PSA time to nadir as a prognostic factor of first-line docetaxel treatment in castration-resistant prostate cancer: evidence from patients in Northwestern China.

Docetaxel-based chemotherapy remains the first-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) in China; however, the prognostic factors associated with effects in these patients are still controversial. In this study, we retrospectively reviewed the data from 71 eligible Chinese patients who received docetaxel chemotherapy from 2009 to 2016 in our hospital and experienced a reduction of prostate-specific antigen (PSA) level ≥50% during the treatment and investigated the potential role of time to nadir (TTN) of PSA. TTN was defined as the time from start of chemotherapy to the nadir of PSA level during the treatment. Multivariable Cox regression models and Kaplan-Meier analysis were used to predict overall survival (OS). In these patients, the median of TTN was 17 weeks. Patients with TTN ≥17 weeks had a longer response time to chemotherapy compared to TTN <17 weeks (42.83 vs 21.50 weeks, P < 0.001). The time to PSA progression in patients with TTN ≥17 weeks was 11.44 weeks compared to 5.63 weeks when TTN was <17 weeks. We found several factors to be associated with OS, including TTN (hazard ratio [HR]: 3.937, 95% confidence interval [CI]: 1.502-10.309, P = 0.005), PSA level at the diagnosis of cancer (HR: 4.337, 95% CI: 1.616-11.645, P = 0.004), duration of initial androgen deprivation therapy (HR: 2.982, 95% CI: 1.104-8.045, P = 0.031), neutrophil-to-lymphocyte ratio (HR: 3.963, 95% CI: 1.380-11.384, P = 0.011), and total PSA response (Class 1 [<0 response] compared to Class 2 [0-50% response], HR: 3.978, 95% CI: 1.278-12.387, P = 0.017). In conclusion, TTN of PSA remains an important prognostic marker in predicting therapeutic outcome in Chinese population who receive chemotherapy for mCRPC and have >50% PSA remission.

Prognostic factors of first-line docetaxel treatment in castration-resistant prostate cancer: roles of neutrophil-to-lymphocyte ratio in patients from Northwestern China.

OBJECTIVE: To evaluate the potential role of neutrophil-to-lymphocyte ratio (NLR) with therapeutic response in patients who were treated with docetaxel for mCRPC. MATERIALS AND METHODS: We retrospectively analyzed the clinical data from 111 consecutive patients who were treated with docetaxel for mCRPC from 2009 to 2016 in a single center from Northwestern China. Pretreatment baseline and follow-up data including age, PSA response, Gleason score, and cycle number were reviewed, and multivariable Cox regression models and Kaplan-Meier analysis were used to predict overall survival (OS) and progression-free survival (PFS). RESULTS: In Kaplan-Meier analyses, the NLR (optimal threshold 3.3), total PSA response, number of chemotherapy cycles, stage T, baseline of PSA, albumin, presence of visceral metastases, and PSA level at the diagnosis of cancer were significantly associated with OS, respectively. In multivariable analyses, higher NLR (>3.3), PSA level at the diagnosis of cancer (≥162 ng/ml), number of chemotherapy cycles, and albumin (<40.5 g/l) were associated with increased risk of death, respectively. Meanwhile, young age, higher NLR, number of chemotherapy cycles, presence of visceral metastases, and poor PSA response were associated with shorter PFS. CONCLUSION: NLR combined with PSA level at the diagnosis of cancer remains an important prognostic marker in predicting therapeutic outcome in Chinese men who receive chemotherapy for mCRPC.

[Efficacy and tolerability of dapoxetine in the treatment of premature ejaculation].

OBJECTIVE: To investigate the efficacy and adverse effects of dapoxetine in the treatment of premature ejaculation. METHODS: We randomly assigned outpatients with premature ejaculation in the proportion of 2:1 to receive 30 mg dapoxetine on demand (n =78) or 50 mg sertraline qd for one month (n = 39). Follow-up was accomplished in 95 cases, 63 in the dapoxetine group and 32 in the sertraline group. We recorded the intravaginal ejaculatory latency time (IELT), clinical global impression of change (CGIC) score, and adverse reactions of the patients and compared them between the two groups. RESULTS: IELT was significantly increased in both the dapoxetine (from [0.87 ± 0.31] to [2.84 ± 0.68] min, P < 0.05) and the sertraline group (from [0.84 ± 0.28] to [2.71 ± 0.92] min, P < 0.05) after medication. Based on the CGIC scores in premature ejaculation, the rate of excellence or effectiveness was 36.5% in the dapoxetine and 37. 5% in the sertraline group, and the rate of improvement was 63.5% in the former and 71.9% in the latter. The incidence rates of dizziness, nausea, headache, and diarrhea were slightly higher (P > 0.05) while those of fatigue, somnolence, and dry mouth significantly higher (P < 0.05) in the sertraline than in the dapoxetine group. CONCLUSION: On-demand oral medication of dapoxetine is effective and well-tolerated for the treatment of premature ejaculation.

[DAB2IP expression in bladder transitional cell carcinoma and its correlation with clinical outcome].

OBJECTIVE: To investigate the expression of DAB2IP in bladder transitional cell carcinoma (BTCC) and its correlation with clinical characteristics and prognosis of BTCC patients. METHODS: Immunohistochemical staining was applied to detect DAB2IP protein level in 79 cases of TCCB tissues and 11 cases of normal bladder tissues, and the relationships of the staining results with pathological grade, stage, lymph node metastasis, gender, age and the 3-year survival rate of the patients were analyzed. RESULTS: The expression of DAB2IP in BTCC tissues was significantly lower than that in normal bladder epithelium, and the expression score and rate of DAB2IP in the high-grade, invasive and metastatic BTCC were significantly lower than those in low-grade, superficial and non-metastatic BTCC (P < 0.05). The 3-year survival rate of the patients with high DAB2IP expression was significantly higher than that of the patients with low DAB2IP expression. CONCLUSION: DAB2IP may be one of the important inhibitory factors during the occurrence and progression of BTCC.

Interaction of CCN1 with αvß3 integrin induces P-glycoprotein and confers vinblastine resistance in renal cell carcinoma cells.

Renal cell carcinoma (RCC) ranks among the most chemoresistant tumors, and P-glycoprotein (P-gp) predominates multidrug resistance mechanisms by reducing the accumulation of intracellular chemotherapy drugs such as vinblastine (VBL), which is considered the most effective chemotherapeutic agent for this neoplasia. Unfortunately, the mechanism by which the expression of P-gp is regulated and the ways to inhibit the function of P-gp are poorly understood. Our study was carried out to determine the possible role of CCN1 in P-pg-mediated drug resistance on the basis of the validated function of CCN1, an extracellular matrix protein, in promoting chemoresistance. As expected, CCN1 was overexpressed in VBL-resistant cell lines (ACHN/VBL, A498/VBL, Caki-1/VBL, and Caki-2/VBL) as measured by enzyme-linked immunosorbent assay. We then transfected non-VBL-resistant cell lines with Ad-CCN1 and observed that the IC50 of VBL increased by about 3-5 times. Furthermore, both CCN1 antibody neutralization and αvß3 integrin antibody blockade decreased the IC50 of VBL, which showed that CCN1 and αvß3 are associated with resistance to VBL in RCC. Simultaneously, the enhanced expression of CCN1 triggered the intracellular PI3K/Akt pathway by binding αvß3 integrin, as shown by western blot. P-gp expression was augmented in response to activation of the PI3K/Akt pathway, which could be modified by PI3K inhibitor LY294002 or multidrug resistance siRNA transfection. Therefore, targeted restraint of CCN1 or αvß3 integrin in combination with the administration of VBL may be beneficial in the treatment of primary and metastatic RCC.

[Study on bladder cancer tissues with Raman spectroscopy].

The scope of this research lies in diagnosis of bladder cancer through Raman spectra. The spectra of bladder cancer and normal bladder were measured by using laser confocal Raman micro-spectroscopy. Principal component analysis/support vector machines was applied to the spectral dataset to construct diagnostic algorithms, then to detect the accuracy of these algorithms to determine histological diagnosis by leave-one-out cross validation from its Raman spectrum. It was showed that the peak intensity of nucleic acid (782, 1 583 cm(-1)) in bladder cancer and protein (1 061, 1 295, 2 849, 2 881 cm(-1)) in normal bladder increased significantly. Additionally, Principal component analysis (PCA) and support vector machines (SVM) provided an effective tool for differentiating the bladder cancer from normal bladder tissue. Excellent sensitivity (86.7%), specificity (87.5%), positive predictive value (92.9%), and negative predictive value (72. 8%) for the diagnosis of bladder cancer were obtained by leave-one-out cross validation. It was concluded that Raman spectroscopy can be used to accurately identify bladder cancer in vitro, and it suggests the promising potential application of PCA/SVM-based Raman spectroscopy for the diagnosis of bladder cancer.

Silibinin inhibits prostate cancer invasion, motility and migration by suppressing vimentin and MMP-2 expression.

AIM: Silibinin is known to exert growth inhibition and cell death together with cell cycle arrest and apoptosis in human prostate cancer cells. Whether silibinin could inhibit the invasion, motility and migration of prostate cancer cells remains largely unknown. This study was designed to evaluate this efficacy and possible mechanisms using a novel highly bone metastatic ARCaP(M) cell model. METHODS: Four prostate cancer cell lines, LNCaP, PC-3, DU145, and ARCaP(M), were used in this study. These cells were treated with increasing concentrations of silibinin (50, 100, and 200 micromol/L) for different periods of time. After treatment, cell viabilities of four prostate cancer cells were compared by MTT assay. Alterations of ARCaP(M) cell invasion, motility and migration were assessed by cell invasion, motility and wound healing assays. The changes of vimentin expression were observed by Western blotting and immunofluorescence staining, and the expression of MMP-2, MMP-9, and uPA was analyzed by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: ARCaP(M) cells showed less sensitivity to the growth inhibition of pharmacological doses of silibinin than LNCaP, PC-3, and DU145 cells. However, silibinin exerted significant dose- and time-dependent inhibitory effects on the invasion, motility and migration of ARCaP(M) cells. Furthermore, the expression of vimentin and MMP-2, but not MMP-9 or uPA, was down-regulated in a dose- and time-dependent manner after treatment of silibinin. CONCLUSION: This study shows that silibinin could inhibit the invasion, motility and migration of ARCaP(M) cells via down-regulation of vimentin and MMP-2 and therefore may be a promising agent against prostate cancer bone metastasis.

A novel anti-cancer effect of genistein: reversal of epithelial mesenchymal transition in prostate cancer cells.

AIM: The aim of the present study was to investigate whether low dose genistein affects the invasion and epithelial mesenchymal transition (EMT) of prostate cancer (PCa) cells. METHODS: Human PCa cell lines, IA8-ARCaP and LNCaP/ HIF-1a, were used in this study. The cell lines were found to process EMT in our previous study. The PCa cells were treated with increasing concentrations, from 0.1 to 75 micromol/L. Proliferation was assessed with 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide assay. EMT was proven by cell morphological transition and the expression changes of EMT-related markers, which were confirmed by RT-PCR, Western blotting, and indirect immunofluorescence labeling. Transwell invasion assay was used to analyze the invasive potency. RESULTS: The addition of genistein to the medium reduced the IA8-ARCaP and LNCaP/HIF-1a viable cell number in a dose-dependent manner (with increasing concentrations from 15 to 75 micromol/L). Less than 15 micromol/L genistein was selected as the low dose concentration, which did not affect cell proliferation. The treatment of cells with low-dose genistein induced the reversal of EMT, which was confirmed by cell morphological transition and the expression changes of EMT-related markers. The reversal of EMT in the PCa cells by low-dose genistein was in a dose-dependent manner. Moreover, low-dose genistein effectively inhibited invasion of the PCa cells in vitro. CONCLUSION: These results showed that treatment with low-dose genistein may be a potential strategy for the suppression of invasive growth through the reversal of EMT in cancer cells, which justifies the potential use of soybean foods as a practical chemopreventive approach for patients with PCa.

[Establishment of bone metastasis model of prostate cancer in nude mice by intratibia injection of human prostate cancer cell line Du145].

OBJECTIVE: To establish a bone metastasis model of prostate cancer by intratibia injection of Du145 in nude mice, observe the local growth of tumor in tibia and then assess application value of this model. METHODS: For 9 male nude mice, Du145 (5 x 10(6)) was injected in tibia by a TB syringe with a 29-gauge needle at a dose of 30 microl per mouse. Then the vital signs of the nude mice were observed. When the mice were dying, they were sacrificed, and the tissues of right hindlimbs, lymphatic nodes, lungs and livers were taken out, fixed in 10% formalin, embedded in paraffin, stained by HE and then observed microscopically. RESULTS: Incidence of bone tumor after intratibia injection was 67% (6 out of 9). About 48 days later, there were some small palpable nodes in right hind-limbs of the 6 mice and they couldn't walk normally. About 55 days later, cachexia occurred in them. After dissection, some carrion-like tissue grew from marrow cavity to muscular spatium, which was identified as tumor tissue by HE. The envelop of livers became crampy, and acute hepatitis could be diagnosed through microscopy, which represented a large scale of hepatocytic death, liver sinus dilatation and hyperemia, hepatic lobule infiltrated by lymphocyte, macrophage and inconspicuous hyperplasia. Since hypohepatia occurred too early, we couldn't detected distant metastases. CONCLUSION: The intratibia injection model is an optimal animal model to study metastasis of prostate cancer. It mimics the natural situation of human prostate cancer and will help to understand the mechanisms of androgen-independence and osseous metastasis, and tumor-host determinants of PSA expression.

[Survey of the prevalence of chronic prostatitis in men with premature ejaculation].

OBJECTIVE: To investigate the prevalence of chronic prostatitis in men with premature ejaculation. METHODS: The segmented urine specimens before and after prostatic massage and the expressed prostatic secretion specimens from 106 patients with premature ejaculation and 38 controls were evaluated by microscopic and/or bacteriological studies. The prevalence of premature ejaculation was also investigated in 120 patients with chronic prostatitis. RESULTS: Prostatic inflammation was found in 46.2% and chronic bacterial prostatitis in 34.7% of the subjects with premature ejaculation, respectively. Compared with the controls, the findings were statistically significant (P < 0.05). The prevalence of premature ejaculation in the patients with chronic prostatitis was 47.5% (57/120). CONCLUSIONS: Chronic prostatic inflammation may play a role in the pathogenesis of some cases of premature ejaculation and it is important to give a careful examination of the prostate before initiating any therapy for premature ejaculation.

[Telomerase expression in various lesions of adrenal cortex].

OBJECTIVE: To investigate the expression of telomerase in various lesions of adrenal cortex. METHODS: By autoradiography-based telomeric repeat amplification protocol, telomerase expression was detected in 36 samples of adrenocortical lesions, including 29 cases adrenocortical adenoma (8 Cushing's syndrome, 17 aldosteronism and 4 nonfunctional adenomas), 5 cases of hyperplasia of adrenal cortex (presented with Chushing' syndrome), 2 cases adrenocortical carcinoma, and 4 samples of normal adrenal cortex. RESULTS: Of the 40 samples, 2 cases of adrenocortical carcinomas had telomerase expression, and the others had no telomerase expression detected. CONCLUSIONS: No significant telomerase expression was found among different endocrine functional benign adrenocortical lesions. Telomerase expression may be used as an important marker of malignant adrenocortical tumor.