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I Goldberg

Publications and source records attributed to I Goldberg.

At least 37 records · Page 2Linked to original sources
PubMed2001

Leptin induces angiopoietin-2 expression in adipose tissues.

Adipose tissues consisting of adipocytes, microvasculature, and stroma are completely ablated upon over-expression of leptin in rats. This tissue regression is mediated by enhanced lipid beta-oxidation, adipocyte dedifferentiation, and apoptosis. To further characterize this phenomenon, we studied the possible effect of leptin on the adipose microvasculature. Tissue microvasculature is maintained by the interplay between positive and negative signals mediated by factors including vascular endothelial growth factor (VEGF), basic fibroblast growth factor, angiopoietin-1 (Ang-1), and Ang-2. Expression of the negative signal Ang-2 was reported in fetal tissues and in the adult ovary, which undergoes vascular remodeling or regression. We demonstrate that leptin induces the expression of Ang-2 in adipose tissue without a concomitant increase in VEGF. Induction of Ang-2 occurred in an autocrine manner, as demonstrated in cultured adipocytes but not in several other cell types. This tissue-specific induction of Ang-2 coincided with initiation of apoptosis in adipose endothelial cells. We propose that induction of Ang-2 by leptin in adipose cells is one of the events leading to adipose tissue regression.

3T3 Cells↗
PubMed2001

The effect of intravenous immunoglobulins on the progression of experimental autoimmune myocarditis in the rat.

The aim of this study was to evaluate the efficacy of two experimental regimes of human intravenous immunoglobulins (IVIG) on the progression of experimental autoimmune myocarditis (EAM). EAM is induced by immunization against myosin and represents a T-cell-dependent disorder that progresses toward dilated cardiomyopathy similar to the human equivalent. No effective treatment is currently at hand for management of the disorder, as immunosuppressant drugs are associated with multiple side effects. Three groups of Lewis rats were induced to develop EAM by immunization with porcine myosin and sacrificed 21 days later. Group A received a 5-day regimen of IVIG (800 mg/kg) following induction of the disorder; Group B received a daily dose of IVIG (800 mg/kg) and group C was treated with PBS. IVIG given daily but not during the first 5 days significantly suppressed myocarditis score (0.81 +/- 0.26 and 1.14 +/- 0.42, respectively) in comparison with controls (mean score of 1.78 +/- 0.36). The effect was accompanied by a reduction in the cellular and humoral immune response of the respective animals toward myosin. IVIG was deposited within the extracellular matrix surrounding the damaged myocytes. TNF-alpha expression was reduced in both groups treated with IVIG, whereas iNOS expression paralleled the extent of myocardial inflammation regardless of treatment. IVIG at doses twice those applied for human disease are effective in ameliorating the progression of EAM. The effect may be mediated by suppression of the cellular and humoral response to myosin. IVIG may be found clinically feasible in humans as an adjuvant or single therapy for autoimmune myocarditis.

Animals↗
PubMed2001

Caveolin-1 expression in advanced-stage ovarian carcinoma--a clinicopathologic study.

OBJECTIVE: The aim of this study was to analyze the correlation among the expression of caveolin-1, the protein constituent of caveolae, and disease outcome in advanced-stage ovarian carcinomas. METHODS: Sections from 76 primary ovarian carcinomas and metastatic lesions from 45 patients diagnosed with advanced-stage ovarian carcinoma (FIGO stages III-IV) were evaluated for caveolin-1 expression using immunohistochemistry. Patients were divided into long-term survivors and short-term survivors based on disease outcome. Twenty nonneoplastic fallopian tubes and ovaries were additionally studied. RESULTS: The mean follow-up period was 70 months. The mean values for disease-free survival and overall survival were 109 and 125 months for long-term survivors, compared to 3 and 21 months for short-term survivors, respectively. Caveolin-1 expression was localized to the cell membrane in 24/76 (32%) specimens and was detected in the cytoplasm in 52/76 (68%) cases. Both patterns were more often detected in metastases, when compared with primary tumors. In addition, membrane immunoreactivity was more often seen in tumor of short-term survivors. These differences did not reach statistical significance (P > 0.05). Combined membrane and cytoplasmic immunoreactivity was seen in 17/20 (85%) nonneoplastic lesions. Despite its role in tyrosine-kinase-mediated signal transduction in vitro studies, caveolin-1 expression in carcinomas showed no association with the protein expression of c-erbB-2 and epidermal growth factor receptor, evaluated in a previous study of this patient cohort. CONCLUSIONS: This study provides the first in vivo evidence of caveolin-1 membrane expression in human malignancies. Caveolin-1 is often expressed in advanced-stage ovarian carcinoma, but does not appear to be a powerful predictor of disease outcome in these tumors. The reduced expression level in carcinomas compared to nonneoplastic epithelium may point to a role for caveolin-1 as a tumor suppressor gene.

Adult↗
PubMed2001

Topoisomerase II immunostaining as a prognostic marker for survival in ovarian cancer.

OBJECTIVE: This study aimed to evaluate topoisomerase II compared to Ki-67 expression as a marker for tumor behavior and for prognosis of patients with ovarian cancer. METHODS: In order to screen for potential prognostic markers, two groups of patients with advanced stage (FIGO stages III and IV) epithelial ovarian carcinoma were selected based on differences in survival (mean survival, 11 years versus 2 years). Pathology slides were reviewed, and immunohistochemistry using antibodies to topoisomerase II and Ki-67 was performed on the original cell blocks. No patients were lost to follow-up. RESULTS: Detectable expression of topoisomerase II was present in 70.0 +/- 30.3% of cells in patients with rapidly progressing disease, compared to only 12.3 +/- 12.4% of cells in long-term survivors (P = 0.0001). Ki-67 expression was also more frequent in short-term survivors compared to long-term survivors, but the difference was less prominent than with topoisomerase II (P = 0.01). Specificity and sensitivity as prognostic factors reached 88.2 and 93.8% for topoisomerase II, compared to 55.6 and 88.2% for Ki-67. CONCLUSIONS: Topoisomerase II expression as detected by immunohistochemistry in tumor samples emerged as a promising clinically relevant biomarker for survival in advanced epithelial ovarian cancer.

Biomarkers, Tumor↗
PubMed2001

Reduced expression of plakoglobin correlates with adverse outcome in patients with neuroblastoma.

Plakoglobin and its homologue beta-catenin are cytoplasmic proteins that mediate adhesive functions by interacting with cadherin receptors and signaling activities by interacting with transcription factors. It has been suggested that plakoglobin can suppress tumorigenicity whereas beta-catenin can act as an oncogene. We investigated the correlation between the expression pattern of N-cadherin, beta-catenin, and plakoglobin and tumor behavior in primary tumors of 20 neuroblastoma patients of all stages and in 11 human neuroblastoma cell lines. N-cadherin and beta-catenin were detected in 9 of 11 and 11 of 11 cell lines, respectively, whereas plakoglobin was undetectable or severely reduced in 6 of 11 cell lines. Tumor cells from 16 of 20 patients expressed N-cadherin and 20 of 20 patients expressed beta-catenin at levels similar to those of normal ganglion cells. Plakoglobin was undetectable in 9 of 20 tumors. Plakoglobin deficiency in the primary tumors was significantly associated with adverse clinical outcome. Five of the patients with plakoglobin-negative tumors died whereas four patients are alive without evident disease. In contrast, all patients with plakoglobin-positive tumors are alive; 2 of 11 are alive with the disease and 9 of 11 are alive without evident disease. These results suggest that down-regulation of plakoglobin may be of prognostic value for neuroblastoma patients as predictor of poor outcome.

Blotting, Western↗
PubMed2001

Ovarian carcinoma cells in serous effusions show altered MMP-2 and TIMP-2 mRNA levels.

The expression of matrix metalloproteinases (MMP) and their inhibitor TIMP-2 in serous effusions from patients with ovarian carcinoma and its association with clinico-pathological parameters were analysed. The findings in carcinoma cells in effusions were compared with corresponding primary and metastatic lesions. Sixty-six effusions and 96 tissue sections were stained for MMP-1, MMP-2 and MMP-9 applying immunohistochemistry (IHC) and analysed for MMP-2, MMP-9 and TIMP-2 expression using mRNA in situ hybridisation (ISH). MMP-2 and MMP-9 mRNA levels in 30 effusions were subsequently analysed using reverse transcription- polymerase chain reaction (RT-PCR). MMP and TIMP expression was detected in both carcinoma and mesothelial cells in effusions. The levels were consistently higher in malignant cells, significantly so for MMP-1 (P=0.016) and MMP-2 (P=0.036) proteins, as well as for TIMP-2 mRNA (P=0.008). In tissue sections, MMP-1, MMP-2 and MMP-9 protein expression was mostly localised to tumour cells, while MMP-2, MMP-9 and TIMP-2 mRNA were predominantly detected in stromal cells. Adenocarcinoma cells in effusions showed a significant upregulation of MMP-2 expression compared with primary tumours, with a concomitant downregulation of TIMP-2. RT-PCR demonstrated the presence of MMP-2 and MMP-9 in 28/30 and 0/30 specimens, respectively. MMP and TIMP are thus mainly synthesised by cancer cells in effusions, while stromal cells have a similar role in solid tumours. MMP-1 and MMP-2 production predominates over that of MMP-9 in effusions. Increased MMP-2 and reduced TIMP-2 levels are seen in ovarian carcinoma cells in effusions, possibly marking the acquisition of a metastatic phenotype.

Ascitic Fluid↗
PubMed2001

Tissue-specific gene therapy directed to tumor angiogenesis.

Gene therapy directed specifically to the vascular wall, particularly to angiogenic endothelial cells is a prerequisite in vascular disease treatment. Angiogenesis is a major feature in many pathological conditions including wound healing, solid tumors, developing metastases, ischemic heart diseases and diabetic retinopathy. In the present study we developed a tissue-specific gene therapy to the angiogenic blood vessels of tumor metastasis using an adeno-based vector containing the murine preproendothelin-1 (PPE-1) promoter. Genes activated by the PPE-1 promoter were highly expressed in bovine aortic endothelial cells in vitro. Systemic injection of the adenoviral vectors AdPPE-1-luciferase and AdCMV-luciferase to normal C57BL/6 mice, resulted in higher activity of PPE-1 promoter compared with CMV promoter in the aorta and vascularized tissues such as heart, kidney, lung and pancreas. Systemic administration of the adenoviral vector, in mice bearing Lewis lung carcinoma, resulted in high and specific activity of PPE-1 in the new vasculature of primary tumors and lung metastasis. Cellular distribution of the delivered gene revealed highest expression of GFP in angiogenic endothelial cells of the metastasis. We expect that this approach of 'vascular-directed' gene therapy will be applicable to both vascular diseases and cancer.

Adenoviridae↗
PubMed2001

The efficacy and safety of intraoperative and/or postoperative 5-fluorouracil in trabeculectomy and phacotrabeculectomy.

PURPOSE: First, to assess the safety and efficacy of using 5-fluorouracil (5-FU) to improve trabeculectomy and phacotrabeculectomy success rates, and second, to assess the efficacy of intraoperative and reduced postoperative 5-FU following trabeculectomy compared with a more intensive course of postoperative 5-FU alone. METHODS: In a retrospective, unmatched, non-randomized consecutive series study, 186 eyes of 186 patients who had filtration surgery were followed for 2 years in four groups: 51 patients had undergone trabeculectomy surgery with postoperative 5-FU, 51 had phacotrabeculectomy with postoperative 5-FU, 56 had trabeculectomy with both intraoperative and postoperative 5-FU, and 28 patients had trabeculectomy without antifibrotics. RESULTS: At all times mean intraocular pressure (IOP) was reduced n all groups (P < 0.001 for each group). Success was defined as IOP < 16 mmHg and > 30% IOP reduction at the 2-year follow up. It was achieved in 71% of the trabeculectomy patients with intraoperative and postoperative 5-FU, 76% of the trabeculectomy group with only postoperative 5-FU, 55% of the phacotrabeculectomy/5-FU group, and in 29% of the trabeculectomy-only eyes (between-group differences P < 0.01). Success rates were not significantly different for the intraoperative and postoperative 5-FU trabeculectomy versus the postoperative 5-FU-only eyes, but the former had fewer postoperative 5-FU injections and corneal ulceration (P < 0.01 for both). CONCLUSIONS: 5-Fluorouracil was safe and improved trabeculectomy survival. Intraoperative 5-FU allowed fewer postoperative 5-FU injections and fewer side-effects without compromising success rates. Phacotrabeculectomy with postoperative 5-FU had a lower surgical success rate than did trabeculectomy with 5-FU and this was not statistically different from trabeculectomy without 5-FU.

Adolescent↗
PubMed2001

Ets-1 mRNA expression in effusions of serous ovarian carcinoma patients is a marker of poor outcome.

Ets-1 proto-oncogene is a transcription factor with a role in the activation of metastasis-associated molecules. We recently found that Ets-1 mRNA expression in solid tumors is a marker of poor prognosis in ovarian carcinoma. The objective of this study was to compare the expression of Ets-1 mRNA in effusions and primary and metastatic tumors of serous ovarian carcinoma patients and to evaluate its prognostic role in effusions. Sections from 67 malignant effusions and 90 primary and metastatic lesions were evaluated for expression of Ets-1 using mRNA in situ hybridization. Expression of Ets-1 mRNA was detected in carcinoma cells in 24 of 67 (36%) effusions. Expression in cancer cells was similar in peritoneal and pleural effusions. In solid lesions Ets-1 expression was detected in both tumor cells and stromal cells in 34 of 90 (38%) lesions. Ets-1 expression in tumor cells showed a strong association with that of stromal cells (p <0.001). Ets-1 expression in effusions showed an association with mRNA expression of basic fibroblast growth factor, previously studied in this patient cohort (p = 0.019). Ets-1 expression in solid lesions showed an association with mRNA expression of vascular endothelial growth factor (p <0.001 for both carcinoma and stromal cells), basic fibroblast growth factor (p = 0.007 for carcinoma cells, p = 0.006 for stromal cells), and interleukin-8 (IL-8) (p = 0.001 for tumor cells). Ets-1 mRNA showed upregulation in metastases when compared with effusion specimens (p = 0.028). In univariate survival analysis Ets-1 expression in carcinoma cells in effusions correlated with poor survival (p = 0.003). Our findings confirm the role of Ets-1 as a novel prognostic marker in advanced-stage ovarian carcinoma and extend it to effusion specimens. The elevated expression in solid metastases supports a central role in tumor progression as well. The association between Ets-1 mRNA expression and the expression of angiogenic genes, documented also in our previous study, points to the close link between these molecules, in agreement with the role of angiogenic genes in the transcriptional activation of Ets-1. The identical phenotype of carcinoma cells in pleural and peritoneal effusions provides further evidence for our theory that cells at these sites share similar genotypic and phenotypic profiles.

Adult↗
PubMed2001

Central corneal thickness, tonometry, and ocular dimensions in glaucoma and ocular hypertension.

PURPOSE: To assess possible correlations between central corneal thickness, tonometry, and ocular dimensions. PATIENTS AND METHODS: One hundred seventeen eyes of 117 patients who were not taking any intraocular pressure-lowering medications were studied prospectively. Forty-one patients had ocular hypertension; 13 patients had primary open-angle glaucoma; and 10 patients had normal-pressure glaucoma. Twenty-three healthy eyes were included. Thirty glaucoma suspects (10 patients monitored for possible normal-pressure glaucoma and 20 patients with intermittent ocular hypertension) were included for correlation analysis. Tonometry was performed with Goldmann applanation and pneumotonometry, and central corneal thickness, anterior chamber depth, lens thickness, and axial length were measured ultrasonically. RESULTS: Central corneal thickness was lowest in eyes with normal-pressure glaucoma (538 +/- 51 microm), highest in eyes with ocular hypertension (570 +/- 32 microm), and intermediate and similar in eyes with primary open-angle glaucoma and healthy eyes (547 +/- 34 microm and 554 +/- 32 microm, respectively). These differences were significant (P = 0.028). Goldmann applanation tonometry and central corneal thickness were weakly correlated (r = 0.12, P = 0.205), with a 0.2-mm Hg change per 10-microm variation in central corneal thickness. Pneumotonometry measurements were more strongly correlated with central corneal thickness (r = 0.21, P < 0.05). Lens thickness was strongly correlated with age (r = 0.57, P < 0.001). Anterior chamber depth was negatively correlated with lens thickness and age (r = -0.29, P < 0.005 and r = -0.25, P < 0.01). Axial length was correlated with anterior chamber depth and age (r = 0.5, P < .001 and r = -0.19, P < 0.05). CONCLUSION: Eyes diagnosed as having ocular hypertension have thicker corneas and eyes labeled as having normal-pressure glaucoma have thinner corneas, when compared with healthy eyes or eyes with primary open-angle glaucoma. The effect of central corneal thickness on Goldmann applanation tonometry accuracy appears to be small and usually not clinically relevant. When corneal thickness is markedly different from normal, the clinician may need to factor this into diagnosis and management.

Aged↗
PubMed2001

Comparison of topical travoprost eye drops given once daily and timolol 0.5% given twice daily in patients with open-angle glaucoma or ocular hypertension.

PURPOSE: This 9-month study compared the intraocular pressure (IOP)-lowering efficacy and safety of once-daily travoprost ophthalmic solutions (0.0015% and 0.004%) with twice-daily timolol 0.5%. PATIENTS AND METHODS: This study was conducted using a double-masked, randomized, parallel-group design; adult patients with open-angle glaucoma or ocular hypertension (IOP between 24 and 36 mm Hg, inclusive at 9 am and between 21 and 36 mm Hg, inclusive, at 11 am and 4 pm on two eligibility visits after an appropriate washout of previous treatments). In both eyes, the travoprost vehicle (placebo) was instilled at 9 am and travoprost (0.0015% or 0.004%) was instilled at 9 pm, or timolol 0.5% was instilled at both times. The primary efficacy variable was mean IOP measured at 9 am, 11 am, and 4 pm at baseline and follow-up visits. RESULTS: Five hundred seventy-three patients were randomized to the study treatments. Mean IOP, which was combined across study visits, was lower with travoprost 0.004% than with timolol 0.5% at 9 am (P = 0.0246), 11 am (P = 0.0039), and 4 pm (P = 0.0004). Intraocular pressure was lower with travoprost 0.004% than with travoprost 0.0015% at 11 am (P = 0.0314), the time of peak drug activity. Mean IOP was consistently lower with travoprost 0.0015% than with timolol 0.5%. Mean IOP reductions from baseline were significantly (P less than equal 0.0001) greater with travoprost 0.004% (8.0-8.9 mm Hg) than with timolol 0.5% (6.3-7.9 mm Hg). The most frequent related adverse events were hyperemia, pruritus, discomfort, pain, and iris pigmentation changes. The local tolerance was better in the timolol group compared with patients receiving travoprost. There were no serious unexpected treatment-related adverse events in any group. CONCLUSIONS: Travoprost 0.004% reduced diurnal mean intraocular pressure significantly more than timolol 0.5%. Both concentrations of travoprost were well tolerated and safe for use in patients with open-angle glaucoma or ocular hypertension.

Administration, Topical↗
PubMed2001

Insulin-like growth factor I and II preserve myocardial structure in postinfarct swine.

BACKGROUND: Insulin-like growth factors (IGF) I and II improve myocardial function after coronary occlusion in different animal models. OBJECTIVES: To investigate the mechanism of improved myocardial function after administration of IGF-I or IGF-II in acute myocardial infarction. METHODS: Female pigs (mean (SD) weight 25 (5) kg) were subjected to acute myocardial infarction by microembolisation with 75-150 micrometer affigel blue beads. The beads contained and slowly released 150 microgram/pig of IGF-I (n = 6), IGF-II (n = 6), or pig albumin (n = 6). Echocardiography, perfusion imaging, and haemodynamic measurements were performed before infarction and during four weeks after infarction. Regional wall motion of different left ventricular segments was scored semiquantitatively on the basis of a three point scoring system, from normal = 0 to dyskinesia = 3. Serum cardiac troponin I concentration was measured before, immediately after, and three hours after the infarct. Excised hearts were analysed for actin, desmin, blood vessel density, and DNA laddering within the infarct, border, and normal myocardial areas. RESULTS: Myocardial function of the infarct related area improved significantly during the four weeks of follow up in both the IGF groups (p = 0.01). Myocardial perfusion, heart rate, and blood pressure were similar in all the animals during the study. Treated animals had lower serum cardiac troponin I concentration (p = 0.001), more actin in the border area (p = 0.01) and infarct area (p = 0.0001), and reduced DNA laddering in the infarct area compared with the controls (p < 0.05). IGF groups had more blood vessels in the border area (p = 0.04) and the infarct area (p = 0.003). CONCLUSIONS: Both types of IGF improved myocardial function and the improvement was associated with preservation of myocardial structure. IGF-I was more effective than IGF-II.

Actins↗
PubMed2001

Immunohistochemical analysis of candidate gene product expression in the duodenal epithelium of children with coeliac sprue.

BACKGROUND: Coeliac sprue is a chronic disease, in which there is a characteristic mucosal lesion of the small intestine and impaired nutrient absorption, which improves upon the withdrawal of wheat gliadins and related grain proteins from the diet. Biopsy specimens demonstrate diffuse enteritis with pronounced atrophy or total loss of villi. There is also a long term risk of malignant disease. AIMS: To compare the immunoexpression of DCC (deleted in colon cancer), p53, E-cadherin, and beta-catenin in the duodenal mucosa of children with coeliac disease with that seen in children with no evidence of small intestinal disease. METHODS: To gain more insight into the genetic and immunohistochemical alterations of the duodenal epithelium in coeliac disease, 21 endoscopic biopsies from children with coeliac disease and 10 duodenal biopsies from children without coeliac disease were immunohistochemically evaluated for p53, DCC, E-cadherin, and beta-catenin. RESULTS: DCC expression was not reduced in patients with coeliac disease compared with those without coeliac disease. p53 positive nuclear immunostaining was seen in seven of the 21 patients with coeliac disease. Positive nuclear staining was seen mainly in the deep and the lateral aspects of the crypts. All patients in the control group were negative for p53. In nine and three of the 21 patients with coeliac disease, respectively, the immunohistochemical expression of E-cadherin and beta-catenin was reduced. However, both E-cadherin and beta-catenin immunostaining in the control group was not altered. CONCLUSIONS: E-cadherin and beta-catenin were reduced in the duodenal epithelium of children with coeliac disease when compared with normal mucosa. p53 was overexpressed in the duodenal mucosa of patients with coeliac disease. The reduced expression of E-cadherin and beta-catenin and p53 overexpression may contribute to the morphological changes seen in the small intestinal mucosa in coeliac disease.

Adolescent↗
PubMed2001

Career success after flexible training in psychiatry: a survey of former flexible trainees in the Thames regions.

This article outlines the findings of a study which indicate that flexible training in psychiatry was considered adequate to prepare doctors for both full-time and part-time work and that those wishing to work part time had no difficulty in finding jobs after accreditation. However, there was evidence to suggest that part-time consultants experienced more problems and less job satisfaction and that part-time training and working may restrict opportunities for an academic career.

Adult↗
PubMed2001

Expression of membrane-type 1, 2, and 3 matrix metalloproteinases messenger RNA in ovarian carcinoma cells in serous effusions.

We studied the levels of matrix metalloproteinase (MMP)-2, membrane-type (MT)1-MMP, MT2-MMP, and MT3-MMP in 43 malignant pleural and peritoneal effusions using reverse transcription-polymerase chain reaction (RT-PCR) and cellular localization of MT1-MMP in 66 effusion specimens and 85 corresponding primary and metastatic tumors using messenger RNA (mRNA) in situ hybridization (ISH). In 43 effusions, MMP-2 mRNA was detected in 37, MT1-MMP in 25, and MT2-MMP in 32. Expression of MT1-MMP and MT2-MMP was found in 21 specimens; in 16 MT-MMP-positive specimens, mRNA for only 1 of 2 enzymes was expressed. MT3-MMP mRNA was not detected. High levels of MMP-2 mRNA were detected more often in effusions with high MT1-MMP and/or MT2-MMP mRNA expression. Using ISH, MT1-MMP mRNA was localized to cancer cells in 27 of 58 malignant effusions; focal signals were detected in mesothelial cells in 7 of 42. MT1-MMP was localized to tumor cells in 32 of 85 primary and metastatic solid lesions, and stromal cells expressed MT1-MMP in 3. Tumor cell MT1-MMP expression in effusion specimens did not differ from primary or metastatic lesions. MT-MMP expression in tumor cells in effusions showed no association with effusion site or tumor type using ISH and RT-PCR.

Ascitic Fluid↗
PubMed2001

Positron emission tomography with injection of methionine as a prognostic factor in glioma.

OBJECT: Positron emission tomography with L-[methyl-11C]methionine (MET-PET) provides information on the metabolism of gliomas. The aim of this study was to determine the predictive value of MET-PET in the treatment of patients with gliomas. METHODS: Since 1992, 85 patients with a World Health Organization (WHO) classification-verified glioma underwent PET studies in which MET was injected before (74 cases) or after treatment (11 cases). Analysis of PET data was conducted by the same investigator using two scales: a qualitative visual grading scale and a quantitative scale (ratio between tumor uptake and normal brain uptake, classified on a seven-level scale). Uptake of MET was present in 98% of gliomas. The investigator judged this uptake to be moderate to very high based on visual inspection (qualitative scale). For all grades of gliomas, a visual grade of 3 was statistically associated with a shorter patient survival period (p < 0.005). The tumor/normal brain uptake ratio was significantly influenced by the histological grade of the tumor. A statistically poor outcome was demonstrated when this ratio was higher than a threshold of 2.2 for a WHO Grade II tumor and 2.8 for WHO Grade III tumor. For Grade II and III tumors, oligodendrogliomas had a higher uptake of MET than astrocytomas. CONCLUSIONS: Uptake of MET was present in 98% of the gliomas studied. A high uptake is statistically associated with a poor survival time. The intensity of MET uptake represents a prognostic factor for WHO Grade II and III tumors considered separately.

Adult↗
PubMed2001

Ets-1 messenger RNA expression is a novel marker of poor survival in ovarian carcinoma.

Ets-1 proto-oncogene is a transcription factor involved in several cellular functions, including the activation of several proteases participating in tumor invasion and metastasis. The objective of this study was to analyze the possible correlation between Ets-1 mRNA expression and survival in advanced-stage ovarian carcinomas, studying two patient groups with extremely different disease outcome. Sections from 66 primary ovarian carcinomas and metastatic lesions from 41 patients diagnosed with advanced-stage ovarian carcinoma (International Federation of Gynecologists and Obstetricians stages III and IV) were evaluated for expression of Ets-1 using mRNA in situ hybridization. Patients were divided into long-term (n = 17) and short-term (n = 24) survivors. The mean values for disease-free survival and overall survival were 116 and 133 months for long-term survivors, as compared to 3 and 21 months for short-term survivors, respectively. Expression of Ets-1 mRNA was detected in carcinoma cells and stromal cells in 28 of 66 (42%) and 22 of 66 (33%) lesions, respectively. Ets-1 expression showed an association with mRNA expression of vascular endothelial growth factor (P = 0.001 for carcinoma cells; P = 0.004 for stromal cells), basic fibroblast growth factor (P = 0.049 for carcinoma cells), and membrane type-1 matrix metalloproteinase (P = 0.045), which were previously studied in this patient cohort. Ets-1 mRNA was detected more often in both carcinoma and stromal cells in tumors of short-term survivors (P = 0.038 for carcinoma cells). In univariate survival analysis for all cases, Ets-1 expression in both tumor (P = 0.018) and stroma (P = 0.026) correlated with poor survival. These findings were reproduced in an analysis of primary tumors alone (P = 0.039 for tumor cells; P < 0.001 for stromal cells). Ets-1 mRNA expression in stromal cells retained its predictive power in a multivariate survival analysis in which all molecules studied previously in this patient cohort were included (P = 0.007). To our knowledge, this is the first evidence associating Ets-1 mRNA expression and poor survival in human epithelial malignancy. Ets-1 is thus a novel prognostic marker in advanced-stage ovarian carcinoma. The association between Ets-1 mRNA expression and the expression of membrane type-1 matrix metalloproteinase and angiogenic genes, first documented here in a study of patient material, points to the central role of this transcription factor in tumor progression in ovarian carcinoma.

Adult↗