Discoidin domain receptor 1 belongs to a subfamily of tyrosine kinase receptors activated by various types of collagen. Alternative splicing in the juxtamembrane region of the receptor results in the insertion of 37 amino acids. Here we used primer flanking the juxtamembrane region to search for additional isoforms. From human colon carcinoma Colo 206F cells, we identified two novel isoforms, DDR1d and DDR1e. In the DDR1d sequence, exon 11 and 12 are deleted, which results in a frame‐shift mutation and premature termination of translation. DDR1e arises from an alternative usage of a splice acceptor site in exon 10 and deletion of exon 11 and12. Both new isoforms are predicted to be membrane‐anchored, but kinase‐deficient, receptors. Transcripts for DDR1d and DDR1e were present to various degrees in a panel of human colon cancer cell lines. Using antibodies to several different receptor epitopes, we found correlating expression of DDR1d and DDR1e protein with the expected molecular weight of 68 and 95 kDa in colon carcinoma cell lines. Despite the abundant expression of truncated DDR1d in Colo 206F cells, stimulation with collagen induced full‐length receptor phosphorylation, thereby suggesting a lack of dominant‐negative inhibition by DDR1d. Exogenous overexpression of DDR1d in transient transfection assays supported a nondominant negative mechanism of signal modulation.

PurposeThe PELICAN trial evaluates for the first time efficacy and safety of pegylated liposomal doxorubicin (PLD) versus capecitabine as first-line treatment of metastatic breast cancer (MBC).MethodsThis randomized, phase III, open-label, multicenter trial enrolled first-line MBC patients who were ineligible for endocrine or trastuzumab therapy. Cumulative adjuvant anthracyclines of 360 mg/m2 doxorubicin or equivalent were allowed. Left ventricular ejection fraction of >50 % was required. Patients received PLD 50 mg/m2 every 28 days or capecitabine 1250 mg/m2 twice daily for 14 days every 21 days. The primary endpoint was time-to-disease progression (TTP).Results210 patients were randomized (n = 105, PLD and n = 105, capecitabine). Adjuvant anthracyclines were given to 37 % (PLD) and 36 % (capecitabine) of patients. No significant difference was observed in TTP [HR = 1.21 (95 % confidence interval, 0.838–1.750)]. Median TTP was 6.0 months for both PLD and capecitabine. Comparing patients with or without prior anthracyclines, no significant difference in TTP was observed in the PLD arm (log-rank P = 0.64). For PLD versus capecitabine, respectively, overall survival (median, 23.3 months vs. 26.8 months) and time-to-treatment failure (median, 4.6 months vs. 3.7 months) were not statistically significantly different. Compared to PLD, patients on capecitabine experienced more serious adverse events (P = 0.015) and more cardiac events among patients who had prior anthracycline exposure (18 vs. 8 %; P = 0.31).ConclusionBoth PLD and capecitabine are effective first-line agents for MBC.

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BackgroundType A Dissection in pregnancy is a devastating medical condition with 2 lives at stake and unclear strategy at early gestational stages. We describe a successful outcome, clearly dependent on the coordination of all involved disciplines.Case presentationThis case history describes a 28 year old female with a 24th week pregnancy gravida 2 para 0 with a DeBakey Type I aortic dissection, diagnosed via ultrasound. Surgery was perfomed on the day of diagnosis. After conferral with the mother, caesarean section was performed and a 690 g fetus could be delivered and was immediately transferred to the neonatal unit. Subsequent aortic repair was performed after hysterectomy, with replacement of the ascending aorta and hemiarch treatment. Intraoperatively no entry in the ascending aorta or transverse arch could be demonstrated, so that a retrograde Type A with entry distal to the left subclavian had to be postulated. We decided to perform subsequent computer tomography, demonstrating multiple entry sites in the descending aorta distal to the left subclavian artery. Successful endovascular treatment could be performed with a Medtronic Valiant Stent via a transfemoral approach. The further hospital stay was uneventful and the patient could be discharged on the 18th postoperative day. The baby demonstrated fighter qualities and could be discharged home after a 3 month hospital stay to be reunited with his mother.ConclusionPrompt diagnosis, precise coordination between all involved subspecialties and ultimately, as in this case, definitive treatment in consensus with operative and interventional departments have led to a successful outcome and encourages us in our daily struggle in this often demanding surgery.