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The prostate (ˈprɒs.teɪt) is both an accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found in all male mammals. It differs between species anatomically, chemically, and physiologically. Anatomically, the prostate is found below the bladder, with the urethra passing through it. It is described in gross anatomy as consisting of lobes and in microanatomy by zone. It is surrounded by an elastic, fibromuscular capsule and contains glandular tissue, as well as connective tissue. The prostate glands produce and contain fluid that forms part of semen, the substance emitted during ejaculation as part of the male sexual response. This prostatic fluid is slightly alkaline, milky or white in appearance. The alkalinity of semen helps neutralize the acidity of the vaginal tract, prolonging the lifespan of sperm. The prostatic fluid is expelled in the first part of ejaculate, together with most of the sperm, because of

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Low-Dose Prostate Cancer Brachytherapy with Radioactive Palladium-Gold Nanoparticles

Marc-André Fortin

Prostate cancer (PCa) is one of the leading causes of death among men. Low-dose brachytherapy is an increasingly used treatment for PCa, which requires the implantation of tens of radioactive seeds. This treatment causes discomfort; these implants cannot be removed, and they generate image artifacts. In this study, the authors report on intratumoral injections of radioactive gold nanoparticles (Au NPs) as an alternative to seeds. The particles (Pd-103:Pd@Au-PEG and Pd-103:Pd@Au-198:Au-PEG; 10-14 nm Pd@Au core, 36-48 nm hydrodynamic diameter) are synthesized by a one-pot process and characterized by electron microscopy. Administrated as low volume (2-4 mu L) single doses (1.6-1.7 mCi), the particles are strongly retained in PCa xenograft tumors, impacting on their growth rate. After 4 weeks, a tumor volume inhibition of 56% and of 75%, compared to the controls, is observed for Pd-103:Pd@Au-PEG NPs and Pd-103:Pd@Au-198: Au-PEG NPs, respectively. Skin necrosis is observed with Au-198; therefore, Au NPs labeled with Pd-103 only are a more advisable choice. Overall, this is the first study confirming the impact of Pd-103@Au NPs on tumor growth. This new brachytherapy procedure could allow tunable doses of radioactivity, administered with smaller needles than with the current technologies, and leading to fewer image artifacts.

Wiley2017

An extended regulatory landscape drives Tbx18 activity in a variety of prostate-associated cell lineages

Christopher Chase Bolt, Soumya Negi

The evolutionarily conserved transcription factor, Tbx18, is expressed in a dynamic pattern throughout embryonic and early postnatal life and plays crucial roles in the development of multiple organ systems. Previous studies have indicated that this dynamic function is controlled by an expansive regulatory structure, extending far upstream and downstream of the gene. With the goal of identifying elements that interact with the Tbx18 promoter in developing prostate, we coupled chromatin conformation capture (4C) and ATAC-seq from embryonic day 18.5 (E18.5) mouse urogenital sinus (UGS), where Tbx18 is highly expressed. The data revealed dozens of active chromatin elements distributed throughout a 1.5 million base pair topologically associating domain (TAD). To identify cell types contributing to this chromatin signal, we used lineage tracing methods with a Tbx18 Cre "knock-in" allele; these data show clearly that Tbx18-expressing precursors differentiate into wide array of cell types in multiple tissue compartments, most of which have not been previously reported. We also used a 209 kb Cre-expressing Tbx18 transgene, to partition enhancers for specific precursor types into two rough spatial domains. Within this central 209 kb compartment, we identified ECR1, previously described to regulate Tbx18 expression in ureter, as an active regulator of UGS expression. Together these data define the diverse fates of Tbx18+ precursors in prostate-associated tissues for the first time, and identify a highly active TAD controlling the gene's essential function in this tissue.

ACADEMIC PRESS INC ELSEVIER SCIENCE2019

Gene expression profiling of the stromal reaction to invasive human breast and prostate cancer

Anne Planche

Primary tumor growth induces host tissue responses that are believed to support and promote tumor progression. Identification of the molecular characteristics of the tumor microenvironment and a deeper knowledge of its crosstalk with tumor cells may therefore be crucial for improving our understanding of the processes implicated in cancer progression, for discovering potential therapeutic targets, and for finding a stromal signature that may predict clinical outcome. To selectively address stromal gene expression changes during cancer progression, oligo-based Affymetrix microarray technology was used to analyze laser-microdissected stromal cells derived from invasive human breast and prostate carcinoma in comparison to their normal counterparts. Statistical analysis of the gene expression profile of breast and prostate stroma revealed genes differentially expressed in tumor stroma compared to normal stroma together with genes common to the stromal reaction in both tumor types. Several up and downregulated genes were validated by quantitative real-time RT-PCR and one common upregulated gene, periostin (POSTN), was validated by immunohistochemistry. The tumor-specific stromal genes as well as common stromal genes were observed to cluster breast and prostate cancer patients into two groups with statistically different clinical outcome. Univariate Cox analysis identified the genes whose expression level was most strongly associated with patient survival. Taken together, these observations provide evidence of the implication of the tumor microenvironment in tumor progression and its survival-predictive value.

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