BackgroundThe murine double minute 2 (MDM2) is an oncogene and a negative regulator of the tumor suppressor protein p53. MDM2 is known to be amplified in numerous human cancers, and upregulation of MDM2 is considered to be an alternative mechanism of p53 inactivation. The presence of many splice variants of MDM2 has been observed in both normal tissues and malignant cells; however their impact and functional properties in response to chemotherapy treatment are not fully understood.Here, we investigate the biological effects of three widely expressed alternatively spliced variants of MDM2; MDM2-A, MDM2-B and MDM2-C, both in unstressed MCF-7 breast cancer cells and in cells subjected to chemotherapy. We assessed protein stability, subcellular localization and induction of downstream genes known to be regulated by the MDM2-network, as well as impact on cellular endpoints, such as apoptosis, cell cycle arrest and senescence.ResultsWe found both the splice variants MDM2-B and -C, to have a much longer half-life than MDM2 full-length (FL) protein after chemotherapy treatment indicating that, under stressed conditions, the regulation of degradation of these two variants differs from that of MDM2-FL. Interestingly, we observed all three splice variants to deviate from MDM2-FL protein with respect to subcellular distribution. Furthermore, while MDM2-A and -B induced the expression of the pro-apoptotic gene PUMA, this effect did not manifest in an increased level of apoptosis.ConclusionAlthough MDM2-B induced slight changes in the cell cycle profile, overall, we found the impact of the three MDM2 splice variants on potential cellular endpoints upon doxorubicin treatment to be limited.Electronic supplementary materialThe online version of this article (doi:10.1186/s12860-017-0134-z) contains supplementary material, which is available to authorized users.

Abstract. Background

PurposeTo analyze survival after early palliative radiotherapy (RT) in patients managed exclusively by regular oncology staff or a multidisciplinary palliative care team (MPCT) in addition.MethodsRetrospective matched pairs analysis. Comparison of two groups of 29 patients each: MPCT versus none. Early RT started within three months after cancer diagnosis.ResultsBone and brain metastases were common RT targets. No significant differences in baseline characteristics were observed between both groups. Twelve patients in each group had non-small cell lung cancer. Median performance status was 2 in each group. Twenty-seven patients in each group had distant metastases. Median survival was not significantly different. In multivariate analysis, MPCT care was not associated with survival, while performance status and liver metastases were. Rate of radiotherapy during the last month of life was comparable. Only one patient in each group failed to complete radiotherapy.ConclusionsMPCT care was not associated with survival in these two matched groups of patients. The impact of MPCT care on other relevant endpoints such as symptom control, side effects and quality of life should be investigated prospectively.

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This study aims to explore patterns of practice of tumor marker analyses and potential prognostic impact of abnormal markers in patients with brain metastases from solid tumors. Previously, lactate dehydrogenase (LDH) and albumin were identified as relevant biomarkers. We performed a retrospective analysis of 120 patients with known LDH and albumin treated with whole-brain radiotherapy (WBRT) in two different situations: (1) brain metastases detected at initial cancer diagnosis (n = 46) and (2) brain metastases at later time points (n = 74, median interval 13 months). Twenty-six patients (57 %) from group 1 had at least one tumor marker analyzed, and 11 patients (24 %) had abnormal results. Twenty-two patients (30 %) from group 2 had at least one tumor marker analyzed, and 16 patients (22 %) had abnormal results. When assuming that LDH and albumin would be standard tests before WBRT, additional potential biomarkers were found in 36 % of patients with normal LDH and albumin. Marker positivity rates were for example 80 % for carcinoembryonic antigen (CEA) in colorectal cancer and 79 % for CA 15-3 in breast cancer. Abnormal markers were associated with presence of liver metastases. CA 15-3 values above median predicted shorter survival in patients with breast cancer (median 1.9 vs. 13.8 months, p = 0.1). Comparable trends were not observed for various markers in other tumor types. In conclusion, only a minority of patients had undergone tumor marker analyses. Final group sizes were too small to perform multivariate analyses or draw definitive conclusions. We hypothesize that CA 15-3 could be a promising biomarker that should be studied further.

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BackgroundThe aim of the study was to explore the prognostic impact of different abnormal blood tests and the tumor marker CA 15-3 as well as established parameters such as disease extent and receptor status in patients with bone metastases from breast cancer who received palliative radiotherapy in addition to contemporary systemic treatment.MethodsThis was a retrospective uni- and multivariate analysis of 118 female patients treated in the time period from 2007 to 2014 (median follow-up 28 months).ResultsThe median age was 61 years and the median time interval from the initial diagnosis of breast cancer was 57 months (median time interval from metastatic disease to radiotherapy was 7 months). Only 16% of patients had normal serum CA 15-3. HER2 receptor status correlated with CA 15-3. The median survival was 17.6 months (lowest CA 15-3 quartile), 14.7 months (intermediate), and 6.9 months (highest quartile) (P = 0.002). However, multivariate analysis showed that survival was influenced by extent of extra-skeletal metastases, pleural metastases/effusion, lung metastases, estrogen receptor status, serum C-reactive protein, and anemia with need for blood transfusion (all P < 0.05) rather than CA 15-3.ConclusionsSurvival was highly variable. The tumor marker CA 15-3 did not provide independent prognostic information. Nevertheless, the results of simple blood tests contributed to the multivariate prognostic model.

Polypharmacy is a common phenomenon in older patients receiving palliative radiotherapy and it does not predict adverse radiotherapy outcomes.