Differential gene expression in preoperative study of selenium and vitamin E chemoprevention in prostate cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1523-1523
Author(s):  
J. Kim ◽  
D. Tsavachidou ◽  
K. Do ◽  
S. Wen ◽  
R. Babaian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Vitamin E ◽  
Nearest Neighbor ◽  
Controlled Trial ◽  
Clinical Stage ◽  
Specific Antigen ◽  
Therapeutic Interventions ◽  
Double Blind ◽  
Prostate Carcinogenesis

1523 Background: To identify genes that distinguish between treatments, tumor types, and their interaction, we undertook a microarray analysis of tissue in a preoperative chemoprevention study of L-selenomethionine (SeMet) and vitamin E (VE) in prostate cancer. Methods: Forty-eight men with prostate cancer were enrolled in a single-institution, double-blind, placebo-controlled trial that randomized patients into four groups receiving 200 μg SeMet, 400 IU VE, a combination of the two, or placebo (see 2006 ASCO abstract 1007). All patients also received a multivitamin and vitamin C (250 mg) daily. Modeled on the Selenium and Vitamin E Cancer Prevention Trial, this study included patients scheduled for prostatectomy within 3 to 6 wk of registration who had a prostate-specific antigen level <10 ng/mL within 3 mo of registration, clinical stage T1c/T2 disease, and a Gleason score =7. From core biopsy specimens, we isolated cancerous and noncancerous cells, tumor-adjacent stroma, and non-tumor adjacent stroma of 38 evaluable radical prostatectomy specimens using laser capture microdissection. The cDNA hybridized to oligonucleotide microarrays was generated from extracted RNA, which had undergone two rounds of linear amplification. Expression levels were extracted using the positional-dependent nearest-neighbor model, and after ANOVA model analysis, effects were contrasted using the approximate z-test with statistic z. The beta-uniform mixture model was used to analyze p values and control the false discovery rate. Ingenuity Pathway Analysis followed. Results: Differentially expressed genes were selected that were common in the combination and selenium arms or in the combination and VE arms: unique in tumor-69 in combination and selenium, 71 in combination and VE; unique in stroma-64 in combination and selenium, 45 in combination and VE; unique in normal tissue-48 in combination and selenium, 38 in combination and VE. Conclusions: This work demonstrates that gene expression may be correlated with specific therapeutic interventions, and this analysis indicates that dietary antioxidants modulate gene expression in human prostate cancer cells and pathways relevant to prostate carcinogenesis. No significant financial relationships to disclose.

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.

scholarly journals Dong Quai (angelica sinensis) in the treatment of hot flashes for men on androgen deprivation therapy: results of a randomized double-blind placebo controlled trial

2013 ◽  
Vol 4 (1) ◽  
pp. 49 ◽  
Author(s):  
Reem J. Al-Bareeq ◽  
A. Andrew Ray ◽  
Linda Nott ◽  
Stephen E. Pautler ◽  
Hassan Razvi
Keyword(s):  
Prostate Cancer ◽  
Controlled Trial ◽  
Hot Flashes ◽  
Specific Antigen ◽  
Therapeutic Benefit ◽  
Small Pilot Study ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Average Percentage ◽  
Essai Randomisé

Objective: To determine whether Dong Quai, a Chinese herbalcompound purported to be efficacious in treating menopausalvasomotor symptoms, has a therapeutic benefit in treating hotflashes among prostate cancer patients receiving androgen deprivationtherapy.Methods: A randomized double-blind placebo controlled trial wasconducted involving 22 men receiving luteinizing hormone-releasinghormone agonist therapy for prostate cancer with bothersomehot flashes. After recording a baseline log of the frequency, durationand severity of daily hot flashes, patients were randomlyassigned in a 1:1 ratio to receive daily placebo or Dong Quai for3 months. Vasomotor and adverse events were recorded daily.Blood work including serum prostate-specific antigen (PSA), internationalnormalized ratio of prothrombin time and partial thromoboplastintime were recorded at baseline and at the terminationof the study.Results: Seventeen of the 22 patients enrolled completed the trial.Baseline vasomotor duration and severity were equivalent betweenthe groups, however the number of hot flashes were significantlymore in the Dong Quai group (p = 0.02). With respect to thechange in number of hot flashes per day, there was a slight decreasein the mean number among the Dong Quai group which wasinsignificant. The absolute change and average percentage changein perceived hot flash severity was similar in both groups. Therewas no significant decrease in the duration of the hot flashes betweenthe 2 groups. Disease progression based on either PSA increaseor change in digital rectal exam was not observed in any patient.Conclusion: In this small pilot study, there were no significant differencesin the severity, frequency or duration of hot flashes amongmen receiving placebo or Dong Quai.Introduction : Nous avons cherché à déterminer si le Dong Quai(Angelica sylvestris chinensis ou angélique chinoise), une plantemédicinale chinoise censée être efficace dans le traitement dessymptômes vasomoteurs liés à la ménopause, procure des bienfaitsthérapeutiques aux patients atteints de cancer de la prostateprésentant des bouffées vasomotrices pendant un traitement antiandrogène.Méthodologie : On a mené un essai randomisé à double insu etcontrôlé par placebo auprès de 22 hommes recevant un agonistede l’hormone de libération de l’hormone lutéinisante (LHRH) pourle traitement d’un cancer de la prostate et présentant des boufféesvasomotrices incommodantes. Après avoir noté au départ lafréquence, la durée et la gravité des épisodes quotidiens de boufféesvasomotrices, on a réparti les patients aléatoirement selonun rapport de 1:1 pour recevoir chaque jour un placebo ou duDong Quai pendant 3 mois. Les effets vasomoteurs et les réactionsindésirables ont été notés chaque jour. Des analyses sanguinescomprenant le taux sérique d’APS et le rapport internationalnormalisé du temps de Quick et du temps de thromboplastinepartielle ont été effectuées au départ et à la fin de l’étude.Résultats : Dix-sept des 22 patients inscrits ont participé à l’étudejusqu’à la fin. La durée et la gravité des épisodes de bouffées vasomotricesétaient similaires dans les deux groupes au départ, maisle nombre d’épisodes de bouffées vasomotrices était significativementplus élevé dans le groupe recevant le Dong Quai (p = 0,02).En ce qui a trait à la variation dans le nombre d’épisodes quoti -diens, une légère diminution a été notée dans le nombre moyendans le groupe sous Dong Quai mais cette diminution s’est avéréenon significative. La variation absolue et le pourcentage moyende variation dans la gravité perçue des épisodes de bouffées vasomotricesétaient similaires dans les deux groupes. On n’a notéaucune diminution de la durée des épisodes dans les deux groupes.Aucune progression de la maladie, en fonction de changementsdans les taux d’APS ou lors des touchers rectaux n’a été notée.Conclusion : Dans cette petite étude pilote, aucune différence signi -ficative n’a été observée dans la gravité, la fréquence ou la duréedes bouffées vasomotrices

Limitation of prostate-specific antigen doubling time as a predictor of outcome in hormone-naive prostate cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4566-4566 ◽  
Author(s):  
J. B. Nelson ◽  
D. J. Sleep ◽  
J. D. Isaacson ◽  
M. A. Carducci
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Doubling Time ◽  
Controlled Trial ◽  
Specific Antigen ◽  
Controlled Study ◽  
Primary Therapy ◽  
Double Blind ◽  
Psa Velocity ◽  
Baseline Psa

4566 Background: Prostate-specific antigen doubling time (PSADT) is used to monitor progression after primary therapy for prostate cancer. Increasingly in this population, PSADT is an efficacy measure in therapeutic trials, many of which are uncontrolled. Examination of PSADT response on placebo in a randomized controlled study may evaluate the utility of PSADT as an outcome measure in patients with hormone-naive prostate cancer. Methods: Patients with biochemical failure post radical prostatectomy were enrolled in a randomized, double-blind, placebo-controlled trial of atrasentan 10 mg. Eligibility criteria included baseline PSA between 0.4 ng/mL and 5 ng/mL with a PSADT ≤12 months based on two PSA values at least 2 weeks apart. On-treatment PSADT was compared between treatment groups in patients with at least 3 on-treatment PSA values collected every 12 weeks while on study drug. Categorical analysis comparing PSADT between groups was performed using Cochran-Mantel-Haenszel methodology. Mean change from baseline in PSA velocity (log PSA vs time) was analyzed using a one-way analysis of variance with treatment as the factor. Results: Of 222 patients enrolled, 209 had 3 PSA values on study: N=107 for placebo; N = 102 for atrasentan. Baseline PSA was lower for patients in the placebo arm than for those in the atrasentan arm (mean of 1.4 ng/mL [SE 0.1] vs 1.8 ng/mL [SE 0.1] P =.012). On-treatment PSADT was similar between treatment arms (P =.363); the proportion of patients whose PSADT was >1 year on study was 55% with placebo and 51% with atrasentan. More notably, PSADT lengthened on study for most patients in both arms (76/107, 71% for placebo and 68/102, 64% for atrasentan). PSA velocity was also protracted for patients in both treatment arms (placebo: slope = 1.47 at baseline to 0.96, P < .001; atrasentan: slope = 1.56 at baseline to 1.26, P =.017). Conclusions: The fact that over 70% of patients receiving placebo experienced lengthened PSADT suggests that, in the absence of a control arm, changes in PSADT from baseline are not a reliable measure of treatment effect in trials in early prostate cancer. PSADT data from trials in this population should be interpreted with caution. [Table: see text]

Overall survival (OS) analysis of a phase II randomized controlled trial (RCT) of a poxviral-based PSA targeted immunotherapy in metastatic castration-resistant prostate cancer (mCRPC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5013-5013
Author(s):  
P. W. Kantoff ◽  
T. Schuetz ◽  
B. A. Blumenstein ◽  
M. M. Glode ◽  
D. Bilhartz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Viral Vectors ◽  
Controlled Trial ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Gm Csf

5013 Background: Therapeutic poxviral vaccines for prostate cancer are safe with preliminary evidence of clinical benefit in phase I/II studies. PROSTVAC-VF (PV) comprises 2 recombinant viral vectors (Vaccinia and Fowlpox), each encoding transgenes for prostate specific antigen (PSA) and 3 immune costimulatory molecules (B7.1, ICAM-1, and LFA3: TRICOM). PV is administered subcutaneously in a heterologous prime-boost regimen with concurrent low-dose GM-CSF. Methods: 122 patients (pts) were treated in a multi-center, double-blind, RCT of a vaccination series. Pts were randomized 2:1 to PV + GM-CSF vs. placebo empty vector + control saline injections (C). Vaccinia-based vector was used for priming followed by 6 planned Fowlpox-based vector boosts. The trial completed enrollment in July 2005. Eligible pts had metastatic disease, a rising PSA despite castrate testosterone levels, and a Gleason score of ≤7. Pts with a history of prior chemotherapy use, visceral metastasis, or narcotic use were excluded. The 1º endpoint was progression free survival (PFS), with progression defined as 2 new lesions on bone scan or RECIST-defined progression. Vaccination was discontinued after progression. Results: 82 pts received PV and 40 received C. Pt characteristics were similar (means): age (72PV/76C), PSA (134PV/188C), Alk-Phos (142PV/159C), LDH (207PV/218C), Hgb (13PV/13C), and number bone metastatic sites (5.3PV/6.5C). Mean number of vaccinations was 5.4 PV and 5.3 C. PFS was similar in the 2 groups (p = 0.56). However, at 3 years post study, PV patients had a better overall survival than C patients (25 alive, 30%, PV, versus 7 alive, 17%, C) and a longer median survival (24.5 months PV, versus 16 months C); estimated hazard ratio 0.6 (95% CI 0.4–0.9); stratified log rank p = 0.016. Conclusions: In a RCT, PV immunotherapy was associated with an 8.5 month improvement in median OS in men with mCRPC. These data provide evidence of prolonged anti-tumor activity, but need to be confirmed in a larger phase III study. [Table: see text]

Results from a phase 3, randomized, double-blind, multicenter, placebo-controlled trial of orteronel (TAK-700) plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) that has progressed during or following docetaxel-based therapy (ELM-PC 5 trial).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 7-7 ◽  
Author(s):  
Robert Dreicer ◽  
Robert Jones ◽  
Stephane Oudard ◽  
Eleni Efstathiou ◽  
Fred Saad ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Primary Endpoint ◽  
Controlled Trial ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Castration Resistant ◽  
Key Enzyme

7^ Background: Orteronel is an investigational, non-steroidal selective inhibitor of 17,20-lyase; a key enzyme in the production of steroidal hormones. Methods: Eligible men with metastatic castration-resistant prostate cancer (mCRPC) had progressive disease (PD; radiographic or prostate-specific antigen), castrate levels of testosterone, and had received more than or equal to 360 mg/m2docetaxel within the prior 6 months. Prior orteronel, abiraterone, or ketoconazole was not permitted. Patients were randomized 2:1 to continuous 28-day cycles of oral orteronel 400 mg BID + prednisone 5 mg BID, or placebo + prednisone without regard to food. Primary endpoint: overall survival (OS); other key endpoints: radiographical progression-free survival (rPFS), 50% or more PSA decrease at 12 weeks, pain response at 12 weeks and safety (NCT01193257). Results: One thousand ninety nine patients were randomized.The study was terminated for failing to meet its primary endpoint: median overall survival (OS) was 17.0 months (95% CI 15.2, 19.9) in patients receiving orteronel versus 15.2 months (95% CI 13.5, 16.9) in those receiving placebo (HR: 0.886 [95% CI: 0.739, 1.062]; P=0.1898). Substantial regional differences were seen in OS benefit: median OS (orteronel vs. placebo) was 20.9 vs. 16.9 mo (HR: 0.889) in North America (n=112), 18.3 vs. 17.8 mo (HR: 1.048) in Europe (n=590), and 15.3 vs 10.1 mo (HR: 0.709) in the rest of the world (n=397). In the overall population, rPFS was significantly improved in the orteronel arm, with a median of 8.3 months vs. 5.7 months in the placebo arm (HR: 0.76 [95% CI: 0.653, 0.885]; P=0.00038). Drug-related adverse events (AEs; any grade) included (orteronel/placebo) nausea (30/16%), vomiting (23/8%), fatigue (17/11%), and diarrhea (16/9%); grade 3 or higher drug-related AEs included increased lipase (12/less than 1%), increased amylase (8/less than 1%), and fatigue (3/3%). Additional sub-analyses looking at potential factors that affected OS will also be reported. Conclusions: Whileorteronel + prednisone did not show a statistically significant overall OS improvement versus placebo + prednisone, rPFS findings and striking regional OS differences suggest that orteronel has clinically meaningful activity. Clinical trial information: NCT01193257.

scholarly journals The Effects of Dietary Supplementation of Lactococcus lactis Strain Plasma on Skin Microbiome and Skin Conditions in Healthy Subjects—A Randomized, Double-Blind, Placebo-Controlled Trial

2021 ◽  
Vol 9 (3) ◽  
pp. 563
Author(s):  
Ryohei Tsuji ◽  
Kamiyu Yazawa ◽  
Takeshi Kokubo ◽  
Yuumi Nakamura ◽  
Osamu Kanauchi
Keyword(s):  
Gene Expression ◽  
Lactococcus Lactis ◽  
Healthy Subjects ◽  
Controlled Trial ◽  
Dietary Supplementation ◽  
Skin Microbiome ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Lactis Strain ◽  
Skin Conditions

(1) Background: Lactococcus lactis strain Plasma (LC-Plasma) is a unique strain which directly activates plasmacytoid dendritic cells, resulting in the prevention against broad spectrum of viral infection. Additionally, we found that LC-Plasma intake stimulated skin immunity and prevents Staphylococcus aureus epicutaneous infection. The aim of this study was to investigate the effect of LC-Plasma dietary supplementation on skin microbiome, gene expression in the skin, and skin conditions in healthy subjects. (2) Method: A randomized, double-blind, placebo-controlled, parallel-group trial was conducted. Seventy healthy volunteers were enrolled and assigned into two groups receiving either placebo or LC-Plasma capsules (approximately 1 × 1011 cells/day) for 8 weeks. The skin microbiome was analyzed by NGS and qPCR. Gene expression was analyzed by qPCR and skin conditions were diagnosed by dermatologists before and after intervention. (3) Result: LC-Plasma supplementation prevented the decrease of Staphylococcus epidermidis and Staphylococcus pasteuri and overgrowth of Propionibacterium acnes. In addition, LC-Plasma supplementation suggested to increase the expression of antimicrobial peptide genes but not tight junction genes. Furthermore, the clinical scores of skin conditions were ameliorated by LC-Plasma supplementation. (4) Conclusions: Our findings provided the insights that the dietary supplementation of LC-Plasma might have stabilizing effects on seasonal change of skin microbiome and skin conditions in healthy subjects.

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