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Christiane Bruns

Publications and source records attributed to Christiane Bruns.

5 recordsLinked to original sources
PubMed2006

P60-c-src suppresses apoptosis through inhibition of caspase 8 activation in hepatoma cells, but not in primary hepatocytes.

BACKGROUND/AIMS: Failure to induce apoptosis triggered by members of the death receptor family has been described in hepatocellular carcinoma (HCC) and sensitization of malignant cells to pro-apoptotic molecules such as TRAIL has been proposed as an alternative cancer therapy. Limiting to this approach are the resistance of many tumor cells to TRAIL and safety concerns about the toxicity of TRAIL in normal hepatocytes. METHODS: We here explored the possibility that the protooncogene c-Src, known to be overexpressed in a variety of tumors, could be specifically responsible for the loss of response to receptor-mediated apoptosis. RESULTS: Cotreatment of several hepatoma cell lines with the Src inhibitor PP2 potently sensitized these cells to TRAIL and CD95, dramatically decreasing effective doses of TRAIL to as low as 1 ng/ml. Remarkably, Src-inhibition did not synergize with TRAIL signaling in primary hepatocytes. Specific siRNAs showed that the effect was due to blockade of p60(c-Src) and occurred through increased recruitment of caspase 8. CONCLUSIONS: We provide evidence that p60(c-Src) is an important and effective suppressor of receptor-mediated apoptosis in hepatoma cells but not in primary human hepatocytes. Inhibition of Src sensitizes tumor cells to apoptosis and decreases effective doses of TRAIL to therapeutic concentrations.

Apoptosis↗
PubMed2006

Chemoradiotherapy with gemcitabine and continuous 5-FU in patients with primary inoperable pancreatic cancer.

CONTEXT: Gemcitabine and 5-fluorouracil (5-FU) sensitize tumor cells to radiation. Furthermore, 5-FU enhances the cytotoxic effect of gemcitabine. OBJECTIVE: We report the efficacy and the toxicity of concurrent chemoradiation with gemcitabine and 5-FU in the treatment of patients with locally advanced, unresectable pancreatic cancer. PATIENTS: Thirty-two patients (20 men, 12 women; median age 69.9 years) with histologically proven advanced pancreatic carcinoma were included in the study. INTERVENTIONS: The patients received chemotherapy with gemcitabine 300 mg/m2 on days 1, 15, 29 and 5-FU as continuous infusion 350 mg/m2/day of radiation while concurrent radiation (45-50 Gy) was given to the tumor and regional lymph nodes (1.8-2.0 Gy/fraction on 5 days/week). Subsequent to chemoradiotherapy, the treatment was continued with an additional two cycles of gemcitabine (1,000 mg/m2) and cisplatin (50 mg/m2) applied on days 1 and 15 of a four-week cycle. MAIN OUTCOME MEASURES: Patient survival, time to progression, and toxicity of chemoradiation. Tumor responses (complete resolution; partial response; stable disease, and progressive disease) were also evaluated. RESULTS: After the completion of chemoradiotherapy, 2 patients (6.3%) achieved complete resolution and 18 patients (56.3%) a partial response, for an overall response rate of 62.5%. Twelve patients (37.5%) were considered resectable and 9 underwent laparotomy, 7 of whom had definitive pancreatic resection. Four patients had negative surgical margins. With a median follow-up of 49.7 months (95% CI: 48.6-60.8 months) after the completion of chemoradiation, distant metastasis occurred in 25 patients (78.1%) while local recurrence was seen only in 4 of 32 patients (12.5%). Median time to progression was 9.2 months (95% CI: 8.2-10.2 months). Median survival amounted to 13.6 months (95% CI: 12.7-14.6 months) for all patients while it was prolonged to 16.4 months (95% CI: 13.4-19.4 months) for those undergoing secondary resection. In addition, performance status proved to be another prognostic factor for overall survival. The main toxicity of chemoradiation included grade 3-4 leukopenia in 18 patients (56.3%) and thrombocytopenia in 8 patients (25.0%). Episodes of cholangitis were observed in 7 patients (21.9%). CONCLUSION: Gemcitabine and 5-FU can safely be combined with external beam radiation. This preoperative treatment approach is highly effective and appears to improve survival in patients with good performance status and in those who are eligible for a secondary resection.

Aged↗
PubMed2006

Combined chemoradiotherapy for isolated local recurrence after primary resection of pancreatic cancer.

CONTEXT: Primary resectability is expected in up to 20% of pancreatic cancer patients. While most patients relapse with distant metastases, approximately 30% of patients show isolated local recurrence without evidence of distant metastases. OBJECTIVE: The present analysis investigates the efficacy of chemoradiotherapy in this particular patient group. DESIGN: Retrospective study. PATIENTS: Eighteen consecutive pancreatic cancer patients presenting with isolated locoregional recurrence after surgical resection. The median interval between primary surgery and diagnosis of local recurrence was 10.4 months (range: 2.0-19.3 months). INTERVENTIONS: Patients received 3-D conformal radiation with 45 Gy in 25 fractions of 1.8 Gy/day. Simultaneous chemotherapy was employed either with continuous 5-FU infusion, partly in combination with gemcitabine, or with gemcitabine and cisplatin. Sequential chemotherapy with gemcitabine and cisplatin was given to some patients before and after the chemoradiotherapy. RESULTS: In 17 of the 18 patients included, radiotherapy was employed at the intended dose. While WHO grade 3-4 gastrointestinal toxicity was not reported, hematotoxicity was more pronounced. Grades 3 and 4 leukocytopenia occurred in 4 patients (22.2%) and 1 (5.6%) patient, respectively, and grades 3 and 4 thrombocytopenia occurred in 4 patients (22.2%) and 1 patient(5.6%), respectively. Six (37.5%) complete remissions, 6 (37.5%) partial remissions, and 4 (25.0%) stable diseases were noted in 16 evaluable patients. Median progression-free survival calculated from the start of the chemoradiotherapy was 14.7 months (range: 8.4-21.0 months) . Seven (28.9%) patients had another local relapse, while 11 (61.1%) patients developed distant metastases. Median overall survival from the start of the chemoradiotherapy was 17.5 months (95% CI: 15.6-19.4 months) and median survival from the initial diagnosis was 27.2 months (95% CI: 23.9-30.6 months). CONCLUSION: The data provide a first indication that chemoradiotherapy is feasible and may be an effective treatment option in those patients who present with local metastasis after primary surgery for pancreatic cancer.

Aged↗
PubMed2004

Vascular endothelial growth factor in colorectal cancer.

BACKGROUND: Angiogenesis plays an important role in colorectal cancer progression. Evidence from preclinical and clinical studies indicates that vascular endothelial growth factor (VEGF) is the predominant angiogenic factor in human colorectal cancer and is associated with formation of metastases and poor prognosis. Based on these results it was hypothesized that attacking one or more of the VEGF-mediated mechanisms may be promising in the treatment of colorectal cancer. AIMS. This article reviews the role of VEGF in colon cancer and summarizes recent advances in the treatment of colorectal cancer by anti-VEGF strategies.

Antineoplastic Agents↗