Biomedical subjects

M R Oliva

Publications and source records attributed to M R Oliva.

26 records · Page 2Linked to original sources

PubMed1991

Altered HLA class I expression in non-small cell lung cancer is independent of c-myc activation.

We studied the expression of major histocompatibility complex class I antigens in 59 bronchogenic carcinomas, as well as in pneumocytes and epithelial respiratory cells distant from the tumor. We observed in all cases that normal lung tissue expressed major histocompatibility complex class I antigens, while this expression was completely lost in 16 tumors (27%). The defect in HLA gene expression affected both heavy chain and beta 2-microglobulin, as demonstrated by the null reactivity with the monoclonal antibodies GRH1, W6/32, and HC10. Selective underexpression was detected in 1 tumor for HLA-A locus antigens and in 3 tumors for HLA-B locus antigens. Southern blot analyses of major histocompatibility complex class I genes were performed in 20 tumor tissue specimens and 6 cell lines. No class I gene rearrangements were detected using HLA coding and locus specific noncoding probes. We also used the Southern blot method to investigate the possible relationship between c-myc amplification and HLA class I antigens in non-small cell lung cancers and detected no apparent amplification in 20 tumor tissue specimens (5 negative for HLA class I antigens) and 6 cell lines (3 with decreased expression). Northern blot analysis revealed no relationship between c-myc mRNA levels and specific mRNA for HLA-A and HLA-B antigens in cell lines with imbalanced HLA-A or HLA-B expression.

Carcinoma, Bronchogenic↗

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↗

PubMed1989

HLA class I gene expression on human primary tumours and autologous metastases: demonstration of selective losses of HLA antigens on colorectal, gastric and laryngeal carcinomas.

The expression of HLA class I antigens was studied in 99 primary tumour (colorectal, gastric and laryngeal carcinomas) and 57 autologous metastases using immunohistological techniques and monoclonal antibodies against class I monomorphic determinants, HLA-B isotypic determinants and HLA polymorphic determinants. Fourteen per cent of colorectal, 9.6% of gastric and 20% of laryngeal carcinomas completely lacked class I molecules. Selective losses of HLA-B antigens were also detected in 8.8, 3.4 and 5.8% of these tumours respectively. Taking into account complete and selective loss of HLA-B the average alteration in the class I molecules expression totalled 21%. The comparison of class I expression between primary tumours and autologous metastases showed differences in 24% of the patients. These differences consisted mainly in a decrease of class I expression by metastases. Nevertheless, four types of divergence were detected in laryngeal carcinomas, namely: +/-, +/+, -/+, -/-. In addition, a clear correlation between degree of differentiation and class I expression was observed in laryngeal tumours. Finally, when class I gene RFLPs were compared with DNA from 15 tumours and autologous normal mucosa or peripheral lymphocytes, no differences were detected between these samples.

Blotting, Southern↗

PubMed1988

Phenotypic and genetic analysis of HLA class I and HLA-DR antigen expression on human melanomas.

Class I and HLA-DR antigen expression were studied with histochemical techniques involving monomorphic monoclonal antibodies in 49 cases of human malignant melanomas, 20 primary and 29 metastatic. A large percentage (90%) of primary melanomas were positive for HLA class I, while those primary lesions showing lowest levels of class I antigen expression were at the upper end of the range of invasiveness and possessed a higher metastatic potential. Expression of HLA-DR molecules on primary melanomas was low (25% of all cases) and HLA-DR-positive melanomas were among the most aggressive. In metastatic melanomas, HLA class I expression was less common than in primary lesions. The lowest percentage of cases positive for HLA class I was found for cutaneous metastases. HLA-DR molecules were more frequently expressed by lymph node metastases than on primary melanomas. The comparison of the expression of HLA class I and HLA-DR molecules by primary melanomas and their autologous metastases revealed a high degree of heterogeneity. Class I genes were further studied by Southern blot assays. No differences were found in restriction fragments for class I genes among 4 melanomas and their autologous lymphocytes, 2 of which were positive and 2 negative for class I expression.

Blotting, Southern↗

PubMedDate not supplied

Phenotypic expression of histocompatibility antigens in human primary tumours and metastases.

HLA class I and II expression was studied on 244 (177 primary and 67 metastatic) solid human tumours of different origin. Alkaline immunophosphatase (APAAP) and immunoperoxidase were used on cryostatic sections to stain MHC antigens. Monomorphic MoAbs were used against class I heavy chain, beta 2-microglobulin, DR, DQ and DP molecules. Class I expression was homogeneous on colon, melanoma and epidermoidal primitive tumours. Loss of HLA class I antigens was more frequent on basal cell carcinomas and sarcomas and was related to tumour differentiation on larynx carcinoma. Class I expression was heterogeneous on breast, larynx and stomach primitive neoplasias. Class I negative tumours were more frequent on metastatic than on primitive melanomas. Divergence of class I between primary tumours and autologous metastases was observed on melanomas, larynx and colorectal carcinomas. Class II expression was heterogeneous on all tumours and in a large number of cases was associated with high intensity of leukocytic infiltrate. HLA-DR expression was higher than HLA-DP and HLA-DQ (DR greater than DP greater than DQ) and was related to tumour progression. Four human tumour cell lines were modulated with recombinant interferon-gamma for HLA class I and II antigens. Different HLA profiles were obtained: increased class I and II expression, increased class II or a low response. Finally, class I genes from 22 tumours were compared with autologous normal cells by Southern blot analysis: 12 tumours were class I positive and 10 negative. No clear differences in RFLP were observed that could be associated with class I rearrangement. The results are discussed in relation to the role that histocompatibility antigens may play in tumour progression and invasiveness.

Genes, MHC Class I↗

PubMedDate not supplied

Glomerulocystic kidney disease: MRI findings.

Glomerulocystic kidney disease (GCKD) is a rare form of renal cystic disease characterized by cystic dilation of Bowman's capsule. The imaging findings of small renal cysts with a predominant cortical and subcapsular distribution allows for distinction from other, more common, polycystic kidney diseases. The appearance and distribution of the renal cysts by magnetic resonance imaging allow for a definitive diagnosis of GCKD.

Aged↗

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↗