Prognostic value of HPV-mRNA in sentinel lymph nodes of cervical cancer patients with pN0-status

Up to 15% of patients with cervical cancer and pN0-status develop recurrent-disease. This may be due to occult metastatic spread of tumor cells. We evaluated the use of human-papillomavirus-(HPV)-mRNA as a molecular marker for disseminated tumor cells to predict the risk of recurrence. For this prospective, multi-center prognostic study, 189 patients free of lymphnode metastases by conventional histopathology could be analyzed. All patients underwent complete lymphadenectomy. Of each sentinel node (SLN) a biopsy was taken for the detection of HPV-E6-E7-mRNA. Median follow-up time after surgery was 8.1 years. HPV-mRNA could be detected in SLN of 52 patients (27.5%). Recurrence was observed in 22 patients. Recurrence-free-survival was significantly longer for patients with HPV-negative SLN (log rank p = 0.002). By Cox regression analysis the hazard ratio (95%CI) for disease-recurrence was 3.8 (1.5 – 9.3, p = 0.004) for HPV-mRNA-positive compared to HPV-mRNA-negative patients. After adjustment for tumor size as the most influential covariate the HR was still 2.8 (1.1 – 7.0, p = 0.030). In patients with cervical cancer and tumor-free lymph nodes by conventional histopathology HPV-mRNA-positive SLN were of prognostic value independent of tumor size. Particularly, patients with tumors larger than 20mm diameter could possibly benefit from further risk stratification using HPV-mRNA as a molecular marker.     

In vivo multicolor molecular MR imaging using diamagnetic chemical exchange saturation transfer liposomes

A variety of (super)paramagnetic contrast agents are available for enhanced MR visualization of specific tissues, cells, or molecules. To develop alternative contrast agents without the presence of metal ions, liposomes were developed containing simple bioorganic and biodegradable compounds that produce diamagnetic chemical exchange saturation transfer MR contrast. This diamagnetic chemical exchange saturation transfer contrast is frequency-dependent, allowing the unique generation of "multicolor" images. The contrast can be turned on and off at will, and standard images do not show the presence of these agents. As an example, glycogen, L-arginine, and poly-L-lysine were encapsulated inside liposomes and injected intradermally into mice to image the lymphatic uptake of these liposomes. Using a frequency-dependent acquisition scheme, it is demonstrated that multicolor MRI can differentiate between different contrast particles in vivo following their homing to draining lymph nodes. Being nonmetallic and bioorganic, these diamagnetic chemical exchange saturation transfer liposomes form an attractive novel platform for multicolor imaging in vivo.     

Über cerebrale Blasenstörungen

Ohne ZusammenfassungAbkürzungen N. C. Neurologisches Zentralblatt - D. Z. f. N. Deutsche Zeitschrift für Nervenheilkunde - Jbt. f. N. u. Ps. Jahresbericht für Neurologie und Psychiatrie - Schm. Jb. Schmidts Jahrbücher - Jbt. d. ges. Med. Jahresbericht der gesamten Medizin An dieser Stelle ist es mir eine angenehme Pflieht, Herrn Geheimrag Prof. Dr. v. Striimpell für die Anregung zu dieser Arbeig and Herrn Privadozent Dr. Eduard Müller sowohl für die ständige Unterstützung and Leitung bei der Ausführung derselben, wie auch für die liebenswürdige Uberlassung des von ihm gesammelten Minischen Materials meinen ergebensten Dank auszuspreehen.     

Bowenoid papulosis of the male and female genitalia: risk of cervical neoplasia

Sixteen patients with bowenoid papulosis (eleven male patients with bowenoid papulosis of the penis and five female patients with bowenoid papulosis of the vulva) were studied clinically, histologically, and virologically and followed up from 12 months to 5 years. In eleven of sixteen cases of bowenoid papulosis, molecular hybridization disclosed the presence of human papillomavirus type 16. In four cases we found new, not fully characterized human papillomavirus, and in two cases, we found both human papillomavirus 16 and new human papillomavirus (double infection). The mean age of male patients was 33 years and of female patients, 31 years. The mean duration of the disease was 2.4 and 3.6 years, respectively. The lesions cleared or did not recur in eight of eleven male patients after repeated partial excisions and in two of five female patients after conservative surgery. Cervical intraepithelial neoplasia (severe dysplasia) was present in three of five female patients, and human papillomavirus infection of the cervix was present in five of six sexual partners of male patients available for examination. Thus bowenoid papulosis presents a high risk for cervical neoplasia both for female patients and for sexual partners of male patients.     

CD95 and TRAIL receptor-mediated activation of protein kinase C and NF-kappaB contributes to apoptosis resistance in ductal pancreatic adenocarcinoma cells.

The molecular alterations in tumour cells leading to resistance towards apoptosis induced by CD95 and TRAIL-receptors are not fully understood. We report here that the stimulation of the CD95- and TRAIL-resistant human pancreatic adenocarcinoma cell line PancTuI with an agonistic anti-CD95 antibody or TRAIL resulted in activation of protein kinase C and NF-kappaB. Inhibition of protein kinase C by G?6983 sensitized these cells to apoptotic challenges and strongly diminished activation of NF-kappaB by anti-CD95 and TRAIL. Similarly, inhibition of NF-kappaB by MG132 or by transient transfection with a dominant negative mutant of IkappaBalpha restored the responsiveness of PancTuI cells to both death ligands. In the CD95 and TRAIL-sensitive cell line Colo357 the induction of protein kinase C and NF-kappaB following activation of CD95 and TRAIL-R was very moderate compared with PancTuI cells. However, pre-incubation of these cells with PMA strongly reduced their apoptotic response to anti-CD95 and TRAIL. Taken together, we show that activation of protein kinase C operates directly in a death receptor-dependent manner in PancTuI cells and protect pancreatic tumour cells from anti-CD95 and TRAIL-mediated apoptosis by preventing the loss DeltaPsim and Cytochrome c release as well as by induction of NF-kappaB.     

Differentiation of the observed low frequency (1200MHz) EPR signals in whole human teeth.

We have determined the properties of the various signals that are observed in vivo so this information can be used to develop procedures for data acquisition and data analysis that will enable the accurate determination of radiation-induced dose with a resolution of 50cGy. Using the 1200MHz in vivo EPR spectrometer and isolated human teeth, we found four types of signals whose properties overlap, but also have some distinct properties that can be exploited to resolve them. The intrinsic background signal in human teeth differs modestly from the radiation-induced signal in g-factor, shape, and power saturation. Random noise from instrumental conditions can be reduced with signal averaging. The microphonic signal varies with the particular experimental setup and has some properties similar to real EPR signals, but is constant if the conditions are not changed. It can be suppressed by improvements in hardware and software, or subtracted.     

Small particles of fusinite and carbohydrate chars coated with aqueous soluble polymers: Preparation and applications for in Vivo EPR oximetry

The development of oxygen-sensitive paramagnetic materials is being pursued actively because of their potential applications in in vivo EPR oximetry. Among these materials, several charcoals and carbohydrate chars are of special interest because of their desirable EPR properties: high sensitivity of the EPR linewidth to the partial pressure of oxygen, simple EPR spectra, and high spin density. Their potential use in humans, however, is limited by the need to demonstrate that they will not lead to deleterious effects. A strategy was used to optimize the biocompatibility of the oxygen-sensitive materials by decreasing the size of the particles and coating them with suspending or surfactive agents such as arabic gum, polox-amer (Pluriol 6800®), and polyvinylpyrrolidone. The coated particles of a carbohydrate char and fusinite were characterized in vitro for their size, stability, and pO₂ sensitivity. The feasibility of performing pO₂ measurement was examined in vivo by inducing ischemia in the gastrocnemius muscle of mice. The use of arabic gum for coating the fusinite particles preserved the pO₂ sensitivity in vivo, whereas the other surfactive agents led to a loss of the pO₂ sensitivity in vivo. Small particles of fusinite coated by arabic gum and intravenously administered to mice accumulated in the liver, whereas the uncoated fusinite was toxic when injected intravenously due to the large size and aggregation of the particles. Histological studies performed up to 6 months after the injection in muscles of mice did not indicate any toxicity from the materials used in the present study.