The borderline syndrome is one of the most severe disturbances of psychosomatic dermatology.Patients with borderline syndrome are situatedon the borderof psychosis, neurosis and personality disorders.The skin as a...The borderline syndrome is one of the most severe disturbances of psychosomatic dermatology.Patients with borderline syndrome are situatedon the borderof psychosis, neurosis and personality disorders.The skin as a borderline organ carries a symbolic role.The clinical picture includes artefactual skin diseases due to self-mutilation by conscious or unconscious cutting, and rubbing, scratching or para-artefactual manipulations of pre-existing dermatoses.Leading symptoms of the borderline syndrome are poor impulse control, emotional instability and poor ego strength with low frustration tolerance and unstable personal relationships.We present the case of a 38-year-old female patient with borderline syndrome suffering from para-artefactual skin diseases of the face and a massive hyperhidrosis of the hands and feet.Within 9 months she was treated in four acute psychiatric hospitals and by 12 psychiatrists and psychotherapists.Early and accurate diagnosis and high-quality, sophisticated long-term therapy are necessary.展开更多
To advance preclinical testing of novel targeted drugs in colorectal cancer (CRC) we established a panel of 133 mouse xenograft models from fresh tumor specimens of 239 patients with CRC of all four UICC stages. A sub...To advance preclinical testing of novel targeted drugs in colorectal cancer (CRC) we established a panel of 133 mouse xenograft models from fresh tumor specimens of 239 patients with CRC of all four UICC stages. A subgroup of 67 xenograft models was treated with cetuximab, bevacizumab and oxaliplatin as single agents. Mutation status of KRAS (G12, G13, A146T), BRAF (V600E) and PIK3CA (E542K, E545K, H1047R) was assessed in all xenografts by allelespecific real-time PCR. KRAS codon 61 was assessed by conventional sequencing. AREG and EREG expression levels were analyzed by real-time PCR expression assays. In the treatment experiment we observed response rates of 27% (18/67) for cetuximab, 3% (2/67) for bevacizumab, and 6% (4/67) for oxaliplatin. Classification based on KRAS, BRAF and PIK3CA mutation status identified 15 of the responders (sensitivity 83%, confidence interval at p = 0.05 (CI): 59% - 96%), and 38 nonresponders (specificity 78%, CI: 63% - 88%). If any mutation except in KRAS codon 13 were considered, the classifier reached sensitivity of 94% and specificity of 69%. We improved specificity of the classifiers to 90% and 86% respectively by adding AREG and EREG RNA expression thresholds retrospectively. In patient-derived xenograft models, we found a predictive classifier for response to cetuximab that is more accurate than established biomarkers. We confirmed its potential performance in primary human tumors. For patients, the classifier’s sensitivity promises increased response rates and its specificity limits unnecessary toxicity. Given the scope of our xenograft models across all UICC stages, this applies not only to mCRC but also to the adjuvant setting of earlier stages. The xenograft collection allows to mimic randomized phase II trials and to test novel drugs effectively as single agents or in combinations. It also enables the development of highly accurate companion diagnostics as demonstrated by us for cetuximab.展开更多
文摘The borderline syndrome is one of the most severe disturbances of psychosomatic dermatology.Patients with borderline syndrome are situatedon the borderof psychosis, neurosis and personality disorders.The skin as a borderline organ carries a symbolic role.The clinical picture includes artefactual skin diseases due to self-mutilation by conscious or unconscious cutting, and rubbing, scratching or para-artefactual manipulations of pre-existing dermatoses.Leading symptoms of the borderline syndrome are poor impulse control, emotional instability and poor ego strength with low frustration tolerance and unstable personal relationships.We present the case of a 38-year-old female patient with borderline syndrome suffering from para-artefactual skin diseases of the face and a massive hyperhidrosis of the hands and feet.Within 9 months she was treated in four acute psychiatric hospitals and by 12 psychiatrists and psychotherapists.Early and accurate diagnosis and high-quality, sophisticated long-term therapy are necessary.
文摘To advance preclinical testing of novel targeted drugs in colorectal cancer (CRC) we established a panel of 133 mouse xenograft models from fresh tumor specimens of 239 patients with CRC of all four UICC stages. A subgroup of 67 xenograft models was treated with cetuximab, bevacizumab and oxaliplatin as single agents. Mutation status of KRAS (G12, G13, A146T), BRAF (V600E) and PIK3CA (E542K, E545K, H1047R) was assessed in all xenografts by allelespecific real-time PCR. KRAS codon 61 was assessed by conventional sequencing. AREG and EREG expression levels were analyzed by real-time PCR expression assays. In the treatment experiment we observed response rates of 27% (18/67) for cetuximab, 3% (2/67) for bevacizumab, and 6% (4/67) for oxaliplatin. Classification based on KRAS, BRAF and PIK3CA mutation status identified 15 of the responders (sensitivity 83%, confidence interval at p = 0.05 (CI): 59% - 96%), and 38 nonresponders (specificity 78%, CI: 63% - 88%). If any mutation except in KRAS codon 13 were considered, the classifier reached sensitivity of 94% and specificity of 69%. We improved specificity of the classifiers to 90% and 86% respectively by adding AREG and EREG RNA expression thresholds retrospectively. In patient-derived xenograft models, we found a predictive classifier for response to cetuximab that is more accurate than established biomarkers. We confirmed its potential performance in primary human tumors. For patients, the classifier’s sensitivity promises increased response rates and its specificity limits unnecessary toxicity. Given the scope of our xenograft models across all UICC stages, this applies not only to mCRC but also to the adjuvant setting of earlier stages. The xenograft collection allows to mimic randomized phase II trials and to test novel drugs effectively as single agents or in combinations. It also enables the development of highly accurate companion diagnostics as demonstrated by us for cetuximab.
