Interleukin-21 (IL-21) is a recently discovered cytokine with immunomodulatory activity. It is a new member of the IL-2 family and mainly secreted by the activated CD4~+ T cells. IL-21 can promote proliferation, differentiation and function of T cells, natural killer (NK) cells, and B cells after binding with its receptor, thereby effectively strengthen the innate immunity and acquired immunity. The antitumor activity of IL-21 has been demonstrated in several tumor models. Its phase Ⅱ trials is being carried out in metastatic melanoma and renal cell carcinoma. IL-21 has a broad application prospects in the treatment of malignant tumors. Here, we review the anti-tumor effects of IL-21 and the application foreground of combination of IL-21 with other drugs in future tumor immunotherapy.

The high mobility group A2 (HMGA2) is a non-histone chromatin protein. It has no transcriptional activity of itself but could alter chromatin structure to regulate the transcription of other genes. HMGA2 gene is weakly expressed or does not express in normal tissues. The expression of HMGA2 is up-regulated during embryogenesis and malignant neoplasias. In several malignant tumors, HMGA2 is used as a diagnostic molecular marker or an independent prognostic indicator. Furthermore, HMGA2 not only elicits epithelial-mesenchymal transition but also maintains the differentiation potential and self-regeneration capability of stem cells. It plays an important role in initiation, proliferation, and metastasis of malignant neoplasias.

As a functional imaging method, positron emission tomography (PET) is widely used in tumor diagnosis, pathological classification, stage assessment, and clinical outcome evaluation. Combination of metabolic information acquired from ~(18)F-fluorodeoxyglucose (~(18)F-FDG) PET with pathological grading results is helpful for further defining the grade of sarcomas and predicting prognosis. ~(18)F-FDG PET appears to be superior to other imaging modalities in detecting bone metastases or pulmonary metastases of sarcoma patients, so it could be used in clinical staging and restaging of sarcoma. Tumor-to-background ratio (TBR) and standardized uptake value (SUV) are two important parameters for quantitative analysis and are helpful for assessing chemotherapy response of tumor. PET imaging offers important information to help maximize the clinical benefit of patients with sarcoma. This article reviews the clinical value of ~(18)F-FDG PET and ~(18)F-FDG PET/CT in diagnosis of sarcoma.

Objective:To study the variation of recent bladder function of the patients who received radical hysterectomy and evaluate its significance. Methods:Sixty-three patients with cervical carcinoma in International Federation of Gynecology and Obstetrics(FIGO) stage IB1 to ⅡA received urodynamic examination before and after operation. The urodynamic parameters included filling cystometry, pressure-flow rate, and electromyography of sphinctienter. Results:Radical hysterectomy induced significant increase in the first sensation (P<0.01)and post voiding residual of bladder (P<0.01) ;whereas caused significant decrease in the maximum volume(P<0.01), compliance(P<0.01),maximum flow rate(P<0.01) and the pressure at the maximum flow rate(P<0.01), respectively, compared with the corresponding values before the operation. Short-term bladder dysfunctions were observed in 34 patients (54.0%) including bladder detrusor dysfunction, low compliance bladder, bladder outlet obstruction, dyssynergia of urethral external sphincter and detrusor overactivity. The incidences of low compliance bladder and bladder detrusor dysfunction increased significantly after operation (P<0.01). Urinary retention was found in 28.6%(18/63) patients. The incidences of bladder detrusor dysfunction (66.7% vs 20.0%) and detrusor overactivity (33.3% vs 4.4%) in the group with urinary retention were significantly higher than those of corresponding group without urinary retention. Conclusion:The bladder function had obvious short-term changes following radical hysterectomy. In the many types of bladder dysfunction the main dysfunctions were low compliance bladder and bladder detrusor dysfunction. The bladder detrusor dysfunction might be the major cause of the urinary retention following the surgery. Urodynamic test was important for post-operative analysis and treatment of bladder dysfunction.

Objective:To observe the dynamic variation of serum ferritin (SF), folic acid, and vitamin B_(12) levels in patients with acute promyelocytic leukemia (APL) at different disease stages. Methods:Serum SF, folic acid and vitamin B_(12) levels were successively tested in thirty-six patients with primary APL every 1 to 3 months by using chemiluminescence analysis. Five different disease stages were selected as dynamic observation time points: first diagnosed, first complete remission (CR1), six months after CR1, relapsed stage,and CR1 for three years. Results:There were 75.0%(27/36)of patients with abnormal high levels of SF, 77.8% (28/36)of patients with abnormal low levels of folic acid, and 100%(36/36)of patients with increased vitamin B_(12) levels in first diagnosed stage. The number of patients with abnormal variations of SF, folic acid and vitamin B_(12) level was decreased in CR1 stage compared with those in first diagnosed stage (SF: P<0.05;folic acid and vitamin B_(12): P<0.01). The serum SF, folic acid and vitamin B_(12) levels tended to recover step by step with chemotherapy. At six months after CR1 the three parameters of most patients recovered to normal levels. APL was relapsed in 4 patients after 1-year CR. Both SF and vitamin B_(12) levels were increased and the folic acid level was decreased compared with those before replase, but the difference had no significance (P>0.05). The serum SF, folic acid and vitamin B_(12) levels were in normal ranges in the patients who had 3-year CR. Conclusion:The serum SF, folic acid and vitamin B_(12) levels had dynamic variation in APL course. Increase in serum SF and vitamin B_(12) as well as decrease in folic acid are related with the active degree of APL and its tumor load.

Objective:To systematically assess the efficacy and safety of bevacizumab (BEV) plus chemotherapeutic agents as first-line therapy for metastatic colorectal cancer (mCRC). Methods:We retrieved randomized controlled clinical trials (RCTs) of BEV plus chemotherapeutic agents as first-line therapy for mCRC from the databases of PubMed (1966 to August 2009), Embase (1974 to August 2009), Cochrane Library (Issue 3, 2009), China Journal Full Text Database (CJFD, 1994 to August 2009), Chinese Bio-medical Literature Database(CBM, 1978 to August 2009) and Chinese Scientific Journals Full Text Database (CSJD, 1989 to August 2009). Then we evaluated the methodological quality of included studies. Meta-analysis was performed using RevMan 5.0 software developed by the Cochrane Collaboration. Results:Only 6 clinical studies were selected and 2 646 eligible patients were included in the systematic review. Meta-analysis showed that BEV plus chemotherapy increased the overall response rate (complete response+partial response) compared with chemotherapy alone. The relative risk was 1.27 (95%CI: 1.00-1.61, P=0.05), and the median survival time and progression-free survival (PFS) were longer. In terms of safety, there was a significant difference in the frequency of grade 3/4 adverse events, grade 3/4 hypertension, adverse events-induced study discontinuation and gastrointestinal perforation between the two groups. The relative risk was 1.12 (95%CI: 1.07-1.61), 4.51 (95%CI: 2.81-7.23), 1.37 (95%CI: 1.16-1.63)and 4.32(95% CI:1.24-15.05), respectively. There was no statistical difference between the two groups in the incidence of grade 3/4 bleeding, 60-day all-cause mortality, grade 3/4 proteinuria, grade 3/4 diarrhea, grade 3/4 leukopenia and pulmonary embolism. The relative risk was 1.50(95%CI: 0.87-2.57), 0.71(95%CI: 0.45-1.11), 2.26(95%CI: 0.69-7.33), 1.18(95%CI: 0.99-1.41), 1.17 (95%CI: 0.97-1.42)and 0.84(95%CI: 0.46-1.53), respectively. Conclusion:BEV plus chemotherapeutic agents as first-line the-rapy increases the response rate and prolongs PFS and median survival time of mCRC patients, but results in a higher incidence of any grade 3/4 adverse event, grade 3/4 hypertension and gastrointestinal perforation.

Objective:To study the expression of extracellular matrix metalloproteinase (MMP-9) inducer CD147 and MMP-9 protein in hepatocellular carcinoma (HCC) and explore their correlation with invasion, metastasis, and prognosis of HCC.Methods:SP immunohistochemistry was used to evaluate the expression of CD147 and MMP-9 in 83 HCC tissues and 15 normal liver tissues. Results:The positive rate was 73.5% for MMP-9 and 68.7% for CD147, significantly higher than normal tissues (MMP-9: 6.7%;CD147: 0%, P<0.05). Expressions of CD147 and MMP-9 were positively correlated with the tumor size, pTNM stages, differentiation degree, the portal vein cancer embolism, and postoperative recurrence (P<0.05), but not with the patient's age, gender, the serum level of alpha-fetal protein (AFP), and the Child-Pugh grades. Patients with positive expression of CD147 and MMP-9 had shorter survival time than those with negative expression of CD147 and MMP-9. Expression of CD147 was positively related with expression of MMP-9 in HCC tissues.Conclusion:CD147 and MMP-9 had positive correlation with tumor size, pTNM stages, differentiation degree, portal vein cancer embolism, and postoperative recurrence. Detection of the expression of CD147 and MMP-9 may be helpful to make a comprehensive prediction of the prognosis of HCC.

Objective:To construct a specific small hairpin RNA (shRNA) expressing vectors against human receptor for advanced glycation end product (RAGE) gene and study its inhibitory effect on the proliferation of androgen-independent prostate cancer cells DU145. Methods:Four RAGE specific oligonucleotides were designed and synthesized. These oligonucleotides were annealed to forill double strand DNA fragments and this fragment was cloned into psi-U6 plasmid. The recombinants were transfected into RAGE-overexpressing sub DU145-2C1 cells. Cellular morphology and transfection efficiency were observed under fluorescence microscope. The inhibitory effect of RAGE shRNA construct on RAGE mRNA and protein expression was examined with semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting, respectively. The cellular proliferation was detected with cell counting kit-8 (CCK-8). Scratch test was used to observe the migration of DU145 cells.Results:RAGE shRNA expression plasmids were successfully constructed and transfected into sub DU145-2C1 cells. It can effectively inhibit the expression of RAGE mRNA (P<0.05). The inhibitory effects of shRNA RAGE-1 (R1) was the most stronger. The RAGE mRNA expression was inhibited by 84% and RAGE protein expression was inhibited by 27%. Compared with negative control, the proliferation potential was significantly decreased in shRNA RAGE-transfected cells. The cell migration capability had no significant changes. Conclusion:RAGE shRNA effectively inhibited the expression of RAGE mRNA and protein and suppressed the proliferation of DU145 cells in vitro.

Objective:To construct RNA interference plasmid specific for integrin β1 gene, and to explore the effects of inhibition of integrin β1 protein expression on the biological behavior of non-small cell lung carcinoma(NSCLC) cells. Methods:Genomic sequences of integrin β1 gene was retrieved from GenBank, and cDNA encoding small hairpin RNA(shRNA) for integrin β1 was designed and named as 17-2. A non-specific sequence was designed as negative control and named as N. The cDNA was synthesized and inserted into plasmids pUC19. Recombinant plasmids were then transformed into competent E.coli. The positive clones were selected and recombinant plasmids were extracted.The two shRNA vectors were transfected into NSCLC cell line PC-9/AB2 mediated by lipofectAMINE 2000. The stably transfec-ted cell clones were selected by G418 screening. Fluorescence microscope, real-time fluorescent quantitative (RFQ)-PCR, and Western blotting were performed to examine integrin β1 mRNA and protein expressions.Cell scratch test and adhesion test were used to detect the influences of silencing integrin β1 on cell migration and adhesion capacity. Results:The stably transfected 17.2 cell clones and N cell clones were screened by G418. The green fluorescence-staining cells were observed in full-field under fluorescence microscope. The level of integrin β1 was significantly down-regulated in 17-2 group compared with N group and primary PC-9/AB2 cells.Scratch test and adhesion test showed that the migration and adhesion capacity of PC-9/AB2 cells was significantly reduced after silencing integrin β1. Conclusion:This study successfully constructed integrin β1 specific shRNA expression vector. The expression of integrin β1 was significantly silenced in NSCLC cells transfected with that vecton. Silencing integrin β1 can significantly reduce the migration and adhesion capacity of NSCLC cells.

Objective:To elucidate action mechanism of δ-tocotrienol in inducing apoptosis of human hepatoma HepG2 cells. Methods:Cell proliferation and viability were assessed by MTT assay; cell cycle distribution, apoptotic rate and mitochondrial membrane potential were measured by using high content screening system; the expression of apoptosis-related protein such as caspase-3, caspase-8, caspase-9, Bcl-2, Bax, tBid and cytochrome C in the HepG2 cells were evaluated by Western blotting. Results:δ-Toco-trienol inhibited HepG2 cell proliferation and induced apoptosis in a dose-dependent manner. This growth-inhibiting effect of δ-toco-trienol correlated with loss of mitochondrial membrane potential and release of cytochrome C from mitochondria to cytoplasm, and regulation of the protein expression of Bcl-2 family members, such as up-regulation of Bax and tBid and down-regulation of Bcl-2. Subsequently tocotrienol induced the activation of caspase-3, caspase-8, and caspase-9 which finally induced apoptosis of hepatoma HepG2 cells. Conclusion:δ-Tocotrienol induced apoptosis of human hepatoma HepG2 cells via mitochondrial pathway and membrane death receptor pathway.