Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kallikreins are a subgroup of serine proteases with diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis. By using molecular cloning techniques, we identified a new human kallikrein gene, tentatively named KLK15 (for kallikrein 15 gene). This new gene maps to chromosome 19q13.4 and is located between the KLK1 and KLK3 genes. KLK15 is formed of five coding exons and four introns, and shows structural similarity to other kallikreins and kallikrein-like genes. KLK15 has three alternatively spliced forms and is primarily expressed in the thyroid gland and to a lower extent in the prostate, salivary, and adrenal glands and in the colon testis and kidney. Our preliminary results indicate that the expression of KLK15 is up-regulated by steroid hormones in the LNCaP prostate cancer cell line. The KLK15 gene is also up-regulated, at the mRNA level, in prostate cancer in comparison to normal prostatic tissue. KLK15 up-regulation was found to be associated with more aggressive forms of prostate cancer. This newly discovered gene has the potential of being used as a diagnostic and/or prognostic marker for prostate cancer.
 ...
PMID:Molecular cloning of the human kallikrein 15 gene (KLK15). Up-regulation in prostate cancer. 1101 Sep 66

Kallikreins are a subgroup of serine proteases that are involved in the posttranslational processing of polypeptide precursors. Growing evidence suggests that many kallikreins are implicated in carcinogenesis. In rodents, kallikreins are encoded by a large multigene family, but in humans, only three genes have been identified. By using the positional candidate approach, we were able to identify a new kallikrein-like gene, tentatively named KLK12 (for kallikrein gene 12). This new gene maps to chromosome 19q13.3-q13.4, is formed of five coding exons, and shows structural similarity to serine proteases and other known kallikreins. KLK12 is expressed in a variety of tissues including salivary gland, stomach, uterus, lung, thymus, prostate, colon, brain, breast, thyroid, and trachea. We identified three splicing forms of KLK12 that are expressed in many tissues. Our preliminary results indicate that the expression of KLK12 is down-regulated at the mRNA level in breast cancer tissues and is up-regulated by steroid hormones in breast and prostate cancer cell lines. This gene may be involved in the pathogenesis and/or progression of certain cancer types and may find applicability as a novel cancer biomarker.
 ...
PMID:KLK12 is a novel serine protease and a new member of the human kallikrein gene family-differential expression in breast cancer. 1105 51

Appreciation of the clinical utility of the protein product of kallikrein gene 3, prostate-specific antigen (PSA), has resulted in earlier diagnosis of prostate cancer and an associated increase in the number of radical prostatectomies performed. A consequence of this change in surgical practice has been an improved understanding of sphincter anatomy and methods for sphincter preservation, which in turn have led to enhanced popularity for orthotopic urinary diversion for invasive bladder cancer. In this paper, molecular and basic science research being undertaken in an to attempt to overcome problems and limitations of the PSA/transrectal ultrasonographic biopsy approach to diagnosis are discussed. Also detailed are (1) the development of a bladder acellular matrix graft to serve as an "off the shelf" scaffold on which urothelium regenerates, (2) attempts to create a simpler, more durable bowel continence mechanism, and (3) a novel experimental technique for renal preservation based on considering the urine-producing and urine-directing roles of the upper tract as surgically separable entities. These research endeavors serve to illustrate how developments at the molecular and basic science levels promise to lead to further reconstructive surgical approaches when translating new developments into patient benefits during the year 2000 and beyond.
 ...
PMID:Molecular and reconstructive urology: a coming together. 1107 52

Treatment of metastatic prostate cancer with androgen-ablation often elicits dramatic tumor regressions, but the response is rarely complete, making clinical recurrence inevitable with time. To gain insight into therapy-related progression, changes in gene expression that occurred following androgen-deprivation of an androgen-dependent prostate tumor xenograft, CWR22, and the emergence of an androgen-independent tumor, CWR22-R, were monitored using microarray analysis. Androgen-deprivation resulted in growth arrest of CWR22 cells, as evidenced by decreased expression of genes encoding cell cycle components and basal cell metabolism, respiration and transcription, and the induced expression of putative negative regulatory genes that may act to sustain cells in a nonproliferative state. Evolution of androgen-independent growth and proliferation, represented by CWR22-R, was associated with a reentry into active cell cycle and the up-regulation of several genes that were expressed at low levels or absent in the androgen-dependent tumor. Androgen repletion to mice bearing androgen-independent CWR22-R tumors induced, augmented, or repressed the expression of a number of genes. Expression of two of these genes, the calcium-binding protein S100P and the FK-506-binding protein FKBP51, was decreased following androgen-deprivation, subsequently reexpressed in CWR22-R at levels comparable with CWR22, and elevated further upon treatment with androgens. The dysregulated behavior of these genes is analogous to other androgen-dependent genes, e.g., prostate-specific antigen and human kallikrein 2, which are commonly reexpressed in androgen-independent disease in the absence of androgens. Other androgen-responsive genes whose expression decreased during androgen-deprivation and whose expression remained decreased in CWR22 were also identified in CWR22-R. These results imply that evolution to androgen-independence is due, in part, to reactivation of the androgen-response pathway in the absence of androgens, but that this reactivation is probably incomplete.
 ...
PMID:Dysregulated expression of androgen-responsive and nonresponsive genes in the androgen-independent prostate cancer xenograft model CWR22-R1. 1108 37

Prostate-specific antigen (PSA) is the most useful marker in the early detection of prostate cancer and for the monitoring of patients with this diagnosis. Molecular forms of PSA and also human kallikrein 2 have been used to discriminate between benign prostatic hyperplasia and prostate cancer as well as for the detection of prostate cancer within the gray zone of PSA. In this respect, a literature survey on the diagnostic validity of free PSA (fPSA) related to total PSA (tPSA), PSA bound to alpha1-antichymotrypsin (ACT-PSA), and complexed PSA is given together with our results. The ratio of fPSA:tPSA has been shown to improve the specificity of prostate cancer diagnosis on the basis of tPSA measurements. Unnecessary biopsies can be reduced by about 19-64% in the total PSA range of 4-10 microg/liter while only missing 5-10% of cancers. Furthermore, carcinomas in patients with PSA values <4 microg/liter can be detected, indicating an improved sensitivity because of the percent fPSA at low PSA values. ACT-PSA or complexed PSA alone and the calculated derivatives are not superior in their discriminatory power compared with the percent fPSA. The diagnostic significance of the other molecular PSA forms and human kallikrein 2 needs to be evaluated in more extensive clinical trials.
 ...
PMID:Molecular forms of prostate-specific antigen and human kallikrein 2 as promising tools for early diagnosis of prostate cancer. 1109 20

Prostate-specific antigen is a serine protease that is a member of the kallikrein family. It is widely used as an indicator of tumor burden and as a surrogate marker for disease progression in men with androgen-independent prostate cancer. It has been shown that the expression and/or secretion of this glycoprotein can be regulated by pharmacological agents. The effects of these agents on PSA may be independent of their effects on cell growth. For example, a pharmacological agent may down-regulate PSA expression/secretion but have no effect on tumor cell growth. In this case, a patient receiving this therapeutic agent might be falsely considered as having a clinical response. Alternatively, an agent might up-regulate PSA expression/secretion and have an inhibitory effect on cell growth. A patient receiving this therapeutic agent might be diagnosed with progressive disease unless an alternative method for assessing tumor burden is used. Thus, when an agent is to be evaluated in a clinical trial utilizing PSA as a marker for disease progression, it is important to prospectively test whether the agent has an effect on PSA expression and/or secretion. In addition, it is equally important to understand how these regulatory effects relate to cell growth. The purpose of this review is to describe several agents that have been tested for their regulatory effects on PSA and to discuss potential mechanisms of by which this regulation may occur. The implications of these findings in the evaluation of new agents in androgen-independent prostate cancer will be considered.
 ...
PMID:The control of prostate-specific antigen expression and gene regulation by pharmacological agents. 1117 39

A close relationship exists between prostate volume and prostate-specific antigen (PSA). Clinical decisions must be determined based on the variability of PSA. Screening with the PSA assay has contributed to early detection of prostate cancer. Some important undetermined issues are the optimal cutoff values of PSA, the proportion of free to total PSA, and the clinical usefulness of complexed PSA. Current articles demonstrating novel markers (human kallikrein-2, BPSA, and pro PSA) and artificial neural networks are introduced.
 ...
PMID:Early detection of prostate cancer: is PSA a reliable option? 1123 61

The tissue kallikreins (KLKs) form a family of serine proteases that are involved in processing of polypeptide precursors and have important roles in a variety of physiologic and pathological processes. Common features of all tissue kallikrein genes identified to date in various species include a similar genomic organization of five exons, a conserved triad of amino acids for serine protease catalytic activity, and a signal peptide sequence encoded in the first exon. Here, we show that KLK4/KLK-L1/prostase/ARM1 (hereafter called KLK4) is the first significantly divergent member of the kallikrein family. The exon predicted to code for a signal peptide is absent in KLK4, which is likely to affect the function of the encoded protein. Green fluorescent protein (GFP)-tagged KLK4 has a distinct perinuclear localization, suggesting that its primary function is inside the cell, in contrast to the other tissue kallikreins characterized so far that have major extracellular functions. There are at least two differentially spliced, truncated variants of KLK4 that are either exclusively or predominantly localized to the nucleus when labeled with GFP. Furthermore, KLK4 expression is regulated by multiple hormones in prostate cancer cells and is deregulated in the androgen-independent phase of prostate cancer. These findings demonstrate that KLK4 is a unique member of the kallikrein family that may have a role in the progression of prostate cancer.
 ...
PMID:Distinctly different gene structure of KLK4/KLK-L1/prostase/ARM1 compared with other members of the kallikrein family: intracellular localization, alternative cDNA forms, and Regulation by multiple hormones. 1150 7

Prostate-specific antigen (PSA), a 33 kDa glycoprotein produced in the epithelium of the human prostate, has become established as a useful tumor marker for prostate cancer in man. Since reports of homologous proteins in animals other than primates have been lacking, the present investigation was carried out to identify any PSA-like protein in rats. Immunoblot analysis using a specific monoclonal anti-human PSA antibody detected a 32 kDa immunoreactive protein in the ventral lobe of the rat prostate, but not in other lobes or in other tissues. Positive immunostaining was observed only for the luminal surface of the glandular epithelium and the intraductal fluid in the ventral prostate. Sequence analysis of a cDNA for the rat PSA-like protein, cloned by immunoscreening of an expression cDNA library prepared from the ventral lobe, revealed identity to the rat submaxillary gland S3 kallikrein. Human PSA also belongs to the kallikrein family. Thus, this protein produced in the rat ventral prostate was suggested to be a possible counterpart of human PSA.
 ...
PMID:Detection and cloning of a protein recognized by anti-human prostate-specific antigen (PSA) antibody in the rat ventral prostate. 1150 18

Prostate-specific antigen (PSA) is a widely used serum marker for prostate cancer (PCa) but has limited specificity for distinguishing early PCa from benign prostatic hyperplasia, because both PCa and benign prostatic hyperplasia release PSA into the serum. We have identified previously a truncated form of precursor PSA (pPSA) in prostate tumor extracts consisting of PSA with a serine-arginine pro leader peptide ([-2]pPSA) instead of the normally expressed 7 amino acid pro leader peptide. In the current study we developed monoclonal antibodies to detect [-2]pPSA and other isoforms of pPSA for Western blot analysis. PSA was immunoaffinity purified from 100 to 200 ml of serum from each of five men with biopsy-proven cancer and three biopsy-negative men, all with total PSA levels in the diagnostically relevant range near 10 ng/ml. The truncated [-2]pPSA was estimated to range from 25 to 95% of the free PSA in the five PCa samples but only 6-19% of the free PSA in the biopsy-negative men. Immunohistochemical studies showed positive staining for [-2]pPSA in PCa epithelium and that [-2]pPSA was enriched in cancer cell secretions. In vitro activation studies showed that human kallikrein 2 and trypsin readily activated full-length pPSA but were unable to activate [-2]pPSA to mature PSA. Thus, [-2]pPSA, once formed, is a stable but inactive isoform of PSA. Truncated [-2]pPSA may represent an important new diagnostic marker for the early detection of PCa.
 ...
PMID:A truncated precursor form of prostate-specific antigen is a more specific serum marker of prostate cancer. 1155 76


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>