Ai zheng = Aizheng = Chinese journal of cancer最新文献

Background and objective: Our previous studies have shown that dendritic cell (DC)-tumor cell fusion vaccine can induce specific antitumor response against esophageal carcinoma cells. This study was to investigate the inhibitory effect of intratumor injection of the antigen-specific cytotoxic T lymphocytes (CTLs) induced by DC-tumor cell fusion vaccine against subcutaneously transplanted esophageal carcinoma cells in nude mice, and to analyze the influence of DC/tumor cell fusion vaccine on proliferation and apoptosis of esophageal carcinoma cells.

Methods: Fusion cell vaccine of mature DCs with EC109 cells were generated by the polyethylene glycol (PEG) protocol and the antigen-specific CTLs were induced. The models of transplanted human esophageal carcinoma in nude mouse were established using EC-109 cell line. Thirty-three nude mice with subcutaneous tumors were randomly divided into three groups. Subcutaneous tumors of group A (n=11), group B (n=11) and group C (n=11) were intratumorally injected with the CTLs induced by DC/tumor fusion vaccine, T lymphocytes and RPMI 1,640 medium respectively once a week. After four weeks of intratumor injection, the nude mice were killed and the nodules were anatomized. The mean volume and weight of tumors of each group were measured, and the tumor inhibitory rates of the Group A and the Group B were calculated and compared. The expression of proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry (S-P method). The mean PCNA-label index (LI) of three groups was compared. The cell cycle and cell apoptosis of the xenograft tumor cells were analyzed by flow cytometry. The mean S-phase fraction (SPF) and the mean rate of cell apoptosis of three groups was compared respectively.

Results: Both the mean volume and the mean weight of xenograft tumors in group A (881.45+/-31.14 mm3 and 0.88+/-0.04 g) were significantly smaller than those of group B (1493.37+/-51.67 mm3 and 1.38+/-0.07 g) and group C (2065.77+/-87.55 mm3 and 2.04+/-0.11 g). The tumor inhibitory rates of Group A was significantly higher than that of group B (56.86% vs. 32.35%, F=1218.08, P=0.001). The mean PCNA-LI of xenograft tumors was less in the group A (26.83+/-0.95)% than in the group B (51.82+/-1.51)% and group C (68.93+/-2.40)% (F=1528.39, P=0.000). The mean SPF of xenograft tumors was less in the group A (12.46+/-0.36)% than in the group B (29.39+/-0.96)% and the group C (42.25+/-1.43)% (P<0.05). The mean apoptotic rate of xenograft tumors was less in the group A (38.03+/-1.21)% than in the group B (17.75+/-0.56)% and the group C (6.59+/-0.22)% (P<0.05).

Conclusion: The model of subcutaneous xenograft tumors in nude mice using human esophageal carcinoma cell line EC-109 has been successfully established. CTLs induced by DC/tumor fusion vaccine has specific antitumor immunity efficacy in vivo. CTLs can inhibit the proliferation of tu

Background and objective: Induction chemotherapy and radiotherapy or concurrent chemoradiotherapy are the most two effective treatments for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). This study was to compare the efficacy of induction-concurrent chemoradiotherapy versus induction chemotherapy and radiotherapy for patients with locoregionally advanced NPC.

Methods: From August 2002 to April 2005, 408 patients were randomly divided into the induction-concurrent chemoradiotherapy (IC/CCRT) group and the induction chemotherapy and radiotherapy (IC/RT) group. Patients in both groups received the same induction chemotherapy, including two cycles of floxuridine (FuDR) plus carboplatin (FuDR750 mg/m2, d1-5; carboplatin AUC=6). All the patients underwent radiotherapy one week after completing the induction chemotherapy. The patients in the IC/CCRT group also received carboplatin (AUC=6) on day 7, 28, and 49 during radiotherapy. Eight patients did not meet the inclusion criteria and were excluded. The remaining 400 cases were analyzed.

Results: Grade III/IV toxicity was found in 28.4% of the patients in the IC/CCRT group and 13.1% in the IC/RT group (P < 0.001). After a median follow up time of 3.9 years, the three-year overall survival was 75.9% and 83.4% (P = 0.12) in the IC/CCRT and IC/RT groups, respectively. No significant differences in the failure-free survival rate, the locoregional control rate, and the distant control rate were found between the two groups.

Conclusion: The IC/CCRT program does not improve the overall survival rate in patients with locoregionally advanced NPC compared with the IC/RT program.

Background and objective: Macrophage migration inhibitory factor (MIF) is closely related to tumorigenesis. This study was to investigate the effects of MIF gene on migration, invasion and proliferation of ovarian cancer cells and to evaluate the significance of MIF protein expression in ovarian cancer tissues.

Methods: Small interfering RNA was used to transiently knock down the expression of MIF gene in HO-8,910 and OVCAR-3 cells. The effect of RNAi was assessed by RT-PCR and western blot. The migration, invasion and proliferation of ovarian cancer cells were determined by transwell chamber assay, invasion assay and MTT assay, respectively. Immunohistochemistry was utilized to examine the expression status of MIF in ovarian cancer tissues.

Results: MIF RNAi significantly inhibited MIF expression in HO-8910 and OVCAR-3 cells and decreased cell proliferation of the two cells (P<0.05). The numbers of migrated and invaded HO-8910 cells were significantly less in the MIF-si1 and MIF-si2 groups than in the NC group, respectively [migration: (48.0+/-7.3) and (38.0+/-3.6) vs. (78.0+/-8.5), P<0.05; invasion: (35.0+/-5.0) and (30.0+/-5.6) vs. (65.0+/-4.6), P<0.05]. The numbers of migrated and invaded OVCAR-3 cells were significantly less in the MIF siRNA groups than in the NC group, respectively [migration: (40.0+/-4.5) and (42.0+/-3.0) vs. (65+/-2.1), P<0.05; invasion: (25.0+/-3.0) and (27.0+/-3.4) vs. (48.0+/-2.4), P<0.05]. Positive expression of MIF protein was detected in 53.5% of ovarian carcinoma tissues and was positively correlated to clinical stages of patients (P<0.01).

Conclusion: MIF might play an important role in the pathogenesis and progression of ovarian cancer. Thus, MIF might be used as a potential therapeutic target in ovarian cancer.

Background and objective: Controversies remain regarding the therapeutic principle for and prognosis of breast cancer patients with isolated local-regional recurrence after mastectomy. This study was to evaluate the role of radiotherapy in treating these patients and to investigate the prognosis.

Methods: Clinical data of 255 breast cancer patients with chest-wall and/or regional lymph node recurrence as first failure after mastectomy from 1990 to 2005 were analyzed. All patients received radiotherapy for recurrence.

Results: The median follow-up time was 45 months (9 months-15.5 years). The median disease-free interval (DFI) was 22 months (2-260 months); it was 37 months in patients with positive hormonal receptor and 17 months in those with unknown or negative receptor. The 2-, 5-, and 8-year overall survival (OS) rates were 86.4%, 56.5%, and 35.0%, respectively. The median survival time was 79 months. The 2-, 5-and, 8-year local control rates were 6.1%, 36.3%, and 27.6%, respectively. Univariate prognostic analysis showed that DFI, site and number of recurrence, receptor status, short-term therapeutic response, initial T status and axillary involvement significantly affected the survival (all P<0.05); multivariate analysis showed that DFI, receptor status, site and number of recurrence were independent prognostic factors. Prognostic index was established to classify the patients. The 2-, 5-and 8-year OS rates were 100%, 91.6%, and 56.4% in the favorable prognosis group, 88.1%, 59.1%, and 36.8% in the medium prognosis group, 68.0%, 8.5%, and 0 in the poor prognosis group (P<0.001).

Conclusion: Radiotherapy is effective for breast cancer patients with isolated local-regional recurrence after mastectomy. Prognostic index could be applied to predict the prognosis.

The advantages of the Chinese 2008 staging system for nasopharyngeal carcinoma included as follows: 1.Application of MRI as the major staging means; discard of the subjective factors. 2.Adoption of some new independent predictor such as metastatic retropharyngeal lymph nodes and RTOG cervical levels. 3.Simplification of the T category. 4.Categorization of N and clinical substage can distinct the risk of distant metastasis and overall survival. All these changes adapted to the modern diagnosis and treatment pattern with a higher degree of practicality. Therefore, developing a prospective, multicenter clinical verification of the existing standards, thereby correcting itself, fulfill the developmental and scientific principles. It may improve as follows: 1.The definition of anatomical structure is restrictive such as nasal cavity and oropharynx, and the expression of masticator space is not intuitive. 2.Proof of evidence-based medicine for the size of lymph nodes included in the N category is insufficient. 3.The risk of local recurrence between the subgroups of T category was not significant. 4.Different definition of the index such as oropharynx and cervical level between the sixth edition UICC / AJCC staging system and the current system will hinder the international exchange of experience and information.

Background and objective: Given the limited information regarding the impact of BMI on treatment outcomes for nasopharyngeal carcinoma, we sought to examine the relationship between body mass index (BMI) and cancer control after radiotherapy.

Methods: We compared clinic outcome information across BMI groups from 1,489 patients treated with radiotherapy between 1990 and 2003. Multivariate analysis was used to determine if BMI significantly predicted adverse recurrence.

Results: In comparison with normal group, there were statistical difference in age, T staging, N staging, and clinical staging (P<0.0001). In survival analysis, in comparison with under-weight group, we could found the hazard ratio was less than one, in the risk of death, cancer recurrence and local recurrence. Meanwhile, the hazard ratio gradually declined when the body weight increased. In univariate survival analysis, under-weight patient had a significant decrease in overall survival,(P<0.0001). When Cox regression model was applied to multivariate analysis, we could found age, T staging, N staging, and BMI grades could be a significant independent prognosis factors(P<0.05).

Conclusion: Under-weight patients had a significant decrease in overall survival rate, distant metastasis failure-free survival, and local relapse-free survival. Pretherapy BMI grades could be a significant independent prognosis factors.

Background and objective: As a new cryptolepine derivative containing indole and quinoline structures, SYUIQ-5 has been reported to induce and stabilize G-quadruplex, inhibit c-myc promoter and telomerase activity. This study was to investigate autophagy induced by a G-quadruplex ligand SYUIQ-5 and its mechanisms in nasopharyngeal cancer cells.

Methods: The protein levels of microtubule-associated protein 1 light chain 3 (LC3), Akt, p-Akt, autophagy-related genes BNIP3 (adenocarcinoma E1B19KD interacting protein 3) and Beclin1 were determined by Western blot in nasopharyngeal cancer cell lines CNE1, CNE2 and HONE1. The mRNA levels of LC3 and BNIP3 was detected using reverse transcription polymerase chain reaction (RT-PCR). RNA interference was used to block the expression of BNIP3 and the effect of BNIP3 was evaluated in SYUIQ-5-induced autophagy. The localization of FOXO3a was observed using confocal immunofluorescence.

Results: The protein and mRNA levels of LC3 in CNE1, CNE2 and HONE1 were up-regulated in a dose-dependent manner after being treated with 0.25-2 microg/mL SYUIQ-5 for 48 h. Incubation of CNE2 cells with SYUIQ-5 markedly inhibited the phosphorylation of Akt, but did not statistically change the total Akt level. After incubation with 3 microg/mL SYUIQ-5 for 24 h, nuclear translocation of FOXO3a was observed under confocal immunofluorescence in CNE2 cells. Autophagy-related gene BNIP3 was significantly elevated in nasopharyngeal cancer cells, whereas Beclin1 was not significantly changed. Knockdown of BNIP3 expression using small interfering RNA caused LC3-II down-regulation.

Conclusion: SYUIQ-5 induces autophagy in cancer cells. This may be related to SYUIQ-5-mediated p-Akt down-regulation and FOXO3a nuclear translocation, which promot LC3 transcription. BNIP3 is involved in SYUIQ-5 induced autophagy.

Background and objective: Survivin, a member of inhibitors of apoptosis protein (IAP) family, is expressed in most tumors as well as in different subcelluar units of tumors. This study was to investigate the clinical significance of survivin in different subcellular units in non-small cell lung cancer (NSCLC).

Methods: The protein expression of survivin was detected by immunohistochemistry (IHC) in the specimens from 51 cases of NSCLC and 21 cases of paracancerous tissues. The relationship between survivin expression and clinical characteristics of patients was analyzed using SPSS 13.0 software.

Results: Positive expression of survivin was mainly detected in cytoplasm and / or nucleus of NSCLC tissues, and the positive rates were 49.0%(25/51), 72.5%(37/51), 3.9%(2/51), 27.5%(14/51) and 23.5%(12/51) in cytoplasm only, in cytoplasm, in nucleus only, in nucleus, and both in cytoplasm and nucleus, respectively. The positive expression rate of survivin was significantly higher in NSCLC tissues (76.5%, 39/51) than in paracancerous tissues (19.0%, 4/21) (P=0.000). The expression of survivin in cytoplasm was correlated with differentiation of tumors (P=0.007). Positive staining of survivin in nucleus, both in cytoplasm and nucleus were significantly related to clinical stage and N stage of NSCLC (P<0.05). The positive rate of survivin was higher in III+IV or N1+N2 stage patients than in I+II or N0 stage patients, respectively (P<0.05). The five-year survival rate was lower in patients with positive expression of survivin in nucleus than in those with negative expression in nucleus(P<0.05). The clinical stage and status of recurrence or metastasis were two independent prognostic factors for the survival of NSCLC patients.

Conclusions: Expression of survivin might be related to the origin and development of NSCLC. The positive expression of survivin in nucleus might be associated with invasion, progression and poor prognosis of NSCLC.