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Biomedical subjects

M Voss

Publications and source records attributed to M Voss.

At least 55 records · Page 3Linked to original sources
PubMed1999

Regulation of muscarinic acetylcholine receptor sequestration and function by beta-arrestin.

After activation, agonist-occupied G protein-coupled receptors are phosphorylated by G protein-coupled receptor kinases and bind cytosolic beta-arrestins, which uncouple the receptors from their cognate G proteins. Recent studies on the beta2-adrenergic receptor have demonstrated that beta-arrestin also targets the receptors to clathrin-coated pits for subsequent internalization and activation of mitogen-activated protein kinases. We and others have previously shown that muscarinic acetylcholine receptors (mAChRs) of the m1, m3, and m4 subtype require functional dynamin to sequester into HEK-293 tsA201 cells, whereas m2 mAChRs sequester in a dynamin-independent manner. To investigate the role of beta-arrestin in mAChR sequestration, we determined the effect of overexpressing beta-arrestin-1 and the dominant-negative inhibitor of beta-arrestin-mediated receptor sequestration, beta-arrestin-1 V53D, on mAChR sequestration and function. Sequestration of m1, m3, and m4 mAChRs was suppressed by 60-75% in cells overexpressing beta-arrestin-1 V53D, whereas m2 mAChR sequestration was affected by less than 10%. In addition, overexpression of beta-arrestin-1 V53D as well as dynamin K44A significantly suppressed m1 mAChR-mediated activation of mitogen-activated protein kinases. Finally, we investigated whether mAChRs sequester into clathrin-coated vesicles by overexpressing Hub, a dominant-negative clathrin mutant. Although sequestration of m1, m3, and m4 mAChRs was inhibited by 50-70%, m2 mAChR sequestration was suppressed by less than 10%. We conclude that m1, m3, and m4 mAChRs expressed in HEK-293 tsA201 cells sequester into clathrin-coated vesicles in a beta-arrestin- and dynamin-dependent manner, whereas sequestration of m2 mAChRs in these cells is largely independent of these proteins.

Arrestins↗
PubMed1999

The ADP-ribosylation factor (ARF)-related GTPase ARF-related protein binds to the ARF-specific guanine nucleotide exchange factor cytohesin and inhibits the ARF-dependent activation of phospholipase D.

ADP-ribosylation factor-related protein (ARP) is a membrane-associated GTPase with remote similarity to the family of ADP-ribosylation factors (ARF). In a yeast two-hybrid screen designed to identify proteins interacting with ARP, we isolated a partial cDNA of the ARF-specific guanine nucleotide exchange factor mSec7-1/cytohesin encoding its N terminus and most of the Sec7 domain (codons 1-200). ARP and ARP-Q79L (GTPase-negative ARP) exhibited a higher affinity to mSec7-1-(1-200) than ARP-T31N (nucleotide exchange-defective ARP) in the two-hybrid assay. Similarly, full-length [35S]mSec7-1/cytohesin was specifically adsorbed to glutathione-Sepharose loaded with glutathione S-transferase (GST)-ARP-Q79L, GST-ARP, or GST-ARP-T31N, the latter exhibiting the lowest binding affinity. Overexpression of ARP-Q79L, but not of ARP-T31N, in COS-7 cells reduced the fluorescence from co-expressed green fluorescent protein fused with mSec7-1/cytohesin or mSec7-2/ARNO in plasma membranes as detected by deconvolution microscopy. Recombinant ARP and ARP-Q79L, but not ARP-T31N, inhibited the phospholipase D (PLD) activity stimulated by mSec7-2/ARNO and ARF in a system of isolated membranes. Furthermore, transfection of HEK-293 cells with ARP or ARP-Q79L, but not ARP-T31N, inhibited the muscarinic acetylcholine receptor-3 induced PLD stimulation and translocation of ARF from cytosol to membranes. These data suggest that the GTP-bound form of ARP specifically binds mSec7-1/cytohesin, and that ARP may be involved in a pathway inhibiting the ARF-controlled activity of PLD.

ADP-Ribosylation Factors↗
PubMed1999

Axillary lymph node involvement in stage III breast cancer: treatment implications.

BACKGROUND AND OBJECTIVES: The introduction of multimodal therapy has improved the prognosis in stage III breast cancer. A knowledge of the likely axillary lymph node status at presentation is important, both to plan surgical therapy to the axilla and to establish the effect of induction therapy on the axillary nodes. METHODS: The study involved a chart review of 114 patients with stage III breast cancer who were treated by modified radical mastectomy without prior systemic therapy. A standard method was used for axillary dissection and numbers and levels of pathologically involved lymph nodes were recorded. The incidence of lymph node metastases was correlated with tumour size, grade, and clinical T stage. The accuracy of clinical axillary staging and the relationship between level III invasion and the number of level I and II nodes invaded was also assessed. RESULTS: Overall, 96 of 114 (84%) patients had axillary nodal metastases, and 37 of 114 (32%) patients had level III metastases. Eighteen of 43 tumours (42%) 30 mm or less had level III metastases and 27% of larger tumours had level III metastases (6/25 31-49-mm tumours, and 12/42 50+-mm tumours). Of 98 gradable cancers, only 1 out of 10 well-differentiated tumours had level III metastases, but the rate in moderately and poorly differentiated tumours was 36% (19/53) and 37% (13/35), respectively. Clinical node staging was unreliable. A group of patients with a low likelihood of level III metastases who might benefit from an axillary procedure less than level III dissection could not be identified preoperatively. CONCLUSIONS: Patients with stage III breast cancer have a high incidence of level III axillary lymph node metastases. A subgroup with a low incidence of level III metastases could not be identified in this study. Until axillary downstaging has been convincingly demonstrated with induction therapy, a less than complete axillary procedure may leave the patient at high risk of axillary relapse.

Axilla↗
PubMed1999

Inter- and intra-observer variability in the assessment of atelectasis and consolidation in neonatal chest radiographs.

BACKGROUND: Radiology is an essential part of neonatal intensive care. Interpretation of chest radiographs frequently contributes to respiratory management of neonates, but there has been little assessment of the consistency of this interpretation. OBJECTIVE: To assess the inter- and intra-observer variability for the reporting of atelectasis and/or consolidation in neonatal chest radiographs. MATERIALS AND METHODS: A total of 585 chest radiographs from the 220 babies ventilated in our nursery over a 2-year period were coded by two radiologists for generalised, lobar and segmental atelectasis and/or consolidation. Two months later one of the radiologists re-coded a random sample of these films (n = 117, 20 %). Agreement was assessed by the kappa statistic and by proportions of agreement for normality and abnormality. RESULTS: The reported incidence of focal atelectasis was low (5-6 %). Focal changes of any nature were found in 21-26 % of films. Inter-observer agreement was fair to moderate (kappa = 0.25-0.44). Intra-observer agreement was mostly moderate to good (kappa = 0.38-0.66). CONCLUSION: The poor inter-observer agreement for the diagnosis of pulmonary parenchymal abnormalities on chest radiographs of neonates receiving intensive care suggests that abnormalities should be described rather than diagnoses given or that a list of differential diagnoses be offered. When research involves radiographic interpretation, the potential lack of consistency in reporting abnormalities must be borne in mind.

Gestational Age↗
PubMed1999

Altered force-frequency relation in hypertrophic obstructive cardiomyopathy.

The present study was designed to test the hypothesis that in hypertrophied myocardium of patients with hypertrophic obstructive cardiomyopathy (HOCM) a reduced contractile reserve provided by frequency dependent potentiation of force of contraction contributes to the myocardial dysfunction. Myectomy was performed in 8 HOCM patients with normal systolic left ventricular function at rest. Nonfailing myocardium from the hearts of three multiorgan donors was investigated for comparison. In thin myocardial strips we measured the inotropic effects of different stimulation frequencies (0.5-3.0 Hz) at different extracellular Ca2+ concentrations (1.8-16.2 mmol/l). At 1.8 mmol/l extracellular Ca2+ concentration, increasing stimulation rates had no positive inotropic effect in HOCM myocardium, whereas in nonfailing myocardium force of contraction increased up to 3 Hz. Increasing extracellular Ca2+ concentrations induced a positive force-frequency relation in HOCM with a maximum at 5.4 mmol/l Ca2+. A further increase to 16.2 mmol/l Ca2+ resulted in a negative force-frequency relation in these specimens. The time to peak tension and the time to relaxation decreased at increasing stimulation frequencies at all Ca2+ concentrations investigated. In conclusion, in hypertrophied myocardium of HOCM patients increasing stimulation frequencies failed to have a positive inotropic effect at physiological extracellular Ca2+ concentrations. The induction of a positive force-frequency relation by higher Ca2+ concentrations suggests that an abnormal cellular Ca2+ handling may play an important pathophysiological role.

Calcium↗
PubMed1999

Calcium-sensitivity of the SR calcium release channel in failing and nonfailing human myocardium.

BACKGROUND: Altered Ca2+ metabolism of the sarcoplasmic reticulum results in changes of the contractile behavior in failing human myocardium. The ryanodine-sensitive Ca2+ release channel of the sarcoplasmic reticulum plays a key role in the intracellular Ca2+ handling in cardiac myocytes. Recently, we showed that the density of 3H-ryanodine binding sites which correspond to the SR Ca2+ release channel in human myocardial homogenates is unchanged in failing human myocardium. However, the sensitivity of the channel towards Ca2+, which acts as the trigger signal of channel activation and thereby initiates contraction, has not yet been investigated in failing and nonfailing myocardium. METHODS: Homogenates (100 micrograms protein) from hearts with dilated (DCM, n = 10) or ischemic (ICM, n = 9) cardiomyopathy were incubated with a saturating concentration of 3H-ryanodine (12 nM) in the presence of different Ca2+ concentrations ranging from 1 nM to 10 mM. For comparison, myocardium of 8 nonfailing hearts which could not be transplanted for technical reasons was investigated. Non-specific binding was determined in the presence of a high concentration (10 microM) of unlabeled ryanodine. RESULTS: 3H-ryanodine binding to the Ca2+ release channel showed a bell-shaped pattern with an increase in specific binding at submicromolar Ca2+ concentrations and a decrease at higher Ca2+ concentrations than 0.5 mM, whereas nonspecific binding was not influenced by different Ca2+ concentrations. In nonfailing myocardium, maximal 3H-ryanodine binding (Bmax) was 85.2 +/- 3.1 fmol/mg protein and half-maximal binding was reached at a free Ca2+ concentration of 0.25 (0.22-0.30) microM (EC50). Neither EC50 values nor maximal specific 3H-ryanodine binding differed between nonfailing and failing myocardium of both etiologies. EC50 values were 0.24 (0.23-0.26) microM (DCM, n = 10) or 0.28 (0.25-0.31) microM (ICM, n = 9), respectively. Caffeine (2 mM) and the ATP-analogon AMP-PCP (1 mM) led to a shift towards lower Ca2+ concentrations consistent with an activation of the channel by these compounds, whereas Mg2+ (0.7 mM) shifted the Ca(2+)-dependence of 3H-ryanodine binding towards higher Ca2+ concentrations indicating inhibition of channel opening. After activation of the Ca2+ release channel by caffeine or AMP-PCP as well as after the inhibition with Mg2+ EC50 values were the same in failing and nonfailing myocardium. CONCLUSION: Caffeine and AMP-PCP sensitize, whereas Mg2+ desensitizes the myocardial Ca2+ release channel to Ca2+. The determination of Ca(2+)-dependent 3H-ryanodine binding to the human myocardial Ca2+ release channel is a useful tool to investigate its open probability. Furthermore, the Ca(2+)-sensitivity and the pharmacological behavior of the human SR Ca2+ release channel are similar in failing and nonfailing myocardium.

Calcium↗
PubMed1999

Surgical therapy of fulminant pulmonary embolism: early and late results.

BACKGROUND: Pulmonary embolectomy remains the only option for patients with fulminant pulmonary embolism and failure or contraindication of thrombolysis even today. Increasing prevalence of heparin-induced thrombocytopenia type II (HIT) adds a new significant problem, which was investigated in a retrospective study. METHODS: Between 1/1979 and 1/1998 41 patients (21 male; age: 51.1 +/- 14.8 years) with fulminant pulmonary embolism underwent pulmonary embolectomy under cardiopulmonary bypass: group I (1979-89): 31 patients; group II (1990-98): 10 patients. Group II included only patients who did not meet the criteria for acute thrombolysis, in 4 patients a HIT was preoperatively assured. All patients were in strongly compromised hemodynamic condition (33/41 high-dose catecholamines, 24/41 mechanical ventilation, 14/41 preoperative cardiopulmonary resuscitation). RESULTS: Perioperative mortality was 29% (group I: 9/31; group II: 3/10; n.s.) Preoperative resuscitation was the only predictive factor (with resuscitation: 9/14; without resuscitation: 3/27; p < 0.001). Severe but not fatal complications occurred in 11 patients: they fully recovered following treatment. Follow-up was completed to 93% (281 patient-years; mean: 10.6 years) and discovered 5 late deaths (late mortality: 1.7%/patient-year; 1 patient: bleeding due to anticoagulation; 4 patients: not related to operation). 26/28 (93%) patients were in NYHA functional class I or II. No recurrent pulmonary embolism or late clinical symptoms related to embolectomy were observed. There was no difference between group I and group II (including the 4 patients with HIT) regarding perioperative mortality, complication, and late results. CONCLUSIONS: Pulmonary embolectomy on cardiopulmonary bypass remains an adequate therapy in patients with failure of or contraindication to thrombolysis, and HIT is not a contraindication.

Acute Disease↗
PubMed1999

TGFbeta-induced growth inhibition involves cell cycle inhibitor p21 and pRb independent from p15 expression.

It is generally assumed that TGFbeta induces cell cycle arrest through the cooperative action of cell cycle inhibitors p15, p27 and p21. Here, we found that several pancreatic carcinoma cell lines exert TGFbeta-induced negative growth control in spite of the loss of p15 and p16 expression. In these cell lines, TGFbeta-induced growth control correlates with the upregulation of the p21 protein and active pRb expression. Conversely, cells without p21 and/or pRb expression are resistant to TGFbeta -induced growth inhibition. Moreover, overexpression of p21 in the p21-deficient cell line Panc Tu1 leads to growth arrest. Thus, TGFbeta-induced growth control correlates with p21 expression and pRb status independent of p15 and/or p16 expression.

Cell Cycle Proteins↗
PubMed1999

Intensified treatment and education of type 1 diabetes as clinical routine. A nationwide quality-circle experience in Germany. ASD (the Working Group on Structured Diabetes Therapy of the German Diabetes Association).

This contribution describes the nationwide implementation of an intensive treatment and education program for type 1 diabetic patients in the clinical routine of the German health care system. Based on the formation of a working group (Arbeitsgemeinschaft Strukturierte Diabetestherapie [ASD]) of presently 57 general internal medicine departments, mainly from secondary and tertiary care levels in city and country hospitals throughout the country, a peer-review quality circle was formed as an official working group of the German Diabetes Association. The participating institutions performed a structured program of intensive treatment and education in all type 1 diabetic patients referred to them on a routine basis. The program includes multiple daily insulin injections or continuous subcutaneous insulin infusion, several times daily blood glucose self-monitoring and self-adaptation of insulin dosages and other aspects of treatment by the patients, and a far-reaching liberalization of the nutrition regimen. The group has attempted to document and to improve the quality of the structure and process of type 1 diabetes care in its participating institutions by a system of peer supervision. Furthermore, all member institutions volunteered to collect outcome data based on systematic 1-1.3 years' follow-up examinations of consecutive type 1 diabetic patients. For the 1997 evaluation of 1,103 type 1 diabetic patients, significant decreases of GHb levels and of incidence rates of severe hypoglycemia (from 0.35 to 0.16 cases per patient-year) and ketoacidosis (from 0.08 to 0.02 cases per patient-year) are presented. The ASD quality circle represents a model to improve principal aspects of type 1 diabetes care on a nationwide basis.

Cohort Studies↗
PubMed1998

Human pancreatic adenocarcinomas express Fas and Fas ligand yet are resistant to Fas-mediated apoptosis.

The Fas system, comprising the Fas receptor (Fas, CD95, APO-1) and its ligand, Fas ligand (FasL), is a central mediator of programmed cell death in various physiological and pathological processes. Recent evidence indicated that tumor cells can exploit this system to their benefit in the dialogue with the host immune system. We have shown that all human pancreatic adenocarcinoma cell lines tested by fluorescence-activated cell sorting analysis (6 of 6) and immunocytochemistry (12 of 12) were positive for Fas expression, as were normal and malignant duct cells in pancreatic tissue sections. However, despite Fas expression, pancreatic tumor cells have become largely resistant toward recombinant FasL- or anti-APO-1 agonistic antibody-induced apoptosis. This resistance correlated with high levels in pancreatic tumor cells of mRNA for FAP-1, a Fas-associated phosphatase that can block the apoptotic function of Fas. Using a variety of methodological approaches, we also present evidence for the production of FasL by pancreatic tumor cells because 6 of 6 pancreatic tumor cell lines were found to contain FasL mRNA as well as the Mr 40,000 and Mr 26,000 forms of the FasL protein. Likewise, pancreatic tissue revealed FasL-specific immunostaining in pancreatic tumor cells but not in the surrounding stroma. In coculture experiments, pancreatic tumor cells displayed a cytotoxic effect toward the Fas-sensitive Jurkat T-cell line, which could be inhibited by a FasL-specific neutralizing antibody. Together, these results support the recently proposed "counterattack model" for local deletion of tumor-reactive T-cells by tumor cell-derived FasL.

Adenocarcinoma↗
PubMed1998

Specific inhibition of phorbol ester-stimulated phospholipase D by Clostridium sordellii lethal toxin and Clostridium difficile toxin B-1470 in HEK-293 cells. Restoration by Ral GTPases.

Activation of m3 muscarinic acetylcholine receptor (mAChR), stably expressed in human embryonic kidney (HEK)-293 cells, leads to phospholipase D (PLD) stimulation, a process apparently involving Rho GTPases, as shown by studies with Clostridium botulinum C3 exoenzyme and Clostridium difficile toxin B (TcdB). Direct activation of protein kinase C (PKC) by phorbol esters, such as phorbol 12-myristate 13-acetate (PMA), also induces PLD stimulation, which is additive to the mAChR action and which is only poorly sensitive to inactivation of Rho proteins by TcdB. To study whether Ras-like GTPases are involved in PLD regulation, we studied the effects of the TcdB variant TcdB-1470 and Clostridium sordellii lethal toxin (TcsL), known to inactivate Rac and some members of the Ras protein family, on PLD activities. TcdB-1470 and TcsL did not affect basal PLD activity and PLD stimulation by mAChR or direct G protein activation. In contrast, PMA-induced PLD stimulation was inhibited by TcdB-1470 and TcsL in a time- and concentration-dependent manner, without alteration in immunologically detectable PKC isozyme levels. In membranes of HEK-293 cells pretreated with TcdB-1470 or TcsL, basal and stable GTP analog-stimulated PLD activities measured with exogenous phosphatidylcholine, in the presence or absence of phosphatidylinositol 4,5-bisphosphate, were not altered. In contrast, pretreatment with TcdB-1470 and TcsL, but not TcdB, strongly reduced PMA-stimulated PLD activity. The addition of recombinant Rac1, serving as glucosylation substrate for TcdB, TcsL, and TcdB-1470, did not restore PLD stimulation by PMA. Furthermore, PMA-stimulated PLD activity, suppressed by prior treatment with TcdB-1470 or TcsL, was not rescued by the addition of recombinant Ras (RasG12V) or Rap proteins, acting as glucosylation substrates for TcsL only (Ras) or TcdB-1470 and TcsL (Rap). In contrast, the addition of recombinant Ral proteins (RalA and RalB), glucosylation substrates for TscL and TcdB-1470, but not for TcdB, to membranes of TcdB-1470- or TcsL-treated cells fully restored PLD stimulation by PMA without altering the strict MgATP dependence of PMA-induced PLD stimulation. RalA-mediated restoration of PMA-stimulated PLD activity in membranes of TcsL-treated cells was not enhanced by coaddition of RasG12V. In conclusion, the data presented indicate that TcdB-1470 and TcsL selectively interfere with phorbol ester stimulation of PLD and suggest an essential role of Ral proteins in PKC signaling to PLD in HEK-293 cells.

3T3 Cells↗
PubMed1998

Fulminanting necrotising enterocolitis: outcome and prognostic factors.

In order to determine the outcome of infants with fulminant necrotising entercolitis (NEC), the records of 128 surgically-treated neonates were reviewed. Fifty-two were found to have severe, rapid-onset disease. The 30-day survival was determined and correlated with birth weight, gestational age, laboratory and radiological findings, and extent of disease. Seven patients did not respond to resuscitative measures and were treated by percutaneous drainage with a uniformly fatal outcome. For patients who could be made fit for surgery, the only absolute predictor of survival was extent of disease. Pan-necrosis occurred in 19 patients and all of these died. Conversely, patients who had resectable disease had a 30-day survival of 61%. Pan-necrosis could not be determined preoperatively by radiological findings. Patients with severe, rapid-onset NEC and evidence of gangrene who respond to resuscitation should have active surgical management, as approximately one-half of them have resectable disease and a reasonable short-term outcome may be expected. Patients who do not respond to resuscitative measures and those with a surgical finding of pan-necrosis had a uniformly fatal outcome in this study, and if resources are limited, it is reasonable to withdraw active management in this group of patients.

Analysis of Variance↗
PubMed1998

The role of neonatal chest physiotherapy in preventing postextubation atelectasis.

We retrospectively assessed atelectasis in 297 postextubation radiographs from 220 babies who underwent ventilation over a 2-year period. All 95 babies in the first year received peri-extubation chest physiotherapy; none of the 125 babies in the second year received chest physiotherapy. There was no difference in the incidence of postextubation atelectasis between the two groups.

Female↗
PubMed1998

Prognostic factors in patients with endocrine tumours of the duodenopancreatic area.

BACKGROUND: The development of endocrine tumours of the duodenopancreatic area (ETDP) is thought to be slow, but their natural history is not well known. The aim of this study was to determine the factors that influence survival of patients with ETDP. PATIENTS/METHODS: Eighty two patients with ETDP (44 non-functioning tumours, 23 gastrinomas, seven calcitonin-secreting tumours, four glucagonomas, three insulinomas, one somatostatinoma) followed from October 1991 to June 1997 were included in the study. The following factors were investigated: primary tumour size, hormonal clinical syndrome, liver metastases, lymph node metastases, extranodular/extrahepatic metastases, progression of liver metastases, local invasion, complete resection of the primary tumour, and degree of tumoral differentiation. The prognostic significance of these factors was investigated by uni- and multi-variate analysis. RESULTS: Twenty eight patients (34%) died within a median of 17 months (range 1-110) from diagnosis. Liver metastases (p = 0.001), lymph node metastases (p = 0.001), progression of liver metastases (p < 0.00001), lack of complete resection of the primary tumour (p = 0.001), extranodular/extrahepatic metastases (p = 0.001), local invasion (p = 0.001), primary tumour size > or = 3 cm (p = 0.001), non-functioning tumours (p = 0.02), and poor tumoral differentiation (p = 0.006) were associated with an unfavourable outcome by univariate analysis. Multivariate analysis identified only liver metastases (risk ratio (RR) = 8.3; p < 0.0001), poor tumoral cell differentiation (RR = 8.1; p = 0.0001), and lack of complete resection of the primary tumour (RR = 4.8; p = 0.0007) as independent risk factors. Five year survival rates were 40 and 100% in patients with and without liver metastases, 85 and 42% in patients with and without complete resection of primary tumour, and 17 and 71% in patients with poor and good tumour cell differentiation respectively. CONCLUSION: Liver metastases are a major prognostic factor in patients with ETDP. Progression of liver metastases is also an important factor which must be taken into account when deciding on the therapeutic approach. The only other independent prognostic factors are tumoral cell differentiation and complete resection of the primary tumour.

Adenoma, Islet Cell↗
PubMed1998

Mechanisms and clinical implications of apoptosis.

The importance of controlled cell death in a variety of diseases has now been recognized and apoptosis research has become one of the fastest growing fields in medical science. Scientific advances are rapidly being applied to clinical practice.

Annexin A5↗
PubMed1998

[CD95 resistance and Fas ligand synthesis as mechanism of defense by immunocompetent cells in pancreatic tumors].

Tumor cells have developed a variety of passive and active strategies to escape surveillance by the host immune system. In the present work we have investigated the role of the CD95 system comprising the CD95 receptor (Fas, CD95, APO-1) and its ligand Fas-ligand (FasL) in the dialogue between pancreatic tumor cells and tumor-reactive/cytotoxic T cells. Despite abundant expression of CD95 in pancreatic tumor cells from tumor tissue and in various pancreatic tumor cell lines, we found all (6/6) pancreatic tumor cell lines to be largely resistant to CD95-mediated apoptosis when compared to the CD95-sensitive T cell line Jurkat. Intriguingly, all pancreatic tumor cell lines tested synthesized FasL. In coculture experiments it was shown that two were capable of increasing Jurkat cell apoptosis in a FasL-dependent manner. These data suggest that pancreatic tumor cells have exploited the CD95 system to their benefit in order to protect themselves against tumor-reactive T cells.

Cell Survival↗