Search PubMed⌕ Search

Biomedical subjects

Dan H Moore

Publications and source records attributed to Dan H Moore.

At least 37 records · Page 2Linked to original sources
PubMed2004

Id-1 and Id-2 proteins as molecular markers for human prostate cancer progression.

PURPOSE: Id proteins are dominant-negative regulators of basic helix-loop-helix transcription factors that control malignant cell behavior in many different tissues. This study aimed to identify the potential role of Id-1 and Id-2 proteins as molecular makers for prostate cancer progression. EXPERIMENTAL DESIGN: Using the technique of immunohistochemistry, we determined Id-1 and Id-2 expression in a panel of 67 human prostate biopsies. We also manipulated Id-1 and Id-2 expression in LNCaP and PC3 prostate cancer cell lines and determined the effects on invasion in vitro, matrix metalloproteinase secretion, and proliferation. RESULTS: Both Id-1 and Id-2 proteins were up-regulated during human prostate cancer progression in vivo and were overexpressed in highly aggressive prostate cancer cells. In vitro, constitutive expression of Id-1, and to a lesser extent Id-2, converted nonaggressive LNCaP prostate cancer cells into more proliferative and invasive cells and increased their secretion of matrix metalloproteinases. Conversely, the down-regulation of Id-2 expression in highly metastatic PC3 cells reduced their growth potential and invasiveness. CONCLUSIONS: We propose that both Id-1 and Id-2 proteins control prostate cancer cell phenotypes and could serve as molecular markers of aggressive human prostate cancer.

Biomarkers, Tumor↗
PubMed2004

High-resolution analysis of DNA copy number alterations in colorectal cancer by array-based comparative genomic hybridization.

Array-based comparative genomic hybridization (CGH) allows for the simultaneous examination of thousands of genomic loci at 1-2 Mb resolution. Copy number alterations detected by array-based CGH can aid in the identification and localization of cancer causing genes. Here we report the results of array-based CGH in a set of 125 primary colorectal tumors hybridized onto an array consisting of 2463 bacterial artificial chromosome clones. On average, 17.3% of the entire genome was altered in our samples (8.5 +/- 6.7% gained and 8.8 +/- 7.3% lost). Losses involving 8p, 17p, 18p or 18q occurred in 37, 46, 49 and 60% of cases, respectively. Gains involving 8q or 20q were observed 42 and 65% of the time, respectively. A transition from loss to gain occurred on chromosome 8 between 41 and 48 Mb, with 25% of cases demonstrating a gain of 8p11 (45-53 Mb). Chromosome 8 also contained four distinct loci demonstrating high-level amplifications, centering at 44.9, 60, 92.7 and 144.7 Mb. On 20q multiple high-level amplifications were observed, centering at 32.3, 37.8, 45.4, 54.7, 59.4 and 65 Mb. Few differences in DNA copy number alterations were associated with tumor stage, location, age and sex of the patient. Microsatellite stable and unstable (MSI-H) tumors differed significantly with respect to the frequency of alterations (20 versus 5%, respectively, P < 0.01). Interestingly, MSI-H tumors were also observed to have DNA copy number alterations, most commonly involving 8q. This high-resolution analysis of DNA copy number alterations in colorectal cancer by array-based CGH allowed for the identification of many small, previously uncharacterized, genomic regions, such as on chromosomes 8 and 20. Array-based CGH was also able to identify DNA copy number changes in MSI-H tumors.

Chromosome Mapping↗
PubMed2004

Cytology of ductal lavage fluid of the breast.

The cytologic evaluation of nipple aspirate fluids has been shown to identify women at increased risk for developing breast cancer. One limitation of this assay is the often scant cellularity of the specimen. An improved technique, ductal lavage, utilizes a microcatheter inserted into individual breast ducts to collect large numbers of cells for cytologic evaluation. Epithelial cells in ductal lavage fluids can be categorized as benign, malignant, or showing mildly or markedly atypical changes. The cell characteristics which were most helpful in identifying abnormal cells were related to cell arrangement, cell size, nuclear size, and size variation, nuclear membrane irregularity, chromatin granularity, and the presence of large nucleoli. Cell size, nuclear size variation, and large nucleoli were the most robust features, as determined by agreement between two pathologists. Moderate cell enlargement and the presence of large nucleoli were the features selected by structured tree analysis for classifying the specimens into the diagnostic groups. The similarity of the cytology of ductal lavage fluid to nipple aspirate fluid strongly suggests that these specimens will also be useful for predicting breast cancer risk.

Body Fluids↗
PubMed2004

Amyotrophic lateral sclerosis: delayed disease progression in mice by treatment with a cannabinoid.

Effective treatment for amyotrophic lateral sclerosis (ALS) remains elusive. Two of the primary hypotheses underlying motor neuron vulnerability are susceptibility to excitotoxicity and oxidative damage. There is rapidly emerging evidence that the cannabinoid receptor system has the potential to reduce both excitotoxic and oxidative cell damage. Here we report that treatment with Delta(9)-tetrahydrocannabinol (Delta(9)-THC) was effective if administered either before or after onset of signs in the ALS mouse model (hSOD(G93A) transgenic mice). Administration at the onset of tremors delayed motor impairment and prolonged survival in Delta(9)-THC treated mice when compared to vehicle controls. In addition, we present an improved method for the analysis of disease progression in the ALS mouse model. This logistic model provides an estimate of the age at which muscle endurance has declined by 50% with much greater accuracy than could be attained for any other measure of decline. In vitro, Delta(9)-THC was extremely effective at reducing oxidative damage in spinal cord cultures. Additionally, Delta(9)-THC is anti-excitotoxic in vitro. These cellular mechanisms may underlie the presumed neuroprotective effect in ALS. As Delta(9)-THC is well tolerated, it and other cannabinoids may prove to be novel therapeutic targets for the treatment of ALS.

Age Factors↗
PubMed2004

ALSFRS-R.

The ALSFRS-R is an attractive primary outcome measure in clinical trials of ALS because it is validated, easy to administer, minimizes dropout, reduces cost, and correlates with survival. Unlike the other standard outcome measures currently employed, the ALSFRS-R is also a measure of global function.

Activities of Daily Living↗
PubMed2004

Improving efficiency of ALS clinical trials using lead-in designs.

We describe designs for clinical trials in ALS including two that are more efficient than the standard two-arm, parallel design. The more efficient designs incorporate a lead-in period followed by a randomized intervention (drug or placebo) period. Efficacy of the more efficient designs is based on measuring, within each patient, the difference in slope while on the new treatment compared to the lead-in period. We demonstrate, with sample size calculations, that the lead-in designs are considerably more efficient than the standard two-arm, parallel design. Sample sizes can be reduced by 44% for a 12-month study using ALSFRS rate of decline as a primary endpoint for a two-arm trial with 4 months lead-in compared to a parallel design. A sample size reduction of 70% can be realized with variable lead-in compared to a parallel design.

Amyotrophic Lateral Sclerosis↗
PubMed2003

Characteristics associated with recurrence among women with ductal carcinoma in situ treated by lumpectomy.

BACKGROUND: Clinical and histopathologic characteristics that may predict risks of recurrence in women with ductal carcinoma in situ (DCIS) have not been consistently identified. We identified factors associated with recurrence as DCIS versus invasive breast cancer and determined the 5-year absolute risks of recurrence as a function of these factors. METHODS: We conducted a population-based cohort study among 1036 women in the San Francisco Bay Area who were aged 40 years or older when diagnosed with DCIS and treated by lumpectomy alone from January 1983 through December 1994. Standardized pathology reviews were conducted to determine disease recurrence, defined as DCIS or invasive breast cancer diagnosed in the ipsilateral breast containing the initial DCIS lesion or at a distant site more than 6 months after the initial diagnosis and treatment of DCIS. Conditional logistic regression models were used to determine factors associated with recurrence. All statistical significance tests were two-sided. RESULTS: During a median follow-up of 77.9 months, 209 women (20.2%) experienced a recurrence. Overall, the 5-year risks of recurrence as invasive cancer and as DCIS were 8.2% (95% confidence interval [CI] = 6.6% to 9.8%) and 11.7% (95% CI = 9.9% to 13.3%), respectively. The 5-year risks of recurrence as invasive cancer and as DCIS were 4.8% (95% CI = 3.7% to 6.8%) and 4.8% (95% CI = 3.8% to 5.8%), respectively, for women with low-nuclear-grade DCIS; 11.8% (95% CI = 9.9% to 14.1%) and 17.1% (95% CI = 15.5% to 18.7%), respectively, for women with high-nuclear-grade DCIS; 11.6% (95% CI = 11.3% to 12.0%) and 8.6% (95% CI = 7.1% to 10.2%), respectively, for women whose initial DCIS lesion was detected by palpation; and 6.6% (95% CI = 6.2% to 7.1%) and 14.1% (95% CI = 11.4% to 17.8%), respectively, for women with DCIS detected by mammography alone. High- (versus low-) nuclear-grade DCIS lesions and detection of the initial DCIS lesion by palpation (versus mammography) were associated with recurrence as invasive cancer. High- (versus low-) nuclear-grade lesions; resection margins that were positive, uncertain, or less than 10 mm disease-free (versus > or = 10 mm disease-free); and age 40-49 years at diagnosis (versus > or =50 years) were associated with recurrence as DCIS. CONCLUSIONS: Nuclear grade is strongly associated with recurrence but not with the type of recurrence. Women with high-nuclear-grade DCIS or DCIS detected by palpation who are treated by lumpectomy alone are at relatively high risk of having an invasive breast cancer recurrence, compared with women with low-nuclear-grade or mammographically detected DCIS, and may be appropriate candidates for additional treatment.

Adult↗
PubMed2003

Cyclooxygenase-2 expression is related to nuclear grade in ductal carcinoma in situ and is increased in its normal adjacent epithelium.

Cyclooxygenase-2 (COX-2) is emerging as an important cancer biomarker and is now an experimental target for solid tumor treatment.However, no study has exclusively focused on COX-2 expression in early lesions such as ductal carcinoma in situ (DCIS). We examined COX-2 expression by immunohistochemistry in 46 cases of women undergoing surgical resection for DCIS. We found that COX-2 expression was detected in 85% of all DCIS specimens, with increased COX-2 staining correlating with higher nuclear grade. Strikingly, COX-2 staining intensity in the normal adjacent epithelium was stronger than in the DCIS lesion itself. Our observations demonstrate that COX-2 is up-regulated in the normal adjacent epithelium and supports the hypothesis that the surrounding epithelial tissue is part of the disease process in DCIS.

Adult↗
PubMed2003

Multi-endpoint biological monitoring of phosphine workers.

The pesticide phosphine (PH(3)) is a suspected carcinogen and a known clastogen which has been shown to produce chromosome damage in agricultural workers. To confirm and extend these results we evaluated 22 phosphine appliers and 26 controls matched for age and smoking status. Two independent methods were used to evaluate exposure: fluorescence in situ hybridization (FISH) with whole-chromosome paints of chromosomes 1, 2, and 4 labeled in a single color to quantify translocations in peripheral lymphocytes, and the glycophorin A (GPA) assay to quantify phenotypically mutant (NØ or NN) erythrocytes. No differences in the frequency of translocations were found in the phosphine appliers compared to the controls, and no effect of cigarette smoking was observed. However, a significant increase in the frequency of translocations with age (P<0.0001) was seen. No effect of phosphine exposure or cigarette smoking was observed in the GPA assay. These results are in contrast to previous findings from this same population which showed an increase in chromosome aberrations among phosphine appliers. The results are most easily interpreted as supporting the effectiveness of the personal protective equipment that is now worn by the workers but which was not employed prior to and during the earlier studies.

Adult↗
PubMed2003

Geographic excess of estrogen receptor-positive breast cancer.

Elevated and more rapidly increasing breast cancer incidence rates have been described for Marin County, California (CA), a homogeneous, high socioeconomic status population for which yearly surveillance is facilitated by its status as a county. The present study evaluates the histology and hormonal phenotype of the excess breast cancer cases occurring in white, non-Hispanic women living in Marin County between 1992 and 2000 and compares them with patterns occurring in the rest of the San Francisco Bay Area (SFBA) and other urban parts of CA. Incidence data for invasive breast cancer histological subtypes and estrogen receptor (ER) and progesterone receptor (PR) status were obtained from the 1992-2000 Surveillance, Epidemiology, and End Results program. Expected numbers for Marin County were computed based on age-specific rates for five other SFBA counties. Incidence rates were age-adjusted to the 2000 United States standard. Marin County breast cancer diagnoses during 1992-2000 compared with other SFBA and other urban CA Surveillance, Epidemiology, and End Results county rates for white, non-Hispanic women consisted of a disproportionate increase in ER+/PR+ tumors. The observed absolute excess (versus expected) numbers of Marin County ER+/PR+ lobular and nonlobular (predominantly ductal) cases were similar; however, the relative increase appeared greatest for lobular breast cancer. The progressive increase in breast cancer incidence rates observed in Marin County over the past decade is occurring in women with high prevalence of risk factors predisposing toward excess development of ER+/PR+ breast cancer.

Adult↗
PubMed2002

Causes of physician delay in the diagnosis of breast cancer.

BACKGROUND: Understanding sources of physician delay in diagnosis of breast cancer will assist efforts to expedite diagnosis. OBJECTIVE: To test whether increased reliance on screening mammography has affected causes of physician delay in diagnosis of breast cancer. DESIGN: Survey of delays in a case series. SETTING: Practice specializing in breast diseases in a region with high use of screening mammography. PATIENTS: Four hundred thirty-five consecutive patients treated for 454 breast cancers of any stage. INTERVENTION: Customary patient care. MAIN OUTCOME MEASURES: Whether delay was related to how cancer was identified, patient age, individual cancer characteristics (such as tumor type), mammography reports, or physician expertise. RESULTS: Twenty-one women (5%) were inappropriately reassured that a malignant lump was benign without biopsy, 14 women (3%) had a misread mammogram, 4 women (1%) had a misread pathologic finding, and 5 women (1%) had cancer missed by a poorly performed fine-needle aspiration biopsy. Delay was associated with a benign mammography report (relative risk, 10.8; 95% confidence interval, 5.1-22.8), a woman finding her own mass (relative risk, 3.3; 95% confidence interval, 1.8-6.2), and current hormone replacement therapy (relative risk, 3.1; 95% confidence interval, 1.2-8.5). CONCLUSIONS: The leading cause of physician delay in diagnosis of breast cancer continues to be inappropriate reassurance that a mass is benign without biopsy. Reducing delay in diagnosis will require less willingness to rely on clinical examination to decide that a mass is benign, less reliance on benign mammography reports to decide not to biopsy a mass, and a requirement that fine-needle aspiration biopsy be done by persons with demonstrated competence for the procedure.

Adult↗
PubMed2002

Array-based comparative genomic hybridization for the differential diagnosis of renal cell cancer.

Array-based comparative genomic hybridization (CGH) uses multiple genomic clones arrayed on a slide to detect relative copy number of tumor DNA sequences. Application of array CGH to tumor specimens makes genetic diagnosis of cancers possible and may help to differentiate relevant subsets of tumors, biologically and clinically, which would allow better prognostic and therapeutic decision making. In this study, we have used array-based CGH to detect DNA copy number alterations in distinct types of renal cell carcinomas for diagnostic purposes. We were able to correctly diagnose 33 of 34 malignant tumors by automated computational means and to group together eight benign neoplasms and normal kidney samples. These results indicate that array-based CGH is capable of diagnosing the vast majority of renal cell carcinomas based on their genetic profiles.

Carcinoma, Renal Cell↗
PubMed2002

Increased risk of local recurrence is associated with allelic loss in normal lobules of breast cancer patients.

Allelic losses characteristic of tumor cells, when displayed by morphologically normal terminal ductal lobular units (TDLUs) adjacent to carcinoma [G. Deng et al., Science (Wash. DC), 274: 2057-2059, 1996], may indicate an extended field of increased cancer susceptibility within the affected breast tissue. We investigated this possibility by asking whether the presence of loss of heterozygosity (LOH) at chromosome 3p11-26 in histologically normal TDLUs (3pLOHn) could lead to an increased risk of local tumor recurrence. We assessed LOHs in normal TDLUs adjacent to 48 informative cases of early-stage invasive breast cancer samples and found 3pLOHn in approximately 25% (13 of 48) of patients whose tumors had 3pLOH in this region. Our analyses suggest that the most frequent region of LOH is localized at 3p24.3. We also demonstrate, using a Cox proportional hazards regression model, that the presence of 3pLOHn was the only variable significantly related to local tumor recurrence, leading to a 3.9-5.2-fold increase in the hazard ratio (P < 0.05). The time to recurrence was longer in such cases than in those without 3pLOHn, suggesting de novo tumor development. These data provide a strong rationale to assess histologically normal breast tissue at the margins of surgically excised cancers for molecular predictors of local recurrence after breast-conserving treatment.

Adult↗
PubMed2002

Overall clinical breast examination as a factor in delayed diagnosis of breast cancer.

HYPOTHESIS: A standardized description of clinical breast examination (CBE) can predict the risk of delayed diagnosis of breast cancer. DESIGN: Survey of case series. SETTING: Breast surgery referral practice. PATIENTS: Consecutive sample of 371 women with 386 breast cancers of any stage for whom overall characteristics of CBE were recorded at the initial consultation. INTERVENTION: None. MAIN OUTCOME MEASURES: Overall breast "durity" (from Latin duritia, meaning "hardness") was recorded as the inverse of whether rib edges could be felt through breast tissue in the most "dur" (firm or hard) part of the breast, usually the upper outer quadrant adjacent to the areola. "Nodularity" was recorded in this same area by means of an ordinal scale ranging from "surface is smooth" to "coarse nodularity." Delayed diagnosis was tabulated if the patient was told that cancer was not present when there was a sign of cancer on CBE, mammogram, and/or pathology slides. Relative risk of delayed diagnosis was determined within categories of nodularity or durity and within nodularity and durity categories combined. RESULTS: Diagnosis was delayed for 35 (9.1%) of cancers. Delay was least common (2 [2.2%] of 92) for less dur and less nodular breasts (relative risk, 1.0), most common (18 [13.5%] of 133) for less dur and more nodular breasts (relative risk, 6.23; 95% confidence interval, 3.58-10.22), and intermediate for other descriptions (chi(2) = 9.08; P =.03). Neither nodularity alone nor durity alone correlated with delay. CONCLUSIONS: A standardized system to describe CBE will alert physicians to an increased risk of delayed diagnosis of breast cancer (especially for women with less dur and more nodular breasts), help improve interpretation of CBE, and reduce delayed diagnosis of breast cancer.

Biopsy↗
PubMed2002

Age-associated biomarker profiles of human breast cancer.

To explore the hypothesis that aging not only increases breast cancer incidence but also alters breast cancer biology, we correlated patient age and diagnosis with tumor histology, stage and biomarkers independently determined from two different tumor archives: an American collection of approximately 800 paraffin-embedded and immunohistochemically analyzed primary breast cancers, and an European collection of approximately 3000 cryobanked primary breast cancers analyzed by ligand-binding and enzyme immunoassay (EIA). The prognostic biomarkers chosen for comparison represented surrogate measures of tumor: (i). proliferation, growth and genetic instability (mitotic and apoptotic indices, Ki-67/MIB-1-positivity, nuclear grade, p53-positivity), (ii). endocrine-dependence (estrogen receptor (ER), progesterone receptors (PR), pS2, Bcl2), (iii). growth factor receptor-dependence (ErbB2, EGFR/ErbB1), and (iv). angiogenic, invasive and proteolytic potential (uPA, PAI-1, Cathepsin D, VEGF). No biomarker reflecting tumor angiogenic, invasive or proteolytic potential showed a significant correlation with patient age at diagnosis. In contrast, significant inverse correlations (|r|>0.1; P< or =0.05) were observed for all measures of tumor growth and genetic instability as well as growth factor receptor overexpression (ErbB2 or EGFR positivity). Only one marker of endocrine-dependence, ER expression, showed a significant positive correlation with patient age at diagnosis. In summary, these findings support the hypothesis that breast cancer biology is significantly affected by patient age. In particular, breast tumors arising in older patients have slower growth rates, are more likely to be ER-positive, and are less likely to be p53-positive, EGFR-positive or ErbB2-positive.

Adult↗
PubMed2002

Invasive micropapillary carcinoma of the breast is associated with chromosome 8 abnormalities detected by comparative genomic hybridization.

Invasive micropapillary carcinoma (IMC) of the breast is a rare variant of invasive ductal carcinoma (IDC) characterized by unique histology and an extremely high incidence of lymph node metastases (approximately 95%). Comparative genomic hybridization (CGH) was used to characterize DNA extracted from 16 archival IMC cases to identify clonal genetic changes associated with this unique and highly metastatic cancer subtype. The average number of chromosomal alterations per IMC tumor was 7.4 +/-2.9 (3.4 gains and 3.9 losses), fewer than the number that we have observed in IDCs not otherwise specified (9.5 +/-6.6), IDCs with erbB-2 gene amplification (12.6 +/-5.9), and invasive lobular carcinomas (8.2 +/-5.5). The mean number of changes in IMC was significantly higher than we have observed in the rarely metastasizing tubular subtype of IDC (3.9 +/-2.3, P = 0.001), but less than the more aggressive subset of erbB-2-amplified IDC (P = 0.02). Remarkably, 100% of IMCs demonstrated loss involving the short arm of chromosome 8 (8p). Six cases showed loss of the entire 8p arm, whereas in 10 cases the loss was limited to the distal portion (8p21-pter) with localized gain of proximal 8p (8p11-p12). A reciprocal gain of 8q was detected in 14 cases (88%). Other common alterations included loss of 17p in 50% of tumors and loss of 16q in 50% of IMC cases. Gains of 17q (38%), 1q (31%), and 16p (25%) were also commonly detected. In comparison, IDCs (not otherwise specified), IDCs of the tubular subtype, and invasive lobular carcinomas showed only modest 8p loss (33%, 28%, and 13%, respectively). This region of chromosome 8 may contain 1 or more genes whose loss leads to this particular histology and/or the lymphotrophic phenotype associated with this histopathologic pattern.

Breast Neoplasms↗