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Clinical applications of magnetic resonance spectroscopic imaging (MRSI) for the study of brain and prostate cancer have expanded significantly over the past 10 years. Proton MRSI studies of the brain and prostate have demonstrated the feasibility of noninvasively assessing human cancers based on metabolite levels before and after therapy in a clinically reasonable amount of time. MRSI provides a unique biochemical “window” to study cellular metabolism noninvasively. MRSI studies have demonstrated dramatic spectral differences between normal brain tissue (low choline and high N-acetyl aspartate, NAA) and prostate (low choline and high citrate) compared to brain (low NAA, high choline) and prostate (low citrate, high choline) tumors. The presence of edema and necrosis in both the prostate and brain was reflected by a reduction of the intensity of all resonances due to reduced cell density. MRSI was able to discriminate necrosis (absence of all metabolites, except lipids and lactate) from viable normal tissue and cancer following therapy. The results of current MRSI studies also provide evidence that the magnitude of metabolic changes in regions of cancer before therapy as well as the magnitude and time course of metabolic changes after therapy can improve our understanding of cancer aggressiveness and mechanisms of therapeutic response. Clinically, combined MRI/MRSI has already demonstrated the potential for improved diagnosis, staging and treatment planning of brain and prostate cancer. Additionally, studies are under way to determine the accuracy of anatomic and metabolic parameters in providing an objective quantitative basis for assessing disease progression and response to therapy. Neoplasia (2000) 2, 166–189.J Kurhanewicz, citeulike.org

Computer-Based Medical Systems, 2003. Proceedings. 16th IEEE Symposium (2003), pp. 263-268.PET and MW images of mouse prostate tumors were correlated with histology, flow cytometry, DNA fragmentation analysis and NMR peaks. Hypotheses were: 1. signal intensities of intracellular sodium (/spl mu/MRI) and flouro-2-deoxy-glucose utilization (/spl mu/PET) increased in tumors; 2. image signal intensities were associated with apoptosis as result of DNA fragmentation and accumulation of NMR visible metabolites.PC-3 cell lines were compared with DU-145, LNCaP cell lines in culture for the /sub i/ and /sub l/ ion sensing dyes, cell death NMR peaks and apoptosis staining for chemotherapeutic action of different drugs. After PC3 tumor imaging, taxotere (40 mg/kg; n=5) and VP-16 etoposide (1.2 mg/kg; n=7) was administered i.v. and imaging was done after 12 hours and 24 hours. Tumors were taken out for immunohistological staining by pentachrome, feulgen and ss-DNA antibody. /spl mu/PET and /spl mu/MRI images showed increased 18-FDG uptake and sodium signal intensities in tumor. In tumors, taxotere induced an increase in IC-Na 30 % (p, citeulike.org

European Journal of Nuclear Medicine and Molecular Imaging, Vol. 35, No. 2. (19 February 2008), pp. 253-263.Abstract Purpose  To evaluate the accuracy of -choline (FCH) positron emission tomography/computed tomography (PET/CT) for staging and restaging of prostate cancer. Methods  FCH PET/CT was performed in 111 patients with prostate cancer using 200 MBq FCH: 43 patients were examined for initial staging, and 68 patients (mean age 66.4 years) were examined for restaging (mean PSA 10.81 ?g/l). FCH PET/CT results were correlated to histopathology, bone scan, morphology as revealed by magnetic resonance imaging (MRI) and CT, PET/CT follow-up and PSA follow-up after therapy. Results  FCH PET/CT scans at initial staging correctly showed no metastases in 36/38 patients undergoing radical surgery, as confirmed by PSA levels 2 ?g/l.Daniela Husarik, Raymond Miralbell, Markus Dubs, Hubert John, Olivier Giger, Albert Gelet, Tibor Cservenyàk, Thomas Hany, citeulike.org

The Prostate, Vol. 66, No. 7. (15 May 2006), pp. 708-717.BACKGROUND: Mouse prostate cancer modeling presents unique obstacles to the study of spontaneous tumor initiation and progression due to the anatomical location of the tissue. RESULTS: High resolution (130 microm(x) x 130 microm(y) x 300 microm(z)), three-dimensional MRI allowed for the visualization, segmentation, and volumetric measurement of the prostate from normal and genetically engineered animals, in vivo. Additionally, MRS performed on the prostate epithelia of probasin-ErbB-2Delta x Pten(+/-) mice identified changes in the relative concentrations of the metabolites choline and citrate, which was not observed in TRAMP mice. METHODS: T1-weighted MRI was performed on normal, TRAMP, probasin-ErbB-2/Her2/Neu (probasin-ErbB-2Delta), and probasin-ErbB-2Delta in the context of decreased Pten activity (probasin-ErbB-2Delta x Pten(+/-)) mice. Volume-localized single-voxel proton magnetic resonance spectroscopy (SVS (1)H MRS) was also performed. CONCLUSIONS: The data presented supports the use of combined MRI and MRS for the measurement of biochemical and morphometric alterations in mouse models of prostate cancer.ST Fricke, O Rodriguez, J Vanmeter, LE Dettin, M Casimiro, CD Chien, T Newell, K Johnson, L Ileva, J Ojeifo, MD Johnson, C Albanese, citeulike.org

Radiology, Vol. 233, No. 3. (1 December 2004), pp. 709-715.PURPOSE: To use contrast material-enhanced magnetic resonance (MR) imaging and a distributed-parameter tracer kinetics model for prospectively evaluating the vascular characteristics of prostate cancer. MATERIALS AND METHODS: Twenty-two patients between 57 and 76 years of age (mean age, 67 years) with histologically proved adenocarcinoma of the prostate were examined by using three-dimensional dynamic contrast-enhanced T1-weighted MR imaging at 1.5 T. The local research ethics committee approved this study, and written consent was obtained from all patients. Data from regions of interest drawn in tumor, normal-appearing peripheral zone tissue, and muscle were analyzed to provide estimates of perfusion, blood volume, interstitial volume, and microvascular permeability-surface area product. These estimates were compared by using the nonparametric Wilcoxon signed rank test. RESULTS: Mean blood flow was significantly (P < .001) higher in 22 prostate tumors than in 20 contralateral peripheral zones (66 vs 32 mL/100 mL/min). Similarly, the interstitial distribution volume in tumors was enlarged compared with the interstitial distribution volume in normal peripheral zones (42 vs 27 mL/100 mL). Blood volume and microvascular permeability-surface area product values in tumors (1.0 mL/100 mL and 22 mL/100 mL/min, respectively) were similar to estimated values in peripheral zone tissue (1.5 mL/100 mL and 21 mL/100 mL/min, respectively). CONCLUSION: These findings show considerable promise for isolating vascular characteristics of prostate cancer. (C) RSNA, 2004 10.1148/radiol.2333032098David Buckley, Caleb Roberts, Geoff Parker, John Logue, Charles Hutchinson, citeulike.org

Rofo, Vol. 177, No. 7. (July 2005), pp. 935-939.PURPOSE: To differentiate orthotopically implanted prostate cancer from normal prostate tissue using magnetic resonance imaging (MRI) and Gd-DTPA-BMA-enhanced dynamic MRI in the rat model. MATERIAL AND METHODS: Tumors were induced in 15 rats by orthotopic implantation of G subline Dunning rat prostatic tumor cells. MRI was performed 56 to 60 days after tumor cell implantation using T1-weighted spin-echo, T2-weighted turbo SE sequences, and a 2D FLASH sequence for the contrast medium based dynamic study. The interstitial leakage volume, normalized permeability and the permeability surface area product of tumor and healthy prostate were determined quantitatively using a pharmacokinetic model. The results were confirmed by histologic examination. RESULTS: Axial T2-weighted TSE images depicted low-intensity areas suspicious for tumor in all 15 animals. The mean tumor volume was 46.5 mm(3). In the dynamic study, the suspicious areas in all animals displayed faster and more pronounced signal enhancement than surrounding prostate tissue. The interstitial volume and the permeability surface area product of the tumors increased significantly by 420 % (p < 0.001) and 424 % (p < 0.001), respectively, compared to normal prostate tissue, while no significant difference was seen for normalized permeability alone. CONCLUSION: The results of the present study demonstrate that quantitative analysis of contrast-enhanced dynamic MRI data enables differentiation of small, slowly growing orthotopic prostate cancer from normal prostate tissue in the rat model.O Gemeinhardt, L Lüdemann, D Prochnow, C Abramjuk, M Taupitz, B Hamm, D Beyersdorff, citeulike.org

BMC Medical Genomics, Vol. 1, No. 1. (2008)BACKGROUND::The early detection of prostate cancer has resulted in an increase in the number of patients with localized prostate cancer and has paralleled the reported reduction in prostate cancer mortality. The increased rate of detection of patients with localized prostate cancer may also increase the risk of potentially morbid therapy in a patient with indolent cancer. Defining the biomarker correlates of prostate cancer virulence will facilitate the appropriate application and development of therapy for patients with early disease.METHODS::A 255 core prostate cancer tissue microarray (TMA) from 47 prostatectomy specimens with organ confined tumor was constructed. Prostate cancer foci of transition and peripheral zone origin were represented on the TMA. Further, replicate cores of the two Gleason grades comprising the Gleason score, representative of Gleason scores 5-9, were arrayed from each prostatectomy specimen. Standard immunohistochemical techniques were used to assess expression of nine, cell death and cell cycle regulatory proteins implicated in the pathogenesis of prostate cancer (bax, bcl-2, bcl-xL, bin1, CD95, mdm2, p21, p53, and NFkB).RESULTS::The Spearman correlation coefficient revealed a strong correlation of bax, bin1, FAS, p65 and p21 expression with Gleason grade. Spearman correlation coefficients showed that expression of, bax and bin1, bax and MDM2, Bax and p21, and bax and p65 NFkB was highly associated. Other significant associations were identified between bin1 and p21, bin1 and MDM2, bin1 and p65 NFkB and between p21 and p65 NFkappaB. A model for predicting the biological potential of Gleason score 7 prostate cancer using multivariable logistic regression methods was developed. The findings also indicate that the profile of specific markers for Gleason grade 3 prostate cancer correlates with the overall context of the Gleason score.CONCLUSION::These data support the view that important molecular differences exist among and between the Gleason scores. Furthermore, there is significant molecular heterogeneity among prostatectomy specimens containing Gleason grade 3 cancer. This observation may have broader implications regarding the determination of risk among patients with prostate cancer that is currently considered to be of either good prognosis or unclear prognosis, i.e. Gleason score 7 tumors.Timothy Mcdonnell, Nikhil Chari, Jeong Vega, Patricia Troncoso, Xuemei Wang, Carlos Ramos, Kevin Coombes, Shawn Brisbay, Remigio Lopez, George Prendergast, Christopher Logothetis, Kim Do, citeulike.org

Urology, Vol. 57, No. 4. (April 2001), pp. 31-38.Environment determines the risk of both prostate and breast cancer, and this risk can vary >10-fold. In contrast, no risk exists for human seminal vesicle cancer demonstrating tissue specificity. There is also species specificity, because there is no risk for prostate cancer in any other aging mammal except the dog. A study of evolution indicates that the prostate and breast appeared at the same time 65 million years ago with the development of mammals. All male mammals have a prostate; however, the seminal vesicles are variable and are determined by the diet so that species primarily eating meat do not have seminal vesicles. The exception is the human, who has seminal vesicles and consumes meat, although this is a recent dietary change. Human lineage departed from other higher primates 8 million years ago. The closest existing primate to humans is the bonobo (pigmy chimpanzee), which does not eat meat but exists primarily on a high fruit and fresh vegetable diet. Homo sapiens evolved only about 150,000 years ago, and only in the last 10% of that time (10 to 15 thousand years ago) did humans and dogs dramatically alter their diets. This is the time when humans domesticated the dog, bred animals, grew crops, and cooked, processed, and stored meats and vegetables. All current epidemiologic evidence and suggestions for preventing prostate and breast cancer in humans indicates that we should return to the original diets under which our ancestors evolved. The recent development of the Western-type diet is associated with breast and prostate cancer throughout the world. It is believed that the exposure to and metabolism of estrogens, and the dietary intake of phytoestrogens, combined with fat intake, obesity, and burned food processing may all be related to hormonal carcinogenesis and oxidative DNA damage. An explanatory model is proposedD Coffey, citeulike.org

J Clin Endocrinol Metab, Vol. 89, No. 12. (1 December 2004), 6359.10.1210/jc.2004-1824 The article by Dr. Rosner (1) points out an important problem of long-term side effects of finasteride treatment brought about by the surprising results of the Prostate Cancer Prevention Trial (PCPT) (2). In this study, chronic inhibition of 5alpha-reductase was associated not only with sexual dysfunction and gynecomastia, but also with a worrisome increased risk of high-grade prostate cancer. Keeping in mind a higher incidence of breast cancer reported by the other group (3), it seems reasonable to believe that long-term treatment with finasteride may disturb androgen-estrogen balance to the extent that may result in carcinogenesis. Many epidemiological and experimental studies have shown that prostate hyperplasia and cancer develop more frequently in a hormonal milieu where estrogens predominate over androgens, as it happens in aging males. The inhibition of 5alpha-reductase further shifts the hormonal imbalance associated with aging by decreasing 5alpha-dihydrotestosterone and increasing testosterone, which in turn may be locally aromatized to estrogens. The aberrant up-regulation of aromatase expression in benign prostate hypertrophy and prostate cancer (4) makes this scenario even more probable. The other possible mechanism by which hormonal changes may affect prostate cancer development is the capacity of sex hormones to modulate immune response. Androgen and estrogen receptors are present on most immune competent cells, and sex hormones are known to affect T helper 1 (Th1)/Th2 cell balance (5, 6). Th1 response is associated with cell-mediated immunity, e.g. elimination of cancerous cells, whereas Th2 response is credited with immune tolerance such as fetus survival during pregnancy. Therefore, finasteride could potentially be involved in alteration of immune surveillance against cancer in aging males. In this context, the alternative method of prostate cancer prevention in elderly men could paradoxically be a substitutive treatment with 5alpha-dihydrotestosterone. In many studies, this nonaromatizing androgen restored estrogen/androgen balance by decreasing plasma levels of estradiol and testosterone. Dihydrotestosterone supplementation appears to have favorable effects on sexual function and cardiovascular system, with no adverse effects on the prostate as measured by symptoms, prostate-specific antigen levels, or prostate volume (7). Therefore, it would be of great clinical importance if the rigorous assessment of the prevalence of prostate cancer, such as in PCPT, were accommodated in long-term studies employing treatment with non-5alpha-reducible androgens (e.g. dihydrotestosterone).Robert Palusinski, Wojciech Barud, citeulike.org

Infection, Genetics and Evolution, Vol. 8, No. 3. (May 2008), pp. 297-301.Recent research implicates viral infection as a factor that may contribute to the risk of prostate cancer. Allelic variation at the RNASEL locus is associated with the risk of infection by a newly discovered retrovirus called XMRV, and with hereditary risk of prostate cancer. This evidence suggests that the RNASEL locus has undergone antagonistic coevolution with the retrovirus over evolutionary time. If this is the case, then both the RNASEL locus and the retrovirus should show evidence of positive selection. Here we use molecular-evolutionary methods to investigate the prediction that the RNASEL locus will exhibit evidence of positive selection. We find evidence that positive selection has acted on this locus over evolutionary time. We further find, using a Bayesian estimation procedure, that Asp541Glu, which was found to be associated with prostate cancer risk in Caucasians in a recent meta-analysis, shows an elevated probability of positive selection. Previous studies provide evidence for rapid evolution of the infection-mediating gag gene in the XMRV retrovirus. Taken together, these results suggest that antagonistic coevolution may have occurred between a specific host locus involved in immune defense (RNASEL) and a viral pathogen. In turn, genetic variation associated with this apparent coevolution may influence susceptibility to prostate cancer.K Summers, B Crespi, citeulike.org