Biomedical subjects

I Arany

Publications and source records attributed to I Arany.

At least 73 records · Page 4Linked to original sources

PubMed1980

Effect of carcinogenic and non-carcinogenic chemicals on the activities of four glycolytic enzymes in mouse lung.

The activities of four glycolytic enzymes were measured in the lung homogenate of CFLP mice treated with a variety of carcinogens and non-carcinogens for mouse lung. The carcinogenic urethane, dimethylnitrosamine (DMNA), 3-methylcholanthrene (MCA), benzo[a]pyrene (BP), 7,12-dimethylbenz[a]anthracene (DMBA) and aflatoxin B1 enhanced the activity of hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK) and lactate dehydrogenase (LDH) 28 days after a single intraperitoneal administration. These carcinogens also altered the ratio of LDH H and M subunits. In contrast, under the same conditions the non-carcinogenic phenylurethane, ethylformate, chrysene, perylene and pyrene, as well as the pulmonarily toxic Paraquat, butylated hydroxytoluene (BHT) and cadmium chloride (CdCl2), did not influence either the activities of the enzymes tested or the isozyme pattern of LDH.

Animals↗

PubMed1979

Activities of four glycolytic enzymes (HK, PFK, PK, and LDH) and isozymic pattern of LDH in mouse lung tumor induced by urethan.

In the lungs of CFLP mice the activities of glycolytic key enzymes (HK, PFK, PK) and LDH as well as LDH isozymic pattern change in the course of life. The activities of these glycolytic enzymes in the lung tumors induced by urethan in CFLP mice are significantly higher than those in the normal adult lung and they are similar to those in the normal fetal lung. The isozymic pattern of LDH of pulmonary adenomas resembles that of the normal fetal lung, too.

Age Factors↗

PubMedDate not supplied

Activity of pyruvate kinase and lactic acid dehydrogenase in mouse lung after transplacental exposure to carcinogenic and non-carcinogenic chemicals.

The carcinogenic urethane (URTH), dimethylnitrosamine (DMN), 3-methylcholanthrene (MCA), benzo[a]pyrene (BP), 7,12-dimethylbenz[a]anthracene (DMBA) and aflatoxin B1 (B1) administered to pregnant CFLP mice increased the activity of pyruvate kinase (PK) and lactate dehydrogenase (LDH) and decreased the ratio of LDH H and M subunits in the lungs of offsprings. However, under the same conditions, the non-carcinogenic phenylurethane (PHUR), ethylformate (EF), chrysene (CHRY), perylene (PER) and pyrene (PYR), as well as the toxic Paraquat (PAR), butylated hydroxytoluene (BHT) and cadmium chloride (CdCl2), did not influence the activities of the enzymes tested.

9,10-Dimethyl-1,2-benzanthracene↗

PubMedDate not supplied

Status of local cellular immunity in interferon-responsive and -nonresponsive human papillomavirus-associated lesions.

BACKGROUND AND OBJECTIVES: Anogenital warts are caused by human papillomaviruses (HPVs), which should induce cellular immune responses in immunocompetent patients. However, the natural history of these warts shows considerable variation between persons, ranging from spontaneous regression to prolonged persistence. In addition, the efficiency of immunologically based modalities for the therapy of anogenital warts, such as interferon (IFN) treatment, is highly variable. METHODS: Considering that preexisting conditions of the host are important factors in an appropriate immune response, the authors determined the pretreatment status of local cell-mediated immune response to HPV infection by reverse transcription-polymerase chain reaction in patients with condyloma acuminatum, who later received IFN treatment and responded well or poorly to that therapy. RESULTS AND CONCLUSIONS: The authors found that biopsies from nonresponders were depleted markedly in Langerhans cells, leading to decreases in major histocompatibility complex class II expression and, therefore, to diminished attraction of CD4+ T cells. An inappropriate major histocompatibility complex class I expression also was observed in those nonresponders with decreased CD8+ levels. The mRNA levels of cytokines (interleukin-1a, interleukin-1b, granulocyte-macrophage-colony stimulating factor, tumor necrosis factor that participate in immune responses were low in nonresponders. In contrast, responders demonstrated high macrophage-natural killer cell (CD16-positive) and activated CD4 (IL-2, interferon gamma-positive, TH1 cells) T-cell recruitment against HPV-infected keratinocytes, which is consistent with a delayed-type hypersensitivity-like cellular immune response. Lack of immune response in nonresponders appeared to correlate with high expression levels of the HPV E7 gene. These differences in local cellular immunity might determine the response rate of HPV-infected cells to immunomodulatory therapies.

Antigen-Presenting Cells↗

PubMedDate not supplied

Human papillomavirus infections: epidemiology, pathogenesis, and therapy.

BACKGROUND: Human papillomaviruses (HPV) are common human pathogens and are classified into more than 80 different types. These viruses produce benign warts in many cases and aggressive squamous cell carcinomas in other cases. OBJECTIVE: The goal of this review is to update the reader on the epidemiology, pathogenesis, and therapy of HPV infections. Nonanogenital warts are transmitted by skin-to-skin contact while anogenital warts are usually transmitted sexually. Both types of warts produce much morbidity but rarely undergo malignant transformation. They are commonly treated with surgical or cytodestructive therapy, but immunomodulatory agents, such as imiquimod, have been proven to be very effective in anogenital warts and are being evaluated in nonanogenital warts. Other types of HPV have marked oncogenic potential such that over 99% of all cervical cancers and over 50% of other anogenital cancers are due to infection with oncogenic HPV. Many cofactors, such as cigarette smoking, genetics, and helper viruses, have potential roles in HPV oncogenesis, but their relative contributions are poorly understood. Other control measures for warts and HPV-associated cancers are under study, but the greatest future potential may be from the development of prophylactic and therapeutic vaccines. CONCLUSIONS: Infection with HPV is very prevalent as are the clinical manifestations of this family of pathogens. Improved therapies for warts (e.g., imiquimod) have recently become available. Vaccines for HPV offer hope for future interventions for warts as well as for prevention of anogenital malignancies.

Humans↗

PubMedDate not supplied

Local inflammation may influence oral tumor cell differentiation.

The mRNA levels of keratin K13, involucrin, protein kinase C alpha and epsilon, and interferon-gamma and its receptors were examined in biopsies from human oral squamous cell carcinomas. Expression of all the genes was elevated in the histologically more differentiated tumors, but it was at or below normal (perilesional control) levels in the poorly differentiated ones. For the same set of biopsies, we had previously shown that the well differentiated tumors expressed higher levels of T cell markers. As interferon-gamma stimulates differentiation, its secretion by inflammatory cells at the tumor site may influence the differentiation status of the tumor.

Cell Differentiation↗

PubMedDate not supplied

Differentiation-dependent expression of growth regulatory cytokines and their receptors in squamous cell carcinomas of the head and neck.

Cytokines, such as IFN-alpha and TNF-alpha are capable of affecting keratinocyte proliferation in the microenvironment of the tumor. Their elevated expression along with high levels of their receptor mRNAs was determined by a semiquantitative reverse transcription- polymerase chain reaction (RT-PCR) method in biopsies of head and neck squamous cell carcinomas that were established as histologically well or moderately differentiated. In contrast, tumors with poor differentiation exhibited low levels of these growth suppressive factors, although levels of their receptors were elevated. In fact, expression of these growth suppressive cytokines highly correlated with the histological status of tumors suggesting a role of these agents in growth regulation of those tumors. Apparently, growth signaling in these tumors differs in the availability of either the ligand or the receptor.

Antigens, CD↗

PubMedDate not supplied

Correlation between mRNA levels of IL-6 and TNF alpha and progression rate in anal squamous epithelial lesions from HIV-positive men.

BACKGROUND: The incidence of anal high-grade intraepithelial lesions (HSILs) and progression of anal low-grade intraepithelial lesions (LSILs) to HSIL are high in HIV-positive men. Endogenous cytokines might support the pathogenesis of this progression. MATERIALS AND METHODS: Accordingly, we determined mRNA levels of IL-6 and TNF alpha and their receptors together with viral genes (HIV-gag and HPV E7) in biopsies of anal condylomas, LSILs and HSILs from HIV-positive individuals by a semiquantitative RT-PCR method. RESULTS: We found that HSIL significantly differs in expression of these genes from LSIL and condylomas, and the latter two lesions were virtually undistinguishable from each other. A correlation between cytokine levels and HIV as well as HPV E7 transcripts suggests that changes might be associated with each other. CONCLUSIONS: These findings reveal important molecular events associated with progression of anal intraepithelial lesions (ASILs) in HIV-infected men.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

Early effects of different cytostatic protocols for head and neck cancer on oncogene activation in animal experiments.

In vivo investigations on oncogenes and onco-suppressor genes may provide new findings on the potential carcinogenic effects of various cytostatic protocols inducing secondary tumours of the head and neck. Further surgeries are often necessary due to regional recurrence after the Cisplatin-supplemented BVM (Bleomycin, Vincristine, Methotrexate) protocol in the treatment of human head and neck tumours. Our earlier studies have illustrated the carcinogenic and mutagenic potential of Cisplatin. The effect of Cisplatin on the alteration of different onco- and suppressor genes has also been proven. Our present study aimed at investigating the early effects of the BVM and the CFu (Cisplatin, 5-Fluorouracil) protocols on early oncogene and tumour suppressor gene expressions in mice. Body weight equivalent amounts of cytostatics were administered intraperitoneally to 6- to 8-week-old, inbred, female CBA/Ca mice. Twenty-four, 48 and 72 hours after the treatment, RNA was isolated from the target organs and the quantitative expression of c-myc, Ha-ras and p53 genes were examined. The protocols caused detectable changes. A "short-term" in vivo test, the 24-hour examination of gene expression, is suitable for detecting early effects of carcinogen exposure. The alterations of gene expression, caused by the Cisplatin-containing protocol, draw attention to the probable role of Cisplatin in the development of regional recurrence and to the possibility of prevention.

Animals↗

PubMedDate not supplied

Early effects of transplatin on oncogene activation in vivo.

The aim of the study was to investigate the early effect of Transplatin (the stereo-isomer of Cisplatin) on oncogenes in inbred CBA/Ca mice. Cisplatin is commonly used for the treatment of squamous cell carcinomas of the head and neck. Cisplatin has a strong oncogene activation effect compared to the structural analogue Transplatin. Body weight equivalent amounts of a human dose of Transplatin were administered intra-peritoneally to 6- to 8-week-old, inbred, female CBA/Ca mice. Twenty-four, 48 and 72 hours after the treatment, RNA was isolated from the target organs and the expressions of c-myc, Ha-ras and p53 genes were examined. Investigation of early changes showed no significant overexpression compared to Cisplatin, which had a significant effect on oncogene expression in the "short-term" in vivo test system.

Animals↗

PubMedDate not supplied

Interferon resistance is independent from copy numbers in benign HPV-induced lesions.

Interferons (IFNs) are successfully used in treatment of different human papillomavirus (HPV)-related diseases, such as condyloma acuminatum. Unresponsiveness can be seen in a number of patients which is related to a differential expression of early (E7) and late (L1) viral genes, according to our preliminary studies rather than to impaired IFN-signalling. The molecular basis for this differential expression might imply differential viral replication (copy numbers) in responder vs. nonresponder patients. PCR analysis revealed that the two groups did not differ significantly in HPV copy numbers before treatment. In contrast E7 and L1 levels significantly differed in responders versus nonresponders, regardless of copy numbers. Also, the IFN-mediated antiproliferative effect was mostly influenced by other factors rather than just the copy number. Our data imply that the unresponsiveness of certain patients to IFN treatment may relate to differential viral gene transcription rather than different copy numbers of infecting HIVs.

Biopsy↗

PubMedDate not supplied

Interferon response depends on viral transcription in human papillomavirus-containing lesions.

Human papillomaviruses (HPVs) express various proteins which have been proven to interact with some cellular functions playing a role in cell cycle progression and differentiation. Therefore, these viral gene products might be candidates for interfering with IFN-mediated antiproliferative actions. Condyloma biopsies from patients subsequently demonstrated to be responsive or non-responsive to IFN treatment were investigated. mRNA levels of HPV genes and IFN-responsive genes were determined by RT-PCR and correlated with IFN responsiveness. Patients clinically nonresponsive to IFN demonstrated a characteristic HPV transcriptional activity differing from responder patients. Nonresponders expressed mostly early E7 mRNAs; responders demonstrated higher expression of the late L1 gene. This differential transcription of infecting HPV also correlated with the extent of IFN mediated antiproliferative effect. A hypothesis for further study is that HPV E7 may inhibit IFN responsiveness, while HPV L1 may promote IFN responsiveness.

Antiviral Agents↗

PubMedDate not supplied

Differentiation and IFN gamma regulate WAF1/CIP1 transcription in p53-independent and p53-dependent pathways in epithelial cells.

In normal epithelia differentiation and proliferation are regulated by factors involving p53 and related pathways. WAF1/CIP1 protein is believed to inhibit cell growth as a downstream mediator of p53 function. Also, WAF1/CIP1 is identified as a candidate gene linking differentiation signals to G1 arrest. Different epithelia with different keratinizing profiles respond differently to differentiation/proliferation signals, such as calcium or interferon gamma (IFNgamma). Other factors, such as p53 mutation or presence of human papillomaviruses (HPVs) also affect responses to those signals. Since WAF1/CIP1 can be regulated via a p53-dependent or an independent manner, our study aimed to determine: a.) differentiation-related expression of WAF1/CIP1 in keratinocytes, b.) involvement of WAF1/CIP1 in IFNgamma action, and c.) p53-dependence of WAF1/CIP1 transcription under these conditions. The results demonstrated that differentiation increases WAF1/CIP1 transcription in keratinizing but not in nonkeratinizing keratinocytes in a p53-independent manner. IFNgamma upregulated WAF1/CIP1 in keratinizing keratinocytes in a differentiation and p53 dependent manner. Inactivation of wild type p53 by mutation or by presence of HPVs uncouples IFNgamma-mediated WAF1/CIP1 transcription from p53 and from differentiation. Our data suggest a mechanism which operates via WAF1/CIP1 in keratinocytes and regulates epithelial differentiation/proliferation under different physiological conditions.

Cell Differentiation↗

PubMedDate not supplied

Response of cultured cells from the epidermis and the buccal mucosa to TGF-beta 1 and comparison to interferon-gamma.

Normal human cells from epidermis and from buccal mucosa were cultured to confluence in three media with graded differentiation potential (at low Ca2+, high Ca2+, and supplemented with serum) and treated with transforming growth factor beta 1 (TGF-beta 1), as had been done previously with interferon-gamma (IFN-gamma). The response of the cells to TGF-beta 1 was monitored in terms of the expression of regulatory genes associated with proliferation and differentiation (cdc2, c-myc, p53) and of genes for structural proteins expressed at varying stages of maturation (keratins K5 and K10, involucrin, flaggrin). For both tissues, the results obtained with both agents were very similar for those genes expressed in the basal cells (cdc2, c-myc, p53, K5), regardless of their function, but diverged for the other genes, which are expressed in the suprabasal cells. Another related contrast is that, although IFN-gamma induced apoptosis in epidermal keratinocytes cultured in the serum containing medium, TGF-beta 1 did not. Thus, the two agents appear to affect the earlier stages of cell differentiation in the same way but to differ at the later stages, particularly in that IFN-gamma pushes maturation further than does TGF-beta 1).

CDC2 Protein Kinase↗

PubMedDate not supplied

p53, WAF1/CIP1 and mdm2 expression in skin lesions associated with human papillomavirus and human immunodeficiency virus.

Human papillomaviruses (HPVs) express various gene products, such as E6 protein which complexes with the p53 tumor suppressor protein and therefore diminishes p53-related regulatory mechanisms. This interaction is assumed to be HPV type-specific as "high risk" or oncogenic HPV types have more affinity for p53 binding than their "low risk" or non-oncogenic counterparts. Furthermore, HIV infection is believed to activate latent HPV infection and transcription via direct and indirect interaction with HPVs as well as cellular genes and functions. Accordingly, we carried out experiments on biopsies which originated from condylomas ("low risk" HPVs), HIV-positive condylomas (infection with multiple "low risk" and "high risk" HPVs) and anogenital squamous cell carcinomas (SCCs, "high risk" HPV infection). Using reverse transcription PCR (RT-PCR) and western immunoblotting, mRNA and protein levels of p53 and genes regulated by p53, such as mdm2 and WAF1/CIP1 were determined. We found that the presence of HPV can diminish p53 and increase WAF1/CIP1 and mdm2 protein levels. There were no significant differences in this regulation between "low risk" and "high risk" lesions. Our data suggest that these HPV-mediated cellular effects are not type-specific, and they might be part of a viral-cell interaction or represent a cellular defense mechanism against the virus. However, HIV-seropositivity renders HPV lesions containing both "low risk" and "high risk" significantly different. This may be due to the alteration of HPV-controlling cellular pathways by HIV tat and/or activation of cellular pathways different from HIV-negative counterparts. Either possibility is of great interest and needs further verification.

Carcinoma, Squamous Cell↗

PubMedDate not supplied

Interferons alpha, beta and gamma induce different patterns of gene expression in cultured human epidermal keratinocytes.

Differences in the effects on confluent epidermal keratinocytes of treatment with interferons (IFNs) alpha, beta, and gamma were observed in their modulation of the mRNA levels of representative structural and functional cellular proteins. Comparisons of the responses in culture media with varying cellular maturation potential indicated the dependence of the modulation on the stage of differentiation. Differentiation was correlated with upregulation of all the genes by interferon gamma, but this effect was not seen with the other interferons. Even though IFNs alpha and beta share the same cell surface receptor, their effects on gene expression were clearly distinguishable and varied with the culture medium. These findings might have relevance in the treatment of skin lesions with varying degrees of differentiation.

CDC2 Protein Kinase↗

PubMedDate not supplied

Gene expression of zinc-alpha 2-glycoprotein in normal human epidermal and buccal epithelia.

Zinc-alpha 2-glycoprotein (Zn alpha 2gp) is almost ubiquitous in body fluids. We have found it to be also present in stratified epithelia. We compare its mRNA expression in cells from human epidermis and buccal mucosa cultured in media of graded differentiation potential (attained by varying calcium ion concentration and adding serum). The Zn alpha 2gp gene is upregulated in both epithelia with differentiation and further with exposure to interferon gamma or transforming growth factor beta 1. The upregulation by these agents increases with differentiation in epidermal cells, but peaks in the low-differentiation medium in buccal epithelia. We compared gene expression levels of Zn alpha 2gp with those of characteristic cytokeratins of stratified epithelia (k5 for basal cells, K10 for epidermal suprabasal cells, and K13 for mucosal suprabasal cells). This pattern correlation associates Zn alpha 2gp cell-type dependently with late differentiation, i.e. with keratin K10 in epidermis and with K13 in buccal epithelium.

Cells, Cultured↗

PubMedDate not supplied

Modulation by interferon-gamma of zinc-alpha 2-glycoprotein gene expression in human epithelial cell lines.

Zinc-alpha 2-glycoprotein has been detected in most body fluids, and its antibody labels the corresponding glandular epithelia. We have also detected it in human stratified epithelia (epidermis and buccal mucosa). In this study, the mRNA levels of zinc-alpha 2-glycoprotein were found to be about twice as high in epithelial cells of mucosal origin (whether normal primaries or neoplastic cell lines) as in epidermoid cells (normal epidermal primary cultures, an immortalized but non-tumorigenic epidermal cell line, and neoplastic vulvar and cervical cell lines). Interferon-gamma strongly upregulated gene expression, but substantially less in mucosal than epidermoid cells. To compare responses as a clue to the function of zinc-alpha 2-glycoprotein, we ran parallel experiments with three markers of distinct properties, all known to be induced by interferon-gamma. There was the least resemblance for involucrin, a qualitative similarity for HLA-DR, and a rather better match for 2'-5' oligoadenylate synthetase.

2',5'-Oligoadenylate Synthetase↗