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M Chiriva-Internati

Publications and source records attributed to M Chiriva-Internati.

28 records · Page 2Linked to original sources
PubMed1998

Effects of retinoic acid combined with interferon-gamma on the expression of major-histocompatibility-complex molecules and intercellular adhesion molecule-1 in human cervical cancer.

Retinoids and interferons are important regulators of human epithelial cell differentiation and have been successfully used in the clinical treatment of HPV-involved cervical cancer. In this study, 2 HPV-positive human cervical-carcinoma cell lines were analyzed for their surface expression of MHC-Class-I, MHC-Class-II and ICAM-1 surface antigens before and after exposure to all-trans retinoic acid, interferon-gamma and the combination of the 2 compounds. In addition, the effects on HLA-Class-I-mRNA expression were evaluated after such treatments. Both cell lines expressed MHC-Class-I molecules, and their levels were markedly up-regulated after exposure to IFN-gamma. Similarly, MHC-Class-II and ICAM-1 antigens were either induced or significantly up-regulated by IFN-gamma. Exposure to all-trans retinoic acid was also able to significantly increase the expression of MHC-Class-I and ICAM-I antigens as compared with untreated tumor cells. However, unlike IFN-gamma, retinoids were not able to induce the expression of HLA-Class-II surface antigens. Exposure to the combination of IFN-gamma plus retinoic acid significantly up-regulated (in an additive manner) HLA-Class-I and ICAM-1 molecules as compared with the levels obtainable after exposure to IFN-gamma alone. Finally, Northern-blot analysis of HLA-Class-I-mRNA expression confirmed that the activity of both of these biologic response modifiers was at transcriptional level. These data indicate that the combination of these modalities could induce an additive effect on the expression of immunologically important surface antigens on human cervical-cancer cells. These findings, together with the known anti-proliferative effects mediated by retinoids and IFN-gamma on tumor cells, further support the combination of these agents in the treatment of pre-invasive and invasive human cervical cancer.

Blotting, Northern↗
PubMed1998

Effects of retinoic acid combined with irradiation on the expression of major histocompatibility complex molecules and adhesion/costimulation molecules ICAM-1 in human cervical cancer.

OBJECTIVES: Radiation treatment is one of the most standardized and effective modalities for contemporary cervical cancer therapy. In addition, the radiation-potentiating effects of retinoic acid have been recently described. In order to investigate whether enhanced immunogenicity might be responsible for such potentiation, we have evaluated the effects of retinoic acid combined with high doses of gamma-irradiation on the expression of major histocompatibility complex (MHC) Class I and II and intercellular adhesion molecule-1 (ICAM-1) in human cervical carcinoma cell lines. METHODS: The expression of surface antigens (MHC Class I and II and ICAM-1) was evaluated by FACS analysis in untreated control cells and in cells following their exposure to retinoic acid, high doses of gamma-irradiation (i.e., 5000 and 10,000 cGy), or the combination of the two procedures. RESULTS: HT-3 and SiHa cervical cancer cells expressed variable levels of MHC Class I and ICAM-1 antigens while Class II surface antigens were not detectable. Exposure to either 5000 or 10,000 cGy completely inhibited cell replication in both cell lines and significantly and consistently increased the expression of all surface antigens present on the cells prior to irradiation. Irradiation was unable to induce neoexpression of antigens previously not expressed by these cells (i.e., MHC Class II). In a similar fashion, retinoic acid was also able to significantly increase the expression of MHC Class I and ICAM-1 antigens when compared to untreated tumor cells but was not able to induce the expression of HLA Class II surface antigens. Exposure to the combination of radiation plus retinoic acid significantly upregulated HLA Class I and ICAM-1 molecules in an additive manner when compared to the levels obtainable with the exposure to radiation or retinoic acid alone. CONCLUSIONS: These data indicate that the combination of these two treatments could induce an additive effect on the expression of immunologically important surface antigens in human cervical cancer cells. These findings, together with the powerful antiproliferative effect of retinoids and irradiation on tumor cells, suggest that the combined regimen may be a promising and more effective combination for the treatment of cervical cancer.

Antineoplastic Agents↗
PubMed1998

Retinoic acid up-regulates the expression of major histocompatibility complex molecules and adhesion/costimulation molecules (specifically, intercellular adhesion molecule ICAM-1) in human cervical cancer.

OBJECTIVE: Retinoids are a class of compounds that are structurally related to vitamin A and have been found to be effective in the prevention and treatment of cervical cancer. To investigate whether enhanced immunogenicity might be responsible for such efficacy, we evaluated the effects of retinoic acid on the expression of major histocompatibility complex class I and class II and intercellular adhesion molecule ICAM-1 in human cervical carcinoma cell lines. STUDY DESIGN: The expression of surface antigens (major histocompatibility complex class I and class II and ICAM-1) was evaluated by fluorescence-activated cell sorter analysis in 3 human cervical carcinoma cell lines after exposure to therapeutic doses of retinoic acid. In addition, the effects on human leukocyte antigen class I messenger ribonucleic acid expression were also evaluated by Northern blot analysis after such treatment. RESULTS: CaSki, SiHa, and HT-3 cervical cancer cells expressed variable levels of major histocompatibility complex class I and ICAM-1 antigens, whereas class II surface antigens were not detectable. Exposure to therapeutic doses of retinoic acid were able to significantly increase the expression of major histocompatibility complex class I and ICAM-1 antigens in all the cell lines when compared with untreated tumor cells but were not able to induce the expression of class II surface human leukocyte antigens. Northern blot analysis showed that for major histocompatibility complex class I molecules such up-regulation was the result of an increased expression at the transcriptional level of major histocompatibility complex class I messenger ribonucleic acid. CONCLUSIONS: These data indicate that retinoic acid increases the expression of immunologically important surface antigens, suggesting that the efficacy of retinoic acid in the treatment of cervical cancer may be, at least in part, the result of immunologic modulation. Such findings support additional clinical research investigating the use of retinoids for the treatment of cervical cancer.

Blotting, Northern↗
PubMed1998

The effects of irradiation on the expression of a tumour rejection antigen (heat shock protein gp96) in human cervical cancer.

PURPOSE: Studies were designed to analyse the effects of high doses of gamma-irradiation on the expression of a tumour rejection antigen (heat shock protein gp96) in human cervical carcinoma cell lines. MATERIALS AND METHODS: The expression of heat shock protein gp96 was evaluated at the transcriptional (Northern blot) and post-transcriptional levels (Western blot) in two human cervical carcinoma cell lines following exposure to high doses of gamma-irradiation. RESULTS: Doses of gamma-irradiation ranging from 25 to 100 Gy significantly and consistently increased the expression of heat shock protein gp96 on CaSki and HT-3 cervical cancer cells. The increase in the amount of protein was due to transcriptional up-regulation of this gene. Radiation doses unable to inhibit completely cell replication in the totality of tumour cells (i.e. 25 Gy), as well as higher (fully lethal) doses of irradiation (i.e. 50 to 100 Gy), were shown to up-regulate significantly the expression of heat shock protein gp96 mRNA in a dose-dependent manner. CONCLUSIONS: Recently, gp96 molecules have been implicated in the presentation of endogenous and viral antigens. A number of key elements in this pathway, including major histocompatibility complex (MHC) class I molecules as well as adhesion/co-stimulation molecules such as ICAM-1, are known to be sensitive to irradiation effects. The results show that radiation can also increase the expression of other immunologically important cell molecules such as a tumour rejection antigen (heat shock protein gp96) in human cervical cancer. Such findings may partially explain the increased immunogenicity of tumour cells following irradiation and further support a role for local radiation therapy as a powerful biologic response modifier.

Antigens, Neoplasm↗
PubMed1998

Effects of retinoic acid on the expression of a tumor rejection antigen (heat shock protein gp96) in human cervical cancer.

Retinoids are a class of compounds structurally related to vitamin A which have been found to be active agents experimentally as well as clinically in the prevention and treatment of cervical cancer. Recent data have suggested that in addition to their key regulatory role during epithelial cell differentiation, they could also contribute to enhanced cellular and humoral immunity against tumor cells. Hsp gp96 molecules have recently been implicated in the presentation of tumor and viral antigens. A number of key elements in this pathway, including major histocompatibility complex (MHC) class I molecules as well as adhesion/co-stimulation molecules such as ICAM-1 have reported to be sensitive to retinoic acid up-regulation. In this study we analyzed at the transcriptional (Northern blot) and post-transcriptional levels (Western blot) the effects of retinoic acid on the expression of the tumor rejection antigen (heat shock protein gp96) in three human cervical carcinoma cell lines. Exposure of therapeutic doses of retinoic acid (i.e. 1 microM) significantly and consistently increased the expression of heat shock protein gp96 (Western blot analysis) on CaSki, SiHa and HT-3 cervical cancer cell lines. Northern blot analysis demonstrated that the increase in the amount of protein was due to the transcriptional upregulation of this gene. Taken together, our results show that retinoic acid can significantly increase the expression of yet another immunologically important cell molecule, the tumor rejection antigen heat shock protein gp96 in human cervical cancer. Such findings provide new information on the effects of retinoic acid on tumor cells and further support the role of retinoic acid as a powerful biologic response modifier.

Antigens, Neoplasm↗
PubMed1997

Effects of irradiation on the expression of major histocompatibility complex class I antigen and adhesion costimulation molecules ICAM-1 in human cervical cancer.

PURPOSE: We initiated studies to analyze the effects of high doses of gamma irradiation on the surface antigen expression of MHC Class I, Class II, and ICAM-1 on human cervical carcinoma cell lines. METHODS AND MATERIALS: The expression of surface antigens (MHC Class I, Class II, and ICAM-1) was evaluated by FACS analysis on two cervical cell lines at different time points, following their exposure to high doses of gamma irradiation (i.e., 25.00, 50.00, and 100.00 Gy). RESULTS: The CaSki and SiHa cervical cancer cells we analyzed in this study expressed variable levels of MHC Class I and ICAM-1 antigens, while Class II surface antigens were not detectable. Whereas irradiation doses of 25.00 Gy were not sufficient to totally block cell replication in both cell lines, exposure to 50.00 or 100.00 Gy was able to completely inhibit cell replication. Range doses from 25.00 to 100.00 Gy significantly and consistently increased the expression of all surface antigens present on the cells prior to irradiation but were unable to induce neoexpression of antigens previously not expressed by these cells (i.e., MHC Class II). Importantly, such upregulation was shown to be dose dependent, with higher radiation doses associated with increased antigen expression. Moreover, when the kinetic of this upregulation was studied after 2 and 6 days after irradiation, it was shown to be persistent and lasted until all the cells died. CONCLUSIONS: These findings may partially explain the increased immunogenicity of tumor cells following irradiation and may suggest enhanced immune recognition in tumor tissue in patients receiving radiation therapy.

Antigens, Neoplasm↗
PubMedDate not supplied

Mast cell density, hepatic stellate cell activation and TGF-beta1 transcripts in the aging Sprague-Dawley rat during early acute liver injury.

Mast cells (MCs) have been indicated as a source of various inflammatory cytokines, chemokines and growth factors. This study evaluates liver tissue MC density as a quantitative marker of acute liver inflammation in 2- and 19-month old rats treated with carbon tetrachloride (CCl4) toassess the relationships between MC density, hepatocellular damage, mRNA encoding TGF-beta1, hepatic stellate cell (HSC) activation and collagen levels. Consecutive histological sections from each age group were stained with toluidine blue to identify granulated MCs, Direct Red 80 to recognize collagen matrix, and by immunohistochemistry to identify activated hepatic stellate cells (HSCs), which were subsequently counted by means of a computer-aided image analysis. Histology showed hepatocellular necrosis with inflammatory cell infiltration and collagen matrix deposition. Two and 24 hours after intoxication, MC density had considerably increased in the younger rats, but less in those aged 19 months. Although the untreated older rats had a larger area occupied by activated HSCs than the untreated younger rats, the increase in the number of HSCs was greater in the younger rats both two and 24 hours after intoxication. The greater MC density in younger rats suggests that older rats have a reduced immune response or recruit fewer MCs. The activated HSCs and TGF-beta1 transcripts did not increase significantly during the study period, thus indicating that these are later events in chemically induced hepatic toxicity. In conclusion. MC density may be an index of acute liver inflammation after CCl4 intoxication.

Aging↗
PubMedDate not supplied

Human papillomavirus DNA is present in a subset of unselected breast cancers.

OBJECTIVE: The major molecular events in the genesis of most breast cancers are unknown. However, human papillomaviruses (HPV) have been reported to be found in a significant portion of breast cancers of women with concomitant cervical intraepithelial neoplasia III. To investigate a potential HPV-breast cancer link, we carried out a small survey to identify HPV in unselected, general breast cancer tissues. STUDY DESIGN/METHODS: Deoxyribonucleic acid (DNA) was isolated from 17 breast cancer tissues (and one cervical swab) taken from our local, randomly selected patient population. Two different previously characterized broad-spectrum primer sets (targeting the E6/E7 or L1 regions) were used to amplify HPV DNA, and another primer set was used to amplify the ColE1/pBR322 origin of replication by polymerase chain reaction amplification. The polymerase chain reaction product DNA was analyzed by dot blot hybridization with HPV-16, -18, -31, or pRB322 DNA probes. Total cellular DNA was also analyzed by one- and two-dimensional Southern blot analysis. Finally, the E6/E7 polymerase chain reaction products were cloned, sequenced, and compared to previously cloned HPV types. RESULTS: Polymerase chain reaction/dot blot analysis by both the HPV E6-E7 and L1 primer sets identified the same 6 out of 17 (35%) breast cancers as being HPV positive. ColE1/pBR322 origin targeted polymerase chain reaction/dot blot analysis failed to identify plasmid contamination. One- and two-dimensional Southern blot analysis showed that the breast cancers specimens contained significant levels of HPV DNA and that the viral DNA was largely episomal. The sequences of the HPV clones demonstrated that HPV-16, -18, and possibly type 11 were present within the breast cancer specimens. Furthermore, the HPV sequences cloned from the cervical swab and breast cancer of the same patient were found to be identical. CONCLUSIONS: These data suggest that HPV may be associated with a significant subset of breast cancers, and further suggest that additional studies are warranted.

Breast Neoplasms↗