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Biomedical subjects

C Moroz

Publications and source records attributed to C Moroz.

At least 19 recordsLinked to original sources
PubMed1992

Expression of p43 in breast cancer tissue, correlation with prognostic parameters.

Placental isoferritin (PLF) and its unique superheavy chain p43 have been recently described as being synthesized by breast cancer cell lines but not by normal breast epithelial cells. Since previous reports have demonstrated a correlation between the content of 'normal' ferritin in breast cancer tissue and the degree of differentiation and prognosis, we have determined p43 in the cytosol of 122 breast cancer samples by use of the new monoclonal antibody CM-H-9. The synthesis of p43 showed a significantly negative correlation with tumor size (P = 0.0001), histologic grading (P = 0.0038), nuclear pleomorphism (P = 0.0019), rate of mitosis (P = 0.0002), lymphocytic reaction (P = 0.0001) and a significantly direct correlation with estrogen receptor status (P = 0.0009). Although patients with a higher p43 content showed a trend for a better outcome (median follow-up: 61.4 months), an independent influence of the cytosolic p43 content on survival could not be confirmed by a multiple Cox model. Therefore it seems that p43's prognostic impact is linked to the highly significant correlation with features of differentiation although a statistical bias in the Cox model due to the limited number of patients must also be taken into account. On the other hand, the significant correlation of p43 expression with factors for good prognosis was striking and consistent and warrants further research of this tumor product.

Breast Neoplasms↗
PubMed1992

Placental isoferritin associated p43 antigen correlates with features of high differentiation in breast cancer.

Placental isoferritin (PLF), an acidic isoform of ferritin, and its unique superheavy chain p43 have been recently described to be synthesized by breast cancer cell lines but not by normal breast epithelial cells. Since previous reports have demonstrated a correlation between the content of 'normal' ferritin in breast cancer tissue, degree of differentiation, and prognosis, we have tried to evaluate the correlation of p43 in the cytosol of 122 breast cancer samples with commonly applied prognostic factors and features of proliferation and differentiation. In parallel, we investigated the correlation of p43 expression in MCF-7 and T47-D breast cancer cell lines during proliferation induced by estradiol plus fetal calf serum (assessed by 3H-thymidine incorporation), compared to p43 expression in stationary non-stimulated cell cultures. The levels of p43 in breast cancer cytosols correlated significantly negatively with tumor size (p = 0.0001), histologic grading (p = 0.0038), nuclear pleomorphism (p = 0.0019), rate of mitosis (p = 0.0002), and lymphocytic reaction (p = 0.0001), and significantly directly with the estrogen receptor status (p = 0.0009). Although patients with a higher p43 content showed a trend for a better outcome (median follow-up: 61.4 months), an independent influence of the cytosolic p43 content on survival could not be confirmed by a multivariate Cox model. In accordance with the observed negative correlation of features of differentiation vs. p43 expression, induction of proliferation by estradiol plus FCS added to serum-free tissue culture medium correlated with a decrease of p43 synthesis in both cell lines. Expression of p43 in estrogen and FCS-absent media revealed also a decrease in relation to a low spontaneous proliferation. However, the drop of p43 synthesis was significantly stronger in cell lines with estrogen-stimulated proliferation. Our in vitro and cytosol results confirm recent clinical observations describing an inverse correlation of p43 synthesis with the degree of proliferation and differentiation in breast cancer. However, the pathologic mechanisms leading to this phenomenon as well as the negative correlation with lymphocytic infiltration are still unclear and need to be further elucidated.

Breast Neoplasms↗
PubMed1991

Placental isoferritin (PLF) in comparison with MCA and CEA in advanced breast cancer--first data from a pilot study.

The development of new and effective marker substances has optimized tumor-marker-guided follow-up programs to monitor generalization of disease and to assess the therapeutic outcome. Isoferritins of placental origin were first determined in the serum of patients with lymphoproliferative disease by way of the recently developed monoclonal antibody CMH-9. We have set up an Austro-Israeli working group and analysed 64 patients in terms of the sensitivity of placental ferritin (PLF) compared with the standard markers carcinoembryonic antigen (CEA) and mucinous-like cancer-associated antigen (MCA) in patients with metastatic breast cancer. We have additionally evaluated the importance of combined marker determination. Analysis of the data in view of site of metastatic spread yielded satisfying results both for PLF (sensitivity 70.4%) as well as MCA (sensitivity 76.9%) for visceral metastases; a combination of these two markers revealed a striking sensitivity of 88.4%, which, however, could not be improved by adding the third marker (CEA). With regard to non-visceral metastases, CEA and MCA were clearly superior.

Adult↗
PubMed1991

Monoclonal antibody CM-H-9 detects circulating placental isoferritin in the serum of patients with visceral metastases of breast cancer.

The aim of the current pilot study was to determine whether placental isoferritin (PLF) can be detected in the serum of patients with metastatic breast cancer. Sera were obtained from breast cancer patients with metastatic disease (n = 100), from breast cancer with no evidence of disease (n = 70) and from healthy female controls (n = 34). PLF and total serum ferritin levels were independently measured using specific monoclonal antibody ELISAs in a double-blind study. It was found that the mean serum PLF levels were significantly elevated only in patients with visceral metastases (lung, liver, brain) compared with the levels of patients with non-visceral metastases (bone, skin) or with healthy controls. Contrary to this, analysis of total serum ferritin levels did not reveal significant differences between these groups. Considering 0-10 units/ml as a PLF negative result, it was found that PLF was negative in 87.5% of healthy controls and in 96% of breast cancer patients with no evidence of disease. In contrast, PLF was positive in 73% of the patients with visceral metastases and in 29.7% of those with non-visceral metastases. The striking difference between visceral and non-visceral metastases is not yet understood. It could result from a difference in the degree of vascularisation or, alternatively, a difference in the cell types and genes expressed by cells metastasizing to visceral or non-visceral organs.

Adult↗
PubMed1991

Placental ferritin in coeliac disease: relation to clinical stage, origin, and possible role in the pathogenesis of malignancy.

Placental ferritin is a tumour associated antigen present in the serum of patients with active Hodgkin's and non-Hodgkin's lymphoma, and the serum values fall during remission of the disease. There is no correlation between placental and total blood ferritin values. Because of the strong association between coeliac disease and lymphoma, 19 children with active and 25 with inactive coeliac disease were screened for the presence of placental ferritin. Thirty two children with other intestinal disorders served as controls. Placental ferritin was identified by using a monoclonal antibody in an ELISA procedure. The mean (SEM) placental ferritin value in the control serum was 12.6 (2.4) while the values in serum of patients with active and inactive coeliac disease were 117 (22.8) and 43.8 (10.2) U/ml respectively. Patients with active coeliac disease differed significantly from both control subjects (p = 0.0004) and those with inactive disease (p = 0.03). Peripheral blood lymphocytes contained no placental ferritin. It was present, however, in lamina propria lymphocytes of intestinal biopsy specimens from active coeliacs. Placental ferritin was also found in some of the better differentiated malignant cells in two patients with adult onset enteropathy associated lymphoma. Placental ferritin is known to have an immunosuppressive effect, and this may be one of the necessary steps in the development of malignancy associated with coeliac disease. Gluten free diet, by reversing this state, may have a role in the prevention of lymphoma.

Adolescent↗
PubMed1991

Comparison of transferrin receptors, iron content and isoferritin profile in normal and malignant human breast cell lines.

We studied the mode of iron transport and storage in a human breast cancer cell line (HT-24) in comparison with a breast epithelial cell line (HBL-100). It was found that HT-24 cells incorporated over 18 h more 59Fe as compared to HBL-100 (24 vs. 16%). Yet, the number of surface transferrin-binding sites was less in cancer cells (6.2 x 10(5)) than in epithelial cells (8 x 10(5)). Moreover, the transferrin receptors in cancer cells were less affected by iron overloading as compared with epithelial cells. Following immunoprecipitation of isoferritins with specific monoclonal antibodies (MoAbs), it was found that the quantity of de novo synthesized normal ferritin immunoprecipitated with CM-G-8 MoAb was similar in both cancer and epithelial cells. However, the amount of 59Fe incorporated into the protein was significantly higher in HBL-100 cells. In contrast, HT-24 cells synthesized a high amount of placental-like isoferritin (PLF) immunoprecipitated with CM-H-9 MoAb which was significantly higher (p less than 0.001) than in epithelial cells. This isoferritin was characterized by its low iron incorporation. It is noteworthy that the ratio of PLF to normal ferritin was 2:1 in cancer cells and 0.7:1 in epithelial cells, indicating that PLF is a major type of isoferritin synthesized by HT-24 breast cancer cells. Furthermore, a significant amount of PLF was expressed on the surface of cancer cells as compared to epithelial cells. The results of this study suggest that iron supply and distribution in breast neoplastic cells are not controlled similarly to normal cells.

Adenocarcinoma↗
PubMed1990

Elevated serum placental isoferritin in newly diagnosed type 1 (insulin-dependent) diabetes mellitus. A possible marker for identification of high risk subjects.

Placental isoferritin is produced by activated T lymphocytes and may, therefore, be considered as a manifestation of T cell involvement. Placental isoferritin is measured using CM-H-9 monoclonal antibody which binds exclusively to placental isoferritin. Placental isoferritin has been determined in the serum of 80 patients with Type I (insulin-dependent) diabetes mellitus, 100 healthy first degree relatives and 81 healthy children. Serum levels which were measured in Type 1 diabetic patients, (24.0-140 U/ml; median and range) were significantly higher than those of family members (0,0-73; median and range; p less than 0.0001) and normal control subjects (0,0-48; median and range; p less than 0.0001). Using 0-10 U/ml as the upper limit of normal, it was found that 31 of 50 (62%) of Type 1 diabetic patients, 25 of 100 (25%) family members and 7 of 81 (8.6%) healthy control subjects had abnormal placental isoferritin levels. Islet cell antibodies were positive in 31 of 44 tested diabetic patients and, in 8 of 71 tested family members, and among them 54.8% and 50% respectively also had elevated placental isoferritin levels. However, no statistically significant correlation was found between islet cell antibodies and placental isoferritin levels. Treatment of Type 1 diabetic patients with insulin was accompanied by a significant decrease (p less than 0.002) of serum placental isoferritin within 2-4 weeks of treatment. It is noteworthy that placental isoferritin was below detection in 34 of 35 Type 2 (non-insulin-dependent) diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Expression of messenger RNA species coding for a Mr 43,000 peptide associated with ferritin in human leukemia-K562 cells and its down regulation during differentiation.

In the current study it was found that K-562 erythroleukemia cells express the superheavy (S) mRNA and the 43 Kd S peptide which were recently discovered in activated T-lymphocytes. The S mRNA was identified by its cross-hybridization with ferritin H complementary DNA probe and the S peptide (Mr 43,000) was identified by its immunoprecipitation with CM-H-9 monoclonal antibody specific for placental isoferritin. During terminal differentiation by hemin the level of S mRNA decreased below detection, with a concomitant diminution in the biosynthesis of the S peptide. In contrast, a significant increase in the level of ferritin light (L) and heavy (H) mRNAs was observed, resulting in an increase in the rate of biosynthesis of the H and L ferritin subunits. Removal of iron by desferrioxamine reduced the biosynthesis of ferritin L and H chains without altering the level of the corresponding mRNAs. Treatment with desferrioxamine did not affect either the level of S mRNA or the biosynthesis of the S peptide. This is a demonstration of a new mRNA species which is expressed in leukemic cells and is down-regulated during cell differentiation.

Cell Line↗
PubMed1989

The use of oncofetal ferritin-bearing lymphocytes as a marker for the screening, diagnosis, and follow-up of patients with early breast malignancy screening of 3400 women.

The potential of using a blood test enumerating oncofetal ferritin-bearing lymphocytes (FBL) as a biomarker for early breast cancer was further explored. Nine hundred women attending a high-risk breast cancer clinic and 2500 normal-risk women were physically examined and their blood drawn for FBL determination using a newly developed radioimmunoassay. The FBL test results were compared to clinically or histopathologically diagnosed breast disease and to known breast cancer risk factors. A gradual increase in the mean FBL ratio was seen from normal risk disease-free women to those with in situ or early stage breast cancer. The percentage of women with positive FBL was 13.6% for the normal risk group, 19% and 25.7% for clinically and histopathologically diagnosed benign breast disease, respectively, and 100, 77.8, and 66.7% for in situ, Stage I, and Stage II breast cancer, respectively. In locally advanced disease (Stage III) the percentage of positive women was only 17.2%. It was further found that a negative FBL result in known breast cancer patients at Stage I, II of the disease was a bad prognostic marker indicating a shorter disease-free survival. The follow-up of patients after surgery by periodical clinical examination and the FBL test revealed that the positive FBL was declining after removal of the precancerous or malignant tumor and that it was highly sensitive (100%) in predicting tumor development and recurrence. Using a logistic regression analysis, an FBL-positive test indicated a significant association with risk of early breast cancer (odds ratio = 2.9; 95% confidence interval = 1.4-5.8). Being a measure of the immune response the positive FBL was associated with early breast cancer and good prognosis. Since patients with locally advanced cancer and poor prognosis were FBL negative but such patients were shown to have increased serum ferritin levels. It is suggested to use the FBL and serum ferritin assays for screening and diagnosis of breast cancer.

Antigens, Neoplasm↗
PubMed1989

Characterization of T-lymphocyte subpopulations infiltrating primary breast cancer.

Characterization of T-lymphocyte subpopulations adjacent to and infiltrating the primary tumor of breast cancer was carried out using a direct immunofluorescence procedure with the antibodies anti-(Leu-2a) for suppressor/cytotoxic (CD8+) and anti-(Leu-3a) for helper/inducer (CD4+) T-lymphocytes. Fifty-six primary malignant tumors with lymphoid infiltration were studied. The majority (58.9%) were infiltrating duct carcinoma. There were metastases to axillary lymph nodes in 6.67% of the patients. Massive lymphoid infiltration (greater than 40 lymphocytes per x 400 microscopic field) was found in 19.6% of the tumors and moderate infiltration (20-40 lymphocytes per field) in 51.8%. In all the tumors studied there was a reversed CD4+/CD8+ ratio as compared to that found in normal peripheral blood. In 66.1% the CD4+/CD8+ ratio (helper/suppressor) was less than 1.0. The reversed ratio was due to a significant decrease in the number of helper cells (P less than 0.0005). The most significant drop was in the stroma area (P less than 0.0001) as well as in the tumor tissue (P = 0.001). Of particular interest was the significant positive correlation between the age of the patients and an increased number of CD4+lymphocytes in the stroma (P = 0.02). Significant negative correlations were found between a reduced number of CD4+ lymphocytes or CD4+/CD8+ ratio and several histological parameters: tumor diameter, pleomorphism, nucleus/cytoplasm ratio. There was also a significant positive correlation between the total number of CD8+ lymphocytes infiltrating the tumor tissue and the number of axillary lymph nodes with metastatic disease (P = 0.03). It is suggested that the reversed ratio of CD4+/CD8+ lymphocytes may significantly affect the host/tumor immune surveillance.

Adult↗
PubMed1989

Placental isoferritin: a new serum marker in toxemia of pregnancy.

The serum concentrations of placental isoferritin and normal ferritin were determined in 20 patients with preeclamptic toxemia of pregnancy and were compared with the level measured in normal pregnant women at the third trimester and in labor at term. The mean serum concentration of placental isoferritin for the women with preeclamptic toxemia was found to be low: 7.5 +/- 23 U/ml compared with 81.6 +/- 89.3 U/ml in normal pregnancy during the third trimester and 54.8 +/- 53 U/ml in term delivery. In comparison, there was no significant difference in the serum levels of normal ferritin in both pregnant women with toxemia and in those without toxemia. These results suggest that placental isoferritin may be a useful marker for preeclamptic toxemia of pregnancy.

Biomarkers↗
PubMed1989

T-cell mitogenesis stimulates the synthesis of a mRNA species coding for a 43-kDa peptide reactive with CM-H-9, a monoclonal antibody specific for placental isoferritin.

In studying the changes that occur in concanavalin A-activated T lymphocytes, an mRNA species was discovered by hybridization of poly(A)+ mRNA with a human ferritin heavy chain cDNA probe. This ferritin mRNA, termed superheavy chain mRNA, differed from the known human ferritin heavy chain mRNAs by its larger size and degree of homology. The superheavy chain mRNA was isolated by sucrose-gradient centrifugation and translated in vitro in a cell-free system. The products obtained included two peptides (superheavy) of 43kDa that reacted with CM-H-9, a monoclonal antibody specific for placental isoferritin. De novo synthesis in intact transformed T cells revealed the synthesis of the superheavy chain peptides that were immunoprecipitated by anti-ferritin monoclonal antibody CM-G-8 and by placental isoferritin specific monoclonal antibody CM-H-9. The above results indicated that blast transformation of human T cells stimulated the appearance of a unique mRNA species that coded for a superheavy chain peptide associated with placental isoferritin, which was not detected in resting T cells.

Antibodies, Monoclonal↗
PubMed1989

Radioimmunodetection of tumors with monoclonal antiplacental ferritin antibody: preliminary results.

Two mouse monoclonal antiferritin antibodies were employed to detect tumors. In the first case a solitary hepatoma was defined, while in the second one, mediastinal metastases of breast cancer were detected. In both cases serum ferritin levels were raised. The availability of monoclonal antiferritin antibodies offers certain advantages over polyclonal antibodies (ease of production, purification and reproducibility). These antiferritin antibodies may be found useful in diagnosis and therapy of certain tumors.

Aged↗
PubMed1989

Isoferritins in HIV infection: relation to clinical stage, CD8 lymphocyte binding and the pathogenesis of AIDS.

Placental isoferritins (PLF), known to be immunosuppressive in Hodgkin's disease and other states, were found to be increased in sera of subjects infected with HIV. We assayed for PLF using a 'sandwich' antigen capture enzyme-linked immunosorbent assay (ELISA) employing two monoclonal antibodies. Individuals with lymphadenopathy, with or without symptoms suggestive of AIDS-related complex, had the highest serum levels, which declined with progressive immunodeficiency. Total (normal) ferritins, in contrast, increased progressively with stage of disease. PLF was found on a subset of CD8 lymphocytes and appeared to block detection of the CD8 antigen by specific monoclonal antibodies. Elution of PLF by incubation with levamisole, but not by culture medium alone, led to the unblocking of the CD8 determinant on these cells. Profiles of isoferritins in HIV infection may provide clues to prognosis. PLF, a physiologic down-regulator of hematopoiesis and cellular immunity, could play a role in the progressive immune deficiency, marrow suppression and HIV expression that lead to AIDS.

AIDS-Related Complex↗
PubMed1989

Placental isoferritin as a physiological downregulator of cellular immunoreactivity during pregnancy.

CM-H-9 monoclonal antibody specific for placental isoferritin (PLF) was used to quantify PLF in the serum and on peripheral blood lymphocytes derived from term delivery women and healthy controls. It was found that the mean level of PLF in maternal sera was 50.4 +/- 50.1 U/ml, whereas in normal adults the mean serum PLF level was very low (4.5 +/- 7.7 U/ml). Furthermore, term mothers exhibited a sub-population of peripheral blood lymphocytes (PBL) which stained positively with CM-H-9 MoAb (mean 11.6 +/- 7.8%). Such lymphocytes were scarce in normal non-pregnant women (mean 0.8 +/- 1.2%). The effect of PLF on lymphocyte transformation in MLC was studied in mixed lymphocyte cultures of maternal-newborn and normal non-related PBL controls. It was found that placental isoferritin was immunosuppressive in comparison to normal adult ferritin. The suppressive effect was significantly higher in maternal-newborn MLC compared to normal adult controls. Furthermore, it was found that PLF which is present in maternal serum has an immunosuppressive activity since, its removal on CM-H-9 MoAb affinity column abrogated this effect. The results of this study suggest that both PLF and PLF binding lymphocytes play a role in the development of immunosuppression during pregnancy. Therefore the lack of one of the factors may result in diminished immunosuppression or in fetal rejection.

Female↗
PubMed1989

Placental isoferritin measured by a specific monoclonal antibody as a predictive marker for preterm contraction outcome.

The serum levels of placental isoferritin and normal ferritin in 25 women with preterm contractions (mean +/- SE gestational age 28.8 +/- 4.7 weeks) were compared with those in 14 control women with uncomplicated pregnancies (29.1 +/- 7.3 weeks). The serum concentration of placental isoferritin in women with preterm contractions (15.3 +/- 6.2 U/mL) was significantly lower than that in normal pregnant women (87.6 +/- 22.6 U/mL) (P = .005). The level of normal ferritin in women with preterm contractions (30.6 +/- 4.16 ng/ml) was lower than that in women with normal pregnancies (67 +/- 9.6 ng/mL) (P = .01); however, both were within the normal range. Serum placental isoferritin levels correlated with pregnancy outcome; low placental isoferritin (up to 10 U/mL) was a sensitive (71.5%) indicator of preterm labor. Low placental isoferritin had a positive predictive value of 59% and a negative predictive value of 71%. These results suggest that placental isoferritin may serve as a predictive marker for the prognosis of preterm contractions.

Antibodies, Monoclonal↗