Advantages with prophylactic PEG-rhG-CSF versus rhG-CSF in breast cancer patients receiving multiple cycles of myelosuppressive chemotherapy: an open-label, randomized, multicenter phase III study.

BACKGROUND: PEG-rhG-CSF reduces neutropenia and improves chemotherapy safety. In China's registration trial (CFDA: 2006L01305), we assessed its efficacy and safety against rhG-CSF, and prospectively explored its value over multiple cycles of chemotherapy. METHODS: In this open-label, randomized, multicenter phase 3 study, breast cancer patients (n = 569) were randomized to receive PEG-rhG-CSF 100 µg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 µg/kg/d after chemotherapy. The primary endpoints were the incidence and duration of grade 3/4 neutropenia during cycle 1. Secondary endpoints included the incidence and duration of grade 3/4 neutropenia during cycles 2-4, the incidence of febrile neutropenia, and the safety. RESULTS: A once-per-cycle PEG-rhG-CSF at either 100 µg/kg or 6 mg was not different from daily injections of rhG-CSF for either incidence or duration of grade 3/4 neutropenia. Interestingly, a substantial difference was noted during cycle 2, and the difference became bigger over cycles 3-4, reaching a statistical significance at cycle 4 in either incidence (P = 0.0309) or duration (P = 0.0289) favoring PEG-rhG-CSF. A significant trend toward a lower incidence of all-grade adverse events was noted at 129 (68.98%), 142 (75.53%), and 160 (82.47%) in the PEG-rhG-CSF 100 µg/kg and 6 mg and rhG-CSF groups, respectively (P = 0.0085). The corresponding incidence of grade 3/4 drug-related adverse events was 2/187 (1.07%), 1/188 (0.53%), and 8/194 (4.12%), respectively (P = 0.0477). Additionally, PFS in metastatic patients preferred PEG-rhG-CSF to rhG-CSF despite no significance observed by Kaplan-Meier analysis (n = 49, P = 0.153). CONCLUSIONS: PEG-rhG-CSF is a more convenient and safe formulation and a more effective prophylactic measure in breast cancer patients receiving multiple cycles of chemotherapy.

[Effect of downregulation of prostate cancer antigen-1 expression on malignant biological behavior of prostate cancer LNCaP cells].

OBJECTIVE: To detect the expression of prostate cancer antigen-1 (PCA-1) in prostate cancer, and to analyze the effects of downregulation of PCA-1 expression on malignant biological behavior of prostate cancer LNCaP cells, and to explore their possible molecular mechanisms. METHODS: PCA-1-siRNA and control siRNA were transfected into LNCaP cells with lipofectamine 2000. The cell cycle, proliferation and migration were determined by methyl thiazolyl tetrazolium (MTT) assay, flow cytometry and Transwell chambers, respectively. Western blotting was used to detect the expression of cyclin E, matrix metallopeptidase 9 (MMP-9) and p21. Immunohistochemistry was used to detect the expression of PCA-1 protein in 126 cases of prostate cancer and 88 cases of benign prostatic hyperplasia (BPH). RESULTS: The positive rate of PCA-1 expression was 77.8% (98/126) in prostate cancer, and 10.2% (9/88) in BPH, and its expression was not significantly related to age, prostate specific antigen (PSA), Eastern Cooperative Oncology Group (ECOG) score (P > 0.05), and was associated with Gleason score, TNM staging and bone metastasis (P < 0.05). Downregulation of PCA-1 expression inhibited cell proliferation, arrested cell cycle at S phase and decreased cell migration of LNCaP cells. The downregulation of PCA-1 expression decreased the expression of Bcl-xl, cyclin E and MMP-9 proteins, but increased the expression of p21 proteins. CONCLUSIONS: PCA-1 may play an important role in the development of prostate cancer. The downregulation of PCA-1 expression can lead to changes in the proliferation, cell cycle and migration of prostate cancer LNCaP cells, and these effects may be associated with the decrease of Bcl-xl, cyclin E and MMP-9 proteins and increase of p21 protein.

Urodynamic parameters development and complications of clean intermittent self-catheterization in Chinese schoolchildren with neurogenic underactive bladder.

OBJECTIVE: To evaluate the urodynamic parameters, development of bladder function and complications of clean intermittent self-catheterization (CIC) in Chinese schoolchildren with neurogenic underactive bladder. METHODS: Ninety-three children with neurogenic underactive bladder were successfully treated with CIC or combined with oxybutynin for two years follow-up. According to bladder compliance before CIC, they were subdivided into a normal bladder compliance (NBC) group and a low bladder compliance (LBC) group. Urodynamic parameters and complications were recorded. RESULTS: At follow-up, the incidence of neurogenic detrusor overactivity was found to have significantly decreased in both groups. Moreover, maximum cystometric capacity (CC) and relatively safe CC in the NBC group was significantly higher than those before CIC. However, relatively safe CC was significantly lower than that before CIC, and detrusor leakage point pressure was significantly higher than that before CIC in the LBC group. The incidences of bacteriuria, vesicureteral reflux (VUR), febrile urinary tract infections (UTI) and macroscopic hematuria were, respectively, 62, 13, 25 and 15%, and those of VUR and febrile UTI in the LBC group were significantly higher than those in the NBC group. CONCLUSION: For these cases, the complications of CIC are rare, and bladder compliance seems to be correlated with the development of bladder function and complications during CIC.

[Transperitoneal laparoscopic adrenalectomy for adrenal neoplasm: a report of 371 cases].

BACKGROUND AND OBJECTIVE: Open adrenalectomy has been almost replaced by mini-invasive laparoscopic surgery. There are two popular mini-invasive laparoscopic adrenalectomy approaches: retroperitoneal and transperitoneal approaches. This study was to summarize our experience in transperitoneal laparoscopic adrenalectomy. METHODS: In total 371 cases undergoing transperitoneal adrenalectomy in the First Affiliated Hospital of Zhengzhou University from February 2003 to August 2008 were reviewed retrospectively. There were 127 cases of primary hyperaldosteronism adenoma, 117 cases of Cushing's adenoma, 58 cases of phaeochromo-cytoma, 37 cases of incidentoma and 32 cases of other types. The type of adrenal diseases, operating time, blood loss, complications and prognosis were summarized and the operating method was analyzed. RESULTS: Three hundred and sixty-five out of 371 patients (98.4%) were successfully operated, five cases (1.4%) were transferred to open surgery, and one patient gave up surgery due to extensive invasion. The operating time was 40-240 min (average, 70 min). The blood loss was 20-1000 ml (average, 80 ml). Two patients suffered from diaphragm injuries, one patient had right renal vein injury and one had colon injury. The mean time of hospital stay was five days. CONCLUSION: Transperitoneal laparoscopic adrenalectomy is one of the favorable approaches for the treatment of adrenal neoplasm.

[Comparison of three different methods of anesthesia during transrectal ultrasound guided prostate biopsy: a prospective, double-blind, randomized trial.].

OBJECTIVE: To assess the clinical efficacy and safety of three different methods of anesthesia during transrectal ultrasound guided prostate biopsy. METHODS: From July 2006 to October 2008, a total of 120 patients who underwent 12-core prostate biopsy with transrectal ultrasound guidance because of elevated prostate specific antigen and/or abnormal digital rectal examination were randomized into 4 groups, each group consisted of 30 patients. Group A received no anesthesia. Group B received an injection of 10 ml dose of 1% lidocaine (5 ml per side) into the region of the prostatic vascular pedicle at the prostate base just lateral to the junction between the seminal vesicle and prostate on each side for periprostatic nerve block (PNB). Group C received intrarectal lidocaine gel plus PNB. Group D received an injection of 4 ml dose of 1% lidocaine (2 ml per side) into 2 sites of the right and left sides of prostate for intraprostatic anesthesia plus PNB. The efficiency of anesthesia was assessed by a visual analog pain scale (VAS). All patients were followed up within one week for the evaluation of complications. RESULTS: The combination of intraprostatic anesthesia and PNB provided significantly better pain control than PNB alone. According to VAS, only group C (2.7 +/- 1.1) scores showed significantly better pain control than other groups (P < 0.05) during probe insertion, and only group D (3.9 +/- 1.3) scores showed significantly better pain control than other groups (P < 0.05) during biopsy. No difference was observed regarding the complications rate in the 4 groups (P > 0.05). CONCLUSIONS: Combination of intraprostatic anesthesia and PNB is effective and safe technique during transrectal ultrasound guided prostate biopsy without increasing the incidence of complications. PNB or PNB plus intrarectal lidocaine gel couldn't significantly reduce pain during biopsy.

[Expression of prostate cancer antigen-1 in prostate cancer and its clinical significance].

OBJECTIVE: To investigate the expression of prostate cancer antigen-1 (PCA-1) in different prostate tissues and analyze its correlation with the clinical parameters of prostate cancer (PCa). METHODS: The expression of PCA-1 mRNA was detected by RT-PCR in the samples from 45 cases of PCa with various clinico-pathologic characteristics, 30 cases of high-grade prostatic intraepithelial neoplasia (HG-PIN), 43 cases of BPH and 39 cases of other carcinoma tissues. The correlation of PCA-1 mRNA expression with the clinical parameters of PCa was statistically analyzed and the PCA-1 expression was examined in different samples by immunohistochemistry. RESULTS: The positive expression rate of PCA-1 mRNA was 88.9% and 60.0% and that of PCA-1 protein was 84.4% and 50.0% in the patients with PCa and HG-PIN, respectively. PCA-1 mRNA and PCA-1 proteins were not expressed in the BPH and other carcinoma tissues. The expression of PCA-1 mRNA was unrelated with the clinical parameters of PCa (P > 0.05). CONCLUSION: It is suggested that PCA-1 is a PCa-specific gene and its expression is unrelated to the clinical parameters of PCa. It might serve as a specific biomarker for the early diagnosis of PCa.

Prostate cancer antigen-1 as a potential novel marker for prostate cancer.

AIM: To examine the expression of prostate cancer antigen-1 (PCA-1) in prostate cancer (PCa) and to validate it as a potential marker for diagnosis of PCa. METHODS: In situ hybridization analysis of PCA-1 mRNA expression was performed on 40 benign prostate hyperplasia (BPH), 16 high-grade prostatic intraepithelial neoplasm (HG-PIN), 74 PCa and 34 other malignant carcinoma specimens. The level of PCA-1 expression was semiquantitatively scored by assessing both the percentage and intensity of PCA-1 positive staining cells in the specimens. We then compared the PCA-1 expression between BPH, HG-PIN and PCa and evaluated the correlation of PCA-1 expression level with clinical parameters of PCa. RESULTS: PCA-1 mRNA was expressed in the majority of both PCa and HG-PIN specimens but not in BPH and other malignant carcinoma. The expression level of PCA-1 increased along with a high Gleason score (P < 0.05), and was unrelated to other clinical parameters of PCa (all P > 0.05). CONCLUSION: The data suggest that PCA-1 might be a novel diagnostic marker for PCa, and that increased PCA-1 expression might denote more aggressive variants of PCa.

[Heme oxygenase-1 gene transfer protects rat kidney transplant from ischemia/reperfusion injury].

OBJECTIVE: To investigate the protective effect of Heme oxygenase-1 (HO-1) gene transfer on rat renal autograft against ischemia/reperfusion injury. METHODS: HO-1 recombinant adenovirus vectors were constructed and transduced into rat renal autograft by renal arterial perfusion. The renal autografts were transplanted orthotopically after store at 4 degrees C for 24 h, followed by contralateral native nephrectomy 5 d after transplantation. There were 25 rats in the control group. 5 h and 3 d after transplantation, reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry were used to detect the expression of HO-1 gene; enzyme-labeled immunosorbent (ELISA) was used to measure HO-1 protein content in the homogenate of renal autograft. RESULTS: The intensity of HO-1mRNA expression at 3 h and 3 d after transplantation were 0.65 +/- 0.11, 0.86 +/- 0.17 in the experimental group and 0.09 +/- 0.01, 0.15 +/- 0.02 in the control group respectively. The differences between the two groups were significant (t = 14.38, 11.73, P < 0.05). HO-1 protein content at 3 h and 3 d after transplantation were significantly increased in the experimental group, as compared with the control group [(297 +/- 61) ng/g and (468 +/- 51) ng/g versus (98 +/- 30) ng/g and (155 +/- 31) ng/g; t = 8.27, 14.83, P < 0.05]. HO-1 transduced autografts had less renal ischemic injury and lower serum creatinine level compared with control animals (P < 0.05). CONCLUSION: Adenoviral vector can successfully transduce rat kidneys with the HO-1cDNA, which can protect rat renal autografts from ischemia/reperfusion injury.