Cancer Metastasis: Building a Framework

In the screening group, 82% of men accepted at least one offer of screening. During a median follow-up of 9 years, the cumulative incidence of prostate cancer was 8.2% in the screening group and 4.8% in the control group. The rate ratio for death from prostate cancer in the screening group, as compared with the control group, was 0.80 (95% confidence interval [CI], 0.65 to 0.98; adjusted P = 0.04). The absolute risk difference was 0.71 death per 1000 men. This means that 1410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent one death from prostate cancer. The analysis of men who were actually screened during the first round (excluding subjects with noncompliance) provided a rate ratio for death from prostate cancer of 0.73 (95% CI, 0.56 to 0.90). Conclusions PSA-based screening reduced the rate of death from prostate cancer by 20% but was associated with a high risk of overdiagnosis. (Current Controlled Trials number, ISRCTN49127736.)

/pdf/screening-and-prostate-cancer-mortality-in-a-randomized-4rctg8nndu.pdf

Screening and Prostate-Cancer Mortality in a Randomized European Study

In multicellular organisms, communication between cells mainly involves the secretion of proteins that then bind to receptors on neighbouring cells But another mode of intercellular communication - the release of membrane vesicles - has recently become the subject of increasing interest Membrane vesicles are complex structures composed of a lipid bilayer that contains transmembrane proteins and encloses soluble hydrophilic components derived from the cytosol of the donor cell These vesicles have been shown to affect the physiology of neighbouring recipient cells in various ways, from inducing intracellular signalling following binding to receptors to conferring new properties after the acquisition of new receptors, enzymes or even genetic material from the vesicles This Review focuses on the role of membrane vesicles, in particular exosomes, in the communication between immune cells, and between tumour and immune cells

Membrane vesicles as conveyors of immune responses

Stromal Fibroblasts Present in Invasive Human Breast Carcinomas Promote Tumor Growth and Angiogenesis through Elevated SDF-1/CXCL12 Secretion

TGFβ in Cancer

Mutation of the Androgen Receptor Causes Oncogenic Transformation of the Prostate

Protein A from Staphylococcus aureus (SpA) has been observed to stimulate the production of human gamma interferon (HuIFN γ) by peripheral blood mononuclear cells (MNC). Dose-response experiments showed donor-to-donor variation in the concentration of SpA required for maximum IFN production although 50 μ g/ml consistently produced near peak IFN γ titers for each donor. Kinetic studies revealed that peak IFNγ production occurred 24 hr after SpA stimulation. Physicochemical and antigenic characterization showed that SpA-induced IFN possessed the characteristics of IFN γ in that it was inactivated by treatment at pH 2, heating at 56 C and anti-HuIFN γ serum but not by anti-HuIFN α serum. Further studies showed that maximum IFN γ production could be achieved by stimulating 5 × 106 MNC/ml and IFN γ could be harvested for 3 successive days by removing IFNγ-containing supernatant fluids and adding fresh medium to stimulated MNC cultures. Preliminary cell fractionation studies suggest that the mononuclea...

Induction of human gamma interferon by protein A from Staphylococcus aureus

In Reply: Re Comparison of Prostate Specific Antigen Concentration Versus Prostate Specific Antigen Density in the Early Detection of Prostate Cancer Receiver Operating Characteristic Curves; Re Selection of Optimal Prostate Specific Antigen Cutoffs for Early Detection of Prostate Cancer Receiver Operating Characteristic Curves

The present invention is directed to methods for inhibiting tumor cell growth, causing tumor regression or eliminating tumor cells in a mammal afflicted with a tumor by administering to a TRAIL-sensitive cell a vector having a DNA expression cassette containing a promoter and a DNA sequence encoding TRAIL, wherein the expression of TRAIL results in tumor inhibition, regression or elimination.

https://ir.uiowa.edu/cgi/viewcontent.cgi?article=1377&context=patents

Method of inducing tumor cell apoptosis using trail/Apo-2 ligand gene transfer

Prostate cancer remains the second leading cause of cancer death among American men. Radiation therapy (RT) is a potentially curative treatment for localized prostate cancer, and failure to control localized disease contributes to the majority of prostate cancer deaths. Neuroendocrine differentiation (NED) in prostate cancer, a process by which prostate adenocarcinoma cells transdifferentiate into neuroendocrine-like (NE-like) cells, is an emerging mechanism of resistance to cancer therapies and contributes to disease progression. NED also occurs in response to treatment to promote the development of treatment-induced neuroendocrine prostate cancer (NEPC), a highly-aggressive and terminal stage disease. We previously demonstrated that by mimicking clinical RT protocol, fractionated ionizing radiation (FIR) induces prostate cancer cells to undergo NED in vitro and in vivo. Here, we performed transcriptomic analysis and confirmed that FIR-induced NE-like cells share some features of clinical NEPC, suggesting that FIR-induced NED represents a clinically-relevant model. Further, we demonstrated that protein arginine methyltransferase 5 (PRMT5), a master epigenetic regulator of the DNA damage response and a putative oncogene in prostate cancer, along with its cofactors pICln and MEP50, mediate FIR-induced NED. Knockdown of PRMT5, pICln, or MEP50 during FIR-inhibited NED sensitized prostate cancer cells to radiation. Significantly, PRMT5 knockdown in prostate cancer xenograft tumors in mice during FIR prevented NED, enhanced tumor killing, significantly reduced and delayed tumor recurrence, and prolonged overall survival. Collectively, our results demonstrate that PRMT5 promotes FIR-induced NED and suggests that targeting PRMT5 may be a novel and effective radiosensitization approach for prostate cancer RT.

Targeting protein arginine methyltransferase 5 (PRMT5) suppresses radiation-induced neuroendocrine differentiation and sensitizes prostate cancer cells to radiation.

Timothy L. Ratliff

Papers

Mutation of the Androgen Receptor Causes Oncogenic Transformation of the Prostate

Induction of human gamma interferon by protein A from Staphylococcus aureus

Method of inducing tumor cell apoptosis using trail/Apo-2 ligand gene transfer

Targeting protein arginine methyltransferase 5 (PRMT5) suppresses radiation-induced neuroendocrine differentiation and sensitizes prostate cancer cells to radiation.