Biomedical subjects

Joachim Drevs

Publications and source records attributed to Joachim Drevs.

22 records · Page 2Linked to original sources

PubMed2002

Soluble Tie-2 receptor levels independently predict locoregional recurrence in head and neck squamous cell carcinoma.

BACKGROUND: This study assessed two circulating angiogenic receptors as tumor markers in patients with head and neck squamous cell carcinoma (HNSCC): soluble vascular endothelial factor growth receptor-1 (sVEGFR1) and soluble Tie-2 receptor (sTie2R). METHODS: Sera from 79 newly presenting patients with HNSCC and from 22 controls were assayed using sandwich ELISA. Median follow-up was 35 months after curative treatment. Analysis was carried out to compare levels between HNSCC patients and controls and to ascertain relationships with clinicopathologic and outcome variables. RESULTS: Soluble VEGFR1 was not elevated in the HNSCC group and was not related to any of the clinicopathologic or outcome variables. Soluble Tie2R was also not elevated in HNSCC patients or related to the clinicopathologic variables but was associated with locoregional recurrence (p =.009). Raised sTie2R (>64 ng/mL) independently predicted recurrence (p =.007) with a relative risk of 3.0 (95% CI, 1.7-5.0). CONCLUSIONS: Soluble Tie2R is an independent predictor of locoregional recurrence in HNSCC.

Adult↗

PubMedDate not supplied

Soluble markers for the detection of hypoxia under antiangiogenic treatment.

Antiangiogenic therapy is a promising new strategy to inhibit tumor growth and formation of metastases. VEGF (vascular endothelial growth factor) is known to be the most important proangiogenic factor, necessary for the development of new tumor vessels. Specific inhibitors of the VEGF receptor tyrosine kinases, like PTK787/ZK222584 (PTK/ZK), have shown antitumoral and antiangiogenic activity in several animal models. Ongoing early clinical trials with antiangiogenic compounds reveal the need for diagnostic methods to detect their biological activity. Pro-angiogenic growth factors like VEGF and bFGF (basic fibroblast growth factor), soluble variants of proangiogenic receptors like sFLT-1 and sTIE-2, as well as endothelial activation markers like sE-Selectin, can be measured in the serum and plasma of patients by the ELISA technique. They were detected in various malignant diseases to assess their use as surrogate markers in tumor angiogenesis. In different clinical Phase I trials with antiangiogenic compounds, these soluble markers were used to detect dose levels for biological activity. Soluble markers of tumor angiogenesis can be used as prognostic markers in various malignancies like colon cancer or multiple myeloma. Furthermore, they correlated with disease activity, prognosis and imaging techniques for the detection of vascular changes. In clinical Phase I trials with specific inhibitors of the VEGF receptor tyrosine kinases, VEGF serum levels increased in patients treated with higher doses, indicating increasing tumor hypoxia. Taking results from imaging techniques such as dynamic enhanced MRI into account, optimal doses for biological activity could be concluded. New biological treatment techniques will need new diagnostic methods to assess their specific biological activity in patients. Soluble markers and imaging techniques are useful tools for the detection of hypoxia under antiangiogenic treatment. Nevertheless, these techniques are still experimental. Therefore, further clinical evaluation is necessary.

Angiogenesis Inhibitors↗

PubMedDate not supplied

Antiangiogenic potency of FK866/K22.175, a new inhibitor of intracellular NAD biosynthesis, in murine renal cell carcinoma.

FK866/K22.175 (FK-866), developed as an anticancer agent, interferes with the NAD+ biosynthesis and therefore might have characteristics distinct from conventional chemotherapeutic agents. We investigated FK-866 in a murine renal cell carcinoma model (RENCA) to assess its antitumor, antimetastatic and antiangiogenic potency. FK-866 was administered twice daily on days 10 to 15 after intrarenal inoculation of RENCA cells in syngenic Balb/c mice at oral doses of 6, 10, 14 and 18 mg/kg to define the optimal dose related to toxicity. For efficacy studies, FK-866 was administered orally twice daily at doses of 6 and 10 mg/kg or twice daily at doses of 3 and 5 mg/kg on days 14 to 19 after tumor cell inoculation. Animals in the positive control group received 30 mg/kg TNP 470 subcutaneously on every other day beginning on day 1. On day 17, all animals were examined for blood flow in the left renal artery by color Doppler imaging (CDI). The animals were sacrificed on day 21 and analyzed for primary tumor weight and volume, number of metastases to the lung and abdominal lymph nodes and vessel density in tumor tissues. Doses of up to 6 mg/kg FK-866 were less toxic than treatment with TNP-470. Significant antitumor efficacy was observed for doses of > or = 10 mg/kg FK-866 only. In contrast, a significant decrease of vessel density in tumor tissues by up to 70% could be detected for all dose groups. Changes in blood flow in the tumor feeding renal artery could not be detected because of the profound strong tumor reduction. FK-866 has antitumoral and antimetastatic activity in RENCA mice. Furthermore, this is the first report to describe a strong antiangiogenic potency of FK-866.

Acrylamides↗

PubMedDate not supplied

Antiangiogenic potency of various chemotherapeutic drugs for metronomic chemotherapy.

From previous preclinical findings continuous low dose (metronomic) chemotherapy is thought to inhibit tumor angiogenesis. This suggests that activated endothelial cells may be more sensitive to chemotherapeutic drugs than tumor cells. Therefore, we assessed the IC50 for several relevant chemotherapeutic drugs in different endothelial and tumor cell lines to identify optimal compounds to be used for metronomic therapy in a murine renal cell carcinoma model. Adriamycin, idarubicin, 5-fluorouracil, paclitaxel and etoposide were chosen for our studies because of their oral availability in patients or previous reports on metronomic potential. IC50s were determined by BrdU cell growth assay after short time as well as long term exposure of the following cell lines: human endothelial cells (HdmVEC/HUVEC), human breast cancer (Mcf-7), melanoma (Skmel), liver cancer (Huh7/Alexander), lung cancer (A549/LXFL), colon cancer (Dld) and murine renal cell carcinoma (RENCA). In addition, FACS analysis was performed to determine the effect on cell cycle. In vivo, doses of 2x12 mg/kg, 2x1.2 mg/kg and 10x0.24 mg/kg adriamycin were applied to 12 RENCA mice each and antitumor as well as antiangiogenic effects were assessed 21 days after tumor cell application. Independent of the exposure time, all chemotherapeutic drugs were more active against the endothelial cell lines. IC50s were significantly lower in endothelial cells (4.02E-06 to 6.16E-14 M) as compared to tumor cells (7.44E-02 to 1.9E-11 M). Cell cycle analysis of all chemotherapeutic drugs revealed a G1-arrest in endothelial cells. Adriamycin applied in metronomic doses of 10x0.24 mg/kg showed significant antiangiogenic activity whereas, in contrast, the application of 2x12 mg/kg significantly increased the vessel density in primary tumors. In summary, all chemotherapeutic agents were more active against endothelial cells in comparison to tumor cells. The hypothesis of an antiangiogenic active metronomic therapy could be confirmed in vivo by the use of adriamycin in RENCA.

Angiogenesis Inhibitors↗