Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In recent studies, we have identified several highly potent all-trans-retinoic acid (ATRA) metabolism blocking agents (RAMBAs). On the basis of previous effects of liarozole (a first-generation RAMBA) on the catabolism of ATRA and on growth of rat Dunning R3227G prostate tumours, we assessed the effects of our novel RAMBAs on human prostate tumour (PCA) cell lines. We examined three different PCA cell lines to determine their capacity to induce P450-mediated oxidation of ATRA. Among the three different cell lines, enhanced catabolism was detected in LNCaP, whereas it was not found in PC-3 and DU-145. This catabolism was strongly inhibited by our RAMBAs, the most potent being VN/14-1, VN/50-1, VN/66-1, and VN/69-1 with IC50 values of 6.5, 90.0, 62.5, and 90.0 nM, respectively. The RAMBAs inhibited the growth of LNCaP cells with IC50 values in the microM-range. In LNCaP cell proliferation assays, VN/14-1, VN/50-1, VN/66-1, and VN/69-1 also enhanced by 47-, 60-, 70-, and 65-fold, respectively, the ATRA-mediated antiproliferative activity. We then examined the molecular mechanism underlying the growth inhibitory properties of ATRA alone and in combination with RAMBAs. The mechanism appeared to involve the induction of differentiation, cell-cycle arrest, and induction of apoptosis (TUNEL), involving increase in Bad expression and decrease in Bcl-2 expression. Treatment of LNCaP tumours growing in SCID mice with VN/66-1 and VN/69-1 resulted in modest but statistically significant tumour growth inhibition of 44 and 47%, respectively, while treatment with VN/14-1 was unexpectedly ineffective. These results suggest that some of our novel RAMBAs may be useful agents for the treatment of prostate cancer.
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PMID:Inhibitory effects of retinoic acid metabolism blocking agents (RAMBAs) on the growth of human prostate cancer cells and LNCaP prostate tumour xenografts in SCID mice. 1644 97

PSA-only recurrence after definitive RP or RT for PCA is an increasingly com-mon scenario. The very definition of advanced prostate cancer is changing. Multimodal therapy improves cancer-specific outcomes especially in men with high-risk disease. After RP, a detectable serum PSA has been considered suggestive of PCA recurrence. After RT, the ASTRO definition of BCR has been widely used to define BCR. Both of these definitions of BCR are subject to dispute. The kinetics of a rising PSA (PSA doubling time) appears to be the best surrogate marker for disease risk, clinical progression, and ultimately cancer-specific death. Therapeutic options include salvage RT after primary RP or systemic HT through surgical/chemical castration, antiandrogens, or nontraditional HT. Re-cent studies suggest that early HT can provide modest survival benefits, but at both an economic cost and decreased quality of life. The diminished side effects of an oral antiandrogen are appealing, and may be as efficacious as castration therapies in low-volume disease. More clinical trials are needed to determine the best treatments, alone and in combination. The potential opportunities for novel therapeutic agents with low associated morbidity are great.
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PMID:Management of the patient with a rising PSA alone. 1686 Nov 21

Technical developments of radiotherapy (RT) over the recent years yielded in better conformation to the target volume thus increasing the therapeutic ratio and decreasing side effects. This paper discusses these options for low-risk prostate cancer. There has been evidence from randomized trials, that for low-risk PCA doses >70 Gy are significant better in case of biochemical disease-free survival (bNED). Image-guided radiotherapy (IGRT) has been proven in several studies for reduced safety margins around the prostate target volume. Intensity-modulated radiotherapy (IMRT) allow treatment with higher doses and 5-year results are reported from several studies. Data from several randomized trials about adjuvant RT after radical prostatectomy (RP) have been reported. In two phase-III trials a significant advantage of 20% bNED was demonstrated for doses between 76 and 79 Gy compared with 70 Gy. Using IGRT, the safety margin around the prostate can be reduced for about 30-50%. Doses of >80 Gy can be given safely to the prostate with IMRT and <5% grade-III/IV late side effects. Adjuvant RT for positive margins after RP has been of proven advantage. Three phase-III trials achieved a significant better bNED of 20% for 5 years. The effect of doses >70 Gy have been proven for low-risk PCA. IGRT resulted in reduced safety margins and a decrease of acute and late side effects. The addition of IMRT allowed higher doses to the prostate. Adjuvant RT after RP for positive margins achieved a significant better bNED.
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PMID:Percutaneous radiotherapy for low-risk prostate cancer: options for 2007. 1736 13

Cancer of the prostate gland (PCA) is the most common invasive malignancy and is the second leading cause of cancer-related death in males. The polyphenolic constituents of black tea have gained considerable attention as chemopreventive agents. Many studies have shown that black tea reduces the risk of several cancer types. In the present study, we studied the effect of a black tea polyphenol, theaflavin (TF), on cellular proliferation and cell death in the human prostate cancer cell line, PC-3. We showed that TF inhibits cell proliferation in a dose- and time-dependent manner. Studies on cell cycle progression have shown that the anti-proliferative effect of TF is associated with an increase in the G2/M phase of PC-3 cells. Western blot results showed that TF-induced G2/M phase arrest was mediated through the inhibition of cyclin-regulated signaling pathways. TF induces cyclin kinase inhibitor p21(waf1/cip1) expression and inhibits cdc25C and cyclin B expression. Increased exposure time to TF caused apoptosis of PC-3 cells, which was associated with up-regulation of the pro-apoptotic proteins Bax, caspase-3 and caspase-9 and down-regulation of anti-apoptotic protein Bcl-2. The role of caspase-induced apoptosis was further confirmed by a reduction in mitochondria membrane potential and the appearance of a DNA laddering pattern. Thus, it can be concluded that TF acts as an effective anti-proliferative agent by modulating cell growth regulators in prostate cancer cells.
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PMID:Theaflavins induce G2/M arrest by modulating expression of p21waf1/cip1, cdc25C and cyclin B in human prostate carcinoma PC-3 cells. 1793 51

Herein, we describe a novel approach in the search for prostate cancer biomarkers, which relies on the transcriptome within tumour exosomes. As a proof-of-concept, we show the presence of two known prostate cancer biomarkers, PCA-3 and TMPRSS2:ERG the in exosomes isolated from urine of patients, showing the potential for diagnosis and monitoring cancer patients status.
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PMID:Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer. 1940 83

Magnetic resonance spectroscopy (MRS) has been shown to have great clinical potential as a supplement to magnetic resonance imaging in the detection of prostate cancer (CaP). MRS provides functional information in the form of changes in the relative concentration of specific metabolites including choline, creatine, and citrate which can be used to identify potential areas of CaP. With a view to assisting radiologists in interpretation and analysis of MRS data, some researchers have begun to develop computer-aided detection (CAD) schemes for CaP identification from spectroscopy. Most of these schemes have been centered on identifying and integrating the area under metabolite peaks which is then used to compute relative metabolite ratios. However, manual identification of metabolite peaks on the MR spectra, and especially via CAD, is a challenging problem due to low signal-to-noise ratio, baseline irregularity, peak overlap, and peak distortion. In this article the authors present a novel CAD scheme that integrates nonlinear dimensionality reduction (NLDR) with an unsupervised hierarchical clustering algorithm to automatically identify suspicious regions on the prostate using MRS and hence avoids the need to explicitly identify metabolite peaks. The methodology comprises two stages. In stage 1, a hierarchical spectral clustering algorithm is used to distinguish between extracapsular and prostatic spectra in order to localize the region of interest (ROI) corresponding to the prostate. Once the prostate ROI is localized, in stage 2, a NLDR scheme, in conjunction with a replicated clustering algorithm, is used to automatically discriminate between three classes of spectra (normal appearing, suspicious appearing, and indeterminate). The methodology was quantitatively and qualitatively evaluated on a total of 18 1.5 T in vivo prostate T2-weighted (w) and MRS studies obtained from the multisite, multi-institutional American College of Radiology (ACRIN) trial. In the absence of the precise ground truth for CaP extent on the MR imaging for most of the ACRIN studies, probabilistic quantitative metrics were defined based on partial knowledge on the quadrant location and size of the tumor. The scheme, when evaluated against this partial ground truth, was found to have a CaP detection sensitivity of 89.33% and specificity of 79.79%. The results obtained from randomized threefold and fivefold cross validation suggest that the NLDR based clustering scheme has a higher CaP detection accuracy compared to such commonly used MRS analysis schemes as z score and PCA. In addition, the scheme was found to be robust to changes in system parameters. For 6 of the 18 studies an expert radiologist laboriously labeled each of the individual spectra according to a five point scale, with 1/2 representing spectra that the expert considered normal and 3/4/5 being spectra the expert deemed suspicious. When evaluated on these expert annotated datasets, the CAD system yielded an average sensitivity (cluster corresponding to suspicious spectra being identified as the CaP class) and specificity of 81.39% and 64.71%, respectively.
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PMID:A hierarchical spectral clustering and nonlinear dimensionality reduction scheme for detection of prostate cancer from magnetic resonance spectroscopy (MRS). 1981 Apr 65

The current review article critically discusses the potential advantages and disadvantages of radical prostatectomy in patients with locally advanced lymph node-positive prostate cancer. It is the purpose of the manuscript to develop a therapeutic algorithm for management of these patients to achieve optimal oncological and functional results. Based on the data in the literature radical prostatectomy as part of a multimodality approach seems to be indicated in the following clinical scenario: limited intrapelvic lymph node metastasis without bulky disease; complete resectability of the primary cancer and metastases by extended radical prostatectomy and extended pelvic lymphadenectomy; inclusion of the patient in a multimodality approach; life expectancy > 10 years. In patients with extensive locally advanced PCA or large pelvic metastases, radical prostatectomy might be indicated to improve local cancer control and to prevent significant local and supravesical complications. In these cases, the indication for extensive surgery includes radical cystoprostatectomy and should be discussed in an interdisciplinary tumour board.
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PMID:[Node-positive prostate cancer. Value of radical prostatectomy]. 2084 59

Serum biomarkers that reflect the complex pathways of cancer progression have contributed to the clinical understanding of many malignancies. Recent studies have suggested that certain neuroendocrine (NE) elements participate in prostate cancer (PCa) progression. Interleukin-6 (IL-6) may serve as a useful marker of and contribute to PCa morbidity. The purpose of this study was to assess the frequency of elevation of two NE factors, chromogranin A (CGA) and bombesin-like immunoreactivity (BLI), in patients with advanced PCa and to determine their relationship to serum prostate-specific antigen PSA) and IL-6 levels, as well as known prognostic indicators (hormonal state, stage). Serum CGA determined by radioimmunoassay was elevated in I (7%) of 15 androgen-dependent (AD) patients and II (52%) of 21 androgen-independent (AI) patients; and urine BLI determined by radioimmunoassay was elevated in 2 (13%) of 16 AD patients and 10 (39%) of 21 AI patients. Frequency of elevation was higher in patients with distant metastasis (bone, visceral) compared with those with local/regional extensions of the disease. Levels of the NE factors correlated well with serum and bone marrow aspirate IL-6 concentrations but not with serum PSA levels. Elevation in either NE factor predicted for shortened survival. Measurement of NE factors in PCa identifies a subset of patients with advanced disease likely to express high levels of IL-6 and have a shorter survival. If confirmed, these findings will support the existence of a clinically relevant subset of patients in whom NE factors are involved in AI PCA progression.
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PMID:Clinical significance of elevation in neuroendocrine factors and interleukin-6 in metastatic prostate cancer. 2122 26

In 2010, early detection of prostate cancer continues to rely on digital rectal examination and serum total PSA. However, selecting patients for prostate biopsy requires taking into account the prostate volume and the evolution of PSA over time. PSA derivatives such as PSA density, PSA velocity and the ratio free PSA / total PSA are useful supplements. However, the choice of the threshold value is not well defined and depends on the relative sensitivity and specificity desired. The real innovations come from basic research that has found potential markers of aggressiveness of prostate cancer and molecular biology tools used routinely as the PCA-3 score and the pro-PSA. The role of these new markers for diagnosis and prognosis of prostate cancer remains unclear.
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PMID:[How to select the best candidates for prostate biopsies? The role of traditional tools and contribution of new biomarkers in prostate cancer]. 2161 46

Direct vaccination with mRNA encoding tumor antigens is a novel and promising approach in cancer immunotherapy. CureVac's mRNA vaccines contain free and protamine-complexed mRNA. Such two-component mRNA vaccines support both antigen expression and immune stimulation. These self-adjuvanting RNA vaccines, administered intradermally without any additional adjuvant, induce a comprehensive balanced immune response, comprising antigen specific CD4+ T cells, CD8+ T cells and B cells. The balanced immune response results in a strong anti-tumor effect and complete protection against antigen positive tumor cells. This tumor inhibition elicited by mRNA vaccines is a result of the concerted action of different players. After just two intradermal vaccinations, we observe multiple changes at the tumor site, including the up-regulation of many genes connected to T and natural killer cell activation, as well as genes responsible for improved infiltration of immune cells into the tumor via chemotaxis. The two-component mRNA vaccines induce a very fast and boostable immune response. Therefore, the vaccination schedules can be adjusted to suit the clinical situation. Moreover, by combining the mRNA vaccines with therapies in clinical use (chemotherapy or anti-CTLA-4 antibody therapy), an even more effective anti-tumor response can be elicited. The first clinical data obtained from two separate Phase I/IIa trials conducted in PCA (prostate cancer) and NSCLC (non-small cell lung carcinoma) patients have shown that the two-component mRNA vaccines are safe, well tolerated and highly immunogenic in humans.
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PMID:Highly potent mRNA based cancer vaccines represent an attractive platform for combination therapies supporting an improved therapeutic effect. 2273 22


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