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

Background and objective: Long-term use of cyclooxygenase-2 (COX-2) inhibitors can reduce the incidence of digestive cancers, such as colorectal cancers. Proliferating cell nuclear antigen (PCNA) is an important marker of cellular abnormal proliferation. This study was to evaluate the roles and correlation of COX-2 and PCNA in the onset and development of familial adenomatous polyposis (FAP) diseases.

Methods: Thirty-six specimens of FAP adenomas tissues and 32 specimens of FAP carcinoma tissues from 11 FAP families, and 34 specimens of normal colonic mucosa were collected under colonoscopy from November 2004 to July 2007 in the General Hospital of Beijing Military Command. Immunohistochemistry was used to detect the expressions of COX-2 and PCNA.

Results: The positive expression rates of COX-2 in normal colonic mucosa, FAP adenoma, and carcinoma tissues were 0 (0/34), 80.6% (29/36), and 93.8% (30/32), respectively. Proliferation index (PI) in normal mucosa, FAP adenoma, and carcinoma tissues were 17.79+/-7.49, 34.47+/-10.57, and 71.75+/-9.22, respectively. Expressions of COX-2 and PCNA were significantly higher in the FAP adenoma and the carcinoma tissues than in the normal colonic mucosa(P<0.01). The expression of PCNA was significantly higher in the FAP carcinoma tissues than in the FAP adenoma (P<0.01). The expression of PCNA was higher in the FAP adenoma tissues with positive COX-2 than in the FAP adenomas tissues with negative COX-2 (P<0.01).

Conclusions: COX-2 may play an important role in the development of FAP adenomas and colorectal carcinogenesis. COX-2 and PCNA may be important factors in the research on colorectal precancerous lesions and interventional therapy for colorectal neoplasm.

Background and objective: Non-Hodgkin's lymphoma (NHL) is a malignant disease originating from immune system. Studies of the possible relationship between NHL and immune suppression status are of great concern. Regulatory T cell (Treg) is a subtype of T cells that exert an immunosuppressive function. However, the relationship between Treg and lymphoma is controversial. The study was to detect peripheral blood levels of Treg in patients with NHL and healthy adults, and to explore the possible relationship between peripheral blood Treg level and NHL.

Methods: By using flow cytometry with surface staining fluorochrome-conjugated antibodies for CD4, CD25, CD127, the percentages of CD4+CD25highCD127low Treg in peripheral blood of 31 healthy adults and 99 newly diagnosed NHL patients, hospitalized in Sun Yet-sen University Cancer Center from December 2006 to March 2008, were detected and analyzed.

Results: The average peripheral blood CD4+CD25highCD127low Treg levels were 8.07+/-1.90 and 11.20+/-4.40 in healthy adults and newly diagnosed NHL patients, respectively. The difference of peripheral blood Treg levels between them was statistically significant (P<0.001,95% CI:2.02-4.23). The peripheral blood level of Treg was significantly higher in the male NHL patients than in the female patients (P=0.030,95% CI:0.19-3.77). Patients with bad habits (smoking, addict to drink, or both) had significantly higher peripheral blood Treg level than patients without bad habits (P=0.045,95%CI:0.04-3.84). It was no significant relation between peripheral blood Treg level and age, stage, IPI, B symptom, bulky disease, LDH level, pathologic subtype, short term response, HBV infection, and so on. The analysis in diffuse large B-cell lymphoma (DLBCL) subtype showed the same results.

Conclusions: Newly diagnosed NHL patients are in an immunosuppressive statue. Patients with bad habits (smoking, addict to drink, or both) have higher peripheral blood Treg level. Peripheral blood Treg level is irrelevant to the status of disease.

Background and objective: The gross tumor volume (GTV) obviously reduces after induction chemotherapy (IC) for primary locoregionally advanced nasopharyngeal carcinoma (NPC). This study was to investigate the impact of changing gross tumor volume delineation on the dose distribution and clinical treatment outcome after IC.

Methods: From January 2008 to April 2009, 24 patients with Stage III-IVb primary locoregionally advanced NPC were treated with TPF regimen IC followed by intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy . The primary GTVs were delineated into two parts: the post-IC primary GTV (GTVpost-IC-NP), and the region of pre-IC primary GTV minus GTVpost-IC-NP (GTVpre-post-IC-NP). The dose distributions of two plans with GTVpost-IC-NP or pre-IC primary GTV were assessed by analyzing ten cases. The clinical treatment outcome and toxicity of all patients were observed.

Results: The post-IC GTV was significantly smaller than the pre-IC GTV (primary GTV 25.5 cm3 vs. 51.1 cm(3),P=0.001; lymph nodes GTV 9.1 cm(3) vs. 31.4 cm(3), P=0.035; primary + lymph nodes GTV 33.2 cm(3) vs. 82.6 cm(3),P=0.004), the overall GTV with an average shrinkage of 61%. The high dose region was also smaller after IC (volumes covered by 64.4 Gy were 422.9 cm3 vs. 457.9 cm3, P=0.003; 274.2 cm(3) vs.334.5 cm(3) by 68 Gy, P=0.041). The complete response rate was 38% after IC, and 100% three month after radiotherapy. The toxicity of following IMRT with concurrent chemotherapy was similar to that of IMRT with concurrent chemotherapy alone. With median follow-up of 9 months, the locoregionally control rate was 100% and only one patient presented metastasis 15 months after treatment.

Conclusions: TPF regimen IC could significantly reduce tumor volume. The following IMRT with GTVpost-IC-NP plan reduced the high dose region, which didn't add toxicity while had excellent short-term treatment outcome.

Background and objective: Intensity-modulated radiotherapy (IMRT) has recently gained popularity in the treatment of nasopharyngeal carcinoma (NPC) and improved the local-regional control rate. This study was to explore whether IMRT could improved the survival rate while reduce the radiation-related injury for primary NPC patients compared with conventional radiotherapy (CRT).

Methods: From Nov. 2003 to Dec. 2005, 190 patients with NPC treated with IMRT in a single hospital were retrospectively analyzed. Another 190 patients treated with conventional radiotherapy at the same period were matched by prognostic factors respectively. The survival status and treatment-induced adverse effects were investigated. Treatment results, the occurrence and severity of adverse effects of two groups were compared.

Results: In the treatment of NPC, IMRT was superior to CRT in term of 4-year local regional control rate, relapse-free survival rate without reducing the overall survival rate. But there were no significant differences in the 4-year progress-free survival rate and distant metastasis-free survival rate between the two groups. Significant reductions of the occurrence rates and severity of acute skin reaction, neck fibrosis, trismus and xerostomia were noted in IMRT arm. But there were no differences in mucositis, hematological toxicity, hearing loss and radiation induced cranial neuropathy between IMRT arm and CRT arm.

Conclusions: IMRT could improve the local regional control rate and relapse-free survival rate while reduce some radiation-related complications in patients with NPC. But the improvement of overall survival rate did not reach significant level.

Background and objective: Adenovirus vector has been widely used in tumor gene therapy. ING4 is a member of growth inhibiting factors and a potent anti-tumor gene which could induce apoptosis of many tumor cells. This study was to investigate the inhibitory effects of adenovirus-mediated ING4 (Ad-ING4) gene on the proliferation of human prostate cancer PC-3 cells in vitro and in vivo, and to explore its mechanisms.

Methods: Ad-ING4 was obtained by virus-amplification technique. After transfection of purified Ad-ING4 into PC-3 cells, the expression of ING4 was detected by reverse transcription-polymerase chain reaction(RT-PCR); the influence of Ad-ING4 transfection on cell proliferation was evaluated using MTT assay. Cell apoptosis was assessed using Hoechst33258 staining and flow cytometry. RT-PCR was performed to detect the mRNA levels of the transcription of apoptosis-related genes such as bcl-2, bax, p53, and caspase-3. Athymic nude mice bearing PC-3 tumors were intratumorally injected with Ad-ING4 (100 microL, 1x10(9) pfu/mL). Tumor growth was recorded. All nude mice were killed at the end of the experiment to observe the growth of xenografts. The expressions of Bcl-2, Bax, Caspase-3, and CD34 proteins in tumor tissues were detected by immunohistochemistry.

Results: Human ING4 gene was successfully transcribed in PC-3 cells and induced apoptosis by up-regulating p53, bax, caspase-3 expression and down-regulating bcl-2 expression. Inhibition of cell proliferation was significant in PC-3 cells. Tumor growth was significantly inhibited in the Ad-ING4 group as compared with that in the Ad-GFP group and the PBS group (P<0.05). The weight inhibitory rate was 37.0% in the Ad-ING4 group. The expressions of Bax and Caspase-3 were up-regulated, and the expressions of Bcl-2 and CD34 were down-regulated in the Ad-GFP group.

Conclusions: Adenovirus-mediated ING4 gene exhibits anti-tumor ability in human prostate cancer PC-3 cells in vitro and in vivo, and induces apoptosis. This may be related to the up-regulations of p53, bax, Caspase-3 and down-regulation of bcl-2.

Background and objective: Several studies have Shown the correlation of high numbers of tumor-infiltrating natural killer (NK) cells with a good prognosis for cancer patients. This study was to investigate the impact of NK cell infiltration on the survival and prognosis of patients with hepatocellular carcinoma (HCC) after resection.

Methods: The proportion of infiltrating NK cells of HCC patients was measured using flow cytometry, and the expression of CD56+ (NK) cells was investigated using immunohistochemistry. Prognostic values of intratumoral and peritumoral NK cell densities were evaluated by Kaplan-Meier method and Cox regression.

Results: The level of NK cells was significantly lower in tumor-infiltrating lymphocytes (TIL) of HCC patients than in nontumor-infiltrating lymphocytes (NIL) [(11.8 +/- 8.1)% vs. (18.0+/-7.9)%, P=0.002]. The density of NK cells was also significantly lower in cancer nests than in peritumoral lesions (2.3 +/- 2.6 vs. 8.5 +/- 4.5 cells per field, P<0.001). Patients with low intratumoral NK cells had shorter disease-free survival (P=0.027) and overall survival (P=0.005) than patients with high intratumoral NK cells. In contrast, NK cells in the peritumoral area showed no prognostic significance for either disease-free survival or overall survival. Multivariate Cox proportional hazards analysis showed that intratumoral NK cell density was an independent prognostic factor of prolonged overall survival (hazard ratio = 2.658, P=0.019).

Conclusion: Low NK cells infiltration could predict poor prognosis in patients with HCC.

After developing for more than 20 years, image-guided local ablation therapy has become one of the major treatments of hepatocellular carcinoma (HCC). In particular, percutaneous radio-frequency ablation has been widely accepted as the first-line treatment of early-stage HCC. A number of randomized controlled trials have shown some differences between these local ablation techniques. This article reviewed the development of local ablation therapy in the past few years.

Background and objective: Resistance to cisplatin (DDP) remains a major obstacle for the successful treatment of ovarian cancer. This study was to determine the reversal effect of Fe3O4-magnetic nanoparticles (MNPs) on DDP-resistance of ovarian carcinoma cell line SKOV3/DDP, and to explore its correlation with apoptosis-associated genes.

Methods: SKOV3/DDP cells were divided into the DDP group, the Fe3O4-MNPs group, the combination (DDP plus Fe3O4-MNPs) group, and the control group. Cell proliferation was determined by MTT assay. Cell apoptosis was analyzed by flow cytometry (FCM). Intracellular DDP level was detected by inductively coupled plasma atomic emission spectrometry (ICP-AES). The expressions of apoptosis-associated genes, bcl-2, and survivin were detected by reverse transcription-polymerase chain reaction (RT-PCR).

Results: Fe3O4-MNPs reversed DDP-resistance of SKOV3/DDP cells by 2.259 folds. The cell apotosis rate and the intracellular DDP level were significantly higher in the combination group than in the DDP group (P<0.05). Moreover, the mRNA levels of bcl-2 and survivin were significantly lower in the combination group than in the DDP group(P<0.05).

Conclusions: Fe3O4-MNPs can reverse the DDP resistance of ovarian carcinoma SKOV3/DDP cells, and the effect may be ascribed to the down-regulation of bcl-2 and survivin expression.

Background and objective: Previous researches have implicated the close relationship between peroxiredoxin I (Prx I) and cancer progression. A lung adenocarcinoma-related human phage antibody library has been constructed by using phage display techniques. This study was to screen out the single chain variable fragment (scFv) antibodies from the library against a lung adenocarcinoma cell line overexpressing Prx I and to analyze their anti-proliferation ability.

Methods: The insertion ratio of scFv gene was identified by polymerase chain reaction (PCR). The products were digested by Sfi I and Not I, and analyzed on 1% agarose gel. Three rounds of panning against lung adenocarcinoma cell line A549 and Prx I were performed separately, and the positive clones were chosen for soluble expression. The internalization of radiolabeled scFv fragments was then quantified. The proliferation and apoptosis of A549 cells were detected by MTT assay and flow cytometry (FCM). The protein expression of Prx I in A549 cells was analyzed by Western blot.

Results: The insertion ratio of scFv gene was 77% (23/30) and enzyme digestion showed the target products. The sixth phage harvest yielded 180 times as much as that of the first one. Positive reactions with A549 cells were detected in six (60%) of ten random clones. The human scFv fragments against Prx I of lung adenocarcinoma were confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and enzyme-linked immunosorbent assay (ELISA). The internalized scFvs mediated cell apoptosis and Prx I expression down-regulation.

Conclusions: The scFv fragments against Prx I of lung adenocarcinoma are acquired by screening the phage antibody library. The soluble antibodies have specific avidity and inhibitory effect on proliferation of human lung adenocarcinoma cells.

Background and objective: Ezrin and inducible nitric oxide synthase (iNOS) may play an important role in regulating tumor proliferation, invasion, and metastasis. This study was to investigate the expression of Ezrin and iNOS and their correlation to malignant proliferation of salivary gland pleomorphic adenoma (PA).

Methods: Expressions of Ezrin, iNOS and nuclear Ki-67 antigen were detected by immunohistochemistry in common type (n=40), active type (n=25) and malignant (n=11) pleomorphic adenoma.

Results: Expressions of Ezrin, iNOS in common type, active type and malignant pleomorphic adenoma were gradually increased (P<0.05). There was a significant positive correlation between the expression of Ezrin and iNOS (P<0.05). Ki-67 proliferation index (Ki-67 PI) was increased with the increasing of Ezrin and iNOS expressions (P<0.05).

Conclusion: Overexpression of Ezrin and iNOS may promote proliferation and malignant transformation of salivary gland pleomorphic adenoma.