[Modified Shenqi Dihuang Decoction acts on hormone-sensitive prostate cancer by inhibiting glycolysis through the PI3K/Akt /mTOR signaling pathway].

Objective: To evaluate the effect of Modified Shenqi Dihuang Decoction (MSDD) on human hormone-sensitive LNCaP prostate cancer cells and its action mechanism. METHODS: LNCaP prostate cancer cells were treated with MSDD, followed by detection of the proliferation and apoptosis of the cells by MTT assay and flow cytometry respectively and measurement of glucose uptake and lactate production by glucose uptake assay and colorimetry respectively. The expressions of the apoptosis-related proteins Bcl-2, Bax and cleaved-caspase-3, glycolysis-related proteins HK2, GLUT1, PKM2 and LDHA, and PI3K/AKT/mTOR pathway-related proteins in the LNCaP cells were determined by Western blot. The effect of MSDD on the LNCaP cells was observed with the glycolysis inducer oligomycin and the PI3K activator 740 Y-P. RESULTS: MSDD inhibited the proliferation, induced the apoptosis, increased the levels of Bax and cleaved-caspase 3 and decreased the level of Bcl-2 in the LNCaP cells in a dose-dependent manner. After MSDD intervention, the glucose uptake and lactate production in the LNCaP cells were significantly reduced, the expressions of HK2, GLUT1, PKM2 and LDHA and the phosphorylation levels of Akt, PI3K and mTOR were markedly suppressed. Oligomycin and 740 Y-P reversed the inhibitory effect of MSDD on the proliferation of the LNCaP cells, and 740 Y-P reversed that on glucose uptake, lactic acid production and the expressions of the glycolysis-related proteins HK2, GLUT1, PKM2 and LDHA in the LNCaP cells. CONCLUSIONS: Modified Shenqi Dihuang Decoction inhibits the proliferation of LNCaP prostate cancer cells by suppressing glycolysis and the PI3K/Akt/mTOR signaling pathway.

[Modified Shenqi Dihuang Decoction for bone metastasis of hormone-sensitive prostate cancer after castration].

OBJECTIVE: To observe the clinical effect of Modified Shenqi Dihuang Decoction (MSDD) on bone metastasis of hormone-sensitive PCa after castration. METHODS: Seventy-six hormone-sensitive PCa patients with bone metastasis were randomly divided into a control and an MSDD group of an equal number, the former treated by maximal androgen blockade (MAB) and the latter with MSDD in addition to MAB, both for 6 months. Comparisons were made between the two groups of patients in their TCM symptom scores, quality of life (QOL) scores and the incidence rates of castration resistance, bone metastasis and adverse events. RESULTS: Totally, 64 of the patients were included in the statistical analysis. Compared with the controls, the MSDD group showed significantly lower rates of castration resistance (71.87% vs 28.12%, P < 0.05) and new bone and visceral metastases (40.63% vs 18.75%, P < 0.05) and level of serum alkaline phosphatase after treatment (ï¼»328.5 ± 170.6ï¼½ vs ï¼»318.5 ± 165.8ï¼½ U/L, P < 0.05), as well as lower scores in the TCM symptoms of frequent micturition (2.05 ± 0.51 vs 1.64 ± 0.66, P < 0.05), loss of appetite (1.95 ± 0.48 vs 1.41 ± 0.39, P < 0.05), fatigue (2.59 ± 0.68 vs 1.39 ± 0.58, P < 0.05), back pain (1.76 ± 0.41 vs 1.26 ± 0.38, P < 0.05), weight loss (1.88 ± 0.75 vs 1.26 ± 0.80, P < 0.05) and self-evaluation (1.89 ± 0.58 vs 1.54 ± 0.63, P < 0.05), but a higher score in the physical status (Karnofsky Performance Scale) (70.45 ± 12.16 vs 79.87 ± 11.23, P < 0.05). There were no statistically significant differences in the Numeric Rating Scale for Pain score and the incidence of adverse events between the two groups of patients. CONCLUSIONS: Modified Shenqi Dihuang Decoction can effectively improve the QOL and TCM symptom scores of the patients with hormone-sensitive PCa after androgen castration, enhance the efficacy of modern drugs in the treatment of hormone-sensitive PCa, decrease the incidence of metastasis, improve the patient's serum indicators, reduce the pain associated with bone metastasis, and improve the patient's quality of life.

Preoperative CD4+CD25+/CD4+ and tumor diameter predict prognosis in male patients with bladder cancer.

Aim: The value of the peripheral blood lymphocyte subpopulation ratios and tumor diameter for prognosis in bladder cancer (BC) patients needs to be explored. Materials & methods: A total of 161 male BC patients and 68 male normal controls were retrospectively reviewed. The value of combining predictor consisted of both CD4+CD25+/CD4+ and computed tomography urography tumor diameter (CTU-D) on stage, overall survival (OS) and recurrence probability was analyzed by logistic regression, Kaplan-Meier method and log-rank test. Results: The combining predictor was a statistically independent risk for stage; dramatic differences in OS and recurrence probability were found between the combining predictor-high (cut-off point >0.08) and combining predictor-low groups (cut-off point ≤0.08). Conclusion: The combining predictor could be a significant predictor for advanced stage, OS and recurrence probability in male patients with BC.

RS 504393 inhibits M-MDSCs recruiting in immune microenvironment of bladder cancer after gemcitabine treatment.

Bladder cancer (BC) is a malignant tumor of urinary epithelium. Gemcitabine is an introduced treatment for BC and also has immunomodulatory function, but the immunoregulation mechanism is not clear. In this study, we found that gemcitabine-treated BC cell recruited more monocyte-myeloid-derived suppressed cells (M-MDSCs), which played a significant role in immune suppression and contributed to cancer progression. We found that this phenomenon was induced by Chemokine (C-C motif) ligand 2 (CCL2), an M-MDSCs recruitment related monomeric polypeptide. Gemcitabine treatment promotes the generation of CCL2 and CCL2 could attach to C-C chemokine receptor type 2 (CCR2) to recruit M-MDSCs. We used RS 504393, a selective CCR2 antagonist, to inhibit the recruitment of M-MDSCs. RS 504393 improved the prognosis by blocking chemotaxis of M-MDSCs, and this finding sheds lights on how to prevent and alleviate the side effects occurred on the gemcitabine-treated BC patients.

miRNA­26a­5p and miR­26b­5p inhibit the proliferation of bladder cancer cells by regulating PDCD10.

MicroRNA (miR)­26a­5p and miR­26b­5p consistently play an antitumor role in many types of cancers, but the underlying mechanism remains unclear in bladder cancer (BC). In the present study, we found that, in BC tissues, the levels of miR­26a­5p and miR­26b­5p were lower than in paired normal tissues. The upregulation of miR­26­5p significantly inhibited the proliferation of BC cell lines (T24 and 5637). Bioinformatics analysis indicated that Programmed Cell Death 10 (PDCD10) was the downstream target gene of miR­26a­5p/miR­26b­5p, and this was ascertained by western blotting and quantitative real­time reverse transcription PCR (RT­qPCR). In addition, in the 3'­UTR of PDCD10, the binding site was identified using a luciferase reporter assay. We determined that clinical BC tissues presented higher PDCD10 levels than adjacent normal tissues and that PDCD10 promoted proliferation of BC cell lines. Overexpression of miR­26a­5p/miR­26b­5p inhibited the stimulatory effect on proliferation of BC cells induced by PDCD10. In addition, in vivo experiments and clinical data revealed that the prognosis of BC patients with high expression of miR­26a­5p/miR­26b­5p and low expression of PDCD10 was better than that of patients with low miR­26­5p and high PDCD10 expression. These data revealed that miR­26a­5p and miR­26b­5p were pivotal regulators in BC progression by targeting the proliferation­related protein, PDCD10. The miR­26­5p/PDCD10 interaction may provide important insight into the pathway of BC progression and present novel opportunities for future diagnosis and treatment strategies, especially for patients with high levels of PDCD10.

Cisplatin inhibits the progression of bladder cancer by selectively depleting G-MDSCs: A novel chemoimmunomodulating strategy.

Bladder cancer (BC) is a disease arising from the malignant cells of the urinary bladder. Myeloid-derived suppressor cells (MDSCs) expand broadly and have strong immunosuppressive activities in the cancer microenvironment. Determining how to inhibit the negative effects of MDSCs requires immediate attention. In this study, we found that granulocytic-MDSCs (G-MDSCs), which constitute one of the two types of MDSCs, were significantly increased in BC tissues compared with those in the adjacent bladder tissues. There was a robust negative correlation between the G-MDSCs and the CD8+ T cells in the BC tissues. In this study, we attempted to identify pharmacological approaches to eliminate MDSCs and restore T cell anti-tumor activities. It is necessary to explore a method to eliminate the detrimental effects of MDSCs. Cisplatin, a chemotherapy medication used to treat BC, not only rapidly kills proliferating cancer cells but also affects the tumor immune microenvironment. However, the mechanism underlying this phenomenon is largely unknown. In this study, we found that Cisplatin directly inhibited the proliferation and induced the apoptosis of T24 cells (a BC cell line), as well as decreased the percentage of the G-MDSCs in the population of peripheral blood mononuclear cells (PBMCs), which restored the expansion of the CD8+ T cells. In the C3H/He mouse BC model, Cisplatin treatment inhibited the progression of BC and effectively decreased the proportion of G-MDSCs. These results suggest that Cisplatin treatment enhances the anti-tumor function of CD8+ T cells by decreasing G-MDSCs. This finding provides a new perspective for Cisplatin treatment to prevent the progression of BC, particularly in patients with abnormally high levels of G-MDSCs.

Five-year follow-up after conversion from calcineurin inhibitor to sirolimus-based treatment in kidney transplant patients with chronic allograft nephropathy.

Chronic allograft nephropathy (CAN) is a major cause of graft loss in long-term kidney transplant recipients. To identify the safety and efficacy of conversion from calcineurin inhibitors (CNI) to sirolimus (SRL) in patients with CAN, we investigated 92 biopsy demonstrated CAN patients during a 5-year follow-up.45 patients were converted to sirolimus treatment (SRL group) and remaining 47 patients continued CNI immunosuppression (CNI group). Renal function, proteinuria, hepatic function, lipid level and blood routine examination were observed for 60 months in each group. During the period of conversion, serum creatinine was superior in SRL group to CNI group. It dropped significantly from (174.0 ± 62.8) umol/L to (150.7 ± 83.4) umol/L in SRL group whereas increased to (200.9 ± 73.5) umol/L in CNI group (P < 0.05). However, SRL group showed increased proteinuria, triglycerides and decreased Plt (P < 0.05). We also found those patients in SRL group with a good baseline of renal function (serum creatinine < 200 umol/L or proteinuria < 800 mg/day at conversion) would ameliorate the impaired renal function from CAN at 60 months. In conclusion, it is safe and effective to convert from CNI to SRL for patients with CAN in our long-term observation. Early conversion is associated with an improvement of renal function.

SUMO-specific protease 2 suppresses cell migration and invasion through inhibiting the expression of MMP13 in bladder cancer cells.

BACKGROUND: SUMO-specific protease 2 (SENP2) is a de-SUMOylation protease family member which has an indispensable role in the regulation of NF-κB transcriptional activation and Wnt signaling. However, whether SENP2 plays a role in tumor metastasis is completely unknown. METHODS: Real-time PCR and Western blot was used to detect the expression of SENP2 in human bladder cancer samples and cell lines. Small interfering RNA (siRNA) was used to silencing the expression of SENP2. Matrigel-coated invasion chambers were used to detect the invasion ability of SENP2 in bladder cancer cells. RESULTS: SENP2 was down-regulated in bladder cancer samples. SENP2 inhibited bladder cancer cells migration and invasion in vitro. Transcriptional analysis of several genes associated with tumor metastasis and invasion demonstrated that SENP2 selectively down-regulated MMP13 in bladder cancer cells. Further analysis indicated that silencing of MMP13 rescued the invasive phenotype in SENP2 expressing T24 cells. CONCLUSION: SENP2 functions as a tumor metastasis suppressor in bladder cancer. The effects of SENP2 on bladder cancer invasion are partially mediated by inhibiting the expression of MMP13.

[Effects of policosanol on serum lipids and heme oxygenase-1 in patients with hyperlipidemia].

OBJECTIVE: To evaluate the effects of policosanol on serum lipid and heme oxygenase-1 (HO-1) in patients with hyperlipidemia. METHODS: This randomized, open study included 72 patients with hyperlipidemia. The patients were randomly assigned to treatment group (policosanol, 20 mg/d, n = 36) or placebo group (placebo, two tablets/d, n = 36). The levels of serum lipids, hypersensitive C-reactive protein (hs-CRP), HO-1 were assessed before and after 16 weeks treatment. Drug-induced adverse effects and events were recorded during the observation period. The serum HO-1 was measured by ELISA. RESULTS: (1) After 16 weeks, all parameters remained unchanged in the placebo group; the level of TC decreased from (7.01 ± 1.03) mmol/L to (5.66 ± 0.83) mmol/L (-19.4%, P < 0.01), the level of LDL-C decreased from (4.78 ± 0.72) mmol/L to (3.70 ± 0.69) mmol/L (-22.5%, P < 0.01) in the treatment group. TG and HDL-C levels remained unchanged (P > 0.05) while the level of HO-1 significantly decreased from (1.82 ± 1.08) µg/L to (1.45 ± 0.81) µg/L (P < 0.01) and the level of hs-CRP decreased from (3.40 ± 3.64) mg/L to (1.86 ± 2.02) mg/L (P < 0.01) in the treatment group. (2) Safety index was similar between placebo and treatment groups (P > 0.05) and there was no adverse events including allergic reaction, muscle pain in all subjects during the observation period. CONCLUSION: The short-term data obtained from this small hyperlipidemia patient cohort suggest that policosanol is a safe lipid-lowering and anti-inflammatory agent for hyperlipidemia patients.

[Efficacy and safety of extended-release niacin alone or with atorvastatin for lipid profile modification].

OBJECTIVE: To evaluate the efficacy and safety of extended-release niacin (niacin ER) either alone or in combination with atorvastatin for the lipid profile modification in the patients with coronary heart disease (CHD) and its equivalents. METHODS: One hundred and ten patients with CHD and its equivalents with serum total cholesterol (TC) > or = 3.5 mmol/L were randomly assigned into three treatment groups: (1) atorvastatin group (n = 38), receiving atorvastatin 10 mg/d for 8 weeks; (2) niacin ER group (n = 38), given niacin ER 500 mg/d for 4 weeks and then 1000 mg/d for 4 weeks; (3) combination treatment group (n = 34), treated with atorvastatin (10 mg/d) plus niacin ER, with the dose initiating from 500 mg/d, and increasing to 1000 mg/d after 4 weeks, for 8 weeks. The serums lipid profiles and adverse effects were assessed in all the patients before treatment, and 4 and 8 weeks after treatment. RESULTS: (1) After 8 weeks of treatment, the serum level of triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) were reduced by 30% and 16% respectively in the niacin ER group compared with the baseline values (both P < 0.05). After 8 weeks, the TC, low-density lipoprotein cholesterol (LDL-C), and TG in the atorvastatin group decreased by 19%, 26%, and 17% respectively compared with the baseline values (all P < 0.05). Combination treatment decreased the TC, LDL-C, and TG levels by 28%, 38%, and 39% respectively, and increased the HDL-C level by 23% (all P < 0.05). The improvement in TC and LDL-C achieved by combination treatment was superior to treatment of atorvastatin alone and treatment of niacin ER alone (all P < 0.05). (2) The rate of achieving the LDL-C goal of The National Cholesterol Education Program (NCEP) in Adult Treatment Panel III (ATP III) in the combination therapy group was 73.5%, significantly higher than those of the atorvastatin and niacin groups (47.7% and 42.1% respectively, both P < 0.05). (3) Adverse effect, such as flushing (15.8%) and gastrointestinal symptoms (23.7%) were found in the niacin ER group, however, no more adverse effects were found in the combination therapy group. There were no serious adverse events in all groups. CONCLUSION: Niacin ER has a favorable effect in modulating the blood lipid profile, especially in reducing TG and elevating HDL-C. Combined statin with niacin may produce a more global and effective improvement in lipid blood levels than monotherapy and is generally safe and well tolerable.

[Clinical analysis of arrthythmogenic right ventricular cardiomyopathy].

OBJECTIVE: To investigate the clinical features of arrthythmogenic right ventricular cardiomyopathy (ARVC), and to evaluate the diagnosis of ARVC. METHODS: Twenty-three cases of ARVC underwent ECG, chest x-ray, Holter, transesophageal atrial pacing (TEAP) and intracardiac electrophysiological examination. RESULTS: A syncope attack occurred; the percentage of frequent ventricular premature beats was 95.7%, salvos of the right ventricular originated ventricular tachycardia (VT) was 87%, and the right bundle branch block (RBBB) demonstrated by ECG was 87%; UCG showed that the enlarged right ventricular diametric was (50.1 +/- 8.83) mm, and the right atrium diametric was (48 +/- 8.79) mm; the ratio of right ventricular diametric to left ventricular diametric in the end-diastolic period was 1.09. The right ventricular function [ejection fraction: (0.325 +/- 0.0902)] decreased, which was confirmed by echocardiogram. CONCLUSION: The diagnosis of ARVE can be established on the basis of the repeated syncope attack; RBBB, frequent ventricular premature beats, VT of LBBB patterms, an enlarged right heart and decreased right ventricular function can be found, the ratio of right ventricular dimaetric to left ventricular diametric increases in the end-diastolic period.