Proteomic analysis of normal and malignant prostate tissue to identify novel proteins lost in cancer

BACKGROUND. Alterations of important protein pathways, including loss of prostate secretory granules, and disruption of the prostatic secretory pathway have been identified as early events in malignancy. In this study, proteomics was used to map the differences in protein expression between normal and malignant prostate tissues and to identify and analyze differentially expressed proteins in human prostate tissue with particular regard to the proteins lost in malignancy. METHODS. Small quantities of normal and malignant prostate tissue were taken fresh from 34 radical prostatectomy cases. After histological examination, proteins were solubilized from selected tissues and separated using two-dimensional electrophoresis. Using image analysis, the proteome of normal and malignant tissues were mapped and differentially expressed proteins (present in normal and absent in malignant tissue) were identified and subsequently analyzed using peptide mass finger printing and N-terminal sequencing. Western blotting and immunohistochemistry were performed to examine expression profiles and tissue localization of candidate proteins. RESULTS. Comparison of protein maps of normal and malignant prostate were used to identify 20 proteins which were lost in malignant transformation, including prostate specific antigen (PSA), alpha-l antichymotrypsin (ACT), haptoglobin, and lactoylglutathione lyase. Three of the 20 had not previously been reported in human prostate tissue (Ubiquitin-like NEDD8, calponin, and a follistatin-related protein). Western blotting confirmed differences in the expression profiles of NEDD8 and calponin, and immunohistochemistry demonstrated differences in the cellular localization of these two proteins in normal and malignant prostate glands. CONCLUSIONS. The expression of NEDD8, calponin, and the follistatin-related protein in normal prostate tissues is a novel finding and the role of these important functional proteins in normal prostate and their loss or reduced expression in prostate malignancy warrants further investigations. (C) 2002 Wiley-Liss, Inc.

Variation in cervical cancer screening by region, socio-economic, migrant and Indigenous status in women in New South Wales

The purpose of this study was to estimate the extent of association of cervical screening in NSW women with socio-economic status (SES), rurality, and proportions of non-English speaking background (NESB) and Indigenous status. Data on women who had at least one Pap test over two years (January 1998-December 1999) were obtained from the NSW Pap test Register. Each local government area (LGA) was allocated to categories of population proportions of NESB and Indigenous status, a rurality classification based on population density and remoteness, and to an SES quintile. The odds ratios (OR) of having a Pap test were estimated and confounding adjusted by multiple logistic regression analysis. Implied Pap test rates in urban NESB and in rural Indigenous women were estimated from the modelled estimates. The adjusted OR for a Pap test in large rural centres (1.14) was significantly higher than those for metropolitan or capital city residents (0.9 and 1.0 respectively). Adjusted OR for a Pap test in other rural centres (0.73) and other remote areas (0.64) were significantly lower than those for metropolitan or capital city residents. In urban populations the lowest OR were in areas with both low SES and high proportion of NESB. The lowest OR for Pap screening in rural populations occurred in the most remote areas with the highest proportion of Indigenous women. For urban NESB women the biennial Pap test rate was estimated as 50%, and for rural Indigenous women 29%, compared with the NSW average of 59%.

Processing of urinary pheromones in Antechinus stuartii (Marsupialia: Dasyuridae): Functional magnetic resonance imaging of the brain

Little is known of the neural mechanisms of marsupial olfaction. However, functional magnetic resonance imaging (fMRI) has made it possible to visualize dynamic brain function in mammals without invasion. In this study, central processing of urinary pheromones was investigated in the brown antechinus, Antechinus stuartii, using fMRI. Images were obtained from 18 subjects (11 males, 7 females) in response to conspecific urinary olfactory stimuli. Significant indiscriminate activation occurred in the accessory olfactory bulb, entorhinal, frontal, and parietal cortices in response to both male and female urine. The paraventricular nucleus of hypothalamus, ventrolateral thalamic nucleus, and medial preoptic area were only activated in response to male urine. Results of this MRI study indicate that projections of accessory olfactory system are activated by chemo-sensory cues. Furthermore, it appears that, based on these experiments, urinary pheromones may act on the hypothalamo-pituitary-adrenocortical axis via the paraventricular nucleus of the hypothalamus and may play an important role in the unique life history pattern of A. stuartii. Finally, this study has demonstrated that fMRI may be a powerful tool for investigations of olfactory processes in mammals.

Cannabis use and cancer (Editorial)

No Abstract

Magnetization transfer imaging for polymer gel dosimetry

Off-resonance RF pre-saturation was used to obtain contrast in MRI images of polymer gel dosimeters irradiated to doses up to 50 Gy. Two different polymer gel dosimeters composed of 2-hydroxyethyl-acryl ate or methacrylic acid monomers mixed with N, N'-methylene-bisacrylamide (BIS), dispersed in an aqueous gelatin matrix were evaluated. Radiation-induced polymerization of the co-monomers generates a fast-relaxing insoluble polymer. Saturation of the polymer using off-resonance Gaussian RF pulses prior to a spin-echo read-out with a short echo time leads to contrast that is dependent on the absorbed dose. This contrast is attributed to magnetization transfer (MT) between free water and the polymer, and direct saturation of water was found to be negligible under the prevailing experimental conditions. The usefulness of MT imaging was assessed by computing the dose resolution obtained with this technique. We found a low value of dose resolution over a wide range of doses could be obtained with a single experiment. This is an advantage over multiple spin echo (MSE) experiments using a single echo spacing where an optimal dose resolution is achieved over only very limited ranges of doses. The results suggest MT imaging protocols may be developed into a useful tool for polymer gel dosimetry.

Is there a role for axillary dissection for patients with operable breast cancer in this era of conservatism?

Background: The trend in breast cancer surgery is toward more conservative operative procedures. The new staging technique of sentinel node biopsy facilitates the identification of pathological node-negative patients in whom axillary dissection may be avoided. However, patients with a positive sentinel node biopsy would require a thorough examination of their nodal status. An axillary dissection provides good local control, and accurate staging and prognostic information to inform decisions about adjuvant therapy. In addition, the survival benefit of axillary treatment is still debated. The objectives of the present study were to examine the pattern of lymph node metastases in the axilla, and evaluate the merits of a level III axillary dissection. Methods : Between June 1997 and May 2000, 308 patients underwent a total of 320 level III dissections as part of their treatment for operable invasive breast cancer. The three axillary levels were marked intraoperatively, and the contents in each level were submitted and examined separately. The patterns of axillary lymph node (ALN) metastases were examined, and factors associated with 4 positive nodes, and level III ALN metastases were evaluated by univariate and multivariate analyses. Results: An average of 25 lymph nodes were examined per case (range: 8-54), and using strict anatomical criteria, the mean numbers of ALN found in levels I, II and III were 18 (range: 2-43), 4 (range: 0 19), and 3 ( range: 0-11), respectively. Axillary lymph node involvement was found in 45% of the cases (143/320). Of the 143 cases, 78% (n = 111) had involvement of level I nodes only, and 21% (n = 30) had positive ALN in levels II and, or, III, in addition to level I. Involvement of lymph nodes in level II or III without a level I metastasis was found in two cases only (0.6%). By including level II, in addition to level I, in the dissection, four cases (1%) were converted from one to three positive nodes to 4 positive nodes (P = 0.64). By the inclusion of level III to a level I and II dissection, three cases (1%) were converted from one to three positive nodes to 4 positive nodes (P = 0.74). Involvement of lymph nodes in level III was found in 22 cases (7%), and 51 cases (16%) had 4 positive nodes. Palpability of ALN, pathological tumour size, and lymphovascular invasion (LVI), were significantly associated with level III involvement and 4 positive nodes by univariate and multivariate analyses. The frequencies of level III involvement and 4 positive nodes in patients with palpable ALN were 22% and 42%, respectively. The corresponding frequencies in patients with a clinically negative axilla, and a primary tumour which was >20 mm and LVI positive, were over 14% and 31%, respectively. Conclusion: Level III axillary dissection is appropriate for patients with palpable ALN, and in those with a tumour which is >20 mm and LVI positive, principally to reduce the risk of axillary recurrence. Staging accuracy is achieved with a level II dissection, or even a level I dissection alone based on strict anatomical criteria. Sentinel node biopsy is a promising technique in identifying pathological node-positive patients in whom an axillary clearance provides optimal local control and staging information.