Oncogene 2006 May 22; (Read article online)

Yeh AH, Bohula EA, Macaulay VM

The type 1 insulin-like growth factor receptor (IGF1R) is overexpressed by malignant melanomas compared with benign naevi, and mediates proliferation, motility and protection from apoptosis. However, the utility of IGF1R targeting as anti-cancer therapy may be limited by activating mutations in downstream signaling intermediates. We previously showed that IGF1R knockdown blocked survival of prostate cancer cells in which Akt activation was deregulated by PTEN loss. The current study investigated effects of IGF1R targeting in cells harboring activating RAS-RAF mutations, found in 70-80% of human melanomas. We assembled a panel of eight human melanoma cell lines: two expressing wild-type (WT) B-RAF and N-RAS, two with activating N-RAS mutations and four harboring V600E B-RAF. We also generated isogenic cell populations overexpressing WT or V600E B-RAF. Cells expressing V600E B-RAF were relatively resistant to apoptosis. However, IGF1R gene silencing was capable of inducing significant inhibition of survival, enhancement of apoptosis, and approximately two-fold sensitization to cisplatin and temozolomide. These effects were independent of mutation status and were associated with reduced activation of Akt and also, unexpectedly, of ERKs. These results support development of IGF1R targeting as therapy for melanoma, regardless of the presence of activating mutations in the RAS-RAF pathway.Oncogene advance online publication, 22 May 2006; doi:10.1038/sj.onc.1209674.

Cesk Patol 2006 Apr; 42(2): 86-90 (Read article online)

Svajdler M, Bohus P, Baumöhlová H, Sokol L, Bielek J

Epithelioid hemangioma (angiolymphoid hyperplasia with eosinophilia, EH/ALHE) is a rare benign angioproliferative lesion which typically occurs in the region of the head and neck. In the literature, occurence on the extremity is only rarely described. A case of multiple occurence of EH/ALHE in the skin of the toes and metatarsal bone with osteolysis is reported. Occurence on the extremity, superficial and deep affection and some "atypical" microscopic features may cause diagnostic dilemma. The key diagnostic features of EH/ALHE are vascular channels lined with epithelioid endothelial cells, surrounding layer of myopericytes, absence of atypia and mitotic activity and characteristic inflammation. Immunohistochemistry may be helpful in settling the diagnosis.

Environ Health 2006 May 22; 5(1): 13 (Read article online)

Prince MM, Hein MJ, Ruder AM, Waters MA, Laber PA, Whelan EA

ABSTRACT: BACKGROUND: The National Institute for Occupational Safety and Health previously reported mortality for a cohort of workers considered highly exposed to polychlorinated biphenyls (PCBs) between 1939 and 1977 at two electrical capacitor manufacturing plants. The current study updated vital status, examined liver and rectal cancer mortality previously reported in excess in this cohort and evaluated mortality from non-Hodgkin's lymphoma (NHL) and cancers of the stomach, intestine, breast, prostate, skin (melanoma) and brain reported to be in excess in other cohort and case-control studies of PCB-exposed persons. METHODS: Mortality was updated through 1998 for 2572 workers. Age-, gender-, race- and calendar year-adjusted standardized mortality ratios (SMRs) and 95% confidence intervals (CI) were calculated using U.S., state and county referent rates. SMRs using U.S. referent rates are reported. Duration of employment was used as a surrogate for exposure. RESULTS: Consistent with the previous follow-up, mortality from biliary passage, liver and gall bladder cancer was significantly elevated (11 deaths, SMR 2.11, CI 1.05 - 3.77), but mortality from rectal cancer was not (6 deaths, SMR 1.47, CI 0.54 - 3.21). Among women, mortality from intestinal cancer (24 deaths, SMR 1.89, CI 1.21 - 2.82) and other diseases of the nervous system and sense organs a category that includes Parkinson's disease and amyotrophic lateral sclerosis (15 deaths, SMR 2.07, CI 1.16 - 3.42) were elevated. Mortality was elevated for myeloma (7 deaths, SMR 2.11, CI 0.84 - 4.34), particularly among workers employed 10 years or more (5 deaths, SMR 2.80, CI 0.91 - 6.54). No linear associations between mortality and duration of employment were observed for the cancers of interest. CONCLUSIONS: This update found that the earlier reported excess in this cohort for biliary, liver and gall bladder cancer persisted with longer follow-up. Excess mortality for intestinal cancer among women was elevated across categories of duration of employment; myeloma mortality was highest among those working 10 years or more. The small numbers of deaths from liver and intestinal cancers, myeloma and nervous system diseases coupled with the lack of an exposure-response relationship with duration of employment preclude drawing definitive conclusions regarding PCB exposure and these causes of death.

Health Rep 2006 May; 17(2): 19-30 (Read article online)

Ellison LF, Gibbons L

OBJECTIVES: This period analysis provides Canadian predictions of the short- and long-term relative survival of people recently diagnosed with cancer. Long-term period and cohort-based estimates are also compared. DATA SOURCES: Data are from the Canadian Cancer Registry, the Canadian Mortality Data Base, and Statistics Canada life tables. ANALYTICAL TECHNIQUES: Relative survival analyses were conducted using the life-table method; expected survival proportions were derived using the Ederer II approach. Period analysis estimates were based on the survival experience of cancer cases followed up in 2002. The cohort analyses involved people diagnosed in 1997 (5-year survival) or 1992 (10-year survival). National estimates exclude Quebec. MAIN RESULTS: Relative survival ratios were highest for thyroid (5-year, 97.7%) and prostate (95.2%) cancer and lowest for pancreatic cancer. Survival for many forms of cancer is higher than previously estimated by cohort-based analysis. The largest increases in 10-year relative survival were predicted for cancers of the prostate (13.0%) and rectum (9.7%). The largest predicted increases for 5-year survival were for cancers of the cervix uteri (5.4%) and rectum (4.5%), and for leukemia (3.7%).

Eur J Pharmacol 2006 Apr 28; (Read article online)

Gray KT, Ventura S

The subtype of alpha(1)-adrenoceptor mediating noradrenaline-induced contractile responses in isolated mouse prostate glands was investigated. Adrenoceptor agonists were able to produce concentration-dependent contractions with the following rank order of potency: adrenaline>/=noradrenaline>/=clonidine=phenylephrine>dopamine>/=isoprenaline. Concentration-response curves to noradrenaline of the prostatic smooth muscle were antagonised by prazosin, N-[2-(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-alpha, alpha-dimethyl-1H-indole-3-ethanamine (RS-17053), 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane (WB 4101), tamsulosin and yohimbine with mean antagonist affinity estimates (pA(2) or apparent pK(B)) of 8.12+/-0.10, 6.56+/-0.11, 8.38+/-0.06, 10.14+/-0.19 and 7.38+/-1.36 respectively. Propranolol (1 muM) had no antagonist activity (P=0.994, n=6). Yohimbine (0.01, 0.1, 1 muM) had no antagonist activity in the presence of prazosin (0.1 muM) (P>/=0.059). The results obtained indicate that alpha(1)-adrenoceptors mediate the contractile response in isolated preparations of the mouse prostate. Furthermore, the particular subtype of alpha(1)-adrenoceptor mediating the response to exogenously administered noradrenaline corresponds to the alpha(1L)-subtype, the same subtype as that which has been shown to mediate noradrenaline-induced contractile activity in the human prostate.

Radiat Med 2006 Feb; 24(2): 133-8 (Read article online)

Takahashi Y, Mori S, Kozuka T, Gomi K, Nose T, Tahara T, Oguchi M, Yamashita T

PURPOSE: We investigated a subtraction-based reprojection approach to reduce CT metal artifacts due to I-125 seeds and evaluated the clinical implications in postimplant dosimetry for prostate permanent implant brachytherapy. MATERIALS AND METHODS: The raw projection data were used to reduce metal artifacts due to I-125 seeds. CT images of the metal parts only were separated from the original CT images by setting the threshold for pixel value to that of the I-125 seeds. Using these images, sinograms of CT images with and without seeds were obtained by inverse Radon transform (iRT), and the sinogram of the metal image was subtracted from that of the original image. Finally, the image was reconstructed using the sinogram by Radon transform (RT). This technique was applied to a prostate phantom and to a patient undergoing prostate permanent implant brachytherapy. RESULTS: Metal artifacts from I-125 seeds were reduced in both the phantom and patient studies. This technique decreased the density of the inner region of seeds but enhanced the density of the seed edge, thereby facilitating the identification of seed number, orientation, and location. CONCLUSION: This method reduces metal artifacts from I-125 seeds, and has potential for decreasing the time required for and improving the accuracy of postimplant dosimetry.

AJR Am J Roentgenol 2006 Jun; 186(6): 1587-96 (Read article online)

Kamel IR, Liapi E, Fishman EK

OBJECTIVE: The purpose of this article is to present the imaging features of focal nodular hyperplasia (FNH) using MDCT and 3D CT angiography. CONCLUSION: MDCT with advanced image processing is a powerful tool that may be utilized to identify the imaging features of FNH. These include the presence of large feeding arteries and draining veins, pseudocapsule, central scar, and septations. These features can help in the differentiation of this benign lesion from other hypervascular lesions without the need for additional imaging, biopsy, or surgery.

Prostate Cancer Prostatic Dis 2006 May 23; (Read article online)

Kaygısız O, Uğurlu O, Koşan M, Inal G, Oztürk B, Cetinkaya M

We investigated the effect of prostatic inflammation on prostate-specific antigen (PSA) and per cent-free PSA levels changing after antibacterial therapy. We evaluated 48 patients whose PSA levels were between 4 and 10 ng/ml, without any suspicious findings on digital rectal examination, with no infection findings in urine analysis. Prostatic inflammation was assessed with prostatic massage. All the patients were given antibiotic therapy for 3 weeks. Patients were re-evaluated 3 weeks after antibacterial therapy with PSA (free/total) and urinalysis. Ten core biopsies were taken with transrectal ultrasound. No differences were found in terms of age, pre- and post-treatment PSA, and PSA varying between patients with and without inflammation in the prostatic massage. In 18 patients, PSA decreased below 4 ng/ml. Prostate cancer was found in 10.8% of the patients with PSA between 4 and 10 ng/ml and none of the patients with PSA values below 4 ng/ml. We suggest an antibiotic therapy for 3 weeks without regarding inflammation findings when PSA is in the gray zone, for biopsy decision.Prostate Cancer and Prostatic Diseases advance online publication, 23 May 2006; doi:10.1038/sj.pcan.4500885.

Br J Radiol 2006 Jun; 79(942): 487-96 (Read article online)

Harrison RM, Wilkinson M, Shemilt A, Rawlings DJ, Moore M, Lecomber AR

In addition to the therapeutic exposure, a course of radiotherapy will involve the additional (concomitant) irradiation of the patient using CT, simulator or portal imaging systems, for localization of the target volume and subsequent verification of treatment delivery. The number of concomitant exposures is likely to increase as the developing technical capabilities for conformal, image-guided radiotherapy make target and critical organ definition an increasingly important aspect of radiotherapy. Estimation of doses and risks to critical organs in the body from all sources is thus necessary to provide the basis for adequate justification of the exposures as required by ICRP. In this paper, doses to selected organs and tissues for which ICRP have identified fatal cancer probabilities have been measured using a realistic anthropomorphic phantom loaded with thermoluminescent dosemeters and irradiated using a treatment protocol for radical radiotherapy of the prostate. Independently, doses to the same organs and tissues have been measured from concomitant CT and portal imaging exposures given for localization and verification purposes. Although negligible in comparison with the target dose, realistic numbers of concomitant exposures give a small but significant contribution to the total dose to most organs and tissues outside the target volume. Generally, this is in the range 5-10% of the total organ dose, but can be as high as 20% for bone surfaces. These data may be used to estimate concomitant doses from any combination of CT and portal imaging and may help in the justification process, especially when additional verification exposures may be required during treatment.

Mol Cell Proteomics 2006 May 19; (Read article online)

van den Bemd GJ, Krijgsveld J, Luider TM, van Rijswijk AL, Demmers JA, Jenster G

Lack of sensitivity and specificity of current tumor markers has intensified research efforts to find new biomarkers. The identification of potential tumor markers in human body fluids is hampered by large variability and complexity of both control and patient samples, laborious biochemical analyses, and the fact that the identified proteins are unlikely produced by the diseased cells, but are due to secondary body defense mechanisms. In a new approach presented here, we eliminate these problems by performing proteomic analysis in a prostate cancer xenograft model in which human prostate cancer cells form a tumor in an immune-incompetent nude mouse. Using this concept, proteins present in mouse serum that can be identified as human, will by definition, originate from the human prostate cancer xenograft and might have potential diagnostic and prognostic value. Using one-dimensional gel electrophoresis, liquid chromatography, and mass spectrometry, we identified tumor-derived human nm23/nucleoside diphosphate kinase (NME) in the serum of a nude mouse bearing the androgen-independent human prostate cancer xenograft PC339. NME is known to be involved in the metastatic potential of several tumor cells, including prostate cancer cells. Furthermore, we identified six human enzymes involved in glycolysis (fructose-bisphosphate aldolase A, triosephosphate isomerase, glyceraldehyde-3-phosphate dehydrogenase, alpha enolase, and lactate dehydrogenase A and B) in the serum of the tumor-bearing mice. The presence of human NME and GAPD in the serum of PC339-bearing mice was confirmed by Western blotting. Although the putative usefulness of these proteins in predicting prognosis of prostate cancer remains to be determined, the present data illustrate that our approach is a promising tool for the focused discovery of new prostate cancer biomarkers.

DNA Cell Biol 2006 May; 25(5): 287-94 (Read article online)

Sobti RC, Onsory K, Al-Badran AI, Kaur P, Watanabe M, Krishan A, Mohan H

To investigate the involvement of the CYP17, SRD5A2, CYP1B1, and CYP2D6 variants with prostate cancer, a case-control study of 100 patients and an equal number of age-matched control men was conducted. There appears to be a nonsignificant increase with risk of prostate cancer for individuals carrying one copy of the CYP17 A2 allele (OR, 1.80; 95% CI, 0.99-3.29, P = 0.05). The risk was increased in individuals having two A2 alleles (OR; 2.81, 95% CI, 1.06-7.40, P = 0.03). Compared with men having the VV genotype of SRD5A2 gene, there was no significant association between the VL genotype and the risk of prostate cancer (OR; 0.54, 95% CI; 0.29-1.03, P = 0.06). There was no difference in the occurrence of the genotype LL between controls and prostate cancer patients (OR; 0.90, 95% CI; 0.43-1.89, P = 0.79). There was a nonsignificant increased risk of prostate cancer for individuals carrying the CYP1B1Leu/Val genotype (OR, 1.70, 95% CI, 0.91-3.17, P = 0.09), which was increased in those having the Val/Val allele (OR, 3.38; 95% CI, 1.13-10.07, P = 0.02). Relative to men homozygous for the wild-type allele in CYP2D6 gene, those heterozygous for the B allele had an odds ratio of 1.78 (95% CI, 0.76-4.17, P = 0.18) for patients, and for homozygous individuals, it was 1.95 (0.55-6.93, P = 0.30). These observations have suggested that the CYP17 A2/A2, CYP1B1 Val/Val, and CYP2D6 genotypes may be associated with an altered risk of prostate cancer, while the CYP2D6 and SRD5A2 V89L polymorphism have no association with its risk in the North Indian population.

J Surg Res 2006 May 19; (Read article online)

Ducasse E, Chevalier J, Cosset JM, Creusy C, Eschwege F, Speziale F, Sbarigia E, Midy D, Baste JC, Lartigau E

BACKGROUND: Although ionizing radiation has been proposed for the prevention of intimal hyperplasia in coronary and peripheral arteries in multicenter clinical trials, information is lacking on how irradiation affects arterial histology after stenting and especially how it affects the edges of the stent. We investigated intimal hyperplasia recasting with histological changes in arterial wall at the edges of the stent after arterial stenting followed by adequate external radiation for the prevention of intimal hyperplasia in pigs. MATERIALS AND METHODS: The aorta was experimentally stented in 30 pigs who were then assigned to two groups: irradiation with 20 Gy and a control group with no irradiation. The aorta was resected for morphometric and histological studies 6 weeks after procedure. RESULTS: Intimal thickness was reduced and the intima/media ratio was significantly lower in irradiated groups than in control pigs. In the irradiated group histological examination at the edges of the stent showed thin neointimal proliferation with an intact endothelium. In all sections analyzed in the 20-Gy irradiated group the vascular media at 45 days contained necrotic areas and fibrosis with calcifications. CONCLUSIONS: After arterial injury, adequate ionizing radiation effectively reduces neointimal thickening. Irradiation-induced histological changes include previously undetected recasting with necrosis and fibrosis at the arterial edges of the stent. The parietal recasting we observed in animal arteries irradiated at high doses is unclear and a cause of concern especially after clinical spontaneous dissection was recently reported. The use of ionizing radiation for the prevention of arterial restenosis awaits confirmation with a long-term follow-up including specific experimental histological analyses.

Radiat Med 2006 Jan; 24(1): 58-64 (Read article online)

Oh RJ, Yoshioka Y, Tanaka E, Shiomi H, Sumida I, Isohashi F, Suzuki O, Konishi K, Kawaguchi Y, Nakamura S, Kato M, Inoue T

PURPOSE: High-dose-rate (HDR) brachytherapy combined with hormonal therapy (HTx), without the addition of external beam radiation therapy (EBRT) for high-risk prostate cancer was evaluated retrospectively. MATERIALS AND METHODS: Between May 1995 and April 2002, 35 patients with prostate cancer [Stage > or = T2b (UICC 1997) or tumor grading=3 or prostate-specific antigen (PSA) level > or = 20 ng/mL] were treated with HDR brachytherapy combined with HTx. Most patients (74%) had two or more of these factors. All patients received Iridium-192 HDR brachytherapy with a total dose of 54 Gy/9 fractions/5 days (48 Gy/8 fractions/5 days for the first 6 cases) in one implant session. The median neoadjuvant HTx [luteinizing hormone-releasing hormone (LH-RH) agonist and antiandrogen] period was 7 months. The median adjuvant HTx (ATH) (LH-RH agonist) period was 40 months, and median follow-up was 57 months (range, 23-117 months). RESULTS: The 5-year actuarial biochemical control, local control, and disease-free rates were 62%, 96%, and 76% respectively. No patients experienced local and/or regional relapse without distant progression. The 5-year actuarial cause-specific survival and overall survival rates were 89% and 87%, respectively. The acute and late toxicity were moderate and well tolerated. CONCLUSION: HDR brachytherapy plus long-term HTx is at least as effective as conventional EBRT plus long-term HTx.

Mol Cell Biochem 2006 May 23; (Read article online)

Manna S, Banerjee S, Saha P, Roy A, Das S, Panda CK

The differential alterations of the spliceosomal UsnRNAs (U1, U2, U4, U5, and U6) were reported to be associated with cellular proliferation and development. The attempt was made in this study to analyze the metabolic pattern of the spliceosomal UsnRNAs during the development of pre-malignant lung lesions induced in experimental mice model system by benzo(a)pyrene (BP) and also to see how tea polyphenols, epigallocatechin gallate (EGCG) and epicatechin gallate (ECG), modulate the metabolism of these UsnRNAs during the lung carcinogenesis. No significant changes in the level of the UsnRNAs were seen in the inflammatory lung lesions at 9th week due to treatment of BP. However, there was significant increase in the level of U1 ( approximately 2.5 fold) and U5 ( approximately 47%) in the hyperplastic lung lesions at 17th week. But in the mild dysplastic lung lesions at 26th week, the level of UsnRNAs did not change significantly. Whereas, in the dysplastic lung lesions at 36th week there was significant increase in the level of the U2 ( approximately 2 fold), U4 ( approximately 2.5 fold) and U5 ( approximately 2 fold). Due to the EGCG and ECG treatment the lung lesions at 9th week appeared normal and in the 17th, 26th, and 36th week it appeared as hyperplasia. The level of the UsnRNAs was significantly low in the lung lesions at 9th week (only U2 and U4 by EGCG), at 17th week (only U1 by EGCG/ECG), at 26th week (U1 by ECG; U2, U4 and U5 by EGCG/ECG) and at 36th week (U1 by ECG, U2 and U4 by EGCG/ECG). Whereas, there was significant increase in the level of U5 (by EGCG/ECG) and U6 (by EGCG only) in the lung lesions at 36th and 26th week respectively. This indicates that the metabolism of the spliceosomal UsnRNAs differentially altered during the development of pre-malignant lung lesions by BP as well as during the modulation of the lung lesions by the tea polyphenols.

Radiat Med 2006 Jan; 24(1): 17-22 (Read article online)

Shiraishi K, Nakagawa K, Yamashita H, Nakamura N, Tago M, Ohtomo K

PURPOSE: Intensity-modulated radiation therapy (IMRT) allows greater dose conformity to the tumor target. However, IMRT, especially static delivery, usually requires more time to deliver a dose fraction than conventional external beam radiotherapy (EBRT). The authors have been using a "two-axis dynamic arc therapy" (2A-DAT) technique for prostate cancer treatment to make a concave dose distribution to spare the rectum and bladder while working with limited time and human resources. The objectives of this study were to (1) clinically implement the 2A-DAT technique, (2) evaluate the dosimetry in comparison with IMRT, and (3) analyze the initial treatment outcome. MATERIALS AND METHODS: The 2A-DAT consists of two dynamic arc therapies (DATs) with half rotation around two isocenters each in two separate symmetrical rhombi. Treatment planning is forward and on a trial-and-error basis. Thirty-four patients received 2A-DAT with a median prescribed dose of 70 Gy. RESULTS: Although inferior in dose uniformity, the 2A-DAT provided equivalent sparing of normal structures to IMRT. Daily fraction delivery time for the 34 patients ranged from 6.4 to 9.6 minutes, with an average of 7.4 minutes. Five-year survival and five-year prostate specific autigen (PSA) failure-free survival were 89.3% and 79.5%, respectively. Three patients developed grade 2 proctitis. CONCLUSION: This technique is a possible alternative to IMRT in EBRT of prostate cancer.

World J Urol 2006 May 19; (Read article online)

Kaul S, Menon M

Following the popularization of Vattikuti Institute Prostatectomy technique of robotic radical prostatectomy (RARP) by Menon et al., RARP has been gaining steady acceptance as a preferred alternative to both open and laparoscopic radical prostatectomy (LRP). Up until now, radical retropubic prostatectomy has been considered the gold standard for treatment of organ confined prostate cancer. Despite significant improvements in intraoperative blood loss and functional outcomes, driven primarily by the description of anatomical radical prostatectomy by Walsh, the perioperative morbidity, analgesic requirement, and recovery times have remained disadvantages of the open approach. LRP has been unable to gain widespread acceptance because of technical difficulty and a steep learning curve. The da Vinci assisted approach incorporates the advantages of minimally invasive approach while improving upon the results of the open approach. This paper traces the evolution of RARP and describes technical modifications incorporated at the Vattikuti Urology Institute including operative data, complications, and functional outcomes.

Blood 2006 May 18; (Read article online)

Murakami M, Iwai S, Hiratsuka S, Yamauchi M, Nakamura K, Iwakura Y, Shibuya M

Vascular endothelial growth factor (VEGF) and VEGF receptor-1 (VEGFR-1/Flt-1) were shown to be involved in pathological angiogenesis, particularly rheumatoid arthritis (RA). However, the molecular basis of their actions is not fully understood. Here we report that in a murine model of RA, deletion of the tyrosine kinase (TK) domain of VEGFR-1 decreased the incidence and clinical symptoms of RA. Pathological symptoms, such as synovial hyperplasia, inflammatory infiltrates, pannus formation and cartilage/bone destruction became milder in Vegfr-1 tk-/- mice compared with Wild-type (Wt) mice in the Human T-cell Leukemia Virus-1 pX (HTLV-1 pX) induced chronic models. VEGFR-1 TK-deficient bone marrow cells showed a suppression of multi-lineage colony formation. Furthermore, macrophages induced to differentiate in vitro showed a decrease in immunological reactions such as phagocytosis and the secretion of Interleukin-6 (IL-6) and VEGF-A. Treatment of this RA model with a small molecule inhibitor for VEGFR TK, KRN951, also attenuated the arthritis. These results indicate that the VEGFR-1 TK signaling modulates the proliferation of bone marrow hematopoietic cells and immunity of monocyte/macrophages, and promotes chronic inflammation, which may be a new target in the treatment of RA.

Clin Chem 2006 May 18; (Read article online)

Azzazy HM, Mansour MM, Kazmierczak SC

BACKGROUND: The use of nanotechnologies for diagnostic applications shows great promise to meet the rigorous demands of the clinical laboratory for sensitivity and cost-effectiveness. New nanodiagnostic tools include quantum dots (QDs), gold nanoparticles, and cantilevers. QDs, which are the most promising nanostructures for diagnostic applications, are semiconductor nanocrystals characterized by high photostability, single-wavelength excitation, and size-tunable emission. QDs and magnetic nanoparticles can be used for barcoding of specific analytes. Gold and magnetic nanoparticles are key components of the bio-barcode assay, which has been proposed as a future alternative to the PCR. METHODS: We examined articles published over the past 10 years investigating the use of QDs, gold nanoparticles, cantilevers, and other nanotechnologies in promising diagnostic applications. RESULTS: Several nanodiagnostic assays have been developed, including a QD-based assay capable of detecting biotinylated prostate-specific antigen (PSA) at 0.38 ng/L, a bio-barcode assay capable of detecting 30 amol/L PSA in a 10-microL sample, and another able to detect 50 molecules of the Alzheimer marker amyloid beta-derived diffusible ligand in 10 microL of cerebrospinal fluid. CONCLUSIONS: Nanodiagnostics promise increased sensitivity, multiplexing capabilities, and reduced cost for many diagnostic applications as well as intracellular imaging. Further work is needed to fully optimize these diagnostic nanotechnologies for clinical laboratory setting and to address the potential health and environmental risks related to QDs.

Ann Urol (Paris) 2006 Apr; 40(2): 101-5 (Read article online)

Perrin P

Prostate cancer screening is controversial since PSA assay has been made available. Screening supporters consider that early diagnosis allows better and less aggressive treatment. These arguments lie on longitudinal cohort studies without controls. Randomized studies are required to assess the correlation between screening and mortality lowering. Two studies are being performed and their results will be available within three or four years. Consequently, the validity of screening is unknown. Nevertheless, the analysis of various parameters demonstrates that the reduction of cancer mortality related to screening is low. According to these data and as recommended by health institutions prostate cancer screening is not required. At the present time, detection asked by the patient himself remains the good attitude between negligence and excessive attitude.

J Clin Invest 2006 May 18; (Read article online)

Yu M, Tsai M, Tam SY, Jones C, Zehnder J, Galli SJ

Bronchial asthma, the most prevalent cause of significant respiratory morbidity in the developed world, typically is a chronic disorder associated with long-term changes in the airways. We developed a mouse model of chronic asthma that results in markedly increased numbers of airway mast cells, enhanced airway responses to methacholine or antigen, chronic inflammation including infiltration with eosinophils and lymphocytes, airway epithelial goblet cell hyperplasia, enhanced expression of the mucin genes Muc5ac and Muc5b, and increased levels of lung collagen. Using mast cell-deficient (Kit(W-sh/W-sh) and/or Kit(W/W-v)) mice engrafted with FcRgamma(+/+) or FcRgamma(-/-) mast cells, we found that mast cells were required for the full development of each of these features of the model. However, some features also were expressed, although usually at less than wild-type levels, in mice whose mast cells lacked FcRgamma and therefore could not be activated by either antigen- and IgE-dependent aggregation of FcepsilonRI or the binding of antigen-IgG1 immune complexes to FcgammaRIII. These findings demonstrate that mast cells can contribute to the development of multiple features of chronic asthma in mice and identify both FcRgamma-dependent and FcRgamma-independent pathways of mast cell activation as important for the expression of key features of this asthma model.