Expression of microRNA‐221 is progressively reduced in aggressive prostate cancer and metastasis and predicts clinical recurrence

Emerging evidence shows that microRNAs (miR) are involved in the pathogenesis of a variety of cancers, including prostate carcinoma (PCa). Little information is available regarding miR expression levels in lymph node metastasis of prostate cancer or the potential of miRs as prognostic markers in this disease. Therefore, we analyzed the global expression of miRs in benign, hyperplastic prostate tissue (BPH), primary PCa of a high risk group of PCa patients, and corresponding metastatic tissues by microarray analysis. Consistent with the proposal that some miRs are oncomirs, we found aberrant expression of several miRs, including the downregulation of miR‐221, in PCa metastasis. Downregulation of miR‐221 was negatively correlated with the expression of the proto‐oncogen c‐kit in primary carcinoma. In a large study cohort, the prostate‐specific oncomir miR‐221 was progressively downregulated in aggressive forms of PCa. Downregulation of miR‐221 was associated with clinicopathological parameters, including the Gleason score and the clinical recurrence during follow up. Kaplan–Meier estimates and Cox proportional hazard models showed that miR‐221 downregulation was linked to tumor progression and recurrence in a high risk prostate cancer cohort. Our results showed that progressive miR‐221 downregulation hallmarks metastasis and presents a novel prognostic marker in high risk PCa. This suggests that miR‐221 has potential as a diagnostic marker and therapeutic target in PCa.     

Guidelines for neuromuscular ultrasound training

Neuromuscular ultrasound has become an essential tool in the diagnostic evaluation of various neuromuscular disorders, and, as such, there is growing interest in neuromuscular ultrasound training. Effective training is critical in mastering this modality. Our aim was to develop consensus-based guidelines for neuromuscular ultrasound training courses. A total of 18 experts participated. Expert opinion was sought through the Delphi method using 4 consecutive electronic surveys. A high degree of consensus was achieved with regard to the general structure of neuromuscular ultrasound training; the categorization of training into basic, intermediate, and advanced levels; the learning objectives; and the curriculum for each level. In this study, a group of neuromuscular ultrasound experts established consensus-based guidelines for neuromuscular ultrasound training. These guidelines can be used in the development of the specialty and the standardization of neuromuscular ultrasound training courses and workshops.     

Long-term treatment of ovariectomized mice with estradiol or phytoestrogens as a new model to study the role of estrogenic substances in the heart

Epidemiological data reveal that the overall risk for heart disease is lower for premenopausal women compared to age-matched men. However, the beneficial effect for the female sex is lost upon menopause. Thus, it has been suggested that estrogens convey the protective effect for the female sex against heart disease. Numerous natural plant products, i.e., phytoestrogens (PE), interfere with or alter the development or function of the endocrine system. Although PEs have been studied intensively with regard to the effects on the reproductive organs, such as the uterus or mammary gland, surprisingly little data are available about the effects of PEs on the heart. Here, we conducted a long-term study with ovariectomized mice to examine putative estrogenic effects of the PEs genistein (GEN), resveratrol (RES), and equol (EQ), using estradiol (E2) as a reference compound on heart size, morphology, and cardiac gene expression. We report for the first time significant changes in these parameters by GEN and E2. Changes in the size of cardiomyocytes were observed by GEN and E2. In line with these observations, cardiac expression of insulin-like growth factor 1 ( IGF1) was significantly induced by both GEN and E2. Thus, we speculate that endocrine active compounds, like the isoflavone GEN, which is used as a food additive or as a drug for the treatment of menopausal symptoms, may directly affect heart function.     

Thermoablation of Malignant Kidney Tumors Using Magnetic Nanoparticles: An In Vivo Feasibility Study in a Rabbit Model

The objective of this study was to assess the technical feasibility of CT-guided magnetic thermoablation for the treatment of malignant kidney tumors in a VX2 tumor rabbit model. VX2 tumors were implanted into the kidneys of five rabbits and allowed to grow for 2 weeks. After preinterventional CT perfusion imaging, CT-guided injection of superparamagnetic iron oxide particles (300 μl) was performed, followed by exposure of the animals to an alternating electromagnetic field for 15 min (≈0.32 kA/m). Then animals underwent CT perfusion imaging again. Afterward, animals were sacrificed and kidneys were dissected for macroscopic and histological evaluation. Changes in perfusion before and after exposure to the alternating magnetic field were analyzed. In one animal no tumor growth could be detected so the animal was used for optimization of the ablation procedure including injection technique and peri-interventional cross-sectional imaging (CT, MRI). After image-guided intratumoral injection of ferrofluids, the depiction of nanoparticle distribution by CT correlated well with macroscopic evaluation of the dissected kidneys. MRI was limited due to severe susceptibility artefacts. Postinterventional CT perfusion imaging revealed a perfusion deficiency around the ferrofluid deposits. Histological workup showed different zones of thermal damage adjacent to the ferrofluid deposits. In conclusion, CT-guided magnetic thermoablation of malignant kidney tumors is technically feasible in an animal model and results in a perfusion deficiency indicating tumor necrosis as depicted by CT perfusion imaging and shown in histological evaluation.     

Treatment of small coronary arteries with a paclitaxel-coated balloon catheter

Background

Treatment of lesions in small coronary arteries by percutaneous transluminal coronary intervention is limited by a high recurrence rate. We assessed the use of a paclitaxel-coated balloon in this indication.

Methods

One-hundred eighteen patients with stenoses in small coronary vessels were treated by a paclitaxel-coated balloon (3 μg/mm²). The main inclusion criteria encompassed diameter stenosis of ≥70% and ≤22 mm in length with a vessel diameter of 2.25–2.8 mm. Follow-up angiography was performed at scheduled 6-month post-intervention or whenever driven by clinical or electrocardiographic signs of ischemia. The primary endpoint was angiographic in-segment late lumen loss.

Results

Eighty-two of 118 patients (70%) with a vessel diameter of 2.35 ± 0.19 mm were treated with the drug-coated balloon only, while 32 patients required additional stent deployment. The mean in-segment late lumen loss was 0.28 ± 0.53 mm. In patients treated with the drug-coated balloon only, the in-segment late lumen loss was 0.16 ± 0.38 mm. At 12 months, the rate of major adverse cardiac events was 15% which was primarily due to the need for target lesion revascularization in 14 patients (12%). In those with additional bare metal stent implantation geographical mismatch between coated-balloon dilatation and stent implantation was significantly associated with the occurrence of restenosis.

Conclusion

Treatment of coronary stenosis in small coronary vessels with the paclitaxel-coated balloon was well tolerated. It may offer an alternative to the implantation of a drug-eluting stent (ClinicalTrials.gov Identifier: NCT00404144).     

Reactive antibodies against bacillus Calmette‐Guerin heat‐shock protein‐65 potentially predict the outcome of immunotherapy for high‐grade transitional cell carcinoma of the bladder

BACKGROUND:

Intravesical immunotherapy with Mycobacterium bovis (M. bovis) bacillus Calmette‐Guerin (BCG) is the current standard of care against superficial, high‐grade transitional cell carcinoma (TCC) of the urinary bladder (carcinoma in situ and pathologic T1, grade 3 disease). However, individual patient outcome is barely predictable because of the lack of serum markers. Consequently, progression to muscle‐invasive bladder cancer and critical delay of treatments (such as neoadjuvant combination chemotherapy and/or radical cystectomy) often occur. The objectives of this study were to identify a marker for measuring the BCG‐induced immune response and to predict the outcomes and potential improvements of BCG immunotherapy.

METHODS:

Because host immunoresponse mediates BCG activity, the authors screened a combinatorial random peptide library on the circulating pool of immunoglobulins (Igs) purified from an index patient after successful BCG immunotherapy to identify the corresponding target antigen(s).

RESULTS:

An immunogenic peptide motif was selected, isolated, and validated from M. bovis BCG heat‐shock protein 65 (HSP‐65) as a dominant epitope of the humoral response to treatment. Increasing IgA and IgG anti‐HSP‐65 titers specifically predicted a positive patient outcome in a cohort of patients with bladder cancer relative to several cohorts of control patients.

CONCLUSIONS:

The current results indicated that antibody production against M. bovis BCG HSP‐65 can serve as a serologic marker for the predictive outcome of BCG immunotherapy. Subsequent studies will determine the value of this candidate marker to modify BCG‐based treatment for individual patients with bladder cancer. Cancer 2010. © 2009 American Cancer Society.