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Experimental local administration of CDDP to in vitro models of gynecological malignant tumors transplanted into nude mice (compared with medroxyprogesterone acetate orally administered).

In order to develop a new method of administration for CDDP, in vitro models of malignant tumors in the field of gynecology were prepared using two cell lines maintained by the authors, and fundamental experiments on the topical injection of CDDP were carried out. In experimental topical injection of CDDP in tumor-bearing nude mice, the test drug demonstrated an excellent tumor regression effect and an inhibitory effect on tumor growth. In the histopathologic examinations, specific necrosis of tumor cells was observed. It was confirmed that this is a highly safe method, as tissue separation, ulceration, or hemorrhagic lesions attributable to the local administration of CDDP were not observed. In the present study, treatment with oral medroxyprogesterone acetate was also used. At the doses used in this study, however, no inhibitory effect on tumor growth or synergism between medroxyprogesterone acetate and CDDP was observed. Topical injection is an excellent pharmacodynamic method that permits the injection of free platin into the tumor itself or in the boundary area between the tumor and normal tissues, with no loss of the drug, and it is considered a safe and effective mode of local administration. Intra-arterial injection of this drug alone or in conjunction with OK-432 can also be used, even though further studies will be required to determine the optimum dosage and reduce side effects. At present, data are being collected on terminal cancer patients for whom no other therapy is available. In the near future this method of administration is expected to be utilized in the clinical treatment of malignant tumors, be it early tumor or progressive cancer.

Administration, Oral↗

Cell culture observations of human postnatal thymic epithelium: an in vitro model for growth and humoral influence on intrathymic T lymphocyte maturation.

Sixteen postnatal human thymuses were obtained at the time of corrective cardiovascular surgery and maintained in vitro as separate cultures of thymocytes and reticulo-epithelial (RE) cells. The stages of differentiation of the thymocytes were investigated in situ with a library of 10 monoclonal antibodies (MoABs) directed against human lymphocyte differentiation antigens. Employing immunofluorescence staining and flow cytometric (FACS) analysis, in vitro immunophenotype (IP) changes were demonstrated, which appeared after use of a combination of mitogen (PHA), recombinant interleukin-2 (rIL-2) and autologous thymic RE cell culture supernatants. RE cell supernatant participated in increasing the expression of the IL-2 receptor (IL-2R) during combined stimulation with phytohaemagglutinin (PHA) and rIL-2. Thymocyte proliferation was measured in 4 hour tritiated-thymidine (3H-TdR) incorporation (proliferation) assay. We were able to isolate the thymic nurse cells (TNC) with and without enzymatic tissue digestion. TNCs were separated from accompanying thymocytes and cultured. They grew as large, sometimes connected cells, but did not display the epithelial type of tissue organization. After in vitro culturing, the cytoskeleton of TNCs expressed high molecular weight cytokeratin and vimentin and intracytoplasmic tonofilaments, characteristic of epithelium. Whole thymic tissue pieces were cultured with and without previous trypsinization. The initial outgrowth of the cuboidal epithelial tissue layer occurred within 24-48 hours, and the RE cells remained functionally active for at least 15 days. RE cell supernatants were collected daily for two weeks and used in thymocyte differentiation experiments. The results indicated that thymic humoral factors contribute to a select, not fully understood differentiation pathway of thymocytes: a) more mature immunophenotype (IP) characterized by CD3 expression; b) de novo synthesis of interleukin-2 receptor (IL-2R); and; c) differentiation of the CD8+ subpopulation, identifying regulatory cells within the two major CD8+ and CD4+ subsets. Use of mitogenic (PHA) stimulation, after 5 days in vitro, resulted in a T helper (CD4+) oriented differentiation pathway of cortical thymocytes. At the same time, the cultured thymocytes expressed CD11 de novo, an early thymocyte differentiation antigen, and CD7, a marker not present on mature peripheral lymphocyte subsets (the IP changes demonstrated a dedifferentiation). Our overall impression, following the studies with the proliferation assays, was that in our experimental in vitro model, thymic hormones did not contribute to the induction of generalized thymocyte proliferation.

Antigens, CD1↗

Exhibition of specific alterations in activities and mRNA levels of rat islet glycolytic and mitochondrial enzymes in three different in vitro model systems for attenuated insulin release.

We studied the possible relationships between the functional status of the beta-cell and activities or mRNA contents of enzymes involved in the catabolism of glucose. Three different in vitro models with attenuated insulin response were used: rat islets cultured at a low glucose concentration, rat islets incubated in vitro with streptozocin, and fetal rat islets. The fetal and streptozocin-administered islets were compared with adult islets cultured in RPMI-1640 containing 11 mM glucose, and the effects of the in vitro glucose concentrations (3.3, 11, and 28 mM) were assessed on adult islets only. Cellular mRNA levels for the mitochondrial DNA-encoded cytochrome b and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were determined by Northern-blot analysis. Enzymatic activities of high-Km (glucokinase) and low-Km (hexokinase) glucose-phosphorylating enzymes and succinate-cytochrome c reductase were also determined. Islets cultured at 3.3 mM glucose displayed a decreased activity of glucokinase compared with islets cultured at 28 mM glucose (23.3 +/- 12%), whereas there was no difference in hexokinase activity or the level of GAPDH mRNA. The activity of succinate-cytochrome c reductase was similar in islets cultured at the different glucose concentrations. The level of cytochrome b mRNA increased at 28 mM glucose compared with islets cultured at 11 mM glucose (140 +/- 14%). Islets incubated with streptozocin and subsequently cultured for 7 days at 11 mM glucose exhibited a decreased level of cytochrome b mRNA (65 +/- 5%) and no differences in the activities of glucokinase, hexokinase, succinate-cytochrome c reductase, or the level of GAPDH mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Osmotic stress in an in vitro model of the outer blood-retinal barrier.

Because of the difficulty involved in in vivo experimental manipulations of the outer blood-retinal barrier, we developed an in vitro model. Retinal pigment epithelium (RPE) from bovine eyes was grown on semipermeable membranes. A continuous monolayer of RPE developed a measurable transepithelial electrical resistance (TER). TER was used as a parameter of barrier function. The tightness of the cellular monolayer was also tested with fluorescein. The TER increased in confluent cultures by 60-70 ohms-cm2, and there was no fluorescein leakage. After exposure of the cultures to 0.2% trypsin or 1% ethylenediaminetetraacetic acid (ETDA), we detected a reversible breakdown of the epithelial barrier function. Under transmission electron microscopy, we detected no disassembly of the junctional components after breakdown of the barrier function with trypsin or EDTA. A hyperosmotic NaCl solution in the basal medium as well as a hypoosmotic NaCl solution in the apical medium induced a breakdown in the TER, whereas a hyperosmotic NaCl solution in the apical medium induced only a slight decrease in the TER. Under transmission electron microscopy, we detected an intracellular blistering and large intercellular widening. A hypo-osmolar NaCl solution in the basal medium induced a rise in the TER. With regard to these experiments, it seems, at least in vitro, that the function of occluding junctions in bovine RPE as permeability barriers depends on extracellular calcium. Furthermore, our results were such as if the outer blood-retinal barrier were designed to prevent subretinal inflow of free water.

Animals↗

Comet-tail artifact from cholesterol crystals: observations in the postlithotripsy gallbladder and an in vitro model.

The "comet tail" is a well-known ultrasound artifact that appears as a series of parallel bands radiating from a source. This artifact was observed in the gallbladder lumen in eight of 10 patients after extracorporeal shock wave lithotripsy of radiolucent calculi. To investigate the cause of the comet tail artifact, cholesterol crystals were studied in an in vitro model. The comet-tail appearance was reproduced in vitro and was found to be directly related to the interrogating frequency and the size of the crystal aggregates. The authors conclude that cholesterol crystals can serve as the source of the comet-tail artifact secondary to reverberation within the crystals.

Cholelithiasis↗

Thrombolytic potency of acid-stabilized plasmin: superiority over tissue-type plasminogen activator in an in vitro model of catheter-assisted thrombolysis.

Plasmin, the direct fibrinolytic enzyme, was compared with tissue plasminogen activator (t-PA) in an in vitro thrombolysis model. Plasmin has been prepared in a highly pure form from human plasma and has been stabilized against auto-degradation by low-pH formulation. This acidified formulation of plasmin has been designed to have a low buffering capacity so that it can be directly infused into clots in a stable and latently active form. This low-pH formulation has been shown to be equivalent to a neutral-pH formulation of plasmin in its extent of clot lysis. An in vitro model of catheter-assisted thrombolysis has been devised in which large (12 x 0.6 cm), retracted clots are treated with an intrathrombus thrombolytic agent via a multi-sideport catheter. Plasmin dissolves these plasminogen-deficient clots in a dose-dependent manner and is clearly superior to t-PA. In this model system, t-PA exhibits efficacy only when retracted clots are replenished with plasminogen.

Catheterization↗

Vitamin D-regulated calcium transport in Caco-2 cells: unique in vitro model.

The human colon adenocarcinoma cell line Caco-2 is the only intestinal cell line to differentiate spontaneously in culture exhibiting structural and biochemical characteristics of mature enterocytes and to possess a vitamin D receptor in the fully differentiated state. Transepithelial calcium transport was characterized in differentiated Caco-2 cells grown on permeable filters supports to assess the potential utility of this cell line as an in vitro model to study 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]-induced calcium transport. Calcium transport was increased in a dose-dependent manner by 1,25(OH)2D3. Total calcium transport at different calcium concentrations could be fitted to a modified Michaelis-Menten equation containing a linear transport component. The maximum rate of saturable calcium transport was increased by 4.3-fold (P less than 0.005) in cells treated with 10(-8) M 1,25(OH)2D3. This treatment also increased the apparent buffer calcium concentration that results in half-maximal velocity from 0.4 to 1.3 mM but had no significant effect on nonsaturable calcium transport. Caco-2 cells grown on permeable filter supports provide a unique in vitro human cell culture model to study the mechanism of vitamin D-regulated transepithelial intestinal calcium transport.

Adenocarcinoma↗

In vitro model for the response to irradiation of different types of human intracranial tumours.

Twenty-seven human low and high grade gliomas and five meningiomas were cultured in vitro as tumour tissue and/or tumour cells. Cell survival or growth was taken as a measure of radiation response. Astrocytomas II-III and glioblastomas manifested individual patterns of radiosensitivity, ranging from 10 to 90 Gy. Meningiomas did not react. Our findings are consistent with the differences in radiosensitivity of human gliomas experienced clinically and corroborate the validity of the in vitro model.

Brain Neoplasms↗

Biological effects of flowable resin composite on erythrocytes and lymphocytes using an in vitro model.

AIM: The purpose of the study was to evaluate the biological effects of a flowable resin composite on erythrocytes and rat spleen lymphocytes (RSL) using an in vitro model. METHODOLOGY: Rat spleen lymphocytes were placed into microcentrifuge tubes as a pulp model. An artificial pulp exposure was made through the top of the microcentrifuge tube with a 16G needle. The exposure site was filled with a flowable resin composite and photo-polymerized, and the other specimens were not polymerized. The survival rates were determined by a haemocytometer. Red blood cell (RBC) suspension (0.5%) was reacted with the flowable resin composite. The haemolytic activity was evaluated at room temperature (20 degrees C) using a supernatant of each sample by measuring 545 nm of absorbency with a spectrophotometer. To evaluate the effect of flowable resin composite on RBCs, supernatant and precipitated samples were analysed by sodium dodecyl sulphate-polyacrylamide gel (SDS-PAGE). RESULTS: The cell survival rate of the polymerized group was significantly lower compared with that of the nonpolymerized group at the same areas (P < 0.05). The values of haemolysis (absorbency) were 2.16 for the polymerized group, 2.14 for the nonpolymerized group, and 2.18 for the control group (saline). There were no significant differences among them (P > 0.05). The protein component in the supernatant and precipitate exhibited the same reaction with flowable resin composite regardless of the completion of the polymerization, resulting in no change of protein band mobility on SDS-PAGE. CONCLUSIONS: The degree of haemolysis was not influenced by the completion of polymerization. The flowable resin composite tested provoked an adverse effect on lymphocytes when it was not polymerized and the degree of haemolysis was not affected by the status of the polymerization.

Animals↗

Bactericidal effect of amoxicillin on Helicobacter pylori in an in vitro model using epithelial cells.

The treatment of Helicobacter pylori with antimicrobial agents has largely been ineffective, and susceptibility results are in disagreement with those obtained by standard in vitro testing. The bactericidal effect of amoxicillin was tested in an in vitro model by using sessile bacteria attached to HEp-2 cells; this bactericidal effect was compared with that against planktonic bacteria. Viable cell counts were performed by standard procedures after 1, 6, and 24 h of contact with the antibiotic at different concentrations. A bactericidal effect (99.9% killing) was observed against sessile bacteria after 24 h with concentrations of only 10, 1, and 0.1 mg/liter, while against planktonic bacteria it was also noted at concentrations of 0.01 and 0.001 mg/liter, and the effect was observed after 6 h with the three highest concentrations. When the results for five strains were studied by analysis of variance at 6 and 24 h, the main variable was the antibiotic concentration, followed by the culture conditions, e.g., planktonic or sessile bacteria, the strain tested, and the time of contact. A decreased pH of 5.4 did not affect the action of amoxicillin. The bactericidal effect of the combination of amoxicillin and metronidazole was additive against sessile H. pylori.

Amoxicillin↗

Pharmacodynamics of piperacillin alone and in combination with tazobactam against piperacillin-resistant and -susceptible organisms in an in vitro model of infection.

The pharmacodynamics of dosage regimens of piperacillin alone or in combination with tazobactam against piperacillin-resistant or -susceptible bacteria were studied in an in vitro model of infection. Experiments were conducted by using a fixed daily exposure of 12 g of piperacillin, given as 3 g alone or in combination with tazobactam at 0.375 g every 6 h, or the same total dose of the combination given as 4 g of piperacillin plus 0.5 g of tazobactam every 8 h. The addition of tazobactam to piperacillin, irrespective of the dosing interval, did not alter the killing of piperacillin-susceptible organisms (Escherichia coli J53 and Pseudomonas aeruginosa ATCC 27853). In contrast, experiments with an isogenic TEM-3-containing transconjugant of E. coli J53 (E. coli J53.2-TEM-3) that was resistant to piperacillin (MIC, 128 micrograms/ml) showed that the addition of tazobactam resulted in bacterial killing similar to that observed with the wild-type strain. Although tazobactam concentrations fell to less than 4 mg/liter (the concentration associated with a reduction in the piperacillin MIC from 128 to 2 mg/liter) 2 to 3 h after a dose, a similar degree of bacterial killing was observed when the same total 24-h dose of piperacillin-tazobactam was fractionated into dosing intervals of every 6 or 8 h. Investigations with Staphylococcus aureus 7176 (piperacillin MIC, 128 micrograms/ml) showed that the addition of tazobactam, again irrespective of dosing interval, also resulted in net bacterial killing which was not seen with piperacillin alone. These data support the use of extended dosing intervals (every 8 h) of piperacillin-tazobactam in the treatment of infections caused by piperacillin-resistant bacteria.

Bacteria↗

Assessment of supra-additive effects of cytotoxic drugs and low dose rate irradiation in an in vitro model for hepatocellular carcinoma.

The use of 5-fluorouracil, topotecan, or gemcitabine was tested for enhancement of the effects of low dose rate (LDR) irradiation in an in vitro model for hepatocellular carcinoma. For comparison, all drugs were tested in combination with high dose rate (HDR) gamma-irradiation as well. Multicellular spheroids of HepG2 cells were exposed to HDR or LDR irradiation by means of external beam cobalt-60 or rhenium-188 (188Re), respectively, dissolved in the culture medium. Secondly, exposure to irradiation was combined with the cytotoxic drug. Toxicity was evaluated by means of a quantitative spheroid outgrowth assay and histology. For 5-fluorouracil, supra-additive effects were observed in combination with HDR irradiation. With 188Re, the supra-additive toxicity was only transient. For topotecan and 188Re, no supra-additive effects were seen, whereas the addition of HDR irradiation at the end of the topotecan exposure yielded lasting supra-additive effects. Incubation with gemcitabine followed by exposure to HDR irradiation, induced a synergistic toxicity on the outgrowth. No supra-additive effects were observed when HDR irradiation was added at the start of the incubation with gemcitabine or combined with LDR irradiation. For all drugs tested, supra-additive effects were observed with HDR irradiation if the timing of the irradiation was appropriate. For 188Re, no lasting supra-additive effects were observed.

Antimetabolites, Antineoplastic↗

Digestibility of resistant starch containing preparations using two in vitro models.

BACKGROUND: Resistant starch (RS) is known for potential health benefits in the human colon. To investigate these positive effects it is important to be able to predict the amount, and the structure of starch reaching the large intestine. AIM OF THE STUDY: The aim of this study was to compare two different in vitro models simulating the digestibility of two RS containing preparations. METHODS: The substrates, high amylose maize (HAM) containing RS type 2, and retrograded long chain tapioca maltodextrins (RTmd) containing RS type 3 were in vitro digested using a batch and a dynamic model, respectively. Both preparations were characterized before and after digestion by using X-Ray and DSC, and by measuring their total starch, RS and protein contents. RESULTS: Using both digestion models, 60-61 g/100 g of RTmd turned out to be indigestible, which is very well in accordance with 59 g/100 g found in vivo after feeding RTmd to ileostomy patients. In contrast, dynamic and batch in vitro digestion experiments using HAM as a substrate led to 58 g/100 g and 66 g/100 g RS recovery. The degradability of HAM is more affected by differences in experimental parameters compared to RTmd. The main variations between the two in vitro digestion methods are the enzyme preparations used, incubation times and mechanical stress exerted on the substrate. However, for both preparations dynamically digested fractions led to lower amounts of analytically RS and a lower crystallinity. CONCLUSIONS: The two in vitro digestion methods used attacked the starch molecules differently, which influenced starch digestibility of HAM but not of RTmd.

Amylose↗

A new in vitro model of specific targeting therapy of cancer: retargeting of PWM-LAK cells with bispecific antibodies greatly enhances cytotoxicity to hepatocellular carcinoma.

For the purpose of establishing a new in vitro model of adoptive immunotherapy, we synthesized two kinds of bispecific antibodies (BsAbs), i.e., (OK x L) BsAbs constructed with both OKT-3 (anti-CD3) and L-7-6 (anti-HCC), and (3G x L) BsAbs constructed with 3-G-8 (anti-CD16) and L-7-6 antibodies. These two BsAbs, having pairs of binding arms on their single molecule, showed similar binding to target cells as the parental monoclonal antibodies (OKT-3, 3-G-8 and L-7-6), when examined with FACS. Newly devised in vitro cytotoxicity tests revealed that LAK or PWM-stimulated LAK (PWM-LAK) cells did not show any significant cytotoxic activity to HCC cells, while both effector cells equally showed greatly enhanced cytotoxicity to HCC even at a low effector/target (0.3) in the presence of BsAbs (OK x L) for the efficient retargeting of the effector cells. Inasmuch as PWM-LAK cells proliferate in vitro 3-5 times faster than LAK cells, adoptive immunotherapy using PWM-LAK cells in combination with (OK x L) BsAbs should be very promising.

Antibodies, Bispecific↗

In vitro model of equine muscle regeneration.

Equine satellite cells are responsible for muscle healing and regeneration in the mature horse. We describe the in vitro cell culture conditions required for clonal populations of equine satellite cells to undergo both proliferation and differentiation. Our hypothesis is that these in vitro conditions model regeneration of muscle and can be used to evaluate potential therapeutics. In this study, 2 areas of satellite cell response were tested: proliferation of clones induced by growth factors, and fusion induced by culture conditions. Equine satellite cell clones showed differences in their response to growth factors as well as accumulation of cellular protein concentrations. Equine satellite cells proliferate in response to both human and bovine FGF. IGF-1, a powerful mitogen of other satellite cell culture systems, was not as effective for inducing equine satellite cell proliferation. Protein concentrations were also measured in satellite cell cultures. Clones differed in cellular protein produced depending on growth conditions. Conditions inducing differentiation into myotubes was also determined for a 96 well assay and can be used to study the final stage of functioning muscle production. This in vitro model is the first step in identifying potential therapeutics to speed wound healing and promote muscle regeneration in horses.

Animals↗

Compression induced cell damage in engineered muscle tissue: an in vitro model to study pressure ulcer aetiology.

The aetiology of pressure ulcers is poorly understood. The complexity of the problem, involving mechanical, biochemical, and physiological factors demands the need for simpler model systems that can be used to investigate the relative contribution of these factors, while controlling others. Therefore, an in vitro model system of engineered skeletal muscle tissue constructs was developed. With this model system, the relationship between compressive tissue straining and cell damage initiation was investigated under well-defined environmental conditions. Compression of the engineered muscle tissue constructs revealed that cell death occurs within 1-2 h at clinically relevant straining percentages and that higher strains led to earlier damage initiation. In addition, the uniform distribution of dead cells throughout the constructs suggested that sustained deformation of the cells was the principle cause of cell death. Therefore, it is hypothetised that sustained cell deformation is an additional mechanism that plays a role in the development of pressure ulcers.

Animals↗

Development of an in vitro model to study carcinogen-induced neoplastic progression of initiated mouse epidermal cells.

Initiation and promotion in mouse skin carcinogenesis produce multiple benign tumors, squamous papillomas, but only a few squamous cell carcinomas. The spontaneous conversion from the benign to the malignant phenotype occurs over many months and in stages, but induced malignant conversion can be accomplished more rapidly by exposure of papilloma-bearing mice to mutagens or by transfection of papilloma cell lines with specific oncogenes. The analysis of genetic targets responsible for carcinogen-induced neoplastic progression would be facilitated by the development of in vitro models where the process is rapid, focal, and quantitative. To this end, primary newborn mouse keratinocytes were initiated in vitro by the introduction of the v-rasHa oncogene via a defective retrovirus. Recipient cells produce squamous papillomas and have a high proliferation rate in culture medium with 0.05 mM Ca2+, but fail to grow in medium with 0.5 mM Ca2+ which is permissive for growth of malignant keratinocytes. When v-rasHa-keratinocytes were exposed to mutagens in vitro, proliferative foci emerged after culture in 0.5 mM Ca2+ for 4 weeks. These foci stained intensely red with rhodamine stain, could be easily quantitated, and readily incorporated bromodeoxyuridine. Dose-response studies with several mutagens indicated that the number of foci increased with concentration to the point where excessive cytotoxicity developed. Mutagens varied in potency for producing foci in the following order: cis-diamminedichloroplatinum greater than or equal to benzo(a)pyrene diolexpoxide I greater than N-methyl-N'-nitro-N-nitrosoguanidine greater than or equal to 4-nitroquinoline-N-oxide greater than N-acetoxy-acetyl- aminofluorene. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate was inactive in the assay. A subset of cell lines derived from foci produced malignant tumors in vivo, while others were not tumorigenic. Analysis of DNA from cell lines and tumors revealed that most tumorigenic cell lines maintained the v-rasHa genome, whereas the viral sequences were deleted in nontumorigenic cell lines. Immunohistochemical analysis indicated that proliferative foci and quiescent v-rasHa keratinocytes expressed keratin 8, a marker of v-rasHa expression in cultured keratinocytes. Cells in foci, but not v-rasHa control cells, expressed keratin 13, a marker which is strongly associated with the malignant progression of skin tumors in vivo. This in vitro assay provides a quantitative model to study chemically induced focal neoplastic progression at the cellular level and to identify agents which may be selective for enhancing malignant conversion.

Animals↗

Expression of ICAM-1 in colon epithelial cells: an ultrastructural study performed on in vivo and in vitro models.

BACKGROUND: Studies have suggested that in ulcerative colitis (UC), intercellular adhesion molecule-1 (ICAM-1) is involved in migration of leukocytes toward the colonic epithelium. A suitable in vitro model of chronic colonic inflammation does not exist, and the role of the epithelium is based on monolayers of cancer cells. Conflicting results exist on epithelial ICAM-1 expression, and the aim of this study was to compare the expression in various models of colonic epithelium. MATERIALS AND METHODS: Colonic biopsies from four UC patients and four controls were examined by cryoimmuno-electron microscopy using ICAM-1-antibodies. In four other controls, the epithelium was isolated from colonic biopsies, embedded in collagen, and evaluated similarly. Isolated crypts and cultured cancer cells were stimulated with interferon-gamma (IFN-gamma) or tumor necrosis factor-alpha (TNF-alpha). RESULTS: ICAM-1 was not expressed in the biopsies. In contrast, HT29 cells and the collagen-embedded crypts expressed ICAM-1 on the apical membranes proximal to the junctional complexes when stimulated with IFN-gamma or TNF-alpha in a dose-related manner. CONCLUSIONS: ICAM-1 is not expressed on colonic epithelium in vivo. However, both colonocytes and HT29 cells were capable of expressing ICAM-1 on their apical membranes in response to supraphysiologic cytokine concentrations. These observations question the justification of extrapolating observations from colon cancer cell lines to in vivo inflammatory conditions.

Adult↗