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Biomedical subjects

M B Moore

Publications and source records attributed to M B Moore.

At least 19 recordsLinked to original sources
PubMed2001

Comparison of methods of measuring HER-2 in metastatic breast cancer patients treated with high-dose chemotherapy.

PURPOSE: HER-2 is overexpressed in 20% to 30% of human breast cancer and is associated with poor outcome. Studies suggest an association between HER-2 overexpression and resistance to alkylating agents. To further evaluate this relationship, we assessed the interaction of HER-2, measured by different methods, and outcome after dose intensification with alkylating agents in metastatic breast cancer. PATIENTS AND METHODS: From 1988 to 1995 at Duke University, 425 patients with metastatic breast cancer were enrolled in a study of high-dose alkylating agents (HDC) with autologous cellular support after doxorubicin-based therapy (AFM). HER-2 was measured in serum for shed extracellular domain (ECD) and in tissue by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). RESULTS: HER-2 ECD was positive in 29% (19 of 65) of patients pre-AFM and in 11.7% (34 of 290) pre-HDC. Higher pre-AFM and higher pre-HDC HER-2 ECD predicted worse overall survival (P =.045 and P =.0096, respectively). HER-2 overexpression by IHC and FISH showed no correlation with worse disease-free survival or overall survival. FISH and ECD were highly specific for IHC (97.3% and 97.7% respectively). However, ECD had a low sensitivity for IHC-only 22% of patients with HER-2 in the primary tumor shed ECD into the serum. CONCLUSION: These data suggest that the method of measuring HER-2 is important in predicting clinical outcome. HER2 ECD may identify a poor prognosis subgroup of HER-2-positive tumors. Lack of association of HER2 by IHC/FISH with worse outcome suggests that therapy with AFM and/or HDC therapy may be able to overcome the effect of this prognostic factor or it may not be a prognostic factor in this setting.

Adult↗
PubMed2001

Tumor marker expression is predictive of survival in patients with esophageal cancer.

BACKGROUND: This study was designed to determine the prognostic value of immunohistochemical tumor marker expression in a population of patients with node-negative esophageal cancer treated with complete resection alone. METHODS: Resection specimens were collected from 61 patients with node-negative T1 (n = 31), T2 (n = 14), and T3 (n = 16) esophageal cancer. A panel of 10 tumor markers was chosen for immunohistochemical analysis, based on associations with differing oncologic mechanisms: apoptosis (p53), growth regulation (transforming growth factor-alpha, epidermal growth factor receptor, and Her2-neu), angiogenesis (factor VIII), metastatic potential (CD44), platinum resistance (p-glycoprotein and metallothionein), 5-fluorouracil resistance (thymidylate synthetase), and carcinogenic detoxification (glutathione S-transferase-pi). RESULTS: Complete resection was performed in all patients (44 adenocarcinoma, 17 squamous cell carcinoma), with no operative deaths. Multivariable analysis demonstrated a significant relationship between cancer-specific death and the following variables: low-level P-gp expression (p = 0.004), high-level expression of p53 (p = 0.04), and low-level expression of transforming growth factor-alpha (p = 0.03). In addition, the number of involved tumor markers present was strongly predictive of negative outcome (p = 0.0001). CONCLUSIONS: This study supports the prognostic value of immunohistochemical tumor markers, specifically the expression pattern of P-gp, p53, and transforming growth factor-alpha, in patients with esophageal carcinoma treated with complete resection alone.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Predicting the sites of metastases from lung cancer using molecular biologic markers.

BACKGROUND: The use of molecular markers in staging non-small cell lung cancer (NSCLC) has been supported in retrospective prognostic models but has not been evaluated in predicting sites of metastases. METHODS: Pathologic specimens were collected from 202 patients after complete resection for stage I NSCLC, who were subsequently found to have no metastases at 5 years (n = 108), isolated brain metastases (n = 25), or other distant metastases (n = 69). A panel of eight molecular markers of metastatic potential was chosen for immunohistochemical analysis of the tumor: p53, erbB2, angiogenesis factor viii, EphA2, E-cadherin, urokinase plasminogen activator (UPA), UPA receptor, and plasminogen activator inhibitor. RESULTS: Patients with isolated brain relapse had significantly higher expression of p53 (p = 0.02) and UPA (p = 0.002). The quantitative expression of E-cadherin was used to predict the site of metastases using recursive partitioning: 0 of 92 patients with E-cadherin expression of 0, 1, or 2 developed isolated cerebral metastases; 0 of 33 patients with E-cadherin expression of 3 with UPA of 1 or 2 and ErbB2 of 0 developed brain metastases. Of the remaining patients at risk (UPA = 3), the risk of isolated cerebral metastases was 21 of 57 patients (37%). CONCLUSIONS: This study demonstrates that molecular markers may predict the site of relapse in early stage NSCLC. If validated in an ongoing prospective study, these results could be used to select patients with isolated brain metastases for adjuvant therapy, such as prophylactic cranial irradiation.

Biomarkers, Tumor↗
PubMed2001

The prognostic value of molecular marker analysis in patients treated with trimodality therapy for esophageal cancer.

The purpose of this study was to define the prognostic value of a group of molecular tumor markers in a well-staged population of patients treated with trimodality therapy for esophageal cancer. The original pretreatment paraffin-embedded endoscopic esophageal tumor biopsy material was obtained from 118 patients treated with concurrent cisplatin + 5-fluorouracil (5-FU) + 45 Gy radiation followed by resection from 1986 until 1997 at the Duke University Comprehensive Cancer Center. Three markers of possible platinum chemotherapy association [metallothionein (MT), glutathione S-transferase-pi (GST-pi), P-glycoprotein (P-gp or multidrug resistance)] and one marker of possible 5-FU association [thymidylate synthase (TS)] were measured using immunohistochemistry. The median cancer-free survival was 25.0 months, with a significantly improved survival for the 38 patients who had a complete response (P < 0.001). High-level expression of GST-pi, P-gp, and TS were associated with a decreased survival. MT was not significant in this population. Multivariate analysis identified high-level expression in two of the platinum markers (GST-pi and P-gp) and the 5-FU marker TS as independent predictors of early recurrence and death. In conclusion, this investigation measured three possible markers associated with platinum and one possible marker associated with 5-FU in a cohort of esophageal cancer patients. Independent prognostic significance was observed, which suggests that it may be possible to predict which patients may benefit most from trimodality therapy. These data need to be reproduced in a prospective investigation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Hypermethylated APC DNA in plasma and prognosis of patients with esophageal adenocarcinoma.

BACKGROUND: The adenomatous polyposis coli (APC) locus on chromosome 5q21-22 shows frequent loss of heterozygosity (LOH) in esophageal carcinomas. However, the prevalence of truncating mutations in the APC gene in esophageal carcinomas is low. Because hypermethylation of promoter regions is known to affect several other tumor suppressor genes, we investigated whether the APC promoter region is hypermethylated in esophageal cancer patients and whether this abnormality could serve as a prognostic plasma biomarker. METHODS: We assayed DNA from tumor tissue and matched plasma from esophageal cancer patients for hypermethylation of the promoter region of the APC gene. We used the maximal chi-square statistic to identify a discriminatory cutoff value for hypermethylated APC DNA levels in plasma and used bootstrap-like simulations to determine the P: value to test for the strength of this association. This cutoff value was used to generate Kaplan-Meier survival curves. All P values were based on two-sided tests. RESULTS: Hypermethylation of the promoter region of the APC gene occurred in abnormal esophageal tissue in 48 (92%) of 52 patients with esophageal adenocarcinoma, in 16 (50%) of 32 patients with esophageal squamous cell carcinoma, and in 17 (39.5%) of 43 patients with Barrett's metaplasia but not in matching normal esophageal tissues. Hypermethylated APC DNA was observed in the plasma of 13 (25%) of 52 adenocarcinoma patients and in two (6.3%) of 32 squamous carcinoma patients. High plasma levels of methylated APC DNA were statistically significantly associated with reduced patient survival (P =.016). CONCLUSION: The APC promoter region was hypermethylated in tumors of the majority of patients with primary esophageal adenocarcinomas. Levels of hypermethylated APC gene DNA in the plasma may be a useful biomarker of biologically aggressive disease in esophageal adenocarcinoma patients and should be evaluated as a potential biomarker in additional tumor types.

Adenocarcinoma↗
PubMed2000

Molecular biologic substaging of stage I lung cancer according to gender and histology.

BACKGROUND: This study is designed to assess molecular biologic substaging according to gender and histology in patients with stage I non-small cell lung cancer (NSCLC). METHODS: Pathologic specimens were collected from 408 consecutive patients after complete resection for stage I NSCLC, with follow-up of at least 5 years. A panel of nine molecular markers was chosen for immunohistochemical analysis of the tumor: recessive oncogenes p53 and bcl-2, the protooncogene erbB-2, KI-67 proliferation index, retinoblastoma oncogene (Rb), epidermal growth factor receptor (EGFr), angiogenesis factor viii, sialyl-Tn antigen (STN), and CD-44. Cox proportional hazards regression analysis was used to construct a risk model for cancer-specific survival according to marker status, gender, and histologic subtype. RESULTS: Among men, the only molecular marker associated with decreased cancer-specific survival is erbB-2; among women, there are four markers: p53, Rb, CD-44, and factor viii. Among patients with squamous cell carcinoma, the only molecular marker associated with decreased cancer-specific survival is erbB-2; among patients with adenocarcinoma (AC), there are three markers: p53, CD-44, and factor viii. Multivariable analysis of interactions among molecular markers, gender, and histology demonstrates two important relationships (hazard ratio): p53+/women (2.269) and CD-44+/AC (2.266). CONCLUSIONS: Molecular biologic substaging of patients with stage I NSCLC demonstrates differential cancer-specific survival according to marker expression, gender, and histologic subtype.

Carcinoma, Non-Small-Cell Lung↗
PubMed1999

A biologic risk model for stage I lung cancer: immunohistochemical analysis of 408 patients with the use of ten molecular markers.

OBJECTIVE: The standard treatment of patients with stage I non-small cell lung cancer is resection of the primary tumor; however, the recurrence rate is 28% to 45%. This study evaluates a panel of molecular markers in a large population of patients with stage I non-small cell lung cancer to determine the prognostic value of each marker and to create a biologic risk model. METHODS: Pathologic specimens were collected from 408 consecutive patients after complete resection for stage I non-small cell lung cancer at a single institution, with follow-up of at least 5 years. A panel of 10 molecular markers was chosen for immunohistochemical analysis of the primary tumor on the basis of differing oncogenic mechanisms. Local tumor expansion requires growth regulating proteins (epidermal growth factor receptor, the protooncogene erb-b2); apoptosis proteins (p53, bcl-2); and cell cycle regulating proteins (retinoblastoma recessive oncogene, KI-67). Local tumor invasion requires angiogenesis (factor viii). The development of distant metastases involves the expression of adhesion proteins (CD-44, sialyl-Tn, blood group A). Cox proportional hazards regression analysis was used to construct an independent risk model for cancer recurrence and death. RESULTS: Multivariable analysis demonstrated significantly elevated risk for the following molecular markers: p53 (hazard ratio, 1.68; P =.004); factor viii (hazard ratio, 1.47 P =. 033); erb-b2 (hazard ratio, 1.43; P =.044); CD-44 (hazard ratio, 1. 40; P =.050); and retinoblastoma recessive oncogene (hazard ratio, 0. 747; P =.084). CONCLUSIONS: Five molecular markers were associated with the risk of recurrence and death, representing independent metastatic pathways: apoptosis (p53), angiogenesis (factor viii), growth regulation (erb-b2), adhesion (CD-44), and cell cycle regulation (retinoblastoma recessive oncogene). This study demonstrates the validity of this molecular biologic risk model in patients with stage I non- small cell lung cancer.

Biomarkers, Tumor↗
PubMed1997

A cephalometric evaluation of patients presenting with persistent digit sucking habits.

Persistent digit sucking habits are an important aetiological factor for malocclusion, and patients with persistent habits are frequently referred for orthodontic treatment. The present study investigated the effects of digit sucking habits on vertical and anteroposterior dentofacial characteristics by employing a cephalometric analysis of patients with persistent digit sucking habits compared with patients without such habits. Significant differences were seen in maxillary prognathism, relative prognathism, maxillary incisor angulation, interincisal angle, maxillary length and maxillary plane angulation. No significant differences were observed for mandibular prognathism or length, maxillary mandibular plane angle, cranial base measurements nor any measurement of facial height. The digit sucking group were also found to have a larger variation of lower incisor angulation than the controls, although no significant difference in the mean value for this variable was detected. It is concluded that persistent digit sucking may cause largely dentoalveolar change, together with some minor effects on the skeletal pattern.

Adolescent↗
PubMed1997

Neutrophil mediated microvascular injury in acute, experimental compartment syndrome.

The purpose of this study was to determine the contribution of neutrophils and tissue xanthine oxidase to the skeletal muscle microvascular dysfunction in an ex vivo model of acute compartment syndrome. Adult dogs were rendered neutropenic or depleted of tissue xanthine oxidase before gracilis muscle isolation. Compared with continuously perfused, nonischemic muscles, acute, experimental compartment syndrome resulted in a dramatic increase in microvascular permeability, muscle neutrophil content, and muscle vascular resistance. Neutropenia prevented, whereas xanthine oxidase depletion had no effect on, the microvascular dysfunction and muscle neutrophil infiltration elicited by experimental compartment syndrome. These results suggest that neutrophils contribute to the microvascular dysfunction and blood flow distribution abnormalities elicited by acute, experimental compartment syndrome.

Acute Disease↗
PubMed1996

Belle Maudsley Lecture. Digits, dummies and malocclusions.

When considering the aetiology of malocclusion in general, factors are often cited as having a genetic basis or an environmental basis. An individual malocclusion is likely to be a result of the variable effects of multiple environmental influences, upon an equally variable genetic predisposition. One of the most tangible 'environmental' factors is that of sucking habits involving digits or dummies. This review considers the nature of these habits, their effects on the developing dentition and methods used to combat the problem.

Child↗
PubMed1992

Risk factors for complications following pediatric epikeratoplasty.

We studied the prevalence and types of complications that occurred in children treated with epikeratoplasty to identify risk factors. A review of the clinical records of 88 consecutive patients (106 eyes; 114 procedures) revealed that no complications occurred in 58 grafts (54%). Refractive complications (refractive error greater than 3.00 diopters spherical equivalent from emmetropia or astigmatism greater than 3.00 diopters) occurred in 30 eyes (28%). Medical complications occurred in 22 eyes (19%); these included epithelial defects (14 grafts), interface opacities (six grafts), graft vascularization (eight grafts), graft infection (two grafts), graft necrosis (five grafts), graft haziness (four grafts) or opacification (11 grafts), and graft dehiscence (three grafts). Eleven grafts (10%) were removed and five eyes received new grafts. Epikeratoplasty in children will be more successful if risk factors such as patient age less than one year, microcornea, corneal endothelial cell dysfunction, mental retardation, and combining the procedure with cataract surgery are avoided.

Adolescent↗
PubMed1992

p53 overexpression in formalin-fixed, paraffin-embedded tissue detected by immunohistochemistry.

Mutation and overexpression of the p53 gene have been noted in a wide range of human cancers and are thought to play a role in malignant transformation. Previously, immunohistochemical detection of p53 has been possible only in fresh-frozen tissues. We examined p53 expression in paraffin-embedded tissues from 50 epithelial ovarian cancers and 25 primary breast cancers with a modified immunohistochemical (IHC) technique developed in this laboratory, using monoclonal antibody (MAb) PAb1801. The 75 cases were selected from a group of patients in whom the expression levels had already been assessed in a fresh-tissue IHC assay. An identical staining reactivity was observed in both formalin-fixed, paraffin-embedded tissue and fresh-frozen tissue in 48 of 50 (96%) epithelial ovarian cancers and in 23 of 25 (92%) primary breast cancers. Immunodetection of p53 in paraffin-embedded tissue blocks will be a useful alternative to the standard fresh-tissue assay and can accurately reflect the level of p53 expression in human tumors.

Antibodies, Monoclonal↗
PubMed1991

Reassembly of the corneal epithelial adhesion structures following human epikeratoplasty.

Ten epikeratoplasty lenticules removed after surgery were obtained for immunohistochemical and electron microscopic analysis to determine the pattern of re-formation of corneal epithelial adhesion structures. Antibodies to laminin and type VII collagen were used to determine the presence of basement membrane and anchoring fibrils, respectively. Electron micrographs were used to determine the percentage of basal cell membrane occupied by hemidesmosomes, the area of basal lamina per 100 microns of basal cell membrane, and the average maximum depth of penetration of anchoring fibrils into the stoma. Nine normal corneas served as controls. Compared with normal corneas (24.5% of basal cell membrane occupied by hemidesmosomes; 32.0 microns 2 basal lamina per 100 microns of basal cell membrane), lenticules removed for optical reasons had near-normal hemidemosomes as early as 10 weeks following surgery (mean, 20.3%). The area of basement membrane was reduced (16 microns 2 basal lamina per 100 microns of basement cell membrane). During the course of 2 to 3 years, irregularities and duplications of the basement membrane were noted. Compared with normal corneas, the two lenticules removed for persistent defects had a marked reduction of hemidesmosomes and basement membrane present under epithelium at 3 and 4 weeks (9.6% of basal cell membrane occupied by hemidesmosomes and 13.6 microns 2 basal lamina per 100 microns of basal cell membrane, and 5.4% of basal cell membrane occupied by hemidesmosomes and 7.2 microns 2 basal lamina per 100 microns of basal cell membrane, respectively.

Adult↗
PubMed1991

In vitro penetration of human corneal epithelium by Acanthamoeba castellanii: a scanning and transmission electron microscopy study.

Human corneal buttons were exposed to Acanthamoeba castellanii trophozoites and cysts for 12 hours at 35 degrees C. The buttons examined by light microscopy and scanning and transmission electron microscopy had severe epithelial ulceration and penetration by trophozoites. Observations on trophozoites below the surface suggest that penetration is accomplished by both secreted cytolytic enzymes and phagocytosis. It is likely that the secretion of one or more enzymes constitutes the initial step in preparing the host tissue for endocytosis or that the secretory mechanism is used by the amebas to move through the outer squamous layer to the basement epithelium where phagocytosis occurs. Based on this study and a previous study, it appears that entry into the cornea is a two-step process involving adherence and penetration by trophozoites.

Acanthamoeba↗
PubMed1991

In vitro intercellular adherence of Acanthamoeba castellanii: a scanning and transmission electron microscopy study.

Human corneal buttons were exposed to trophozoites and cysts of Acanthamoeba castellanii for 12 hours. Examination of the buttons by scanning electron microscopy showed numerous trophozoites on the surface of the epithelium. Trophozoites examined by transmission electron microscopy had limited regions of attachment to the epithelium but extensive regions of attachment to each other. Attachment regions were characterized as plaque-like maculae of an incomplete desmosome junction. Firm attachment mechanisms may explain how penetration of the human cornea occurs.

Acanthamoeba↗
PubMed1991

In vitro transfer of rabbit corneal epithelium from carriers to denuded corneas or cryolathed lenticules.

Rabbit corneal basal epithelial cells seeded onto fixed gelatin membranes or commercial collagen shields formed 3 to 5 cell layers after 1 to 3 weeks of culture at 35 degrees C in nutrient medium. The cells grew better, by comparison, in the collagen shields and eventually formed a multilayered tissue that resembled the stratified morphology of native epithelium. Transfer of multilayered cultures (prior to stratification) from these carriers in vitro to denuded corneal buttons or cryolathed lenticules resulted in complete adhesion of the grafted tissue to the underlying recipient buttons after 24- to 48-h incubations. After mechanically removing the carriers, most of the epithelial cells remained attached to the stromal surface. Our experimental findings indicated that both kinds of carriers may be suitable for epithelial transplantation, although the collagen shield is probably superior because of its better biocompatibility and physical characteristics.

Animals↗
PubMed1990

The effect of currently available contact lens disinfection systems on Acanthamoeba castellanii and Acanthamoeba polyphaga.

Contact lens disinfection systems were evaluated for their effectiveness in killing Acanthamoeba castellanii and Acanthamoeba polyphaga trophozoites and cysts. Amoebae were inoculated into commercially available contact lens cleaning and soaking solutions. At intervals varying from 30 minutes to 24 hours, solutions were filtered. The filters were removed and cultured for Acanthamoeba organisms. Striking differences were observed in the abilities of the different disinfecting solutions to kill the organisms. Solutions containing chlorhexidine were effective at very short exposure times. Solutions containing benzalkonium chloride required slightly longer exposure times but were faster than solutions containing only thimerosal. Solutions containing sorbate, polyaminopropyl biguanide, or polyquaternium-1 were not effective at killing Acanthamoeba organisms in the time allotted for the experiment. Solutions containing hydrogen peroxide were quite effective if the agent was not prematurely catalyzed. A. polyphaga generally required longer exposure to disinfectants than did A. castellanii for complete inhibition to occur.

Acanthamoeba↗