Biomedical subjects

M Schindel

Publications and source records attributed to M Schindel.

6 recordsLinked to original sources

PubMed1998

Selective suppression of cytokine secretion in whole blood cell cultures of patients with colorectal cancer.

We have investigated the secretion of interferon alpha (IFN-alpha), IFN-gamma, interleukin-1alpha (IL-1alpha), IL-1beta, IL-2 and tumour necrosis factor alpha (TNF-alpha) in whole blood cell cultures (WBCCs) of colorectal cancer patients upon mitogen stimulation. Whereas the values for IL-1beta and TNF-alpha remained virtually unchanged in comparison with healthy control subjects, WBCCs of colorectal cancer patients secreted significantly lower amounts of IFN-alpha (P < 0.005), IFN-gamma (P < 0.0001), IL-1alpha (P < 0.0001) and IL-2 (P < 0.05). This reduction correlated with the progression of the disease. The total leucocyte and monocyte population were almost identical in both groups. In contrast, a dramatic depletion of lymphocytes was observed in colorectal cancer patients, which affected both lymphocyte counts (P < 0.0005) and their distribution (P < 0.0001). Our results suggest a selective suppression of cytokines in colorectal cancer patients that is related to tumour burden. Several mechanisms might account for this phenomenon, one of which might be lymphocyte depletion.

Adult↗

PubMed1997

Tumour-derived, endocrine, exogenous and therapeutic factors differentially modulate cytokine secretion in whole blood cell culture.

Following our previous results which showed that TGF-beta 1 suppressed the secretion of certain cytokines, we investigated the effects of different endogenous and exogenous factors on cytokine secretion in whole blood cell culture by using an enzyme-linked immunosorbent assay (ELISA) for measurement of cytokine concentrations. Several molecules including dexamethasone, noradrenaline (NA) and ethanol differentially inhibited mitogen-induced cytokine secretion. Dexamethasone and noradrenaline suppressed secretion of IL-2, IFN alpha, IFN gamma, TNF alpha, IL-1 alpha and IL-1 beta. beta-Endorphin and Leu-Enkephalin had no significant influence on cytokine secretion. Suppression of cytokine secretion by TGF-beta 1 was further intensified significantly and dose dependently by addition of noradrenaline. GM-CSF stimulated the secretion of IL-1 alpha, IL-1 beta and TNF gamma, but had no influence on the secretion of IL-2, IFN alpha and IFN gamma. G-CSF, IL-3 and SCF did not significantly influence secretion of all cytokines tested. Thus, endogenous and exogenous factors differentially influence cytokine secretion by immunocompetent cells.

Adult↗

PubMed1997

Decrease of interleukin-2 secretion is a new independent prognostic factor associated with poor survival in patients with small-cell lung cancer.

BACKGROUND: We have previously shown that suppression of interleukin-2 (IL-2) secretion was mediated by transforming growth factor (TGF) beta 1 secreted by small-cell lung cancer (SCLC) tumor cells. We have also shown that IL-2 secretion was significantly impaired in patients with SCLC at the time of diagnosis. Reconstitution of cytokine secretion correlated with reduction of tumor load. These data suggested that the immune system was suppressed by the tumor. To address the clinical relevance of cytokine suppression in SCLC, we investigated the correlation of the level of IL-2 secretion with survival. PATIENTS AND METHODS: The significance of correlations between single parameters in the test groups was calculated by using the linear regression analysis, the Wilcoxon rank sum test and the exact test according to Fisher. Using the Kaplan-Meier method, the log-rank test and the Cox-regression model, we analysed the relation of IL-2 secretion in whole blood cell cultures from 52 patients with SCLC at the time of diagnosis to established prognostic factors relevant for survival in SCLC. RESULTS: Impairment of IL-2 secretion significantly correlates to survival in SCLC (P = 0.004). Further univariate and multivariate analysis showed that this prognostic factor is independent from other factors of prognostic relevance in SCLC, namely stage of disease, neurone specific enolase (NSE), lactate dehydrogenase (LDH), age, and sex. More important, the prognostic value of IL-2 secretion is comparable to the most predominant prognostic factors for survival in SCLC identified so far. In the final model of the cox regression analysis, the P-value for IL-2 secretion in relation to stage of disease was 0.012 and 0.019, respectively. CONCLUSIONS: IL-2 secretion at the time of diagnosis represents an independent prognostic factor for survival in SCLC. Although its prognostic value has to be confirmed in a larger group of patients, our results demonstrate that IL-2 secretion may play an important role in diagnosis and treatment of SCLC. Moreover, in contrast to other prognostic factors, impairment of IL-2 secretion may help to understand immunosuppression in SCLC and, thus, important elements of the pathogenesis of this disease.

Adult↗

PubMed1996

[Systematic analysis of cervical lymph node metastasis of larynx and hypopharynx carcinomas--a clinical computerized tomography study with special reference to extension of the primary tumor].

PURPOSE: To assess the incidence and patterns of cervical lymph node metastases in laryngeal and hypopharyngeal carcinomas according to the location, extension, and relation of the primary tumor to the parapharyngeal compartments and tissues arising from different embryological structures as branchial arches and somites. PATIENTS AND METHODS: The findings of clinical and CT examinations of 230 patients with histological evidence of laryngeal and hypopharyngeal carcinoma (44 T1-, 33 T2-, 41 T3-, 112 T4-carcinomas with lymph node involvement in 116 cases) were evaluated retrospectively. Local tumor spread and relation of the primary to the parapharyngeal compartments and to tissues arising from different embryological structures such as branchial arches and somites were analysed and related to cervical lymph node involvement. RESULTS: The pattern of cervical lymph node involvement depends upon location and extension of the primary tumor in the adjacent tissues of the larynx and hypopharynx. The density of the lymphatic vessels in these areas determines the likelihood of lymph node involvement. The frequency of NO cases in carcinomas strictly located in the vocal cord (n = 31) was 100%; in the glottic-supraglottic, supraglottic, and transglottic cancer (n = 106) 85%; in larynx-hypopharynx carcinomas (n = 54) 26%; in hypopharynx carcinomas (n = 12) 17%; and in larynx-hypo-oropharynx carcinomas (n = 46) 9%. Tumors in tissues arising from branchial arches 4, 5, and 6 are glottic-supraglottic, transglottic laryngeal, and laryngeal-hypopharyngeal carcinomas. Metastases of these tumors were frequently found in the jugular lymph node chains, particularly if the developed tissue of the "primitive glottis" was invaded by the primary. Upper jugular nodes ipsilateral to a supraglottic or hypopharyngeal primary were usually involved. The frequency of metastases in the jugular lymph node chains decreased in craniocaudal direction. If the tumor invaded the posterior wall of the hypopharynx or tissues.

Adult↗

PubMed1995

Selective suppression of cytokine secretion in patients with small-cell lung cancer.

BACKGROUND: Whether or not cytokine secretion is impaired in patients with small-cell lung cancer (SCLC), is unknown. We therefore investigated whether cytokine secretion by immunocompetent cells may be suppressed in patients with SCLC. PATIENTS AND METHODS: We determined cytokine secretion by lymphocytes and monocytes in whole blood cell cultures from 58 patients with SCLC, 95 patients with non-small-cell lung cancer (NSCLC), 10 patients with nonmalignant lung disease and from 44 normal healthy individuals by using an enzyme-linked immunosorbent assay (ELISA) specific for the different cytokines measured. RESULTS: Compares to normal controls, immunocompetent cells from patients with SCLC secreted significantly lower amounts of IL-2, IFN alpha, and IFN gamma upon mitogen stimulation. TNF alpha-secretion was significantly reduced in SCLC extensive disease but not in SCLC limited disease. In contrast, secretion of IL-1 alpha and IL-1 beta was not reduced. In patients with NSCLC, secretion of IL-2 and IFN alpha was significantly reduced. Reduction of IFN gamma secretion was significant in metastasized NSCLC and marginally significant in localized NSCLC. Secretion of TNF alpha, IL-1 alpha and IL-1 beta was not impaired. In addition, cytokine secretion in SCLC patients substantially improved upon successful reduction of tumor load by chemotherapy but not upon ineffective chemotherapy. Furthermore, TGF beta 1 suppressed secretion of IL-2, IFN alpha, IFN gamma, TNF alpha but not of IL-1 alpha and IL-1 beta in whole blood cell cultures from healthy individuals. CONCLUSIONS: Suppression of cytokine secretion in patients with SCLC was selective, dependent on tumor load, different from immunosuppression in NSCLC and seemed to be reconstituted upon reduction of tumor load. These results may suggest interactions between tumor cells and the immune system. TGF beta 1 secreted by SCLC cell lines induced the same selective cytokine suppression as that found in SCLC patients. However, whether or not tumor-derived TGF beta 1 is a factor inducing selective immunosuppression in SCLC patients is presently unclear.

Adult↗

PubMed1994

Constitutive secretion of bioactive transforming growth factor beta 1 by small cell lung cancer cell lines.

We investigated effects of soluble mediators secreted by small cell lung cancer (SCLC) cell lines on modulation of cytokine-induced growth of lymphocytes. We found that interleukin-2 (IL-2)-mediated T-cell growth was inhibited by a cytokine constitutively secreted by the SCLC cell line, NCI-N417. Of several cytokines tested, only transforming growth factor beta 1 (TGF beta 1) severely suppressed IL-2-dependent T-cell growth. Using a specific anti-TGF beta 1 antibody, we found that this antibody blocked the immunosuppressive activity secreted by NCI-N417. Thus, the NCI-N417-derived immunosuppressive molecule was serologically identified as TGF beta 1. Further experiments showed that TGF beta 1 was secreted by four of eight SCLC lines tested. mRNA for TGF beta 1 was expressed in NCI-N417 and in SCLC-22H. Constitutive secretion of biologically active TGF beta 1 by SCLC lines suggests that tumour-derived immunosuppression may have clinical relevance.

Carcinoma, Small Cell↗