Biomedical subjects

Christian Röder

Publications and source records attributed to Christian Röder.

6 recordsLinked to original sources

PubMed2005

Detection of tumor cell dissemination in pancreatic ductal carcinoma patients by CK 20 RT-PCR indicates poor survival.

PURPOSE: This prospective study evaluates the diagnostic potential of Cytokeratin 20 (CK 20) RT-PCR for the detection of disseminated tumor cells in bone marrow and blood of a large cohort of patients with ductal adenocarcinoma of the pancreas and the prognostic value on overall survival prediction. METHODS: Between 1994 and 2003, 172 patients (83 male, 89 female; 13-82 years) with pancreatic ductal adenocarcinoma underwent surgery. Bone marrow samples and venous blood were taken preoperatively and analyzed for disseminated tumor cells by nested CK 20 RT-PCR. RESULTS: Disseminated tumor cells were detected in 81 (47.1%) of the 172 patients in the bone marrow and/or the venous blood. Overall, in 45 of the 135 (33.3%) bone marrow samples and in 52 of the 154 (33.8%) blood samples, CK 20 positive cells were detected. Detection rates increased with the UICC-tumor stage. According to Kaplan-Meier, univariate survival analysis of all 172 patients (n = 78 R0-; n = 18 R1- and n = 5 R2-resected; n = 71 palliative surgery) showed a statistically significant relationship of overall survival to radicality of the operation (P < 0.0001), the UICC-stage of the tumors (P = 0.0011) and the detection of disseminated tumor cells in bone marrow and/or venous blood (P = 0.05). Patients with well- and moderately- differentiated tumors (G1 and G2) had a significantly longer survival (P = 0.045) than patients suffering from poorly differentiated tumors (G3). A positive CK 20 status in the bone marrow and/or blood within the group of patients with G1 and G2 tumors had a significantly negative prognostic impact on their survival (P = 0.046). CONCLUSIONS: Disseminated tumor cells can be detected in patients with pancreatic ductal adenocarcinoma by CK 20 RT-PCR. Detection rates are stage dependent, and survival analysis demonstrated statistically relevant data. From a clinical point of view, this finding is especially noteworthy for the group of well- and moderately-differentiated tumors.

Adenocarcinoma↗

PubMed2005

Spontaneous dissociation during functional MRI experiments.

It is assumed that the procedures of functional magnetic resonance imaging (fMRI) are able to provoke significant dissociative responses. Trait and state dissociation of 32 healthy subjects undergoing fMRI have been recorded. At least one-third of the subjects showed dissociative responses of very large effect size (d=4.10). The contributing causal factors for that dissociative response could not yet identified clearly. Considering the impact of dissociation on mental functions, we recommend controlling subjects undergoing fMRI studies for dissociative responses. Further studies on the actual phenomenological experience of subjects undergoing fMRI procedures are warranted.

Adult↗

PubMed2005

CD95 and TRAF2 promote invasiveness of pancreatic cancer cells.

Pancreatic adenocarcinoma represents a tumor type with extremely poor prognosis. High apoptosis resistance and a strong invasive and early metastatic potential contribute to its highly malignant phenotype. Here we identified the death receptor adaptor molecule TRAF2 as a key player in pancreatic cancer pathophysiology. Using immunohistochemistry and Western blot analysis we found TRAF2 overexpressed in 34 of 36 pancreatic tumor samples as well as in pancreatic tumor cell lines resistant to CD95-mediated apoptosis. The high TRAF2 protein level was not related to chromosomal changes, as monitored by FISH analysis. Instead, the NF-kappaB- and MEK-signaling pathways were involved. Introduction of a TRAF2 expression vector in CD95-sensitive Colo357 cells resulted in (i) resistance to CD95-induced apoptosis; (ii) increased constitutive NF-kappaB and AP-1 activity; and (iii) higher basal secretion of matrix metalloproteinases (MMPs), urokinase-type plasminogen activator (uPA), and IL-8, leading to increased invasiveness. High apoptosis resistance and uPA secretion could be reverted by TRAF2-specific siRNA. Stimulation of TRAF2-overexpressing cells with CD95 ligand led to induction of NF-kappaB and AP-1, enhanced IL-8- and uPA-secretion, and a further increased invasiveness. Thus, TRAF2 overexpression does not only block apoptosis induction by CD95 but also converts this death receptor into a mediator of invasiveness.

Adenocarcinoma↗

PubMed2004

Detection of occult tumor cells in lymph nodes from bladder cancer patients by MUC7 nested RT-PCR.

OBJECTIVE: Systemic progression is the prevalent form of bladder tumor recurrence after radical cystectomy. The detection of occult bladder tumor cells in histopathologically normal lymph nodes could be of prognostic value. We examined the possibility that mucin 7 (MUC7) RNA might reflect the presence of occult tumor cells in lymph nodes from bladder cancer patients. We used the polymerase chain reaction (RT-PCR), a highly sensitive assay, to monitor MUC7 RNA. METHODS: We collected 240 pelvic lymph nodes from 25 bladder cancer patients undergoing radical cystectomy. We also obtained 20 lymph nodes from patients with prostate cancer and interstitial cystitis to use as negative controls. Each lymph node was divided in two parts to provide tissue for both histopathological and PCR analysis. RESULTS: 166/240 lymph nodes from bladder cancer patients were usable for MUC7 RT-PCR. By conventional histopathology, six of these nodes contained metastases. MUC7 RT-PCR analysis was positive for five of the six histologically proven lymph node metastases. Histopathological reevaluation of the sixth node revealed tumor in an adjacent vein, not in the lymph node, itself. In contrast, 46/160 (29%) histologically classified normal lymph nodes (pN0) from 17 bladder cancer patients were positive for MUC7. All 20 lymph nodes from control patients were MUC7-negative. CONCLUSION: MUC7 RT-PCR is a specific and sensitive method for the detection of occult tumor cells in lymph nodes from bladder cancer patients. Long-term observation will be necessary to evaluate the clinical value of MUC7 as a prognostic indicator of lymph node metastasis and disease progression.

Aged↗

PubMed2003

PKCmu prevents CD95-mediated apoptosis and enhances proliferation in pancreatic tumour cells.

Loss of growth control and a marked resistance to apoptosis are considered major mechanisms driving tumour progression. Protein kinases C (PKC) have been shown to be important in the regulation of proliferation and apoptosis. In this report, we investigated the role of the PKC-like kinase PKCmu in the control of these processes in pancreatic adenocarcinoma cells. We demonstrate that in these cells, PKCmu expression strongly correlates with resistance to CD95-induced apoptosis. Inhibition of PKCmu with Goe6983 sensitized resistant cells to CD95-induced apoptosis. In CD95-sensitive Colo357 cells, forced overexpression of PKCmu strongly reduced CD95-mediated apoptosis, an effect that could be reversed by pretreatment with Goe6983. In addition, PKCmu overexpression led to a strongly enhanced cell growth and to a significant increase of telomerase activity. In an attempt to identify the signalling pathways affected by PKCmu, we identified the antiapoptotic proteins c-FLIPL and survivin to be strongly upregulated in PKCmu overexpressing cells. Immunohistochemical analysis of pancreatic tumour tissue of 48 patients and 10 normal pancreatic tissues revealed marked overexpression of PKCmu in tumours. In conclusion, we showed that PKCmu controls proliferative, as well as anti-apoptotic, signalling pathways and therefore plays an important role in acquiring the malignant phenotype of pancreatic tumours.

Adenocarcinoma↗

PubMed2002

Subcortical overactivation in untreated schizophrenic patients: a functional magnetic resonance image finger-tapping study.

Functional magnetic resonance imaging (fMRI) is a well established, non-invasive technique for mapping the working brain. Yet imaging of subcortical regions has proven to be difficult. We studied 40 subjects performing an unilateral self-paced finger-tapping task. Patients with schizophrenia according to DSM-IV treated with olanzapine (n =10) or haloperidol (n=10) were compared to healthy controls (n =10) and untreated patients (n=10). Brainvoyager software was used for data-analyzing. All subjects showed highly significant activation in the contralateral sensorimotor area, the supplementary motor area and the ipsilateral cerebellum. In every investigated subject contralateral subcortical regions were also significantly activated (P < 0.001). Activation in ipsilateral pallidum was significantly higher in untreated patients compared with the other groups indicating an increase in subcortical coactivation. In addition, significant correlations were revealed within groups. This study emphasizes the possibility of investigating subcortical brain activation in patients with schizophrenia. The results of the present study outline the importance of further fMRI studies to investigate interindividual activation differences under different conditions especially focusing on basal ganglia.

Adult↗