The relationships of 13 potential prognostic factors to objective response to treatment and survival time were investigated, using data gathered on 1,020 patients with advanced stage prostate cancer who have participated in the clinical trials of the National Prostatic Cancer Project. Multivariate statistical analyses re vealed that previous hormone response status, analgesics, pain, elevated acid phosphatase, and anemia were the important, independent prognostic factors for objective response to treat ment. For survival time, the significant prognostic factors were previous hormone response status, anorexia, elevated acid phosphatase, pain, elevated alkaline phosphatase, obstructive symptoms, tumor grade, performance status, anemia, and age at diagnosis. It is recommended that future treatment protocols for advanced stage prostate cancer take into account hetero geneity of the treatment groups with respect to these factors, either through the design of the protocol, or at the time of analysis.

Prognostic criteria for bladder tumors are the stage and grade of the tumor in the present series of 82 patients, in which all patients received the same treatment. These criteria are related and the combined evaluation increases the prognostic accuracy for the disease. In addition, the diameter and not the number of bladder tumors on primary diagnosis is an important prognostic sign.

The Mars Society is an international private organisation advocating the exploration and settlement of Mars. Part of its mission involves selecting areas for Martian analogue research, to test hardware, technology, strategies and human factors relevant to sending people to Mars. Mars Society Australia has selected an area in the Arkaroola region in the Flinders Ranges as the site for the first Australian analogue facility. The facility will be an invaluable public education and outreach tool for Australian science, focusing on astrobiology, and its role in future human Mars missions; demonstrating Australian contributions to astrobiology related science and work on terrestrial analogues to Martian environments.

Abstract Artificial neural networks (ANNs) are the sole successfully deployed artificial intelligence (AI) applications that attempt to mimic the activities of the human brain and how it physically operates. The “artificial” in artificial neural nets is included to distinguish the computer‐based systems from their biological counterparts. ANNs have become very common in a broad set of problem domains including medical, industrial, and financial applications. Within urology, the 1994 seminal paper by Snow et al. established ANNs as a significant predictive technology in the prostate cancer arena. ANNs are well‐established computational models, with research dating to the 1940s. Within AI, ANNs are generally contrasted with knowledge‐based systems (also known as expert systems). Expert systems use a somewhat contrived structure composed of explicit knowledge rules, while ANNs provide a reasonably faithful representation of biological neural systems. ANNs are generally easier to construct than knowledge‐based systems, but the simple rule structure of knowledge‐based systems provides a more traceable chain of logic from the input to output. There are a large number of different types of ANNs that computer science researchers apply to various problem types. However, one particular type of ANN architecture has emerged as the de facto standard in practice—the so‐called “feedforward” network, which is described in detail below. Other types of networks that the reader may encounter will generally be some sort of a geometric construct, such as probabilistic neural networks or Kohonen networks. Probabilistic neural networks use a “nearest‐neighbor” approach, where prospective cases are associated with the closest case that was available during network construction. Kohonen networks are a clustering technique, where similar cases are identified as being members of the same group. This document does not address these more esoteric constructs, rather it focuses on the ubiquitous feedforward networks. An interested reader can find detailed information on various ANN paradigms in Lawrence or Wasserman.

Over the past 5 years, a steady stream of publications has discussed the use of artificial neural networks (ANNs) for urologic and other medical applications. The pace of this research has increased recently, and deployed products based on this technology are now appearing. Before these tools can be widely accepted by clinicians and researchers, a deeper level of understanding of ANNs is necessary. This article attempts to lay some of the groundwork needed to facilitate this familiarity.

Treatments available for metastatic prostate cancer have failed to demonstrate significant curative potential. Current efforts are now directed towards developments of novel strategies for the treatment of metastatic prostate cancer. Cancer immunotherapeutic strategies utilize patient immune system components to kill cancer cells. This review discusses progress in active specific immunotherapeutic approaches as potential alternative methods in the treatment of metastatic prostate cancer. Various methods of augmenting the immune response against prostate cancer are discussed including systemic cytokine adjuvant therapy, cytokine gene transduced tumor vaccines, non-antigen specific immunization, DNA and peptide vaccines plus adjuvants, as well as dendritic cell-based cancer vaccines.

BACKGROUND. Multiple serum tests were performed on archival samples from patients who participated in trials to assess the ProstaScint((R)) scan staging ability. Traditional statistical analysis as well as artificial neural network (ANN) analysis were employed to evaluate individual patients and the group as a whole. The results were evaluated so that each factor was tested for prognostic value.METHODS. Data obtained from serum tests, bone scans, and ProstaScint((R)) scans were evaluated by traditional statistical methods and ANN to determine the individual value in clinical staging of prostate cancer.RESULTS. Two hundred seventy-five patients (180 postprostatectomy, 95 intact prostate) with prostate cancer (14 with distant metastases) were available for analysis. Data available included: clinical state (remission or progression), most recent clinical TNM stage, bone scan, and ProstaScint((R)) scan. Serum was tested for prostate-specific membrane antigen(PSMA), prostate-specific antigen(PSA), free PSA (fPSA), and complexed PSA (cPSA). Additional calculations included percent free PSA, and percent complexed PSA. Spearman individual statistical assessment for traditional group evaluation revealed no significant factors for T-stage. The free PSA and complex PSA had a significant association with node N-status. The distant metastases (M) stage correlated well with the bone scan and clinical stage. ANN analysis revealed no significant T-stage factors. N-stage factors showed a 95% sensitivity and 49% specificity. These factors included the presence or absence of a prostate, PSA serum levels, bone scan, and ProstaScint((R)) scans as major associated indicators. ANN analysis of the important variables for M-stage included ProstaScint" scan score, and PSA levels (total, percent complexed, percent free, and fPSA). These factors were associated with a 95% sensitivity and 15% specificity level.CONCLUSIONS. Two hundred seventy-five patients receiving treatment for prostate cancer were evaluated by ANN and traditional statistical analysis for factors related to stage of disease. ANN revealed that PSA levels, determined by a variety of ways, ProstaScint((R)) scan, and bone scan, were significant variables that had prognostic value in determining the likelihood of nodal disease, or distant disease in prostate cancer patients. (C) 2000 Wiley-Liss, Inc.

Prostate-specific membrane antigen (PSMA) is a 750-amino acid glycoprotein highly expressed in malignant prostate tissues. PSMA reacts with the murine monoclonal antibody 7E11.C5, whose binding epitope has been mapped to the N-terminal of the protein distributed on the cytoplasmic side of the plasma membrane. We have developed murine monoclonal antibodies specific for extracellular epitopes of PSMA. Three of these antibodies--1G9, 3C6, and 4D4--display distinct binding properties consistent with their recognition of conformational epitopes within native PSMA. Results indicate this panel of antibodies binds to native full-length PSMA, but not to fusion proteins containing portions of the linear sequence of the protein. Antibody binding is greatly reduced upon heat denaturation of native PSMA, and these antibodies do not detect PSMA by Western blot. Immunoprecipitation experiments demonstrate the ability of each to bind to full-length PSMA as well as PSM', a form of the protein missing the first 57 amino acids. These results indicate each antibody is specific for an epitope within the extracellular domain, a region spanning residues 44-750. Flow cytometric experiments indicate strong specific binding to live LNCaP cells. Antibody inhibition studies demonstrate that these antibodies recognize at least two distinct epitopes. Taken together, the results demonstrate that these antibodies are specific for native protein conformational epitopes within the extracellular domain. Their properties, in particular strong binding to live cancer cells, make them ideal candidates that are clearly superior to linear sequence epitope specific antibodies for in vivo applications.

Objectives. To determine the prostate-specific antigen (PSA) levels and PSA change over time in young white and black men 20 to 45 years old.Methods. The Department of Defense Serum Repository, a serum bank that stores all residual serum from the military human immunodeficiency virus screening program at -25 degreesC, was sampled to obtain a total of 588 black and 588 white subjects 20 to 45 years old. This was a retrospective study with only demographic data available on the studied subjects. The samples used for this study were collected between June 24, 1988 and June 12, 1996. Individuals with a history of prostate disease were excluded by query of a centralized Department of Defense diagnosis database. Three serum specimens evenly distributed over a mean of 6 years were selected for each individual to determine the free and total PSA levels and PSA velocity. The Hybritech Tandem-E PSA assay was used for the total PSA measurement, and the Hybritech Tandem-R assay was used for the free PSA measurement.Results. The baseline serum PSA levels differed by race (P = 0.04). The median (25th, 75th percentile) baseline serum PSA levels for black men 20 to 29, 30 to 39, and 40 to 45 were 0.38 ng/mL (0.26, 0.61), 0.45 ng/mL (0.32, 0.67), and 0.52 ng/mL (0.37, 0.73), respectively. The median baseline serum PSA levels for the same decade groups in white men were 0.38 ng/mL (0.27, 0.57), 0.45 ng/mL (0.28, 0.68), and 0.40 ng/mL (0.26, 0.64), respectively. The PSA velocity was higher in white men than in black men (mean 2.8%/yr and 1.6%/yr, respectively, P = 0.032).Conclusions. These results suggest that although black men 20 to 45 years old have higher baseline serum PSA levels than white men of the same age, the PSA velocity is greater in young white than in young black men. Additional work is needed to determine the clinical significance of these findings. UROLOGY 56: 812-816, 2000. Published by Elsevier Science Inc.

This is a report on the current new markers in the serum for prostate cancer diagnosis and follow-up, which were discussed at this International Union Against Cancer (UICC) Tumor Biology Committee Program Meeting held in Whistler, British Columbia, Canada, on July 17–18, 1999.

BACKGROUND:A reliable imaging modality is required to uncover occult soft- tissue recurrence after failure of primary prostate cancer therapy. This retrospective study was done to evaluate the ability of the (111)Indium-labeled monoclonal antibody (ProstaScint(R)) scan in detection of prostatic bed recurrence and/or metastases to regional and/or distant lymph nodes. METHODS:One hundred sequential patients were evaluated with repeated ProstaScint(R) scans because of evidence of recurrence during the course of their disease. These 100 patients were followed closely from November 1994 and April 1999, and had concurrent bone scans and serum prostate-specific antigen (PSA) evaluations. They have had hormone therapy (n = 53) and/or experienced a rising PSA after radical prostatectomy (n = 38) or after radiation therapy (n = 56). Scan images were scored 0-3, where score 0 = negative, score 1= prostate bed uptake, score 2 = regional lymph node uptake, and score 3 = distant lymph node uptake. In each patient, the uptake of the follow-up scan(s) was compared to that of the initial scan. RESULTS:The median age was 70 years (range, 45-87), and 23 patients had a positive bone scan. The average PSA was 40.5 ng/ml (standard deviation, 223.5). There was 257 scans representing 100 patients. All patients had at least 2 scans, 35 patients had 3 scans, and 11 patients had 4 scans. No individual exhibited detectable adverse clinical reactions during or after the scan. The findings of the initial and consecutive scans were anatomically consistent in 79%, whereas in 21% there were skip metastases. In 24 patients the lesions progressed by scan and PSA, 10 patients showed progression of scan but no PSA progression, 49 patients showed no change, and 17 patients showed a remission related to adjuvant therapy. CONCLUSIONS:The consistency on repeating the scan (79%) and the high percentage of patients showing persistent uptake at the prostate bed (43%) as well as the percentage of detection of regional nodes (20%) and distant nodes (32%) reflects the importance of using the ProstaScint(R) scan in finding occult recurrences after primary treatment failure of prostate cancer. These results are similar to those reported earlier in autopsy series studies in similar populations.

BACKGROUND Human Nr-CAM (Neuroglia related Cell Adhesion Molecule) is over expressed in glioblastoma multiforme tissue (GMT) as compared to normal brain tissue (NBT). MATERIALS AND METHODS We transfected a human glioblastoma cell line (2020-CRL) with a vector that overexpresses antisense hNr-CAM using a CMVpromoter. RESULTS Antisense hNr- CAM caused reduction in the native hNr-CAM expression, changed cell morphology, reduced the cell proliferation rate and lengthening of the cell cycle. Furthermore, antisense hNr-CAM overexpression in these cells caused extensive reduction in the number of soft agar colonies and invasion through extra cellular matrix (ECM) gel in vitro. Subcutaneous injection of antisense hNr-CAM overexpressing glioblastoma cells into nude mice caused complete inhibition of tumor formation as compared to vector only transfected cells. Intra-tumoral inoculation of antisense hNr-CAM expressing plasmid also caused slow tumor growth in nude mice in vivo. CONCLUSION On the basis of these results, we conclude that hNr-CAM is a valid target for potential gene therapy of glioblastoma tumors.