R. Mota

Gene expression of circulating tumour cells in breast cancer patients

BackgroundThe diagnostic tools to predict the prognosis in patients suffering from breast cancer (BC) need further improvements. New technological achievements like the gene profiling of circulating tumour cells (CTC) could help identify new prognostic markers in the clinical setting. Furthermore, gene expression patterns of CTC might provide important informations on the mechanisms of tumour cell metastasation.Materials and methodsWe performed realtime-PCR and multiplex-PCR analyses following immunomagnetic separation of CTC. Peripheral blood (PB) samples of 63 patients with breast cancer of various stages were analyzed and compared to a control group of 14 healthy individuals. After reverse-transcription, we performed multiplex PCR using primers for the genes ga733.3, muc-1 and c-erbB2. Mammaglobin1, spdef and c-erbB2 were analyzed applying realtime-PCR.Resultsga733.2 overexpression was found in 12.7% of breast cancer cases, muc-1 in 15.9%, mgb1 in 9.1% and spdef in 12.1%. In this study, c-erbB2 did not show any significant correlation to BC, possibly due to a highly ambient expression. Besides single gene analyses, gene profiles were additionally evaluated. Highly significant correlations to BC were found in single gene analyses of ga733.2 and muc-1 and in gene profile analyses of ga733.3*muc-1 and GA7 ga733.3*muc-1*mgb1*spdef.ConclusionOur study reveals that the single genes ga733.3, muc-1 and the gene profiles ga733.3*muc-1 and ga733.3*3muc-1*mgb1*spdef can serve as markers for the detection of CTC in BC. The multigene analyses found highly positive levels in BC patients. Our study indicates that not single gene analyses but subtle patterns of multiple genes lead to rising accuracy and low loss of specificity in detection of breast cancer cases.

Cystatin C - a fast and reliable biomarker for glomerular filtration rate in head and neck cancer patients.

Purpose:Determination of renal function is a prerequisite for planning therapy in cancer patients. Limitations of creatinine as marker for the glomerular filtration rate (GFR) led to the proposal of cystatin C as a more accurate biomarker especially in mild renal insufficiency or in patients with low muscle mass. We compared the accuracy of cystatin C- and creatinine-based equations to estimate GFR in head and neck cancer (HNC) patients receiving platinum-based radiochemotherapy.Patients and Methods:The study population consisted of 52 HNC patients (GFR range, 37–105 mL/min/1.73 m2 complemented by 17 patients with known renal insufficiency (GFR range, 10–60 mL/min/1.73 m2). Intraclass correlation coefficients were calculated between the reference method (51)Cr-EDTA clearance and estimated GFR by creatinine clearance and equations based on creatinine (Cockroft-Gault, modification of diet in renal disease (MDRD), Wright) or cystatin C (Larsson, Dade-Behring, Hoek). In addition, sensitivity and specificity to discriminate GFR > 60 mL/min/1.73 m2 were evaluated by receiver operating characteristic curve (ROC).Results:The highest correlation coefficients were found for the cystatin C-based estimates in comparison with creatinine-based estimates or creatinine clearance, even though Bland-Altman plots revealed GFR overestimation for all equations tested. The cystatin C-based Hoek formula exhibited the highest overall precision and accuracy. GFR of < 60 mL/min/1.73 m2 was assumed as a cut-off for chemotherapy. ROC analyses revealed the highest AUC to predict a GFR > 60 mL/min/1.73 m2 for the creatinine-based Wright formula, closely followed by the MDRD formula and cystatin C-based equations of Larsson, Dade-Behring, and Hoek.Conclusion:Cystatin C-based GFR estimates showed the overall strongest correlation to the reference method. Thus, we recommend cystatin C for GFR estimation in HNC patients as an alternative method to the estimated creatinine clearance in clinical practice.ZusammenfassungZielsetzung:Bei Tumorpatienten ist die exakte Bestimmung der Nierenfunktion eine wichtige Voraussetzung für die individuelle Therapieplanung. Die Aussagefähigkeit des Serumkreatinins als Marker der glomerulären Filtrationsrate (GFR) ist jedoch limitiert aufgrund seiner Abhängigkeit von der Muskelmasse sowie fehlendem Anstieg der Serumkonzentration bei einer GFR > 60 ml/ min/1,73 m2. Cystatin C wird als sensitiverer Parameter für das Vorliegen einer Niereninsuffizienz in den Frühstadien sowie bei Muskelschwachen Patienten diskutiert. In der vorliegenden Studie wurde die Präzision von Cystatin-C-basierten sowie Kreatinin-basierten Formeln zur Berechung der GFR in Kopf-Hals-Tumorpatienten verglichen.Patienten und Methodik:Die Studienkohorte bestand aus 52 Kopf-Hals-Tumorpatienten (GFR 37–105 mL/min/1,73 m2) sowie 17 Patienten mit bekannter Niereninsuffizienz Stadium 3–5 (GFR 10–60 mL/min/1,73 m2). Es wurde der Intra-Class-Correlation factor berechnet zwischen der Referenzmethode (51)Cr-EDTA-Clearance und der Kreatinin-Clearance, den Kreatinin-basierten Formeln (Cockroft-Gault, Modified Diet in Renal Disease, Wright) und den Cystatin-C-basierten Formeln (Larsson, Dade-Behring, Hoek) zur GFR-Berechnung. Zusätzlich ermittelten wir Sensitivität und Spezifität der verschiedenen Clearance-Bestimmungen zur Erkennung einer GFR > 60 ml/min/1,73 m2 mittels Receiver Operating Characteristic Curve (ROC).Ergebnisse:Die beste Korrelation zur Referenzmethode wurde für die Cystatin-C-basierten Formeln zur GFR-Bestimmung im Vergleich zu Kreatinin-basierten Formeln oder der Kreatinin-Clearance ermittelt. Jedoch zeigte der Bland-Altman-Plot, dass im Vergleich zur Referenzmethode alle Formeln – sowohl Cystatin-C- als auch Kreatinin-basiert – die Nierenfunktion überschätzen. Die höchste Genauigkeit und Präzision wurde bei der Hoek-Formel beobachtet. Da eine GFR < 60 ml/min/1,73 m2 häufig als Grenze angesehen wird zur Durchführung einer Chemotherapie, ermittelten wir die Präzision, mit der die verschiedenen GFR-Bestimmungen dies für den Einzelnen voraussagen konnten. Bei der ROC-Analyse zeigte die Kreatinin-basierte Formel nach Wright die höchste Area Under the Curve, dicht gefolgt von der Modified-Diet-in-Renal-Disease-Formel und den Cystatin-C-basierten Formeln nach Larsson, Dade-Behring und Hoek.Schlussfolgerung:Die Cystatin-C-basierten Formeln zur GFR-Berechnung zeigten insgesamt die beste Präzision und Korrelation zur Referenzmethode in Kopf-Hals-Tumorpatienten. Daher empfehlen wir Cystatin-C-basierte Formeln zur GFR-Berechnung im klinischen Alltag bei diesen Patienten.

Evaluation of the tissue toxicity of antiseptics by the hen's egg test on the chorioallantoic membrane (HETCAM)

BackgroundAntiseptics are frequently used for the prophylaxis and treatment of local infections of chronic wounds. Whereas local antiseptics in general have a positive effect on wound healing an uncritical use may impair wound healing due to toxic side effects.ObjectiveWe sought to assess the vascular irritation potential of different antiseptic solutions and ointments commonly used for short and long term application as a measure of tissue toxicity.MethodThe vascular irritation was evaluated by the hens egg test (HET) on the chorioallantoic membrane (CAM). The effects on the vessels of a mucous membrane were directly assessed by stereomicroscopic observation in vivo.ResultsSevere CAM irritation was observed after short-term applications of 1% octenidin-2HCl (Octeni sept™), 72% isopropanol (Cutasept™), 0.35% chloroxylenol (Dettol™) and 10% PVP-I ointment (Betaisodona™). Medium irritations were observed for 10% PVP-I solution (Betaisodona™), 3% lysosomal PVP-I ointment (Repithel™), 1.8% cadexomer-iodine ointment (Iodosorb™) and 1% cadexomer-iodine pellets (Iodosorb™). Finally, slight irritations were observed for 1% PVP-I solution (Betaisodona™), 0.1% polyhexanid plus betain (Prontosan™) and 1% silver-sulfadiazine ointment (Flammazine™), whereas 0.04% polyhexanid solution (Lavanid™), washings from sterile maggots of Lucilia sericata and filtrated enzymes from Clostridium histolyticum (Iruxol-N™) showed no effects of irritation. In the long-term approaches, no vascular irritations were found for polyhexanid, washings from Lucilia sericata and enzyme filtrations from Clostridium histolyticum.ConclusionThe vascular injuries caused by the studied antiseptics are an indirect indicator of their tissue toxicity. Strikingly, even therapeutic substances, which have been regarded as safe in their application for the treatment of chronic wounds in clinical studies, showed severe irritations on the CAM. We suggest that agents with no or low irritation potential on the CAM should be preferred in the clinical practice in order to obtain optimal results.

GENE EXPRESSION OF CIRCULATING TUMOUR CELLS AND ITS CORRELATION WITH TUMOUR STAGE IN BREAST CANCER PATIENTS

BackgroundBreast cancer (BC) represents one of the leading causes of cancer related deaths worldwide. New tools for diagnostic staging and therapeutic monitoring are needed to improve individualized therapies and improve clinical outcome. The analyses of circulating tumour cells may provide important prognostic information in the clinical setting.Materials and methodsCirculating tumour cells (CTC) of 63 BC patients were isolated from peripheral blood (PB) through immunomagnetic separation. Subsequently, RT-PCR or mPCR for the genes ga733.2, muc-1, c-erbB2, mgb-1, spdef and c-erbB2 were performed. Subsequently, expression data were correlated with the tumour stages. Fourteen healthy individuals served as controls.ResultsSignificant correlations with tumour stages were found in single gene analyses of ga733.2, muc-1 and in multi-gene analyses of ga733.2/muc-1/mgb1/spdef. Furthermore, a significant correlation of Ca 15-3 and all studied genes was also observed.ConclusionHerein, we demonstrated a positive correlation of a gene signature consisting of ga733.2, muc-1, mgb1 and spdef and advanced stages of BC. Moreover, all studied genes and gene patterns revealed a significant correlation with Ca 15-3 positive cases.

Malassezia folliculitis in an immunocompromised patient

ZusammenfassungDie Malassezia-Follikulitis (Synonym: Pityrosporum-Follikulitis) ist eine polymorphe kutane Mykose mit Ausbildung von follikelgebundenen Papeln und Papulopusteln, wobei schwere Verlaufsformen zudem durch das Vorhandensein von molluskoiden Komedopapeln gekennzeichnet sind. Prädilektionsstellen der Malassezia-Follikulitis sind seborrhoische Hautareale im Gesicht und am Stamm. Die Erkrankung wird gehäuft bei immunsupprimierten Patienten beobachtet. Wir berichten über einen herztransplantierten Patienten mit ausgeprägter Malassezia-Follikulitis, der erfolgreich mit Itraconazol therapiert wurde. Die Taxonomie der Gattung Malassezia sowie diagnostische und therapeutische Maßnahmen der von ihr ausgelösten Follikulitis werden zusammengefasst.AbstractMalassezia folliculitis (synonym: Pityrosporum folliculitis) is a polymorphic dermatomycosis characterized by the development of small papules and pustules. In severe cases, molluscoid comedonal papules are typical. The disease occurs mainly in sebum-rich areas of the face, back and chest, frequently affecting patients under immunosuppressive therapy. We report a case of Malassezia folliculitis observed in a heart transplant recipient who was successfully treated with itraconazole. Moreover, we summarize the taxonomy of the genus Malassezia as well as diagnostic and therapeutic measures of the related folliculitis.

[Successful use of allogeneic stem cell transplantation for treatment-refractory mycosis fungoides].

Mycosis fungoides is the most common type of cutaneous T-cell lymphoma and characterized by a chronic progressive course spanning decades. The choice of treatment options should be tailored to the stage depending on the extent and aggressiveness of the disease and taking the individual situation of the patient into consideration. Long-term complete remissions can only be achieved in the early phase of the disease, while there is no therapy that results in a cure or long-term remission in advanced stages. In young patients with a treatment-refractory course of mycosis fungoides, allogeneic stem cell transplantation represents an important alternative option to manage the disease since complete clinical remission can be obtained even in advanced stages.ZusammenfassungDie Mycosis fungoides ist das häufigste kutane T-Zell-Lymphom und durch einen über Jahrzehnte chronisch-progredienten Verlauf gekennzeichnet. Die Auswahl der Behandlungsoptionen sollte sich stadienabhängig an der Ausdehnung und der Aggressivität der Erkrankung orientieren und die individuelle Situation des Patienten in Betracht ziehen. Nur in der Frühphase der Erkrankung sind Langzeitvollremissionen erreichbar, in fortgeschrittenen Stadien kann keine Therapie eine Heilung oder langfristige Remission erzielen. Bei jungen Patienten mit therapierefraktärem Verlauf der Mycosis fungoides ist die allogene Stammzelltransplantation als alternative Therapieoption von großer Bedeutung, da auch in fortgeschrittenen Stadien noch klinische Vollremissionen erreicht werden können.AbstractMycosis fungoides is the most common type of cutaneous T-cell lymphoma and characterized by a chronic progressive course spanning decades. The choice of treatment options should be tailored to the stage depending on the extent and aggressiveness of the disease and taking the individual situation of the patient into consideration. Long-term complete remissions can only be achieved in the early phase of the disease, while there is no therapy that results in a cure or long-term remission in advanced stages. In young patients with a treatment-refractory course of mycosis fungoides, allogeneic stem cell transplantation represents an important alternative option to manage the disease since complete clinical remission can be obtained even in advanced stages.

Erfolgreicher Einsatz einer allogenen Stammzelltransplantation bei therapierefraktärer Mycosis fungoides

Mycosis fungoides is the most common type of cutaneous T-cell lymphoma and characterized by a chronic progressive course spanning decades. The choice of treatment options should be tailored to the stage depending on the extent and aggressiveness of the disease and taking the individual situation of the patient into consideration. Long-term complete remissions can only be achieved in the early phase of the disease, while there is no therapy that results in a cure or long-term remission in advanced stages. In young patients with a treatment-refractory course of mycosis fungoides, allogeneic stem cell transplantation represents an important alternative option to manage the disease since complete clinical remission can be obtained even in advanced stages.ZusammenfassungDie Mycosis fungoides ist das häufigste kutane T-Zell-Lymphom und durch einen über Jahrzehnte chronisch-progredienten Verlauf gekennzeichnet. Die Auswahl der Behandlungsoptionen sollte sich stadienabhängig an der Ausdehnung und der Aggressivität der Erkrankung orientieren und die individuelle Situation des Patienten in Betracht ziehen. Nur in der Frühphase der Erkrankung sind Langzeitvollremissionen erreichbar, in fortgeschrittenen Stadien kann keine Therapie eine Heilung oder langfristige Remission erzielen. Bei jungen Patienten mit therapierefraktärem Verlauf der Mycosis fungoides ist die allogene Stammzelltransplantation als alternative Therapieoption von großer Bedeutung, da auch in fortgeschrittenen Stadien noch klinische Vollremissionen erreicht werden können.AbstractMycosis fungoides is the most common type of cutaneous T-cell lymphoma and characterized by a chronic progressive course spanning decades. The choice of treatment options should be tailored to the stage depending on the extent and aggressiveness of the disease and taking the individual situation of the patient into consideration. Long-term complete remissions can only be achieved in the early phase of the disease, while there is no therapy that results in a cure or long-term remission in advanced stages. In young patients with a treatment-refractory course of mycosis fungoides, allogeneic stem cell transplantation represents an important alternative option to manage the disease since complete clinical remission can be obtained even in advanced stages.

Alitretinoin – molecular and cellular mechanisms of action

Background Chronic hand eczema (CHE) represents an inflammatory skin disease with a high prevalence ranging from 7-12% in Western industrialized countries. It was only starting from 2008 that the first, and until now the only, systemic treatment option, i.e. oral alitretinoin was approved in several countries for severe CHE unresponsive to potent topical corticosteroids. However, as the precise mechanism of actions (MOA) of alitretinoin in CHE are so far unknown, we undertook following investigations in order to shed some light on potential underlying immunomodulatory mechanisms.

Malassezia-Follikulitis bei einem immunsupprimierten Patienten

ZusammenfassungDie Malassezia-Follikulitis (Synonym: Pityrosporum-Follikulitis) ist eine polymorphe kutane Mykose mit Ausbildung von follikelgebundenen Papeln und Papulopusteln, wobei schwere Verlaufsformen zudem durch das Vorhandensein von molluskoiden Komedopapeln gekennzeichnet sind. Prädilektionsstellen der Malassezia-Follikulitis sind seborrhoische Hautareale im Gesicht und am Stamm. Die Erkrankung wird gehäuft bei immunsupprimierten Patienten beobachtet. Wir berichten über einen herztransplantierten Patienten mit ausgeprägter Malassezia-Follikulitis, der erfolgreich mit Itraconazol therapiert wurde. Die Taxonomie der Gattung Malassezia sowie diagnostische und therapeutische Maßnahmen der von ihr ausgelösten Follikulitis werden zusammengefasst.AbstractMalassezia folliculitis (synonym: Pityrosporum folliculitis) is a polymorphic dermatomycosis characterized by the development of small papules and pustules. In severe cases, molluscoid comedonal papules are typical. The disease occurs mainly in sebum-rich areas of the face, back and chest, frequently affecting patients under immunosuppressive therapy. We report a case of Malassezia folliculitis observed in a heart transplant recipient who was successfully treated with itraconazole. Moreover, we summarize the taxonomy of the genus Malassezia as well as diagnostic and therapeutic measures of the related folliculitis.

Malassezia-Follikulitis bei einem immunsupprimierten Patienten@@@Malassezia folliculitis in an immunocompromised patient

ZusammenfassungDie Malassezia-Follikulitis (Synonym: Pityrosporum-Follikulitis) ist eine polymorphe kutane Mykose mit Ausbildung von follikelgebundenen Papeln und Papulopusteln, wobei schwere Verlaufsformen zudem durch das Vorhandensein von molluskoiden Komedopapeln gekennzeichnet sind. Prädilektionsstellen der Malassezia-Follikulitis sind seborrhoische Hautareale im Gesicht und am Stamm. Die Erkrankung wird gehäuft bei immunsupprimierten Patienten beobachtet. Wir berichten über einen herztransplantierten Patienten mit ausgeprägter Malassezia-Follikulitis, der erfolgreich mit Itraconazol therapiert wurde. Die Taxonomie der Gattung Malassezia sowie diagnostische und therapeutische Maßnahmen der von ihr ausgelösten Follikulitis werden zusammengefasst.AbstractMalassezia folliculitis (synonym: Pityrosporum folliculitis) is a polymorphic dermatomycosis characterized by the development of small papules and pustules. In severe cases, molluscoid comedonal papules are typical. The disease occurs mainly in sebum-rich areas of the face, back and chest, frequently affecting patients under immunosuppressive therapy. We report a case of Malassezia folliculitis observed in a heart transplant recipient who was successfully treated with itraconazole. Moreover, we summarize the taxonomy of the genus Malassezia as well as diagnostic and therapeutic measures of the related folliculitis.