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PubMed1982

Clinical, parasitological and serological studies on onchocerciasis in the Yemen Arab Republic.

Dermatological symptoms of onchocerciasis and microfilaria densities in the skin were studied in 108 infected persons in the Governorate of Taizz, and the levels of antifilarial antibodies and IgA, IgE, IgG, and IgM were determined in 75 of them. Predominantly in old men the generalized form of the disease was observed, which is characterized by symmetrical, mostly atrophic skin lesions, rather high microfilaria densities at various sites of the body and the presence of diagnostically unequivocal levels of antifilarial antibodies. In younger men, children and women of various age groups a localized form was observed, of which the typical features are: an intensely itching, mostly asymmetrical, well circumscribed onchodermatitis with or without oedema, pachydermia and darkening of the skin; considerable enlargement of several local lymph nodes; very or extremely low microfilaria density; the microfilariae are mostly restricted to the area of the skin lesion; manifestation of the microfilariae by a clear papular Mazzotti reaction after the application of microfilaricidal drugs; and diagnostically utilizable levels of antifilarial antibodies. The localized form can develop into the generalized form during later years. Intermediate and so far undefined forms, among which indeterminate forms may exist, are also seen. Patients with severe localized onchocerciasis demonstrated significantly higher antifilarial antibody levels than other infected persons. As a characteristic feature of onchocerciasis in the Yemen, onchocercomata were frequently found over the muscles of the calf, thigh and forearm distant from prominent bones. Onchocerciasis is endemic in all major wadis with permanent, westward flowing streams at altitudes of 300-1200 m between the southern Wadi Ghail and Wadi Surdud in the north and in some of their tributaries.

Adolescent↗
PubMed1989

Biology, cytogenetics, and sensitivity to immunological effector cells of new head and neck squamous cell carcinoma lines.

Twenty-one head and neck squamous cell carcinoma (HNSCC) cell lines were established from 89 fresh tumor specimens in order to study the biology of HNSCC lines, establish tumors in nude mice, and evaluate the sensitivity to immunological effector cells of these tumors in vitro and in vivo in nude mice. The lines were established from explants using differential trypsinization and culture for 2 to 20 mo. The explants were derived from 11 different sites. Three pairs of lines were derived from both the primary tumor and metastatic lymph nodes in the same patients. All cultures grew as either compact or diffuse adherent monolayers, and they had a median doubling time of 86 h (range, 33 to 531 h). DNA fingerprinting confirmed that the HNSCC lines were individual isolates. Thirteen of 14 lines tested induced tumors in athymic mice. The histology of each line growing in nude mice was similar to that of the original tumor tissue. Immunocytochemistry showed keratin production in all lines tested. Aneuploidy (36 to 87 chromosomes) was present in all 16 lines studied; the median chromosome number for lines derived from primary tumors was 70, whereas for lines originating from metastatic or recurrent tumors, it was 54. Karyotypic analysis showed deletion of the short arm of chromosome 3 (3p-) in 12 of 16 cell lines and trisomy 6 in 12 of 16 lines. In addition, translocations between chromosomes 9 and 11 or 9 and 12 were each present in five of 16 lines tested. The HNSCC lines were resistant to lysis by natural killer cells, but were efficiently lysed by lymphokine-activated killer cells in 4-h 51Cr release assays. These new lines have allowed us to establish a model of local adoptive immunotherapy of HNSCC in tumor-bearing nude mice, and they provide a resource for future studies of the biology of HNSCC.

Adult↗
PubMed1999

High-affinity antibodies from hen's-egg yolks against human mannose-6-phosphate/insulin-like growth-factor-II receptor (M6P/IGFII-R): characterization and potential use in clinical cancer studies.

The mannose-6-phosphate/insulin-like growth-factor-II receptor (M6P/IGFII-R) involved in trafficking of newly synthesized lysosomal enzymes, degradation of IGFII and activation of TGFbetaI, was suggested as being coded by a tumor-suppressor gene. No specific antibodies are currently available for clinical studies. Since M6P/IGFII-R is a highly conserved protein in mammals, we immunized chicken with human M6P/IGFII-R. Up to 200 mg of specific IgY from weekly pooled egg yolk was extracted by the polyethylene glycol procedure. Chicken IgY antibodies specifically recognized the human and bovine 270-kDa M6P/IGFII-R but not the 46-kDa M6P-R, as documented by immunoprecipitation and immunobloting. Using biosensor analysis, IgY antibodies were shown to bind M6P/IGFII-R with high affinity (K(D) = 7.5 x 10(-9) M). A solid-phase competitive ELISA using bovine M6P/IGFII-R coated on 96-well microplates, allowed us to titrate the M6P/IGFII-R in human sera at a sensitivity of 300 ng/ml. The M6P/IGFII-R was stained by immunoperoxidase in breast- and ovarian-cancer cell lines (T47D, MDA-MB231, MCF7 and BG1) and in frozen breast-cancer tissues, showing predominant localization in the trans-Golgi network. Staining specificity was shown with irrelevant IgY and by extinction with antigen excess. Quantitative immunohistochemical analysis of frozen sections from 40 invasive breast carcinomas indicated varying levels (from 5 to 400 units) of the M6P/IGFII-R protein which were not correlated with tumor size, histological grade and estrogen receptor or progesterone receptor. There was a trend (p = 0.08) between lymph-node invasiveness and low receptor level. Moreover, the M6P/IGFII-R level was significantly lower in cancer cells than in normal cells in 10 out of the 21 tumors in which the peritumoral normal glands could be quantified in parallel. These 2 last results agree with the hypothesis of a tumor-suppressor gene for this receptor and suggest more basic and clinical studies to prove it.

Animals↗
PubMed2001

Mucosal immune responses and protection against tetanus toxin after intranasal immunization with recombinant Lactobacillus plantarum.

The use of live microorganisms as an antigen delivery system is an effective means to elicit local immune responses and thus represents a promising strategy for mucosal vaccination. In this respect, lactic acid bacteria represent an original and attractive approach, as they are safe organisms that are used as food starters and probiotics. To determine whether an immune response could be elicited by intranasal delivery of recombinant lactobacilli, a Lactobacillus plantarum strain of human origin (NCIMB8826) was selected as the expression host. Cytoplasmic production of the 47-kDa fragment C of tetanus toxin (TTFC) was achieved at different levels depending on the plasmid construct. All recombinant strains proved to be immunogenic by the intranasal route in mice and able to elicit very high systemic immunoglobulin G (IgG1, IgG2b, and IgG2a) responses which correlated to the antigen dose. No significant differences in enzyme-linked immunosorbent assay IgG titers were observed when mice were immunized with live or mitomycin C-treated recombinant lactobacilli. Nevertheless, protection against the lethal effect of tetanus toxin was obtained only with the strains producing the highest dose of antigen and was greater following immunization with live bacteria. Significant TTFC-specific mucosal IgA responses were measured in bronchoalveolar lavage fluids, and antigen-specific T-cell responses were detected in cervical lymph nodes, both responses being higher in mice receiving a double dose of bacteria (at a 24-h interval) at each administration. These results demonstrate that recombinant lactobacilli can induce specific humoral (protective) and mucosal antibodies and cellular immune response against protective antigens upon nasal administration.

Administration, Intranasal↗
PubMed1994

[PS2 as a prognostic factor in 1065 cases of human breast cancer. A multicenter study].

pS2 protein assay was performed with Elsa-pS2 kit (CIS-Biointernational) on a group of 1,065 patients with operable breast cancer who underwent breast surgery in the years 1982 through 1990. The median follow-up was 57 months. This group included exclusively infiltrating ductal carcinoma with primary surgery. Age mean was 58 yr; T0-T1, 33.6%; T2-T4, 66.4%; Differentiation grade I, 29%; node negative, 53%; estrogen receptor (ER) positive, 62.4%; progesterone receptor (PR) positive, 55.2%; mean tumor size, 2.4 cm; local recurrence, 5.2%; metastasis, 17.5%. pS2 values varied from 0.1 to 707 ng/mg of cytosol protein (median, 5.6; mean 24.5; 95th percentile 112 ng/mg p). There was no significant relationship between the mean level of pS2 and age, tumor size, nodal status, whereas pS2 was related to histological grade (P < 10(-3)), ER (P < 10(-5)), and PR (P < 10(-5)). By using 2 ng/mg p as pS2 cutoff, 77/391 (19.7%) of ER+PR+ tumors were pS2-, and 122/345 (35.4%) of ER-PR-tumors were pS2+; with this cutoff, a strong relationship existed between pS2 and overall survival, but not between pS2 and relapse-free survival. With Cox multivariate analysis, pS2 protein was classified after lymph node status, histological size, ER, differentiation grade, age, clinical stage, PR. In patients with axillary lymph node involvement (N+), pS2 status could discriminate between good and bad prognosis, specially for patients with small tumors (< 2 cm) and with less than seven invaded nodes. This study showed that pS2 protein was a poor prognostic factor in comparison with classical factors.

Breast Neoplasms↗
PubMedDate not supplied

Microsatellite instability in squamous cell carcinomas and dysplasias of the esophagus.

Microsatellite instability (MSI) caused by the defective functions of mismatch repair genes plays an important role in the carcinogenesis of gastrointestinal tumors. However, little is known about the role of MSI in esophageal carcinogenesis. In the present study, we conducted microsatellite assays on 41 esophageal carcinomas and also on 44 dysplasias of the esophagus with 7 separate microsatellite loci. MSI was detected in 17 cases (42%) among 41 esophageal carcinomas. MSI negative cases revealed greater lymph node metastasis, metastasis at a more advanced stage, a higher recurrence level and a poorer prognosis (statistically not significant). In the analysis of dysplasias, MSI was detected in 26 lesions (59%) among 44 lesions. Interestingly, MSI was detected in 21 lesions (78%) from the mutator phenotype dysplasias, but detected in only 5 lesions (29%) from the non-mutator phenotype cases. Although the significance of MSI in esophageal carcinoma was not clear, these results indicate that MSI occurs in the early stage of esophageal carcinogenesis.

Adult↗
PubMed2000

Carcinogen-modified dendritic cells induce immunosuppression by incomplete T-cell activation resulting from impaired antigen uptake and reduced CD86 expression.

Exposure of the skin to environmental stimuli, such as chemical or physical carcinogens, modifies the local skin environment, including depletion of epidermal Langerhans' cells (LC). Any subsequent exposure of the LC-depleted skin to antigen results in the generation of antigen-specific tolerance. In this study we evaluated the antigen-bearing cells in the draining lymph nodes by capitalizing on the fluorescent nature of the contact sensitizer, fluorescein isothiocyanate (FITC). When FITC was applied to the skin of normal mice, two distinct populations of antigen-bearing cells were identified in the draining lymph nodes. They were classified as either FITChi or FITClo on the basis of their fluorescence intensity and thus the amount of antigen they internalized. Only FITClo cells were detected in the lymph nodes draining FITC-treated murine skin that had been depleted of epidermal LC by prior treatment with the complete carcinogen 9,10-dimethyl 1,2-benzanthracene (DMBA). Functional analysis of these cells revealed that the FITChi cells, but not the FITClo cells, induced antigen-specific T-cell proliferation. Further analysis of the FITClo cells from the DMBA-treated mice demonstrated that these cells had reduced levels of CD80 expression, had substantially reduced levels of CD86 expression and performed poorly as co-stimulator cells in an anti-CD3-mediated proliferative assay. Nonetheless these cells still induced early signs of T-cell activation and interleukin-12 production. Consequently the FITClo cells migrating from the LC-depleted skin, through a combination of reduced antigen presentation and reduced co-stimulatory activity, induced a state of unresponsiveness or anergy in the responder T cells in a similar manner to that observed when antigen presentation occurs in the absence of co-stimulation. We propose that these unresponsive, or anergic cells, account for the antigen-specific tolerance observed in these experiments.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Abnormal expression of four novel molecular markers represents a highly aggressive phenotype in breast cancer. Immunohistochemical assay of p53, nm23, erbB-2, and cathepsin D protein.

BACKGROUND: In view of the cumulative results to date, p53, nm23, erbB-2, and cathepsin D are the most promising investigational prognostic factors in breast cancer. OBJECTIVES: The clinical utility of these molecular markers to predict recurrence was evaluated. METHODS: Archival pathology tissues of 100 breast cancer patients were analyzed by immunohistochemical assay. Molecular biologic data were merged with clinicopathologic variables. RESULTS: Thirty-two patients (32%) had recurrence of disease at a median follow-up of 48 months (range 26-72 months). Investigational factor expression had statistical correlation for recurrence with increasing coexpression: one variable 20.6%, two variables 34.2%, three variables 47.1%, four variables 80.0% (P = 0.003). In univariate analysis, lymph node metastasis, tumor size, erbB-2 protein overexpression, and loss of nm23 protein expression were significant variables to determine recurrence; in multivariate analysis, node status and tumor size emerged as the most significant variables for recurrence. CONCLUSIONS: Coexpression of the studied investigational variables functioned as significant prognostic correlates for recurrence. These findings suggest that the studied investigational prognostic factors possess the ability to discriminate a highly aggressive phenotype in breast cancer.

Biomarkers, Tumor↗
PubMed2001

[Eradication of paratuberculosis in dairy herds: determination of the initial herd prevalence and modelling of prevalence development].

A prerequisite for the success of any eradication programme is the accurate determination of the initial herd prevalence as well as a herd-specific prediction of prevalence development. This prerequisite is not currently given for the eradication of paratuberculosis in infected herds. In the work presented a method to predict the initial paratuberculosis prevalence in infected herds is presented; it is based on the formation of two groups (ELISA-positive and negative) and the determination of generally applicable factors (positive predictive value [ppvn] of the ELISA and sensitivity of fecal culture in the ELISA-negative group [senF]). The ppvn of the ELISA was determined to be 0.6 based on the cultural examination of the ileocaecal lymph node of 64 ELISA-positive animals; the value for senF was set to be 0.64 based on the cultural examination of feces and ileocaecal lymph nodes of 40 ELISA-negative animals. To calculate the initial herd prevalence the number of animals in each of the groups was multiplied with the ppvn of the ELISA or with the reciprocal value of senF (1.5). The values were added and divided by the size of the herd. The practicability of this model was examined on nine herds with a total of 708 animals. The development of herd prevalence was modelled based on the examination scheme given in the paratuberculosis control programme of the "Niedersächsische Tierseuchenkasse" (local board for infectious disease control in food animals in the state of Lower Saxony, Germany). For the calculation a yearly turnover-rate of 33% with restocking from within the herd and a possibility of paratuberculosis diagnosis only in animals two years and older were assumed. The development of herd prevalence is exemplarily presented for four herds with different initial prevalences.

Animals↗
PubMed2003

Systemic and local cytokine response of young piglets to oral infection with Salmonella enterica serotype Typhimurium.

One-week-old breast-fed miniature piglets were orally infected either with virulent LT2 strain or with a non-virulent SF1591 rough mutant of Salmonella Typhimurium for 1 d. Both microorganisms were cultivated from mesenteric lymph nodes but not from the blood of infected piglets. Interleukins (IL) 1 beta, 8, 18, tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) were quantified by ELISA in plasma and washes of a terminal part of the small bowel. In plasma, cytokines were mostly missing in non-infected piglets and either missing or low in infected piglets. In the gut of non-infected piglets, IL-1 beta, IL-8 and IL-18 were detected whereas TNF-alpha and IFN-gamma were mostly missing. IFN-gamma levels highly increased (p < 0.05) after infection with nonvirulent salmonellae. The variability of cytokine levels in the gut of suckling piglets is discussed.

Animals↗
PubMed1989

Differential expression of helper versus effector activity in mice rendered neonatally tolerant of class II MHC antigens.

Since tolerogen-specific helper activity is present in MLR-positive class II MHC tolerant mice, a loss of helper activity is unlikely to be responsible for the maintenance of tolerance in these mice. An alternative hypothesis, that effector cell function is selectively down-regulated, has been examined with lymphocytes from MLR-positive class-II MHC tolerant mice on both the A strain and the B10 background. The results demonstrate that lymphocytes from A-strain-tolerant mice were unable to generate tolerogen-specific effector cells in any of the assays tested (CML with or without exogenous growth factor and DTH following in vivo priming or local adoptive transfer), even though these mice possess tolerogen-responsive T helper cells. In contrast, a majority of MLR-positive tolerant mice on the B10 background generated measurable tolerogen-specific cytotoxic activity in the absence of exogenous growth factor, and all the mice examined generated substantial cytotoxic activity in the presence of exogenous growth factor. However, in a local adoptive transfer reaction, lymphocytes from these mice failed to display DTH. It is concluded that tolerance is maintained by selective impairment of class II specific effector functions and that regulation of DTH rather than CTL activity may be central to maintenance of in vivo tolerance to class II MHC antigens.

Animals↗
PubMed1993

Clinical, morphological and virological features of an HTLV-I-positive case of ATL in a white man from the Caucasus.

An HTLV-I-associated case of adult T-cell leukemia (ATL) was described in a 51-year-old white man, native from Georgia, the former U.S.S.R. Clinical manifestation of the disease (enlarged lymph nodes, bone marrow and peripheral blood changes, CNS-involvement, cutaneous lesions and hypercalcemia) as well as laboratory findings were recognized to be very similar to those frequently observed in ATL patients from endemic regions. Mature T-helper surface phenotype detected on peripheral blood lymphocytes of the patient (OKT3-, OKT4+ and OKT8-) and aggressive course of the disease were also in favour of classical type ATL developed in the patient. The HTLV-I antibody presence in an ATL patient was repeatedly confirmed by serological tests (Abbott HTLV-I EIA and Serodia HTLV-I), immunofluorescence and Western blot assay. The latter revealed the presence of a large spectrum of HTLV-I-specific antibodies (to p19, p24, p26, p28, p32, p36, pr53, gp21, gp46, gp62 and gp68 of HTLV-1). The HTLV-I-specific antibodies have also been detected in serum samples of the patient's wife and son. The presence of HTLV-I provirus in the primary ATL patient's PBL was clearly demonstrated by PCR and Southern blot analysis. This case, with the HTLV-I infections detected in two other family members, suggests that in Europe, HTLV-I-positive cases of ATL can occur in virus-infected local people with much wider distribution than that hitherto supposed.

Antibodies, Viral↗
PubMed2003

Quantitative tumor apoptosis imaging using technetium-99m-HYNIC annexin V single photon emission computed tomography.

PURPOSE: Radiolabeled annexin V may allow for repetitive and selective in vivo identification of apoptotic cell death without the need for invasive biopsy. This study reports on the relationship between quantitative technetium-99m- (99mTc-) 6-hydrazinonicotinic (HYNIC) radiolabeled annexin V tumor uptake, and the number of tumor apoptotic cells derived from histologic analysis. PATIENTS AND METHODS: Twenty patients (18 men, two women) suspected of primary (n = 19) or recurrent (n = 1) head and neck carcinoma were included. All patients underwent a spiral computed tomography (CT) scan, 99mTc-HYNIC annexin V tomography, and subsequent surgical resection of the suspected primary or recurrent tumor. Quantitative 99mTc-HYNIC annexin V uptake in tumor lesions divided by the tumor volume, derived from CT, was related to the number of apoptotic cells per tumor high-power field derived from terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) assays performed on sectioned tumor slices. RESULTS: Diagnosis was primary head and neck tumor in 18 patients, lymph node involvement of a cancer of unknown primary origin in one patient, and the absence of recurrence in one patient. Mean percentage absolute tumor uptake of the injected dose per cubic centimeter tumor volume derived from tomographic images was 0.0003% (standard deviation [SD], 0.0004%) at 1 hour postinjection (PI) and 0.0001% (SD, 0.0000%) at 5 to 6 hours PI (P =.012). Quantitative 99mTc-HYNIC annexin V tumor uptake correlated well with the number of apoptotic cells if only tumor samples with no or minimal amounts of necrosis were considered. CONCLUSION: In the absence of necrosis, absolute 99mTc-HYNIC annexin V tumor uptake values correlate well with the number of apoptotic cells derived from TUNEL assays.

Aged↗
PubMed1992

EGF receptor expression in primary laryngeal cancer: correlation with clinico-pathological features and prognostic significance.

Epidermal-growth-factor-receptor(EGFR) expression was evaluated in 103 primary laryngeal tumors and in 42 normal laryngeal tissue specimens. Significantly higher EGFR levels were found in cancer specimens than in normal mucosa (p = 0.0053). EGFR expression did not correlate with age, tumor localization, T classification, cervical-lymph-node involvement or type of surgery, whereas it was higher in poorly differentiated tumors (G3) than in well/moderately differentiated (G1-G2) tumors (p < 0.05). Follow-up data were available for 74 patients. When EGFR status and the most important clinico-pathological characteristics were submitted to univariate analysis, tumor localization, type of surgery and EGFR status were found to be significantly correlated with disease-free survival. The 24-month disease-free survival rate was 58% for EGFR+ cancer patients and 82% for EGFR- ones. With multivariate analysis, only EGFR status and tumor localization were identified as significant independent prognostic parameters. Data reported here suggest that high EGFR levels may identify a sub-set of laryngeal-cancer patients with a particularly unfavorable prognosis.

Adult↗
PubMed2002

Prognostic significance of cytokeratin-20 reverse transcriptase polymerase chain reaction in lymph nodes of node-negative colorectal cancer patients.

PURPOSE: Approximately 20% to 30% of patients with curatively resected, node-negative (pN0) colorectal cancer die of tumor recurrence, which can be caused by minimal residual disease. To identify patients with an increased risk of tumor recurrence and evaluate the prognostic value of cytokeratin-20 (CK-20), we detected CK-20-positive cells in histopathologically tumor-free lymph nodes (pN0) of patients with colorectal cancer. PATIENTS AND METHODS: Two peritumoral lymph nodes each from 85 patients with completely resected (R0) colorectal cancer without lymph node metastases (pN0) by routine examination were analyzed using a CK-20-specific reverse transcriptase polymerase chain reaction (RT-PCR) and compared with CK-20-specific immunohistochemistry (IHC). The results were correlated with histopathologic findings and with survival. RESULTS: CK-20 RT-PCR was positive in 44 patients (52%) and detected 83% of cancer-related death. Positive RT-PCR was significantly correlated with poorer overall survival (P <.009). Comparing RT-PCR with IHC, 13 patients with positive RT-PCR were identified, where the CK-20 expression was caused by tumor cell contamination located exclusively outside the lymph node capsule and had no prognostic impact. Defining these 13 patients as RT-PCR negative improved specificity of the RT-PCR assay from 57% to 75%. The 5-year overall survival of the 31 RT-PCR-positive patients was 71%, compared with 96% in the 54 negative patients (P <.001). Multivariate analysis showed expression of CK-20 mRNA to be an independent prognostic factor with a relative risk of cancer-related death of 6.1. CONCLUSION: CK-20 RT-PCR in peritumoral histopathologic tumor-free (pN0) lymph nodes of colorectal cancer is an independent prognostic factor for overall survival. Additional CK-20 IHC improves the specificity and prognostic value of RT-PCR for cancer-related death.

Aged↗
PubMed1995

Are murine marginal-zone macrophages the splenic white pulp analog of high endothelial venules?

The entry of lymphocytes into the spleen, in contrast to lymph nodes, does not involve high endothelial venule (HEV) interaction. The precise point of entry, as well as the mechanism by which lymphocytes enter the lymphoid areas of the spleen, remains controversial. We examined in detail the effect of two agents, pertussis toxin (PT) and the sulfated polysaccharide fucoidan, on splenic lymphocyte entry and positioning. These have previously been shown to interfere with lymphocyte extravasation across HEV. PT prevents lymphocyte extravasation, but not binding, to HEV, whereas fucoidan prevents binding and thus subsequent extravasation. Studies presented here show that pretreatment of murine lymphocytes with PT does not numerically affect entry into spleen, but profoundly alters lymphocyte positioning within the spleen. When fluorescently labeled, PT-treated lymphocytes are injected intravenously, they initially accumulate in the marginal zone, in apparent association with the layer of marginal zone macrophages (MZM phi) which form a shell around the white pulp. They fail to traverse this layer into the white pulp, and subsequently localize in the red pulp. In contrast, untreated cells initially appear in the marginal zone, then continue to migrate into the white pulp after traversing the MZM phi layer. The localization of PT-pretreated lymphocytes adjacent to the MZM phi layer is disrupted by intravenous administration of fucoidan. Using a flow cytometric assay of aggregation between MZM phi and lymphocytes, we confirmed that fucoidan is also able to inhibit this association in vitro, whereas PT has no effect on this interaction. We propose that MZM phi in the mouse are the splenic analog of HEV, forming the port of entry of lymphocytes into the white pulp of the spleen.

Animals↗
PubMed1990

Relationship between epidermal growth factor receptor status and various prognostic factors in human breast cancer.

Relationship between epidermal growth factor receptor (EGFR) status and various prognostic factors was investigated in 91 human breast cancer tissues. Epidermal growth factor receptor was measured by biochemical competitive binding assay using iodine 125 epidermal growth factor (125I)-EGF. The EGFR status was not correlated with axillary lymph node involvement, tumor size, stage, and histologic type, but significantly correlated with histologic grading (P less than 0.05) and lymphatic invasion (P less than 0.01). Between EGFR and estrogen receptor (ER) status, a clear inverse relationship was observed (P less than 0.01). The Ki-67-positive stained cell rate, which reveals the proportion of cycling cells, was significantly higher in EGFR-positive tumor tissues than in EGFR-negative cases. Furthermore, preliminary postoperative survey demonstrated a high tendency of recurrence rate of patients with EGFR-positive tumors as compared with those with EGFR-negative tumors. These data suggest that EGFR status may be important for the prediction of biologically high malignant potential.

Antigens, Neoplasm↗
PubMed1996

Contact allergens and epidermal proinflammatory cytokines modulate Langerhans cell E-cadherin expression in situ.

After exposure to antigen, Langerhans cells (LC) migrate from the epidermis to lymph nodes, where they initiate primary immune responses in T cells. The adhesion molecule E-cadherin mediates adhesion of LC to keratinocytes in vitro and may be responsible for localization of LC in epidermis. To determine if levels of LC E-cadherin are modulated during LC emigration from epidermis, we utilized flow cytometry to evaluate E-cadherin expression on BALB/c LC exposed in situ to the contact allergen 2,4,6-trinitrochlorobenzene (TNCB). TNCB induced increased I-A/E antigen and decreased E-cadherin expression on a subpopulation of LC as early as 12 h, and as late as 48 h, after application. At 24 h, approximately 30% of LC in TNCB-treated skin expressed increased I-A/E antigens; of these activated LC, approximately 40% expressed decreased levels of E-cadherin. E-cadherin levels on this latter subset were approximately 15% of those expressed by LC in normal skin, and were similar to levels on cultured LC and LC that migrated from skin explants. The effect was specific for allergens; no changes occurred in LC following treatment with several contact irritants or the tolerogen dinitrothiocyanobenzene. To determine if cytokines modulated LC E-cadherin expression, we introduced various cytokines into BALB/c ear skin and assayed I-A/E antigen and E-cadherin levels. Of the cytokines tested, only interleukin-1 and tumor necrosis factor alpha reproduced the effects of TNCB. We propose that downmodulation of E-cadherin expression occurs as a consequence of local cytokine production during antigen-induced LC activation, facilitating LC emigration and the initiation of immune responses against antigens encountered in epidermis.

Allergens↗