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PubMed1994

The National Cancer Data Base report on prostate cancer.

BACKGROUND: Previous Commission on Cancer studies on prostate cancer have examined time trends in disease stage, treatment patterns, and survival. The most current National Cancer Data Base data for prostate cancer are reviewed in this report. METHODS: Two Calls for Data have yielded a total of 85,813 prostate cancer reports from hospital registries across the country. RESULTS: The proportion of early stage, curable prostate cancers diagnosed in the United States has increased. In 1990, African-American patients were more likely to be diagnosed with metastatic prostate cancer than were non-Hispanic whites. The proportion of patients treated by prostatectomy increased between 1974 and 1990. Consistent with the pattern of more advanced disease at diagnosis, African-American patients were less likely to have received prostatectomy or radiation treatment and more likely to have received only hormonal treatment. Prostate cancer survival was associated strongly with disease stage. African-American men had a lower 5-year survival than did non-Hispanic white men. CONCLUSIONS: This information provides national points of reference against which individual hospital performance can be compared and should be particularly helpful to cancer committees, tumor boards, and cancer registrars for the monitoring and evaluation of prostate cancer management in hospital cancer programs. Not all segments of the population-at-risk are benefiting from earlier detection of prostate cancer. Improvements in early detection have important consequences for treatment patterns, allowing the increased use of curative surgical or radiotherapeutic treatment.

Black or African American↗

PubMedDate not supplied

Cancer immunomics: using autoantibody signatures in the early detection of prostate cancer.

Prostate cancer remains the most common malignancy among men and the second leading cause of cancer death of men in the United States. Although measurement of prostate-specific antigen (PSA) has led to earlier detection of many prostate cancers, new serum biomarkers are still needed to improve the accuracy of prostate cancer detection. Considerable evidence has shown that an immune response in the form of autoantibodies to various tumor antigens develops in many patients with cancer. By using phage-epitope microarray analysis, we were able to identify peptides expressed by prostate cancer tissue, which commonly induce formation of autoantibodies in the sera of patients with prostate cancer. Using a panel of 22 peptides, we were able to detect prostate cancer with a specificity of 88.2% and a sensitivity of 81.6%. These results were significantly better than PSA, especially among men with a PSA between 4 and 10 ng/ml. Measurement of the immune response to prostate cancer, as well as other malignancies, has the potential to improve significantly the detection of these cancers and possibly assist in the determination of prognosis.

Antigens, Neoplasm↗

PubMed2006

[Establishment of bone metastasis model of prostate cancer in nude mice by intratibia injection of human prostate cancer cell line Du145].

OBJECTIVE: To establish a bone metastasis model of prostate cancer by intratibia injection of Du145 in nude mice, observe the local growth of tumor in tibia and then assess application value of this model. METHODS: For 9 male nude mice, Du145 (5 x 10(6)) was injected in tibia by a TB syringe with a 29-gauge needle at a dose of 30 microl per mouse. Then the vital signs of the nude mice were observed. When the mice were dying, they were sacrificed, and the tissues of right hindlimbs, lymphatic nodes, lungs and livers were taken out, fixed in 10% formalin, embedded in paraffin, stained by HE and then observed microscopically. RESULTS: Incidence of bone tumor after intratibia injection was 67% (6 out of 9). About 48 days later, there were some small palpable nodes in right hind-limbs of the 6 mice and they couldn't walk normally. About 55 days later, cachexia occurred in them. After dissection, some carrion-like tissue grew from marrow cavity to muscular spatium, which was identified as tumor tissue by HE. The envelop of livers became crampy, and acute hepatitis could be diagnosed through microscopy, which represented a large scale of hepatocytic death, liver sinus dilatation and hyperemia, hepatic lobule infiltrated by lymphocyte, macrophage and inconspicuous hyperplasia. Since hypohepatia occurred too early, we couldn't detected distant metastases. CONCLUSION: The intratibia injection model is an optimal animal model to study metastasis of prostate cancer. It mimics the natural situation of human prostate cancer and will help to understand the mechanisms of androgen-independence and osseous metastasis, and tumor-host determinants of PSA expression.

Animals↗

PubMed1988

Immunologically measured serum markers and their role in the management of prostate cancer.

Serum prostatic acid phosphatase and prostate-specific antigen have been measured in a group of 106 cases of newly diagnosed prostate cancer. The serum levels of the tumour markers have been correlated with the clinical and ultrasound staging of the prostate cancer at diagnosis. All patients were managed by a deferred treatment policy. Patients without detectable metastases at presentation have been assessed after a period of 2 years to determine if the level of serum tumour markers at diagnosis could predict subsequent disease progression. The study has demonstrated that a combination of immunologically measured acid phosphatase and prostate-specific antigen is the best method of assessing the prognosis of an individual prostate cancer at the time of presentation.

Acid Phosphatase↗

PubMed1999

Somatic mutations at the SRD5A2 locus encoding prostatic steroid 5alpha-reductase during prostate cancer progression.

Prostate cancer is a serious public health problem in many industrialized countries. Androgens appear to play a critical role in its etiology. Specifically, the active androgen in the prostate, dihydrotestosterone (DHT) which is synthesized by the enzyme steroid 5alpha-reductase from testosterone (T), acts as a mitogen. Hence androgen-deprivation is commonly used during prostate cancer therapy. Two isozymes for steroid 5alpha-reductase have been reported. The type II enzyme is prostate-specific and encoded by the SRD5A2 gene. We have investigated a polymorphic (TA)n dinucleotide repeat in the 3' UTR (untranslated region) of the SRD5A2 gene in 30 matched samples of constitutional ("germline") DNA from peripheral blood lymphocytes and microdissected, pure tumor DNA. We report here 8 LOH (loss of heterozygosity) events and 9 cases of microsatellite instability at this marker. Therefore, almost 57% of the samples examined showed evidence of somatic mutations at the 3' UTR of the SRD5A2 locus. Our data suggest that the SRD5A2 gene may be involved in prostate cancer progression and that this may have relevance for treatment of the disease.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed1996

Three distinct commonly deleted regions of chromosome arm 16q in human primary and metastatic prostate cancers.

Human prostate cancers frequently show loss of heterozygosity (LOH) at loci on the long arm of chromosome 16 (16q). In this study, we analyzed prostate cancer specimens from 48 patients (Stage B, 20 cases; Stage C, 10 cases; cancer death, 18 cases) for allelic loss on 16q, using either restriction fragment length polymorphism (RFLP)- or polymerase chain reaction (PCR)-based methods. Allelic losses were observed in 20 (42%) of 48 cases, all of which were informative with at least one locus. Detailed deletion mapping identified three distinct commonly deleted regions on this chromosome arm: q22.1-q22.3, q23.2-q24.1, and q24.3-qter. On the basis of a published sex-averaged framework map, the estimated sizes of the commonly deleted regions were 4.7 (16q22.1-q22.3), 17.2 (16q23.2-q24.1) and 8.4 cM (16q24.3-qter). Allelic losses on 16q were observed more frequently in the cancer-death cases (11 of 18; 61%) than in early-stage tumor cases (9 of 30; 30%; P < 0.05). In 7 of 11 patients from whom DNA was available from metastatic cancers as well as from normal tissues and primary tumors, the primary cancer foci had no detectable abnormality of 16q, but the metastatic tumors showed LOH. These results suggest that inactivation of tumor suppressor genes on 16q plays an important role in the progression of prostate cancer. We also analyzed exons 5-8 of the E-cadherin gene, located at 16q22.1, in tumor DNA by means of PCR-single strand conformation polymorphism and direct sequencing, but we detected no somatic mutations in this candidate gene.

Adenocarcinoma↗

PubMed2004

Molecular markers and prostate cancer prognosis.

Prostate cancer is the most common malignancy among American men and is the second-leading cause of cancer-related mortality. Although radical prostatectomy and radiation therapy offer hope for cure for the majority of men with localized tumors, we continue to lack the tools to definitively determine which cancers need to be treated, which cancers will recur after treatment, and which cancers will behave aggressively when they have metastasized. Recent breakthroughs in molecular biology have led to the identification of a number of potential biomarkers for prostate cancer, many of which have been suggested to have prognostic significance. Eventually, combinations of these markers will hopefully enable us to more rationally facilitate counseling and direct management for men with prostate cancer.

Adenocarcinoma↗

PubMed1996

Prostate cancer screening.

Prostate cancer is a common cancer and a leading cause of cancer death in men. It is potentially detectable at early, possibly curative stages through various combinations of testing, including DRE, PSA, and TRUS of the prostate. Still unproven is the effectiveness of prostate cancer treatment, and because of that lack of proof, the optimal screening strategies are also elusive. It is possible that what is known as prostate cancer today may be, in fact, multiple entities with different natural histories, different treatment needs, and, consequently, different screening strategies. The role of informed consent has been suggested as a means to involve patients in the decision process, especially because the literature presents an environment of intense controversy. It is hoped that the PIVOT trial or similar efforts and further research into the basic mechanisms of the disease will provide clearer answers in the future.

Adult↗

PubMed2004

Identification and characterization of somatic steroid 5alpha-reductase (SRD5A2) mutations in human prostate cancer tissue.

Prostate cancer is a very common disease in industrialized countries and it is known to be androgen-dependent. The human SRD5A2 gene encodes the prostatic (or type II) steroid 5alpha-reductase, which catalyses the irreversible conversion of testosterone to dihydrotestosterone (DHT), the most active androgen in the prostate. We have sequenced the entire protein-coding region of this locus in 30 microdissected prostate adenocarcinomas. We identified a total of 17 de novo amino-acid substitutions in 13 of these tumors. We also identified six additional silent substitutions. In total, 18 out of 30 (60%) of the tumors examined had de novo somatic substitutions in the prostatic steroid 5alpha-reductase-coding region. We also characterized all of the SRD5A2 missense substitutions biochemically and pharmacologically, using three 5alpha-reductase inhibitors, including finasteride. The biochemical parameters of the distinct 5alpha-reductase missense substitutions varied substantially. We note that two out of the three recurrent SRD5A2 missense substitutions increased 5alpha-reductase in vitro activity, while the third one is essentially neutral. These findings are consistent with a role for increased DHT levels in the prostate through increased activity of the SRD5A2 locus in prostate cancer progression, in a subset of patients. Our pharmacologic studies also reveal substantial variability for each 5alpha-reductase inhibitor. These data, therefore, should be taken into account in both prevention as well as therapeutic trials of prostate cancer utilizing 5alpha-reductase inhibitors.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed2004

Bone scintigraphy predicts the risk of spinal cord compression in hormone-refractory prostate cancer.

In prostate cancer, confirmation of metastatic involvement of the skeleton has traditionally been achieved by bone scintigraphy, although the widespread availability of prostate-specific antigen (PSA) measurements has tended to eliminate the need for this investigation. The potential of bone scintigraphy to predict skeletal-related events, particularly spinal cord compression, after the onset of hormone refractoriness has never been investigated. The aim of this study was to establish whether a new method of evaluating bone scintigraphy would offer a better predictive value for this complication of the metastatic process than is achieved with currently available grading methods. We studied 84 patients with hormone-refractory prostate cancer who had undergone bone scintigraphy at the time of hormone escape. Tumour grading and parameters of tumour load (PSA and alkaline phosphatase activity) were available in all patients. The incidence of spinal cord compression was documented and all patients were followed up until death. Bone scintigraphy was evaluated by the conventional Soloway grading and by an additional analysis determining total or partial involvement of individual vertebrae. In contrast to the Soloway method, the new method was able to predict spinal cord compression at various spinal levels. Our data suggest that there is still a place for bone scintigraphy in the management of hormone-refractory prostate cancer.

Antineoplastic Agents, Hormonal↗

PubMed1996

Free to total prostate-specific antigen (PSA) ratio improves the discrimination between prostate cancer and benign prostatic hyperplasia (BPH) in the diagnostic gray zone of 1.8 to 10 ng/mL total PSA.

OBJECTIVES: Improved discrimination between prostate cancer (PC) and benign prostatic hyperplasia (BPH) is clearly needed. Our aim in this study was to evaluate whether the free to total prostate-specific antigen (PSA) ratio would be useful in the gray zone of 1.8-10 ng/mL total PSA range. METHODS: In a consecutive series of 435 clinic patients referred for prostate evaluation, 308 had a total PSA < 10 ng/mL (92 had PC and 216 BPH). Free and total PSA were measured, and the free to total PSA ratio calculated. RESULTS: Total PSA values were significantly different between the two groups. For the 200 patients with a total PSA < 6 ng/mL, no significant difference in total PSA values were seen (P = 0.411), whereas free to total PSA ratios remained statistically different (P < 0.001). Receiver operating characteristic (ROC) curve analysis comparing the performances of total PSA over the ratio of free to total PSA showed a clear advantage for the ratio at all sensitivity levels. CONCLUSIONS: These data demonstrate that in a significant number (n = 308) of prostatic patients in the diagnostic gray zone of 1.8-10 ng/mL total PSA, the routine use of free to total PSA might be advantageous in discriminating between cancer and benign hyperplasia. This advantage remained for total PSA < 4 ng/mL. Further study is warranted to confirm these findings in an unselected population.

Aged↗

PubMed2004

[PSA-screening for prostate cancer--yes or no?].

Prostate cancer is a mayor health care problem, especially in the industrialised countries of the Western world. At this time it is the second most common cancer reason for death (CH: 1500 men/year) which will even get more importance in the future by demographic developments. While there is no doubt that in individuals early detection of organ confined disease with localised treatment the prostate cancer can be eradicated and individual men be cured there are uncertainties whether mass screening a population will contribute to reducing prostate cancer related mortality. Its value has not been proved definitively by prospective randomised controlled studies. Most of Medical Societies recommend a "well informed" decision by family physicians, where the men between 50-70 years know about the benefits and harms including: risk of cancer, diagnostic procedures, therapeutic consequences and possible side effects. After agreement of early detection a biopsy has to be done directly above a PSA level of 4.0 ng/ml or a suspicious digital rectal examination. A PSA "grey zone" 4-10 ng/ml can not further be postulated. The ratio of free/total PSA gives no support to prolong biopsy in this moment, because an elevated benign prostate with a higher production of free PSA can mask the tumor in the peripheral zone. Results of the ERSPC and the PLCO trials are expected to give information about the benefits and harms of mass screening in 2006/8.

Aged↗

PubMed1999

Raf-1-induced cell cycle arrest in LNCaP human prostate cancer cells.

Prostate cancer is the most commonly diagnosed neoplasm in men. LNCaP cells continue to possess many of the molecular characteristics of in situ prostate cancer. These cells lack ras mutations, and mitogen-activated protein kinase (MAPK) is not extensively phosphorylated in these cells. To determine the effects of ras/raf/MAPK pathway activation in these cells, we transfected LNCaP cells with an activatable form of c-raf-1(deltaRaf-1:ER). Activation of deltaRaf-1:ER, with resultant MAPK activation, reduced plating efficiency and soft agarose cloning efficiency 30-fold in LNCaP cells. Cell cycle distribution showed an accumulation of cells in G1 and was associated with the induction of CDK inhibitor p21WAF1/CIP1 at the protein and mRNA levels. p21WAF1/CIP1 mRNA stability was increased after deltaRaf-1:ER activation. In addition, activated deltaRaf-1:ER induced the senescence associated-beta-galactosidase in LNCaP cells. These data demonstrate that raf activation can activate growth inhibitory pathways leading to growth suppression in prostate carcinoma cells and also suggest that raf/MEK/MAPK pathway activation, rather than inhibition, may be a therapeutic target for some human prostate cancer cells.

Calcium-Calmodulin-Dependent Protein Kinases↗

PubMedDate not supplied

Prostate specific antigen in as a dynamic model in advanced prostate cancer.

BACKGROUND: Prostate specific antigen doubling time (PSADT) is a prognostic factor after radical prostatectomy, radiation therapy, and hormonal therapy respectively for prostate cancer. However, its role in patients receiving chemotherapy has not been evaluated to date. PATIENTS AND METHODS: Thirty patients (pts.) with hormone resistant prostate cancer were enrolled in a prospective phase II study to receive oral Idarubicin. The drug was administered at a dose of 35 mg on day 1 and 8 of each cycle, and treatment was repeated every 3 weeks. RESULTS: Fully evaluable for response were 26 pts. 13 of these 26 had measurable disease and 3 out of 13 had no change (NC) after therapy. Ten pts. had progression. All 13 pts. with non-measurable disease showed no response. PSA values increased exponentially over time in all pts., except for the 3 pts. with NC, in whom PSA values remained stable. Median PSADT of pts. with a rising PSA was 2.1 months (mean 2.6; range 0.7-6.1). CONCLUSIONS: PSA levels in pts. not responding to treatment with Idarubicin rose in an exponential fashion similar to pts. who were only on hormonal therapy. PSADT should be evaluated in a larger number of hormone resistant prostate cancer pts. as a possible surrogate endpoint.

Aged↗

PubMed2006

Spinal leptomeningeal metastases from prostate cancer.

OBJECTIVE: Prostate cancer is a well known cause of spinal column metastases; however, an intradural location is extremely rare. It is considered to be a type of leptomeningeal spread. Cerebral seeding has usually occurred by the time of presentation. Due to a poor prognosis, surgery is rarely indicated, and controversially discussed. PATIENT AND RESULTS: We review the known cases of spinal leptomeningeal prostate cancer spread, including our patient, who developed paraparesis over 6 weeks, 3 years after prostate cancer was diagnosed. Following surgical decompression and resection, the patient additionally received radiation therapy of the spinal meninges and antihormonal treatment. Six months after surgery, the patient is still ambulatory with a good quality of life. CONCLUSION: Spinal leptomeningeal metastases occur at a late stage of systemic disease, and the prognosis is generally poor. In literature, outcomes after surgery are reported as devastating, with mortality and morbidity rates of up to 20 and 60%. The aim of surgery is to relieve pain, preserve or even restore neurological function, and reveal histology if uncertain. This may be achieved by debulking the tumor without placing the patient at an unacceptably high risk. Surgery should be performed in selected cases of spinal leptomeningeal metastases, in patients who are still ambulatory with controlled systemic disease, and should be followed by adjuvant therapy.

Aged↗

PubMed2003

Protein kinase Cepsilon interacts with Bax and promotes survival of human prostate cancer cells.

Prostatic glandular epithelial cells express protein kinase Cepsilon (PKCepsilon ), an oncoprotein that coordinately disrupts the reactivation of the tumor suppressor Rb, derepressess transcriptional elongation of the c-myc oncogene, and propagates survival signals in LNCaP cells. Since the activation of such a program may contribute to the progression of human prostate cancer, a proteomic analysis was performed to gain a more global perspective on the signaling network that PKCepsilon might be capable of engaging in prostate cancer cells. Using CWR22 xenografts, we identified at least 18 different structural, signaling, and stress-related proteins that associated with PKCepsilon, including an interaction with the proapoptotic protein Bax that was novel to recurrent CWR22 tumors. An investigation into the biological significance of the PKCepsilon association with Bax provided the first evidence of an inverse relationship between endogenous levels of PKCepsilon and susceptibility of prostate cancer cells to the apoptotic effects of phorbol esters. Western blot and antisense experiments demonstrated that CWR-R1 cells expressed moderate levels of PKCepsilon and relied on this protein to survive in the presence of phorbol esters, while the apoptosis normally induced by phorbol esters in PKCepsilon -deficient LNCaP cells was dependent on the presence of Bax. Forced expression of PKCepsilon in LNCaP cells was sufficient to confer a significant resistance to phorbol esters and this resistance was associated with an inhibition of phorbol ester-induced Bax conformational rearrangements that are important for Bax oligomerization, mitochondrial integration, and cytochrome c release. Considered in their entirety, our data suggest that an association of PKCepsilon with Bax may neutralize apoptotic signals propagated through a mitochondrial death-signaling pathway.

Animals↗

PubMed2005

Spinal leptomeningeal metastases from prostate cancer.

OBJECTIVE: Prostate cancer is a well known cause of spinal column metastases; however, an intradural location is extremely rare. It is considered to be a type of leptomeningeal spread. Cerebral seeding has usually occurred by the time of presentation. Due to a poor prognosis, surgery is rarely indicated, and controversially discussed. PATIENT AND RESULTS: We review the known cases of spinal leptomeningeal prostate cancer spread, including our patient, who developed paraparesis over 6 weeks, 3 years after prostate cancer was diagnosed. Following surgical decompression and resection, the patient additionally received radiation therapy of the spinal meninges and antihormonal treatment. 6 months after surgery, the patient is still ambulatory with a good quality of life. CONCLUSION: Spinal leptomeningeal metastases occur at a late stage of systemic disease, and the prognosis is generally poor. In the literature, outcomes after surgery are reported as devastating, with mortality and morbidity rates of up to 20% and 60%. The aim of surgery is to relieve pain, preserve or even restore neurological function, and reveal histology if uncertain. This may be achieved by debulking the tumor without placing the patient at an unacceptably high risk. Surgery should be performed in selected cases of spinal leptomeningeal metastases, in patients who are still ambulatory with controlled systemic disease, and should be followed by adjuvant therapy.

Arachnoid↗

PubMed2004

Detection of telomerase activity in prostate massage samples improves differentiating prostate cancer from benign prostatic hyperplasia.

PURPOSE: We performed a case-control study in which we tested the ability of a non-invasive assay to detect telomerase activity and to distinguish between prostatic cancer (Pca) and benign prostatic hyperplasia (BPH) on samples of epithelial cells obtained after prostatic massage. METHODS: Telomerase activity was determined by a telomeric repeat amplification protocol (TRAP) assay. We selected 60 patients with histologically proven Pca (30 cases) or BPH (30 cases). Specimens included in this study were from patients who had no suspicious findings on digital rectal examination for cancer, had clinical evidence of lower urinary tract symptoms, had no sonographic signs of Pca at the transrectal ultrasound evaluation, had total PSA values moderately elevated (2.6-15 ng/ml), and had no evidence of other urological cancers. The whole procedure was conducted in double blind between pathologists and molecular biology operators. RESULTS: Telomerase activity was detected in 90% of Pca cases and in 13% of BPH cases. The sensitivity (90%) and specificity (76%) of this method were calculated. The positive predictive value, negative predictive value, and diagnostic efficiency were 87%, 90%, and 88% respectively. CONCLUSION: Our data indicate that telomerase activity detected by TRAP assay on prostate epithelial cells collected by prostate massage can substantially improve the distinction between Pca and BPH conditions. One of the clinical benefits resulting from the use of this new assay would be to refine the biopsy indication and to avoid for several patients without Pca the unnecessary cost and the complications of prostate biopsy.

Aged↗