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PVP-stabilized tungsten oxide nanoparticles: pH sensitive anti-cancer platform with high cytotoxicity.
Popov, AL, Han, B, Ermakov, AM, Savintseva, IV, Ermakova, ON, Popova, NR, Shcherbakov, AB, Shekunova, TO, Ivanova, OS, Kozlov, DA, et al
Materials science & engineering. C, Materials for biological applications. 2020;:110494
Abstract
Photochromic tungsten oxide (WO3) nanoparticles stabilized by polyvinylpyrrolidone (PVP) were synthesized to evaluate their potential for biomedical applications. PVP-stabilized tungsten oxide nanoparticles demonstrated a highly selective cytotoxic effect on normal and cancer cells in vitro. WO3 nanoparticles were found to induce substantial cell death in osteosarcoma cells (MNNG/HOS cell line) with a half-maximal inhibitory concentration (IC50) of 5 mg/mL, while producing no, or only minor, toxicity in healthy human mesenchymal stem cells (hMSc). WO3 nanoparticles induced intracellular oxidative stress, which led to apoptosis type cell death. The selective anti-cancer effects of WO3 nanoparticles are due to the pH sensitivity of tungsten oxide and its capability of reactive oxygen species (ROS) generation, which is expressed in the modulation of genes involved in reactive oxygen species metabolism, mitochondrial dysfunction, and apoptosis.
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In vivo detection of changes in cutaneous carotenoids after chemotherapy using shifted excitation resonance Raman difference and fluorescence spectroscopy.
Jung, S, Darvin, ME, Schleusener, J, Thiede, G, Lademann, J, Braune, M, Maiwald, M, Sumpf, B, Tränkle, G, Kutzer, D, et al
Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI). 2020;(2):301-307
Abstract
BACKGROUND Various cutaneous toxicities under chemotherapy indicate a local effect of chemotherapy by secretion after systemic application. Here, changes in the fluorescence and Raman spectral properties of the stratum corneum subsequent to intravenous chemotherapy were assessed. METHODS Twenty healthy subjects and 20 cancer patients undergoing chemotherapy were included. Measurement time points in cancer patients were before the first cycle of chemotherapy (Tbase ) and immediately after intravenous application of the chemotherapy (T1 ). Healthy subjects were measured once without any further intervention. Measurements were conducted using an individually manufactured system consisting of a handheld probe and a wavelength-tunable diode laser-based 488 nm SHG light source. Hereby, changes in both skin fluorescence and shifted excitation resonance Raman difference spectroscopy (SERRDS) carotenoid signals were assessed. RESULTS Healthy subjects showed significantly (P < .001) higher mean concentrations of carotenoids compared to cancer subjects at Tbase . An increase in fluorescence intensity was detected in almost all patients after chemotherapy, especially after doxorubicin infusion. Furthermore, a decrease in the carotenoid concentration in the skin after chemotherapy was found. CONCLUSION The SERRDS based noninvasive detection can be used as an indirect quantitative assessment of fluorescent chemotherapeutics. The lower carotenoid SERRDS intensities at Tbase might be due to cancerous diseases and co-medication.
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Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives.
Moghadam, ER, Ang, HL, Asnaf, SE, Zabolian, A, Saleki, H, Yavari, M, Esmaeili, H, Zarrabi, A, Ashrafizadeh, M, Kumar, AP
Biomolecules. 2020;(10)
Abstract
Pharmacological profile of phytochemicals has attracted much attention to their use in disease therapy. Since cancer is a major problem for public health with high mortality and morbidity worldwide, experiments have focused on revealing the anti-tumor activity of natural products. Flavonoids comprise a large family of natural products with different categories. Chrysin is a hydroxylated flavonoid belonging to the flavone category. Chrysin has demonstrated great potential in treating different disorders, due to possessing biological and therapeutic activities, such as antioxidant, anti-inflammatory, hepatoprotective, neuroprotective, etc. Over recent years, the anti-tumor activity of chrysin has been investigated, and in the present review, we provide a mechanistic discussion of the inhibitory effect of chrysin on proliferation and invasion of different cancer cells. Molecular pathways, such as Notch1, microRNAs, signal transducer and activator of transcription 3 (STAT3), nuclear factor-kappaB (NF-κB), PI3K/Akt, MAPK, etc., as targets of chrysin are discussed. The efficiency of chrysin in promoting anti-tumor activity of chemotherapeutic agents and suppressing drug resistance is described. Moreover, poor bioavailability, as one of the drawbacks of chrysin, is improved using various nanocarriers, such as micelles, polymeric nanoparticles, etc. This updated review will provide a direction for further studies in evaluating the anti-tumor activity of chrysin.
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The Role of Diet in Cancer Prevention and Chemotherapy Efficacy.
Mittelman, SD
Annual review of nutrition. 2020;:273-297
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Abstract
Despite great advances in treatment, cancer remains a leading cause of death worldwide. Diet can greatly impact health, while caloric restriction and fasting have putative benefits for disease prevention and longevity. Strong epidemiological associations exist between obesity and cancer, whereas healthy diets can reduce cancer risk. However, less is known about how diet might impact cancer once it has been diagnosed and particularly how diet can impact cancer treatment. In the present review, we discuss the links between obesity, diet, and cancer. We explore potential mechanisms by which diet can improve cancer outcomes, including through hormonal, metabolic, and immune/inflammatory effects, and present the limited clinical research that has been published in this arena. Though data are sparse, diet intervention may reduce toxicity, improve chemotherapy efficacy, and lower the risk of long-term complications in cancer patients. Thus, it is important that we understand and expand the science of this important but complex adjunctive cancer treatment strategy.
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Cost-effectiveness analysis of ramucirumab treatment for patients with hepatocellular carcinoma who progressed on sorafenib with α-fetoprotein concentrations of at least 400 ng/ml.
Zheng, H, Qin, Z, Qiu, X, Zhan, M, Wen, F, Xu, T
Journal of medical economics. 2020;(4):347-352
Abstract
Objective: This study aimed to compare the cost-effectiveness of ramucirumab versus placebo for patients with hepatocellular carcinoma who progressed on sorafenib with α-fetoprotein concentrations (AFP) of at least 400 ng/ml in the United States.Methods: A Markov model was constructed to assess the cost-effectiveness of ramucirumab. Health outcomes were measured as quality-adjusted life years (QALYs). With TreeAge software, the disease process was modeled as three health states: progression-free survival (PFS), progressive disease (PD), and death. Costs were extracted from the REACH-2 trial, and utility was derived from published literature. Incremental cost-effectiveness ratios (ICERs) were calculated to compare ramucirumab with placebo. Probabilistic sensitivity analyses were developed to examine the robustness of the results.Results: In the base case analysis, ramucirumab therapy had a cost of $55,508.41 and generated 0.54 QALYs, while placebo therapy had a cost of $761.09 and generated 0.47 QALYs, leading to an additional $54,747.32 in costs and 0.07 QALYs. The ICER was $782,104.57 per QALY, which was much higher than the willingness-to-pay threshold of $100,000 per QALY. According to sensitivity analyses, the utility of PD in the two groups was the dominant parameter influencing the ICER.Conclusion: Although ramucirumab was associated with prolonged survival for patients with advanced hepatocellular carcinoma who progressed on sorafenib treatment with an AFP of at least 400 ng/ml, it is not a cost-effective treatment from a United States payer perspective.
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Novel therapeutic approaches in chronic myeloid leukemia.
Özgür Yurttaş, N, Eşkazan, AE
Leukemia research. 2020;:106337
Abstract
The tyrosine kinase inhibitors (TKIs) have revolutionized the management of chronic myeloid leukemia (CML) and BCR-ABL1 inhibitors form the mainstay of CML treatment. Although patients with CML generally do well under TKI therapy, there is a subgroup of patients who are resistant and/or intolerant to TKIs. In these group of patients, there is the need of additional treatment strategies. In this review, we provide an update on the current knowledge of these novel treatment approaches that can be used alone and/or in combination with TKIs.
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Statins as Anticancer Agents in the Era of Precision Medicine.
Longo, J, van Leeuwen, JE, Elbaz, M, Branchard, E, Penn, LZ
Clinical cancer research : an official journal of the American Association for Cancer Research. 2020;(22):5791-5800
Abstract
Statins are widely prescribed cholesterol-lowering drugs that inhibit HMG-CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate metabolic pathway. Multiple lines of evidence indicate that certain cancers depend on the mevalonate pathway for growth and survival, and, therefore, are vulnerable to statin therapy. However, these immediately available, well-tolerated, and inexpensive drugs have yet to be successfully repurposed and integrated into cancer patient care. In this review, we highlight recent advances and outline important considerations for advancing statins to clinical trials in oncology.
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Comparative efficacy and safety of interventions for preventing chemotherapy-induced oral mucositis in adult cancer patients: a systematic review and network meta-analysis.
Wilairat, P, Kengkla, K, Kaewpanan, T, Kaewthong, J, Ruankon, S, Subthaweesin, C, Stenehjem, DD, Saokaew, S
European journal of hospital pharmacy : science and practice. 2020;(2):103-110
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Abstract
OBJECTIVE To examine the comparative efficacy and safety of interventions for preventing chemotherapy-induced oral mucositis (OM) in adult cancer patients. METHODS We searched PubMed, Embase and the Cochrane Central systematically for the randomised control trials (RCTs) of interventions for preventing OM. Network meta-analysis (NMA) was performed to estimate risk ratios (RR) and 95% confidence intervals (CI) from both direct and indirect evidence. The primary outcome was any grade of OM. Secondary outcomes were mild-moderate OM, severe OM and adverse events, such as taste disturbance and gastrointestinal adverse events. This study was registered with PROSPERO, number CRD42016052489. RESULTS A total of 29 RCTs with 2348 patients (median age, 56.1 years; 57.5% male) were included. Cryotherapy was associated with a significantly lower risk of OM than control (RR 0.51, 95% CI 0.38 to 0.68), and zinc sulphate (RR 0.47, 95% CI 0.23 to 0.97), but not significantly lower than sucralfate and palifermin. No significant differences were observed between cryotherapy and control for taste disturbance and gastrointestinal adverse events. Palifermin was associated with the highest risk of taste disturbance. CONCLUSIONS This NMA suggests that cryotherapy was the most effective intervention for preventing chemotherapy-induced OM with a safety profile similar to control, but not significantly lower than sucralfate and palifermin. Large RCTs are needed to confirm these findings.
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miR-139-mediated NOTCH1 regulation is crucial for the inhibition of osteosarcoma progression caused by resveratrol.
Xiao, X, Zhang, Y, Pan, W, Chen, F
Life sciences. 2020;:117215
Abstract
AIMS: Osteosarcoma (OS) has the highest incidence among primary malignancies. It is characterized by high tumor heterogeneity, poor prognosis and high lung metastases. Here, we aimed to investigate the role of resveratrol on an OS cell line and its mechanism. MATERIALS AND METHODS Cell apoptosis and proliferation were analyzed by MTT and flow cytometry analysis respectively. In U2OS cells miR-139-5p overexpression or knock-down and NOTCH1 knock-down cell models were constructed. Quantitative real-time PCR were used to determine the expression of miR-139-5p. Western bot was used to detect levels of NOTCH1, caspase3 and cleaved-caspase-3. Dual luciferase activity assay was used to assess the target of miR-139-5p. KEY FINDINGS The apoptosis of U20S and MG63 cell were induced by resveratrol, and lower levels of miR-139-5p in both U2OS and MG63 cells than in osteoblast cells. Alteration of miR-139-5p had an outstanding effect on apoptosis of U2OS cell. The expression of miR-139-5p in U2OS and MG63 cells can be induced by resveratrol. Bioinformatic analysis indicated that the 3'UTR of NOTCH1 contained the motif for microRNA-139-5p binding. Co-transfection with the luciferase reporter contained the wild-type, but not the mutant, of 3'UTR of NOTCH1, together with miR-139-5p decreased the luciferase activity in U2OS cells. NOTCH1 gene knockout altered the apoptosis of U2OS cell. SIGNIFICANCE Collectively, these findings indicate that resveratrol induces the apoptosis of OS cells via the miR-139-5p/NOTCH1 signaling pathway, and provides an experimental and theoretical basis for the development of natural plant-derived compounds that can effectively prevent and treat OS.
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Covariate-adjusted analysis of the Phase 3 REFLECT study of lenvatinib versus sorafenib in the treatment of unresectable hepatocellular carcinoma.
Briggs, A, Daniele, B, Dick, K, Evans, TRJ, Galle, PR, Hubner, RA, Lopez, C, Siebert, U, Tremblay, G
British journal of cancer. 2020;(12):1754-1759
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Abstract
BACKGROUND In the Phase 3 REFLECT trial in patients with unresectable hepatocellular carcinoma (uHCC), the multitargeted tyrosine kinase inhibitor, lenvatinib, was noninferior to sorafenib in the primary outcome of overall survival. Post-hoc review revealed imbalances in prognostic variables between treatment arms. Here, we re-analyse overall survival data from REFLECT to adjust for the imbalance in covariates. METHODS Univariable and multivariable adjustments were undertaken for a candidate set of covariate values that a physician panel indicated could be prognostically associated with overall survival in uHCC. The values included baseline variables observed pre- and post-randomisation. Univariable analyses were based on a stratified Cox model. The multivariable analysis used a "forwards stepwise" Cox model. RESULTS Univariable analysis identified alpha-fetoprotein (AFP) as the most influential variable. The chosen multivariable Cox model analysis resulted in an estimated adjusted hazard ratio for lenvatinib of 0.814 (95% CI: 0.699-0.948) when only baseline variables were included. Adjusting for post-randomisation treatment variables further increased the estimated superiority of lenvatinib. CONCLUSIONS Covariate adjustment of REFLECT suggests that the original noninferiority trial likely underestimated the true effect of lenvatinib on overall survival due to an imbalance in baseline prognostic covariates and the greater use of post-treatment therapies in the sorafenib arm. TRIAL REGISTRATION Trial number: NCT01761266 (Submitted January 2, 2013).