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D H Moore

Publications and source records attributed to D H Moore.

At least 55 records · Page 3Linked to original sources
PubMed1999

Invasive micropapillary carcinoma of the breast: a prognostic study.

Invasive micropapillary carcinoma (IMC) of the breast is a rare variant of infiltrating ductal carcinoma that has been associated with an extremely high incidence of lymph node metastases. Follow-up studies on patients with pure IMC breast cancer histology have been limited by low patient numbers, short duration of follow-up, and a lack of multivariate analyses. Using invasive breast cancers from 1,287 patients (median follow-up, 13.8 years), histological review showed 21 cases (1.7%) with pure IMC histology. Pure IMC histology was associated with high-grade histology (P = .04), metastases to regional lymph nodes (P < .001), a high mitotic index (P = .02), and erbB-2 immunopositivity (P = .007). Univariate analyses showed a strong association between IMC histology and shortened survival (disease-free survival [DFS], P = .0052; median, 44 months for IMC and 63 months for non-IMC; disease-specific survival [DSS], P = .014; medians, 71 and 78 for IMC and non-IMC, respectively) only in an analysis of all patients. Because only 1 case of node-negative IMC histology was available, univariate analysis of IMC histology was performed only on node-positive patients without significance. Multivariate analyses comparing IMC histology with either node-positive or all other breast cancers failed to show independent prognostic significance. In summary, breast cancer patients with pure IMC histology showed survival rates similar to those of other patients with equivalent numbers of lymph node metastases.

Aged↗
PubMed1999

Comparison of mitotic index, in vitro bromodeoxyuridine labeling, and MIB-1 assays to quantitate proliferation in breast cancer.

PURPOSE: To investigate the hypothesis that in vitro bromodeoxyuridine (BrDu) labeling might be superior to MIB-1 immunostaining for prognostic value, because it more selectively labels cells during the S phase. METHODS: Four hundred eighty-six patients with breast cancers (59% lymph node-negative, 41% lymph node-positive) surgically excised between 1988 and 1993 (median follow-up, 62 months) were evaluated for cellular proliferation using prospective in vitro BrDu uptake assays, retrospective mitotic indices, and MIB-1 labeling. RESULTS: MIB-1, BrDu labeling, and mitotic index-derived proliferation data were highly correlated. Each was similarly associated with most other markers of prognosis, although these relationships were not identical. By univariate analysis, nodal status was the most significant prognostic variable for all patients. Higher BrDu labeling index, MIB-1 immunolabeling, and mitotic index were also associated with shortened disease-free survival (DFS) and disease-specific survival for the entire patient group, as well as for node-negative patients. The association between cellular proliferation and survival was much weaker for node-positive patients. Multivariate models confirmed that nodal status, tumor size, and proliferation data predicted survival in all patients as well as those with node-negative disease, although MIB-1 was somewhat more closely associated with outcome than mitotic index or in vitro BrDu data. For patients with T1NOMO disease (n = 172), the only significant predictors of DFS were proliferation rate (mitotic index or MIB-1) and tumor grade. CONCLUSIONS: Proliferation rate predicts recurrence and survival in breast cancer. This effect is more pronounced in node-negative patients. In vitro BrDu data are not superior to MIB-1 and mitotic counting.

Adult↗
PubMed1998

Preoperative chemoradiation for advanced vulvar cancer: a phase II study of the Gynecologic Oncology Group.

PURPOSE: To determine the feasibility of using preoperative chemoradiotherapy to avert the need for more radical surgery for patients with T3 primary tumors, or the need for pelvic exenteration for patients with T4 primary tumors, not amenable to resection by standard radical vulvectomy. METHODS AND MATERIALS: Seventy-three evaluable patients with clinical Stage III-IV squamous cell vulvar carcinoma were enrolled in this prospective, multi-institutional trial. Treatment consisted of a planned split course of concurrent cisplatin/5-fluorouracil and radiation therapy followed by surgical excision of the residual primary tumor plus bilateral inguinal-femoral lymph node dissection. Radiation therapy was delivered to the primary tumor volume via anterior-posterior-posterior-anterior (AP-PA) fields in 170-cGy fractions to a dose of 4760 cGy. Patients with inoperable groin nodes received chemoradiation to the primary vulvar tumor, inguinal-femoral and lower pelvic lymph nodes. RESULTS: Seven patients did not undergo a post-treatment surgical procedure: deteriorating medical condition (2 patients); other medical condition (1 patient); unresectable residual tumor (2 patients); patient refusal (2 patients). Following chemoradiotherapy, 33/71 (46.5%) patients had no visible vulvar cancer at the time of planned surgery and 38/71 (53.5%) had gross residual cancer at the time of operation. Five of the latter 38 patients had positive resection margins and underwent: further radiation therapy to the vulva (3 patients); wide local excision and vaginectomy necessitating colostomy (1 patient); no further therapy (1 patient). Using this strategy of preoperative, split-course, twice-daily radiation combined with cisplatin plus 5-fluorouracil chemotherapy, only 2/71 (2.8%) had residual unresectable disease. In only three patients was it not possible to preserve urinary and/or gastrointestinal continence. Toxicity was acceptable, with acute cutaneous reactions to chemoradiotherapy and surgical wound complications being the most common adverse effects. CONCLUSION: Preoperative chemoradiotherapy in advanced squamous cell carcinoma of the vulva is feasible, and may reduce the need for more radical surgery including primary pelvic exenteration.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Assessing genetic markers of tumour progression in the context of intratumour heterogeneity.

This is a report from the Kananaskis working group on quantitative methods in tumour heterogeneity. Tumour progression is currently believed to result from genetic instability and consequent acquisition of new genetic properties in some of the tumour cells. Cross-sectional assessment of genetic markers for human tumours requires quantifiable measures of intratumour heterogeneity for each parameter or characteristic observed; the relevance of heterogeneity to tumour progression can best be ascertained by repeated assessment along a tumour progressional time line. This paper outlines experimental and analytic considerations that, with repeated use, should lead to a better understanding of tumour heterogeneity, and hence, to improvements in patient diagnosis and therapy. Four general principles were agreed upon at the Symposium: (1) the concept of heterogeneity requires a quantifiable definition so that it can be assessed repeatably; (2) the quantification of heterogeneity is necessary so that testable hypotheses may be formulated and checked to determine the degree of support from observed data; (3) it is necessary to consider (a) what is being measured, (b) what is currently measurable, and (c) what should be measured; and (4) the proposal of working models is a useful step that will assist our understanding of the origins and significance of heterogeneity in tumours. The properties of these models should then be studied so that hypotheses may be refined and validated.

Disease Progression↗
PubMed1998

Gynecologic cancers metastatic to the breast.

BACKGROUND: We report a series of gynecologic cancers metastatic to the breast, illustrating the diagnostic and prognostic implications of this rare event. STUDY DESIGN: By reviewing the gynecologic oncology data base, we identified 10 women with gynecologic cancer metastatic to the breast who were treated at Indiana University School of Medicine between August 1978 and February 1995. Medical records were reviewed for pertinent data concerning the presentation, evaluation, and treatment of the primary gynecologic malignancy and the metastatic breast tumor. RESULTS: The mean patient age was 56.8 years (range, 30-80 years). The most common gynecologic malignancy was ovarian cancer (five patients), followed by cervical cancer (two patients) and cancers of the vagina, endometrium, or peritoneum (one patient each). A palpable solitary breast mass was found in 8 of 10 patients (80%), and the upper outer quadrant of the breast was the most common site of tumor involvement. One woman presented with examination findings resembling inflammatory breast cancer, and one patient presented with multiple firm subcutaneous nodules. Despite further treatment, which in all cases consisted of systemic chemotherapy, 83% of the patients died with a breast metastasis within 1 year of presentation. CONCLUSIONS: Secondary breast malignancy should be suspected in any patient with a breast tumor and a known history of gynecologic cancer. A breast metastasis implies widespread tumor dissemination and a poor prognosis. Radical breast surgery should be avoided.

Adult↗
PubMed1998

The functional relationship between in vivo bromodeoxyuridine labeling index and Ki-67 proliferation index in human breast cancer.

Proliferation indices are used, along with other parameters, to estimate the risk of recurrence of breast cancer for individual patients. Because it is unlikely one index will be practical for all patients, it is important to understand the relationship between various indices of proliferation. For this reason, we compared a proliferation index based on in vivo labeling of S-phase tumor cells with the thymidine analog bromodeoxyuridine (BrdUrd), to a proliferation index based on an estimate of the growth fraction with the MIB-1 antibody to the Ki-67 antigen. With informed consent, we gave 145 patients 200 mg/m2 BrdUrd intravenously just prior to surgical removal of breast cancer. On histology sections, we visually counted S-phase cells which had incorporated BrdUrd using the Br-3 antibody which is specific to DNA-incorporated BrdUrd, and we counted cells in the growth fraction using the MIB-1 antibody to the Ki-67 antigen. We found that both indices were positively correlated with tumor size, number of positive nodes, and tumor grade, and both were negatively correlated with age and estrogen-progesterone receptor positivity. Using a linear functional relationship model, we found that the best (i.e. the maximal) fit between the two indices (correlation coefficient 0.79; p < 0.0001) occurred when each index was square root transformed, as is appropriate when counts follow a Poisson distribution. When we used the median as a cutpoint for each index, the classification of 19 percent of data pairs changed depending upon which index was used. We also estimated that the Ki-67 intercept (1.02 +/- 0.25) was significantly greater than zero. We conclude that the BrdUrd index of DNA synthesis in S-phase correlates highly with the MIB-1 index of the growth fraction, and both indices correlate well with other parameters of tumor aggressiveness. Because this correlation is driven by concordance of the extremes of high and low counts, clinical comparison will be necessary to determine which is the better prognostic marker for human breast cancer.

Adult↗
PubMed1998

Health effects of exposure to low doses of nerve agent--a review of present knowledge.

Extensive data are available on nerve agents as they relate to low dose toxicity. Highly sensitive in vitro and in vivo mutagenicity and clastogenicity screens as well as subchronic toxicity studies in various animal models have been carried out. The majority of such closely controlled toxicological studies in the United States have been conducted at the National Center for Toxicological Research or at the University of California. Data available on humans exposed to nerve agents are obtained primarily from human volunteer studies and accidental exposures. The former consists of experiments conducted by the U.S. Army between 1958 and 1975. Cases of accidental exposures were occupational hazards of chemical munition production workers. Controlled studies of human exposures, reports of accidental exposures, and animal studies collectively indicate that exposures to OP nerve agents at levels causing no acute signs or symptoms do not produce chronic illness.

Animals↗
PubMed1998

Genetic analysis of glioblastoma multiforme provides evidence for subgroups within the grade.

We analyzed 72 primary and 25 recurrent glioblastoma multiforme (GBM) samples for DNA sequence copy number abnormalities (CNAs) by comparative genomic hybridization (CGH). The number of aberrations per tumor ranged from 2 to 23 in primary GBM and 5 to 25 in recurrent GBM. There were 26 chromosome regions with CNAs in more than 20% of tumors. 7q22-36 was the most common gain and 10q25-26 was the most common loss; each occurred in more than 70% of tumors. Of 27 amplification sites, epidermal growth factor receptor (EGFR) was the most common; it was observed in 25% of primary GBMs. Statistical analysis based on pairwise correlation of CNAs indicated that there is more than one class of primary GBM.

Adolescent↗
PubMed1998

The overexpression of RHAMM, a hyaluronan-binding protein that regulates ras signaling, correlates with overexpression of mitogen-activated protein kinase and is a significant parameter in breast cancer progression.

RHAMM is an oncogene that regulates signaling through ras and controls mitogen-activated protein kinase [extracellular signal-regulated protein kinase (ERK)] expression in embryonic murine fibroblasts. ERK is a dual-specificity kinase that controls expression of proteins relevant to tumorigenesis, proliferation, and motility. To assess whether RHAMM and ERK are involved in human breast tumor progression, we examined RHAMM, ras, and ERK expression in two cohorts of breast cancer patients using reverse transcription-PCR and immunocytochemistry. We show that overexpression of RHAMM in primary tumors of two patient cohorts was significantly prognostic of poor outcome in breast cancer progression. Furthermore, RHAMM overexpression occurred within subsets of tumor cells in the primary tumor, and this staining pattern was associated with lymph node metastases. The metastases exhibited a significantly higher level of staining for RHAMM than did the primary tumor. RHAMM expression strongly correlated with overexpression of both ras and ERK, although overexpression of either of these two signaling molecules was not by itself a prognostic indicator. These results identify a new parameter that is involved in lymph node metastasis of primary breast cancers and suggest that quantification of RHAMM overexpression may be a useful prognostic indicator for breast carcinoma progression.

Breast Neoplasms↗
PubMed1997

Factors affecting survival after orthotopic liver transplantation in infants.

The technical and medical management of small infants requiring orthotopic liver transplantation remains a challenge. The present study examined 117 orthotopic liver transplantations performed in 101 infants from <1 to 23 months of age between March 1988 and February 1995 to determine factors that influence patient and graft outcome. Factors analyzed included etiology of liver disease, recipient and donor age and weight, United Network for Organ Sharing (UNOS) status, retransplantation, ABO-compatibility, full-size (FS) versus reduced-size grafts, vascular thrombosis (VT), including hepatic artery and portal vein (PVT), and the presence of lymphoproliferative disease (LPD). UNOS status 1, fulminant hepatic failure, and the development of Epstein-Barr virus-associated LPD were each associated with 10-20% lower patient and graft survival rates. Of 101 infants, 11 (11%) developed LPD with an associated 36% mortality. VT occurred in 10 (9 hepatic artery and 1 portal vein) of 117 orthotopic liver transplantations (9%), all less than 1 year of age, and was associated with significantly poorer 1-year (50% vs. 85% no VT, P<0.01) and 5-year patient survival rates (50% vs. 83% no VT, P<0.01). One-year graft survival rates for FS grafts in recipients <12 months versus 12-23 months were 67% vs. 94% (P<0.01); the patient survival rate was also significantly lower in FS graft recipients <12 months (76% vs. 100%, P<0.05). Recipients <5 months of age had the worst survival rates: 1-year and 5-year patient survival rates were 65% and 46% for recipients 0-4 months (n=17) versus 82% and 82% for recipients 5-11 months (n=56), and 93% and 93% for recipients age 12-23 months (n=28; P<0.05). In summary, factors associated with reduced survival rates include recipient age <5 months, recipient age <12 months who received FS grafts, development of VT and donor weight <6 kg. There was a trend for UNOS status 1, fulminant hepatic failure, and presence of LPD to be associated with reduced survival rates.

Aging↗
PubMed1997

A t-statistic for objective interpretation of comparative genomic hybridization (CGH) profiles.

An objective method for interpreting comparative genomic hybridization (CGH) is described and compared with current methods of interpretation. The method is based on a two-sample t-statistic in which composite test:reference and reference:reference CGH profiles are compared at each point along the genome to detect regions of significant differences. Composite profiles are created by combining CGH profiles measured from several metaphase chromosomes for each type of chromosome in the normal human karyotype. Composites for both test:reference and reference:reference CGH analyses are used to generate mean CGH profiles and information about the variance therein. The utility of the method is demonstrated through analysis of aneusomies and partial gain and loss of DNA sequence in a myeloid leukemia specimen. Banding analyses of this specimen indicated inv (3)(q21q26), del (5)(q2?q35), -7, +8 and add (17)(p11.2). The t-statistic analyses of CGH data indicated rev ish enh (8) and rev ish dim (5q31.1q33.1,7q11.23qter). The undetected gain on 17p was small and confined to a single band (17p11.2). Thus, the t-statistic is an objective and effective method for defining significant differences between test and reference CGH profiles.

Humans↗
PubMed1997

Objective aneuploidy detection for fetal and neonatal screening using comparative genomic hybridization (CGH).

Comparative genomic hybridization (CGH) allows entire genomes to be scanned for whole and segmental aneuploidy and thus may be an appropriate tool for the detection of clinically important abnormalities during fetal and neonatal screening. Criteria to distinguish between significant aberrations and experimental artifacts are essential for these applications. This report describes the use of a t-statistic to detect changes in CGH profiles that differ significantly from variations that occur in CGH profiles of normal samples. Eleven cell lines derived from fetal or neonatal patients were analyzed in this study. Aneuploidies in these lines included trisomies for chromosomes 13, 16, 18, and 21 and monosomy for distal 5p and tetrasomy 18p. Aneuploidy was detected in all samples by using the t-statistic, although the extent of the aneuploid region was not correctly estimated in some cases. A detailed description of the t-statistic fused for making these CGH comparisons is described in a companion paper (Moore et al., Cytometry 28:183-190, 1997.

Aneuploidy↗
PubMed1997

Partial enzymatic degradation of stroma allows enrichment and expansion of primary breast tumor cells.

The goal of this study was to isolate and expand tumor cells in culture that closely resemble invasive cells in primary breast carcinoma tissue. Based on the hypothesis that invasive tumor cells are released more readily upon digestion with connective tissue-degrading enzymes because they are not confined within a basement membrane, we have designed a novel procedure for their isolation. Using this method, we have successfully expanded in culture aneusomic tumor cells from several primary breast tumors. Twenty nine of 44 (66%) specimens processed yielded proliferative and passageable cultures of up to 2 x 10(7) cells. The original tumor tissue and cultures derived therefrom were compared for aneusomy and the abnormal expression of the erb-B2, p53, and bcl-2 gene products. Remarkable similarities were observed. However, some intratumor heterogeneity in chromosome content was found between touch preparations and cultured cells. Overexpression of erb-B2 was observed in the vast majority of cases (16 of 20), suggesting that this phenotype may be important for dysregulated proliferation in vitro. The simple and rapid method described in this report could enable routine expansion of primary breast tumors and provide adequate numbers of viable cells for studying and manipulating their functional characteristics.

Aneuploidy↗
PubMed1997

Case-control study of malignant melanoma among employees of the Lawrence Livermore National Laboratory.

During 1972 to 1977, the Lawrence Livermore National Laboratory (LLNL) experienced increased diagnosis of malignant melanoma among employees. In 1984, a report on the results of a case-control study of 39 cases concluded that occupational factors, including exposures to ionizing radiation and to chemicals, caused the excess incidence. The study reported here, based on results from 69 case-control pairs, re-examines the role of the occupational factors implicated by the earlier study in melanoma causation. Results from this study suggest that constitutional factors, including skin reactivity to sunlight, sunbathing frequency, and number of moles, explain most of the excess melanoma. Exposures to occupational factors, including ionizing radiation and chemicals, were found to be no different in cases than in controls.

Algorithms↗
PubMed1997

Analyses of brain tumor cell lines confirm a simple model of relationships among fluorescence in situ hybridization, DNA index, and comparative genomic hybridization.

Several techniques are commonly used for genetic analysis of interphase nuclei. Flow cytometry assays the distribution of DNA content in populations of nuclei stained with a DNA-specific fluorochrome. Fluorescence in situ hybridization (FISH) quantifies the number of copies of a specific DNA sequence in single nuclei. Comparative genomic hybridization (CGH) assesses the relative copy number of DNA sequences throughout a test genome by comparing the signal intensities of test and reference DNA samples hybridized to a template of normal metaphase chromosomes. In principle, there are specific relationship among data obtained from these measurements, and combined measurements should provide a more comprehensive view of the sample that is analyzed. We applied these three techniques to nine brain tumor cell lines and find that a model of CGH that includes unsuppressed repeat sequences describes the data well. We estimate that up to 35% of the fluorescence intensity in well-blocked CGH preparations may not represent unique sequences. Taking these factors into account, our results are, in general, mutually consistent, and highlight issues critical for interpreting CGH preparations.

Algorithms↗
PubMed1997

Persistence of radiation-induced translocations in rat peripheral blood determined by chromosome painting.

In this article, we address the issue of persistence of chromosome exchanges following acute in vitro exposure of rat peripheral blood to 137Cs. Irradiation occurred 24 hr after culture initiation, and metaphase chromosomes were prepared 2, 3, 4, and 5 days later. Chromosomes 1, 2, and 4 were painted in unique colors and scored for structural aberrations. Dicentric chromosomes and acentric fragments diminished rapidly with time, as expected. Translocations exhibited greater persistence, but still showed a reduction in frequency, reaching a plateau of approximately 65 and 55% of their initial values, 4 days after exposure to 1 and 2 Gy, respectively. An exponentially declining model was fit to the combined dicentric, acentric fragment, and translocation frequencies, which showed that all three aberration types declined at equivalent rates. The frequencies of dicentrics and fragments declined to a plateau of zero, while translocations reached a plateau at frequencies significantly greater than zero. The decline in translocations with time is inconsistent with prevailing theoretical expectations, but is consistent with a model where some translocations are fully stable (persistent) and some are unstable (not persistent) through cell division. These results may have implications for radiation biodosimetry in humans.

Animals↗
PubMed1997

Collagenase expression in ovarian cancer cell lines.

BACKGROUND: There are several distinct forms of the matrix metalloproteinases (MMP) that degrade collagen in the extracellular matrix. Most involved in the metastatic process are collagenases exhibiting specificity for type IV collagen, the collagen that makes up the backbone of the basement membrane. We chose to examine the expression of one type IV collagenase, MMP-9, in several ovarian cancer cell lines. METHODS: Under the influence of phorbol esters such as TPA, the fibrosarcoma cell line HT1080 is known to express MMP-9. We examined the effect of TPA on MMP-9 expression with Northern analysis, and on MMP-9 collagenase activity with polyacrylamide gel electrophoresis-zymography, in HT1080 cells (positive control) and in six ovarian cancer cell lines: Hey, HeyA8, CAOV3, PA-1, SKOV3, and OVCAR3. Cells were grown to 70% confluence and the growth medium was changed to a serum-free medium for 24 hr. Cells were then treated with 12 ng/mL TPA or its vehicle for an additional 24 hr. Medium was collected for PAGE-zymographic analysis. The cells were lysed and their RNA collected for Northern analysis. RESULTS: PA-1, a teratocarcinoma, expressed more than 10-fold the amount of RNA for MMP-9 than the other lines following TPA treatment. Both Northern analysis and zymography showed that four of the six ovarian cell lines responded to TPA with increased collagenase expression and activity. The other two cell lines showed no MMP-9 activity either before or after TPA treatment. CONCLUSIONS: These results suggest that ovarian cancer cell lines express collagenase and that this expression may be regulated by phorbol esters which activate the protein kinase C pathway.

Base Sequence↗