title: Nuclear morphometry, nucleomics and prostate cancer progression.
abstract: Prostate cancer (PCa) results from a multistep process. This process includes initiation, which occurs through various aging events and multiple insults (such as chronic infection, inflammation and genetic instability through reactive oxygen species causing DNA double-strand breaks), followed by a multistep process of progression. These steps include several genetic and epigenetic alterations, as well as alterations to the chromatin structure, which occur in response to the carcinogenic stress-related events that sustain proliferative signaling. Events such as evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis are readily observed. In addition, in conjunction with these critical drivers of carcinogenesis, other factors related to the etiopathogenesis of PCa, involving energy metabolism and evasion of the immune surveillance system, appear to be involved. In addition, when cancer spread and metastasis occur, the 'tumor microenvironment' in the bone of PCa patients may provide a way to sustain dormancy or senescence and eventually establish a 'seed and soil' site where PCa proliferation and growth may occur over time. When PCa is initiated and progression ensues, significant alterations in nuclear size, shape and heterochromatin (DNA transcription) organization are found, and key nuclear transcriptional and structural proteins, as well as multiple nuclear bodies can lead to precancerous and malignant changes. These series of cellular and tissue-related malignancy-associated events can be quantified to assess disease progression and management.
authors.affiliation: Fisher Biomarker & Biorepository Laboratory, The Brady Urological Research Institute, Baltimore, MD 21287, USA. rveltri1@jhmi.edu
authors.forename: Robert W
authors.initials: RW
authors.lastname: Veltri
authors.forename: Christhunesa S
authors.initials: CS
authors.lastname: Christudass
authors.forename: Sumit
authors.initials: S
authors.lastname: Isharwal
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics / Q000473:pathology*; D018450:Disease Progression; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006570:Heterochromatin / Q000235:genetics / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007157:Immunologic Surveillance; D008297:Male; D011379:Prognosis; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D057832:Watchful Waiting
chemical_list: D014408:Biomarkers, Tumor; D006570:Heterochromatin