Biomedical subjects

Jonathan Melamed

Publications and source records attributed to Jonathan Melamed.

22 records · Page 2Linked to original sources

PubMed2002

Heterogeneous expression and functions of androgen receptor co-factors in primary prostate cancer.

The androgen receptor (AR), a ligand-activated transcription factor of the steroid receptor superfamily, plays an important role in normal prostate growth and in prostate cancer. The recent identification of various AR co-factors prompted us to evaluate their possible roles in prostate tumorigenesis. To this end, we analyzed the expression of AR and eight of its co-factors by quantitative in situ RNA hybridization in 43 primary prostate cancers with different degrees of differentiation. Our results revealed nearly constant expression of AR and heterogeneous expression of AR co-factors, with increased expression of PIAS1 and Ran/ARA24, decreased expression of ELE1/ARA70, and no change in TMF1/ARA160, ARA54, SRC1, or TRAP220. Interestingly, whereas TMF1/ARA160, ELE1/ARA70, ARA54, RAN/ARA24, and PIAS1 were preferentially expressed in epithelial cells, another co-factor, ARA55, was preferentially expressed in stromal cells. Although the changes in levels of these co-activators did not correlate with Gleason score, their occurrence in high-grade prostatic intraepithelial neoplasia, suggests their involvement in initiation (or an early stage) of cancer. In addition, human prostate tumor cell proliferation and colony formation were markedly reduced by ELE1/ATRA70. Together, these findings indicate that changes in levels of expression of AR co-factors may play important, yet different, roles in prostate tumorigenesis.

Base Sequence↗

PubMed2002

Followup interval prostate biopsy 3 years after diagnosis of high grade prostatic intraepithelial neoplasia is associated with high likelihood of prostate cancer, independent of change in prostate specific antigen levels.

PURPOSE: Repeat biopsy has been advocated following the diagnosis of high grade prostatic intraepithelial neoplasia to exclude coexisting prostate cancer. We further define the natural history of high grade prostatic intraepithelial neoplasia by determining the incidence of prostate cancer 3 years following diagnosis. MATERIALS AND METHODS: A total of 31 men underwent followup interval biopsy 3 years after high grade prostatic intraepithelial neoplasia diagnosis in 1996 to 1997, regardless of change in serum prostate specific antigen (PSA) or digital rectal examination findings. A single pathologist reviewed all biopsy specimens. All men had a minimum of 12 biopsy cores taken at the time of diagnosis. RESULTS: A 3-year followup interval biopsy eight (25.8%) men had prostate cancer, 11 (35.5%) had high grade prostatic intraepithelial neoplasia only and 12 (38.7%) had no disease. Mean serum PSA at diagnosis and before the followup biopsy was 6.88 and 9.69 ng./dl., respectively (p = 0.008). Of the men 48% had less than a 1.0 unit increase in serum PSA. Upon univariate regression analysis change in serum PSA was not associated with the detection of prostate cancer (p >0.10). All 4 patients who subsequently underwent radical prostatectomy had organ confined disease. CONCLUSIONS: In a high proportion of men with high grade prostatic intraepithelial neoplasia prostate cancer will develop in a 3-year interval. Our findings support the concept that high grade prostatic intraepithelial neoplasia is a precursor to prostate cancer and that repeat biopsy at a delayed interval is recommended regardless of changes in PSA.

Adenocarcinoma↗

PubMed2002

Placental transmogrification of the lung is a histologic pattern frequently associated with pulmonary fibrochondromatous hamartoma.

CONTEXT: Placental transmogrification of the lung is a term introduced to describe a peculiar histologic pattern characterized by formation of placental villuslike structures in the lung parenchyma. It has been reported to occur in association with bullous emphysema and lipomatosis. OBJECTIVES: To study the relationship between placental transmogrification and pulmonary hamartomas. DESIGN AND METHODS: Reports of 38 cases of pulmonary hamartomas during 18 years (1982-1999) were reviewed. All histologic slides of these cases were examined for the presence of villuslike papillary projections and placenta-like structures. Hamartomas with prominent papillary projections or placenta-like structures were further investigated to assess the histogenesis and proliferation of epithelial and stromal cells. Immunohistochemical analysis was performed on paraffin-embedded tissue using monoclonal antibodies against Ki-67 and thyroid transcription factor 1 (TTF-1) and polyclonal antibodies against c-Kit antigen (a stem cell factor receptor/mast cell growth factor receptor) in conjunction with Leder stain for naphthol-ASD-chloroacetate esterase. RESULTS: Placental transmogrification was identified in 6 of 38 cases of pulmonary fibrochondromatous hamartomas. The histologic change consisted of an abundant myxoid or edematous fibroadipose stroma with a respiratory epithelial lining, resulting in papillary projections that resembled immature placental villi. Epithelium lining the papillary projections was positive for TTF-1 (70%-90%) and Ki-67 (3%-5%). In contrast, stromal cells were negative for TTF-1 with only rare cells immunoreactive for Ki-67. A number of stromal spindle cells and occasional cells in epithelium were c-Kit immunoreactive; however, concurrent Leder stain demonstrated that these c-Kit-positive cells were mast cells and not stem cells. CONCLUSIONS: Placental transmogrification is frequently associated with pulmonary fibrochondromatous hamartomas and may be induced by or associated with a proliferation of lining epithelial components in the hamartomas. The significance of numerous mast cells within stroma of placental transmogrification is unclear and their possible role in inducing stromal proliferation needs to be further evaluated.

Aged↗

PubMed2002

Chemoprevention strategies for prostate cancer.

Prostate cancer is the most common male malignancy in western countries. Although primary prevention of prostate cancer is not possible, screening using prostate-specific antigen (PSA) may eliminate prostate cancers by definitive treatments. Prevention of clinically detectable prostate cancer requires earlier chemoprevention interventions. Because prostate cancer is histologically present in 30-50% of 30- to 50-year-old men, effective chemoprevention needs to inhibit not only prostate carcinogenesis but also growth and progression of these cancers. A prostate carcinogenesis animal model has been used to screen chemopreventive agents; inhibitory effects were found with 9-cis-retinoic acid, dehydroepiandrosterone, fluasterone, and the Bowman-Birk inhibitor and an isoflavone mixture which both occur in soy. Such results can be used to select agents for clinical trials. Besides large-scale long-duration prevention trials, trials of short/intermediate duration using smaller cohorts prior to or following radical prostatectomy may provide excellent and cost-effective approaches for chemopreventive agent efficacy testing. Intervention prior to surgery allows measurements of intervention agents and intermediate end-points in the prostate. These peri-surgical trials only assess inhibition of growth and progression of preexisting cancer, not real preventive effects, but they focus on clinically significant cancers. Such trials are an essential step in the development of antiprostate cancer chemoprevention agents.

Adenocarcinoma↗