A blinded, randomized controlled trial of neo-adjuvant celecoxib in patients with early prostate cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4563-4563 ◽  
Author(s):  
P. Sooriakumaran ◽  
P. Macanas-Pirard ◽  
S. Fox ◽  
H. Coley ◽  
G. Bucca ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Prostate Cancer ◽  
Cell Proliferation ◽  
Statistical Significance ◽  
Observer Agreement ◽  
Control Groups ◽  
Ki 67 ◽  
In Vivo Models ◽  
Cox 2 ◽  
And Control

4563 Background: Celecoxib inhibits tumorigenesis in many in vitro and in vivo models by anti-angiogenesis, induction of apoptosis, and inhibition of tumour cell proliferation and hypoxia. Methods: 45 cT1–2 prostate cancer patients were block randomized 2:1 to four weeks celecoxib 400mg b.d. or no drug prior to radical prostatectomy (RP). Tumour immunohistochemistry was performed for cell proliferation (Ki-67), angiogenesis (CD-31, VEGF, VEGF-R2), hypoxia (HIF-1), apoptosis (TUNEL), and COX-2. All scoring was performed blind by PS and a random 20% were validated blindly by an immunopathologist (SBF). In 19 patients (12 celecoxib-treated, 7 control), peri-operative peripheral zone biopsies were subjected to cDNA microarray analysis to identify differences in gene expression profiling (GEP) between the groups. Results: There was ‘substantial’ (kappa >0.6) or ‘almost perfect’ (kappa >0.8) inter-observer agreement in immunoscoring for all stains. Baseline scores were not significantly different between the celecoxib and control groups. In the celecoxib group, RP scores were significantly lower for Ki-67 (p = 0.036), and non-significantly lower for hypoxia (p = 0.15), KDR (p = 0.16), COX-2 (p = 0.19), microvessel density (p = 0.53), and VEGF (p = 0.83); tumour apoptosis was non-significantly higher (p = 0.26). MANOVA of the full model of stains showed that the difference between the two groups approached statistical significance (p = 0.058), and this was visualized with principal component analysis. GEP revealed that 76 genes were significantly differentially expressed between the celecoxib and control groups using uncorrected t-tests. In the celecoxib group, the tumour suppressor gene p73 and genes associated with protection against oxidative stress were significantly up-regulated; genes associated with cell adhesion were significantly down-regulated, consistent with a reduction in metastatic potential. Conclusions: Celecoxib appears to have marked anti-cancer effects on prostate tumours, most notably affecting cell cycle regulation, oxidative stress, and cell signalling. It may therefore be a promising agent in the management of prostate cancer and warrants further investigation. No significant financial relationships to disclose.

Role of MicroRNA-101 on Proliferation and Migration of Prostate Cancer Cells

2021 ◽  
Vol 11 (10) ◽  
pp. 2076-2080
Author(s):  
Yiming Weng ◽  
Jun Xiang ◽  
Wei Le ◽  
Yuanshen Mao
Keyword(s):  
Prostate Cancer ◽  
Control Groups ◽  
Cancer Pathogenesis ◽  
Pc3 Cells ◽  
Cox 2 ◽  
And Migration ◽  
And Control ◽  
Mtt Assays ◽  
Proliferation And Migration

Background: MicroRNA-101 is a tumor inhibitor that stimulates tumor progression by reducing or inhibiting the expression of certain oncogenes. Some studies presented that cox-2 is target of MicroRNA 101 in prostate cancer process. Methods: MicroRNA-101 expression was detected by RT-PCR in PC3 cell lines. A and to determine cell proliferation we used MTT assays. Cell would heal and Flow cytometry assays were also used to detect cellular migratory ability and apoptosis, respectively. To assess cox-2 protein expression, Immunohistochemistry was used and data analyzed by data analysis by SPSS 20. Results: PC3 cells treated by MicroRNA-101 mimics displayed a 24% elevation in growth rate compared with blank (P < 0.01) at 48 h, and a 12% increase (P < 0.01) at 72 h. On the other hand, at 48 and 72 h after the MicroRNA-101 inhibitor transfection, proliferation of PC3 cell was decreased significantly. The early apoptosis rate in transfected PC3 cells with MicroRNA-101 mimic (74.4%) and inhibitor (22.8%) were significantly different at 72 h after transfection (P < 0.05), MicroRNA-101 mimics inhibited cell migration, adhesion, and spread was wider relative to the group of control and inhibitor for the PC3 cells. Expression of Cox-2 in transfected PC3 with the MicroRNA-101 inhibitor was higher than the mimic and control groups significantly (P < 0.01). Conclusion: MicroRNA-101 by Cox-2 can play key roles in the prostate cancer pathogenesis.

scholarly journals Effects of two different deep digital flexor tenotomy techniques on distal articular angles of equine cadaver forelimbs

2012 ◽  
Vol 42 (11) ◽  
pp. 2005-2010
Author(s):  
Antonio Cezar de Oliveira Dearo ◽  
Vitor Bruno Bianconi Rosa ◽  
Peter Reichmann ◽  
Milton Luis Ribeiro de Oliveira
Keyword(s):  
Quantitative Data ◽  
Statistical Significance ◽  
Surgical Approaches ◽  
Control Groups ◽  
Before And After ◽  
Distal Interphalangeal ◽  
The Difference ◽  
And Control ◽  
Flexor Tenotomy

Deep digital flexor (DDF) tenotomy is a technique employed for years to treat selected disorders of the musculoskeletal system in horses. Although two different surgical approaches (i.e. mid-metacarpal and pastern) have been described for performing the procedure, in vitro quantitative data regarding the modifications induced by either technique on the distal articular angles is lacking. Therefore, the purpose of the study reported here was to investigate the viability of a proposed biomechanical system of induced-traction used to compare the two DDF tenotomy techniques by measuring the distal articular angles of equine cadaver forelimbs. Ten pairs of forelimbs were collected and mounted to a biomechanical system developed to apply traction at the toe level. Dorsal articular angles of the metacarpophalangeal (MP), proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints were determined by geometric lines on radiographs taken before and after performing each technique. Comparisons between each tenotomy group and its own control, for each joint, and between the two tenotomy groups using as variable the difference between the tenotomy and control groups were tested. Despite the lack of statistical significance, the DDF tenotomy technique at the pastern level produced extension, to a lesser and greater extent, of the PIP and DIP joints, respectively when compared to the mid-metacarpal level. No remarkable differences could be observed for the MP joint. The developed traction-induced biomechanical construct seemed to be effective in producing valuable quantitative estimations of the distal articular angles of equine cadaver forelimbs subjected to different DDF tenotomy techniques.

scholarly journals Impact of ascorbic acid in reducing the incidence of vancomycin associated nephrotoxicity in critically ill patients: A preliminary randomized controlled trial

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 929
Author(s):  
Nouran Hesham El-Sherazy ◽  
Naglaa Samir Bazan ◽  
Sara Mahmoud Shaheen ◽  
Nagwa A. Sabri
Keyword(s):  
Ascorbic Acid ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Statistical Significance ◽  
Intervention Group ◽  
Secondary Outcome ◽  
Control Group ◽  
Control Groups ◽  
The Absolute ◽  
And Control

Background Antioxidants show nephroprotective effect against vancomycin associated nephrotoxicity (VAN) in animals. This study aimed to assess the ascorbic acid nephro-protective role against VAN clinically. Methods Forty-one critically ill patients were randomly assigned to one of two groups: intervention group (vancomycin IV plus ascorbic acid, n=21) or control group (vancomycin IV only, n=20). Primary outcomes were the incidence of VAN and the absolute change in creatinine parameters, while mortality rate was the secondary outcome. Nephrotoxicity was defined as an increase in serum creatinine (S.cr) by at least 0.5 mg/dL or 50% of baseline for at least two successive measurements. This study is registered at Clinicaltrials.gov (NCT03921099), April 2019. Results Mean absolute S.cr increase was significant when compared between both groups, P-value = 0.036, where S.cr increased by 0.05(0.12) and 0.34(0.55) mg/dL in the intervention and control groups, respectively. Mean absolute Cr.cl decline was significant when compared between both groups, P-value = 0.04, where Cr.cl was decreased by 5.9(17.8) and 22.3(30.4) ml/min in the intervention and control groups, respectively. Incidence of VAN was 1/21(4.7%) versus 5/20(25%) in the intervention and control groups, respectively (RR: 0.19; CI: 0.024–1.49; P-value = 0.093). Mortality was higher in the control group; however, it was not statistically significant, P-value = 0.141. Conclusion Co-administration of ascorbic acid with vancomycin preserved renal function and reduced the absolute risk of VAN by 20.3%, however, the reduction in VAN incidence didn’t reach statistical significance level. Further large multicenter prospective trials are recommended.

scholarly journals Oxidative Stress in BPH

2009 ◽  
Vol 48 (173) ◽  
Author(s):  
Murat Savas ◽  
A Verit ◽  
H Ciftci ◽  
E Ciftci ◽  
E Aktan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Statistical Significance ◽  
Previous Treatment ◽  
Oxidative Status ◽  
Prostatic Hyperplasia ◽  
Newly Diagnosed ◽  
Antioxidative Status ◽  
Total Antioxidant ◽  
And Control ◽  
The Relationship

INTRODUCTION:In the present study, we investigated the relationship between potency of oxidative stress and BPH and this may assist to contribute to the realistic explanation of the ethiopathogenesis of BPH.METHODS:Seventy four newly diagnosed men with BPH (mean age: 54+/-11.2), who had not undergone any previous treatment for BPH, and 62 healthy volunteers (mean age: 55+/-14) were enrolled in the present study. To determine the antioxidative status of plasma, total antioxidant capacity (TAC) was calculated, and to determine the oxidative status of plasma (TOS) total peroxide levels were measured. The ratio of TAC to total peroxide was accepted as an indicator of oxidative stress (OSI). Data are presented as mean SD +/- unless specified. Student t-test and correlation analyses were used to evaluate the statistical significance differences in the median values recorded for all parameters between BPH and control group.RESULTS:Plasma TAC TOS were found in patients and controls (1.70 +/- 0.32, 1.68 +/- 0.19 micromol Trolox Equiv./L), (12.48 +/- 1.98, 12.40 +/- 1.14 micromol / L) respectively. OSI was calculated as 7.57 +/- 1.91, 7.48 +/- 1.33, respectively. Plasma TAC, TOS and OSI levels were not found to be significantly difference between patients and control subjects (p>0.05, p>0.05, p>0.05).CONCLUSIONS:The present study has shown that there were not relationship between potency of oxidative stress and BPH. Further well designed studies should be planned to find out whether the oxidative stress-related parameters play role in BPH as an interesting pathology in regard of the etiopathogenesis.Keywords: benign prostatic hyperplasia, oxidative stress, prostate

scholarly journals Oxidative stress and outcome of antioxidant supplementation in patients with polycystic ovarian syndrome (PCOS)

2018 ◽  
Vol 7 (5) ◽  
pp. 1667 ◽  
Author(s):  
Abubakar A. Panti ◽  
Constance E. Shehu ◽  
Yusuf Saidu ◽  
Karima A. Tunau ◽  
Emmanuel I. Nwobodo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Serum Levels ◽  
Clinical Pregnancy ◽  
Oxidative Stress Marker ◽  
Randomised Control Trial ◽  
Antioxidant Supplementation ◽  
Control Groups ◽  
Stress Marker ◽  
And Control

Background: PCOS is a condition with significant decrease in antioxidant with an increased risk of oxidative stress. Antioxidant supplementation has been shown to improve insulin sensitivity in PCOS and may improve outcome of management of PCOS. Objectives of this study were to determine the oxidative stress level of PCOS patients, to assess the effect of antioxidant supplementation on the outcome of management of PCOS and to compare with a control group.Methods: The study was a single blind randomised control trial involving 200 patients with PCOS. The study was conducted at Usmanu Danfodiyo University Teaching Hospital Sokoto. They were randomly divided into intervention and control groups and base line serum levels of oxidative stress marker, antioxidant enzymes, vitamins and minerals were determined. Antioxidant supplementation and placebo were given to the intervention and control groups respectively. All the patients had ovulation induction with clomiphene citrate and were followed up for 6 months. Outcome measures were clinical pregnancy or menstrual regularisation. Level of significance was <0.05.Results: There was statistical significance in the serum levels of oxidative stress marker, antioxidant enzymes, vitamins and minerals between the two groups (post intervention). Glutathione peroxidase (p = 0.001), superoxide dismutase (p = 0.0001), catalase (p= 0.0369), melondialdehyde (p= 0.007), Vitamin A, Vitamin C, Vitamin E (p = 0.0001), zinc and copper (p = 0.0001). The clinical pregnancy outcomes were 22 (22%) versus 2 (2%); live births 18 (18%) versus 2 (2%) and menstrual regularisation 48 (48%) versus 46 (46%) in the intervention and control groups respectively.Conclusions: Antioxidant supplementation in this study significantly affected pregnancy rate in patients with PCOS. Larger studies are suggested to revisit the conclusion of the Cochrane review that antioxidants supplementation had no significant role in female infertility.

scholarly journals The Effects of Serum from Prostate Cancer Patients with Elevated Body Mass Index on Prostate Cancer Cells in Vitro

2015 ◽  
Vol 8 ◽  
pp. LPI.S23135
Author(s):  
Benjamin C. Mora ◽  
Neil E. Fleshner ◽  
Laurence H. Klotz ◽  
Vasundara Venkateswaran
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cancer Patients ◽  
Migration And Invasion ◽  
Obese Patients ◽  
Control Groups ◽  
Necrosis Factor Alpha ◽  
Pc3 Cells

We examined whether serum from obese, compared to non-obese, PCa (prostate cancer) patients creates a growth-enhancing tumor micro-environment in vitro. Serum from 80 subjects was divided into four groups: normal weight men with and without PCa and overweight/obese men with and without PCa. Cell proliferation, migration, and invasion were measured in LNCaP, and PC3 cells treated with patient serum were obtained from the above groups. The results reveal that proliferation of LNCaP cells was significantly ( P = 0.05) greater with serum from non-obese (mean = 1.26 ± 0.20) compared to that from obese patients (mean = 1.16 ± 0.19). Serum from obese PCa patients compared to non-obese PCa patients induced significantly greater amounts of cell migration ( P < 0.01) in PC3 cells. Serum from obese patients induced significantly ( P < 0.01) lower amounts of cell invasion (mean = 8.2 ± 4.5) compared to non-obese patients (mean = 18.1 ± 5.0) when treated on PC3 cells. Serum TNF-α (tumor necrosis factor alpha) levels correlated with LNCaP cell proliferation in vitro in non-obese PCa ( P < 0.01) and non-obese control groups ( P = 0.05). All statistical calculations controlled for age, since the PCa patient groups were significantly older than the control groups ( P < 0.01). In conclusion, serum from obese PCa patients induced greater PCa cell migration and lower cell proliferation and invasion in vitro.

scholarly journals Reduction of Escherichia coli O157:H7 Populations in Cattle by Addition of Colicin E7-Producing E. coli to Feed

2004 ◽  
Vol 70 (10) ◽  
pp. 6053-6060 ◽  
Author(s):  
Gerry P. Schamberger ◽  
Ronald L. Phillips ◽  
Jennifer L. Jacobs ◽  
Francisco Diez-Gonzalez
Keyword(s):  
Escherichia Coli ◽  
Statistical Significance ◽  
Control Group ◽  
Control Groups ◽  
Tissue Samples ◽  
Fecal Shedding ◽  
E Coli ◽  
Colicin E7 ◽  
Maximum Decrease ◽  
And Control

ABSTRACT A cattle trial using artificially inoculated calves was conducted to determine the effect of the addition of colicinogenic Escherichia coli strains capable of producing colicin E7 (a 61-kDa DNase) to feed on the fecal shedding of serotype O157:H7. The experiment was divided into three periods. In period 1, which lasted 24 days, six calves were used as controls, and eight calves received 107 CFU of E. coli (a mixture of eight colicinogenic E. coli strains) per g of feed. Both groups were orally inoculated with nalidixic acid-resistant E. coli O157:H7 strains 7 days after the treatment started. In periods 2 and 3, the treatment and control groups were switched, and the colicinogenic E. coli dose was increased 10-fold. During period 3, which lasted as long as period 1, both groups were reinoculated with E. coli O157:H7. The numbers of E. coli O157:H7 were consistently greater in the control groups during the three periods, but comparisons within each time period determined a statistically significant (P < 0.05) difference only at day 21 of period 1. However, when the daily average counts were compared between the period 1 control group and the period 3 treatment group that included the same six animals, an overall reduction of 1.1 log10 CFU/g was observed, with a maximum decrease of 1.8 log10 CFU/g at day 21 (overall statistical significance, P = 0.001). Serotype O157:H7 was detected in 44% of the treatment group's intestinal tissue samples and in 64% of those from the control group (P < 0.04). These results indicated that the daily addition of 108 CFU of colicin E7-producing E. coli per gram of feed could reduce the fecal shedding of serotype O157:H7.

scholarly journals Phase II, Randomized, Placebo-Controlled Trial of Neoadjuvant Celecoxib in Men With Clinically Localized Prostate Cancer: Evaluation of Drug-Specific Biomarkers

2009 ◽  
Vol 27 (30) ◽  
pp. 4986-4993 ◽  
Author(s):  
Emmanuel S. Antonarakis ◽  
Elisabeth I. Heath ◽  
Janet R. Walczak ◽  
William G. Nelson ◽  
Helen Fedor ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Controlled Trial ◽  
Clinical Stage ◽  
Specific Antigen ◽  
Prostate Tissue ◽  
Localized Prostate Cancer ◽  
Double Blind ◽  
Ki 67 ◽  
End Points ◽  
Cox 2

Purpose Cyclooxygenase-2 (COX-2) is a potential pharmacologic target for the prevention of various malignancies, including prostate cancer. We conducted a randomized, double-blind trial to examine the effect of celecoxib on drug-specific biomarkers from prostate tissue obtained at prostatectomy. Patients and Methods Patients with localized prostate cancer and Gleason sum ≥ 7, prostate-specific antigen (PSA) ≥ 15 ng/mL, clinical stage T2b or greater, or any combination with greater than 45% risk of capsular penetration were randomly assigned to celecoxib 400 mg by mouth twice daily or placebo for 4 to 6 weeks before prostatectomy. The primary end point was the difference in prostatic prostaglandin levels between the two groups. Secondary end points were differences in COX-1 and -2 expressions; oxidized DNA bases; and markers of proliferation, apoptosis and angiogenesis. Tissue celecoxib concentrations also were measured. Tertiary end points were drug safety and compliance. Results Seventy-three patients consented, and 64 were randomly assigned and included in the intention-to-treat analysis. There were no treatment differences in any of the primary or secondary outcomes. Multivariable regression revealed that tumor tissue had significantly lower COX-2 expression than benign prostatic tissue (P = .01) and significantly higher levels of the proliferation marker Ki-67 (P < .0001). Celecoxib was measurable in prostate tissue of patients on treatment, demonstrating that celecoxib reached its target. Celecoxib was safe and resulted in only grade 1 toxicities. Conclusion Treatment with 4 to 6 weeks of celecoxib had no effect on intermediate biomarkers of prostate carcinogenesis, despite the achievement of measurable tissue levels. We caution against using celecoxib 400 mg twice daily as a preventive agent for prostate cancer in additional studies.

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