PubMed Health⌕ Search

Biomedical subjects

Anthony G Montag

Publications and source records attributed to Anthony G Montag.

At least 19 recordsLinked to original sources
PubMed2006

Estrogen receptor-beta expression in extraabdominal fibromatoses: an analysis of 40 cases.

BACKGROUND: Early experiments using ligand-binding assays demonstrated the presence of estrogen receptor (ER) in fibromatoses. These findings were not confirmed by later studies using immunohistochemical analysis. METHODS: To verify the expression of ERs in fibromatosis as well as to clarify the inconsistency between radioligand and early immunohistochemical studies, the authors examined a series of 40 extraabdominal fibromatoses using antibodies raised against ERbeta. RESULTS: All 40 cases of extraabdominal fibromatosis were at least focally positive for ERbeta. Thirty-three of 40 (83%) displayed 3+ (>50%) expression, 5 of 40 (12%) were 2+ (11-50%), and 2 of 40 (5%) cases showed 1+ (<10%) expression. All cases were negative for ERalpha. CONCLUSIONS: Although extraabdominal fibromatosis does not express ERalpha, there appears to be nearly uniform expression of ERbeta. This finding clarifies discrepancies in the literature regarding estrogen expression in fibromatosis, and provides a biological mechanism for the action of antiestrogenic compounds in the treatment of fibromatosis. Estrogen antagonists may have a role in the treatment of refractory or recurrent extraabdominal fibromatoses.

Abdomen↗
PubMed2006

CCN1/Cyr61 is regulated by the canonical Wnt signal and plays an important role in Wnt3A-induced osteoblast differentiation of mesenchymal stem cells.

Marrow mesenchymal stem cells are pluripotent progenitors that can differentiate into bone, cartilage, muscle, and fat cells. Wnt signaling has been implicated in regulating osteogenic differentiation of mesenchymal stem cells. Here, we analyzed the gene expression profile of mesenchymal stem cells that were stimulated with Wnt3A. Among the 220 genes whose expression was significantly changed by 2.5-fold, we found that three members of the CCN family, CCN1/Cyr61, CCN2/connective tissue growth factor (CTGF), and CCN5/WISP2, were among the most significantly up-regulated genes. We further investigated the role of CCN1/Cyr61 in Wnt3A-regulated osteogenic differentiation. We confirmed that CCN1/Cyr61 was up-regulated at the early stage of Wnt3A stimulation. Chromatin immunoprecipitation analysis indicates that CCN1/Cyr61 is a direct target of canonical Wnt/beta-catenin signaling. RNA interference-mediated knockdown of CCN1/Cyr61 expression diminished Wnt3A-induced osteogenic differentiation. Furthermore, exogenously expressed CCN1/Cyr61 was shown to effectively promote mesenchymal stem cell migration. These findings suggest that tightly regulated CCN1/Cyr61 expression may play an important role in Wnt3A-induced osteoblast differentiation of mesenchymal stem cells.

Adenoviridae↗
PubMed2006

Degenerative spine disease : pathologic findings in 985 surgical specimens.

A number of pathologic changes have been reported in spinal surgery specimens. The frequency of many of these is not well defined. We retrospectively reviewed the histologic features of 985 extradural spinal surgery specimens. Of the cases, 1.6% were identified clinically as synovial cysts. In addition, synovial tissue was seen in another 5.3% of cases, often embedded within disk material. Neovascularization of disk tissue was present in 8.1% of cases, chondrocyte clusters in 18.3%, and calcium pyrophosphate crystals in 2.8%, predominantly within disk material. With the exception of crystal deposits, all of these changes were significantly more common in the lumbar spine. A better understanding of cell-based degenerative changes will become essential with increasing research into cell-based therapies for spinal disk disease. We report data on the frequency of different pathologic changes and describe synovial metaplasia as a reactive change not previously reported.

Adult↗
PubMed2006

Steroid hormone receptor expression in nasopharyngeal angiofibromas. Consistent expression of estrogen receptor beta.

Nasopharyngeal angiofibroma is an uncommon tumor arising in adolescent males, suggesting that the tumor may be hormonally responsive. Previous studies have found androgen receptor (AR) expression but variable expression of estrogen receptor (ER). The recently described ss receptor for estrogen has not been analyzed in angiofibroma. We analyzed 13 cases of nasal angiofibroma by immunohistochemical analysis for the presence of ARs, progesterone receptors (PR), and ER-a and ER-ss. All 13 cases were positive for ER-ss, in stromal pericytic and endothelial cells, and 12 of 13 stained strongly. Five cases were positive for AR in stromal cells, most staining weakly, and with no staining in endothelial or pericytic cells. None of the cases displayed staining for ER-a or PR. The findings confirm that nasopharyngeal angiofibromas express ER and suggest that new modulators of ER-ss activity may provide an alternative therapy for these lesions.

Angiofibroma↗
PubMed2005

Increased expression of S100A6 is associated with decreased metastasis and inhibition of cell migration and anchorage independent growth in human osteosarcoma.

While most osteosarcoma patients have metastatic or micrometastatic lesions, less than 15% of them have clinically detectable metastatic diseases at presentation. To identify potential markers that may predict osteosarcoma metastasis, we analyzed the expression of S100A6 in 50 osteosarcoma cases and found that 84% of the analyzed specimens stained positive for S100A6. There is a trend towards decreased clinically evident metastasis with increased S100A6 staining. Overexpression of S100A6 in osteosarcoma cells decreases cell motility and anchorage independent growth on collagen gels. Our findings provide evidence that, while S100A6 is commonly overexpressed in human osteosarcoma, loss of its expression correlates with a metastatic phenotype.

Adolescent↗
PubMed2005

An orthotopic model of human osteosarcoma growth and spontaneous pulmonary metastasis.

Osteosarcoma is the most common primary malignancy of bone and patients often develop pulmonary metastases. In order to investigate the pathogenesis of human osteosarcoma, there is a great need to develop a clinically relevant animal model. Here we report the development of an osteosarcoma animal model using three related human osteosarcoma lines, the parental TE-85 and two derivative lines MNNG/HOS and 143B. In vitro characterization demonstrated that the 143B line had the greatest cell migration and the least cell adhesion activities among the three lines. The 143B line also exhibited the greatest ability for anchorage independent growth. When GFP-tagged osteosarcoma cells were injected into the proximal tibia of athymic mice, we found that 143B cells were highly tumorigenic and metastatic, and MNNG/HOS cells were tumorigenic but significantly less metastatic. TE85 cells were neither tumorigenic nor metastatic. The number of pulmonary metastases was found 50-fold higher in 143B injected animals than that in MNNG/HOS injected mice. No pulmonary metastases were detected in TE85 injected animals for up to 8 weeks. Primary tumors formed by MNNG/HOS and 143B cells could be visualized by whole body fluorescence imaging, while the pulmonary metastases were visualized on the necropsied samples. The GFP tagged 143B cells (and to a lesser extent, MNNG/HOS cells) were readily recovered from lung metastases. This clinically relevant model of human osteosarcoma provides varying degrees of tumor growth at the primary site and metastatic potential. Thus, this orthotopic model should be a valuable tool to investigate factors that promote or inhibit osteosarcoma growth and/or metastasis.

Animals↗
PubMed2005

Altered expression of alpha-methylacyl-coenzyme A racemase in prostatic adenocarcinoma following hormone therapy.

alpha-Methylacyl-coenzyme A racemase (AMACR) is a sensitive and specific tissue marker for the diagnosis of prostatic carcinoma. However, limited data are available on AMACR expression in residual prostatic carcinoma following hormone therapy. We analyzed 64 residual or recurrent prostatic adenocarcinomas following hormonal therapy for the expression of AMACR using a monoclonal antibody (P504S) to AMACR. In 20 localized cases, AMACR staining was absent in 11 (55%), 1+ in 6 (30%), and 2+ or 3+ in 3 (15%). However, in 15 metastatic cases, AMACR was absent in 1 (7%), 1+ in 3 (20%), and 2+ or 3+ in 11 (73%). None of the 29 postradiotherapy cases showed complete absence of AMACR staining: 2 (7%) were 1+, and 27 (93%) were 2+ or 3+. AMACR expression was reduced significantly in the majority of posthormonal residual carcinomas, whereas in postradiotherapy and in hormone-refractory metastatic prostatic adenocarcinoma, AMACR expression was retained. Therefore, the diagnosis of residual prostatic carcinoma after hormonal therapy using AMACR immunostaining must be interpreted with caution. Furthermore, AMACR might have a role in the recurrence of prostatic adenocarcinoma after medical therapy.

Adenocarcinoma↗
PubMed2005

Special relationships between fetal inflammatory response syndrome and bronchopulmonary dysplasia in neonates.

OBJECTIVE: To confirm previous known relationships between Fetal Inflammatory Response Syndrome (FIRS) and neonatal bronchopulmonary dysplasia (BPD) and to present information on previously unknown special relationships between inflammatory variables and BPD. STUDY DESIGN: At delivery, we obtained biological specimens including umbilical cord venous blood for plasma interleukin-6 levels, as well as placental histology and bacteriology. Among other neonatal outcomes, we collected prospective information on BPD. RESULTS: Of 141 newborns in the study, 16 had BPD; 79% of these had antecedent FIRS, 27% of those without FIRS had BPD. By multivariable regression, only very low birth weight (adjusted [adj] odds ratio [OR] 32.0, 95% Confidence Interval [CI] 5.0 to positive infinity) and FIRS (adj OR 5.7, 95% CI 1.1 to 42.3) remained significant risk factors. Escherichia coli, perhaps due to its pyogenic nature (strongly elicits inflammatory responses), may have had a special relationship with BPD. CONCLUSIONS: In our data, FIRS and neonatal BPD are highly associated. It is possible that certain pyogenic bacteria in the chorioamnion space may be implicated more often than others. CONDENSATION: Neonates having Fetal Inflammatory Response Syndrome at delivery may later develop BPD. Pyogenic bacteria, such as Escherichia coli, may be implicated more frequently.

Bronchopulmonary Dysplasia↗
PubMed2004

Connective tissue growth factor (CTGF) is regulated by Wnt and bone morphogenetic proteins signaling in osteoblast differentiation of mesenchymal stem cells.

Osteoblast lineage-specific differentiation of mesenchymal stem cells is a well regulated but poorly understood process. Both bone morphogenetic proteins (BMPs) and Wnt signaling are implicated in regulating osteoblast differentiation and bone formation. Here we analyzed the expression profiles of mesenchymal stem cells stimulated with Wnt3A and osteogenic BMPs, and we identified connective tissue growth factor (CTGF) as a potential target of Wnt and BMP signaling. We confirmed the microarray results, and we demonstrated that CTGF was up-regulated at the early stage of BMP-9 and Wnt3A stimulations and that Wnt3A-regulated CTGF expression was beta-catenin-dependent. RNA interference-mediated knockdown of CTGF expression significantly diminished BMP-9-induced, but not Wnt3A-induced, osteogenic differentiation, suggesting that Wnt3A may also regulate osteoblast differentiation in a CTGF-independent fashion. However, constitutive expression of CTGF was shown to inhibit both BMP-9- and Wnt3A-induced osteogenic differentiation. Exogenous expression of CTGF was shown to promote cell migration and recruitment of mesenchymal stem cells. Our findings demonstrate that CTGF is up-regulated by Wnt3A and BMP-9 at the early stage of osteogenic differentiation, which may regulate the proliferation and recruitment of osteoprogenitor cells; however, CTGF is down-regulated as the differentiation potential of committed pre-osteoblasts increases, strongly suggesting that tight regulation of CTGF expression may be essential for normal osteoblast differentiation of mesenchymal stem cells.

Adenoviridae↗
PubMed2004

Prognostic significance of E-cadherin protein expression in pathological stage I-III endometrial cancer.

PURPOSE: Decreased expression of E-cadherin in endometrial cancer cells is associated with adverse prognostic features. This study aimed to evaluate the prognostic significance of decreased E-cadherin expression in patients with endometrial cancer. EXPERIMENTAL DESIGN: Between 1992 and 1999, 102 endometrial cancer patients with stage I-III disease underwent primary surgery at the University of Chicago. Representative tissue specimens were immunostained with a monoclonal antibody to E-cadherin. A semiquantitative evaluation scale was developed based on the percentage of endometrial cancer cells with membranous E-cadherin staining. Tissue sections were scored as "3" if >75%, "2" if 25-75%, "1" if 5-25%, and "0" if <5% of cells stained. E-Cadherin staining was correlated with overall survival (OS), cause-specific survival (CSS), progression-free survival (PFS), and extrapelvic progression. Multivariate Cox proportional hazards modeling was used to estimate hazard ratios, controlling for clinicopathological characteristics and adjuvant treatment. Median follow-up for the study group was 58.5 months. RESULTS: E-Cadherin staining was scored as 0, 1, 2, and 3 in 29.4%, 18.6%, 26.5%, 25.5% of cases, respectively. E-Cadherin expression was positively correlated with myometrial invasion (Kendall tau: 0.30, P < 0.01), and negatively correlated with grade (Kendall tau: -0.13, P = 0.15) and papillary serous or clear cell histology (Kendall tau: -0.14, P = 0.12). Five-year actuarial OS, CSS, PFS, and extrapelvic recurrence rates for negative (score = 0), heterogeneous (score = 1-2), and positive (score = 3) staining were as follows: OS, 69.2 versus 75.7 versus 81.0% (P = 0.64); CSS, 78.8 versus 91.2 versus 95.5% (P = 0.19); PFS, 69.1 versus 88.6 versus 92.2% (P = 0.079), and extrapelvic progression, 20.8 versus 7.3 versus 4.0% (P = 0.17). On multivariate Cox regression, a higher E-cadherin expression score was associated with decreased overall mortality [hazard ratio (HR), 0.59; 95% confidence interval (CI), 0.34-1.03; P = 0.066), and statistically significant decreases in endometrial cancer mortality (HR, 0.23; 95% CI, 0.055-0.94; P = 0.040), disease progression (HR, 0.28; 95% CI, 0.10-0.77; P = 0.014), and extrapelvic recurrence (HR, 0.24; 95% CI, 0.062-0.97; P = 0.045). CONCLUSIONS: Decreased E-cadherin expression is an independent prognostic factor for disease progression and mortality in pathological stage I-III endometrial cancer. Evaluation of E-cadherin expression may aid in the selection of patients for more aggressive adjuvant therapy.

Aged↗
PubMed2004

Inhibitor of DNA binding/differentiation helix-loop-helix proteins mediate bone morphogenetic protein-induced osteoblast differentiation of mesenchymal stem cells.

Bone morphogenetic proteins (BMPs) belong to the TGF-beta superfamily and play an important role in development and in many cellular processes. We have found that BMP-2, BMP-6, and BMP-9 induce the most potent osteogenic differentiation of mesenchymal stem cells. Expression profiling analysis has revealed that the Inhibitors of DNA binding/differentiation (Id)-1, Id-2, and Id-3 are among the most significantly up-regulated genes upon BMP-2, BMP-6, or BMP-9 stimulation. Here, we sought to determine the functional role of these Id proteins in BMP-induced osteoblast differentiation. We demonstrated that the expression of Id-1, Id-2, and Id-3 genes was significantly induced at the early stage of BMP-9 stimulation and returned to basal levels at 3 days after stimulation. RNA interference-mediated knockdown of Id expression significantly diminished the BMP-9-induced osteogenic differentiation of mesenchymal progenitor cells. Surprisingly, a constitutive overexpression of these Id genes also inhibited osteoblast differentiation initiated by BMP-9. Furthermore, we demonstrated that BMP-9-regulated Id expression is Smad4-dependent. Overexpression of the three Id genes was shown to promote cell proliferation that was coupled with an inhibition of osteogenic differentiation. Thus, our findings suggest that the Id helix-loop-helix proteins may play an important role in promoting the proliferation of early osteoblast progenitor cells and that Id expression must be down-regulated during the terminal differentiation of committed osteoblasts, suggesting that a balanced regulation of Id expression may be critical to BMP-induced osteoblast lineage-specific differentiation of mesenchymal stem cells.

Adenoviridae↗
PubMed2004

Meissner corpuscles and somatosensory acuity: the prehensile appendages of primates and elephants.

Meissner corpuscles (MCs) are specialized mechanoreceptors located exclusively in the papillae of glabrous skin. They are confined largely to cutaneous pads of the extremities and respond to transient, phasic, or vibratory stimuli. Though absent in most eutherian taxa, MCs are reported in all primates studied, being most developed in modern humans. The location of MCs between the internal ridges of the epidermis indicates they are well situated to detect friction or deformation at the external surface. Accordingly, MCs are hypothesized to provide primates generally with an enhanced tactile perception. However, the selective pressures favoring greater somatosensory acuity in primates are seldom considered. Interestingly, primate digital dexterity varies greatly. In general, dexterity improves with the extent to which foraging requires food manipulation or textural evaluation. This observation implies that MC density could vary accordingly. Here we report on the density of MCs in five anthropoid taxa selected to represent diverse dietary regimes. Results show that greater MC density correlates with the extent to which primates are frugivorous; however, locomotor and/or phylogenetic effects cannot be discounted.

Adaptation, Physiological↗
PubMed2004

Estrogen receptor beta expression in vascular neoplasia: an analysis of 53 benign and malignant cases.

The importance of estrogen in vascular neoplasia is suggested by a predilection for women and a tendency for rapid growth during pregnancy. Although early experiments using radioligand assays demonstrated estrogen receptor (ER) expression, these findings were not confirmed by subsequent immunohistochemical studies which were performed with antibodies raised against ER alpha. A newly discovered estrogen receptor subtype, ER beta, has not been previously characterized in vascular lesions. In order to verify the expression of estrogen receptors in vascular neoplasms as well as to clarify the inconsistency between radioligand and early immunohistochemical studies, we examined a series of 53 benign and malignant vascular neoplasms for ER beta expression. All of the subtypes of vascular neoplasia examined had nuclear expression of ER beta. The majority of cases (94%) displayed 2+ to 3+ staining. The discrepancy between radioligand studies and previous immunohistochemical studies is attributable to the use of antibodies raised against ER alpha, which is not expressed in vascular lesions, and not ER beta, which is broadly expressed in both benign and malignant vascular neoplasms. Although ER beta may be of limited diagnostic use in vascular neoplasia due to its broad expression, the potential exists for a therapeutic approach using ER agonists.

Estrogen Receptor beta↗
PubMed2003

Myoid differentiation and prognosis in adult pleomorphic sarcomas of the extremity: an analysis of 92 cases.

BACKGROUND: The results of a recent study demonstrated an association between myoid differentiation and an adverse prognosis in adult patients with pleomorphic sarcoma, as determined by 5-year metastasis-free survival rates. METHODS: To confirm the importance of muscle differentiation on prognosis in a well controlled clinical context, 92 samples from patients with pleomorphic sarcoma of the extremity from a single institution were immunostained with 4 monoclonal antibodies believed to be correlated with myoid differentiation: alpha-smooth muscle actin, muscle-specific actin, desmin, and myoglobin. RESULTS: Forty-two cases were positive for at least 1 muscle marker and 50 cases were uniformly negative. Between the two groups, there was no significant difference in tumor size, tumor extent, or patient age found; however, histologic grade was significantly higher (P = 0.038) in the myoid tumors. The 5-year survival differed significantly between patients with myoid tumors (35%) and those without myoid tumors (65%) (P = 0.0054). Myoid differentiation remained an adverse prognostic indicator after adjusting for clinically significant factors (i.e., histologic grade, tumor size, tumor extent, and patient age) (P = 0.01) (hazard ratio, 2.39; 95% confidence interval, 1.24-4.63). Furthermore, there was an inverse relation found between the number of myoid markers present and survival (P = 0.004). CONCLUSIONS: Myoid differentiation was found to be an independent indicator of adverse prognosis in adult patients with pleomorphic spindle cell sarcoma of the extremity.

Actins↗
PubMed2003

Components of the systemic fetal inflammatory response syndrome as predictors of impaired neurologic outcomes in children.

OBJECTIVE: The purpose of this study was to compare interleukin-6 and funisitis as predictors of impaired neurologic outcomes in children by performing a secondary analysis on data that were collected prospectively for another purpose. STUDY DESIGN: We examined umbilical cords for funisitis and obtained cord blood for interleukin-6 levels. A psychomotor developmental index score was determined for each child at age 18 months. RESULTS: The prevalence (46%) of elevated interleukin-6 levels (> or = 10 pg/mL) among children with low psychomotor developmental index scores (<100) was not significantly different from that of children with normal scores (47%). Among children with funisitis (n = 21), the median psychomotor developmental index score was 94; for children without funisitis (n = 92), it was 99 (P <.02). When the data were regressed for confounding, funisitis remained significant (adjusted odds ratio, 1.3; 95% CI, 1.1-1.9). Furthermore, funisitis was a more specific predictor of low psychomotor developmental index scores (P <.001), although elevated interleukin-6 levels were more sensitive. CONCLUSION: When used for the prediction of impaired neurologic outcomes in children, funisitis has better specificity and thus a better positive predictive value than does interleukin-6.

Adult↗
PubMed2003

A comparison study of staging systems for bone sarcomas.

A retrospective study of 250 patients treated at one institution was done to evaluate the prognostic significance of the new American Joint Committee on Cancer staging system compared with the Musculoskeletal Tumor Society staging system for patients with sarcomas of bone. Regarding the Musculoskeletal Tumor Society system, there were significant differences in survival among patients with Stage I, Stage II, and Stage III disease. There were no significant differences between patients with Stages I-A and I-B disease, nor between patients with Stages II-A and II-B disease. Similarly, regarding the new American Joint Committee on Cancer staging system, there were significant differences among patients with Stage I, Stage II, and Stage IV disease. No significant differences were seen between patients with Stages I-A and I-B disease, between patients with Stages II-A and II-B disease, nor between patients with Stages IV-A and IV-B disease. A significant advantage in the ability to predict prognosis for one staging system over the other staging system was not shown with the relatively small number of patients in this study.

Ameloblastoma↗
PubMed2003

Oncologic outcomes of primary lymphoma of bone in adults.

A retrospective analysis of adult patients who had lymphomatous involvement of bone was done to evaluate the prognostic factors and the oncologic outcome. Between 1984 and 1994, 28 patients (nine women and 19 men) were diagnosed with lymphoma of bone. The median age was 45 years (range, 23-76 years). The median followup was 40.3 months (range, 0.5 months-15.8 years). Eighteen patients (64%) were classified as having Stage IE disease, two patients (36%) were classified as having stage II disease, and eight patients were classified as having Stage IV disease. Twenty-one of the lesions were classified as diffuse large B cell with multilobulated nuclei. Two patients had local recurrence. Three patients had osteonecrosis develop at the site of their radiation therapy. The 5-year Kaplan-Meier survival estimate was 57.8% (95% confidence interval range, 40-33 82.8). Statistically improved survival was seen in patients younger than 40 years and those patients with diffuse large B cell with multilobulated nuclei. Patients with primary lymphoma of bone did not have a statistically improved survival compared with patients with systemic disease. The results of the current study suggest that age at diagnosis and histologic subtypes are important prognostic factors; however, the diagnosis of primary lymphoma of bone does not confer improved prognosis.

Adult↗