P. acnes has been isolated from prostatic tissues in men who underwent radical prostatectomy for localized cancer and has been shown to be positively associated with prostatic inflammation. This inflammation may then be linked to the evolution of carcinoma. Furthermore, organisms infecting these patients with prostate cancer differ genetically and phenotypically from the commonly identified cutaneous P. acnes isolates, suggesting that specific subtypes may be involved in development of prostatic inflammation.
A total of 122 specimens of colorectal cancer were re-assessed in relation to the reporting of invasive growth pattern (expanding vs. infiltrating) and presence or absence of peritumoral lymphocytic infiltrate as used in the Jass prognostic classification. Jass agreed with 69% of cases reported as infiltrating and 90% of reported as expanding. This parameter was distributed similarly amongst Dukes B and C cases in the original assessment (P = 0.27), whereas in the reviewed data infiltrating cases were more likely to be staged as Dukes C (P = 0.04). Jass agreed with 44% of lymphocyte present and 94% of lymphocyte absent assessments. The original lymphocyte assessments showed no significant differences in distribution between Dukes A and B cases (P = 0.12) or B and C cases (P = 0.75), whereas the reviewed data showed significant differences for A vs. B (P = 0.015) and B vs. C cases (P = 0.0025). Criteria for assessment were circulated to eight observers who revisited 20 of the cases in which there was disagreement. Consensus agreement with Jass was achieved in nine of 10 cases for invasive growth pattern and seven of 10 cases for lymphocyte infiltration (with two being evenly split). Most observers showed at least fair levels of agreement with Jass and some achieved excellent levels of agreement. This study indicates that assessment of criteria used in the Jass prognostic system for colorectal cancer is less than optimal in routine practice, but is improved through the provision of simple guidelines.
Molecular chaperones of the heat shock protein-90 (Hsp90) family promote cell survival, but the molecular requirements of this pathway in tumor progression are not understood. Here, we show that a mitochondria-localized Hsp90 chaperone, tumor necrosis factor receptor-associated protein-1 (TRAP-1), is abundantly and ubiquitously expressed in human high-grade prostatic intraepithelial neoplasia, Gleason grades 3 through 5 prostatic adenocarcinomas, and metastatic prostate cancer, but largely undetectable in normal prostate or benign prostatic hyperplasia in vivo. Prostate lesions formed in genetic models of the disease, including the transgenic adenocarcinoma of the mouse prostate and mice carrying prostate-specific deletion of the phosphatase tensin homolog tumor suppressor (Pten(pc-/-)), also exhibit high levels of TRAP-1. Expression of TRAP-1 in nontransformed prostatic epithelial BPH-1 cells inhibited cell death, whereas silencing of TRAP-1 in androgen-independent PC3 or DU145 prostate cancer cells by small interfering RNA enhanced apoptosis. Targeting TRAP-1 with a novel class of mitochondria-directed Hsp90 inhibitors, ie, Gamitrinibs, caused rapid and complete killing of androgen-dependent or -independent prostate cancer, but not BPH-1 cells, whereas reintroduction of TRAP-1 in BPH-1 cells conferred sensitivity to Gamitrinib-induced cell death. These data identify TRAP-1 as a novel mitochondrial survival factor differentially expressed in localized and metastatic prostate cancer compared with normal prostate. Targeting this pathway with Gamitrinibs could be explored as novel molecular therapy in patients with advanced prostate cancer.
We found that needle core biopsy was a safe and accurate technique for distinguishing between malignant and benign tumors in small asymptomatic incidentally detected renal masses. Biopsy of small tumors is associated with a relatively high rate of technical biopsy failure, although this may be addressed by adopting improved biopsy techniques, as discussed.
Neuro-endocrine cells are a recognised component of prostatic ducts and acini. Half of all clinically manifest cancers show neuro-endocrine differentiation. Occult carcinomas have a lower incidence of such differentiation. Neuro-endocrine cells are of major prognostic importance and appear more reliable in predicting patients' survival than do conventional histological grading systems.
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