Improved semiclassical dynamics through adiabatic switching trajectory sampling

We introduce an improved semiclassical dynamics approach to quantum vibrational spectroscopy. In this method, a harmonic-based phase space sampling is preliminarily driven toward non-harmonic quantization by slowly switching on the actual potential. The new coordinates and momenta serve as initial conditions for the semiclassical dynamics calculation, leading to a substantial decrease in the number of chaotic trajectories to deal with. Applications are presented for model and molecular systems of increasing dimensionality characterized by moderate or high chaoticity. They include a bidimensional Henon-Heiles potential, water, formaldehyde, and methane. The method improves accuracy and precision of semiclassical results and it can be easily interfaced with all pre-existing semiclassical theories

Is there still a place for vinorelbine in advanced metastatic castration resistant prostate cancer?

The aim of this paper was to evaluate the activity and tolerability of oral vinorelbine in patients with advanced castration resistant prostate cancer (CRPC) who progressed after a minimum of three lines including: abiraterone acetate, docetaxel, cabazitaxel, and enzalutamide.Treatment consisted of weekly oral vinorelbine 60\u200amg/m. Chemotherapy was administered until disease progression or unacceptable toxicity.Twenty-six patients received vinorelbine: their median age was 74 years (range 58-84 years). Twenty-four (92.3%) patients had bone metastases. A decrease in PSA levels 6550% was observed in 2 patients (7.7%). Among the subjects who were symptomatic at baseline, pain was reduced in 3 patients (13.6%) with a significant decrease in analgesic use. Median progression-free survival was 9 weeks (95% CI: 7 to 11) and median overall survival was 17 weeks (95% CI: 12 to 22). Treatment was well tolerated, and no grade 4 toxicities were observed.Our findings do not suggest the use of oral vinorelbine on a weekly schedule, in CRPC heavily pre-treate

Current status of androgen receptor-splice variant 7 inhibitor niclosamide in castrate-resistant prostate-cancer

Castrate-Resistant Prostate-Cancer (CRPC) is one of the most common malignancies occurring in men. Unfortunately, even if several recently approved agents clinically improved the outcome of CRPC patients, none of these is curative especially for a splice version of the Androgen Receptor (AR) AR-V7, which is a variant of the receptor constitutively activated and does not require the presence of androgens for the activation AR down-stream pathways. Since high AR-V7 expression is one of the most common features of CRPC, targeting this receptor variant is considered as one of the most promising strategies for treating this disease. Therefore anti-AR-V7 molecules could lead to a potential shift in paradigm in the treatment of CRPC. Niclosamide, an already FDA-approved anti-helminthic drug, was identified as a potent AR-V7 inhibitor in prostate cancer cells. Due to the recent positive preclinical results, niclosamide may be an interesting and novel type of targeted treatments for CRPC. This mini-review outlines the most recent pre- and clinical- data on the current status of niclosamide in the treatment of ARV7-positive CRPC patients

Effect of Feijoa Sellowiana Acetonic Extract on Proliferation Inhibition and Apoptosis Induction in Human Gastric Cancer Cells

Gastric cancer (GC) still represents a relevant health problem in the world for both incidence and mortality rates. Many studies underlined that natural products consumption could reduce GC risk, indicating flavonoids as responsible for the beneficial eects through the modulation of several biological processes, such as the inhibition of cancer antioxidant defense and induction of apoptosis. Since Feijoa sellowiana fruit is known to contain high amounts of flavonoids, among which is flavone, we evaluated the antiproliferative and proapoptotic eects of F. sellowiana acetonic extract on GC cell lines through MTS and Annexin-V FITC assays. Among three GC cell lines tested, SNU-1 results being sensitive to both the F. sellowiana acetonic extract and synthetic flavone, which was used as the reference treatment. Moreover, we evaluated their antioxidant eects, assessing the activity of the antioxidant enzymes supeoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in polymorphonuclear cells. We found a significant increase of their activity after exposure to both F. sellowiana acetonic extract and flavone, supporting the idea that a diet that includes flavone-rich fruits could be of benefit for health. In addition to this antioxidant eect on normal cells, this study indicates, for the first time, an anticancer eect of F. sellowiana acetonic extract in GC cells

Role of IL-6/STAT3 Axis in Resistance to Cisplatin in Gastric Cancers

Gastric cancer, the second most common cause of death worldwide, is characterized by poor prognosis and low responsiveness to chemotherapy. Indeed, multidrug resistance, based mainly on cellular and molecular factors, remains one of the most limiting factors of the current approach to gastric cancer (GC) therapy. We employed a comprehensive gene expression analysis through data mining of publicly available databases to assess the role of the signal transducer and activator of transcription 3 (STAT3) in gastric cancer drug efficiency. It has been proposed that gastric cancer cells are less sensitive to these drugs because they develop resistance to these agents through activating alternative signalling pathways responsible for overcoming pharmacological inhibition. Our study evaluated the hypothesis that activating STAT3 signalling in response to cisplatin reduces the reaction to the drug. Consistent with this hypothesis, inhibition of interleukin 6 (IL-6)/STAT3 in combination therapy with cisplatin prevented both STAT3 activation and more lethality than induction by a single agent. The data suggest that the IL-6/STAT3 axis block associated with cisplatin treatment may represent a strategy to overcome resistance

The evolving role of monoclonal antibodies in the treatment of patients with advanced renal cell carcinoma: a systematic review

Introduction: While the majority of the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors currently used for the therapy of metastatic renal cell carcinoma (mRCC) are small molecule agents inhibiting multiple targets, monoclonal antibodies are inhibitors of specific targets, which may decrease off-target effects while preserving on-target activity. A few monoclonal antibodies have already been approved for mRCC (bevacizumab, nivolumab), while many others may play an important role in the therapeutic scenario of mRCC. Areas covered: This review describes emerging monoclonal antibodies for treating RCC. Currently, bevacizumab, a VEGF monoclonal antibody, is approved in combination with interferon for the therapy of metastatic RCC, while nivolumab, a Programmed Death (PD)-1 inhibitor, is approved following prior VEGF inhibitor treatment. Other PD-1 and PD-ligand (L)-1 inhibitors are undergoing clinical development. Expert opinion: Combinations of inhibitors of the PD1/PD-L1 axis with VEGF inhibitors or cytotoxic T-lymphocyte antigen (CTLA)-4 inhibitors have shown promising efficacy in mRCC. The development of biomarkers predictive for benefit and rational tolerable combinations are both important pillars of research to improve outcomes in RCC

Third-line sorafenib after sequential therapy with sunitinib and mTOR inhibitors in metastatic renal cell carcinoma

Background: Sunitinib and everolimus have been approved for first- and second-line treatment, respectively, in metastatic renal cell carcinoma (mRCC). The role of sorafenib, which is approved for second-line treatment after cytokines failure, is presently to be defined. Objective: To determine whether third-line sorafenib after sequential use of sunitinib and mammalian target of rapamycin inhibitors (everolimus or temsirolimus) is feasible and effective. Design, setting, and participants: One hundred fifty medical records of patients with mRCC treated with first-line sunitinib between January 2006 and January 2010 were reviewed at four participating centers. Data regarding patients treated with the sequence sunitinib-everolimus or temsirolimus-sorafenib were extracted. Central analysis of radiographic images was performed using RECIST criteria to determine progression-free survival (PFS) and overall response rate (oRR) to sorafenib treatment. Measurements: PFS and oRR to sorafenib were the primary end points. Secondary outcomes were safety and overall survival (OS). Results and limitations: Thirty-four patients were eligible for the study. A median PFS of 4 mo (range: 3-6 mo) and a median OS of 7 mo since sorafenib treatment (range: 6-10 mo) were reported. Of the patients, 23.5% showed response to sorafenib, with an overall disease control rate (complete responses plus partial responses plus stable disease) of 44%. Selection bias, data incompleteness, and absence of study design are inevitable limitations of the study, although central review can strengthen the quality of presented data. Conclusions: Third-line sorafenib appears to be active and well tolerated in mRCC after first-line sunitinib and second-line everolimus or temsirolimus, with no patients interrupting sorafenib because of toxicity or lack of compliance. Prospective, placebo-controlled trials are completely lacking and are required in this setting