Does urothelial cancer of bladder behave differently in young patients? / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Bladder urothelial cancer has been diagnosed at an increasing rate among young adults in China while the clinical outcomes remain highly controversial. To optimize the management of young patients with bladder cancer, we examined whether bladder urothelial cancer in young patients behaved differently from that in the elder patients.</p><p><b>METHODS</b>From 1994 to 2008, a database of bladder urothelial cancer patients at a major tertiary medical center was retrospectively reviewed. The clinical and pathological parameters of patients who were less than 40 years of age and a series of patients older than 40 years of age as the control group during the same period were compared. A survival analysis was performed using the Kaplan-Meier method and log-rank test, and Cox regression was performed to identify clinical parameters that affected the clinic outcomes.</p><p><b>RESULTS</b>Young bladder cancer patients had a lower male-to-female ratio and were less likely to have advanced stages and high-grade cancers at the initial diagnosis. Tumors in young bladder cancer patients tended to be less multifocal at diagnosis. In addition, young patients had a lower recurrence rate and longer recurrence interval than older patients. The Kaplan-Meier curve and Log-rank test showed that young patients had significantly better cancer specific survival than old patients. The univariate and multivariate Cox regression analysis revealed that tumor grade is the sole predictor for tumor recurrence in young patients.</p><p><b>CONCLUSIONS</b>Young patients with bladder cancer have favorable pathological features and clinical outcomes than older patients. These findings argue for more conservative management approaches for young patients with bladder cancer.</p>

Clinical features on chromophobe renal cell carcinoma / 中华外科杂志

<p><b>OBJECTIVES</b>To explore the clinical, pathological features and prognosis of patients with chromophobe renal cell carcinoma.</p><p><b>METHODS</b>From January 1998 to January 2008, clinical data of 29 patients with chromophobe renal cell carcinoma including clinical manifestations, imaging examinations, treatment models, pTNM stages and follow-up results, were summarized to investigate its features and prognosis.</p><p><b>RESULTS</b>All cases had no obvious clinical and preoperative imaging presentation. There were 23 patients underwent radical nephrectomy, and 6 cases underwent nephron sparing surgery. Postoperative pathological findings confirmed the diagnosis of chromophobe renal cell carcinoma. Macroscopically, the cut surface of the tumors were generally beige in color. Histologically, it showed polygonal chromophobe cells and small round eosinophilic cells with eccentric hyaline degeneration. These tumor cells had a clear and sharp membrane, lightly stained abundant cytoplasm with a fine reticular translucent pattern and irregular nuclei. And a perinuclear halo was often seen in these cells. Histochemically, the tumor cells generally show a diffuse and strong reaction for CK-8 with a negative expression of Vimentin. The pTNM stages of the tumor were as follows, pT1N0M0 in 11 cases, pT2N0M0 in 8 cases, pT3aN0M0 in 5 cases, pT1N1M0 in 3 cases, pT2N1M0 in 2 cases. Twenty-six cases of patients were followed up (24 to 144 months, with an average of 90 months), 3 cases died of cardio-cerebrovascular disease, and local recurrence involved in 6 cases with reoperation in 4 cases, as well as distant metastasis in 1 case. Twenty-one cases survived with tumor-free. The statistical results indicated that the survival rates of the patients with chromophobe renal cell carcinoma in five years and ten years were 83.9%, 77.9%, respectively, compared with renal cell carcinoma of the same stage 63.8% and 49.9% at the same periods, and there is no difference in the survival rate of five years (P > 0.05) but significant difference in that of ten years (P < 0.01).</p><p><b>CONCLUSIONS</b>Chromophobe renal cell carcinoma is a morphologically uncommon subtype of renal cell carcinoma with the good prognosis. Definite diagnosis depends on its typical pathological feature. Radical nephrectomy is the first choice for the treatment of chromophobe renal cell carcinoma.</p>

Curcumin inhibits the expression of vascular endothelial growth factor and androgen-independent prostate cancer cell line PC-3 in vitro / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the effects of curcumin on the expression of the vascular endothelial growth factor (VEGF) and androgen-independent prostate cancer cell line PC-3, and to explore its anticarcinogenic mechanism.</p><p><b>METHODS</b>PC-3 cells were treated with curcumin at the concentration of 0, 6.25, 12.5, 25 and 50 micromol/L respectively. Then the cell activity was assayed by dyed rate of Typan blue and MTT at 12, 24, 36, 48, 72 and 96 hours, the cell cycle and morphological changes observed by flow cytometry (FCM) and electronic microscopy at 24 hours, the VEGF mRNA expression measured by semi-quantitative RT-PCR, and the secreting protein levels of VEGF in the supernatants determined by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>The growth of PC-3 cells was suppressed obviously by curcumin in a dose- and time-dependent manner in vitro. There were significant differences in inhibition rate among different concentration and time groups (P < 0.01). Furthermore, curcumin arrested the cell cycle of PC-3 cells in the G2/M phase in a dose-dependent manner (P < 0.01). The percentages of apoptotic cells were significantly higher in different concentration groups than in the controls (P < 0.01). Apoptosis-associated morphological changes were observed in PC-3 cells at 24 hours, and a marked decline in the expression of VEGF was noted after the exposure to different concentrations of curcumin within 24 hours.</p><p><b>CONCLUSION</b>Curcumin can suppress the growth of PC-3 cells, promote their apoptosis and arrest their cell cycle in the G2/M phase, and reduce the expression of VEGF mRNA and proteins, which may sever to explain its inhibitory effect on tumor and angiogenesis.</p>

Efficacy and safety of long-acting gonadotropin-releasing hormone analogue in the treatment for metastatic prostate cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of gonadotropin-releasing hormone analogue (GnRHa) triptorelin 11.25 mg 3-month sustained release formulations in the treatment of metastatic prostate cancer.</p><p><b>METHODS</b>From January 2004 to March 2006, a randomized, parallel-controlled, multicenter clinical trial was conducted. One hundred and twenty-seven patients with documented metastatic prostate cancer were randomized to receive one injection of the 11.25 mg formulation triptorelin (n = 65) or three injections at 28-day intervals of the 3.75 mg formulation (n = 62). Changes from baseline of TPSA, prostate volume, testosterone, LH, FSH, PRL and estradiol were assessed over 3 months. Changes of the metastatic lesions were also observed and evaluated. The occurrences of adverse events were evaluated as well.</p><p><b>RESULTS</b>After 3 months treatment, total PSA level decreased significantly from baseline both in 11.25 mg group and 3.75 mg group. At 30, 60 and 90 days, TPSA (median level) declined from 164.55 microg/L into 11.34, 4.12, 3.89 microg/L in 11.25 mg group, and from 101.38 microg/L into 6.88, 2.41, 2.57 microg/L in control group respectively. The patients ratio with over 90% decreasing from TPSA baseline were 78.6% and 75.5% respectively in two groups (P = 0.700). Prostate volume were also decreased significantly in both groups, median volume declined from 48.0 mm(3) into 21.5 mm(3) in 11.25 mg group and from 45.0 mm(3) into 21.0 mm(3) in 3.75 mg group. No significant differences were found between the two groups in changes of TPSA (P = 0.601) and prostate volume (P > 0.05). Both formulations were able to induce castration levels, 0.31 microg/L in 11.25 mg group and 0.26 microg/L in 3.75 mg group (P > 0.05). 13.8% and 17.7% of adverse events were recorded respectively in two groups, and no differences were found (P = 0.547).</p><p><b>CONCLUSION</b>As a new long-acting sustained release formulation, triptorelin 11.25 mg is comparable to triptorelin 3.75 mg formulation in the aspect of efficacy and safety for the treatments of metastatic prostate cancer.</p>

Matrine inhibits the proliferation of prostate cancer cells and the activity of androgen receptor / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the inhibitory effect of matrine on the proliferation of the prostate cancer cell line LNCaP and the expression of the androgen receptor (AR).</p><p><b>METHODS</b>LNCaP cells were treated with matrine at the concentration of 0.5, 1.0, 1.5, 2.0 and 3.0 g/L for 12, 24 and 36 hours, the cell growth activity determined by MTT colorimetry and trypan blue staining at 36 hours, the cell cycle changes detected by flow cytometry and the expression of AR by Western blot at 24 hours.</p><p><b>RESULTS</b>Matrine suppressed the in vitro growth of the androgen-sensitive prostate cancer cell line LNCaP in a time- and dose-dependent manner, blocked the cell cycles in the G2/M phase and decreased the expression of AR in the cell line in a dose-dependent manner (P < 0.01).</p><p><b>CONCLUSION</b>Matrine can significantly inhibit the in vitro growth of NCaP cells by down-regulating the expression of AR and blocking cell cycles.</p>

In vitro anti-tumor effect of CTL induced by HSP70-Id complex-modified dendritic cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To prepare the tumor antigen peptide complex (HSP70-1d) of HSP70 and idiotype (Id) from SmIg ScFv fragment in patients with Chronic B cell leukemia (B-CLL), and to study the anti-tumor effect of cytotoxic T lymphocyte (CTL) induced by HSP70-Id complex-modified dendritic cell (DC) in vitro and explore their immune mechanism.</p><p><b>METHODS</b>Purified HSP70 was combined into peptide complex (HSP70-Id) with the prepared Id-ScFv from B-CLL cells in vitro by using biochemical technique. The plastic-adherent monocytes from human peripheral blood were cultured and induced into DC with rhGM-CSF and rhIL-4 using cell culture and separation technique. The cultured DC were harvested and pulsed by HSP70-Id complex. DC morphology was observed under converted phase microscope and its phenotype was characterized by FCM on 8th day as well as their secreting cytokines were measured. Host lymphocytes were stimulated by DC loaded with HSP70-Id complex and co-cultured in the medium containing IL-2. The activation and proliferation of lymphocytes were examined by MTr test, which was also used to assay cytotoxicity of CTL elicited by modified DC to Daudi, K562 and HepG2 tumor cells, and FCM analyzed the changes of T lymphocyte subsets.</p><p><b>RESULTS</b>Mature DCs were obtained successfully, showing typical morphology and phenotypic properties, the expression ratio of cellular surface molecules, CD1a was 20% - 30%, CD83 was more than 72% , both CD86 and HLA-DR over-expressed obviously in the complex-loaded DC group secreting cytokines of Thl type, IL-12 and TNF-alpha. The culturing lymphocytes that were activated by modified DC could more effectively and specifically kill Daudi (71. 24%), but not K562 and HepG2 tumor cells. Results of FCM assay demonstrated that percentage of CD4+ and CD8+ T lymphocytes cocultured with complex-modified DC increased notably to 56.51% and 70.21%, respectively. CD4+ T/ CD8+ T proportion was changed from 1.49 to 0.81. The dose of peptide would be reduced to 1/50 if specific CTL induced by complex-modified DC instead of directly by peptide complex.</p><p><b>CONCLUSION</b>DCs modified by HSP70-Id complex exhibit powerful biological activities, and could induce CTL to specific cytotoxicity against carcinoma cells. It might be produced by cooperation of CD4+ T, CD8+ T lymphocytes and DC. The results also suggested that DC modified by HSP70-Id complex can present antigen and induce CTL with high efficacy and specificity.</p>

Proliferation and identification of dendritic cells from peripheral blood of patients with bladder cancer in vitro / 中华泌尿外科杂志

Objective To investigate the proliferation and identification of dendritic cells(DC)de- rived from peripheral blood of patients with bladder cancer in vitro.Methods The mononuclear cells were prepared from peripheral blood of patients with bladder cancer by Ficoll-Hypaque centrifugation method,and were induced by the recombinant cytokines hGM-CSF(50 ng/ml),hlL-4(10 ng/ml)and hTNF-?(50 ng/ ml)for 2 weeks.The growth and morphology of DC were observed through the phase contrast or electron mi- croscope,and their pheuotypes were determined by flow cytometry.The capacity of DC to activate T cell-de- pendent anti-tumor immune responses was tested by MTT method.Results The DC cultured in vitro turned into suspensive growth from adhesive situation on the 6th day,then the number of DC increased con- tinuously and the cells showed the irregular morphologic appearance of DC with veiled edges on the 8th day. Flow cytometry showed that the mature DC expressed high levels of specific markers such as CD_(1a),CD_(83), CD_(86)and HLA-DR.T cells activated by DC showed strong cytotoxicity to bladder cancer cell line BIU87 with a killing rate of(48.8?3.7)%,while the killing rate of T cells which were not activated by DC was(25.7?1.5)%;the difference of the rate between them was significant(P＜0.01). Conclusions The DC can be cultured from peripheral blood of patients with bladder cancer by induction of rhGM-CSF,rhIL-4 and hT- NF-?in vitro.This may lay an experimental foundation for further research on DC vaccine.