The effects of quercetin on liver regeneration after liver resection in rats

The aim of the present study was to assess the influence of quercetine (QE) on liver regeneration after partial hepatectomy (PH) in rats. A total of 24 male Wistar albino rats were divided into three groups: sham-operated (SH), PH and PH+QE; each group contain 8 animals. The rats in QE-treated groups were given QE (15 mg/kg body weight) once a day i.p., for 7 days starting 3 days prior to hepatectomy operation. At 7 days after resection, liver samples were collected. The malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were estimated in liver homogenates. Moreover, histopathological examination, mitotic index (MI), proliferating cell nuclear antigen labelling, proliferation index (PI), transferase-mediated dUTP nick end-labelling assay, apoptotic index (AI) were evaluated at 7 days after hepatectomy. As a result, QE significantly increased MI, PI, and significantly decreased AI in PH rats. Additionally, QE remarkably inhibited the elevation of MDA, restored impaired antioxidant SOD activity and GSH level, and also attenuated hepatic vacuolar degeneration and sinusoidal congestion. These results suggested that QE treatment had a beneficial effect on liver regenerative capacity of the remnant liver tissue after hepatectomy, probably due to its antioxidative, antiapoptotic and proliferative property

MLP (muscle LIM protein) as a stress sensor in the heart

Muscle LIM protein (MLP, also known as cysteine rich protein 3 (CSRP3, CRP3)) is a muscle-specific-expressed LIM-only protein. It consists of 194 amino-acids and has been described initially as a factor involved in myogenesis (Arber et al. Cell 79:221–231, 1994). MLP soon became an important model for experimental cardiology when it was first demonstrated that MLP deficiency leads to myocardial hypertrophy followed by a dilated cardiomyopathy and heart failure phenotype (Arber et al. Cell 88:393–403, 1997). At this time, this was the first genetically altered animal model to develop this devastating disease. Interestingly, MLP was also found to be down-regulated in humans with heart failure (Zolk et al. Circulation 101:2674–2677, 2000) and MLP mutations are able to cause hypertrophic and dilated forms of cardiomyopathy in humans (Bos et al. Mol Genet Metab 88:78–85, 2006; Geier et al. Circulation 107:1390–1395, 2003; Hershberger et al. Clin Transl Sci 1:21–26, 2008; Knöll et al. Cell 111:943–955, 2002; Knöll et al. Circ Res 106:695–704, 2010; Mohapatra et al. Mol Genet Metab 80:207–215, 2003). Although considerable efforts have been undertaken to unravel the underlying molecular mechanisms—how MLP mutations, either in model organisms or in the human setting cause these diseases are still unclear. In contrast, only precise knowledge of the underlying molecular mechanisms will allow the development of novel and innovative therapeutic strategies to combat this otherwise lethal condition. The focus of this review will be on the function of MLP in cardiac mechanosensation and we shall point to possible future directions in MLP research

Effect of context exposure after fear learning on memory generalization in mice

BackgroundThe conditions under which memory generalization occurs are not well understood. Although it is believed that fear memory generalization is gradually established after learning, it is not clear whether experiences soon after learning affect generalization.ResultsUsing a contextual fear conditioning paradigm in mice, we found that fear memory generalization occurred when mice were exposed to a familiar, unconditioned context soon after fear learning.ConclusionsOur results suggest that the familiarity of contexts and the timing of their exposure influences memory generalization, which increases our understanding of the mechanisms of generalization

Pertuzumab, trastuzumab and taxane-based treatment for visceral organ metastatic, trastuzumab-naïve breast cancer: real-life practice outcomes

PubMedID: 30377778Purpose: In this study, we aimed to describe the real-life practice outcomes of pertuzumab–trastuzumab–taxane (PTT) combination in visceral organ metastatic, trastuzumab-naive breast cancer (BC) patients. Methods: This study was conducted by Turkish Oncology Group and included 317 patients’ data from 36 centers. Results: Median age was 51 (22–82). Median PFS was 28.5 months, while median OS was 40.3 months. Patients with brain metastases (n: 13, 4.1%) had worse PFS (16.8 m vs. 28.5 m; p = 0.002) and OS (26.7 m vs. 40.3 m; p = 0.009). Patients older than 65 years of age (n: 42, 13.2%) had significantly lower OS results (19.8 m vs. 40.3 m; p = 0.01). Two hundred sixty-eight patients (86.7%) received docetaxel while 37 patients (11.7%) received paclitaxel. PFS and OS were similar between taxane groups. In eight patients (2.5%), 5–40% ejection fraction decrement from baseline was detected without any clinical sign of heart failure. Conclusions: Our RLP trial included only visceral metastatic, trastuzumab-naïve BC patients including cases with brain involvement who received PTT combination in the first-line treatment. Regardless of negative prognostic characteristics, our results are in parallel with pivotal trial. Further strategies for brain metastasis should be developed to improve outcomes despite encouraging results with PTT treatment. Taxane selection can be personalized and endocrine maintenance may further improve outcomes after taxanes were discontinued. To our knowledge, this is the largest scale real-life clinical practice study of pertuzumab–trastuzumab–taxane therapy to date. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.Bangladesh University of Health Sciencesand with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the committee of University of Health Sciences, Ankara Oncology Education and Research Hospital (TUEK meeting number: 40-15.5.2018)

Pertuzumab, trastuzumab and taxane-based treatment for visceral organ metastatic, trastuzumab-naive breast cancer: real-life practice outcomes

WOS: 000458407200014PubMed ID: 30377778PurposeIn this study, we aimed to describe the real-life practice outcomes of pertuzumab-trastuzumab-taxane (PTT) combination in visceral organ metastatic, trastuzumab-naive breast cancer (BC) patients.MethodsThis study was conducted by Turkish Oncology Group and included 317 patients' data from 36 centers.ResultsMedian age was 51 (22-82). Median PFS was 28.5months, while median OS was 40.3months. Patients with brain metastases (n: 13, 4.1%) had worse PFS (16.8m vs. 28.5m; p=0.002) and OS (26.7m vs. 40.3m; p=0.009). Patients older than 65years of age (n: 42, 13.2%) had significantly lower OS results (19.8m vs. 40.3m; p=0.01). Two hundred sixty-eight patients (86.7%) received docetaxel while 37 patients (11.7%) received paclitaxel. PFS and OS were similar between taxane groups. In eight patients (2.5%), 5-40% ejection fraction decrement from baseline was detected without any clinical sign of heart failure.ConclusionsOur RLP trial included only visceral metastatic, trastuzumab-naive BC patients including cases with brain involvement who received PTT combination in the first-line treatment. Regardless of negative prognostic characteristics, our results are in parallel with pivotal trial. Further strategies for brain metastasis should be developed to improve outcomes despite encouraging results with PTT treatment. Taxane selection can be personalized and endocrine maintenance may further improve outcomes after taxanes were discontinued. To our knowledge, this is the largest scale real-life clinical practice study of pertuzumab-trastuzumab-taxane therapy to date

Relation between sarcopenia and dose-limiting toxicity in patients with metastatic colorectal cancer who received regorafenib

BackgroundSarcopenia is related to poor prognosis and drug toxicities in solid tumors. The aim of our study is to investigate the predisposition of patients with metastatic colorectal carcinoma who started regorafenib treatment to sarcopenia and prolonged survival.MethodsPatients with metastatic colorectal carcinoma who receives regorafenib were search retrospectively. Dose-limiting toxicity was defined as dose reduction or toxicity requiring drug withdrawal. Sarcopenia evaluation was made with computed tomography performed within a month before treatment. Progression-free survival and overall survival were estimated.ResultsThirty-six patients were found as suitable for the study. 63.9% of patients were found as basally sarcopenic. Dose-limiting toxicity occured 13 of 23 patients (56.5%) with basal sarcopenia, whereas only 1 of 13 patients (7.6%) with no sarcopenia exhibited dose-limiting toxicity (p=0.005). Three patients suffered from grade 3-4 toxicity. Hand-foot syndrome, hypertension, and mucosal rash were the most seen side effects. Mean regorafenib treatment duration was 3.36 months. There was no significant difference in the progression-free survival (PFS) and the overall survival (OS) between sarcopenic patients and patients with no sarcopenia. Durations were as OS 24.2 weeks in patients with sarcopenia (95% CI 16.7-31.7), 28.1 weeks in patients with no sarcopenia (95% CI 20.5-35.7) (p=0.36), and as PFS 14.2 weeks in patients with sarcopenia (95% CI 12.1-16.4), 14.8 weeks in patients with no sarcopenia (95% CI 9.7-20.1) (p=0.65).ConclusionDose-limiting toxicity was significantly higher in basally sarcopenic patients who were started regorafenib as treatment of metastatic colorectal carcinoma. There was no significant relationship between overall survival and progression-free survival with sarcopenia