Prostate cancer diagnosis and management

Frydenberg, Mark; Stricker, P.D.; Kaye, Keith W.

doi:10.1016/s0140-6736(96)07393-x

Cited by 86 publications

(58 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…17 One milligram peptide of histone H3 (residues [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] carrying one or two methyl groups at lysine 4 were incubated with 2 lg of GST-LSD1 in the absence or presence of Namoline. The reaction mixture was incubated in demethylation buffer for 4 hr at 37 C and analyzed by mass spectroscopy.…”

Section: Demethylase Assaymentioning

confidence: 99%

Impairment of prostate cancer cell growth by a selective and reversible lysine‐specific demethylase 1 inhibitor

Willmann

Lim

Wetzel

et al. 2012

Intl Journal of Cancer

129

108

View full text Add to dashboard Cite

Post-translational modifications of histones by chromatin modifying enzymes regulate chromatin structure and gene expression. As deregulation of histone modifications contributes to cancer progression, inhibition of chromatin modifying enzymes such as histone demethylases is an attractive therapeutic strategy to impair cancer growth. Lysine-specific demethylase 1 (LSD1) removes mono-and dimethyl marks from lysine 4 or 9 of histone H3. LSD1 in association with the androgen receptor (AR) controls androgen-dependent gene expression and prostate tumor cell proliferation, thus highlighting LSD1 as a drug target. By combining protein structure similarity clustering and in vitro screening, we identified Namoline, a cpyrone, as a novel, selective and reversible LSD1 inhibitor. Namoline blocks LSD1 demethylase activity in vitro and in vivo. Inhibition of LSD1 by Namoline leads to silencing of AR-regulated gene expression and severely impairs androgen-dependent proliferation in vitro and in vivo. Thus, Namoline is a novel promising starting compound for the development of therapeutics to treat androgen-dependent prostate cancer.Prostate cancer is the second leading cause of cancer deaths in Western countries. As long as tumors are prostate confined, they can be efficiently treated by surgery and/or radiation therapy in a curative intent. In cases, however, where the tumor has already disseminated an androgen ablation therapy has to be applied. 1 Patients initially respond to androgen ablation, but tumors become androgen resistant within a period of 12-18 months, 2 after which no curative treatment exists. Thus, the urgent need to identify novel therapeutic targets for the treatment of androgen-resistant prostate cancer is evident.We recently identified lysine-specific demethylase 1 (LSD1), an amine oxidase, as a novel target for prostate cancer therapy. 3 Expression of LSD1 positively correlates with the malignancy of prostate tumors. 3,4 LSD1 functions as a histone demethylase that removes mono-and dimethyl, but not trimethyl marks from either lysine 4 or lysine 9 of histone H3 (H3K4 and H3K9, respectively). 3,5 As a component of corepressor complexes, LSD1 demethylates active methyl marks at H3K4. 5,6 In comparison, when associated with the androgen receptor (AR), the enzyme removes repressive methyl marks from H3K9, thereby enhancing AR-dependent gene expression and prostate tumor cell proliferation. 3 Thus, we hypothesized that selective LSD1 inhibitors are useful precursors for the development of novel drugs for prostate cancer therapy.Previous studies showed that inhibitors of other members of the amine oxidase family also impair the activity of LSD1. 7-13 However, these amine oxidase inhibitors including clorgyline, pargyline, tranylcypromine, polyamines and derivatives thereof, many of them do not selectively target LSD1 and therefore, limits their use as therapeutics owing to potential side effects. In this study, we found a novel and selective LSD1 inhibitor called Namoline by combining protein structure similar...

show abstract

Section: Demethylase Assaymentioning

confidence: 99%

Impairment of prostate cancer cell growth by a selective and reversible lysine‐specific demethylase 1 inhibitor

Willmann

Lim

Wetzel

et al. 2012

Intl Journal of Cancer

129

108

View full text Add to dashboard Cite

show abstract

“…The 5-year survival rate for men with organ-confined disease is almost 100% because of the current treatment options. 1 However, the prognosis becomes much worse when the cancer metastasizes to other organs. Greater than 80% of the patients with advanced prostate cancer will develop secondary lesions within the skeleton, indicating bone as a preferred site for the growth of disseminated disease.…”

mentioning

confidence: 99%

Integrin αv Expression Is Required for the Acquisition of a Metastatic Stem/Progenitor Cell Phenotype in Human Prostate Cancer

Hoogen

Horst

Cheung

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

Integrins participate in multiple cellular processes, including cell adhesion, migration, proliferation, survival, and the activation of growth factor receptors. Recent studies have shown that expression of ␣v integrins is elevated in the prostate cancer stem/progenitor cell subpopulation compared with more differentiated, committed precursors. Here, we examine the functional role of ␣v integrin receptor expression in the acquisition of a metastatic stem/progenitor phenotype in human prostate cancer. Stable knockdown of ␣v integrins expression in PC-3M-Pro4 prostate cancer cells coincided with a significant decrease of prostate cancer stem/progenitor cell characteristics (␣2 integrin, CD44, and ALDH hi ) and decreased expression of invasion-associated genes Snail, Snail2, and Twist. Consistent with these observations, ␣v-knockdown strongly inhibited the clonogenic and migratory potentials of human prostate cancer cells in vitro and significantly decreased tumorigenicity and metastatic ability in preclinical models of orthotopic growth and bone metastasis. Our data indicate that integrin ␣v expression is functionally involved in the maintenance of a highly migratory, mesenchymal cellular phenotype as well as the acquisition of a stem/ progenitor phenotype in human prostate cancer cells with metastasis-initiating capacity. Prostate cancer is the most commonly diagnosed cancer in men and the second leading cause of death. The 5-year survival rate for men with organ-confined disease is almost 100% because of the current treatment options.

show abstract

“…Serum prostate specific antigen (PSA) level and clinico-pathological factors like Gleason score and pT-stage are accepted diagnostic and prognostic factors, which, however, often fail to predict accurately the clinical outcome in individual cases (Frydenberg et al, 1997). Therefore, it is of major importance to further elucidate the molecular aberrations present in this disease.…”

mentioning

confidence: 99%

Expression analysis of imbalanced genes in prostate carcinoma using tissue microarrays

et al. 2006

View full text Add to dashboard Cite

To identify candidate genes relevant for prostate tumour prognosis and progression, we performed an exhaustive gene search in seven previously described genomic-profiling studies of 161 prostate tumours, and four expression profiling studies of 61 tumours. From the resulting list of candidate genes, six were selected for protein-expression analysis based on the availability of antibodies applicable to paraffinised tissue: fatty acid synthase (FASN), MYC, b-adrenergic receptor kinase 1 (BARK1, GRK2) the catalytic subunits of protein phosphatases PP1a (PPP1CA) and PP2A (PPP2CB) and metastasis suppressor NM23-H1. These candidates were analysed by immunohistochemistry (IHC) on a tissue microarray containing 651 cores of primary prostate cancer samples and benign prostatic hyperplasias (BPH) from 175 patients. In univariate analysis, expression of PP1a (P ¼ 0.001) was found to strongly correlate with Gleason score. MYC immunostaining negatively correlated with both pT-stage and Gleason score (Po0.001 each) in univariate as well as in multivariate analysis. Furthermore, a subgroup of patients with high Gleason scores was characterised by a complete loss of BARK1 protein (P ¼ 0.023). In conclusion, our study revealed novel molecular markers of potential diagnostic and therapeutic relevance for prostate carcinoma.

show abstract

Prostate cancer diagnosis and management

Cited by 86 publications

References 75 publications

Impairment of prostate cancer cell growth by a selective and reversible lysine‐specific demethylase 1 inhibitor

Impairment of prostate cancer cell growth by a selective and reversible lysine‐specific demethylase 1 inhibitor

Integrin αv Expression Is Required for the Acquisition of a Metastatic Stem/Progenitor Cell Phenotype in Human Prostate Cancer

Expression analysis of imbalanced genes in prostate carcinoma using tissue microarrays

Contact Info

Product

Resources

About