0000000000505508

AUTHOR

Manfred Kaufmann

Comparison of Prognostic Signatures in Node-Negative Tamoxifen-Treated Breast Cancer Patients.

Abstract Background: A number of molecular signatures have been published to aid breast cancer prognosis and therapy response prediction. A 76-gene signature has been developed in a node-negative patient cohort that did not receive systemic therapy.1 Another prognostic 97-gene signature measures predominantly proliferation-associated genes.2 Finally, a 21-gene signature has been developed for node-negative and estrogen receptor–positive breast cancer patients treated with tamoxifen in the adjuvant setting.3 Here we compare the prognostic performance of all three published algorithms in a cohort of 189 node-negative breast cancer patients treated with tamoxifen.Materials and Methods: Fresh-f…

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Anti-fetal immune response mechanisms may be involved in the pathogenesis of placental abruption

Placental abruption is an unpredictable severe complication in pregnancy. In order to investigate the possibility that the activation of the fetal nonadaptive immune system may be involved in the pathogenesis of this disease, IL-6 release from cord blood monocytes was examined by intracellular cytokine staining and flow cytometric analysis. Our results demonstrate that preterm placental abruption (n = 15) in contrast to uncontrollable preterm labor (n = 33) is associated with significantly (P < 0.001) increased release of IL-6 from the fetal monocytes. The same holds true for rhesus disease (n = 9, P < 0.001) that is characterized by a maternal production of antibodies against the rhesus-D …

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Spontaneous labour at term is associated with fetal monocyte activation.

SUMMARYThe aetiology of both term and preterm labour remains incompletely understood. Maternal infectious diseases as well as intra-uterine infections were shown to be a well established cause of uncontrollable preterm delivery, indicating that inflammatory reactions, regulated by maternal immunecompetent cells, are implicated in labour-promoting mechanisms. To investigate the possibility that the activation of the fetal immune system may be involved in labour induction, we examined cytokine production patterns of different cord blood cell populations obtained from neonates after spontaneous onset of normal term labour and vaginal delivery (n = 25), vaginal delivery but induced term labour …

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Is first-line single-agent mitoxantrone in the treatment of high-risk metastatic breast cancer patients as effective as combination chemotherapy? No difference in survival but higher quality of life were found in a multicenter randomized trial.

BACKGROUND: To determine whether patients with high-risk metastatic breast cancer draw benefit from combination chemotherapy as first-line treatment. PATIENTS AND METHODS: A total of 260 women with measurable metastatic breast cancer fulfilling high-risk criteria, previously untreated with chemotherapy for their metastatic disease, were randomized to receive either mitoxantrone 12 mg/m(2) or the combination of fluorouracil 500 mg/m(2), epirubicin 50 mg/m(2) and cyclophosphamide 500 mg/m(2) (FEC) every 3 weeks. Treatment was continued until complete remission plus two cycles, or until disease progression. In the case of partial remission or stable disease, treatment was stopped after 12 cycl…

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O6-methylguanine-DNA methyltransferase activity in breast and brain tumors.

The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) is a main determinant of resistance of tumor cells to the cytostatic activity of chemotherapeutic alkylating agents (methylating and chloroethylating nitrosoureas) and is effective in protecting normal cells against genotoxic and carcinogenic effects resulting from DNA alkylation. Therefore, the level of expression of MGMT is significant for the response of both the tumor and the non-target tissue following application of nitrosoureas in tumor therapy. To determine the expression of MGMT in tumor tissue, we have assayed MGMT activity in 68 breast carcinomas and 38 brain tumors. There was a wide variation of MGMT expression…

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Preeclampsia, a pregnancy-specific disease, is associated with fetal monocyte activation.

The maternal syndrome of preeclampsia is an exclusively pregnancy-related illness involving multiple organs and severe forms may be complicated by HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome. Recently, it has been proposed that both normal pregnancy and preeclampsia are associated with a systemic activation of the nonspecific maternal immune system and that, in particular, monocytes have a central role in the adjustment of maternal immune functions in pregnancy. Here we have investigated the role of the fetal nonadaptive immune system in normal term delivery, uncontrollable preterm labor, and preeclampsia. We demonstrate that spontaneous delivery at term as well as pre…

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