Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The identification of 2 or 3 different grades of prostate intraepithelial neoplasia has led to a number of difficult concepts and treatment possibilities. Postmortem examination of the prostates of men over the age of 20, who have died of other causes, mainly road traffic accidents, have been examined and the earliest signs of intraepithelial neoplasia can be seen in some of them. The most common age for prostate cancer to present clinically is between 60 and 65 years and because the majority of men do not develop clinical prostate cancer, there must be a very large number who never progress further than PIN I or II. It is very rare for the early stages of intraepithelial neoplasia to be associated with frank carcinoma. However, it is known that PIN III is frequently found in the presence of carcinoma elsewhere in the gland and this stage is seen as a premalignant development. PIN III in the presence of prostate carcinoma is treated by whatever modality is used to treat the carcinoma. In the absence of carcinoma, there are urologists who consider that it should be regarded as a T1 tumor and radical prostatectomy or radiotherapy with delayed hormonal therapy are definite alternatives. From a certain amount of anecdotal evidence, it seems that the transition from PIN III to a focal carcinoma may take in the order of 2-3 years. Whether this transition can be definitely postponed by the early use of hormonal therapy is not known. Prostate intraepithelial neoplasia may also be treated by other modalities such as anti-angiogenesis agents, gene therapy, anti-metastatic agents, or metalloproteinase inhibitors. The effects of these treatments can be examined histologically by repeated biopsies to ensure that the process remains arrested. If the process of intraepithelial neoplasia can be identified at early stages, dietary modifications may well reduce mitogenic influences and slow down the process or even halt it altogether.
 ...
PMID:PIN I-III: when should we interfere? 1032 14

Several mouse models of human prostate cancer were studied to identify and characterize potential precursor lesions containing foci of atypical epithelial cells. These lesions exhibit a sequence of changes suggesting progressive evolution toward malignancy. Based on these observations, a grading system is proposed to classify prostatic intraepithelial neoplasia (PIN) in genetically engineered mice (GEM). Four grades of GEM PIN are proposed based on their architecture, differentiation pattern, and degree of cytological atypia. PIN I lesions have one or two layers of atypical cells. PIN II has two or more layers of atypical cells. PIN III has large, pleomorphic nuclei with prominent nucleoli and the cells tend to involve the entire lumen with expansion of the duct outlines. PIN IV lesions contain atypical cells that fill the lumen and bulge focally into, and frequently compromise, the fibromuscular sheath. Within the same cohorts, the lower grade PINs first appear earlier than the higher grades. Morphometric and immunohistochemical analyses confirm progressive change. Although the malignant potential of PIN IV in mice has not been proven, GEM PIN is similar to human PIN. This PIN classification system is a first step toward a systematic evaluation of the biological potential of these lesions in GEM.
 ...
PMID:Prostatic intraepithelial neoplasia in genetically engineered mice. 1216 97

GATA transcription factors are essential in mammalian cell lineage determination and have a critical role in cancer development. In cultured prostate cancer cells, GATA2 coordinates with androgen receptor (AR) to regulate gene transcription. In the murine prostate, among six GATA members, GATA2 and GATA3 are expressed. Immunofluorescence staining revealed that both GATA factors predominantly localize in the nuclei of luminal epithelial cells. The pioneer factor FoxA1 is exclusively detected in the luminal cells, whereas AR is detected in both luminal and basal cells. Using genetic engineering, we generated prostate-specific GATA2 and GATA3 knockout (KO) mice. Ablation of single GATA gene had marginal effect on prostate morphology and AR target gene expression, likely due to their genetic compensation. Double KO mice exhibited PIN III to IV lesions, but decreased prostate to body weight ratio, altered AR target gene expression, and expansion of p63-positive basal cells. However, deletion of GATA2 and GATA3 did not reduce the mRNA or protein levels of AR or FoxA1, indicating that GATA factors are not required for AR or FoxA1 expression in adult prostate. Surprisingly, GATA2 and GATA3 exhibit minimal expression in the ventral prostatic (VP) lobe. In contrast, FoxA1 and AR expression levels in VP are at least as high as those in anterior prostatic (AP) and dorsal-lateral prostatic (DLP) lobes. Together, our results indicate that GATA2 and GATA3 are essential for adult murine prostate function and in vivo AR signaling, and the lack of the GATA factor expression in the VP suggests a fundamental difference between VP and other prostatic lobes.
 ...
PMID:The essential role of GATA transcription factors in adult murine prostate. 2737 5