The aim of this pilot study was to evaluate whether the technique of magnetic fluid hyperthermia can be used for minimally invasive treatment of prostate cancer. This paper presents the first clinical application of interstitial hyperthermia using magnetic nanoparticles in locally recurrent prostate cancer. Treatment planning was carried out using computerized tomography (CT) of the prostate. Based on the individual anatomy of the prostate and the estimated specific absorption rate (SAR) of magnetic fluids in prostatic tissue, the number and position of magnetic fluid depots required for sufficient heat deposition was calculated while rectum and urethra were spared. Nanoparticle suspensions were injected transperineally into the prostate under transrectal ultrasound and flouroscopy guidance. Treatments were delivered in the first magnetic field applicator for use in humans, using an alternating current magnetic field with a frequency of 100 kHz and variable field strength (0-18 kA m À1). Invasive thermometry of the prostate was carried out in the first and last of six weekly hyperthermia sessions of 60 min duration. CT-scans of the prostate were repeated following the first and last hyperthermia treatment to document magnetic nanoparticle distribution and the position of the thermometry probes in the prostate. Nanoparticles were retained in the prostate during the treatment interval of 6 weeks. Using appropriate software (AMIRA), a non-invasive estimation of temperature values in the prostate, based on intra-tumoural distribution of magnetic nanoparticles, can be performed and correlated with invasively measured intra-prostatic temperatures. Using a specially designed cooling device, treatment was well tolerated without anaesthesia. In the first patient treated, maximum and minimum intraprostatic temperatures measured at a field strength of 4.0-5.0 kA m À1 were 48.5 C and 40.0 C during the 1st treatment and 42.5 C and 39.4 C during the 6th treatment, respectively. These first clinical experiences prompted us to initiate a phase I study to evaluate feasibility, toxicity and quality of life during hyperthermia using magnetic nanoparticles in patients with biopsy-proven local recurrence of prostate cancer following radiotherapy with curative intent. To the authors' knowledge, this

Magnetic #uid hyperthermia (MFH) selectively heats up tissue by coupling alternating current (AC) magnetic "elds to targeted magnetic #uids, so that boundaries of di!erent conductive tissues do not interfere with power absorption. In this paper, a new AC magnetic "eld therapy system for clinical application of MFH is described. With optimized magnetic nanoparticle preparations it will be used for target-speci"c glioblastoma and prostate carcinoma therapy.

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Betaine improves the co-amplification of the two alternatively spliced variants of the prostate-specific membrane antigen mRNA as well as the amplification of the coding cDNA region of c-jun. It is suggested that betaine improves the amplification of these genes by reducing the formation of secondary structure caused by GC-rich regions and, therefore, may be generally applicable to ameliorate the amplification of GC-rich DNA sequences.

Interstitial heating using magnetic nanoparticles was feasible and well tolerated in patients with locally recurrent prostate cancer. Deposition of nanoparticles in the prostate was highly durable. Further refinement of the technique is necessary to allow application of higher magnetic field strengths.

Using quantitative reverse transcription-polymerase chain reaction (RT-PCR), reference genes are utilized as endogenous controls for relative quantification of target genes in gene profiling studies. The suitability of housekeeping genes for that purpose in prostate cancer tissue has not been sufficiently investigated so far. The objective of this study was to select from a panel of 16 potential candidate reference genes the most stable genes for gene normalization. Expression of mRNA encoding ACTB, ALAS1, ALB, B2M, G6PD, GAPD, HMBS, HPRT1, K-ALPHA-1, POLR2A, PPIA, RPL13A, SDHA, TBP, UBC, and YWHAZ was examined in matched, microdissected malignant and nonmalignant tissue specimens obtained from 17 nontreated prostate carcinomas after radical prostatectomy by real-time RT-PCR. The genes studied displayed a wide expression range with cycle threshold values between 16 and 37. The expression was not different between samples from pT2 and pT3 tumors or between samples with Gleason scores <7 and >or=7 (P>0.05). ACTB, RPL13A, and HMBS showed significant differences (P<0.02 at least) in expressions between malignant and nonmalignant pairs. All other genes did not differ between the matched pairs, and the software programs geNorm and NormFinder were used to ascertain the most suitable reference genes from these candidates. HPRT1, ALAS1, and K-ALPHA-1 were calculated by both programs to be the most stable genes covering a broad range of expression. The expression of the target gene RECK normalized with HRPT1 alone and with the normalization factors generated by the combination of these three reference genes as well as with the unstable genes ACTB or RPL13A is given. That example shows the significance of using suitable reference genes to avoid erroneous normalizations in gene profiling studies for prostate cancer. The use of HPRT1 alone as a reference gene shown in our study was sufficient, but the normalization factors generated from two (HRPT1, ALAS1) or all three genes (HRPT1, ALAS1, K-ALPHA-1) should be considered for an improved reliability of normalization in gene profiling studies of prostate cancer.

The authors evaluated a magnetic resonance (MR) imaging-compatible biopsy device comprising a needle guide that can be visualized with MR imaging and manipulated mechanically from outside the MR unit. With approval from the local ethics committee and patient consent, this device was tested in 12 patients by using a closed 1.5-T MR unit and a body phased-array coil. Patients had elevated prostate-specific antigen levels (6-60 ng/mL) and one or more areas in the prostate that were suspicious for carcinoma at prebiopsy MR imaging. Biopsy was performed with transrectal access and with the patient prone. A 16-gauge MR imaging-compatible needle was successfully positioned with the device, and between six and nine tissue cores were obtained in each patient. In one patient, two suspicious basal areas could not be reached with the device. Histologic analysis showed prostate cancer in five patients and prostatitis in six. No complications were observed. The device enabled MR imaging-guided core-needle biopsy of prostate areas suspicious for cancer on MR images.

Our aim was to assess the diagnostic accuracy of bone markers in serum of patients with prostate cancer (PCa) for early detection of bone metastases and their usefulness as predictors of PCa-caused mortality. In sera of 117 PCa patients (pN0M0, n ‫؍‬ 39; pN1M0, n ‫؍‬ 34; M1, n ‫؍‬ 44), 35 healthy men and 35 patients with benign prostatic hyperplasia, bone formation markers [total and bone-specific alkaline phosphatase (tALP, bALP), amino-terminal procollagen propeptides of type I collagen (P1NP), osteocalcin ( Key words: bone turnover marker; prostate carcinoma; bone metastasis; osteoprotegerin; diagnostic accuracyThe most frequent cancer in men, PCa, is characterized by the occurrence of skeletal metastases in about 65-75% of patients with advanced disease. 1 Bone metastases alter the balance between bone formation and bone resorption by influencing the involved bone cells (osteoblasts and osteoclasts) through local release of cytokines and growth factors. To detect and monitor this metastatic bone involvement, bone scintigraphy is the widely applied standard method. Altered bone remodeling activity can also be assessed either directly by measuring components of the affected bone cells (osteoblasts and osteoclasts) or indirectly by analyzing metabolic products released from the bone matrix following the changed bone formation or resorption. Bone turnover markers that reflect either bone formation in consequence of osteoblast proliferation or analytes indicating bone resorption as the opposite bone remodeling activity have been recommended as tools in the assessment of bone metastasis in PCa. [2][3][4][5][6][7] The balance between osteoblastic and osteoclastic activity in bone is essentially determined by osteoclastogenesis, which is regulated by 3 proteins: RANK, RANKL and OPG. OPG and RANKL could be, in addition to bone formation and resorption markers, biomarkers to detect bone metastases. 8,9 It was therefore interesting that these 2 proteins were overexpressed in bone metastases of PCa patients. 10,11 Several studies have assessed the diagnostic efficacy of both bone formation and resorption markers for the detection of bone metastases in PCa. 6 However, they often included only a few bone markers or a limited number of patients. 7,12 While little comparative data are available on the diagnostic accuracy of the newly developed assays for the various analytes including OPG and RANKL, the conclusions regarding the diagnostic usefulness need to be reconsidered. 9,13 In addition, the recommendation of diagnostic tests was often substantiated by the univariate evaluation of data without taking into account the usefulness of multivariate analysis. Therefore, our aims were (i) to measure serum markers of bone formation, bone resorption and osteoclastogenesis as noninvasive, easy-to-determine analytes of bone metastases in the same serum samples; (ii) to evaluate and compare the diagnostic validity of all analytes concerning their differential efficiency between patients with and without metastases; (iii) to recom...