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Biomedical subjects

M Ghazizadeh

Publications and source records attributed to M Ghazizadeh.

At least 37 records · Page 2Linked to original sources

Prognostic value of proliferative activity of ovarian carcinoma as revealed by PCNA and AgNOR analyses.

Proliferative activity of a malignant tumor is known to reflect its biologic aggressiveness. Proliferating cell nuclear antigen (PCNA) is a marker of cellular proliferation, and silver-stained nucleolar organizer regions (AgNORs) have been shown to correlate with ploidy and proliferative activity of cells depending on the method of assessment; the mean number of AgNORs per nucleus reflects ploidy, whereas the mean percentage of nuclei with five or more AgNORs per nucleus indicates proliferative activity. In ovarian carcinoma, the prognostic value of these markers has not been well defined. We studied PCNA expression and the AgNOR count in 43 ovarian carcinomas (25 serous, 13 mucinous, and 5 clear cell types) to assess their potential prognostic significance compared with the stage of disease and histopathologic features of the tumors. Eight benign (four serous and four mucinous) and six normal ovarian tissues were also evaluated. A standard colloidal silver staining and an immunohistochemical method were used. The mean percentage of PCNA positivity (PCNA index), the mean number of AgNORs per nucleus (mAgNOR), and the mean percentage of nuclei with more than five AgNORs per nucleus (pAgNOR) for each lesion were determined. In univariable analysis, PCNA indexes and mAgNOR and pAgNOR values were significantly higher in benign ovarian tumors compared with normal ovarian tissues and in adenocarcinomas compared with benign ovarian tumors. In multivariable analysis, PCNA indexes were significantly associated with histologic grade (P=.003), whereas associations of mAgNOR and pAgNOR values were highly significant with both histologic grade and disease stage (P=.0001). Histologic grade, but not subtype, was also associated with disease stage at a significant level (P=.008). Our findings indicate that differences in biologic behavior of ovarian carcinomas may, in part, be defined by differences in their ploidy and proliferative activity, and that whereas PCNA expression is of limited value, assessment of AgNORs holds promise in providing valuable prognostic information on the biologic behavior of the tumors.

Adenocarcinoma, Clear Cell↗

Silver-stained nucleolar organizer regions in hypertrophic and keloid scars.

Silver-stained nucleolar organizer regions (AgNORs) have been widely used as a marker of cellular activity and proliferation. In a retrospective study, we investigated the potential value of AgNORs in 12 hypertrophic and 24 keloid scar tissues. Ten normal skin tissues served as controls. A standard silver-staining method was used, and the mean AgNOR count of dermal fibroblastic cells in each tissue was determined. In normal skin, the mean AgNOR count of dermal fibroblasts was 1.79+/-0.55, whereas fibroblastic cells in hypertrophic and keloid scars had mean AgNOR counts of 3.18+/-0.56 and 5.10+/-0.97, respectively. There was a statistically significant difference between the mean AgNOR counts of fibroblastic cells from normal skin, hypertrophic scar, and keloid scar [one-factor analysis of variance (ANOVA), p < 0.0001]. Our findings suggest that AgNOR count may be a useful marker for assessment of fibroblastic cell activity in hypertrophic and keloid scars, which may have potential value for histologic and biologic characterization of the two lesions.

Analysis of Variance↗

Tn and sialyl-Tn antigens as potential prognostic markers in human ovarian carcinoma.

OBJECTIVE: Carcinoma-associated Tn and sialyl-Tn antigens have been shown to aid in the prediction of tumor aggressiveness. The purpose of this study was to evaluate the prognostic value of Tn and sialyl-Tn antigen expression in human ovarian carcinoma. METHODS: Formalin-fixed, paraffin-embedded tissue sections from 32 primary ovarian carcinomas, 6 benign and 2 normal ovarian tissues were immunostained using monoclonal antibodies against Tn and sialyl-Tn antigens and a streptavidin-biotin-peroxidase method Immunostainings were assessed semiquantitatively and the measurements were then correlated with the established prognostic factors of ovarian carcinoma. i.e. disease stage and histological grade. RESULTS: Of the 32 ovarian carcinomas, 22 (69%) expressed Tn and 28 (87.5%) sialyl-Tn antigens. Immunostaining measures for Tn antigen were significantly associated with the clinical stage (p < or = 0.02) and histological grade (p < or = 0.05) of the tumors. The results for sialyl-Tn antigen revealed more significant associations with the clinical stage (p < or = 0.002) and histological grade (p < or = 0.007). The clinical stage and histologic grade of the tumors were also highly correlated with each other. Similarly, combined Tn and sialyl-Tn antigen expression revealed significant correlations with the prognostic factors. Benign and normal ovarian tissues showed no reactive Tn and sialyl-Tn antigen. CONCLUSIONS: The extent of Tn and sialyl-Tn antigen expression in primary ovarian carcinoma may contribute to the prognosis of the disease.

Antigens, Tumor-Associated, Carbohydrate↗

Synthesis of endothelin-1 in rat uterus during pregnancy.

Endothelin is a potent vasoconstrictive peptide first isolated from the supernatant of cultured porcine aortic endothelial cells. The purpose of this study was to determine the source of endothelin-1 (ET-1) production in rat uterus during pregnancy and to clarify its role in normal pregnancy. ET-1, as recognized by immunohistochemistry, was weakly expressed only in endometrial glandular cells in nonpregnant rats but was intensely expressed in both glandular and myometrial cells in the early postpartum period. In situ hybridization confirmed the localization of prepro-ET-1 mRNA in the cytoplasm of endometrial glandular and myometrial cells but not in stromal cells or in smooth muscle cells of blood vessels. Northern blot analysis detected prepro-ET-1 mRNA in myometrial tissue from pregnant but not nonpregnant rats. In particular, the expression of prepro-ET-1 mRNA was strongest in the early postpartum period compared with the various stages of pregnancy. These results indicate that, in addition to endothelial cells and endometrial glandular cells, myometrial cells also produce ET-1 and its production significantly increases in the early postpartum period. Therefore, ET-1 may play a pivotal role in controlling bleeding from the placental bed through myometrial contraction.

Animals↗

T/Tn pancarcinoma autoantigens: fundamental, diagnostic, and prognostic aspects.

Pathogenetic aspects of pancarcinoma T/Tn autoantigens were investigated; they are present in approximately 90% of all carcinomas from incipience and throughout. T/Tn are occluded in noncarcinoma (non-CA) diseased and healthy tissues. By serological and immunohistochemical methods, we found that well-differentiated carcinomata express a higher proportion of T than Tn, while in poorly differentiated carcinomata, Tn predominates over T. Tn density of primary carcinomas correlates positively with aggressiveness, early clinical relapse, and early death. Delayed-type skin hypersensitivity to T (DTHR-T) and solid-phase anti-T antibody immunoassay (SPIA-T), respectively, detected 85% of 461 and 88% of 222 carcinoma patients; < 7% of over 450 benign diseased and healthy subjects reacted positively in these assays. T/anti-T assays are highly effective in detecting incipient (TisN0M0 and T1N0M0) carcinomas: DTHR-T-85% of 41, and SPIA-T-96% of 26 patients. Positive anti-T tests predicted CA in 74% of 47 patients months to years before their biopsy/X-ray turned positive.

Adenocarcinoma↗

Silver staining of nucleolar organizer regions in prostatic lesions.

Variations in the number of silver-stained nucleolar organizer region-associated proteins (AgNORs) were studied in paraffin sections of 42 benign prostatic lesions, comprising four cases of granulomatous prostatitis, five of squamous or transitional metaplasia, eight of atypical and 25 of regular hyperplasia, and 37 of prostatic adenocarcinoma, with their metastases. There was a significant difference between the mean AgNOR counts of the benign and malignant prostatic lesions (1.58 +/- 0.26 v. 4.34 +/- 1.53; P less than 0.01). The mean AgNOR counts significantly increased with increasing Gleason's grade (P less than 0.01) and clinical stage (P less than 0.05) of the tumours. AgNOR counting may contribute to the conventional diagnostic and prognostic indices of cancer of the prostate.

Adenocarcinoma↗

A histological, ultrastructural and immunohistochemical study of superficial temporal arteries and middle meningeal arteries in moyamoya disease.

Pathologic changes in superficial temporal arteries (STA) and middle meningeal arteries (MMA) biopsied from 15 patients with moyamoya disease (MD) who had undergone cerebro-temporal arterio-synangiosis were studied histologically, ultrastructurally and immunohistochemically. The main pathologic features were: proliferation of smooth muscle cells (SMCs) and thickening of the intima, degeneration and destruction of SMCs in the media and intima, and the presence of condensed organelles in necrosed SMCs or the interstitium among SMCs, or both outside and within the elastica interna (EI). The EI had become thin, porous, fragmented and was even absent in some segments. These changes are different from those of other forms of angiopathy, but identical with those at the ends of internal carotid arteries (ICA) reported by us previously, being pathognomonic for MD. These changes in the STA and MMA reveal that MD involves not only the ICA but also the intra- and extracranial branches of external carotid arteries. The medial necrosis of SMCs seems to be the primary injury of the arterial wall in MD. STA tissue blocks from two cases of MD were stained immunohistochemically. By electron microscopy, IgG-, IgM-, and C3-positive granules were observed on the ER of endothelial and intimal cells. Further studies on more cases are needed to determine whether an immunoreaction has occurred in these arteries.

Adolescent↗

Immunohistochemical and ultrastructural localization of T antigen in ovarian tumors.

Thomsen-Friedenreich (T) antigen, the immediate precursor antigen of the human blood group MN system, has been found in many carcinomas, but it is suppressed in normal tissues and nonmalignant diseases. Using a monoclonal antibody specific for the T epitope and an indirect immunoperoxidase technique at light and electron microscopic levels, the authors studied the expression of T antigen and its potential diagnostic value in ovarian tumors. Among 30 serous and mucinous ovarian cystadenocarcinomas, 20 (67%) were positive and 10 (33%) were negative for T antigen. In carcinomas, positive rates increased in parallel with the tumor grade and were 37%, 75% and 80% for grade 1, 2, and 3 tumors, respectively. Of the nine patients with metastasis, seven (78%) had positive and two had negative reactions in their primary and metastatic tumors. T antigen staining was observed at the intraluminal cell surfaces and peripheral cell membranes. The ultrastructural localization of T antigen revealed electron-dense reaction products at the cell surface and microvillous surfaces. Of the ten benign ovarian tumors, three (30%) were weakly positive and seven (70%) were negative for T antigen. These findings indicate a positive correlation between the presence of immunoreactive T antigen and conventional unfavorable prognostic indicators in ovarian carcinoma. The surface location of T antigen suggests that it may have a functional role at the cell membrane and the membrane may be involved in secretion (shedding) of T antigen. Detection of T antigen may be a useful marker of prognosis in ovarian carcinoma.

Antibodies, Monoclonal↗

Combined immunohistochemical study of tissue polypeptide antigen and cancer antigen 125 in human ovarian tumours.

An indirect immunoperoxidase method was used to study the expression of tissue polypeptide antigen (TPA) and cancer antigen 125 (CA 125) in 47 benign and malignant ovarian tumours. Tissue polypeptide antigen and CA 125 antigen were expressed respectively in 22 (73%) and 16 (53%) of the 30 adenocarcinomas and in five (29%) and four (23%) of the 17 benign tumours. Co-expression of TPA and CA 125 antigen occurred in 12 (40%) malignant and four (23%) benign tumours. Ultrastructurally, TPA and CA 125 antigens were located at the cell surface and microvillous surfaces. Evaluation of combined TPA and CA 125 antigen results revealed a remarkable improvement in the positivity rate and a significant decrease (P less than 0.05) in the negativity rate of ovarian carcinomas as compared with the result of each one separately. These findings provide complementary evidence for the previous results on the plasma levels of TPA and CA 125 antigen and suggest that specific combinations of tumour markers may be more effective for the diagnosis and monitoring of ovarian carcinomas, than the use of any single marker.

Antigens, Neoplasm↗

Differences in sialic acid expression of lung alveolar cells between normal and intrauterine growth-retarded rat fetuses.

The expression of sialic acid on the luminal surface of lung alveolar epithelial cells was compared in normal developing and intrauterine growth-retarded (IUGR) rat fetuses during the late gestational and early neonatal periods using neuraminidase treatment of the tissues and staining with a galactose-binding lectin from peanut. In IUGR fetal lung tissues, there were more staining for free galactosyl residues (before neuraminidase treatment) and less staining for sialic acid-bound galactosyl residues (after neuraminidase treatment) than in normal fetal lung tissues during the developmental stages. The staining reaction after neuraminidase treatment was mostly confined to the type 2 alveolar cell surfaces especially on microvillous surfaces. These findings suggest that in IUGR rat fetuses galactosyl residues of the lung alveolar epithelial cell surfaces are not sufficiently masked with terminal sialic acids resulting in a disturbance in the normal maturation process of the alveolar epithelial cells.

Animals↗

Tissue polypeptide antigen expression in human prostate tumors.

Thirty-seven specimens of benign and malignant prostatic tumors were studied for the localization of tissue polypeptide antigen (TPA) by an avidin-biotin-peroxidase complex technique. In addition, 23 metastases of prostatic carcinoma in other organs and 12 nonepithelial tumors of prostate also were studied. All benign and malignant tumors of epithelial origin, including their metastasis, stained positively. Nonepithelial tumors were uniformly negative. In the metastatic lesions, small foci of tumor cells and even single tumor cells could be identified by TPA staining. Immunohistochemical localization of TPA appeared to be a useful tool for assessing the micrometastases of prostatic carcinoma in other organs, especially lymph nodes, or elucidating the epithelial origin of an otherwise undifferentiated prostatic cancer.

Adenocarcinoma↗

Immunohistochemical and ultrastructural localization of tissue polypeptide antigen in human ovarian tumours.

Forty specimens of benign and malignant ovarian tumours were studied for localization of tissue polypeptide antigen (TPA) at light and electron microscopic levels by an indirect immunoperoxidase technique. Of the 30 ovarian carcinomas, 23 (77%) were positive and 7 (23%) were negative for TPA, while of the 10 benign ovarian tumours 3 (30%) were positive and 7 (70%) were negative. Positive reaction did not correlate with the tumour grade. Of the 10 patients with metastasis, 8 (80%) had positive tumours. Staining for TPA was observed at the intraluminal cell surfaces and peripheral cell membranes. The ultrastructural localization of TPA revealed electron-dense reaction products at the cell surface and microvillous surfaces. These results provide confirmatory and supplementary evidence to support the previous findings of TPA in the serum and suggest that testing for TPA in ovarian tumors has a limited prognostic importance and a poor diagnostic value. The surface property of TPA suggests that the cell membrane is involved in secretion and probably synthesis of TPA.

Female↗

Serum and urinary uric acid in primary hyperparathyroidism.

Serum and 24-h urinary uric acid were measured in 29 patients with primary hyperparathyroidism pre- and post-operatively. No significant difference was observed. A positive correlation was found between the ratios of urinary calcium/creatinine and urinary uric acid/creatinine pre-operatively but not after surgery. The serum uric acid level showed an increase from the first to the third day post-operatively and returned to normal within a week, but in patients undergoing other urological operations there was no post-operative increase. On a low calcium diet the level of serum uric acid was found to be increased. These findings suggest that primary hyperparathyroidism has some influence on uric acid metabolism.

Adult↗

Immunohistochemical localization of CA 125 antigen in formalin-fixed paraffin sections of ovarian tumors with the use of Pronase.

The OC 125 monoclonal antibody was used to localize CA 125 antigen in routine paraffin sections of ovarian tumors with the use of a modified avidin-biotin-peroxidase complex (ABC) technic. Pretreatment of the paraffin sections with Pronase allowed subsequent detection of CA 125 antigen. OC 125 stained 4 (80%) of 5 benign and borderline serous ovarian tumors, 12 (86%) of 14 serous adenocarcinomas, and 3 (23%) of 13 benign and malignant mucinous ovarian tumors. The pattern of distribution of CA 125 antigen was mostly at the intraluminal and peripheral cell surfaces, while intracytoplasmic staining also was seen. Overall, CA 125 antigen detectability rate in paraffin sections was found to be compatible with those reported in frozen sections. The method allows retrospective immunohistochemical examination of a large number of cases with ovarian tumors.

Antibodies, Monoclonal↗

Further studies on specificity of red cell adherence test: nonmalignant bladder lesions.

Specific red cell adherence test for blood group antigens was utilized in 32 nonmalignant bladder lesions, none of which was associated with bladder cancer, to determine the specificity of this test. All of the 14 lesions of cystitis cystica, cystitis glandularis, and chronic cystitis retained their antigens. Of the 18 lesions of squamous metaplasia, 13 (72%) were antigen positive. Testing for blood group antigens showed an overall 84 per cent specific rate in 27 of the 32 nonmalignant bladder lesions.

ABO Blood-Group System↗

Immunohistochemical studies of human renal cell carcinomas for ABO(H) blood group antigens, T antigen-like substance and carcinoembryonic antigen.

Immunohistochemical methods were used to examine human renal cell carcinoma tissues for the presence of ABO(H) blood group antigens, T antigen-like substance and carcinoembryonic antigen. None of the 30 tumors examined showed positive staining for the blood group antigens. In the normal adjacent kidney tissues blood group antigens were noted in the glomeruli, distal tubules and collecting ducts, while proximal convoluted tubules were uniformly negative. The presence of T antigen-like substance was noted in 10 of the 30 tumors (33 per cent). Likewise, T antigen-like substance appeared at the distal tubules and collecting ducts in the normal adjacent kidney tissues, while proximal convoluted tubules were negative. With a monoclonal antibody to carcinoembryonic antigen, 19 of the 30 tumors (63 per cent) showed positive staining. Carcinoembryonic antigen also was observed in the glomeruli and tubular epithelia in the normal kidney tissues. Immunohistochemical findings of T antigen-like substance and carcinoembryonic antigen were not found to be correlated with the tumor grade, cell type and stage, as well as survival of patients with renal cell carcinoma.

ABO Blood-Group System↗