The prognostic value of angiogenesis and metastasis-related genes for progression of transitional cell carcinoma of the renal pelvis and ureter.

PURPOSE: We reported previously that angiogenesis evaluated by intratumor microvessel density (MVD), expression of such angiogenic factors as vascular endothelial cell growth factor (VEGF) and basic fibroblast growth factor (bFGF), and the matrix metalloproteinase-9:E-cadherin ratio (M:E ratio) could identify patients with advanced transitional cell carcinoma (TCC) of the bladder for whom chemotherapy and cystectomy will be unsuccessful. In the present study, we evaluated the significance of the M:E ratio as a predictor for prognosis for patients with TCC in the upper urinary tract (TCC-UUT). EXPERIMENTAL DESIGN: We evaluated MVD by immunohistochemistry and the expression of angiogenic and metastasis-related factors by in situ hybridization in 55 nephroureterectomy specimens from patients who received no neoadjuvant therapy. The expression of angiogenesis, angiogenic and metastasis-related factors, and clinicopathological characteristics were evaluated for their correlation with metastasis, recurrence, and disease prognosis. RESULTS: We found that tumor grade and pathological stage were important predictors for metastasis and survival in these patients. The expression level of matrix metalloproteinase type 9 (MMP-9) and type 2 (MMP-2) and the M:E ratio correlated with MVD. Increased MVD, elevated expression levels of MMP-9 and MMP-2, and a higher M:E ratio were associated with poor prognosis. Moreover, lower expression levels of E-cadherin were associated with fewer recurrences in the urinary bladder. Multivariate analysis indicated that the M:E ratio and E-cadherin expression were independent prognostic factors for disease progression and intravesical recurrence, respectively. CONCLUSION: We suggest that the M:E ratio and E-cadherin expression may be targets for novel therapeutic strategies.     

CA 125: a potential tumor marker for gallbladder cancer

BACKGROUND: CA 125 is a glycoprotein and a commonly used tumor marker in ovarian carcinoma. Its use in gallbladder carcinoma (GBC) has not yet been reported. We have henceforth examined for the first time the diagnostic utility of CA 125 in patients with gallbladder diseases. PATIENTS AND METHODS: Serum CA 125 was measured in 64 patients with GBC, 47 Gallstone disease (GSD) and 23 healthy volunteers by ELISA. CA 125 level was compared between different cohorts by non-parametric test (Kruskal Wallis and Mann-Whitney test). Receiver operating characteristic curve (ROC) was constructed to see the diagnostic utility of CA 125. Its level was also correlated with age, sex and clinico-pathological parameters of the patients included in the study. RESULTS: Mean value of CA 125 in patients with GBC, GSD and healthy volunteers was 77.44 +/- 141.31 U/ml, 7.85 +/- 5.40 U/ml, and 8.08 +/- 3.26 U/ml respectively and showed a statistically significant difference (P < 0.001). CA 125 at cut off value of 11 U/ml yielded 64% sensitivity and 90% specificity in differentiating benign from malignant gallbladder disease. CA 125 level increased with stage and grade of the GBC though this was not statistically significant. A higher level of CA 125 was found in presence of gallbladder mass, weight loss, ascites and loss of appetite compared to patients with GSD. No association of CA 125 was apparent with either age or sex of the patients. CONCLUSION: CA 125 has a diagnostic potential for GBC and can differentiate GBC from GSD in light of other clinical details.     

Effect of mangiferin on mitochondrial energy production in experimentally induced myocardial infarcted rats

Mangiferin, from the leaves of Mangifera indica Linn., has been suggested as useful in the treatment of cardiovascular disorders. In the present study this drug was examined on the alteration of cardiac energy metabolism in isoproterenol (ISPH) administered myocardial infarcted rats. ISPH (20 mg/kg b.w.), which was administered s.c. twice at an interval of 24 h, caused a significant decrease in the activities of TCA cycle enzymes and antioxidant defense enzymes with a concomitant increase in the lipid peroxidation of heart mitochondria in rat model. The ATP production and the oxidation of succinate in State 3 and 4 decreased significantly in the cardiac mitochondria of ISPH administered rats. These functional alterations were supported by severe modifications in mitochondrial ultrastructure. Pretreatment with mangiferin (100 mg/kg b.w. i.p.) for 28 days prevented these mitochondrial alterations, oxidation with energy metabolism and restored the TCA cycle enzyme activities to near normal values following ISPH administration. The structural integrity of the heart was protected by mangiferin in ISPH administered rats when compared to the untreated controls. The present findings suggest that the protective effect of mangiferin can be attributed to its reducing effect on oxidative damage and activation of mitochondrial energy metabolism. These results could be useful to study and understand the cellular events involved in this cardioprotective mechanism of mangiferin. Our studies of mangiferin on heart failure may have important implication for future therapeutic approaches involving in the prevention of cardiovascular diseases.     

Absence of telomerase and shortened telomeres have minimal effects on skin and pancreatic carcinogenesis elicited by viral oncogenes

The telomere-stabilizing enzyme telomerase is induced in tumors and functionally associated with unlimited replicative potential. To further explore its necessity, transgenic mice expressing SV40 or HPV16 oncogenes, which elicit carcinomas in pancreas and skin, respectively, were rendered telomerase-deficient. Absence of telomerase had minimal impact on tumorigenesis, even in terc(-/-) generations (G5-7) exhibiting shortened telomeres and phenotypic abnormalities in multiple organs. Analyses of chromosomal aberrations were not indicative of telomere dysfunction or increased genomic instability in tumors. Quantitative image analysis of telomere repeat intensities comparing biopsies of skin hyperplasia, dysplasia, and carcinoma revealed that telomere numbers and relative lengths were maintained during progression, implicating a means for preserving telomere repeats and functionality in the absence of telomerase.     

Etiology and clinical predictors of intractable epilepsy

The aim of this study was to evaluate neuropsychologic and motor performance in term small-for-gestation preschool children. A patient-based sample of 311 5-year-old children with birth weights less than the fifteenth percentile for gestation was compared with a random sample of 321 appropriate-for-gestation control subjects. The main assessment tools were subscales from the Wechsler Preschool and Primary Scale of Intelligence Revised, subscales from the Illinois Test of Psycholinguistic Abilities, tests of manual dexterity and figure copying, and the Peabody Developmental Motor Scales. The small-for-gestation children had mean scores on tests of visuospatial and visuomotor abilities that were one fourth standard deviation lower than appropriate-for-gestation control subjects and slightly lower scores on manual dexterity. The small-for-gestation children were comparable to appropriate-for-gestation children regarding motor performance. We therefore conclude that the neuropsychologic and neuromotor performance in preschool years of term small-for-gestation children is reassuring.     

Multiple cutaneous horns of the penis: a case report

Cutaneous horns of the penis are rare. Frequently they are unusual presentations of squamous cell carcinomas of the penis; therefore prompt surgical intervention is warranted. This is a report on a 70-year-old man with multiple cutaneous horns of the penis. The possible causes of cutaneous horns are reviewed.