Introduction Prostate cancer is the most commonly diagnosed male malignancy and the second leading cause of cancer death, representing 29% of all male cancer deaths. Molecular studies are required for creating agents that could treat or prevent prostate cancer at its molecular level. Inhibitor of apoptosis proteins: translating basic knowledge into clinical practice. The parent compound, doxazosin induces cell death via the death receptor mediated apoptotic signaling and inhibition of Akt survival signaling. There is an overwhelming body of evidence suggesting the ability of tumor cells to avoid programmed cellular attrition, or apoptosis, is a major molecular force driving the progression of human tumors. Moreover, the experimental evidence gathered so far points to a potent primary prevention activity of the lead drugs in impairing the onset of prostate tumor development in a xenograft model. The net result is the production of polypeptides, amongst which are growth factors.
Recent biochemical and genetic studies have substantially increased our understanding of death signal transduction pathways, making it clear however, that apoptosis is not a single-lane, one-way street. Maspin was found to be overexpressed in response to hypoxia in prostate cancer cells, but not in benign prostate cells. The role of cytokines and inflammatory response in prostate tumor progression Our current understanding of the contribution of inflammation to the tumorigenic process points to an enticing question: could it be possible that the immune response generated to combat cancer initiation and progression, provides yet another opportunistic interaction within the tumor microenvironment? Chapters highlighting the direct links between cancer researchand clinical applications. Novel quinazoline-based compounds impair prostate tumorigenesis by targeting tumor vascularity. This enhanced sensitivity to hypoxia-induced apoptosis leads to a significant suppression of tumor growth and tumor vascularity in vivo by targeting Akt and focal adhesion kinase activation. The loss of function or deletion of this gene appears to be an early event in prostate cancer.
In contrast, exposure of cells to suramin following irradiation enhanced the cytotoxic effect of ionizing radiation. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. The patients in the present study showed a different pattern of apoptosis positivity compared to other reports. Genetic alterations of this gene, such as deletions and loss of function have been found in a minority of high grade prostate cancers ,. Apoptosis evasion: the role of survival pathways in prostate cancer progression and therapeutic resistance. Emuss,Institute of Cancer Research, London. Hypoxia has been previously linked to the development of both benign prostatic hyperplasia and prostate cancer.
Four areas of prostatic intraepithelial neoplasia also stained positively with a 2+ staining pattern. The major component of senile plaques is a small protein of 39—43 amino acids called amyloid-β Aβ. In reciprocal fashion, prostatic epithelium induces smooth muscle differentiation in the mesenchyme. These findings support a role for bcl-2 expression in conferring androgen-independent growth during prostate cancer progression. Prostate cancer is a heterogeneous disease that often develops from prostatic intraepithelial neoplasia to locally invasive carcinoma and eventually to an aggressive, hormone-refractory metastatic carcinoma Debes and Tindall, 2004; McKenzie and Kyprianou, 2006. The indolent history of this disease led initially to the hypothesis that mutations of the p53 gene would be an infrequent event in this patient population.
It is concluded that targeting Brn-3a could be a useful strategy for controlling the expression of multiple genes that promote CaP. Abstract: Focuses on the functional significance of targeting apoptosis for the treatment of prostate cancer. Suramin has recently surfaced as a potential antineoplastic agent on the basis of its ability to exert a cytostatic effect on human prostate carcinoma cells. Exploitation of quinazolines: lifting Anoikis resistance to impair metastasis. Overexpression of p53 may also control cancer development in that its expression is associated with higher levels of apoptosis in early and late-stage undifferentiated, cancers. These types of advances in prostate cancer research presage an era of new treatment strategies based on an understanding of the cellular and molecular mechanisms of disease. Impairing the route to angiogenesis.
The E-mail message field is required. The ability of tumor microenvironment to alter the apoptotic outcomes of prostate cancer cells is exemplified by recent advances in the understanding of tumor hypoxia. Bcl-2 family also plays a critical role in the androgen-signaling axis operating in prostate cancer cells. Upon cell detachment, anoikis signaling can be activated via three major pathways. These results suggest that treatment of prostate cancer patients with suramin prior to irradiation is likely to inhibit radiation palliation.
Clin Cancer Res 8 11 : 3438— 3444. Anoikis interrupted: survival of the homeless cells. The Ca 2+ homeostasis within cells controls a diversity of cellular processes including gene transcription, proliferation and apoptosis. Its activation is also associated with high histological grade of prostate cancer ,. Normal homeostasis of the prostate gland is maintained by a balance between cell proliferation and apoptosis that is regulated by androgens and growth factors signaling pathways. Reduction of H-Cad transcript level was found in the majority of human prostate cancer cell lines and prostatic adenocarcinoma samples examined.
Kyprianou will be presented with a medallion and certificate at the induction ceremony for new members of the society, which will take place on Thursday, April 11, at the Peabody Institute of the Johns Hopkins University. This volume also provides insightful discussion on the exploitation of the apoptotic and angiogenic synergism towards complete eradication of prostate tumors. Their function is to maintain calcium homeostasis and regulating the cytoskeleton and cell motility. Androgen-independent human prostate cancer cells, however, do not activate this apoptotic pathway of cell death in response to androgen ablation. Moreover, cell lines expressing wild-type p53 showed an increase of the amount of p53 and of its transactivation efficiency. The purpose of this study is to review the recent evidence relating to the initiation and progression of prostate cancer in relation to the familial correlation of the disease, the genetic aberrations resulting in prostate cancer and the new molecular biology data regarding prostate cancer.
Anoikis is a mode of apoptotic cell death, consequential to insufficient cell-matrix interactions and a critical player in tumor angiogenesis and metastasis. A mechanism of Ras-induced resistance to anoikis in intestinal epithelial cells. Its role in hereditary prostate cancer is controversial since there are those who support it , while others have not provided evidence of such a role. It is characterised pathologically by abnormally high levels of neurofibrillary tangles resulting from the accumulation of tau protein in dead and dying neurons, and by elevated numbers of senile plaques in the cortex and hippocampus of the brain. In primary prostate cancer a relatively low incidence 10-20% of p53 gene mutations has been described, however, in advanced stages of the disease the p53 is mutated in 42% of the cases - and it is associated with bone metastases and androgen-independent disease. Executioner caspase-3, -6, and -7 perform distinct, non-redundant roles during the demolition phase of apoptosis.
It may become possible to distinguish between indolent and aggressive types reserving radical treatment for the latter ones. One of the lead drugs of this second generation compounds significantly impaired the metastatic potential in an in vivo prostate metastasis model by specifically targeting tumor vascularity without affecting their proliferative dynamics. Moreover, Trk inhibitors have already been used in phase I clinical trials ;. Other studies have not identified Her-2 neu amplification nor overexpression in prostate cancer ,. Based on family-based linkage analysis, several prostate cancer susceptibility genes have been identified: a. Targeted treatment of prostate cancer. The molecular controls for high cell proliferation of the early stage undifferentiated gastric cancers involve overexpression of both p53 and c-myc.