JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Circulating tumor cell telomerase activity as a prognostic marker for overall survival in SWOG 0421: A phase III metastatic castration resistant prostate cancer trial.
Int. J. Cancer
PUBLISHED: 05-21-2014
Show Abstract
Hide Abstract
Circulating tumor cells (CTC) are promising biomarkers in metastatic castration resistant prostate cancer (mCRPC), and telomerase activity (TA) is a recognized cancer marker. Therefore, we hypothesized that CTC TA may be prognostic of overall survival (OS) in mCRPC. To test this, we used a novel Parylene-C slot microfilter to measure live CTC TA in S0421, a phase III SWOG-led therapeutic trial. Blood samples underwent CTC capture and TA measurement by microfilter, as well as parallel enumeration by CellSearch (Janssen/J&J). Cox regression was used to assess baseline (pre-treatment) TA versus OS, and recursive partitioning was used to explore potential prognostic subgroups and to generate Kaplan-Meier (KM) OS curves. Samples were obtained from 263 patients and generated 215 TA measures. In patients with baseline CTC count ?5 (47% of patients), higher CTC TA was associated with hazard ratio 1.14 (p?=?0.001) for OS after adjusting for other clinical covariates including CTC counts and serum PSA at study entry. Recursive partitioning identified new candidate risk groups with KM OS curve separation based on CTC counts and TA. Notably, in men with an intermediate range baseline CTC count (6-54 CTCs/7.5 ml), low versus high CTC TA was associated with median survival of 19 versus 12 months, respectively (p?=?0.009). Baseline telomerase activity from CTCs live-captured on a new slot microfilter is the first CTC-derived candidate biomarker prognostic of OS in a large patient subgroup in a prospective clinical trial. CTC telomerase activity thus merits further study and validation as a step towards molecular CTC-based precision cancer management.
Related JoVE Video
Circulating tumor cell counts are prognostic of overall survival in SWOG S0421: a phase III trial of docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer.
J. Clin. Oncol.
PUBLISHED: 03-10-2014
Show Abstract
Hide Abstract
Circulating tumor cell (CTC) enumeration has not been prospectively validated in standard first-line docetaxel treatment for metastatic castration-resistant prostate cancer. We assessed the prognostic value of CTCs for overall survival (OS) and disease response in S0421, a phase III trial of docetaxel plus prednisone with or without atrasentan.
Related JoVE Video
Chemotherapy-induced monoamine oxidase expression in prostate carcinoma functions as a cytoprotective resistance enzyme and associates with clinical outcomes.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
To identify molecular alterations in prostate cancers associating with relapse following neoadjuvant chemotherapy and radical prostatectomy patients with high-risk localized prostate cancer were enrolled into a phase I-II clinical trial of neoadjuvant chemotherapy with docetaxel and mitoxantrone followed by prostatectomy. Pre-treatment prostate tissue was acquired by needle biopsy and post-treatment tissue was acquired by prostatectomy. Prostate cancer gene expression measurements were determined in 31 patients who completed 4 cycles of neoadjuvant chemotherapy. We identified 141 genes with significant transcript level alterations following chemotherapy that associated with subsequent biochemical relapse. This group included the transcript encoding monoamine oxidase A (MAOA). In vitro, cytotoxic chemotherapy induced the expression of MAOA and elevated MAOA levels enhanced cell survival following docetaxel exposure. MAOA activity increased the levels of reactive oxygen species and increased the expression and nuclear translocation of HIF1?. The suppression of MAOA activity using the irreversible inhibitor clorgyline augmented the apoptotic responses induced by docetaxel. In summary, we determined that the expression of MAOA is induced by exposure to cytotoxic chemotherapy, increases HIF1?, and contributes to docetaxel resistance. As MAOA inhibitors have been approved for human use, regimens combining MAOA inhibitors with docetaxel may improve clinical outcomes.
Related JoVE Video
Genetic Profiling to Determine Risk of Relapse Free Survival in High-risk Localized Prostate Cancer.
Clin. Cancer Res.
PUBLISHED: 12-18-2013
Show Abstract
Hide Abstract
The characterization of actionable mutations in human tumors is a prerequisite for the development of individualized, targeted therapy. We examined the prevalence of potentially therapeutically actionable mutations in patients with high risk clinically localized prostate cancer.
Related JoVE Video
Docetaxel and atrasentan versus docetaxel and placebo for men with advanced castration-resistant prostate cancer (SWOG S0421): a randomised phase 3 trial.
Lancet Oncol.
PUBLISHED: 07-17-2013
Show Abstract
Hide Abstract
The endothelin pathway has a role in bone metastases, which are characteristic of advanced prostate cancer. Atrasentan, an endothelin receptor antagonist, has shown activity in prostate cancer. We therefore assessed its effect on survival in patients with castration-resistant prostate cancer with bone metastases.
Related JoVE Video
Agent Orange as a risk factor for high-grade prostate cancer.
Cancer
PUBLISHED: 05-13-2013
Show Abstract
Hide Abstract
Agent Orange (AO) exposure (AOe) is a potential risk factor for the development of prostate cancer (PCa). However, it is unknown whether AOe specifically increases the risk of lethal PCa. The objective of this study was to determine the association between AOe and the risk of detecting high-grade PCa (HGPCa) (Gleason score ?7) on biopsy in a US Veteran cohort.
Related JoVE Video
Advances in the multimodality management of high-risk prostate cancer.
Surg. Oncol. Clin. N. Am.
PUBLISHED: 01-18-2013
Show Abstract
Hide Abstract
Prostate cancer is a heterogeneous disease with marked variability in its natural progression and response to therapeutic interventions. It is the most commonly diagnosed visceral cancer of men living in western countries, yet it is life-threatening in only a minority of cases. Thus, appropriate patient selection for treatment based on tumor as well as patient characteristics is essential to achieve optimal outcomes. The combination of early cancer detection and technical improvements in local treatment has led to a reduction in disease burden and an increase in cancer survivorship. However, treatment failure remains common among high-risk cases.
Related JoVE Video
Tubulin-targeting chemotherapy impairs androgen receptor activity in prostate cancer.
Cancer Res.
PUBLISHED: 08-31-2010
Show Abstract
Hide Abstract
Recent insights into the regulation of the androgen receptor (AR) activity led to novel therapeutic targeting of AR function in prostate cancer patients. Docetaxel is an approved chemotherapy for treatment of castration-resistant prostate cancer; however, the mechanism underlying the action of this tubulin-targeting drug is not fully understood. This study investigates the contribution of microtubules and the cytoskeleton to androgen-mediated signaling and the consequences of their inhibition on AR activity in human prostate cancer. Tissue microarrays from docetaxel-treated and untreated prostate cancer patients were comparatively analyzed for prostate-specific antigen (PSA) and AR immunoreactivity. The AR transcriptional activity was determined in prostate cancer cells in vitro, based on PSA mRNA expression and the androgen response element reporter activity. The interaction of AR with tubulin was examined by immunoprecipitation and immunofluorescence. Treatment of prostate cancer patients with docetaxel led to a significant translocation of AR. In untreated specimens, 50% prostate tumor cells exhibited nuclear accumulation of AR, compared with docetaxel-treated tumors that had significantly depleted nuclear AR (38%), paralleled by an increase in cytosolic AR. AR nuclear localization correlated with PSA expression. In vitro, exposure of prostate cancer cells to paclitaxel (1 ?mol/L) or nocodazole (5 ?g/mL) inhibited androgen-dependent AR nuclear translocation by targeting AR association with tubulin. Introduction of a truncated AR indicated the requirement of the NH(2)-terminal domain for AR-tubulin interaction. Our findings show that in addition to blocking cell division, docetaxel impairs AR signaling, evidence that enables new insights into the therapeutic efficacy of microtubule-targeting drugs in prostate cancer.
Related JoVE Video
Contemporary management of high-risk localized prostate cancer.
Curr Urol Rep
PUBLISHED: 04-29-2010
Show Abstract
Hide Abstract
The management of high-risk, localized prostate cancer remains a formidable challenge despite significant technical advances in surgery and radiation therapy. Treatment outcomes of radiation therapy are improved by the addition of adjuvant androgen deprivation therapy, whereas, with surgery, oncologic results are enhanced with either postoperative radiation therapy or androgen deprivation therapy in select cases. In high-risk prostate cancer, disease recurrence after primary therapy may occur at either distant or local sites. Ongoing studies are in the process of evaluating systemic therapy for the eradication of local and micrometastatic disease. Neoadjuvant therapies offer the opportunity to maximize local control as a path to improved outcomes and critically evaluate agent effectiveness in the target tissue. The treatment for high-risk localized prostate cancer is in evolution. It is likely that the development of effective strategies based on understanding prostate tumor biology will lead to significant advances in the treatment of this disease.
Related JoVE Video
ID1 enhances docetaxel cytotoxicity in prostate cancer cells through inhibition of p21.
Cancer Res.
PUBLISHED: 04-13-2010
Show Abstract
Hide Abstract
To identify potential mechanisms underlying prostate cancer chemotherapy response and resistance, we compared the gene expression profiles in high-risk human prostate cancer specimens before and after neoadjuvant chemotherapy and radical prostatectomy. Among the molecular signatures associated with chemotherapy, transcripts encoding inhibitor of DNA binding 1 (ID1) were significantly upregulated. The patient biochemical relapse status was monitored in a long-term follow-up. Patients with ID1 upregulation were found to be associated with longer relapse-free survival than patients without ID1 increase. This in vivo clinical association was mechanistically investigated. The chemotherapy-induced ID1 upregulation was recapitulated in the prostate cancer cell line LNCaP. Docetaxel dose-dependently induced ID1 transcription, which was mediated by ID1 promoter E-box chromatin modification and c-Myc binding. Stable ID1 overexpression in LNCaP increased cell proliferation, promoted G(1) cell cycle progression, and enhanced docetaxel-induced cytotoxicity. These changes were accompanied by a decrease in cellular mitochondria content, an increase in BCL2 phosphorylation at serine 70, caspase-3 activation, and poly(ADP-ribose) polymerase cleavage. In contrast, ID1 siRNA in the LNCaP and C42B cell lines reduced cell proliferation and decreased docetaxel-induced cytotoxicity by inhibiting cell death. ID1-mediated chemosensitivity enhancement was in part due to ID1 suppression of p21. Overexpression of p21 in LNCaP-ID1-overexpressing cells restored the p21 level and reversed ID1-enhanced chemosensitivity. These molecular data provide a mechanistic rationale for the observed in vivo clinical association between ID1 upregulation and relapse-free survival. Taken together, it shows that ID1 expression has a novel therapeutic role in prostate cancer chemotherapy and prognosis.
Related JoVE Video
Histologic changes associated with neoadjuvant chemotherapy are predictive of nodal metastases in patients with high-risk prostate cancer.
Am. J. Clin. Pathol.
PUBLISHED: 03-17-2010
Show Abstract
Hide Abstract
Clinical trials are evaluating the effect of neoadjuvant chemotherapy on men with high-risk prostate cancer. Little is known about the clinical significance of postchemotherapy tumor histopathologic features. We assessed the prognostic and predictive value of histologic features (intraductal carcinoma, vacuolated cell morphologic features, inconspicuous glands, cribriform architecture, and inconspicuous cancer cells) observed in 50 high-risk prostate cancers treated with preprostatectomy docetaxel and mitoxantrone. At a median follow-up of 65 months, the overall relapse-free survival (RFS) rates at 2 and 5 years were 65% and 49%, respectively. In univariate analyses (using the Kaplan-Meier method and log-rank tests), intraductal (P = .001) and cribriform (P = .014) histologic features were associated with shorter RFS. In multivariate analyses, using the Cox proportional hazards regression, baseline prostate-specific antigen (P = .004), lymph node metastases (P < .001), and cribriform histologic features (P = .007) were associated with shorter RFS. In multivariable logistic regression analysis, only intraductal pattern (P = .007) predicted lymph node metastases. Intraductal and cribriform histologic features apparently predict postchemotherapy outcome.
Related JoVE Video
Minimal benefit of an endorectal balloon for prostate immobilization as verified by daily localization.
Med Dosim
PUBLISHED: 03-02-2010
Show Abstract
Hide Abstract
We wanted to investigate whether using an endorectal balloon (ERB) in lieu of image guidance is reasonable. We compared daily prostate motion in 2 cohorts of patients with fiducial markers implanted in the prostate, one group with the ERB and the other without. Twenty-nine patients were treated using intensity-modulated radiation therapy: 14 with an ERB, and 15 without. All had fiducial markers placed in the prostate. We reviewed the daily displacements necessary to place the isocenter on the prostate as determined by portal imaging. In addition, we used the data to determine whether there is a change in prostate motion over the treatment course. The average prostate displacement for patients treated without an ERB was slightly greater than the average displacement for patients treated with the ERB. However, the difference observed with the ERB was not statistically significant (p > 0.05). The margins necessary to encompass the prostate 95% of the time for the patients treated without an ERB in the lateral, cranio/caudal, and anterior/posterior dimensions would be 4.8, 12.1, and 15.2 mm, respectively. When using the ERB, the margins necessary would be 4.1, 10.4, and 11 mm, respectively. Prostate motion in the anterior-posterior direction actually increased over the course of treatment in patients without an ERB. This increase was prevented by use of the ERB. Day-to-day variability of the position of the prostate is reduced in all dimensions with the water-filled ERB, but not significantly statistically. Use of the water-filled ERB did not obviate performing some form of image guidance daily.
Related JoVE Video
Phase 1/2 study of preoperative docetaxel and mitoxantrone for high-risk prostate cancer.
Cancer
PUBLISHED: 02-10-2010
Show Abstract
Hide Abstract
: A study was conducted to determine the 5-year recurrence-free survival in patients with high-risk prostate cancer after neoadjuvant combination chemotherapy followed by surgery. Secondary endpoints included safety, pathologic effects of chemotherapy, and predictors of disease recurrence.
Related JoVE Video
Acupuncture for hot flashes in patients with prostate cancer.
Urology
PUBLISHED: 02-08-2010
Show Abstract
Hide Abstract
To determine the effect of acupuncture on hot flash frequency and intensity, quality of life, and sleep quality in patients undergoing hormonal therapy for prostate cancer. Hot flashes are a common adverse effect of hormonal therapy for prostate cancer.
Related JoVE Video
Folate intake and prostate cancer risk: a case-control study.
Nutr Cancer
PUBLISHED: 10-20-2009
Show Abstract
Hide Abstract
Folate deficiency has been implicated in the carcinogenesis of several tumor types. The role of folate in prostate cancer remains indeterminate. We investigated folate as a risk factor for prostate cancer among 140 biopsy-confirmed prostate cancer patients, 230 age-matched clinic controls, and 250 negative prostate biopsy controls. Dietary folate intake was inversely associated with overall risk of prostate cancer as compared to clinic controls (P for a linear trend = 0.003). When stratified by disease severity, dietary folate and folate from natural sources were associated with reduced risk of high-grade cancer as compared to both clinic controls (P for a linear trend = 0.0009 and 0.02, respectively) and biopsy negative controls (P for a linear trend = 0.03 and 0.05, respectively). There was no interaction between alcohol consumption and folate intake. These analyses support an inverse association between dietary folate intake and prostate cancer risk and primarily risk of high-grade prostate cancer.
Related JoVE Video
Prostate cancer-associated gene expression alterations determined from needle biopsies.
Clin. Cancer Res.
PUBLISHED: 04-14-2009
Show Abstract
Hide Abstract
To accurately identify gene expression alterations that differentiate neoplastic from normal prostate epithelium using an approach that avoids contamination by unwanted cellular components and is not compromised by acute gene expression changes associated with tumor devascularization and resulting ischemia.
Related JoVE Video
Lower urinary tract symptoms increase the risk of falls in older men.
BJU Int.
PUBLISHED: 01-19-2009
Show Abstract
Hide Abstract
OBJECTIVE To evaluate the association of lower urinary tract symptoms (LUTS) with the risk of falls in elderly community-dwelling men. SUBJECTS AND METHODS We evaluated 5872 participants in the Osteoporotic Fractures in Men, a prospective cohort study of risk factors for falls and osteoporotic fractures among community-dwelling men aged > or =65 years. The primary outcome was the 1-year cumulative incidence of falls in men with moderate or severe, vs mild LUTS at baseline, as measured by the American Urological Association Symptom Index. We used Poisson regression models and considered multiple variables as potential confounders. RESULTS At baseline, 3188 (54%) reported mild, 2301 (39%) moderate, and 383 (7%) severe LUTS. Compared with men who had mild symptoms, the adjusted 1-year cumulative incidence of falls was significantly higher among men with moderate or severe LUTS. The risk of at least one fall was increased by 11% among those with moderate (relative risk 1.11, 95% confidence interval, CI, 1.01-1.22; P = 0.02) and by 33% among those with severe LUTS (1.33, 1.15-1.53; P < 0.001). Further, those with moderate LUTS had a 21% (1.21, 1.05-1.40; P = 0.01) and those with severe LUTS a 63% (1.63, 1.31-2.02; P < 0.001) greater risk of at least two falls. LUTS most strongly associated with falls were urinary urgency, difficulty initiating urination, and nocturia. CONCLUSIONS Moderate and severe LUTS independently increase the 1-year risk of falls, particularly recurrent falls, in community-dwelling older men. Because of the serious consequences of falls, these results might justify the routine assessment of LUTS with a validated questionnaire in the primary care of this population.
Related JoVE Video
Benign prostatic hyperplasia: a brief overview of pathogenesis, diagnosis, and therapy.
Tech Vasc Interv Radiol
Show Abstract
Hide Abstract
Benign prostatic hyperplasia is a common condition, causing symptoms in 75% of men over the age of 70. To understand the role of a novel treatment for this condition, an understanding of the pathology, approach to diagnosis, and range of existing therapies are important. This article provides a general overview of benign prostatic hyperplasia evaluation and management.
Related JoVE Video
Cell membrane water exchange effects in prostate DCE-MRI.
J. Magn. Reson.
Show Abstract
Hide Abstract
Prostate Dynamic-Contrast-Enhanced (DCE) MRI often exhibits fast and extensive global contrast reagent (CR) extravasation - measured by K(trans), a pharmacokinetic parameter proportional to its rate. This implies that the CR concentration [CR] is high in the extracellular, extravascular space (EES) during a large portion of the DCE-MRI study. Since CR is detected indirectly, through water proton signal change, the effects of equilibrium transcytolemmal water exchange may be significant in the data and thus should be admitted in DCE-MRI pharmacokinetic modeling. The implications for parameter values were investigated through simulations, and analyses of actual prostate data, with different models. Model parameter correlation and precision were also explored. A near-optimal version of the exchange-sensitized model was found. Our results indicate that ?K(trans) (the K(trans) difference returned by this version and a model assuming exchange to be effectively infinitely fast) may be a very useful biomarker for discriminating malignant from benign prostate tissue. Using an exchange-sensitized model, we find that the mean intracellular water lifetime (?(i)) - an exchange measure - can be meaningfully mapped for the prostate. Our results show prostate glandular zone differences in ?(i) values.
Related JoVE Video
Feasibility of shutter-speed DCE-MRI for improved prostate cancer detection.
Magn Reson Med
Show Abstract
Hide Abstract
The feasibility of shutter-speed model dynamic-contrast-enhanced MRI pharmacokinetic analyses for prostate cancer detection was investigated in a prebiopsy patient cohort. Differences of results from the fast-exchange-regime-allowed (FXR-a) shutter-speed model version and the fast-exchange-limit-constrained (FXL-c) standard model are demonstrated. Although the spatial information is more limited, postdynamic-contrast-enhanced MRI biopsy specimens were also examined. The MRI results were correlated with the biopsy pathology findings. Of all the model parameters, region-of-interest-averaged K(trans) difference [?K(trans) ? K(trans)(FXR-a) - K(trans)(FXL-c)] or two-dimensional K(trans)(FXR-a) vs. k(ep)(FXR-a) values were found to provide the most useful biomarkers for malignant/benign prostate tissue discrimination (at 100% sensitivity for a population of 13, the specificity is 88%) and disease burden determination. (The best specificity for the fast-exchange-limit-constrained analysis is 63%, with the two-dimensional plot.) K(trans) and k(ep) are each measures of passive transcapillary contrast reagent transfer rate constants. Parameter value increases with shutter-speed model (relative to standard model) analysis are larger in malignant foci than in normal-appearing glandular tissue. Pathology analyses verify the shutter-speed model (FXR-a) promise for prostate cancer detection. Parametric mapping may further improve pharmacokinetic biomarker performance.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.