Uwe-Jochen Göhring

Cytokine expression in peripheral blood lymphocytes indicates a switch to Thelper cells in patients with preeclampsia

We sought to determine whether cytokine expression in peripheral blood mononuclear cells is altered in patients with preeclampsia and in patients with a history of recurrent spontaneous abortion (RSA). Twenty-four patients with preeclampsia and twenty patients with a history of RSA were included into the study. Two control groups consisted of twenty healthy pregnant and twenty healthy non-pregnant women. The intracellular expression of interleukin-2 (IL-2), interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) were determined in peripheral blood mononuclear cells (PBMCs) by flow cytometry as a measure of cytokine production. IL-2 synthesis was significantly elevated in the third trimester in preeclamptic patients in comparison with the control group. Non-pregnant women with RSA showed a significantly lower expression of IFN-gamma compared to the non-pregnant control group. Our data suggest an abnormal immune response in preeclamptic patients characterised by a shift to a predominantly Th1-type immunity.

Association of the vitamin D receptor genotype with bone metastases in breast cancer patients.

This study was designed in order to evaluate specific vitamin D receptor (VDR) genotypes as indicators of the likelihood of developing osseous metastases in breast cancer patients. Therefore, we determined polymorphisms of the VDR gene in a study group comprising 183 breast cancer patients. Specific fragments spanning over intron 8 and exon 9 of the VDR gene were amplified by polymerase chain reaction. The fragments were then incubated with each of the specific endonucleases ApaI, BsmI or TaqI, respectively. The VDR gene polymorphisms were detected by the presence or absence of the particular restriction site using agarose gel electrophoresis. Statistical analyses revealed a significant correlation between both the VDR gene polymorphisms indicated as AA (absence of the ApaI restriction site in both alleles) or TT (absence of the TaqI restriction site in both alleles), respectively, and the occurrence of bone metastases. Patients with the AA genotype have a 1.7-fold increased risk of developing bone metastases, whereas patients with the TT genotype have a 0.5-fold risk. Neither other genotypes nor allelic combinations displayed any further correlation with the clinical stage. The data suggest that the AA genotype of the VDR gene might be useful to identify breast cancer patients with a high probability of forming occult bone metastases who are considered to benefit from an adjuvant bone-protective therapy.

The V109G Polymorphism of the p27 Gene CDKN1B Indicates a Worse Outcome in Node-Negative Breast Cancer Patients

Although p27 plays a central role in cell cycle regulation, its role in breast cancer prognosis is controversial. Furthermore, the p27 gene CDKN1B carries a polymorphism with unknown functional relevance. This study was designed to evaluate p27 expression and p27 genotyping with respect to early breast cancer prognosis. 279 patients with infiltrating metastasis-free breast cancer were included in this study. p27 expression was determined in tumor tissue specimens from 261 patients by immunohistochemistry. From 108 patients, the CDKN1B genotype was examined by PCR and subsequent direct sequencing. 55.2% of the tumors were considered p27 positive. p27 expression did not correlate with any of the established parameters except for nodal involvement but significantly correlated to prolonged disease-free survival. In 35% of the tumors analyzed, the CDKN1B gene showed a polymorphism at codon 109 (V109G). The V109G polymorphism correlated with greater nodal involvement. In the node-negative subgroup, V109G correlated significantly with a shortened disease-free survival. In conclusion, the determination of the CDKN1B genotype might be a powerful tool for the prognosis of patients with early breast cancer.

Time to progression is dependent on the expression of the tumour suppressor PTEN in ovarian cancer patients

Background Quantitative analyses of PTEN expression of ovarian cancer tissues were performed in this study. PTEN expression was investigated in terms of each patients progression‐free interval to indicate the role of PTEN in the generation of platinum refractory tumours.

gastric cancer during early pregnancy two case reports

We report two cases of advanced gastric carcinoma in pregnancy.

Immunohistochemical detection of H-ras protooncoprotein p21 indicates favorable prognosis in node-negative breast cancer patients.

We tested primary breast carcinoma tissues from 297 patients using a monoclonal antibody (clone 235-1.7.1.) for the expression of p21ras. 58% of tumors were p21ras-positive. When calculated in a univariate fashion, p21 expression correlated with proliferation activity (proliferating cell nuclear antigen) only. Using the log-rank test (median observation time 94 months) a significantly worse prognosis (disease-free survival, overall survival) relation was found with larger tumors, nodal involvement, anaplasia, rising proliferation activity, and lack of steroid receptors. Detection of p21ras correlated with a more favorable prognosis but only in node-negative patients. Stepwise correlation according to the Cox hazard model ranked p21 expression as a most significant predictor of prognosis second only to nodal status. These data suggest that detection of p21ras indicates the presence of a parameter which may act as tumor suppressor and benefit patients’ survival.

A prospective study concerning psychological characteristics of patients with breast cancer.

In a prospective study we have investigated the question of predisposing and reactive personality traits in breast cancer patients. The design of the study incorporated a prebioptic collection of data by means of an interview and psychological test questionnaires (STAI, SVF, FPI, CIP-DS), as well as follow-up questioning after a one year interval. In comparison with operated women with benign biopsy findings no unequivocal indications of a personality type predisposed to cancer were found. Both patient groups showed a high preoperative potential for anxiety. The tendency to suppress emotions, trivialise and to display self-pity was particularly noticeable in patients with advanced tumours at the time of diagnosis. Even after the disease had run for one year, it was not possible to demonstrate a distinct characterisation of the breast cancer patients by psychological testing methods. An increased concern over health, an inclination towards resignation and social isolation and a diminished contentment with life marked the changes that could be measured by psychological tests in some of the women affected.

Does Center Volume Correlate with Survival from Breast Cancer

With its high incidence and long history of patient advocacy, breast cancer has generated the most concern about the quality of its care and the volume-outcome relationship. In breast cancer surgery, the risk of perioperative morbidity or mortality is low, but surgery is only one single piece in the mosaic of multidisciplinary care that eventually determines survival. Only a limited number of articles is available investigating the relationship between case volume of physicians and hospitals and specialization of surgeons and survival. In summary, there is evidence to support the hypothesis that specialization, research interest, and caseload of physicians and hospitals is positively correlated with providing state-of-the-art care and with survival. However, it is less clear what impact might be attributed to the surgical routine gained with increasing number of procedures compared to the deeper insight into the biology of breast cancer that comes with specialization in oncology and the weight of the multidisciplinary setting that is more easily established and maintained with a higher caseload.

Amplification of the mdr1-gene is uncommon in recurrent ovarian carcinomas

Ovarian carcinomas are known to rapidly develop drug resistance against chemotherapeutic agents. This phenomenon is often associated with the expression of pl70-glycoprotein. A high rate of transcription of the corresponding mdr1-gene in resistant tumors is reported. Amplification of the mdr1-gene has been observed in tumor cell lines exposed to cytotoxic drugs; however, significant information is lacking as to whether this holds true in clinical carcinomas. To fill this gap, we investigated the rate of gene amplification of the mdr1-gene in 63 recurrent ovarian carcinomas and we determined the resistance pattern of these cells using an ex vivo assay. The tumors showed varying ex vivo resistance patterns which did not correlate to clinical parameters. Amplification of the mdr1-gene was not observed in any of the cancer specimens. Therefore, we conclude that mdr1-gene amplification is not a common pathway for the development of chemoresistance in clinical ovarian carcinomas.

Immunologic features of tumor-infiltrating lymphocytes and peripheral blood lymphocytes in ovarian cancer patients.

Objective: To determine the immunologic characteristics of tumor infiltrating lymphocytes (TILs) in comparison with the corresponding peripheral blood lymphocytes (PBLs) of patients with overian cancer in order to detect specific antitumor-reactive-immunocompetent cells. Methods: Tumor infiltrating lymphocytes and PBLs were phenotyped by their surface markers, cytokine pattern, proliferation rate, and cytotoxic ability. Results: The phenotypes of both lymphocyte populations were very heterogeneous. Peripheral blood lymphocytes had a higher proliferative activity and cytotoxicity against natural killer-sensitive tumor cells than the coreesponding TILs. Furthermore TILs showed increased interleukin-4 expression whereas in PBLs, interferon-γ production predominated. Conclusion: Peripheral blood lymphocytes showed more potentially valuable behavioral characteristics than TILs. in the future we need to combine several methods in order to define immune cells with antitumor activity. These cells should be expanded ex vivo and stimulated specifically for use in the immunotherapy of overian cancer.