| 1. |
- Schmidt, Marcus, et al.
(author)
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A comprehensive analysis of human gene expression profiles identifies stromal immunoglobulin kappa C as a compatible prognostic marker in human solid tumors
- 2012
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In: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 18:9, s. 2695-2703
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Journal article (peer-reviewed)abstract
- PURPOSE:Although the central role of the immune system for tumor prognosis is generally accepted a single robust marker is not yet available.EXPERIMENTAL DESIGN:Based on ROC (receiver operating characteristic) analyses robust markers were identified from a 60 gene B-cell derived metagene and analyzed in gene expression profiles of 1810 breast cancer, 1056 non-small cell lung cancer, 513 colorectal and 426 ovarian cancer patients. Protein and RNA levels were examined in paraffin embedded tissue of 330 breast cancer patients. The cell types were identified using immunohistochemical co-staining and confocal fluorescence microscopy.RESULTS:We identified immunoglobulin kappa C (IGKC) which as a single marker is similarly predictive and prognostic as the entire B-cell metagene. IGKC was consistently associated with metastasis free survival across different molecular subtypes in node-negative breast cancer (n=965) and predicted response to anthracycline-based neoadjuvant chemotherapy (n=845) [P less than 0.001]. In addition, IGKC gene expression was prognostic in non-small cell lung cancer and colorectal cancer. No association was observed in ovarian cancer. IGKC protein expression was significantly associated with survival in paraffin embedded tissues of 330 breast cancer patients. Tumor infiltrating plasma cells were identified as the source of IGKC expressionCONCLUSION:Our findings provide IGKC as a novel diagnostic marker for risk stratification in human cancer and support concepts to exploit the humoral immune response for anti-cancer therapy. It could be validated in several independent cohorts and performed similarly well in RNA from fresh frozen as well as from paraffin tissue and on protein level by immunostaining.
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| 2. |
- Bergemann, Christian A., et al.
(author)
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Constraining long-term fault activity in the brittle domain through in situ dating of hydrothermal monazite
- 2018
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In: Terra Nova. - : Wiley. - 0954-4879. ; 30:6, s. 440-446
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Journal article (peer-reviewed)abstract
- Abstract SIMS Th–Pb dating of hydrothermal fissure-vein monazite-(Ce) has the unique potential to date multiple tectonic events under low-grade metamorphic brittle/ductile conditions over large time frames. Monazites-(Ce) from brittle fault systems in the Eastern Alps allow us to constrain their Cretaceous activity over 20 Ma within single crystals, recording all major tectonic events. Eo-Alpine formation of the fluid-filled fissure-veins occurred 90 Ma ago at 352 ± 19°C and 342 ± 42 MPa. This corresponds to peak conditions during regional metamorphism of the Cretaceous collisional nappe stacking. Several stages of dissolution–reprecipitation/recrystallization record fault activity between 84 and 70 Ma. Corresponding fluid inclusions indicate conditions of 229 ± 10°C and 143 ± 20 MPa. This correlates with the formation of sedimentary basins during post-orogenic extension associated with strike-slip movements. The results strengthen the hypothesis that many large fault systems in the Eastern Alps developed during the Cretaceous orogeny and became reactivated during Neogene Alpine tectonics.
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| 3. |
- Kleef, Ralf, et al.
(author)
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Complete Clinical Remission of Stage IV Triple-Negative Breast Cancer Lung Metastasis Administering Low-Dose Immune Checkpoint Blockade in Combination With Hyperthermia and Interleukin-2
- 2018
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In: Integrative Cancer Therapies. - : SAGE Publications. - 1534-7354 .- 1552-695X. ; 17:4, s. 1297-1303
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Journal article (peer-reviewed)abstract
- The prognosis of triple-negative breast cancer with metastases after chemotherapy remains dismal. We report the case of a 50-year-old female with first disease recurrence at the axillary lymph node and, later on, bilateral pulmonary metastases with severe shortness of breath. The patient received low-dose immune checkpoint blockade (concurrent nivolumab and ipilimumab) weekly over 3 weeks with regional hyperthermia 3 times a week, followed by systemic fever-range hyperthermia induced by interleukin-2 for 5 days. She went into complete remission of her pulmonary metastases with transient WHO I-II diarrhea and skin rash. The patient remained alive for 27 months after the start of treatment, with recurrence of metastases as a sternal mass, and up to 3 cm pleural metastases. This exceptional response should instigate further research efforts with this protocol, which consists only of approved drugs and treatments.
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