Biomedical subjects

Edmond Sabo

Publications and source records attributed to Edmond Sabo.

At least 19 recordsLinked to original sources

PubMed2006

Distribution of GPR30, a seven membrane-spanning estrogen receptor, in primary breast cancer and its association with clinicopathologic determinants of tumor progression.

PURPOSE: The seven transmembrane receptor, GPR30, is linked to estrogen binding and heparan-bound epidermal growth factor release. Here, the significance of GPR30 in human breast cancer was evaluated by comparing its relationship to steroid hormone receptor expression and tumor progression variables. EXPERIMENTAL DESIGN: Immunohistochemical analysis of a National Cancer Institute-sponsored tumor collection comprised of 361 breast carcinomas obtained at first diagnosis (321 invasive and 40 intraductal tumors). Biopsies from 12 reduction mammoplasties served as controls. The distribution pattern of GPR30, estrogen receptor (ER), and progesterone receptor (PR) was correlated with clinicopathologic variables obtained at diagnosis. RESULTS: GPR30, ER, and PR were positive in all 12 normal controls. In contrast, GPR30 expression varied in breast tumors, in which 62% (199 of 321) of invasive tumors and 42% (17 of 40) of intraductal tumors were positive. Codistribution of ER and GPR30 was measured in 43% (139 of 321) of invasive breast tumors, whereas both receptors were lacking (ER-GPR30-) in 19% (61 of 321) of the tumors analyzed, indicating a significant association between ER and GPR30 (P<0.05). The coexpression of PR and ER did not influence GPR30 expression, yet coexpression of GPR30 and ER was linked to PR positivity. Unlike ER, which varied inversely with HER-2/neu and tumor size, GPR30 positively associated with HER-2/neu and tumor size. In addition, GPR30 showed a positive association with metastasis (P=0.014; odds ratio, 1.9). CONCLUSIONS: GPR30 and ER exhibited distinct patterns of association with breast tumor progression variables, including HER-2/neu, tumor size, and metastatic disease. Thus, these results support the hypothesis that GPR30 and ER have an independent influence on estrogen responsiveness in breast carcinoma.

Biomarkers, Tumor↗

PubMed2006

Computerized morphometry as an aid in determining the grade of dysplasia and progression to adenocarcinoma in Barrett's esophagus.

The aims of this study were to use computerized morphometry in order to differentiate between the degree of dysplasia and to predict progression to invasive adenocarcinoma in Barrett's esophagus (BE). Biopsies from 97 patients with BE graded by a consensus forum of expert gastrointestinal pathologists were available for morphometrical analysis. The study group included 36 biopsies negative for dysplasia (ND), none of which progressed to carcinoma; 16 indefinite for dysplasia (IND) and 21 low-grade dysplasia (LGD), of which three progressed in each group and 24 high-grade dysplasia (HGD), of which 15 progressed to invasive carcinoma. Computerized morphometry was used for measuring indices of size, shape, texture, symmetry and architectural distribution of the epithelial nuclei. Low-grade dysplasia was best differentiated from the ND group by nuclear pseudostratification (P=0.036), pleomorphism (P<0.01), and chromatin texture (margination, P<0.01) and from the HGD group by nuclear area (P<0.01), pleomorphism (P<0.01), chromatin texture (margination, P<0.01), symmetry (P<0.01), and orientation (P=0.027). These results were validated on a new set of cases (n=55) using a neural network model, resulting in an accuracy of 89% for differentiating between the ND and LGD groups and 86% for differentiating between the LGD and HGD groups. Within the HGD group, univariate significant predictors of the progression interval to carcinoma were: indices of nuclear texture (heterogeneity: P=0.0019, s.d.-OD: P=0.005) and orientation: P=0.022. Nuclear texture (heterogeneity) was the only independent predictor of progression (P=0.004, hazard=11.54) by Cox's multivariate test. This study proposes that computerized morphometry is a valid tool for determining the grade of dysplasia in BE. Moreover, histomorphometric quantification of nuclear texture is a powerful tool for predicting progression to invasive adenocarcinoma in patients with HGD.

Adenocarcinoma↗

PubMed2006

Cholangiocyte marker-positive and -negative fetal liver cells differ significantly in their ability to regenerate the livers of adult rats exposed to retrorsine.

We have used monoclonal antibodies against cell-surface developmental epitopes in combination with micromagnetic beads to isolate phenotypically defined subpopulations of cholangiocyte marker-positive fetal liver epithelial cells (CMP-FLEC). Differentiation potential was evaluated by injecting cell isolates from dipeptidyl peptidase IV (DPPIV) positive (DPPIV+) Fischer donor rats into the spleen of partially hepatectomized, DPPIV negative (DPPIV-) Fischer host rats exposed to retrorsine. At various time points, liver tissue was harvested and cells in DPPIV+ colonies were phenotyped by immunofluorescence and histochemical protocols. Functional differentiation and liver replacement were determined by comparing donor and host hepatocyte protein expression patterns and DPPIV enzyme activity in extracts from livers of host rats receiving CMP-FLEC. Our results showed that bipotentiality was retained during differentiation and maturation of CMP-FLEC, indicating that the acquisition of ductal morphology and phenotype were not indicative of lineage commitment. CMP-FLEC transplanted into the adult rat liver lost ductal and gained hepatocyte markers, and acquired protein expression patterns in 2D gels with a close similarity (>75% spot match) to host hepatocytes but differing significantly from the transplanted CMP-FLEC cell isolate (<25% spot match). The average size of donor hepatocyte colonies increased with time so that by 1 year, up to 70% of the host rat liver was replaced by CMP-FLEC derived DPPIV+ hepatocytes. Depletion of CMP-FLEC from fetal liver isolates resulted in a marked decrease in adult liver colonization, suggesting that a high percentage of the hepatocyte colonies in animals receiving total fetal liver isolates are derived from CMP-FLEC.

Animals↗

PubMed2006

Prognostic value of humbug gene overexpression in stage II colon cancer.

Overexpression of aspartyl (asparaginyl) beta-hydroxylase (AAH) has been demonstrated in hepatocellular carcinoma, cholangiocarcinoma, and pancreatic carcinoma. AAH has an important role in regulating cell motility and invasiveness. Humbug is a truncated homolog of AAH, with a role in calcium regulation. The present study examines the prognostic use of AAH and humbug gene expression in stage II colon cancer. One hundred thirty cases of TNM stage II colon carcinoma were retrieved from the Rhode Island Hospital pathology archives. Tissue microarrays were immunostained with the FB50 and 15C7 monoclonal antibodies generated to recombinant AAH. However, FB50 also recognizes humbug. In addition, AAH and humbug expression was analyzed in samples of colon cancer and adjacent normal mucosa by real-time quantitative reverse transcriptase-polymerase chain reaction. Humbug (FB50) expression was localized to the tumor cytoplasm, whereas normal colonic epithelium did not exhibit significant immunoreactivity. Humbug staining was detected in 85% of the neoplasms, 23% of which stained strongly. Strong humbug immunoreactivity positively correlated with nuclear grade (P = .006) and inversely with survival (P = .027). In contrast to humbug, AAH (15C7) immunoreactivity was seen in normal and neoplastic epithelium. There was no correlation between AAH immunoreactivity and tumor grade, or survival. Correspondingly, reverse transcriptase-polymerase chain reaction studies demonstrated up-regulation of humbug but not AAH in 95% of colon carcinomas relative to adjacent colon cancer-free mucosa (P < .0001). This study demonstrates that high levels of humbug immunoreactivity in colon carcinomas correlate with histologic grade and tumor behavior, suggesting that humbug can serve as a prognostic biomarker of TNM stage II colon cancers. In addition, molecular studies demonstrated that the increased levels of FB50 detected were due to humbug, as opposed to AAH overexpression.

Adult↗

PubMed2006

Short-term arginine deprivation results in large-scale modulation of hepatic gene expression in both normal and tumor cells: microarray bioinformatic analysis.

BACKGROUND: We have reported arginine-sensitive regulation of LAT1 amino acid transporter (SLC 7A5) in normal rodent hepatic cells with loss of arginine sensitivity and high level constitutive expression in tumor cells. We hypothesized that liver cell gene expression is highly sensitive to alterations in the amino acid microenvironment and that tumor cells may differ substantially in gene sets sensitive to amino acid availability. To assess the potential number and classes of hepatic genes sensitive to arginine availability at the RNA level and compare these between normal and tumor cells, we used an Affymetrix microarray approach, a paired in vitro model of normal rat hepatic cells and a tumorigenic derivative with triplicate independent replicates. Cells were exposed to arginine-deficient or control conditions for 18 hours in medium formulated to maintain differentiated function. RESULTS: Initial two-way analysis with a p-value of 0.05 identified 1419 genes in normal cells versus 2175 in tumor cells whose expression was altered in arginine-deficient conditions relative to controls, representing 9-14% of the rat genome. More stringent bioinformatic analysis with 9-way comparisons and a minimum of 2-fold variation narrowed this set to 56 arginine-responsive genes in normal liver cells and 162 in tumor cells. Approximately half the arginine-responsive genes in normal cells overlap with those in tumor cells. Of these, the majority was increased in expression and included multiple growth, survival, and stress-related genes. GADD45, TA1/LAT1, and caspases 11 and 12 were among this group. Previously known amino acid regulated genes were among the pool in both cell types. Available cDNA probes allowed independent validation of microarray data for multiple genes. Among genes downregulated under arginine-deficient conditions were multiple genes involved in cholesterol and fatty acid metabolism. Expression of low-density lipoprotein receptor was decreased in both normal and tumor cells. CONCLUSION: Arginine-sensitive regulation appears to be an important homeostatic mechanism to coordinate cell response and nutrient availability in hepatic cells. Genes predicted as arginine-responsive in stringent microarray data analysis were confirmed by Northern blot and RT-PCR. Although the profile of arginine-responsive genes is altered and increased, a considerable portion of the "arginome" is maintained upon neoplastic transformation.

Journal Article↗

PubMed2006

RAGE, LRP-1, and amyloid-beta protein in Alzheimer's disease.

The receptor for advanced glycation end products (RAGE) is thought to be a primary transporter of beta-amyloid across the blood-brain barrier (BBB) into the brain from the systemic circulation, while the low-density lipoprotein receptor-related protein (LRP)-1 mediates transport of beta-amyloid out of the brain. To determine whether there are Alzheimer's disease (AD)-related changes in these BBB-associated beta-amyloid receptors, we studied RAGE, LRP-1, and beta-amyloid in human elderly control and AD hippocampi. In control hippocampi, there was robust RAGE immunoreactivity in neurons, whereas microvascular staining was barely detectable. LRP-1 staining, in contrast, was clearly evident within microvessels but only weakly stained neurons. In AD cases, neuronal RAGE immunoreactivity was significantly decreased. An unexpected finding was the strongly positive microvascular RAGE immunoreactivity. No evidence for colocalization of RAGE and beta-amyloid was seen within either microvessels or senile plaques. A reversed pattern was evident for LRP-1 in AD. There was very strong staining for LRP-1 in neurons, with minimal microvascular staining. Unlike RAGE, colocalization of LRP-1 and beta-amyloid was clearly present within senile plaques but not microvessels. Western blot analysis revealed a much higher concentration of RAGE protein in AD hippocampi as compared with controls. Concentration of LRP-1 was increased in AD hippocampi, likely secondary to its colocalization with senile plaques. These data confirm that AD is associated with changes in the relative distribution of RAGE and LRP-1 receptors in human hippocampus. They also suggest that the proportion of amyloid within the brains of AD patients that is derived from the systemic circulation may be significant.

Aged↗

PubMed2006

Shortened QT interval: a distinctive feature of the dysautonomia of chronic fatigue syndrome.

PURPOSE: Because autonomic nervous functioning is frequently abnormal in chronic fatigue syndrome (CFS), we examined whether the corrected QT interval (QTc) in CFS differs from QTc in other populations. METHODS: The QTc was calculated at the end of 10 minutes of recumbence and the end of 10 minutes of head-up tilt. In a pilot study, groups of 15 subjects, CFS, and controls, matched for age and sex, were investigated. In a second phase of the study, the QTc was measured in larger groups of CFS (n = 30) and control patients (n = 96) not matched for demographic features. RESULTS: In the pilot study, the average supine QTc in CFS was 0.371 +/- 0.02 seconds and QTc on tilt, 0.385 +/- 0.02 seconds, significantly shorter than in controls (P = .0002 and .0003, respectively). Results of phase II confirmed this data. CONCLUSIONS: Relative short QTc intervals are features of the CFS-related dysautonomia. The significance of this finding is discussed.

Adult↗

PubMed2006

Enhanced colon tumor induction in uncoupling protein-2 deficient mice is associated with NF-kappaB activation and oxidative stress.

Oxidative stress has a complex effect on cancer development. To further study this process, we induced colon tumors with azoxymethane (AOM) in mice deficient for uncoupling protein-2 (UCP2). UCP2 has recently emerged as a negative regulator of mitochondrial oxidant production. When overexpressed, UCP2 protects cells from oxidative stress, while its absence may cause abundance of reactive oxygen species, release of pro-inflammatory cytokines and persistent activation of nuclear factor kappaB (NF-kappaB), a pleiotropic transcription factor with an increasingly recognized role in cancer. Here we show that Ucp2-/- mice develop more aberrant crypt foci and colon tumors than Ucp2+/+ littermates when examined 24 weeks after the completion of treatment with AOM (10 mg/kg i.p. weekly for a total of 6 weeks, n = 8-12). This effect is primarily seen in the proximal colon of Ucp2-/- mice (P < 0.05), in association with changes indicative of increased oxidative stress (increased staining for malondialdehyde and inducible nitric oxide synthase), enhanced NF-kappaB activation (increased levels of phosphorylated IkappaB and increased nuclear presence of p65) and a disrupted balance between intestinal epithelial cell proliferation (greater 5-bromo-2'-deoxy-uridine incorporation rates and increased phosphorylation of ERK1/2 and AKT) and apoptosis (decreased number of terminal deoxynucleotidyltransferase-mediated nick-end-labeling (TUNEL)-positive cells and increased expression of Bcl-2). In conclusion, our findings provide the first in vivo evidence for a link between UCP2 and tumorigenesis and indicate the need for additional studies to assess the role of mitochondrial uncoupling in cancer development.

Animals↗

PubMed2006

Lack of UCP2 reduces Fas-mediated liver injury in ob/ob mice and reveals importance of cell-specific UCP2 expression.

Fatty liver is vulnerable to conditions that challenge hepatocellular energy homeostasis. Lipid-laden hepatocytes highly express uncoupling protein-2 (UCP2), a mitochondrial carrier that competes with adenosine triphosphate (ATP) synthesis by mediating proton leak. However, evidence for a link between UCP2 expression and susceptibility of liver to acute injury is lacking. We asked whether absence of UCP2 protects ob/ob mice from Fas-mediated acute liver damage. UCP2-deficient ob/ob mice (ob/ob:ucp2-/-) and UCP2-competent littermates (ob/ob:ucp2+/+) received a single dose of agonistic anti-Fas antibody (Jo2). Low-dose Jo2 (0.15 mg/kg intraperitoneally) caused less serum alanine aminotransferase (ALT) elevation and lower apoptosis rates in ob/ob:ucp2-/- mice. High-dose Jo2 (0.40 mg/kg intraperitoneally) proved uniformly fatal; however, ob/ob:ucp2-/- mice survived longer with less depletion of liver ATP stores, indicating that fatty hepatocytes may benefit from lack of UCP2 during Jo2 challenge. Although UCP2 reportedly controls mitochondrial oxidant production, its absence had no apparent effect on fatty liver tissue malondialdehyde levels augmented by Jo2. This finding prompted us to determine UCP2 expression in Kupffer cells, a major source of intrahepatic oxidative stress. UCP2 expression was found diminished in Kupffer cells of untreated ob/ob:ucp2+/+ mice, conceivably contributing to increased oxidative stress in fatty liver and limiting the impact of UCP2 ablation. In conclusion, whereas UCP2 abundance in fatty hepatocytes exacerbates Fas-mediated injury by compromising ATP stores, downregulation of UCP2 in Kupffer cells may account for persistent oxidative stress in fatty liver. Our data support a cell-specific approach when considering the therapeutic effects of mitochondrial uncoupling in fatty liver disease.

Acute Disease↗

PubMed2006

Applicability of the nipple-areola complex-sparing mastectomy: a prediction model using mammography to estimate risk of nipple-areola complex involvement in breast cancer patients.

The purpose of this study was to develop a prediction model that can be used to identify breast cancer patients at lowest risk for neoplastic nipple-areola complex (NAC) involvement to offer total NAC-sparing mastectomy with immediate reconstruction. Medical records, pathology slides, and mammograms were reviewed for all breast cancer patients treated with total mastectomy at Rhode Island Hospital between 2000 and 2004. The distance between the nipple and the closest tumor margin was measured using mammography. NAC involvement was identified in 42% of the 31 study patients. Mammographic distance, pathologic stage, and tumor size were identified as independent predictors of malignant NAC involvement by multivariate analysis (rho < 0.05). Based on these predictors, a linear discriminant score, the NAC Involvement Score (NACIS), was computed to distinguish between the presence and absence of NAC involvement. For individual patients, positive NACIS values (> or = -0.3665) were associated with NAC involvement with a sensitivity of 92%, specificity of 77%, and negative predictive value of 93%. These preliminary findings indicate that the NACIS formula may be a useful clinical tool for selecting low-risk patients for total NAC-sparing mastectomy with immediate reconstruction.

Adult↗

PubMed2006

Heparanase localization and expression by head and neck cancer: correlation with tumor progression and patient survival.

Heparanase is an endoglycosidase that specifically cleaves heparan sulfate (HS) side chains of HS proteoglycans, the major proteoglycans in the extracellular matrix and cell surfaces. Traditionally, heparanase activity was implicated in cellular invasion associated with angiogenesis, inflammation, and cancer metastasis. More recently, heparanase upregulation was documented in an increasing number of primary human tumors, correlating with reduced postoperative survival rate and enhanced tumor angiogenesis. In the present study, we examined the expression of heparanase in squamous cell carcinoma of the head and neck by means of immunostaining, and we correlated expression levels with patient outcome. The intensity and extent of heparanase staining correlated with tumor stage (P = .049 and P = .027, respectively), and the extent of staining further correlated with tumor grade (P = .047). Moreover, heparanase expression inversely correlated with patient status at the end of the study (P = .012). Notably, heparanase localization was found to be an important parameter for patient status. Thus, 63% of patients with nuclear staining, compared to 19% of patients with cytoplasmic staining (P = .0043), were alive, indicating that nuclear localization of the enzyme predicts a favorable outcome.

Cell Nucleus↗

PubMed2005

Multidrug resistance-related phenotype and apoptosis-related protein expression in ovarian serous carcinomas.

OBJECTIVE: Multidrug resistance (MDR) to chemotherapy is a major obstacle in attempts to improve the clinical outcome of ovarian carcinoma patients. The MDR-related phenotype is associated with over-expression of certain drug transporters, such as P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), and lung resistance protein (LRP). The aim of this study was to evaluate the extent and prognostic significance of MDR-related protein expression in ovarian serous carcinomas. In addition, we correlated expression of these proteins with the apoptosis-related proteins p53, bcl-2, and bax. METHODS: Consecutive sections from 60 cases of ovarian serous carcinoma were assessed immunohistochemically for expression of P-gp, MRP1, LRP, p53, bcl-2, and bax. The level of protein expression was scored based on staining intensity and extent. RESULTS: Strong P-gp expression was observed in 12 (20%), MRP1 in 39 (65%), LRP in 27 (45%), p53 in 45 (75%), bcl-2 in 25 (41.7%), and bax in 30 (50%) of the 60 tumors. MRP1 expression was associated with both p53 and bcl-2 expressions (P = 0.01 and P = 0.03, respectively). Univariate analysis of survival revealed a significant inverse correlation between P-gp expression and patient survival (P = 0.015). Moreover, P-gp expression was significantly increased in tumors of patients unresponsive to chemotherapy (P = 0.009). Multivariate analysis revealed that only FIGO stage and P-gp expression were useful negative independent predictors of survival (P = 0.035 and P = 0.045, respectively). CONCLUSIONS: Our pilot study demonstrates that P-gp expression may be a reliable independent prognostic factor of survival in patients with ovarian serous carcinoma. Moreover, P-gp immunostaining may be useful for dividing ovarian carcinoma patients into chemoresponsive and chemoresistant groups.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

Circulating levels of tumor necrosis factor-alpha correlate positively with severity of peripheral oedema in patients with right heart failure.

BACKGROUND: Several previous studies have shown that circulating levels of tumor necrosis factor-alpha (TNF) are elevated in patients with advanced congestive heart failure. However, the relationship between circulating levels of TNF and severity of peripheral oedema in these patients has not been previously evaluated. AIMS: To investigate the relationship between circulating levels of TNF, and severity of peripheral oedema in patients with right-sided heart failure (RHF). METHODS AND RESULTS: Circulating levels of TNF were measured in 15 healthy volunteers, and in 83 patients with RHF with various levels of peripheral oedema. At presentation, 13 patients had no peripheral oedema (grade 0), 22 patients had mild peripheral oedema (grade 1), 23 patients had moderate peripheral oedema (grade 2), and 25 patients had severe peripheral oedema (grade 3). The values of circulating TNF levels (mean +/- S.E.M.) at presentation in the control group and in the RHF patients (oedema grades 0-3) were 2.98+/-0.21, 4.22+/-0.55, 4.67+/-0.29, 7.66+/-0.44, and 10.94+/-0.67 pg/mL respectively. There was a significant difference between the groups (p < 0.0001, ANOVA), and a significant positive correlation was found between circulating TNF levels and severity of peripheral oedema (r = 0.77, p<0.0001). CONCLUSION: A significant relationship is present between circulating levels of TNF and severity of peripheral oedema in patients with RHF.

Adult↗

PubMed2005

Expression of cell cycle regulatory proteins in ovaries prophylactically removed from Jewish Ashkenazi BRCA1 and BRCA2 mutation carriers: correlation with histopathology.

OBJECTIVES: Prophylactic oophorectomy in Ashkenazi Jewish women with BRCA mutations represents a unique opportunity to search for premalignant changes in ovaries. Reports on the presence of dysplastic lesions in these ovaries are contradictory. Our aim was to study the expression of cell cycle regulatory proteins--p53, Skp2, p27, Ki67, Bcl2 and p16--in correlation with histopathological changes. p16(INK4A) was not studied before in prophylactically removed ovaries. METHODS: Ninety-four ovaries from 50 Ashkenazi Jewish BRCA carriers were compared with 42 ovaries removed for reasons unrelated to cancer and with 16 ovarian carcinomas. RESULTS: Three (6%) patients from the high-risk group had an occult carcinoma. A significant association was found between BRCA-positive expression and the presence of atypical changes in the superficial ovarian epithelium (P = 0.014) as well as the presence of epithelial cortical clefts (P = 0.042). Expression of p53 in cortical inclusions was significantly higher in the BRCA-positive cases than in the benign control group (P = 0.03). The high-risk and the benign control group did not differ significantly by the expression of p16, BCL2, Ki67, p27 and SKP2 (P > 0.05). However, both groups significantly differed from the carcinoma group (P < 0.0001). A significant positive correlation was found between the expression of Ki67, and the grade of atypia in the high-risk group (R = 0.3, P = 0.01) and in the benign control group (R = 0.5, P = 0.02). CONCLUSIONS: BRCA mutation carriers had more atypical changes in the superficial epithelium (P = 0.014) and more epithelial cortical clefts (P = 0.042) compared to the benign control group. The histopathology changes were not supported by significantly altered expressions of the proteins used in our study. Additional molecular studies could contribute to the disclosure of precancerous ovarian lesions.

Cell Cycle Proteins↗

PubMed2005

Sjögren's syndrome in the community: can serology replace salivary gland biopsy?

BACKGROUND: It is relatively difficult in a community setting to perform salivary gland biopsy or reliable diagnostic tests for salivary gland involvement in a patient suspected to suffer from Sjögren's syndrome (SS). OBJECTIVE: To investigate whether anti-Ro/La antibodies are a good substitute for salivary gland biopsy in community patients suspected to suffer from SS. METHODS: Forty-one patients suspected as having SS due to dry eyes and mouth, articular complaints, and/or serological findings were examined for the presence of anti-Ro/La, and underwent minor salivary gland biopsy. RESULTS: Sixteen patients (39%) were classified as primary SS by the American-European Consensus Group criteria. Twelve subjects had anti-Ro/La antibodies and 11 subjects in this group had positive biopsy findings. Of 29 patients without anti-Ro/La antibodies, only four manifested positive biopsy findings. A significant association was found between the presence of anti-Ro/La antibodies and positive salivary gland findings characteristic for SS (p<0.0001, Fisher's exact test). CONCLUSION: These findings tend to support the suggestion that a patient suspected to suffer from SS in a community setting may be first tested for the presence of anti-Ro/La antibodies to confirm the diagnosis. Only those with a negative result for the presence of anti-Ro/La antibodies need to be referred for salivary gland biopsy.

Antibodies, Antinuclear↗

PubMed2005

Pediatric nasopharyngeal carcinoma: better prognosis and increased c-Kit expression as compared to adults.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) in children is distinguishable from the adult form by its close association with Epstein-Barr virus (EBV) infection, a higher rate of undifferentiated histology, and a greater incidence of advanced locoregional disease. PATIENTS AND METHODS: Sixteen NPC patients, < or =20 years of age were identified from our 1976-2001 tumor registry records. Clinical stage, treatment, recurrence, and survival were evaluated. Sections were stained by immunohistochemistry for p53, Bcl-2, Ki67, and c-Kit and by in situ hybridization for EBER. Obtained data were compared to 32 adult patients. All patients had undifferentiated or non-keratinizing NPC. RESULTS: EBER was positive in 100% of children, compared to 90% of adults. Comparing children to adults, median Ki67 index was 49% and 30%, p53 positive tumors were 69% and 94%, positive Bcl-2 was 63% and 72%, and positive c-Kit was 88% and 28%, respectively. CONCLUSION: No parameter had significant predictive values for survival, although c-Kit expression had a trend for better prognosis in the pediatric group. By univariate analysis of all 48 cases, positive c-Kit was associated with better survival (P = 0.029), largely due to the better survival of the pediatric group. By multivariate analysis, increased stage (P = 0.006) and older age (P = 0.044) correlated with worse prognosis.

Adolescent↗

PubMed2005

Claudin expression in gastric adenocarcinomas: a tissue microarray study with prognostic correlation.

The claudins comprise a multigene family of integral membrane proteins, which play a major role in tight junction formation. Aberrations in the expression of certain claudins have been described in a number of malignancies. Our aims were to determine the expression pattern of claudins 1, 3, and 4 as well as ZO-1 in a large series of US patients with gastric cancer and to correlate expression with clinicopathologic and prognostic variables. Tissue microarrays were created from paraffinized samples from 146 patients with distal gastric adenocarcinomas (61 intestinal and 85 diffuse or mixed subtypes). In addition, cores of normal mucosa and intestinal metaplasia were taken from most cases. The microarrays were stained for claudins 1, 3, and 4 and ZO-1, and the intensity of staining was determined using a 3-point scale. Moderate claudin 1 and ZO-1 membranous staining were present, whereas only focal weak claudin 3 and 4 membranous staining was present in normal gastric epithelium. Moderate to strong staining of claudins 1, 3, 4, and ZO-1 was detected in 74%, 48%, 62%, and 74% of the intestinal but in only 46%, 24%, 45%, and 36% of the diffuse subtype of adenocarcinomas (P < .05). Cox multivariate analysis revealed that tumor stage, diffuse subtype, and moderate to strong claudin 4 staining were associated with decreased survival (P < .02). In conclusion, claudins 1, 3, and 4 and ZO-1 are strongly expressed in most gastric intestinal-type adenocarcinomas but less frequently in diffuse gastric cancers. The up-regulation of claudin expression during gastric carcinogenesis suggests their potential utility as diagnostic biomarkers and possible targets for therapeutic intervention.

Adenocarcinoma↗

PubMed2005

Comparison of nephron-sparing surgery in central versus peripheral renal tumors.

OBJECTIVES: To determine the feasibility of nephron-sparing surgery (NSS) in patients with centrally located tumors. METHODS: A retrospective cohort study of 118 patients who underwent NSS between 1993 and 2002 (35 patients with centrally located tumors and 83 with peripherally located tumors) was performed. Kaplan-Meier curves were constructed to evaluate freedom from local recurrence and disease-specific survival in patients with conventional histologic subtype tumors. The Wilcoxon test was used to compare the curves (two-tailed P < or =0.05 was considered to be statistically significant). RESULTS: Intraoperatively, in patients with centrally located tumors, the need to close the collecting system (P = 0.035) and for blood transfusions (P = 0.033) was greater. Two perioperative deaths occurred in patients with peripherally located tumors. Two patients with centrally located tumors subsequently underwent nephrectomy. Of the patients with centrally located tumors, 1 patient had a positive margin, 2 patients had local recurrence, and 1 patient developed metastasis. No positive surgical margins or local recurrence was found in patients with peripherally located tumors, although 4 patients developed distant metastasis. Kaplan-Meier curves for patients with conventional histologic subtype tumors demonstrated a statistically significant difference for local recurrence (P = 0.04), but not for survival (P = 0.71). The mean follow-up time was 38.8 and 43.8 months for patients with centrally located and peripherally located tumors, respectively. CONCLUSIONS: NSS can be used to postpone, or eliminate the need for, nephrectomy in 94.3% of patients with centrally located tumors and can achieve oncologic disease control similar to that for exophytic lesions. These data indicate that NSS should be considered even for patients with centrally located tumors, taking into account that performing such surgery is a challenging task.

Cohort Studies↗