PSA Prostate Cancer Research Articles

Differential Detergent Separation of Mouse Liver Microsomal Proteins Using Triton X-114

The plasma membrane mediates many essential biological functions including cell-cell interactions, molecular transport, and signal transduction. Many membrane associated proteins are overexpressed in disease (eg cancer), and the ectodomains proteolytically shed. Several clinically used biomarkers have membranous origin including, CEA in colorectal cancer and PSA in prostate cancer. For this reason membrane proteomes are of interest in the field of biomarker discovery. As part of the AOHUPO membrane protein initiative, we report a solubility-based phase partitioning of mouse liver microsomes, using the non-ionic detergent Triton X-114. The aqueous, detergent, and pellet-insoluble fractions were obtained and subjected to SDS-PAGE in combination with LCMS/MS.

Optimisation de l’utilisation du PSA

PSA is a tumor marker usually determined for prostate cancer at diagnosis for its pronostic value and at therapy follow-up. But lack of specificity of PSA for prostate cancer and variability between assays demonstrated by the quality program survey make this marker not valuable in mass screening program. Market control of Afssaps on analysis devices of PSA showed a correct harmonization for total PSA. Biological tools available and easy to perform could improve ability of PSA for early detection of prostate cancer at a curable stage without induction of unnecessary biopsies prescribed because elevated total PSA values.

Toward the harmonization of immune monitoring in clinical trials: Quo vadis?

A constantly increasing number of cancer immunotherapies are being investigated in clinical trials but no reliable biomarkers to predict clinical benefit currently exist. For some cancer types, biomarkers have proven to be meaningful predictors of patient outcomes (e.g., BCR-ABL in Chronic Myeloid Leukemia or PSA in prostate cancer) and were established as routine tools. As effects of cancer immunotherapy are mediated through the immune system, immune responses may act as natural biomarkers for clinical efficiency if the right factors can be reliably measured. Following this concept, cancer immunotherapy trials over the last decade have often included measures of tumor-specific cellular immune responses as endpoints to identify reliable surrogates for clinical benefit. Substantial efforts were invested throughout the immunotherapy field in setting up suitable cellular immune assays. However, to date, data from clinical trials do not consistently show that immune responses are correlated with clinical endpoints [1]. This lack of correlation is partially interpreted as a consequence of the high variability in assay results, due to the lack of assay standardization, validation and harmonization across laboratories. If harmonization of immune assays can be achieved, assays can be tested as surrogate endpoints in clinical trials, substantially accelerate the development of immunotherapeutic agents and, in addition, offer a rationale to pre-select groups of patients with high probability to benefit from subsequent immunotherapy. A plethora of different immunological assays to monitor antigen-specific T cell responses are available, and some are used by a majority of laboratories. Prime examples are the ELISPOT assay, intracellular cytokine staining (ICS), MHC-peptide multimer staining for detection of antigen-specific CD8+ and increasingly for CD4+ T cells and proliferation assays based on carboxyfluorescein succinimidyl ester (CFSE)-labelling. Additional functional assays that have been introduced more recently are based on CD154 up-regulation on activated antigen-specific CD4+ T cells or the detection of CD107a or cytotoxicity related molecules like perforin or granzyme in CD8+ T cells. For each of these assays, the use of different protocols that have evolved over time translates into a wide range of performances. Differences in the interpretation of the results obtained make comparisons of published data even more complex. This has led to lack of comparability as well as doubts about the integrity of the results that were obtained and published worldwide [2]. Recent developments clearly suggest that “proper” immunomonitoring will have to encompass the parallel use of several tests, which together assess the frequency, function and homing capacity of induced/stimulated T cells present in the circulation and preferentially also locally within the targeted tissue. In view of the influence of both natural and adaptive regulatory T cells on clinical outcome, immunomonitoring should also include screening for these cells. Only the combined use of several techniques may lead to a valid set of surrogate markers for specific immune interventions that allows clinical decisions or optimization of immunotherapeutic strategies. A related proposal was made by a community-wide consensus workshop on clinical trials with cancer vaccines, in which criteria for the use of immune assays were recommended including at least two validated assays to be used in parallel [3]. There is also a surprising disparity between the substantial financial and logistic efforts invested in reagents and man hours to develop immune monitoring techniques and the comparatively minor investment made to date in actually validating and standardizing the available techniques within and between laboratories. This has to be critically re-evaluated as efforts put in the adequate harmonization of assays will support the investments already made. They are also a pre-requisite to meet regulatory requirements on assay standards prior to them being considered as surrogate endpoints for clinical trials. This affects academic institutions and industry partners alike and may reach beyond cancer into the fields of autoimmune and infectious diseases.

Clinically Significant Molecular Markers for Urologic Disease: Focus on Bladder, Kidney, and Prostate Cancer

The most important tools for making therapeutic decisions include stage and grade for bladder and kidney cancer, as well as PSA for prostate cancer. Unfortunately, all tumors of the same stage and grade do not behave the same, indicating the need for additional markers that can provide more accurate prognostic ability. The exponential increase in our understanding of the molecular mechanisms of disease during the past 2 decades has been aided by a large array of bladder, prostate, and kidney cancer biomarkers with potential diagnostic and prognostic value. This article reviews the molecular biomarkers that have shown to be clinically useful in the diagnosis and prognosis of urologic tumors. Ultimately, molecular markers may provide information that can be used to tailor the treatment of individual patients.

Lectin and serum-PSA interaction as a screening test for prostate cancer

Objectives The present investigation was designed to distinguish prostate cancer and benign prostate hyperplasia by lectin-prostate specific antigen (PSA) binding. Design & methods The quantitative precipitin method of concanavalin A (Con A)-carbohydrate interaction was explored with the serum PSA of patients suffering from prostatic complications. Results The carbohydrate content in the precipitate after binding of Con A with serum PSA of prostate cancer was significantly lower than that of benign prostate hyperplasia. This may be due to altered sugar chain structure or less glycosylation of PSA in prostate cancer. Conclusions We conclude that a serum value <3.0 μg/mL of the carbohydrate content of Con A-PSA precipitate indicates strong suspicion for prostate cancer and this cut off level is effective in reducing the rate of unnecessary biopsies in men with total PSA value between 4.0 to 10.0 ng/mL.

Innovations: Cancer vaccines made to order: Antigenics L.L.C.

Antigenics is in a crowded field (Table 1Table 1), but its methods are unique. “The whole Antigenics approach is based on the idea that each person’s cancer has its own antigenic signature,” says cancer immunologist Drew Pardoll (Johns Hopkins University, Baltimore, MD). “In most mouse models that seems to be the case. The jury is still out for human cancer.”Other companies are immunizing with specific antigens, but “ultimately the antigens that will be most useful have not really been identified,” says Pardoll. “Most of the vaccines in play don’t use true tumor-specific antigens,” he says, relying instead on tissue-specific antigens, or antigens from viruses associated with the cancer. In fact, Pardoll says, “true tumor-specific antigens are unlikely [to exist]. But the prospects for getting antigens that are highly expressed in tumors are pretty good. I’m optimistic there will be a pretty good [therapeutic] window.”Genzyme Molecular Oncology (Framingham, MA) is using high-throughput methods to identify promising antigens — after harvesting T cells from tumors they test the T cells for binding to a combinatorial library of peptides. Bruce Roberts, Genzyme’s senior director for gene therapy, agrees that the search for specific mutations is largely a waste of time. “I think the thing that is more reliable is the upregulation of proteins,” he says. “Cancer cells will figure out a way to switch on a protein that will give them a growth advantage,” he says, and the poor regulation of that switch can create an excellent target. Thus the Her2 protein is found in normal epithelial cells, but its gross overexpression in some breast cancers makes the tumors susceptible to Herceptin, a humanized monoclonal antibody made by Genentech, Inc. (South San Francisco, CA).Perhaps there are single antigens that will make good targets, and perhaps the only viable approach will be individualized therapy. For the consumer, at least, it is heartening that both approaches are being pursued vigorously.

Issues reporting PSA in prostate cancer

Issues reporting PSA in prostate cancer

PSA in prostate cancer: Criticai evaluation of clinically available assay methods

PSA is probably the most commonly used tumour marker in oncology. The absolute tissue specificity of PSA, as well as its well-established rote in clinical decision making, nave certainly contributed to its widespread use. Nevertheless, the familiarity that comes from the frequent use of the marker prompts the need for the awareness of the impact of the methods on the interpretation of the assay results. Actually, PSA values obtained by different methods may vary. Differences may be of clinical relevance in some instances such as when evaluating a PSA value with reference to a given cut-off point or, mainly, when assessing any variation among serial samples from the same patient. This potential variability related to the method is due to the molecular heterogeneity of PSA as well as to the lack of standard reference material. The problem of the binding of PSA to circulating protease inhibitors is of major relevance. The occurrence of several PSA isoforms should also be taken into account. Both a strict standardization of the method and the preparation of a reference standard are expected to reduce the method-related variability. In the meantime, the same assay method should be used to monitor the same patient. Moreover, dose co-operation between the urologist and the clinical pathologist is mandatory in order to be aware of the methodological clues which eventually may affect the decision-making process.