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Background Diagnosis of large, heterogenous lesions of the pancreas with solid and cystic components is often challenging. The spectrum of differential diagnoses is broad, and clinical as well as radiological findings may be similar. Methods Detailed analysis of a clinical case and review of literature. Results We present the case of a 28-year-old woman with a large, heterogenous tumour of the pancreatic head that was incidentally found in routine ultrasound during pregnancy. The presence of a solid pseudopapillary neoplasm (SPN) was suspected because of typical clinical and radiological characteristics. The patient underwent partial pancreatoduodenectomy and surprisingly, histological work-up confirmed a pancreatic extra-gastrointestinal stromal tumour (EGIST). Conclusion As clinical and radiological findings may be misleading in a large, heterogenous tumour of the pancreas, a biopsy with histological proof of diagnosis is recommended, especially in situations where a neoadjuvant treatment may be considered. [ABSTRACT FROM AUTHOR]

Background:The randomised phase III TURANDOT trial compared first-line bevacizumab-paclitaxel (BEV-PAC) vs bevacizumab-capecitabine (BEV-CAP) in HER2-negative locally recurrent/metastatic breast cancer (LR/mBC). The interim analysis revealed no difference in overall survival (OS; primary end point) between treatment arms; however, progression-free survival (PFS) and objective response rate were significantly superior with BEV-PAC. We sought to identify patient populations that may be most appropriately treated with one or other regimen.Methods:Patients with HER2-negative LR/mBC who had received no prior chemotherapy for advanced disease were randomised to either BEV-PAC (bevacizumab 10 mg kg−1 days 1 and 15 plus paclitaxel 90 mg m−2 days 1, 8 and 15 q4w) or BEV-CAP (bevacizumab 15 mg kg−1 day 1 plus capecitabine 1000 mg m−2 bid days 1-14 q3w). The study population was categorised into three cohorts: triple-negative breast cancer (TNBC), high-risk hormone receptor-positive (HR+) and low-risk HR+. High- and low-risk HR+ were defined, respectively, as having ⩾2 vs ⩽1 of the following four risk factors: disease-free interval ⩽24 months; visceral metastases; prior (neo)adjuvant anthracycline and/or taxane; and metastases in ⩾3 organs.Results:The treatment effect on OS differed between cohorts. Non-significant OS trends favoured BEV-PAC in the TNBC cohort and BEV-CAP in the low-risk HR+ cohort. In all three cohorts, there was a non-significant PFS trend favouring BEV-PAC. Grade ⩾3 adverse events were consistently less common with BEV-CAP.Conclusions:A simple risk factor index may help in selecting bevacizumab-containing regimens, balancing outcome, safety profile and patient preference. Final OS results are expected in 2015 (ClinicalTrials.gov NCT00600340). [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this retrospective analysis was to assess efficacy and tolerability of trabectedin in soft tissue sarcoma (STS) in the routine clinical setting. Patients and methods: Efficacy and safety data of trabectedin were retrospectively evaluated in patients with advanced STS who had started treatment with trabectedin at six institutions in Austria between January 2008 and May 2012. Results: Data of 101 adult patients were included in the present analysis. Patients had a median age of 56 years; 59 and 41 % received trabectedin as ≤2nd and ≥3rd chemotherapy line for advanced disease, respectively. Median progression-free survival (PFS) and overall survival (OS) were 3.9 and 11.6 months. Median PFS and OS were different in patients who received trabectedin as ≤2nd- or ≥3rd-line treatment: median PFS was 3.9 versus 3.6 months and OS was 15.2 versus 24.8 months, respectively. The extent and severity of trabectedin-induced toxicity were low and manageable. Conclusions: The activity and tolerability of trabectedin in the routine clinical setting is comparable to outcomes reported in phase II trials already published. Regardless of whether trabectedin was given earlier or later in the course of disease, outcomes did not differ in the cohort of analysed patients. [ABSTRACT FROM AUTHOR]

Anti-Her-2/neu antibody is known to induce apoptosis in HER-2/neu overexpressing breast cancer cells. However, exact regulatory mechanisms mediating and controlling this phenomenon are still unknown. In the present study, we have investigated the effect of anti-Her-2/neu antibody on apoptosis of HER-2/neu overexpressing human breast cancer cell lines SK-BR-3, HTB-24, HTB-25, HTB-27, HTB-128, HTB-130 and HTB-131 in relation to p53 genotype and bcl-2 status. SK-BR-3, HTB-24, HTB-128 and HTB-130 cells exhibited mutant p53, whereas wild type p53 was found in HTB-25, HTB-27 and HTB-131 cells. All seven cell lines weakly expressed bcl-2 protein (10-20%). Anti-Her-2/neu antibody, irrespective of p53 and bcl-2 status, induced apoptosis in all 7 cell lines dose- and time-dependently and correlated with Her-2/neu overexpression. In addition, incubation of cell lines with anti-Her-2/neu antibody did not alter p53 or bcl-2 expression. Anti-HER-2/neu antibody did not induce apoptosis in HER-2/neu negative HBL-100 and HTB-132 cell lines. Our results indicate that within the panel of tested breast cancer cell lines, anti-Her-2/neu antibody-induced apoptosis was independent from the presence of intact p53. [ABSTRACT FROM AUTHOR]

Uncontrolled proliferation and a defect of apoptosis constitute crucial elements in the development and progression of tumours. Among many other biological response modifiers known to influence these mechanisms, the efficacy of retinoids and interferons in the treatment of various malignant entities is currently matter of discussion. In the present study, we have investigated the effects of 9-cis-retinoic acid (9cRA), 13-cis-retinoic acid (13cRA), all-trans-retinoic acid (tRA) and interferon-α on proliferation and apoptosis of human soft tissue sarcoma (STS) cell lines HTB-82 (rhabdomyosarcoma), HTB-91 (fibrosarcoma), HTB-92 (liposarcoma), HTB-93 (synovial sarcoma) and HTB-94 (chondrosarcoma) in relation to p53 genotype as well as p53 expression. HTB-91, HTB-92 and HTB-94 STS cells exhibited mutant p53, whereas wild-type p53 was found in HTB-93 STS cells, and a normal p53 status in HTB-82 STS cells, carrying a silent point mutation only. Interferon-α, irrespective of p53 status, inhibited the proliferation of all five cell lines dose- and time-dependently. Similarly, 9cRA, 13cRA and tRA decreased the proliferation of HTB-82 and HTB-93 STS cells, whereas the proliferation of p53-mutated HTB-91, HTB-92 and HTB-94 STS cells remained unchanged. Furthermore, only 9cRA and tRA were capable of inducing apoptosis in HTB-82 and HTB-93 STS cells, whereas HTB-91, HTB-92 and HTB-94 STS cells did not undergo apoptosis under the influence of 9cRA or tRA. Retinoic acid receptor (RAR)-α and RAR-β mRNA were not detectable by Northern blot analysis in the five STS cell lines, whereas mRNA for the universal retinoic acid receptor, RAR-γ, was expressed in all STS cell lines indicating that retinoid resistance was not associated with a lack of RAR expression. Apoptosis was not induced by interferon-α or 13cRA in any of the five STS cell lines tested. Our results indicate that within the panel of tested STS cell lines, inhibition of proliferation... [ABSTRACT FROM AUTHOR]

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Background: Investigations originating from our laboratory have reported deficiencies in antigen presentation and functionality of monocytes derived from patients with early breast cancer (EBC), but not from healthy women with germline mutations of BRCA1. We have now expanded our investigations to dendritic cells (DC) which have been only insufficiently studied in patients with EBC in general and in healthy BRCA1 mutant carriers in particular. Methods: DC derived from patients with EBC and healthy women with BRCA1 mutations were analysed for the expression of DC-specific antigens CD1a, CD11c, CD83, CD80, CD86, CD54 and CD14 and of T cell-associated costimulatory molecules CD28 and CD152 (CTLA4). Antigen presentation by DCs was evaluated by a T-cell proliferation assay using tetanus toxoid (TT) as antigen. Peripheral blood was obtained from 36 patients with EBC, 5 healthy women with germline mutations of BRCA1 and from 26 healthy age-matched control persons. PBMC were prepared for ex vivo DC generation using GM-CSE IL4 and TNF-_ according to standard procedures. DC phenotype was examined by flow cytometry. T cell -- proliferation in response to TT-pulsed DCs was measured by (3H)thymidine assay. Results: DC derived from patients with EBC presented with a significantly reduced expression of DC-associated antigens CDla (p = 0.02), CD83 (p = 0.0001), CD80 (p = 0.01), CD86 (p < 0.0001)and CD54 (p < 0.000l) as compared to DC derived from healthy control females. Moreover, CD3- CD4- CD8- DC derived from the latter patient population had an obviously aberrant expression of costimulatory molecule CD28. In contrast, no significant differences in the expression of CD1a, CD86, CD83 and CD11c, hut significantly higher expression of costimulatory molecules CD80 (p = 0.003) and CD54 (p = 0.009) was found on DCs derived from healthy women with germline mutations of BRCA1, as compared to DCs derived from healthy women. Finally, T cell-proliferation in response to TT-pulsed autologous DCs was significantly decreased in patients with EBC, as compared to healthy control individuals (p < 0.0001). Conclusions: DCs derived from patients with EBC had not only an immature and aberrant phenotype, but also functional impairment in TT presentation which was not detectable prior to the development of disease in high-risk individuals with BRCA1 germline mutation. [ABSTRACT FROM AUTHOR]