Reciprocity of exposure time and irradiance on energy density during photoradiation on wound healing in a murine pressure ulcer model.

BACKGROUND: Energy density and exposure time reciprocity is assumed and routinely used in low-level light therapy (LLLT) regimens. This study examined dose reciprocity effects on wound healing. METHODS: Pressure ulcers were created on seven groups of C57/BL mice (n = 18). Photoradiation was administered (18 days; 5 J/cm(2)/day @ 670 nm) using a custom LED apparatus and treatment matrix varying both intensity and exposure. Control animals were treated similarly, without photoradiation. Ulcer staging was performed using a standardized scale. Changes in stage, wound area and wound closure rates were measured. Histology was performed. RESULTS: Photostimulatory effects at day 7 occurred with parameters of 125 seconds @ 40 mW x 1/day; 625 seconds @ 8 mWx1/day; 62.5 seconds @ 40 mWx2/day; and 312.5 seconds @ 8 mWx2/day; and at day 18 using 625 seconds @ 8 mW and 312.5 seconds @ 8 mWx2/day. Statistically significant increases in wound closure rates occurred using 625 seconds @ 8 mW; 62.5 seconds @ 40 mWx2/day; and 312.5 seconds @ 8 mWx2/day treatments. Mean ulcer grade scores were similar to controls. CONCLUSIONS: Varying irradiance and exposure time to achieve a specified energy density affects phototherapy outcomes in this model. Variation of exposure time and irradiance may account for conflicting results in the literature. Further studies of these effects are warranted.

Elevated expression of PCGEM1, a prostate-specific gene with cell growth-promoting function, is associated with high-risk prostate cancer patients.

PCGEM1 is a novel, highly prostate tissue-specific, androgen-regulated gene. Here, we demonstrate that PCGEM1 expression is significantly higher in prostate cancer (CaP) cells of African-American men than in Caucasian-American men (P=0.0002). Further, increased PCGEM1 expression associates with normal prostate epithelial cells of CaP patients with a family history of CaP (P=0.0400). PCGEM1 overexpression in LNCaP and in NIH3T3 cells promotes cell proliferation and a dramatic increase in colony formation, suggesting a biological role of PCGEM1 in cell growth regulation. Taken together, the cell proliferation/colony formation-promoting functions of PCGEM1 and the association of its increased expression with high-risk CaP patients suggest the potential roles of PCGEM1 in CaP onset/progression, especially in these high-risk groups.

Diagnostic potential of prostate-specific antigen expressing epithelial cells in blood of prostate cancer patients.

PURPOSE: Prostate-specific antigen (PSA) test has become a widely used screening test in prostate cancer (CaP). However, low specificity of serum PSA leads to many false-positive and false-negative results and clinical uncertainty. Development of CaP-specific diagnostic and prognostic markers is needed. Detection of circulating PSA-expressing cells (CPECs) in blood and bone marrow of CaP patients has potential in molecular diagnosis and prognosis. Our novel observations of the frequent presence of CPECs in CaP patients with organ-confined disease by reverse transcription (RT)-PCR-PSA assay in epithelial cells enriched from peripheral blood (ERT-PCR/PSA) have led us to test the hypothesis that CPECs have diagnostic potential for CaP. EXPERIMENTAL DESIGN: Epithelial cells from peripheral blood of radical prostatectomy patients or prostate biopsy patients were isolated using antiepithelial cell antibody, Ber-EP4-coated magnetic beads, and total RNA specimens from these cells were analyzed for PSA expression by RT-PCR. RESULTS: Peripheral blood specimens of 108 of 135 (80.0%) CaP patients were positive in ERT-PCR/PSA assay. Peripheral blood specimens from 45 control men were virtually negative (97.8%). In the blinded investigation, 84 patients who had biopsy for suspicion of CaP were evaluated by ERT-PCR/PSA assay. Eighteen of 22 (81.8%) patients with biopsy-proven CaP were positive, and 54 of 62 (87.1%) patients with biopsy negative for CaP were negative in this assay (P < 0.001). CONCLUSIONS: Our study provides intriguing novel results showing that the majority of patients with clinically organ-confined CaP contain CPECs. Strong concordance between the biopsy results and ERT-PCR/PSA assay (sensitivity 81.8%; specificity 87.1%) suggests a potentially new diagnostic application of this type of assay in CaP diagnosis.

Predictors of extracapsular extension and positive margins in African American and white men.

OBJECTIVE: Radical retropubic prostatectomy (RRP) pathology from African American (AA) and White men from 1988 to 1999 was examined to determine if the pre-treatment factors PSA, clinical stage, biopsy grade, age at surgery, and year of surgery (YOS) were predictive of extracapsular extension (ECE) and positive margins for each ethnic group. METHODS: Clinical and pathologic data was collected on 179 AA and 548 white men undergoing RRP from 1988 to 1999 at a tertiary military medical facility. Logistic regression with multivariate analysis was used to determine which pre-operative data-points were predictive of pathologic ECE and positive margins for each ethnic group. RESULTS: PSA, biopsy grade, age, and YOS (more recent years had better surgical pathology) were predictive of ECE for AA and white men. PSA, biopsy grade, and YOS were predictive of positive margins for AA men, while PSA and YOS were predictive of positive margins for white men. PSA continues to be a strong predictor of ECE and positive margins for both AA and white men. However, we describe for the first time, YOS being predictive of ECE and positive margins for both AA and White men, using multivariate regression analysis. CONCLUSION: This is thought to be reflective of the improving public awareness of prostate cancer that has occurred during the PSA-era, resulting in patients participating in screening programs and being diagnosed earlier. Close follow-up of these patients is warranted to determine if the improved pathologic stage of those patients treated more recently translates into improved disease-specific mortality.

Limitations of tissue microarrays in the evaluation of focal alterations of bcl-2 and p53 in whole mount derived prostate tissues.

Several investigators have reported the correlation of p53 and bcl-2 immunoreactivity with post operative prostate specific antigen (PSA) recurrence. Focal and or clustered expression is typical for these biomarkers. The purpose of this study was to compare the effectiveness of tissue microarrays to detect p53 and bcl-2 overexpression and their prognostic significance. Tissue microarrays (TMA) of 99 patients with mean follow-up of 61 months contained 760 samples from 241 carcinomas, 431 benign glands, and 88 foci of prostatic intraepithelial neoplasia (PIN). Overexpression of p53 was seen in 43.3% of 97 patients, whereas bcl-2 overexpression was noted in 23.7% of 97 patients using TMA technology, compared to 66.0% and 26.9%, respectively in the corresponding radical prostatectomy samples. The tissue microarray technology is a powerful tool to study the multifocal and heterogeneous nature of prostate cancer. However, the prognostic value of p53 and bcl-2 could not be confirmed using this technology in contrast to radical prostatectomy sections. The TMA technique is probably more informative and reliable in evaluating the prognostic value of homogeneously expressed biomarkers.

Improved prostate cancer-specific survival and other disease parameters: impact of prostate-specific antigen testing.

OBJECTIVES: To determine how the implementation of prostate-specific antigen (PSA) testing has affected disease-specific survival and other characteristics of prostate cancer. METHODS: Data were collected on all patients with prostate cancer diagnosed between 1988 and 1998 and registered in the Center for Prostate Disease Research Database at Walter Reed Army Medical Center. Statistical analyses were used to summarize trends over time in survival, mortality, and clinical stage. RESULTS: Between 1988 and 1998, a total of 2042 patients with prostate cancer were registered at Walter Reed Army Medical Center. The 5-year disease-specific survival rate was 86.9% and 93.7% for patients diagnosed in the respective year groups of 1988 to 1991 and 1992 to 1994, with follow-up through December 1, 2000 (P < 0.001). Prostate cancer was the cause of death for 37.5% of the patients in 1988 to 1989 versus 15.4% in 1999 to 2000. Marked stage migration has occurred; from 1988 to 1998, the percentage of patients presenting with metastatic disease decreased from 14.1% to 3.3% (P < 0.001). CONCLUSIONS: A statistically significant improved 5-year disease-specific survival and a decreased chance of dying from prostate cancer has occurred after the widespread implementation of PSA. We suspect that PSA testing has resulted in fewer patients presenting with metastatic disease and more patients presenting with localized disease amenable to curative treatment. This portends well for the use of PSA screening to improve outcomes for prostate cancer. However, randomized trials are needed to confirm the improvements in survival and mortality.

Maspin expression profile in human prostate cancer (CaP) and in vitro induction of Maspin expression by androgen ablation.

PURPOSE: Expression of tumor suppressor gene, MASPIN, is associated with inhibition of tumor cell invasion and metastasis. Loss of or decreased expression of Maspin is found frequently in breast and prostate cancer cells. The objective of this study is to investigate Maspin expression in prostate tumor specimens and explore the mechanisms of hormonal regulation of Maspin expression in prostate tumors. EXPERIMENTAL DESIGN: Immunohistochemical staining of Maspin expression was performed on surgical whole-mounted prostate specimens. The expression of Maspin was scored on individual tumors. Correlation of Maspin expression with clinicopathological features was analyzed for statistical significance. Androgen ablation-induced Maspin expression was analyzed by Maspin promoter luciferase reporter assay and quantitative reverse transcription-PCR analysis of endogenous Maspin expression in LNCaP cells in vitro and in animal model. RESULTS: Comprehensive evaluation of Maspin expression profile in multiple tumor foci from whole mounted prostate specimens of prostate cancer patients revealed absence of Maspin expression in a significant fraction (63%). However, Maspin expression is significantly higher in tumor specimens (92%) of patients treated with neoadjuvant androgen ablation therapy before radical prostatectomy. LNCaP cells cultured in androgen-depleted medium show induction of Maspin promoter activity in a promoter luciferase reporter assay. In addition, Maspin expression is increased after castration in LNCaP prostate cancer cells derived tumors in nude mice. CONCLUSIONS: Maspin expression is frequently absent in primary prostate cancers. Up-regulation of MASPIN in response to androgen ablation strongly suggests a physiological role of Maspin in growth inhibition and/or apoptosis of prostate cancer cells during androgen ablation.