PubMed Health⌕ Search

Biomedical subjects

T Cabrera

Publications and source records attributed to T Cabrera.

49 records · Page 3Linked to original sources
PubMed1991

Tumor aggressiveness and MHC class I and II antigens in laryngeal and breast cancer.

HLA class I and II molecules play an important role in the immune system. Thus, alterations in their expression could affect the immunosurveillance against tumors. The expression of these molecules may therefore be one of the factors responsible for oncogenicity, due to their role as restriction elements in T cell recognition. A series of 78 primary laryngeal and 94 breast tumors were evaluated for the expression of MHC class I and II antigens, using monoclonal antibodies. We found a number of cases presenting total loss of HLA-ABC and selective losses of HLA-A and HLA-B antigens. These losses were statistically associated with clinical and pathological parameters such as T stage, degree of differentiation, scores according to the malignancy grading systems and degree of leukocytic infiltration. On the other hand, the de novo expression of DR antigens in laryngeal cancer was found in a group of neoplasms having a peculiar clinical behavior and excellent prognosis. Expression of class II molecules in breast tumors was also related to a better differentiation and prognosis. Thus, HLA class I and II antigen expression is closely related to aggressiveness and prognosis of laryngeal and breast cancer.

Adenocarcinoma↗
PubMed1990

K-ras mutations (codon 12) are not involved in down-regulation of MHC class-I genes in colon carcinomas.

Fifty-eight colorectal carcinomas were studied for HLA class-I antigen expression and for the presence of point mutations in codons 12 and 61 of the K-ras gene. Eight carcinomas were completely negative for class I by the APAAP technique. Analyses using the polymerase chain reaction (PCR) method, together with selective hybridization using mutation-specific synthetic oligonucleotides, demonstrated K-ras mutations in 14 cases (24.1%), all of them in codon 12. None of the mutations corresponded to the negative cases for class-I HLA antigen expression. We did not observe any correlation between K-ras mutations and the extent of tumor differentiation.

Aged↗
PubMed1990

Presence of HPV 16 sequences in laryngeal carcinomas.

Human papillomavirus types HPV 16 and HPV 11 DNA sequences were analyzed in normal and neoplastic tissues of the larynx, using the technique of polymerase chain reaction (PCR). An amplified region of E6 ORF was hybridized with 3' end-labelled oligonucleotide probe. Twenty six out of 48 (54%) squamous-cell carcinomas, and 3 out of 3 verrucous-cell carcinomas hybridized with HPV 16 DNA sequences, whereas we did not detect HPV 11 sequences. HPV 16 DNA sequences were also found in normal, autologous mucosa and lymphnode metastases, although these were absent in other tissues analyzed. HPV-16-positive tumors were most frequently poorly differentiated squamous-cell carcinomas.

Base Sequence↗
PubMed1990

Class II HLA antigen expression in familial polyposis coli is related to the degree of dysplasia.

Class II HLA antigen expression was studied in 30 polyps from 3 patients who were diagnosed with familial polyposis coli. The highest levels of this expression were associated with the most severe grades of dysplasia (p less than 0.00001), the sequence of positivity being HLA-DR greater than DQ greater than DP. No association was observed between the expression of these antigens and the presence of a specific inflammatory leukocytic infiltrate. Our results imply that HLA class II molecule expression is somehow related to malignant transformation in familial polyposis coli in accordance with the adenoma-dysplastic adenoma-adenocarcinoma sequence. Thus these antigens may be useful markers to tumoral progression.

Adenocarcinoma↗
PubMed1987

Class I and II HLA antigen distribution in normal mucosa, adenoma and colon carcinoma: relation with malignancy and invasiveness.

HLA class I and II antigen expression was studied in normal mucosa, adenoma and colon carcinoma. Alkaline phosphatase anti-alkaline phosphatase (APAAP) staining techniques were used in cryostatic sections with anti-HLA-ABC and DR,DP,DQ monoclonal antibodies. All normal mucosa were intensely positive for HLA class I antigen expression, while failing to express class II molecules, except in mucosa adjacent to tumors (15/19 cases). All adenomatous polyps expressed HLA class I antigen, while the intensity of class II expression (DR greater than DQ greater than DP) was paralleled by the degree of dysplasia. In colon carcinoma, the loss of class I expression was seen in 4 out of 32 cases, and class II expression was found to be heterogeneous in 16 of these 32 cases (DR greater than DP greater than DQ). No relationship was noted between class II expression and degree of differentiation. However a correlation was seen between HLA-DR antigen expression and degree of invasiveness, mononuclear infiltrate and prognosis, according to Jass's criteria.

Adenocarcinoma↗
PubMed1986

Characterization of monoclonal antibodies directed against HLA class II molecules.

Four MAbs recognizing HLA class II antigens were produced by immunization with human leukemic cells, and were characterized through immunoprecipitation and cell distribution studies. They were tested against a panel of normal and leukemic cells, Epstein-Barr virus (EBV)-transformed homozygous typing cells (HTC)s, deletion mutant cell lines, and 11 other cell lines. The immunochemical studies revealed the presence of two bands of 34 and 28 kD, corresponding to the alpha- and beta-subunits of HLA class II antigens, respectively. The cell distribution studies led to the conclusion that GRB1, GRB2, and GRB3 MAbs recognize the HLA-DR monomorphic antigens, and that the GRB4 MAb seems to recognize basically the DR molecules but shows also a cross-reaction to DP molecules.

Antibodies, Monoclonal↗
PubMed1985

A monoclonal antibody GR2110 reactive with a P24 antigen present in a subgroup of acute lymphoid leukemias.

A monoclonal antibody IgG1K against a P24 antigen has been obtained. This antigen is present on a subgroup of non-T-ALL and platelets. GR2110 monoclonal antibody was produced by immunizing with a CALL (CALLA+, Ia+, IgS-, E-, T3-) This P24 antigen is absent in normal T-lymphocytes, monocytes, mitogen-activated T-cells; weakly expressed on B-cells and granulocytes and negative with several cell lines, except with KM3. GR2110 monoclonal antibody was tested with chronic and acute human leukemias. It was positive only with some CALL, NULL ALL, B-ALL and negative with B-CLL, T-CLL, T-cell lymphoma, Hairy cell leukemia, AML, T-ALL. The immunoprecipitation of 125I-labeled cell membrane with the monoclonal antibody and SDS-PAGE analysis revealed a 24 kD molecular weight polypeptide. The comparison of GR2110 and FMC 8 in capping experiments and cellular reaction patterns, showed that both antibodies react with the same molecule but probably with different epitopes.

Antibodies, Monoclonal↗
PubMedDate not supplied

Heterogeneity of the expression of class I and II HLA antigens in human breast carcinoma.

HLA class I and II antigen expression was studied in 19 cases of primary infiltrating ductal carcinoma of the breast. An indirect immunofluorescence technique was used on cryostat sections with monoclonal antibodies directed against HLA class I and II monomorphic determinants. Of the 19 cases studied, 17 were positive for class I antigen expression and two were negative. Class I HLA antigen expression was found to be clearly heterogeneous: in ten of these tumours more than 75% of the cells were class I positive; in two the percentage was decreased to between 50% and 75%; in five tumours it was less than 50%. With respect to class II HLA antigen expression, eight breast tumours were totally negative while two were strongly positive (50-75%) and the nine remaining cases were less than 25% positive. In addition, radioassay techniques were employed to determine the presence of oestrogen and progestagen receptors. The distribution of these receptors was not correlated with HLA class I or II antigen expression, nor could any relationship be demonstrated between the degree of histological differentiation of the tumours and their invasiveness.

Breast Neoplasms↗
PubMedDate not supplied

MHC class I and II antigens on gastric carcinomas and autologous mucosa.

The expression of HLA class I and II antigens was analysed in 30 primary gastric carcinomas, 27 autologous lymph node metastases and 25 autologous gastric mucosae. We used an immune alkaline phosphatase technique on cryostatic sections and mAbs directed against HLA class I monomorphic determinants, HLA-B locus-specific products and HLA-DR, -DP and -DQ molecules. In addition HLA class I genes were analysed in tumour tissue and compared by Southern blots with the RFLP from autologous mucosa using locus-specific HLA probes. Finally the infiltrating mononuclear cells were studied on gastric tumours and adjacent mucosa with mAbs defining CD4, CD8 and CD11b differentiation antigens. The results obtained showed that three out of 27 primary gastric carcinomas completely lack HLA-ABC antigens (10%). In addition, two primary tumours presented a variable expression. The remaining 22 tumours presented a homogeneous positive HLA class I expression. Interestingly, when the autologous mucosa was analysed, only 12 out 25 specimens were homogeneously stained with mAbs against HLA class I antigens, suggesting that this tissue may lack the expression of HLA antigens before becoming malignant. Indeed, the majority of the gastric carcinomas studied presented a higher HLA-ABC antigenic expression than autologous mucosa. Finally, the HLA expression observed in the primary tumour was similar to that observed in autologous metastases. As a second part of the study we have found a direct relationship between the expression of HLA-DR antigens in mucosa and the intensity of inflammatory infiltration. This relationship was not maintained in the tumour tissue. In the mucosa the CD4-positive T cell was the predominant lymphocyte, while it was CD8 in the HLA-DR-positive tumours. Finally the RFLP of class I genes did not show any differences in any of the cases when compared with autologous mucosa. We included in these studies DNAs from HLA class I-negative tumours, HLA positive and HLA-B-negative ones.

Antibodies, Monoclonal↗
PubMedDate not supplied

The biological consequences of altered MHC class I expression in tumours.

The identification of different mechanisms by which tumours escape from the immune system has helped to evaluate the clinical relevance of a variety of phenotypic changes that occur during tumour development. Among them, changes in HLA class I expression play a leading role in the tumour-host environment since HLA class I molecules interact with T lymphocytes for antigen presentation and with NK cells for inhibition/activation of these immune effector cells. Our laboratory has proposed a classification of the altered HLA class I phenotypes frequently found in human tumours, into five major groups. This review focuses on the tumour phenotypes found in primary and metastatic lesions, the molecular mechanisms that give rise to each phenotype and the clinical implications of these findings.

Alleles↗