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Michael M Lieber

Publications and source records attributed to Michael M Lieber.

44 records · Page 3Linked to original sources
PubMed2002

Mapping and gene expression profile of the minimally overrepresented 8q24 region in prostate cancer.

We have recently reported that overrepresentation of 8q24 (c-myc) is associated with clinical progression in prostate cancer. In this study, we map the boundaries of the overrepresented region within 8q23-q24 using interphase fluorescent in situ hybridization analysis of paraffin-embedded prostate cancer specimens. One hundred primary prostate cancers and three prostate cancer cell lines were evaluated, and the minimally overrepresented region could be narrowed to the approximately 8.2-Mb region between D8S514 and H47317. This region includes c-myc and is wholly within 8q24. Eukaryotic translation initiation factor 3 subunit 3 does not seem to be overrepresented independent of c-myc in prostate cancer. The cell lines PC3 and DU145 have and do not have 8q24 overrepresentation, respectively. We then selected 39 expressed sequence tags (ESTs) within and surrounding the minimally overrepresented region and performed expression analysis using Northern blot hybridization. Five ESTs/genes including c-myc were overexpressed in both the PC3 cell line and DU145, but the PC3 to DU145 expression ratios were <2. Seven ESTs were overexpressed twofold or more in PC3 compared to DU145. This group included hyaluronan synthase 2, nephroblastoma-overexpressed gene, eukaryotic translation initiation factor 3 subunit 3, and an EST (R69368) encoding a hypothetical protein (BM009). These seven genes as well as c-myc are candidate target genes within the overrepresented 8q24 region and their overexpression may be associated with prostate cancer progression.

Blotting, Northern↗
PubMed2002

Prevalence of prostatitis-like symptoms in a community based cohort of older men.

PURPOSE: We describe a community based study to estimate the prevalence of prostatitis-like symptoms using questions similar to the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). MATERIALS AND METHODS: Study subjects were a randomly selected sample of Olmsted County, Minnesota white men 40 to 79 years old in January 1990 who participated in a longitudinal study of lower urinary tract symptoms. Subjects were evaluated biennially using self-administered questionnaires. In 2000 questions similar to the NIH-CPSI were incorporated into the questionnaire and questionnaire responses were used to categorize men as having prostatitis-like symptoms. RESULTS: Of 1,541 men 182 (12%) had at least 1 urogenital pain symptom. Pubic (76 men, 4.9%) and testicular (73, 4.7%) pain were the most frequent pain symptoms. A total of 34 men with prostatitis-like symptoms (2.2%) had higher mean pain (6.7 versus 0.5), urinary symptom (3.5 versus 2.1) and quality of life impact (3.7 versus 1.9) scores compared to men who did not (all p <0.001). Pain frequency (OR 39.2, 95% CI 18.8, 81.9) and pain intensity (OR 21.5, 95% CI 8.7, 52.9) were more strongly associated with prostatitis-like symptoms than urinary symptom score (OR 2.8, 95% CI 1.4, 5.6) or quality of life impact score (OR 4.5, 95% CI 1.9, 10.7). CONCLUSIONS: Although urogenital pain is common among community dwelling men, prostatitis-like symptoms based on the modified questions from the NIH-CPSI are less common. While pain measures may be useful in distinguishing between men with and without prostatitis-like symptoms, the urinary symptom and quality of life impact scores could partly reflect benign prostatic hyperplasia.

Adult↗
PubMed2002

Trends and risk factors for prostate biopsy complications in the pre-PSA and PSA eras, 1980 to 1997.

OBJECTIVES: To assess the secular trends in postbiopsy complications and to identify the risk factors for complications. METHODS: Olmsted County residents who underwent a prostate biopsy between 1980 and 1997 were identified. All community medical records for the study subjects were reviewed to identify prostate biopsy-related complications, including gross hematuria, infection, pain, hematospermia, and acute urinary retention. RESULTS: Of the 2258 prostate biopsies, 377 (17%) were associated with at least one complication. The total complication rate per biopsy remained relatively consistent at about 17% from 1980 to 1986, 1987 to 1992, and 1993 to 1997 (P for trend = 0.8). The age-adjusted complication rate (per 100,000 men) increased from 26 to 60 in 1980 to 1986 and 1993 to 1997, respectively (P <0.001). This paralleled the increase in prostate biopsy use from 138 to 374 per 100,000 men in the same periods. The prevalence (per biopsy) of gross hematuria increased, 7.5% to 12.8% (P = 0.04); postbiopsy infection declined, 4.6% to 1.4% (P = 0.001); and hospitalization for infection declined, 1.2% to 0.2% (P = 0.06) between 1980 to 1986 and 1993 to 1997. A urogenital infection 6 weeks before biopsy was associated with an increased risk of a postbiopsy complication (odds ratio = 1.7, 95% confidence interval = 1.0 to 2.8) and an increased risk of a postbiopsy infection (odds ratio = 5.5, 95% confidence interval = 2.2 to 13.8). CONCLUSIONS: Although the complications per biopsy have stayed constant, the prevalence of postbiopsy complications in the community has increased tremendously because of the increased use of prostate biopsies. Specific strategies may be needed to reduce the incidence of postbiopsy infection in men with a recent urogenital infection before biopsy.

Age Factors↗
PubMed2002

Loss of p53 and c-myc overrepresentation in stage T(2-3)N(1-3)M(0) prostate cancer are potential markers for cancer progression.

To determine whether genetic changes are markers of cancer progression and patient survival in Stage T(2-3)N(1-3)M(0) prostatic carcinoma, we compared 26 patients who died of tumor relapse after prostatectomy and lymphadenectomy (case group) with 26 matched patients who were alive at the time of the matched case's death (control group). Nine unmatched cases were also included in this study. In 37 cases, paired primary tumors (119 foci) and lymph node metastases (114 foci) were available for study. Fluorescence in situ hybridization (FISH) with centromere-specific probes for chromosomes 7, 8, and 17 and region-specific probes for D7S486 (7q31), c-myc (8q24), LPL (8p22), and p53 (17p13) was performed on available primary carcinomas and lymph node metastases. In primary tumor foci, +7q31, -8p22, +c-myc, substantial additional increases of myc (AI-c-myc), and -p53 were observed in 65%, 74%, 43%, 29%, and 31% of foci, respectively. AI-c-myc was strongly associated with higher cancer Gleason score (P =.003). Heterogeneity of genetic changes was frequently observed among multiple cancer foci. Lymph node metastases of prostate cancer usually shared genetic changes with paired primary tumors. In addition, the genetic change pattern with -8p, +c-myc or AI-c-myc, +7q, and +p53 was slightly higher in lymph node metastases (22%) than in primary tumors (6%) (P =.08). In matched case and control patients, simultaneous gain of 7q31 (+7q31) and CEP7 (+CEP7) was identified in 59% and 68% of specimens for case and control groups, respectively (P =.48). Loss of 8p22 (-8p22) was identified in 77% and 69% of specimens for case and control groups, respectively (P = 1.0). Simultaneous gain of c-myc (+c-myc) and CEP8 (+CEP8) without overt additional increase of c-myc copy number relative to CEP8 copy number, was identified in 38% and 54% of specimens for case and control groups, respectively (P =.27). AI-c-myc was identified in 54% and 23% of specimens for case and control groups, respectively (odds ratio = 3.0, P =.06). Loss of p53 (-p53) was identified in 46% and 15% of specimens for case and control groups, respectively (odds ratio = 4.0, P =.04). Our results indicate that FISH anomalies are very common in both primary tumors and lymph node metastases of Stage T(2-3)N(1-3)M(0) prostate cancer; that AI-c-myc is associated with higher cancer Gleason score; that AI-c-myc and -p53 are associated with prostate cancer progression and are potential markers of survival in Stage T(2-3)N(1-3)M(0) prostate cancer; and that lymph node metastases usually have similar or additional genetic changes compared with primary tumors, and multiple lymph node metastases usually have similar genetic changes.

Aged↗
PubMed2002

A population-based study of daily nonsteroidal anti-inflammatory drug use and prostate cancer.

OBJECTIVE: To investigate the association between daily use of nonsteroidal anti-inflammatory drugs (NSAIDs) and prostate cancer. PATIENTS AND METHODS: Subjects were 50- to 79-year-old white men randomly selected in January 1990 from the Olmsted County, Minnesota, community (n=1362) from among participants in a longitudinal study of lower urinary tract symptoms. At the beginning of the study, all medications that were used daily, including prescription and nonprescription NSAIDs, were ascertained by trained interviewers. Men who developed a histologically proved diagnosis of prostate cancer during a median of 66 months (maximum, 6 years) of follow-up were identified from a complete review of the community medical record. RESULTS: Twenty-three (4%) of 569 NSAID users and 68 (9%) of 793 nonusers developed prostate cancer during follow-up (P=.001). The relative odds of prostate cancer were 0.45 (95% confidence interval [CI], 0.28-0.73) in NSAID users compared with nonusers. This inverse association with NSAID use increased with increasing age at study onset. Thus, the relative odds of prostate cancer among NSAID users were 0.9 (95% CI, 0.4-2.2) in men aged 50 to 59 years, 0.4 (95% CI, 0.2-0.8) in men aged 60 to 69 years, and 0.2 (95% CI, 0.1-0.5) in men aged 70 to 79 years compared with similarly aged men who did not use NSAIDs. CONCLUSION: The study findings suggest that daily use of NSAIDs may be associated with a lower incidence of prostate cancer in men aged 60 years or older. The stronger effect among older men suggests that NSAIDs may prevent the progression of prostate cancer from latent to clinical disease.

Age Distribution↗
PubMed2002

A comparison of BTA stat, hemoglobin dipstick, telomerase and Vysis UroVysion assays for the detection of urothelial carcinoma in urine.

PURPOSE: We determine the sensitivity and specificity of various assays for the detection of urothelial carcinoma. MATERIALS AND METHODS: A total of 280 voided urine specimens from 265 patients were obtained immediately before cystoscopy for BTA stat, (Bard Diagnostic, Redmond, Washington) hemoglobin dipstick, (Bayer, Elkhart, Indiana) telomerase and UroVysion (Vysis, a wholly owned subsidiary of Abbott Laboratories, Abbott Park, Illinois) analysis. RESULTS: Of the 265 patients 75 had biopsy proven urothelial carcinoma, and the sensitivity of the assays was determined from these patients. From most sensitive to least sensitive, the overall sensitivity of UroVysion (73 cases), BTA stat (72), hemoglobin dipstick (73) and telomerase (70) was 81%, 78%, 74%, and 46%, respectively. Each of the first 3 tests was statistically significantly more sensitive than the telomerase assay (p <0.05). However, the differences in overall sensitivity of UroVysion, BTA stat and hemoglobin dipstick were not statistically significant. The specificity of the tests was calculated for 80 of the 265 patients in this study who had no history of urothelial carcinoma and negative cystoscopy findings despite common urological complaints. From most specific to least specific, the specificity of UroVysion, telomerase, BTA stat and hemoglobin dipstick was 96%, 91%, 74% and 51%, respectively. UroVysion and telomerase were statistically significantly (p <0.01) more specific than the BTA stat and hemoglobin dipstick assays, and all of the assays were more specific than hemoglobin dipstick testing (p <0.001). CONCLUSIONS: Our study reveals that UroVysion is the most sensitive and specific assay among those tested for the detection of urothelial carcinoma. Telomerase testing had good specificity but poor sensitivity. The BTA stat and hemoglobin dipstick tests had good sensitivity but relatively poor specificity. UroVysion is a promising new assay for the detection of urothelial carcinoma in urine specimens. However, further studies are needed to explore the role of the various assays in the treatment of patients with superficial urothelial carcinoma.

Adult↗
PubMedDate not supplied

Towards an understanding of the role of forces in carcinogenesis: a perspective with therapeutic implications.

Carcinogenesis may aberrantly have as its source an underlying dynamic which likely operates in accord with or is expressive of a universal principle of force. This drive can be seen as a type of necessary completion of force configurations giving forth a force-based, completing guidance or dyneotaxis. This completing guidance is a completing communication. Aberrations of this drive can manifest as incomplete communication arising from incomplete or non-uniform force-configurations throughout different levels of organization within the organism. Such non-uniformities of force-configuration manifest themselves through intra- and intercellular distortion. This is represented by changes or distortions within cellular and tissue architecture, or shape, occurring through and enabling a non-uniform loosening. Cycles of non-uniform loosening and distortion would generate a progressive disruption or aberration in an otherwise further adhesively completing, thereby further stabilizing, dyneotaxis. Carcinogenesis ensues as an aberrant means to re-establish a uniformity or symmetry of adhesive and mechanical forces in such tissues, and within the genome. However, it rather results in a further loosening-based reorganization or reshaping. This would be a manifestation of a still further non-uniformity of forces. Uncontrolled mutagenesis, itself stemming from genomic distortion, is also seen as a process that could lead to loosening and further distortion throughout the cell, and thereby, a contributor to carcinogenesis if a transcellular, globally completive or uniform adhesiveness cannot be maintained. A therapeutic approach could be employed to reverse such a cycle of loosening and distortion within cellular and tissue organization. The developmental reversal of carcinogenesis would be the consequence. Such an approach could be through the application of a coherent, uniform and united array of guiding mechanical and electromagnetic forces. The deeper consequence would be the re-establishment of a global, cancer-countering, uniform or symmetrical, guiding adhesiveness via and dependent on a complete and non-distorted network of cellular and intercellular structures, further completing, and thus further stabilizing, such structures in the process.

Biomechanical Phenomena↗