Pathologische Anatomie (Sektionstechnik) und Physiologie

Ohne Zusammenfassung     

TIMP-1 in combination with HER2 and TOP2A for prediction of benefit from adjuvant anthracyclines in high-risk breast cancer patients

HER2 amplification, TOP2A aberrations, and absence of tissue inhibitor of metalloproteinase (TIMP-1) expression in breast carcinomas have been shown to be associated with incremental benefit from anthracycline-containing adjuvant chemotherapy, and this study was undertaken to validate these findings in a similar, but independent, randomized clinical trial. TIMP-1 was examined by immunohistochemistry in archival tumor tissue from 403 of 716 premenopausal high-risk patients with known HER2 and TOP2A status who were randomized to cyclophosphamide, epirubicin, and fluorouracil (CEF) or cyclophosphamide, methotrexate, and fluorouracil (CMF) in the MA.5 trial. Ninety-eight (24%) patients had no TIMP-1 staining of tumor cells, 27% were HER2 amplified, and 18% were TOP2A aberrant. Forty-four percentage was classified as HT responsive (HER2 amplified and/or TIMP-1 negative) and 37% as 2T responsive (TOP2A aberrant and/or TIMP-1 negative). There was no heterogeneity in treatment effect of CEF versus CMF according to TIMP-1. In HT-responsive patients, CEF was superior to CMF with an improved RFS (adjusted HR, 0.64; 95% CI, 0.42-0.97), but this was not significant for OS (adjusted HR, 0.66; 95% CI, 0.42-1.04). A significant HT profile versus treatment interaction was detected for OS (P = 0.03). In 2T-responsive patients, CEF seemed to improve RFS compared to CMF (adjusted HR, 0.67; 95% CI, 0.43-1.03) and improved OS (adjusted HR, 0.58; 95% CI, 0.36-0.93). A significant 2T profile versus treatment interaction was detected for OS (P = 0.01). With this study, we validate a more substantial reduction in mortality by CEF compared to CMF in patients with an HT- or 2T-responsive profile; however, we could not show a similarly significant reduction in RFS events, where a benefit of CEF over CMF was found irrespective of TIMP-1 status. Further studies are necessary before the HT and 2T profiles may be used to direct the use of anthracyclines.     

Correlation between HPV status at T and N sites of oropharyngeal squamous cell carcinomas

Objectives: Human papilloma virus (HPV) is known to be associated with oropharyngeal squamous cell carcinomas (OPSCC) and may potentially play a vital role in tumor metastasis. The purpose of this study was to correlate HPV status of cervical lymph node metastases with their respective primary OPSCC tumor.

Methods: Formalin-fixed, paraffin-embedded (FFPE) tissue samples obtained from 34 patients with cervical lymph node metastases were analyzed with HPV 16 DNA polymerase chain reaction (PCR), p16 immunohistochemistry and HPV typing. The results were correlated with the HPV status and type found in the primary tumors of OPSCC.

Results: Comparing HPV DNA status with p16 we found that 21 primary tumors and lymph node metastases were HPV positive (61.8%) and seven primary tumors and lymph node metastases were HPV negative (20.6%). Six patient samples differed when correlating the primary tumor and lymph node metastasis (17.6%).

Conclusions: In this study, HPV status in OPSCCs and their cervical lymph node metastases correlated in the vast majority of cases. However, HPV detection methods may have certain limitations resulting in varying degree of non-correlation. This should be taken into account when stratifying treatment in regard to HPV status.     

Properties of the Enterotoxic Component in Escherichia coli Enteropathogenic for Swine

The enterotoxic component in sterile syncase broth filtrates of Escherichia coli strains 340 (O9:K.:NM) and P307 (O8:K87,88a,b:H19) was studied. The enterotoxic activity in both strains was retained by an ultrafiltration membrane with a molecular weight retention of 100,000 (XM-100A) and eluted from a Sephadex G-200 column in the void volume. The enterotoxic activity in strain 340 was resistant to heating at 75 C for 30 min, but the activity in strain P307 was destroyed by heating at 60 C for 30 min. The P307 Sephadex G-200 column eluate possessing the enterotoxic activity, when desalted, contained 45.8% carbohydrate and 9.3% protein, and had an ED(50) of 2.2 mg/rabbit ileal loop. Immunodiffusion studies showed that this material contained both endotoxin and acid-polysaccharide capsular material. The enterotoxic activity was acidlabile and was destroyed by Pronase, but was resistant to trypsin and eluted as a single peak in the void volume of a 4% agarose column. The enterotoxic component could not be separated from the endotoxin; in fact, the data indicated that the two components are closely associated and that the enterotoxic activity resides in material of a protein nature.     

Biotransformations of Quercetin and Apigenin by a Cell Suspension Culture of Cannabis sativa

A cell suspension culture of CANNABIS SATIVA without endogenous flavonoids is able to convert quercetin to quercetin 3- O-glucoside, quercetin 3- O-diglucoside, isorhamnetin 3- O-glucoside, and isorhamnetin 3- O-diglucoside. Apigenin is transformed to apigenin 7- O-glucoside and 7- O-glucuronide and to vitexin.     

Use of the psychologic-neurologic questionnaire and the diagnostic follow-up program in long-term CS2 exposed workers

In view of the neurotoxic effect of CS2, psychodiagnostic methods of examination seem to be very suitable for the early detection of that effect. In 1985 we applied those methods to 61 workers of a synthetic-fibre plant exposed to CS2. According to the findings, the examination results were divided into three categories. A comparison was made between them and the PNF findings. Another 38 workers exposed to CS2 were examined in 1987, 20 examinations of which were follow-ups. The findings suggest that it does not seem sufficient just to apply the PNF questionnaire method to detect CS2-related health damage in workers to a satisfactory extent. It is recommended that in job-fitness and regular occupational-health examinations additional methods be applied to supplement the PNF with regard to workers exposed to CS2 levels exceeding the workplace limit values.     

1-[4-(4-Chlorophenyl)-2-(2,6-dichlorophenylthio)-n-butyl]-1H-imidazole nitrate, a new potent antifungal agent.

The preparation and antifungal properties of 1-[4-(4-chlorophenyl)-2-(2,6-dichlorophenylthio)-n-butyl]-1H-imidazole nitrate 1 are described. It is particularly effective against in vivo Candida albicans infections (mice), maintaining good activity down to 0.25% formulation strength and showing unusually low reinfection rates after treatment is ended.