seven patients also received rituximab treatment as the first-line regimen.</p><p><b>RESULTS</b>The objective response (OR) rate was 73.4% (47/64) in these patients with a complete response (CR) rate of 45.3%. The major adverse effects included bone marrow suppression, fatigue, and gastrointestinal toxicity. The side effects of rituximab were mild, including chill, fever and fatigue. The median follow-up was 40.6 (3.7-179.9) months. Twenty-eight patients died of tumor progression and two died from grade 4 myelosuppression accompanied by severe systemic infection. The median survival was 51.6 (3.7-179.9) months in this group. The 1, 3 and 5-year overall survival was 92%, 62% and 37%, respectively, and in patients without rituximab as the first line treatment, the overall survival at 1 and 3 years (97.4% and 73.5%) was much better than that in rituximab-treated patients (83.1% and 42.8%) (P=0.001). The patients of GCB subtype had better survival compared to the non-GCB subtype, with the 5-year overall survival of 42.3% and 21.4%, respectively (P=0.005).</p><p><b>CONCLUSION</b>Rituximab-based salvage regimens are effective and well tolerable, but further clinical trial is warranted.</p>

A prospective multicenter study of rituximab combined with high-dose chemotherapy and autologous peripheral blood stem cell transplantation for aggressive B-cell lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the feasibility and efficacy of rituximab combined with high-dose chemotherapy supported by autologous peripheral blood stem cell transplantation (ASCT) in patients with aggressive B-cell non-Hodgkin lymphoma (NHL).</p><p><b>METHODS</b>Twenty-eight patients with aggressive B-cell NHL (22 newly diagnosed, 6 relapsed) were enrolled in this study. The high-dose chemotherapy included CHOP regimen (CTX + ADM + VCR + PDN) for the newly diagnosed patients and DICE (DEX + IFO + DDP + VP-16) or EPOCH (VP-16 + PDN + VCR + CTX + ADM) for the relapsed patients. Each patient received infusion of rituximab at a dose of 375 mg/m(2) for four times, on D1 before and on D7 of peripheral blood stem cell mobilization, and on D1 before and D8 after stem cell reinfusion.</p><p><b>RESULTS</b>Complete remission was achieved in all patients after high dose chemotherapy and ASCT. At a median follow-up of 37 months, the estimated overall 4-year survival and progression-free survival rate for all patients were 75.0% and 70.3%, respectively, while both were 72.7% for the previously untreated patients. The therapy was generally well tolerated with few side-effects attributable to rituximab.</p><p><b>CONCLUSION</b>These results suggest that adding rituximab to high-dose chemotherapy with peripheral blood stem cell transplantation is feasible and may be beneficial for patients with aggressive B-cell non-Hodgkin lymphoma.</p>

Efficacy and toxicity of trastuzumab combined vinorelbine in 21 patients with HER2 overexpressing metastatic breast cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the efficacy and toxicity in patients with HER2 overexpressing metastatic breast cancer.</p><p><b>METHODS</b>Twenty-one patients with HER2 overexpressing metastatic breast cancer entered into the study. Trastuzumab (8 mg/kg day 1, then 6 mg/kg every 21 days or 4 mg/kg, then 2 mg/kg every week) and vinorelbine (25 mg/m(2)) was given on days 1 and 8 every 21 days.</p><p><b>RESULTS</b>Overall 56 cycles were given to the 21 patients enrolled into the study (mean 2, range 1-6). All can be evaluated. The response rate was 33.33% (7/21), one patient achieved complete response (CR), six patients achieved partial response (PR), four patients achieved stable disease (SD), ten patients achieved progressive disease (PD)]. The median time to progression was 3.5 months. One year overall survival was 33%. The major toxicity was myelosuppression and peripheral neuritis. A few patients were observed with fever and lower grade cardiac failure.</p><p><b>CONCLUSION</b>The combination of trastuzumab and vinorelbine is an effective and well tolerated therapy in patients with pretreated metastatic breast cancer.</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>

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>

Effect of RNA interference targeting for cyclin D1 gene on growth,cell cycle and apoptosis of K562 / 中国基层医药

Objective cyclin D1 gene plays a significant role in regulating cell cycle progression.Suppression of cyclin D1 protcin expression can effect on cellular proliferation,distribution of cell cycle and apoptosis.This study was to determine whether this effect also existed in chronic leukemia ceil line K562 by inhibiting the expression of cyclin D1 protein through RNA interference in vetro.Methods Plasmid vectors expressing small hairpin RNA (shRNA) targeting at cyclin D1 gene were constructed and transfected into K562 cells by chitosan,cyclin D1 protein was examined by using Western blot analysis.Inhibition of cellular proliferation was evaluated hy soft agar colony formation assay.The cell cycle and apoptosis were determined by flow cytometry.Results Expression of cyclin D1 protein was markedly down-regulated and capability of colony formation was suppressed after transfection with pshRNA-419 and pshRNA-575 at 48h.Down-regulation of cyclin D1 protein could effect on distribution of cell cycle arrested at G_0/G_1 phase and markedly induce apoptosis of K562 cells.But there had no above biological effects ob- served after transfection with blank vector and control vector of m-pshRNA-790.Conclusion Down-regulation of cyclin D1 expression can inhibit growth of K562 cells,and effect on distribution of cell cycle arrested at G_0/G_1 phase.The primary results suggest that cyclin D1 gene might serve as an effective target for the treatment of leukemia.

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>

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>