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1.  Malignant Triton Tumor of the Sciatic Nerve as a Secondary Malignancy after Extended Field Radiotherapy and Chemotherapy of Hodgkin's Disease 
Case Reports in Oncology  2014;7(1):239-245.
Late effects of therapy for Hodgkin's disease include secondary malignancies like leukemia, lymphoma or solid tumors developing after long periods of latency. Ionizing radiation often causes the last group. The highest risks have been described for induced breast and lung cancers. We are the first to report a malignant triton tumor (MTT) as a secondary malignancy after radiotherapy and chemotherapy for Hodgkin's lymphoma. MTT is a very rare subtype of malignant peripheral nerve sheath tumors with rhabdomyoblastic differentiation and an aggressive course of disease.
PMCID: PMC3999579  PMID: 24803902
Triton tumor; Radiotherapy; Second malignancy; Hodgkin's disease
2.  Axillary Irradiation as an Imperative Alternative to Axillary Dissection in Clinically Lymph Node-Negative but Sentinel Node-Positive Breast Cancer Patients? 
Breast Care  2011;6(5):353-358.
At the moment, positive sentinel lymph node dissection (SLND) of the axilla is followed by axillary lymph node dissection (ALND) as standard of care. Recent data proves that omitting ALND after positive SLND in clinically lymph node-negative early stage breast cancer patients is feasible with low recurrence rates. The well known effect of radiotherapy to destroy occult tumor cells highly contributes to these results as a large extent of level I and II lymph nodes are unavoidably included in standard tangential radiation treatment fields. Reviewing the up to date published data on axillary lymph node treatment with radiotherapy, we hypothesize that full dosage coverage of level I and II of the axilla in early stage breast cancer will improve outcome and should be further evaluated.
PMCID: PMC3357141  PMID: 22619644
Adjuvant treatment; Breast cancer; Curative radiotherapy; Sentinel lymph node
3.  Fludarabine combined with radiotherapy in patients with locally advanced NSCLC lung carcinoma: a phase I study 
Background and purpose
Fludarabine is an adenine nucleoside analogue that has significant activity in hematological malignancies and has shown promising activity in combination with radiation in preclinical solid tumor models. We designed a phase I trial exploring concurrent fludarabine and radiotherapy in patients with advanced non-small cell lung cancer (NSCLC) to determine the maximum tolerated dose (MTD) of fludarabine given with concurrent irradiation.
Materials and methods
Thirteen patients with stage IIIB NSCLC received thoracic irradiation of 60 Gy. Fludarabine was administered during the 5th and 6th week of radiotherapy. Doses started at 10 mg/m2 per day and increased by steps of 3 mg/m2 per day.
At a daily dose of 16 mg/m2, one out of six patients developed a grade 4 leukopenia, and one a grad 3 pneumonitis. Further grade III toxicity was not observed. The dose of 13 mg/m2 was identified as the MTD. All patients developed a fludarabine dose-dependent lymphocytopenia.
Fludarabine can be safely administered concurrently with radiation at a daily dose of 13 mg/m2 during the final 2 weeks of radiotherapy. Further prospective clinical studies are required to establish the potential role of concurrent fludarabine and radiotherapy in the treatment of locally advanced inoperable NSCLC.
PMCID: PMC3605492  PMID: 22402597
Fludarabine; NSCLC; Nucleoside analogue; Concurrent fludarabine and radiotherapy; Radiotherapy, phase I study; Radiochemotherapy in stage III NSCLC, locally advanced inoperable NSCLC
4.  Thymic alterations in mice deficient for the SNARE protein VAMP8/endobrevin 
Cell and Tissue Research  2008;334(2):227-242.
SNARE (soluble-N-ethylmaleimide-sensitive factor attachment receptor) proteins mediate the recognition and fusion of transport vesicles in eukaryotic cells. The SNARE protein VAMP8 (also called endobrevin) is involved in the fusion of late endosomes and in some pathways of regulated exocytosis. In a subset of mice deficient for the SNARE protein VAMP8, a severe alteration of the thymus and in T lymphocyte development was observed and characterized. The size of the thymus and the number of thymocytes were dramatically reduced compared with those in heterozygous littermates. Further, the compartmentalization into cortex and medulla and the organization of the thymus epithelium were disturbed. The numbers of all thymocyte subpopulations were reduced, with the CD4 and CD8 double-positive thymocytes being most severely affected. The proportion of proliferating thymocytes was reduced, and the staining of apoptotic cells in situ and ex vivo indicated an increased number of apoptotic cells. Isolated thymocytes of Vamp8−/− mice were more susceptible to various apoptotic stimuli including glucocorticoids, FAS receptor, and CD3/CD28-mediated signaling in vitro, even before an increased number of apoptotic cells was detectable in situ. However, bone marrow of phenotypically affected Vamp8−/− mice was readily able to repopulate immunodeficient hosts suggesting that the SNARE protein VAMP8 has a specific function in the thymic stroma affecting the proliferation and apoptosis of T lymphocytes during maturation in the thymus.
PMCID: PMC3085783  PMID: 18923845
SNARE; T-cell; Thymus; Apoptosis; Knockout mouse
5.  No supra-additive effects of goserelin and radiotherapy on clonogenic survival of prostate carcinoma cells in vitro 
Oncological results of radiotherapy for locally advanced prostate cancer (PC) are significantly improved by simultaneous application of LHRH analoga (e.g. goserelin). As 85% of PC express LHRH receptors, we investigated the interaction of goserelin incubation with radiotherapy under androgen-deprived conditions in vitro.
LNCaP and PC-3 cells were stained for LHRH receptors. Downstream the LHRH receptor, changes in protein expression of c-fos, phosphorylated p38 and phosphorylated ERK1/2 were analyzed by means of Western blotting after incubation with goserelin and irradiation with 4 Gy. Both cell lines were incubated with different concentrations of goserelin in hormone-free medium. 12 h later cells were irradiated (0 – 4 Gy) and after 12 h goserelin was withdrawn. Endpoints were clonogenic survival and cell viability (12 h, 36 h and 60 h after irradiation).
Both tested cell lines expressed LHRH-receptors. Changes in protein expression demonstrated the functional activity of goserelin in the tested cell lines. Neither in LNCaP nor in PC-3 any significant effects of additional goserelin incubation on clonogenic survival or cell viability for all tested concentrations in comparison to radiation alone were seen.
The clinically observed increase in tumor control after combination of goserelin with radiotherapy in PC cannot be attributed to an increase in radiosensitivity of PC cells by goserelin in vitro.
PMCID: PMC2034383  PMID: 17718927

Results 1-5 (5)