Biomedical subjects

G Lizard

Publications and source records attributed to G Lizard.

At least 37 records · Page 2Linked to original sources

PubMed1995

Kinetics of plasma membrane and mitochondrial alterations in cells undergoing apoptosis.

Programmed cell death or apoptosis is characterized by typical morphological alterations. By transmission electron microscopy, apoptotic cells are identified by condensation of the chromatin in tight apposition to the nuclear envelope, alteration of the nuclear envelope and fragmentation of the nucleus, whereas integrity of the plasma membrane and organelles is preserved. Conversely cells undergoing necrosis display an early desintegration of cytoplasmic membrane and swelling of mitochondria. In this study we assessed by flow cytometry the sequential alterations of forward angle light scatter, 90 degrees light scatter, and fluorescence associated with fluorescein diacetate, rhodamine 123, and propidium iodide in two human B cell lines undergoing apoptosis induced by the topoisomerase II inhibitor VP-16. The kinetics of these modifications were compared to those of cells undergoing necrosis induced by sodium azide. At the same time intervals, cells were examined by transmission electron microscopy and by UV microscopy after staining with Hoechst 33342. We report that sequential changes in light scatters and fluorescein diacetate are similar in cells undergoing apoptosis or necrosis, whereas apoptosis is characterized by a slightly delayed decrease of mitochondrial activity as assessed by rhodamine 123 staining. Surprisingly a part of cells undergoing apoptosis displayed an early uptake of propidium iodide followed by a condensation and then a fragmentation of their nuclei. It is concluded that uptake of propidium iodide is a very early marker of cell death which does not discriminate between necrosis and apoptosis. Along with biochemical criteria, nuclear morphology revealed by staining with Hoechst 33342 would seem to be of the most simple and most discriminative assay of apoptosis.

Animals↗

PubMed1995

Apoptosis without decrease of cell DNA content.

Apoptosis of human B cells and murine T and B cells was analyzed by DNA agarose gel electrophoresis, clamped homogeneous electric field, measurement of cell DNA content by flow cytometry, transmission electron microscopy and by UV microscopy. Apoptosis was induced by etoposide (an inhibitor of topoisomerase II), by the calcium ionophore ionomycin or by cross-linking of membrane immunoglobulins (Ig) with anti-Ig-antibodies. Two types of apoptosis could be defined. Apoptosis resulting in small DNA fragments (180-200 base pairs and multiples thereof) was associated with a typical 'ladder' in agarose gel electrophoresis and a decrease in cell DNA content assessed by flow cytometry. Conversely apoptosis with large DNA fragments (100-150 kilobase pairs) was only demonstrated by clamped homogeneous electric field but was not associated with decreased cell DNA content or the observation of DNA ladders. Nuclear condensation without fragmentation was more frequent when apoptosis generated large DNA fragments. The type of apoptosis appears to be an intrinsic property of each cell type.

Apoptosis↗

PubMed1995

Isolation of mature olfactory neurones using retrograde labelling and flow cytometry.

Currently we can observe an increasing interest for epithelial olfactory neurones. Several laboratories are involved in elucidation of the odorant-molecule recognition process and transduction cascade which brings information to the olfactory bulb. Others use this model, unique in mammals, to accumulate new knowledge on the neurogenesis phenomenon. Here we describe a simple and efficient method to purify mature olfactory neurone populations extracted from the nasal cavity. The approach relies on retrograde axonal tracing followed by flow cytometry sorting. For this purpose we inject a fluorescent dye (Fast Blue or diI C18(3)) in the olfactory bulb of adult rats. Seven days later, we extract the nasal turbinates and separate the mucosa from the subjacent lamina propria. The tissue is enzymatically dissociated and the labelled cells are sorted with a flow cytometer. Purification of the mature olfactory neurones varies from 80 to 99%.

Amidines↗

PubMed1995

Protective effect of zinc on keratinocyte activation markers induced by interferon or nickel.

Zinc therapies exert beneficial effects in several cutaneous pathologies through their antiinflammatory properties, but target cells and mechanisms of action are still uncertain. We wondered whether markers of the keratinocyte activation state, such as the expression of immune surface antigens (ICAM-1 and HLA-DR) and the production of TNF-alpha, frequently detected in inflammatory reactions, may be reduced by zinc. For this purpose, we used normal human keratinocytes derived from plastic skin surgery and cultured in low-calcium medium (MCDB153). We studied the effects of ZnSO4 (12.5 to 50 microM) alone or in combination with IFN-gamma (5 U/ml), a mediator of inflammation produced by activated T-cells, or nickel (5-10 micrograms/ml), a sensitizing metal hapten. Using FACS analysis, we showed that the combination of zinc with nickel or the addition of ZnSO4 24 h before IFN-gamma or NiSO4 treatments reduced ICAM-1 expression on the keratinocyte surface (p < 0.01). However, zinc did not modify the IFN-gamma induced expression of HLA class II antigen on keratinocytes. Zn2+ could also reduce the TNF-alpha secretion of keratinocytes stimulated by IFN-gamma or Ni2+ during 48 h. Taken together, these data indicate that zinc can directly reduce some keratinocyte activation markers frequently observed in vivo; this action may be involved in the antiinflammatory effect of Zn(2+)-associated therapies in cutaneous inflammatory reactions.

Antigens, Surface↗

PubMed1995

Evaluation of multidrug resistant phenotype by flow cytometry with monoclonal antibodies and functional tests.

Multidrug resistant (MDR) phenotype is characterized by a defect in drug accumulation caused by overexpression of a transmembrane glycoprotein, the P-glycoprotein (P-gp). MDR phenotype can be characterized either with monoclonal antibodies raised against P-gp or with functional tests, most often based on the incorporation of fluorescent compounds. In the present study, data obtained with the monoclonal antibodies C219, JSB1 and MRK16 are compared to those of functional tests performed by flow cytometry including uptake of daunorubicin (DNR), Rhodamine 123 (Rh 123) or Hoechst 33342. Sensitive and resistant cell lines K562S, K562R, KBA1 and KB31, derived either from a human chronic myeloid leukemia or from a human epithelial carcinoma, were used. In resistant cells, P-gp expression was revealed with either the monoclonal antibodies C219, JSB1 or MRK-16. The most specific results were obtained with MRK-16. With functional tests, no matter which dyes were used, the fluorescence was always stronger in sensitive than in resistant cells. However, with DNR and Hoechst 33342, an incorporation of these dyes was exhibited in resistant cells. This phenomenon was not observed with Rh 123, which makes it possible to distinguish clearly between sensitive and resistant cells and to detect as few as 1% of resistant cells. Because of its high sensitivity, the functional test involving incorporation of Rh 123 was successfully used in acute myeloid leukemia to detect multichemoresistant cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1995

[Agents inducing cell death of the vascular wall].

Arterial wall is constituted by endothelial cells, smooth muscle cells and fibroblasts. A number of agents are capable of inducing damages in these cells leading either to apoptosis or necrosis involved in various pathologies. Such agents are constituted by: bacterial endotoxins, mediators and modulators of immunitary and/or inflammatory systems, drugs, reactive oxygen metabolites, free radicals, cholesterol oxidation derivatives included or not in lipoproteins. The study of the mechanisms of action implied in cell death would permit a better understanding of vascular diseases and open new therapeutic perspectives.

Cell Death↗

PubMed1995

Flow cytometry evaluation of the multidrug-resistant phenotype with functional tests involving uptake of daunorubicin, Hoechst 33342, or rhodamine 123: a comparative study.

Multidrug-resistant (MDR) cells are characterized by a defect in drug accumulation caused by overexpression of a transmembrane glycoprotein, the P-glycoprotein (P-gp). The MDR phenotype can be characterized either by use of monoclonal antibodies raised against P-gp or with functional tests based on the intracellular accumulation of fluorescent molecules. The aim of the present study was to compare the effectiveness of functional tests performed by flow cytometry including uptake of daunorubicin (DNR) (2 micrograms/ml), Hoechst 33342 (5 micrograms/ml), or rhodamine 123 (RH 123) (0.1 microgram/ml); and to evaluate the effect of cell death induced by heating at 60 degrees C for 2 h on incorporation of DNR and RH 123. Sensitive and resistant human hematopoietic K 562 cells expressing P-gp were identified by monoclonal antibodies C 219 and MRK-16. Fluorescence of the dyes was always higher in sensitive than in resistant cells. However, DNR and Hoechst 33342 produced a slight incorporation in resistant cells, while RH 123 showed lack of incorporation in resistant cells. Thus, RH 123 allows sensitive and resistant cells to be clearly distinguished. In case of cell death, accumulation of RH 123 and DNR were different. With RH 123, fluorescence intensity strongly decreased in sensitive cells. With DNR, fluorescence intensity was enhanced in resistant cells. Thus, when the MDR phenotype is defined by uptake of DNR or RH 123, artifactual results due to cell death may be avoided by using a dye such as propidium iodide to eliminate dead cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1994

Two human melanoma cell-line variants with enhanced in vivo tumor growth and metastatic capacity do not express the beta 3 integrin subunit.

The alpha v beta 3 integrin complex is thought to play an important role in in vivo melanoma tumor growth and metastasis. However, not all human metastatic melanomas, present in lymph node biopsies, express alpha v beta 3. In this study, we have investigated the possibility that certain melanoma cell lines can grow aggressively in vivo in the absence of alpha v beta 3 expression. Established human melanoma cell lines (M3Da., M4Beu.) were isolated from an achromic skin metastasis or lymph nodes. Two stable variants (7GP, T1P26), derived from a poorly metastatic M4Beu. melanoma cell line, were isolated by sequential selection for spontaneous metastasis formation in an immunosuppressed newborn rat model. Flow-cytometry analysis shows an absence of the beta 3 integrin subunit (less than 2% of parental levels) in the two variant melanoma cell lines (7GP, T1P26) compared to M3Da. and M4Beu. cell lines which express a relatively high number of beta 3 subunits. The expression levels of the integrin subunits beta 1, beta 5, beta 6 and alpha v were found to be similar for all four melanoma cell lines. Northern blot analysis confirmed the absence of beta 3 in 7GP or T1P26 cell lines and its presence in M3Da. and M4Beu. Moreover, similar levels of alpha v transcript were present in the four melanoma cell lines. The functional effect of the absence of beta 3 was investigated by subcutaneously implanting the variants and the melanoma cell lines in nude mice. Variant 7GP and T1P26 cell lines yielded tumors which were larger and grew at a faster rate than tumors in M3Da. or M4Beu. cell lines. The beta 3 integrin subunit was not detectable on the surface of cells harvested from tumors after 20 or 35 days. Similarly, subcutaneous innoculation of the two variants into immunosuppressed newborn rats gave rise to extensive spontaneous lung metastases compared to the M4Beu. cell line. These results provide evidence that a population of melanoma cells can grow aggressively in vivo and metastasize in the absence of beta 3 or alpha v beta 3 integrin complex. Our results may have clinical relevance and suggest that certain types of melanomas in patients may grow and spread in the absence of the alpha v beta 3 integrin complex.

Animals↗

PubMed1994

Apoptosis induced by polyclonal antilymphocyte globulins in human B-cell lines.

Antilymphocyte and antithymocyte globulins (ALG) are currently used as immunosuppressive agents in clinical transplantation and for the treatment of severe aplastic anemia. ALG contain a mixture of antibodies that recognize T- and B-cell-specific antigens but mostly nonlineage-specific molecules. We reported previously that ALG could inhibit the proliferation of activated B cells and B cell lines (Bonnefoy-Bérard et al, Blood 79:2164, 1992). We show here that ALG induce apoptosis of several human hematopoietic cell lines, as shown by nuclear condensation and fragmentation in fluorescence and electronic microscopy and by double-strand DNA breaks shown by DNA electrophoresis. Apoptosis was achieved without elevation of intracellular Ca2+ and requirement for mRNA and protein synthesis. Most of the B-cell lines tested (Epstein-Barr virus [EBV]-transformed lymphoblastoid cell lines, EBV-negative and groups I/III EBV-positive Burkitt's lymphoma cell lines, as well as other B-lymphoma cell lines) were susceptible to ALG-induced cytotoxicity. Myelomonocytic and T-cell lines were much less susceptible than B-cell lines. Susceptibility to ALG-induced cytotoxicity was not correlated with intracellular Bcl-2 level. Most cell lines that express high levels of Fas/Apo-1 antigen were susceptible to ALG. However, several lines of evidence support the conclusion that, in addition to Fas/Apo-1, other cell surface molecules can mediate ALG-induced apoptosis. The cytotoxic activity could be fully removed by adsorption on susceptible cell lines but not on a resistant cell line, indicating that it was mediated by antibodies specific for surface antigens expressed only on susceptible cell lines. Apoptosis was triggered by ALG F(ab')2 fragments as well as by intact ALG. This cytotoxic property of ALG may account for their antiproliferative effect and might contribute to some extent to the relatively lower risk of posttransplant lymphoproliferative disorders previously reported in ALG-treated patients.

Antilymphocyte Serum↗

PubMed1994

Cyclosporin A and FK506 inhibit activation-induced cell death in the murine WEHI-231 B cell line.

The WEHI-231 B lymphoma cell line expresses the phenotype of immature B cells. Cross-linking of surface IgM induces programmed cell death (PCD) with typical features of apoptosis demonstrated by the decrease of cell DNA content, chromatin condensation, and nuclear fragmentation. Activation of protein kinase C (PKC) by phorbol esters was reported to protect WEHI-231 cells against apoptosis induced by ligation of antigen receptors. It was therefore hypothesized that PCD could result from a defect in PKC response with an imbalance in the phosphoinositide pathway in favor of Ca2+ mobilization. In support of this hypothesis, we show here that apoptosis can be readily triggered by the calcium ionophore ionomycin. Furthermore, pretreatment of cells with cyclosporin A or FK506 which inhibit selectively the phosphoprotein calcineurin, a calcium-and calmodulin-dependent serine/threonine phosphatase, protects WEHI-231 cells against apoptosis induced by ionomycin or ligation of surface IgM. Unlike phorbol esters, cyclosporin A did not impair the rise of intracellular Ca2+ induced by cross-linking of antigen receptors. Altogether, the data indicate that the phosphorylation status of yet undefined key cellular substrates controls the cellular response to calcium-dependent apoptotic signals in this B cell lymphoma.

Animals↗

PubMed1994

Laser scanning confocal microscopy and quantitative microscopy with a charge coupled device camera improve detection of human papillomavirus DNA revealed by fluorescence in situ hybridization.

Epithelial cervical CaSki, SiHa and HeLa cells containing respectively 600 copies of human papillomavirus (HPV) DNA type 16, 1-2 copies of HPV DNA type 16 and 10-50 copies of HPV DNA type 18 were used as model to detect different quantities of integrated HPV genome. The HPV DNA was identified on cell deposits with specific biotinylated DNA probes either by enzymatic in situ hybridization (EISH) or fluorescence in situ hybridization (FISH) involving successively a rabbit anti-biotin antibody, a biotinylated goat anti-rabbit antibody and streptavidin-alkaline phosphatase complex or streptavidin-fluorescein isothiocyanate complex. With brightfield microscopy and EISH, hybridization spots were observed in CaSki and HeLa cells but hardly any in SiHa cells. With fluorescence microscopy and FISH, hybridization spots were clearly seen only on CaSki cell nuclei. In an attempt to improve the detection of low quantities of HPV DNA signals revealed by FISH, laser scanning confocal microscopy (LSCM) and quantitative microscopy with an intensified charge coupled device (CCD) camera were used. With both LSCM and quantitative microscopy, as few as 1-2 copies of HPV DNA were detected and found to be confined to cell nuclei counterstained with propidium iodide. Under Nomarski phase contrast, a good preservation of the cell structure was observed. With quantitative microscopy, differences in the number, size, total area and integrated fluorescence intensity of hybridization spots per nucleus were revealed between CaSki, SiHa and HeLa cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Nucleus↗

PubMed1994

Effect of various metals on intercellular adhesion molecule-1 expression and tumour necrosis factor alpha production by normal human keratinocytes.

Nickel, cobalt and chromium are metals very often implicated in allergic contact dermatitis. In vivo, keratinocytes, which are the first target cells, can be directly activated to participate in the local reaction, especially through the expression of the membrane antigen ICAM-1, a ligand of the leucocyte antigen LFA-1, and the production of cytokines. Our aim was to assess the effects of sensitizing metal haptens (nickel, cobalt and chromium) compared with the toxic metal cadmium on the induction of ICAM-1 and the production of TNF alpha by epidermal cells. For this purpose, normal human keratinocytes obtained during plastic skin surgery were cultured in low-calcium defined medium (MCDB153) and the metals were used in non-toxic concentrations. Using FACS analysis, ICAM-1 expression was found to be induced only by nickel. This stimulation appeared as early as 24 h after stimulation. All the metals induced a low expression of TNF alpha detectable by immunocytochemistry correlating with the induction of the nuclear stress protein Hsp72 which is closely linked genetically with the TNF alpha locus. However, only Ni2+, Co2+ and Cr2+ induced a significant release of TNF alpha detectable by ELISA after 48 h stimulation. This secretion was lower than that observed with known stimulants such as lipopolysaccharide. These results indicate that the metals studied are able to induce an aggressive cellular effect, and that nickel, by its ICAM-1 induction, may play a major role in the keratinocyte activation state during allergic contact dermatitis.

Cells, Cultured↗

PubMed1994

Active cell membrane mechanisms involved in the exclusion of Rh 123 allow distinction between normal and tumoral cells.

Human cell lines derived from three epithelial carcinomas (CaSki, HeLa, SiHa), one B lymphoma (BL60), one promyelocytic (HL60), one monocytic (U937) leukemia, one chronic myelogenous leukemia (sensitive K562S; multichemoresistant K562R) and normal human skin fibroblasts were compared for their capacity of staining with rhodamine 123 (Rh 123) and their kinetics of dye exclusion. Cells were exposed for 30 min to 10 micrograms/ml of Rh 123 in culture medium; fluorescence intensity was measured by flow cytometry immediately or 1, 2, 3 and 4 h after staining. The highest fluorescence intensity was observed in carcinoma cell lines; there was no incorporation in multichemoresistant K562R cells. Exclusion of Rh 123 was evaluated from 0 to 4 h, both by flow cytometry and by fluorimetry. Fluorescence intensity measured by flow cytometry decreased slightly in carcinoma and leukemia cells and rapidly in fibroblasts. In all cell lines Rh 123 exclusion was inhibited by 40 mumol/L verapamil and 5 mmol/L probenecid. Thus, incorporation and exclusion of Rh 123 allows distinction between normal and tumoral cells; moreover, inhibition of exclusion by verapamil and probenecid favors the involvement of active cell membrane mechanisms in the exclusion process.

Cell Membrane↗

PubMed1994

Effect of nickel on the activation state of normal human keratinocytes through interleukin 1 and intercellular adhesion molecule 1 expression.

Patch tests with nickel on sensitive subjects induce a characteristic allergic reaction involving epidermal and dermal cells, as well as modulation of cytokines and adhesion molecule production. In order to gain further insight into the role of keratinocytes in this phenomenon, we assessed their activation state induced by Ni2+ by studying interleukin 1 (IL-1) production and intercellular adhesion molecule 1 (ICAM-1) expression, using normal human keratinocytes cultured in defined medium. In comparison with controls, the addition of subtoxic NiSO4 concentrations (0.1-20 micrograms/ml) to keratinocyte cultures induced a significant, but low release of IL-1 alpha and IL-1 beta at 24 and 48 h, detectable by enzyme-linked immunosorbent assay of the supernatants of treated cells. Moreover, IL-1 receptor antagonist was significantly increased in the supernatants and the cell extracts. Using fluorescence-activated cell sorter analysis, ICAM-1 expression at 24 h was found to be induced in a dose-dependent manner, reaching a level comparable with that obtained upon interferon-gamma (10 IU/ml) stimulation. Overall, these data confirm the existence of direct interactions between Ni2+ and keratinocytes, which generate immunological signals of major importance in the pathophysiology of allergic contact dermatitis.

Antigens, CD↗

PubMed1994

Human melanoma cell lines differ in their capacity to release ADP and aggregate platelets.

In this study we have investigated, using three different human melanoma cell lines (M1Do., M3Da., M4Be.). the varying capacity of melanoma cells to induce platelet aggregation in the presence or absence of inhibitors of ADP or thrombin. The expression levels of different integrins (alpha v, beta 3, alpha v beta 3, alpha IIb, alpha v beta 3) were evaluated by immunoprecipitation, binding and flow cytometry studies. The level of ADP in supernatants of melanoma cells were quantified by ADP bioassay and HPLC. Platelets were irreversibly aggregated by M3Da, as shown by electron microscopy, in contrast to M1Do, which induced a slow reversible aggregation. M4Be. did not induce platelet aggregation. In both cases, with M3Da. or M1Do., apyrase but not PPACK inhibited platelet induced aggregation. An anti-alpha v beta 3 monoclonal antibody (LYP18) or polyclonal antibody inhibited platelet aggregation. A similar number of LYP18 molecules bound to the surface of M1Do., M3Da. and M4Be. cell lines. Biological HPLC assays of ADP present in the supernatant of tumour cell lines showed the highest concentration of ADP to be secreted by M3Da., followed by M1Do., and none detected for M4Be. These results show that differences in in vitro aggregating potential of the three human melanoma cell lines are not related to low integrin expression levels but to their ability to generate ADP. Generation of ADP by human melanoma cells may act as important modulator of melanoma-platelet interactions.

Adenosine Diphosphate↗

PubMed1994

Interleukin-4 and interferon-gamma interactions in the induction of intercellular adhesion molecule-1 and major histocompatibility complex class II antigen expression of normal human keratinocytes.

Interleukin-4 (IL-4) that may be produced by T-helper cells in atopic lesions has immunomodulatory activities on skin cells which are poorly known. Our study was aimed at determining whether the cytokine exerts some effects on keratinocyte activation and can either enhance or antagonize interferon-gamma (IFN-gamma)-induced ICAM-1 or HLA-DR antigen expression. Using normal keratinocytes cultured in defined medium and cytofluorography, we showed that treatments of the human cells with the cytokine IL-4 alone had no effect on the induction of ICAM-1 or HLA-DR molecules. However, a transient, but significant enhanced expression of ICAM-1 was observed by the combination of IFN-gamma and IL-4 after 24 h of stimulation, which was followed by a reduction at 48 and 72 h. Conversely, IL-4, when added during the IFN-gamma activation stage, had no effect on MHC class II antigen expression of keratinocytes; however, the cytokine reduced the expression of these antigens when added 24 h before the stimulation by IFN-gamma. These results suggest that IFN-gamma and IL-4 may interact to regulate ICAM-1 and HLA-DR expression on keratinocytes.

Cells, Cultured↗

PubMed1994

Induction of intercellular adhesion molecule 1 expression on normal human keratinocytes by retinoic acid: comparison of cultured keratinocytes and skin explants.

As retinoic acid (RA, all trans) induces irritant reactions when applied topically to skin, we wondered whether it may be involved in the activation state of keratinocytes through ICAM-1 induction. Human skin explants and cultured keratinocytes were treated by RA and/or interferon-gamma (IFN gamma) at different concentrations during 24, 48 and 72 h. ICAM-1 expression was examined and quantified by immunohistochemistry, in situ, on cutaneous frozen sections and in cultured keratinocytes by flow cytometry analysis. Expression of mRNA was checked by Northern blot hybridizations using an oligonucleotide probe. Our results indicate: (1) the absence of spontaneous ICAM-1 expression by normal human keratinocytes both in skin explants and in cultures; (2) an ICAM-1-induced expression after 48 h of treatment by RA concentrations > 10(-6) M; this induction is dose- and time-dependent; in skin explants, ICAM-1 is occasionally observed on foci of epidermal cells; this protein induction is correlated with transcript expression in cultured keratinocytes; and (3) a synergistic effect of RA and IFN gamma (5 IU/ml) on the percentage of ICAM-1-positive cells and the level of expression of the protein. These findings indicate that RA, in a therapeutical range of concentrations can induce or stimulate ICAM-1 expression in normal human keratinocytes. This may in part explain the erythematous reaction observed in vivo after topical applications of RA which may be considered as a mediator of keratinocyte activation.

Adult↗

PubMed1994

[Papillary and cystic tumor of the pancreas. Histological, immunohistochemical and flow cytometric study].

The authors are reporting a case of papillary and cystic neoplasm of the pancreas. This rare malignant epithelial neoplasm occurs mostly in young women and has a more favorable prognosis than the adenocarcinoma. Radiologic investigations showed a well demarcated, heterogeneous, hypovascular mass. The histological study showed the proliferation of epithelial cells in a papillary pattern. The immunochemistry was negative for markers of adenocarcinoma but positive for vimentin, alpha-1-antitrypsin, alpha-1-antichymotrypsin and neuron specific enolase. Receptors of progesterone were also detected. By flow cytometric analysis, the tumours was hypoploid. The histogenesis of these tumours remained controversed. Ultrastructural details of the neoplastic cells suggest that these tumours originate from small duct cells; detection in several cases of markers for endocrine neoplasm suggests that they originate from primitive multipotential cells, that may show exocrine or endocrine differentiation.

Adult↗