Histone deacetylase inhibitor vorinostat suppresses the growth of uterine sarcomas in vitro and in vivo

<p>Abstract</p> <p>Background</p> <p>Uterine sarcomas are very rare malignancies with no approved chemotherapy protocols. Histone deacetylase (HDAC) inhibitors belong to the most promising groups of compounds for molecular targeting therapy. Here, we described the antitumor effects of suberoylanilide hydroxamic acid (SAHA; vorinostat) on MES-SA uterine sarcoma cells <it>in vitro </it>and <it>in vivo</it>. We investigated effects of vorinostat on growth and colony forming ability by using uterine sarcoma MES-SA cells. We analyzed the influence of vorinostat on expression of different HDACs, p21^WAF1and activation of apoptosis. Finally, we examined the antitumor effects of vorinostat on uterine sarcoma <it>in vivo</it>.</p> <p>Results</p> <p>Vorinostat efficiently suppressed MES-SA cell growth at a low dosage (3 μM) already after 24 hours treatment. Decrease of cell survival was even more pronounced after prolonged treatment and reached 9% and 2% after 48 and 72 hours of treatment, respectively. Colony forming capability of MES-SA cells treated with 3 μM vorinostat for 24 and 48 hours was significantly diminished and blocked after 72 hours. HDACs class I (HDAC2 and 3) as well as class II (HDAC7) were preferentially affected by this treatment. Vorinostat significantly increased p21^WAF1expression and apoptosis. Nude mice injected with 5 × 10⁶MES-SA cells were treated for 21 days with vorinostat (50 mg/kg/day) and, in comparison to placebo group, a tumor growth reduction of more than 50% was observed. Results obtained by light- and electron-microscopy suggested pronounced activation of apoptosis in tumors isolated from vorinostat-treated mice.</p> <p>Conclusions</p> <p>Our data strongly indicate the high therapeutic potential of vorinostat in uterine sarcomas.</p

Scientific Reports / Prognostic role of plasma fibrinogen in patients with uterine leiomyosarcoma : a multicenter study

Fibrinogen has an important pathophysiological role in tumor cell progression and development of metastases in different types of cancer. The present study aimed to evaluate the role of pre-treatment fibrinogen plasma concentrations as a biomarker for tumor biology and prognosis in patients with uterine leiomyosarcoma (ULMS). Clinical data of patients with ULMS were assessed in this multi-center study Pre-therapeutic fibrinogen plasma concentrations were evaluated. We investigated the association between fibrinogen plasma levels and clinico-pathological parameters and performed univariate and multivariable survival analyses. In total, 70 women with ULMS were included into the analysis. Mean (SD) pre-treatment fibrinogen plasma levels were 480.2 (172.3) mg/dL. Patients with advanced tumor stage, increased tumor size and higher histological grading had higher fibrinogen levels (p=0.02, p=0.013, and p=0.029, respectively). In ULMS patients with increased fibrinogen levels 5-year overall survival (OS) rates were 25.0% compared to 52.9% in ULMS patients with normal fibrinogen, respectively. Univariate survival analyses revealed that elevated fibrinogen plasma levels (p=0.030), advanced tumor stage (p<0.001) and undifferentiated histology (p=0.003) showed association with unfavorable OS. In multivariable analysis, histological grade (p=0.03) and tumor stage (0.02) were independently associated with survival. Elevated fibrinogen plasma levels were associated with aggressive tumor biology and poor prognosis in women with ULMS. Fibrinogen might be useful as a novel biomarker in ULMS.(VLID)463719

Pan-European Expert Meeting on the Use of Metronomic Chemotherapy in Advanced Breast Cancer Patients: The PENELOPE Project

Metronomic chemotherapy (mCHT) is a treatment regimen in which drugs are administered frequently or continuously and that maintains low, prolonged, and pharmacologically active plasma concentrations of drugs to avoid toxicity associated with traditional chemotherapy regimens, while achieving tumor response. Despite the increasing use of mCHT in patients with metastatic breast cancer (MBC) and the endorsement of mCHT in guidelines, no consensus exists about which patients may substantially benefit from mCHT, which agents can be recommended, and in which treatment setting mCHT is most appropriate

Gamma-glutamyltransferase as novel biomarker in patients with uterine leiomyosarcoma

Gamma-glutamyltransferase (GGT) is an established marker for proliferative/apoptotic balance and has been associated with cancer risk and prognosis. The aim of this study was to evaluate the value of pre-treatment GGT serum levels as prognostic biomarker in patients with primary uterine leiomyosarcoma (ULMS). Data of women with ULMS were extracted from a multi-center database. Pre-treatment GGT serum levels were measured and patients assigned to predefined GGT risk groups. GGT values were correlated with clinico-pathological parameters and univariate and multivariable survival analyses were performed. A total of 44 patients with ULMS were analyzed. Mean (SD) pre-therapeutic GGT serum level was 33.8 (39.8) U/L. In Figo Stage I versus II-IV mean (SD) GGT values were 28.8 (34.0) U/l and 43.5 (49.2) U/l, respectively (p=0.25). Five-year overall survival (OS) rates in ULMS patients with normal low versus higher GGT levels were 70% and 37%, respectively (p=0.043). Univariate and multivariable analyses revealed that higher GGT serum levels (p=0.043, p=0.005) and high histological grade (p=0.029, p=0.012) were independently associated with impaired OS, respectively. Higher pre-treatment GGT serum levels were independently associated with unfavorable prognosis in women with ULMS. Thus, GGT seems to be a useful novel biomarker in ULMS.(VLID)468871