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Biomedical subjects

F Rilke

Publications and source records attributed to F Rilke.

At least 109 records · Page 6Linked to original sources

CD1c but neither CD1a nor CD1b molecules are expressed on normal, activated, and malignant human B cells: identification of a new B-cell subset.

The CD1 cluster of monoclonal antibodies (MoAbs) CD1a, CD1b, and CD1c, identifies molecules that are differentially expressed on hematopoietic and nonhematopoietic tissues. Our earlier finding that the mantle zone (MZ) but not the germinal center (GC) of normal lymph nodes (LN) is CD1c+, CD1a-, and CD1b- prompted us to further investigate the expression of these molecules on normal, activated, and malignant B cells. We report that blood and spleen contain CD1c+ B cells that account for 49% +/- 20.4% (mean +/- SD) and 50.9% +/- 4.4% of the total B cell population, respectively. CD1a- and CD1b-specific MoAbs are unreactive with both B and T cells; these latter are CD1c- as well. When CD1c+ and CD1c- B cells are activated in vitro, the CD1c molecule is upregulated in the former subset and induced de novo in the latter. Conversely, activated blood T cells remain CD1c-. Neither CD1a nor CD1b molecules are detected on activated T and B lymphocytes. At ultrastructural level, the CD1c+ B cells exhibit distinctive features, namely, condensed chromatin with or without a nucleolus and a unique cluster of cytoplasmic vesicles and organelles; the number of nucleolated cells is higher in the spleen (95%) than in the tonsil (40%) or blood (5%). These findings further confirm the similarity between blood and MZ B cells. The CD1c expression assessed on 27 B-cell chronic lymphocytic leukemias (B-CLL) and 46 B non-Hodgkin's lymphomas (B-NHL) was detected on 41% and 32% of cases, respectively; the latter comprised four follicular and 11 diffuse histotypes. The Burkitt's lymphomas were CD1c-negative. The B-cell neoplasms were all CD1a- and, except for four with a weak cytoplasmic staining, all CD1b- as well. The clear-cut CD1c distribution in normal LN (MZ+, GC-) contrasted with the evidence that some B-NHL cells of GC origin (eg, follicular with predominantly small cleaved cells) were CD1c+. Overall, the finding that CD1c expression is restricted to a fraction of B cells present in lymphoid organs and in peripheral blood indicates that CD1c is a powerful marker for the identification and dissection of B-cell subsets whose functional properties can now be evaluated.

Antigens, Differentiation, B-Lymphocyte↗

The Italian registry of soft tissue tumors.

After a review of the incidence data on malignant soft-tissue tumors in Italy (Registro dei Tumori della Regione Lombardia, provincia di Varese), Europe (nine European Cancer Registries considered representative of various geographical areas) and extra-European countries (data of ten World Cancer Registries), the aim and the organization of the Italian Malignant Soft-Tissue Tumor Registry are described. The collection system is based on dedicated forms prepared for the computerization of all data. From 1.1.1985 to 31.3.1987, 207 cases of malignant and potentially malignant soft-tissue tumors entered the Registry, with exclusion of those sarcomas arising in viscera. The distribution, categorized by histologic type, sex and site, and the preliminary results on relapses and metastases are reported.

Adolescent↗

Simultaneous presence of herpes simplex and human papilloma virus sequences in human genital tumors.

Herpes simplex virus (HSV) and human papillomavirus (HPV) sequences were analyzed in tumors of the female lower genital tract, by probing DNA from 13 intraepithelial and 30 invasive neoplastic lesions with radiolabelled HPV-16 and HPV-18 DNA as well as cloned fragments of HSV-2 DNA. Careful removal of stromal tissue from the pathological specimens allowed authentic tumor DNA to be processed. Normal genital tissue obtained from the patients and genital condylomata were included as internal controls. The presence of HPV-16 or 18 DNA was detected in 12/13 (92.3%) intraepithelial neoplasms and in 16/30 (53.3%) invasive carcinomas. No significant difference was detected in titer or frequency of antibodies to HPV group-specific antigen in sera from patients and controls. Hybridization to BgIII N fragment of HSV-2 DNA was detected in 4/13 (30.8%) intraepithelial neoplasms and 4/30 (13.3%) invasive carcinomas but in none of the control tissues. All the 8 samples harboring HSV-2 homologous sequences were also positive for HPV, supporting the hypothesis of a synergistic association between the 2 viruses. The hybridization analyses performed to study c-myc involvement in genital oncogenesis did not reveal c-myc amplification in either invasive or pre-invasive lesions.

Antibodies, Viral↗

Distribution of axillary node metastases by level of invasion. An analysis of 539 cases.

Five hundred and thirty-nine patients with carcinoma of the breast treated with total axillary dissection and with positive axillary nodes were evaluated. The total number of lymph nodes removed was 11,082, with an average of 20.5 nodes per patient. The average number of lymph nodes at the first level was 13.8, at the second level 4.5, at the third level 2.2. The average number of nodes was 20.7 in cases treated with Halsted mastectomy, 20.9 with total mastectomy and axillary dissection, 20.3 with quadrantectomy and axillary dissection. Of 3259 metastatic nodes, 64 were site of micrometastases; 797 were partially involved, 441 were totally involved and 1957 were site of metastases with extracapsular invasion. In 314 (58.2%) the first level only was involved, in 117 cases (21.7%) metastases were present at the first and second level, whereas in 88 cases (16.3%) all the three levels were sites of metastases. Only 20 cases showed skipping distribution. In 1.5% of the cases the first level was skipped by metastases, in 0.4% the first nodes of the first level are clear the chances that metastatic nodes are present at the second and third levels are negligible. When the nodes at the first level are positive, the chances that metastases are also present at the higher levels are of the order of 40.0%.

Axilla↗

Human carcinoma cell lines xenografted in athymic mice: biological and antigenic characteristics of an intraabdominal model.

In order to investigate in vivo clinical applications of murine monoclonal antibodies directed against human ovarian carcinoma a preclinical in vivo model was developed using BALB/c athymic mice. Three human carcinoma cell lines (MCF7, HT29, and SW626) were injected into the peritoneal cavity of pristane-primed animals and the biological and antigenic characteristics of the i.p. grown tumors were studied. The animals were killed when moribund or 6-8 weeks after tumor injection. At autopsy tumor take was observed in 85% of the injected animals, whereas palpable nodules were evident in only 83%. Examination of the peritoneal cavity revealed intraabdominal carcinomatosis with tumor masses varying in size between 0.2 and 0.5 cm in diameter and tumor sheets. The most frequently affected organs were the diaphragm, the liver, and the reproductive system. Ascitic fluid formation was rare and no animal developed tumors outside the peritoneal cavity. To determine whether the in vivo tumors retained the same antigenic characteristics as the in vitro cell lines, four monoclonal antibodies (MBr1, MOv2, MOv8, and MOv15) directed against ovarian carcinoma-associated antigens and two different experimental approaches (immunofluorescence and immunoblotting) were used. Variations at either a quantitative or a qualitative level were observed for some antigens, whereas no evident changes were apparent for others. In particular, the antigens detected by MBr1 and MOv15 on the MCF7 line both maintained high levels of expression and immunoblotting staining pattern, whereas the antigens detected by MOv2 on the HT29 and SW626 lines, although present at a high level, clearly changed their staining pattern. As regards the antigens recognized by MOv8 and MOv15 on the HT29 and SW626 lines, we observed a drastic decrease in the level of their expression and in many cases a drop below the threshold of detectability of the test. The intraabdominal carcinomatosis described partially mimics the growth characteristics of human ovarian cancer and maintains the expression of some antigenic markers associated with epithelial tumors of the ovary and may therefore be useful in devising immunodiagnostic and/or immunotherapeutic strategies for ovarian carcinoma.

Animals↗

Human papillomavirus-associated early vulvar neoplasia investigated by in situ hybridization.

Of 21 consecutive cases of early vulvar neoplasia studied at the Istituto Nazionale Tumori of Milan, 62% appeared to be related to papillomavirus infection. This conclusion is the result of the present study by in situ hybridization with DNA probes of human papillomavirus (HPV) 6/11, 16, and 18 and of previous ultrastructural and immunohistochemical investigations. The proportion of cases associated with HPV was 78.5% for those (11/14) with histologic evidence of viral infection and 33% for those without (2/6). HPV 16 was detected in all cases that were positive by in situ hybridization except for one, which showed HPV 6/11 DNA. In one case there was a mixed triple infection for HPV 6/11, 16, and 18. The patient who was positive for HPV 6/11 had a giant condyloma associated with an inguinal lymph node containing a metastatic well-differentiated squamous cell carcinoma. Three cases were positive for papillomavirus internal capsid species-nonspecific antigen (PV-Ag) (with ultrastructural evidence of virions in one of them) and were negative for HPV-DNA hybridization. They appeared to be infected with a type of HPV not identified by the available probes. Three cases, and two sites of two other cases with double infection, were HPV-DNA-positive and PV-Ag-negative. They illustrate the limitation of immunohistochemical investigation in cases with high-grade intraepithelial neoplasia. Six cases of verrucous carcinoma of the vulva were negative for HPV DNA by in situ hybridization.

Carcinoma, Papillary↗

A cytogenetic, phenotypic, and molecular study of an immunoblastic lymphoma with a 14q + translocation.

An uncultured immunoblastic lymphoma, obtained from an untreated patient, was examined from a cytogenetic, immunophenotypic, and molecular viewpoint. The B-cell lineage, immunoglobulin light-chain type, and percentage of neoplastic cells were determined immunologically. Karyotyping showed the presence of a 14q + marker and suggested that the donor chromosome was chromosome 8. Southern-blot analysis of DNA from normal and lymphoma cells, using a molecular probes sequences related to the IGHJ and IGK immunoglobulin genes, confirmed the immunophenotype. A similar analysis, using probes homologous to IGHAC and MYC genes, showed that the t(8;14) detected by cytogenetic analysis resulted in a IGHAC-MYC rearrangement.

Antigens, Surface↗

Association of human papillomavirus type 16 with neoplastic lesions of the vulva and other genital sites by in situ hybridization.

The authors examined paraffin sections from 85 genital tract tissues from 49 cases for the presence of human papillomavirus (HPV) Types 6/11, 16, and 18 by stringent in situ hybridization using 35S-labeled viral DNA probes, and for viral capsid antigen by the immunoperoxidase test. The cases, selected mostly on the basis of vulvar pathology, were distributed as follows: early neoplasia (Group I, 6 cases); early neoplasia with viral cytopathic effect (CE) (Group II, 24 cases); and papillomavirus infection (PVI) (Group III, 19 cases). Available tissues from all affected sites were examined when the disease was multicentric. One or more viral DNAs were identified in 58% of 77 tissues from Groups II and III and in 2 of 8 tissues from Group I. HPV-6/11, HPV-16 and HPV-18 DNAs were detected, respectively, in 25, 24, and 2 tissues; 3 tissues were infected simultaneously with either two or three viruses. Viral DNA was identified at more than one site in 14 of 30 DNA-positive patients; in 10 of these, a single type was detected at all sites in the same patient. The viral DNA was localized mostly in areas showing viral cytopathology. The presence of HPV-16 correlated with neoplasia. HPV-16 DNA was identified in the 2 virus-positive tissues showing neoplasia, in 17 of 20 (85%) of the DNA-positive tissues showing neoplasia with CE, and in 5 of 25 (20%) of the DNA-positive tissues showing PVI. Conversely, HPV-6/11 was found in 25% of the DNA-positive tissues showing neoplasia with CE and in 80% of the cases of PVI. An HPV genome was identified in neoplastic cells in 14 instances; in all but 1 case, the genome was HPV-16. The association of HPV-16 with neoplasia was seen for both vulvar and cervical lesions. Viral antigen was detected in 83% of lesions associated with HPV 6/11 and in 62% of lesions associated with HPV-16.

Adult↗

Relationship between ER-ICA and conventional steroid receptor assays in human breast cancer.

We applied a new immunocytochemical assay for estrogen receptors (ER-ICA) to 82 human breast tumors. Results were correlated with cytosolic estrogen receptors (ERc) and nuclear ER (ERn) determined on the same sample respectively by the radioligand binding assay and by an ER enzyme immunoassay (ER-EIA). All ER-ICA-positive tumors contained more than 10 fmol/mg of protein of ERc and were therefore considered as ERc positive. In contrast, 15.4% of ERc-positive cases were ER-ICA negative. Comparison of ER-ICA results with ERn showed extensive agreement of negativity (92%), whereas 38% of ER-ICA-positive tumors were ER-EIA negative. However, the latter had ERc levels above the positivity threshold. Quantitative features of the immunocytochemical staining such as intensity and percentage of labelled cells, considered separately, did not reflect the amount of ERc or ERn. Cellularity was not significantly correlated with ER-ICA and biochemical results.

Breast Neoplasms↗

Comparison of Halsted mastectomy with quadrantectomy, axillary dissection, and radiotherapy in early breast cancer: long-term results.

From 1973 to 1980 we randomly assigned 701 patients with breast cancer measuring less than 2 cm in diameter and with no palpable axillary lymph nodes to Halsted radical mastectomy (n 349) or to 'quadrantectomy' with axillary dissection and radiotherapy to the ipsilateral breast tissue (n 352). The two groups were comparable in age distribution, size and site of primary tumor, menopausal status, and frequency of axillary metastases. The average follow-up time was 103 months. Actuarial curves show no difference between the two groups in the disease-free interval after surgery or in the overall survival rate. At 8 yr the disease-free survival was 77% for the patients in the Halsted group and 80% for those in the 'quadrantectomy' group, and the overall survival was 83 and 85% respectively. We conclude that small breast cancers may be safely treated with the conservative treatment described. In our opinion total ablative operations are not justified.

Axilla↗

Improvement of tumor cell detection using a pool of monoclonal antibodies.

It has been proven that monoclonal antibodies which are not strictly tumor specific may be useful in clinical oncology for diagnosis and in in vitro therapy. These applications, however, are hampered by the heterogeneous expression on tumor cells of the epitopes defined by the majority of monoclonal antibodies produced so far. The use of combined monoclonals could complement their antitumor specificity and solve the problem. In this perspective we selected nine monoclonal antibodies directed against different antigens of primary and metastatic breast cancer cells. The reactivity of the pool of these nine monoclonals versus a single antibody (MBr1) was determined by immunofluorescence on tumor cell lines, on frozen sections of various carcinomas, and on live cells obtained from malignant effusions. The results obtained with the pool, compared to those using MBr1 alone, showed a remarkable increase in the number of immunopositive breast and other carcinomas and the number of immunopositive cells within each positive tumor. In fact, the percentage of immunoreactive breast carcinomas increased from 79% to 100%, and the percentage of immunoreactive carcinomas of other sites from 61% to 89%. In addition, the number of positive breast carcinomas showing 100% immunoreactive cells increased from 5% with MBr1 to 71% when the pool was used.

Antibodies, Monoclonal↗

Fetal heavy chain skeletal myosin. An oncofetal antigen expressed by rhabdomyosarcoma.

Fetal heavy chain skeletal myosin is normally present in fetal skeletal muscle. The study of 21 cases of rhabdomyosarcoma using specific antisera for fetal myosin, as well as for slow myosin, myoglobin, and desmin, led to positive findings in all cases with at least one antiserum. Desmin was localized in all cases and fetal myosin in 17 cases (81%), while myoglobin and slow myosin were present in 11 and eight cases, respectively. The localization of fetal myosin in rhabdomyosarcoma indicates that it is a type of oncofetal antigen. Because fetal myosin is found in small rhabdomyoblasts, it can be a useful marker in cases that usually constitute diagnostic problems.

Adult↗

Human papillomavirus type 16 DNA in genital tumours: a pathological and molecular analysis.

The presence of human papillomavirus type 16 (HPV16) DNA in 34 genital tract tumours of Italian female patients was investigated by Southern blot hybridization in high stringency conditions. HPV16 DNA was detected in 16 neoplasias, including cervical invasive and intraepithelial lesions as well as vulvar intraepithelial neoplasias and, to a lesser extent, vulvar invasive carcinomas. Appropriate control tissues included in the study were negative. The data suggest that integration of viral DNA had occurred in most tumours, both in invasive and in intraepithelial lesions. HPV16 variants or defective genomes, lacking the BamHI restriction site, were detected in three tumours.

Carcinoma, Squamous Cell↗

The contribution of molecular biology in the diagnosis of human lymphomas.

The relationship between T cell receptor (TCR) beta and gene immunoglobulin heavy chain locus was investigated in 25 cases of unselected human lymphomas as well as in normal and non-neoplastic lymphoid tissues. Hybridizing our blots with Jurkat 2, a clone specific for the beta chain gene of TCR, did not demonstrate extra bands in non-neoplastic tissues composed of 50-95% T-cells. On the contrary, rearranged bands were detected in six out of six cases of T-cell lymphomas. No TCR beta gene rearrangements were detected in 11 B-cell lymphomas, which in turn presented modification of the immunoglobulin heavy chain gene germline configuration. Our results suggest that TCR beta chain gene rearrangements are a good marker for human T-cell neoplasias in humans and complement the analysis with immunoglobulin genes probes. Eighth samples were devoid of any rearrangements: this group comprises cases of Hodgkin's disease T-lymphoblastic lymphomas in clinical remission and malignancies of unknown origin, as discussed in the text. We conclude that the analysis using DNA probes specific for TCR beta and IgH genes can be of aid to the pathologist in the diagnosis and classification of human lymphomas.

DNA, Neoplasm↗

Tumour-associated antigens in mammary and extramammary Paget's disease.

The immunoperoxidase technique was used to study the immunoreactivities of two murine monoclonal antibodies to carcinoma-associated antigens raised respectively against a human breast cancer line (MBr1) and an ovarian carcinoma (MOv2) and of a conventional anti-CEA serum in 20 cases of mammary Paget's disease of the nipple and in three cases of extramammary Paget's disease. Each of the immunoreagents stained Paget's cells in a high proportion of cases and failed to discriminate mammary from extramammary disease. The antigenic phenotypes of underlying in situ or infiltrating breast carcinomas corresponded to those of the associated Paget's disease of the nipple. The consistent immunoreactivity of eccrine and apocrine sweat glands and of normal mammary epithelia indicated an antigenic relationship between epithelia of adnexal derivation and Paget's cells.

Antibodies, Monoclonal↗

Relation between enzymatic activities and the degree of malignancy of human lymphomas.

The relationship between the intracellular levels of DNA polymerase alpha (DP-alpha), adenosine deaminase (ADA) and lactate dehydrogenase (LDH) and the degree of malignancy of human lymphomas was investigated. Twelve non-neoplastic lymph nodes and 88 malignant lymphomas were examined. For non-Hodgkin's lymphomas (NHL) the low or high grade of malignancy was established according to three classifications: the Rappaport, the Kiel and the Working Formulation for Clinical Usage, with the latter also recognizing an intermediate grade group. Non-neoplastic lymph nodes had significantly lower levels of all the three enzymes than those found in high-grade malignant NHL (the P value ranged from less than 0.02 to less than 0.001). Hodgkin's disease, a slowly evolving neoplasia, showed lower levels of DP-alpha (P less than 0.001) and ADA (P less than 0.001), but not of LDH, than high-grade NHL. Among NHL, whatever classification was used, the low-grade malignant lymphomas had significantly lower levels than the high-grade ones for all the three enzymes (P less than 0.005 or P less than 0.001). The intermediate-grade group of the Working Formulation differed from the high-grade group for DP-alpha (P less than 0.01) and ADA (P less than 0.02) but not for LDH. It differed from the low-grade group only for ADA (P less than 0.005). Lymphoblastic and Burkitt's lymphomas were the groups with the highest levels of the three enzymes. Among low-grade lymphomas very low values were found in the histological entities defined as DLWD in the Rappaport classification, CLL and lymphoplasmacytoid immunocytoma in the Kiel classification and small lymphocytic (group A) in the WF. The levels of all enzymes in these histotypes were always significantly different from the other low-grade histotypes, and from the intermediate-grade ones of the WF. In the Kiel classification polymorphous lymphoplasmacytoid lymphoma, recently recognized as a group with a quite aggressive clinical course, was characterized by high levels of all three enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Deaminase↗