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

Kallikrein hK2 is a new potential marker of prostate cancer. It is the last member of the human kallikrein gene family to be isolated. We propose a simple purification procedure permitting us to obtain the active form of hK2 starting from human seminal plasma and using commonly available chromatography matrices. In contrast to recently published papers, this procedure is carried out without any immunoaffinity chromatography step and without the need for any antibody to follow the purification. Furthermore, it does not require any recombinant DNA technology nor sophisticated instruments.
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PMID:Simple purification procedure for human prostatic kallikrein hK2 in its active form. 974 44

Kallikrein (KLK)4 is a recently described member of the tissue kallikrein gene family that is specifically expressed in normal and prostate tumor tissues. The tissue-specific expression profile of this molecule suggests that it might be useful as a vaccine candidate against prostate cancer. To examine the presence of CD4 T cells specific for KLK4 in PBMC of normal individuals, a peptide-based in vitro stimulation protocol was developed that uses overlapping KLK4-derived peptides spanning the majority of the KLK4 protein. Using this methodology, three naturally processed CD4 epitopes derived from the KLK4 sequence are identified. These epitopes are restricted by HLA-DRB1*0404, HLA-DRB1*0701, and HLA-DPB1*0401 class II alleles. CD4 T cell clones specific for these epitopes are shown to efficiently and specifically recognize both recombinant KLK4 protein and lysates from prostate tumor cell lines virally infected to express KLK4. CD4 T cells specific for these KLK4 epitopes are shown to exist in PBMC from multiple male donors that express the relevant class II alleles, indicating that a CD4 T cell repertoire specific for KLK4 is present and potentially expandable in prostate cancer patients. The demonstration that KLK4-specific CD4 T cells exist in the peripheral circulation of normal male donors and the identification of naturally processed KLK4-derived CD4 T cell epitopes support the use of KLK4 in whole gene-, protein-, or peptide-based vaccine strategies against prostate cancer. Furthermore, the identification of naturally processed KLK4-derived epitopes provides valuable tools for monitoring preexisting and vaccine-induced responses to this molecule.
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PMID:Identification of naturally processed CD4 T cell epitopes from the prostate-specific antigen kallikrein 4 using peptide-based in vitro stimulation. 1207 88

Kallikrein 11 (KLK11, TLSP, hippostatin) is a member of the human kallikrein gene family, which includes PSA, KLK2 and 12 other members, all localized on chromosome 19q13.4. The aim of this study was to investigate whether KLK11 expression could be used to discriminate prostate cancer (CaP) from benign prostatic hyperplasia (BPH) in needle prostate biopsies. We analyzed the expression of the prostate-type variant of the KLK11 gene in 64 CaP and BPH tissues obtained by transrectal ultrasound-guided needle biopsy. Reverse transcription (RT), PCR and image analysis methodologies were developed and used. Of the 42 BPH tissues examined, only 10 (23.8%) were positive for prostate-type KLK11 expression, while of the 22 CaP patients, 12 (54.5%) were KLK11-positive (p=0.025). Logistic regression and receiver operating characteristic curve analyses demonstrated that KLK11 expression has a significant discriminatory value (crude odds ratio=3.84, p=0.016; area under the curve, 0.65, 95% CI 0.51-0.80) between CaP and BPH in needle prostate biopsies.
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PMID:mRNA expression analysis of human kallikrein 11 (KLK11) may be useful in the discrimination of benign prostatic hyperplasia from prostate cancer after needle prostate biopsy. 1680 Jul 41

Molecular forms of serum PSA (prostate specific antigen) have been developped to improve total PSA sensitivity and specificity in prostate cancer diagnosis and staging. Total PSA is measured in bound (complexed PSA) and unbound (free PSA) molecular forms. Their levels in absolute values and in relation to total PSA (f/t PSA and c/t PSA) have been evaluated. The percentage of free PSA is more specific but less sensitive than tPSA and it is not recommended as a first line diagnostic test. It may be useful as a second-line test, prescribed by the urologist after a first series of negative biopsies. There is general agreement that at high sensitivity, cPSA provides higher specificity compared with tPSA in the gray zone (2-10 ng/ml). Nevertheless the widespread use of tPSA an the small benefit in terms of specificity explains why cPSA is not generally recommanded. Molecular derivates of free PSA have been identified: proPSA (precursor inactive form of PSA), intact PSA (an additionnal form of proPSA that is found intact and inactive), human Kallikrein 2 and BPSA (for benign PSA wich is associated to BPH) have been evaluated. Preliminary studies did not have demonstrate their ability to discriminate between cancer and BPH, and did not define cutoff values.
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PMID:[Molecular forms of PSA]. 1748 11

Formalin-fixed paraffin-embedded (FFPE) prostate specimens are rich sources of molecular pathological information. However, FFPE-based microarray analysis of tissue samples may be hampered by the degradation and chemical alteration of RNA molecules due to the preservation procedure. In this report, we employed a probe analyses of Affymetrix oligonucleotide arrays at individual probe level to compensate for the potential loss of gene identifications associated with compromised mRNA quality in FFPE preparations. Furthermore, to increase the sample quality, we utilized laser capture microdissection of prostate tumor and benign epithelial cells. Remarkably, combination of these approaches recapitulated the common prostate cancer-associated gene expression alteration. Identification of prostate cancer associated-gene expression alterations such as AMACR, Kallikrein gene family and genes associated with androgen signaling such as PDEF and STEAP were consistent with previous findings reported in prostate cancer. These data suggest that combination of laser capture dissection with computational enhancement of microarray data may be useful for the assessment of gene expression changes in FFPE prostate cancer specimens.
Prostate Cancer Prostatic Dis 2008
PMID:Transcriptome analyses of benign and malignant prostate epithelial cells in formalin-fixed paraffin-embedded whole-mounted radical prostatectomy specimens. 1776 22

Numerous efforts exist for developing primary prostate cancer cultures for studying the biology of this tumor entity and for evaluation of the effectiveness of novel therapies. However, there is doubt if cultures that represent the fully differentiated phenotype can be established. The aim of the present study was to characterize primary outgrowing prostate epithelial cells due to their basal or luminal characteristics and their potential for serving as androgen-responsible model. From fresh prostate cancer radical prostatectomy specimens, pieces of approximately 2-4 mm diameter were placed on top of transwell culture chambers, which were coated with matrigel and cultured in prostate epithelial selection medium with 10% fetal calf serum. The monolayer of outgrowing cells was incubated with a physiological concentration of 1 nM dihydrotestosterone (DHT). One group was additionally cultivated without DHT and another group was treated with the 5-alpha-reductase-inbitors MK-368 and MK-905. From the monolayer of the outgrowing cells, RNA was isolated and the expression of androgen receptor (AR), prostate-specific antigen (PSA), Kallikrein 2 (KlK2), prostate-specific membrane antigen (PSMA), and prostate stem cell antigen (PSCA), cytokeratin (CK)5, and CK18 was determined by realtime quantitative PCR. The outgrowing cells from the prostate cancer tissue pieces could be characterized as epithelial cells with basal and transit amplifying characteristics as shown by co-expression of CK5 and CK18. In all cultures, a very low expression of the luminal cell marker genes AR, PSA and KLK2 was measured. The levels of PSCA were clearly higher with a broad variation. Upon cultivation without DHT or treatment with alpha-reductase inhibitors no regulation of AR, PSA and KlK2 was found. Due to the co-expression of basal and luminal marker genes, primary prostate cancer cultures can be charaterized as models of transit amplifying cells of the prostatic epithelium. They do not represent the differentiated secretory androgen-responsive cell phenotype.
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PMID:Primary prostate cancer cultures are models for androgen-independent transit amplifying cells. 2004 8

Kallikrein-related peptidases (KLKs), including KLK5, have been proposed as promising biomarkers for prostate cancer diagnosis and prognosis. In the present study, we report that distinct augmentations (up to 6.4-fold) of KLK5 mRNA expressional levels, calculated via quantitative real-time PCR, occur after treatment of DU145 cells with appropriate concentrations, determined by the MTT method, of docetaxel and mitoxantrone. Our data reveal the endogenous need of prostate cancer cells for modified KLK5 expression to cope with the administration of chemotherapeutic drugs. Furthermore, it is proposed that the expression profile of KLK5 could serve as a putative biomarker for monitoring the treatment response in hormone refractory prostate cancer patients.
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PMID:KLK5 gene expression is severely upregulated in androgen-independent prostate cancer cells after treatment with the chemotherapeutic agents docetaxel and mitoxantrone. 2012 92

Kallikrein-related peptidase 2 (KLK2) degrades insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in vitro. IGFBP-3 forms complexes with IGFs, preventing them from binding to their receptors and stimulating cell proliferation and survival. IGF-independent actions have also been described for IGFBP-3. The degradation of IGFBP-3 by KLK2 or other proteases in the prostate may promote the growth of prostate cancer. We studied IGFBP-3 degradation by immunoblotting and two specific immunoassays, one recognizing only native non-fragmented IGFBP-3 and the other one recognizing both intact and proteolytically cleaved IGFBP-3. Peptides were used to inhibit the enzyme activity of KLK2 and cleavage sites in IGFBP-3 were identified by mass spectrometry. KLK2 proteolyzed IGFBP-3 into several small fragments, mostly after Arg residues, in keeping with the trypsin-like activity of KLK2. The fragmentation could be inhibited by KLK2-inhibiting peptides in a dose-dependent fashion. As degradation of IGFBP-3 could lead to a more aggressive cancer phenotype, inhibition of KLK2 activity might be useful for treatment of prostate cancer and other diseases associated with increased KLK2 activity.
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PMID:Identification of IGFBP-3 fragments generated by KLK2 and prevention of fragmentation by KLK2-inhibiting peptides. 2018 Jun 40

The identification of human tumor antigens has potential utility in the diagnosis and treatment of cancers. We demonstrate here a complete strategy to profile immunoreactivity and identify tumor antigens from proteins derived from tumor cell lines. Microarrays of proteins produced from 2-D LC fractionation of prostate tumor cell-line lysates were used to profile immunoreactivity in the sera of prostate cancer patients and control subjects. Cancer-associated immunoreactivity to distinct groups of chromatography fractions was present in about 50% of the patients, with greater immunoreactivity present in patients with non-organ-confined cancer than in patients with organ-confined cancer. We grouped the immunoreactive fractions by similarities in elution order and patterns of immunoreactivity to guide and interpret the MS analysis of selected fractions, which was used to identify the proteins that may be responsible for the immunoreactivity. As a complementary method to further characterize and validate the immunoreactivity of the proteins identified by mass spectrometry, we demonstrate the use of focused microarrays of recombinant proteins. Disease-associated immunoreactivity was confirmed for one of the identified proteins, human Kallikrein 11. These results demonstrate a practical approach to screening, identifying, and validating immunoreactive proteins that could be applied to diverse studies on humoral immune responses.
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PMID:An experimental strategy for quantitative analysis of the humoral immune response to prostate cancer antigens using natural protein microarrays. 2113 1

Kallikrein-related peptidases 7 and 11 (KLK7/KLK11) share a high degree of structural similarity with PSA (KLK3) and other KLKs. The aim of this study was to evaluate differences in KLK7/ KLK11 expression in paired cancer/benign prostate foci and to determine possible associations with clinicopathological parameters. Seventy archived paraffin-embedded tissue samples obtained from radical prostatectomy were stained for KLK7, KLK11, PSA and PSMA and expression was evaluated semiquantitatively. The results showed statistically significant differences for all studied proteins between BPH and CaP foci. Both KLK7 (P=0.026) and KLK11 (P<0.001) expressions were decreased in prostate cancer cells compared to normal/benign prostate cells. Positive correlations were found for both KLK7 (Rs=0.74, P<0.001) and KLK11 (Rs=0.35, P=0.003) between CaP and BPH. We found a statistically significant upregulation of KLK11 in advanced cases compared to localized ones (P=0.026). For the first time, we report lower expression of KLK11 in CaP compared to BPH and slight upregulation of KLK11 in advanced tumors compared to localized ones. Our observations support the diagnostic potential of KLK7/KLK11 for early prostate cancers but further studies on larger cohorts are needed in order to validate the clinical value of these biomarkers and clarify their biological role in prostate development and tumorigenesis.
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PMID:Immunohistochemical localization and analysis of kallikrein-related peptidase 7 and 11 expression in paired cancer and benign foci in prostate cancer patients. 2152 Sep 85


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