Interleukin-1β mediates the effect of macrophage androgen receptor on hyperphosphate-induced vascular smooth muscle cell calcification / 中华肾脏病杂志

Objective:To investigate whether it is by regulating interleukin 1β ( IL-1β) gene expression that androgen receptor (AR) in macrophages affects hyperphosphate-induced vascular smooth muscle cell calcification. Methods:The chromatin immunoprecipitation (ChIP) experiment was used to determine whether AR was bound to the androgen receptor element (ARE) sequence of IL-1β promoter in THP-1 cells. Whether the AR regulated IL-1β gene expression was detected by luciferase assay experiments. AR of THP-1 cells was silenced and transfected by lentivirus with vector or shRNA. Flow cytometry was used to select positive transfected cells THP-1ARsc (control) and THP-1ARsi (AR silencing) with fluorescent markers. Western blotting was used to detect AR protein levels of THP-1ARsc (control) and THP-1ARsi cells (AR silencing in monocytes). Macrophages MФARsc (control) or MФARsi (AR silencing) were induced by 50 ng/ml phorbol ester. Enzyme-linked immunosorbent assay was used to detect IL-1β expression levels of MФARsc or MФARsi conditioned medium. The human aortic smooth muscle cells (HASMC) were cultured in MФARsc or MФARsi conditioned medium with phosphate (2.5 mmol/L final concentration of sodium dihydrogen phosphate), and Alizarin red S staining was used to analyze HASMC calcification degree. Western blotting was used to detect the expression levels of RUNX2 (osteoblast marker) and SM22α (HASMC marker), and neutralization assay was performed to test IL-1β-mediating effect of macrophages AR on HASMC calcification. Results:AR was bound to ARE sequence of IL-1β promoter and regulated IL-1β gene expression. The expression level of IL-1β protein in conditioned medium of MФARsi cells decreased significantly compared to MФARsc cells ( P<0.001). Compared with MФARsc conditioned medium group, HASMC calcium deposition in MФARsi conditioned medium group decreased significantly, RUNX2 protein decreased and SM22α protein increased (all P<0.05). The degree of HASMC calcification in the MФARsi conditioned medium+IgG antibody group decreased than that in the MФARsc conditioned medium+IgG antibody group significantly, and the degree of HASMC calcification in the MФARsc conditioned medium+IL-1β antibody group decreased significantly than that in the MФARsc conditioned medium+IgG antibody group; while the degree of HASMC calcification in the MФARsi conditioned medium+IgG antibody group and MФARsi conditioned medium+IL-1β antibody group decreased than that in the MФARsc conditioned medium+IL-1β antibody group (all P<0.05). Conclusions:Macrophage AR regulates IL-1β expression by binding to ARE sequence within IL-1β promoter, and IL-1β mediates the effect of macrophage AR on hyperphosphate-induced HASMC calcification.

Analysis of the diagnosis and treatment of desmoplastic small round cell tumor / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the clinical diagnostic features and treatment of desmoplastic small round cell tumor (DSRCT), and to improve the understanding and management of this tumor.</p><p><b>METHODS</b>The clinicopathological data of nine patients treated in our hospital from October 2004 to June 2014 were retrospectively analyzed and a review of the literature was made. The clinical manifestations, pathological characteristics, diagnosis and differential diagnosis, treatment and prognosis of this tumor were summarized and analyzed.</p><p><b>RESULTS</b>Nine patients with DSRCT, 5 males and 4 females, with an average age of 21 years (range 8-56 years) were included in this study. Ultrasound examination revealed irregular low-density mass shadow in the abdominal cavity. CT examination found that 6 cases had abdominal and retroperitoneal multiple solid tumor nodules, uneven density, and visible low density fluid area. Postoperative pathological examination revealed that the tumor cells were small, mostly elliptic, gathered to form clear structure of nests with clear irregular boundaries. The central portion of large tumor nests often showed necrosis. Scattered fibroblasts and large amount of hyalinization of collagen fibers were seen in the interstitial tissue around the nests. Six patients received laparotomy surgery, however, all failed to resect the tumor completely. Three patients received postoperative chemotherapy, i. e. two cases had carboplatin and paclitaxel chemotherapy, and one case of chemotherapy regimen not specified. Two patients had radiation and chemotherapy (no concrete plan was available). Another case was lost to follow-up. Two of the three patients without surgery received chemotherapy with CAP (cyclophosphamide+adriamycin+carboplatin) and total rectal lesions, pelvic and inguinal lymph nodes, ilium metastases radiation therapy. Another one patient received EP regimen (DDP+VP16) which was then changed into a TP chemotherapy alone. Eight of the nine cases died shortly after surgery, and only one patient treated with chemotherapy alone was still alive after 11 months of follow-up.</p><p><b>CONCLUSIONS</b>Desmoplastic small round cell tumor is a very rare, special type of soft tissue tumor, with very poor prognosis. This tumor may be preliminarily diagnosed according to the imaging characteristics and detection of tumor markers, however, final diagnosis is made by pathology. Surgery is the priority of treatment, combined with complementary radiation and chemotherapy.</p>

The Expression of Neurotensin in Animal Model of Androgen Independent Prostate Cancer / 天津医药

Objective To study the different expressions of neurotensin (NT) at gene and protein level in orthotopic model of prostate cancer . Methods The animal models of androgen dependent prostate cancer(ADPC,castrated for 3 days) and androgen independent prostate cancer(AIPC) were established by planting tumor tissue or undergoing surgical castra-tion. Affymetrix microarray technology was carried out to compare the gene expressions of NT. The result was verified by qRT-PCR. HE staining was used to observe the change of pathology. ELSIA and immunohistochemistry technology were fi-nally performed to detect protein expression of prostate-specific antigen(PSA) and NT in three different groups of prostate cancer tumor tissues. Results The expression of NT was 5.10 times higher in AIPC group than that in ADPC group. The ex-pression of NT was 0.33 times lower in castrated 3-day group than that in ADPC group. Results of RT-PCR and qRT-PCR showed that the expression levels of NT gene were 1.41 and 7.27 times respectively higher in AIPC group than that in ADPC group,but the expression levels of NT gene were 0.78 and 0.46 times respectively lower in castrated 3-day group than that in ADPC group (P<0.05). HE results showed that nuclear atypia and tumor structure in three groups. Immunohistochemistry and ELISA results showed that the values of PSA and NT were (0.48±0.03) and (0.031±0.008)μg/L in ADPC group;(0.17± 0.03) and (0.021±0.004)μg/L in castrated 3-day group,and (0.87±0.02) and (0.042±0.010)μg/L in AIPC group. There were significantly lower expressions of NT and PSA in castrated 3-day group that those of ADPC group (P<0.01). Conclusion In the transition from ADPC to AIPC, the over-expression of NT suggested that NT may be associated with prostate cancer progression. NT may be used as a new therapeutic target and specific diagnostic method of AIPC.

Epigenetic regulation of androgen receptors in prostate cancer / 中国肿瘤临床

The androgen receptor (AR), a nuclear hormone and transcription factor, is the most therapeutic relevant target in pros-tate cancer (PCa) and in the castration-resistant prostate cancer (CRPC). Significant efforts have been focused on understanding the mechanisms involved in the development and progression of CRPC. Recent work has revealed the importance of epigenetic events in-cluding the regulation of AR signaling by methylation, acetylation, and non-coding RNA in the tumorigenesis and development of PCa. We summarize recent findings on the mechanisms of epigenetic regulation of AR signaling in PCa.

Influence of estrogen receptor a on proliferation and metastasis in bladder cancer cells / 中华泌尿外科杂志

Objective To explore the function and mechanism of estrogen receptor α (ERα) in bladder cancer cell proliferation and aggressivity.Methods The ERα expression bladder cancer cell line T24ERα model was established.The cell growth was detected by MTT assay,apoptosis by flow cytometry,cell invasion by matrigel transwell.Western blot was used to check signals by ERα regulation in bladder cancer cells related to the proliferation and metastatic ability.Results Compared to the control group,the cell inhibition rates of experimental group in 96 h and 144 h were 18.85％ and 37.21％,respectively.The difference was significant compared with the control group (P ＜ 0.05).The apoptosis rates of the experimental group and control group were (18.93 ±1.41)％ and (9.91 ±1.08)％ (P＜0.05).The experimental group through matrix adhesive cell proportion was (10.00 ± 2.00)％,significantly lower than that of the control group (26.00 ± 3.61) ％ (P ＜ 0.05).Western blot showed integrin-β1,p-FAK,p-Src and Scr expression were reduced compared to control group (P ＜ 0.05).Conclusion ERα could inhibit bladder cancer cell growth and metastasis through down-regulating integrin-β1-FAK/Src signal pathway,while promote the apoptosis of bladder cancer cells.