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1.
Transarterial chemoembolization plus sorafenib versus sorafenib for intermediate-advanced hepatocellular carcinoma: A meta-analysis comparing clinical outcomes.
Xie, Y, Tian, H, Xiang, B, Zhang, Y, Liu, J, Cai, Z, Xiang, H
Medicine. 2021;(33):e26958
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Abstract
BACKGROUND Hepatocellular carcinoma (HCC) ranks as the sixth most common cancer and the second leading cause of cancer-related death worldwide, local and systemic therapies are beneficial for those who have more advanced disease or are not suitable for radical treatment. We aim to investigate the clinical outcomes of transarterial chemoembolization (TACE) plus sorafenib compared with sorafenib monotherapy for intermediate-advanced HCC. METHODS A systematic search according to preferred reporting items for systematic reviews and meta-analyses guidelines in the PubMed database was conducted from inception to December 31, 2020 for published studies comparing survival outcomes and tumor response between TACE + sorafenib and sorafenib alone for intermediate-advanced HCC. RESULTS Five eligible cohort studies and a randomized controlled trial with a total of 3015 patients were identified. We found that the TACE + sorafenib group had a significantly better overall survival (OS) (hazard ratio, 0.77; 95% confidence interval [CI] 0.66-0.88, P < .001) than those treated with sorafenib. Median OS ranged from 7.0 to 22.0 months with TACE + sorafenib and from 5.9 to 18.0 months with sorafenib. The combination of TACE + sorafenib had a significantly better time to progression (hazard ratio, 0.74; 95% CI 0.65-0.82, P < .001) than those treated with sorafenib. Median time to progression ranged from 2.5 to 5.3 months with TACE + sorafenib and from 2.1 to 2.8 months with sorafenib. The results showed the TACE + sorafenib group had a higher disease control rate (log odds ratio, 0.52; 95% CI 0.25-0.80, P = .0002), objective response rate (log odds ratio, 0.85; 95% CI 0.37-1.33, P = .0006) than sorafenib group. Hand-foot skin reaction, diarrhea, fatigue, vomiting, and alanine aminotransferase (ALT) elevation were common adverse events. The adverse events were similar between the 2 groups excluding elevated ALT. CONCLUSION Although the TACE + sorafenib group had a higher elevated ALT, the combination of TACE + sorafenib had an OS benefit compared with sorafenib in the treatment of intermediate-advanced HCC. Further research is necessary to affirm this finding and clarify whether certain subgroups benefit from different combinations between TACE and sorafenib.
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siGCD: a web server to explore survival interaction of genes, cells and drugs in human cancers.
Cui, X, Han, L, Liu, Y, Li, Y, Sun, W, Song, B, Zhou, W, Zhang, Y, Wang, H
Briefings in bioinformatics. 2021;(5)
Abstract
It is pivotal and remains challenge for cancer precision treatment to identify the survival outcome interactions between genes, cells and drugs. Here, we present siGCD, a web-based tool for analysis and visualization of the survival interaction of Genes, Cells and Drugs in human cancers. siGCD utilizes the cancer heterogeneity to simulate the manipulated gene expression, cell infiltration and drug treatment, which overcomes the data and experimental limitations. To illustrate the performance of siGCD, we identified the survival interaction partners of EGFR (gene level), T cells (cell level) and sorafenib (drug level), and our prediction was consistent with previous reports. Moreover, we validate the synergistic effect of regorafenib and glyburide, and found that glyburide could significantly improve the regorafenib response. These results demonstrate that siGCD could benefit cancer precision medicine in a wide range of advantageous application scenarios including gene regulatory network construction, immune cell regulatory gene identification, drug (especially multiple target drugs) response biomarker screening and combination therapeutic design.
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A Randomized, Phase III Study of Lenvatinib in Chinese Patients with Radioiodine-Refractory Differentiated Thyroid Cancer.
Zheng, X, Xu, Z, Ji, Q, Ge, M, Shi, F, Qin, J, Wang, F, Chen, G, Zhang, Y, Huang, R, et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2021;(20):5502-5509
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Abstract
PURPOSE Lenvatinib has shown efficacy in treating radioiodine-refractory differentiated thyroid cancer (RR-DTC) in the multinational phase III SELECT study; however, it has not been tested in Chinese patients with RR-DTC. PATIENTS AND METHODS Chinese patients with confirmed RR-DTC (n = 151) were randomly assigned 2:1 to receive lenvatinib 24 mg/day or placebo in 28-day cycles. The primary endpoint was progression-free survival, and key secondary endpoints included objective response rate and safety. Analyses for progression-free survival and objective response rate were conducted using Response Evaluation Criteria in Solid Tumors v1.1 and confirmed by independent imaging review. All adverse events were assessed and monitored. RESULTS Progression-free survival was significantly longer with lenvatinib treatment [n = 103; median 23.9 months; 95% confidence interval (CI), 12.9-not estimable] versus placebo (n = 48; median 3.7 months; 95% CI, 1.9-5.6; hazard ratio = 0.16; 95% CI, 0.10-0.26; P < 0.0001). The objective response rate was 69.9% (95% CI, 61.0-78.8) in the lenvatinib arm and 0% (95% CI, 0-0) in the placebo arm. At data cutoff, 60.2% of patients receiving lenvatinib remained on treatment; treatment-emergent adverse events led to lenvatinib discontinuation in 8.7% of patients. Overall, treatment-emergent adverse events of grade ≥3 occurred in 87.4% of patients in the lenvatinib arm, the most common being hypertension (62.1%) and proteinuria (23.3%). CONCLUSIONS Lenvatinib at a starting dose of 24 mg/day significantly improved progression-free survival and objective response rate in Chinese patients with RR-DTC versus placebo. There were no new or unexpected toxicities. Results are consistent with those from SELECT involving patients with RR-DTC.
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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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A Pilot Study of Amino Acids in Unresectable Non-Small-Cell Lung Cancer Patients During Chemotherapy: A Randomized Serial N-of-1 Trials Design.
Liu, L, Zhang, Y, Wei, J, Chen, Z, Yu, J
Nutrition and cancer. 2019;(3):399-408
Abstract
The aim of this study was to evaluate the effect of amino acids (AAs) on immune function and inflammation level in patients with NSCLC receiving chemotherapy. We conducted a series of randomized, multiple-crossover, double-blind, placebo-controlled N-of-1 trials comparing AAs with isocaloric glucose in unresectable NSCLC patients and combined the individual results using Bayesian statistical modeling. 25 patients completed two cycles of chemotherapy. The baseline total blood albumin (ALB) level in all patients was 28 ± 3.3 g/l, and the mean total ALB level in patients receiving AAs supplementation and isocaloric glucose was 29.2 ± 2.2 and 28.1 ± 3.7 g/l, respectively (P = 0.028). Patients' baseline C-reactive protein (CRP) level was 4 ± 1.2 mg/l, the mean total CRP level in patients receiving AAs supplementation and isocaloric glucose was 11 ± 2.8 and 13 ± 3.2 mg/l, respectively (P = 0.028). The baseline total blood CD4+ T cells level was 36 ± 7.8%. The percentage of CD4+ T cells in patients receiving AAs supplementation and isocaloric glucose was 42 ± 6.4 and 33.7 ± 17.3, respectively (P = 0.034). Our preliminary results indicated that AAs improve immune status and suppress inflammation in unresectable NSCLC patients receiving chemotherapy.
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Effect of rutin on cisplatin-induced damage in human mesangial cells via apoptotic pathway.
Zhang, Y, Wang, Q, Wang, YD, Sun, B, Leng, XW, Li, Q, Ren, LQ
Human & experimental toxicology. 2019;(1):118-128
Abstract
Cisplatin (CP) is one of the most effective and widely used compounds in the treatment of disease, including cancer, but is known to induce toxicity in patients. Rutin (RUT) is a flavonoid glycoside from Sophora japonica L. that has been shown to possess antioxidative, anti-inflammatory, and antiviral properties. RUT is also known to attenuate cardiotoxicity, isoproterenol-induced cardiac fibrosis, and ischemia/reperfusion-associated hemodynamic alteration, and prevents high glucose-induced renal glomerular endothelial hyperpermeability. In this study, we investigated the effect of RUT on CP-induced nephrotoxicity. CP was used to induce toxicity in human mesangial cells (HMCs), HMCs were pretreated with different concentrations of RUT before being exposed to 10 μg/mL of CP. A positive group was pretreated with antioxidant agent N-acetylcysteine prior to CP administration. At doses between 12.5 and 25 μM, RUT prevented CP-induced reduction in cell viability. Treatment with RUT suppressed intracellular reactive oxygen species and malonic dialdehyde levels and inhibited cell apoptosis. RUT reversed the CP-induced upregulation of p53, cleaved-caspase-3, and increased pro-caspase-3 and pro-caspase-9 levels. In conclusion, the RUT can relieve CP-induced nephrotoxicity by inhibiting the p53/caspase signaling pathway.
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Topical application of honey in the management of chemo/radiotherapy-induced oral mucositis: A systematic review and network meta-analysis.
Yang, C, Gong, G, Jin, E, Han, X, Zhuo, Y, Yang, S, Song, B, Zhang, Y, Piao, C
International journal of nursing studies. 2019;:80-87
Abstract
BACKGROUND Mucositis is an inflammatory response of mucosal epithelial cells to the cytotoxic effects of chemotherapy and radiation therapy. To assess the comparative efficacy of honey for patients with cancer undergoing chemo/radiotherapy-induced oral mucositis through a systematic review and network meta-analysis. METHODS A network meta-analysis was used to identify evidence from relevant randomized controlled trials (RCTs). We searched PubMed, Embase, and the Cochrane Library for publications up to November 2017. The prespecified primary efficacy outcome was the treatment effect of moderate-severe oral mucositis with honey. We performed subgroup analyses and meta-regressions according to the age group, cancer type, mucositis cause, honey type, control arm and type of assessment scale. Moreover, secondary efficacy outcomes were treatment completed, onset time of mucositis, swallowing diary, fungal colonization, bacterial colonisation and analgesic use. And, we did standardize meta-analyses using the random-effects model, later completing the random-effects network meta-analyses by different treatment/control arms. RESULTS A total of 17 RCTs were eligible (22 analyses), involving 1265 patients and 13 arms. Honey treatment arm significantly increased the therapeutic effect of chemo/radiotherapy-induced moderate-severe oral mucositis (0.25, 0.14-0.46); significant efficacy was observed in a large proportion of subgroups. The meta-regression may have identified the causes of heterogeneity as the honey type (P = 0.038). Therefore, we need to perform further comparisons of difference in honey types and controls by network meta-analysis, and the results from network meta-analysis revealed that pure natural honey was superior in therapeutic effect (0.05, 0.01-0.46). For secondary outcomes, significant effect was found in decreasing onset time of mucositis (0.41, 0.08-0.73), while no increase in adverse effects was observed. The study is registered with PROSPERO (CRD42017070873). CONCLUSIONS The adjuvant treatment honey is effective and safe for patients with cancer undergoing chemo/radiotherapy-induced oral mucositis, especially applied pure natural local honey can be invoked as a first-line adjuvant therapy agent.
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Which is the best combination of TACE and Sorafenib for advanced hepatocellular carcinoma treatment? A systematic review and network meta-analysis.
Feng, F, Jiang, Q, Jia, H, Sun, H, Chai, Y, Li, X, Rong, G, Zhang, Y, Li, Z
Pharmacological research. 2018;:89-101
Abstract
The aim of this study was to assess the comparative efficacy and safety of combination therapy with transarterial chemoembolization (TACE) and Sorafenib for patients with advanced hepatocellular carcinoma (HCC) through a systematic review and network meta-analysis and identify the best combination of TACE and Sorafenib. We searched databases for publications prior to May 2018. The prespecified efficacy outcomes were the objective response rate, overall survival rate, and time to progression. adverse effects included dermatologic, gastrointestinal, and general disorders. Subgroup analyses, meta-regression, and a network meta-analysis regarding two types of outcomes by different chemotherapy agents in TACE (5-fluorouracil, Adriamycin, Platinum, mitomycin C, hydroxycamptothecin) were included. The study is registered with PROSPERO (CRD42018098541). For efficacy outcomes, subgroups which included 5-fluorouracil and hydroxycamptothecin ranked higher than other chemotherapy agents, while mitomycin C ranked the lowest. For advanced effects, the use of mitomycin C or 5-fluorouracil as the chemotherapy agent ranked higher, while hydroxycamptothecin ranked the lowest. Therefore, we excluded 5-Fu and Mitomycin C in subsequent studies. Additionally, in the evaluation of primary adverse effects by the network meta-analysis, Platinum ranked the highest while hydroxycamptothecin ranked the lowest. Therefore, we excluded Platinum this time. Furthermore, all types of Adriamycin are not same, and some studies included two types of Adriamycin. The network meta-analysis results showed that the TACE (hydroxycamptothecin + pirarubicin) +Sorafenib arm and TACE (hydroxycamptothecin + epirubicin) +Sorafenib arm had significant efficacy differences. In conclusion, for patients with advanced HCC, combination therapy with HCPT plus THP/EPI in TACE and Sorfenib may be used as a first-line treatment.
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Anlotinib for the Treatment of Patients with Locally Advanced or Metastatic Medullary Thyroid Cancer.
Sun, Y, Du, F, Gao, M, Ji, Q, Li, Z, Zhang, Y, Guo, Z, Wang, J, Chen, X, Wang, J, et al
Thyroid : official journal of the American Thyroid Association. 2018;(11):1455-1461
Abstract
BACKGROUND The prognosis of advanced or metastatic medullary thyroid carcinoma (MTC) is poor, and there are few therapeutic options. Anlotinib has previously shown promising antitumor activity on MTC in preclinical models and a Phase I study. This Phase II clinical trial was devised to confirm the antitumor activity of anlotinib in patients with advanced or metastatic MTC. METHODS Patients with unresectable locally advanced or metastatic MTC received once daily oral anlotinib 12 mg, two weeks on/one week off, until disease progression, death, unacceptable toxicity, or withdrawal of consent for any reason. The dose was adjusted on the basis of observed toxicity. The primary endpoint was progression-free survival (PFS). RESULTS Fifty-eight patients received anlotinib treatment. The primary endpoint PFS has not yet been reached at the time of analysis. On the basis of investigator assessments, 56.9% of patients experienced a partial response. PFS rate at 48 weeks was 85.5%. Forty-five patients had a ≥50% decrease in serum calcitonin concentration from baseline. The most common adverse events were hand-foot syndrome, hypertriglyceridemia, cholesterol elevation, fatigue, and proteinuria. CONCLUSIONS Anlotinib demonstrated a durable antitumor activity with a manageable adverse event profile in locally advanced or metastatic MTC.
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Significant efficacy and well safety of apatinib in an advanced liver cancer patient: a case report and literature review.
Kou, P, Zhang, Y, Shao, W, Zhu, H, Zhang, J, Wang, H, Kong, L, Yu, J
Oncotarget. 2017;(12):20510-20515
Abstract
Apatinib is a novel and highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2. Previous studies have suggested that apatinib is safe and effective in some solid tumors. We report one case with advanced hepatocellular carcinoma (HCC), who received apatinib combined with transhepatic arterial chemotherapy and embolization (TACE), and chemotherapy respectively. TACE was administered three times once a month, using lipiodol 10ml, oxaliplatin 150mg, and tegafur 1g. The dose of apatinib was 500 mg/d from day 4 to 24. After TACE, the patient received chemotherapy of regimen FOLFOX4, oxaliplatin intravenously at 85 mg/m2 on day 1, calcium levofolinate 200 mg/m2 on day 1 and 2, 5-fluorouracil 400 mg/m2 intravenously and 5-fluorouracil 600 mg/m2 intravenously pumped for 22h on day 1 and 2, cycled every two weeks for seven cycles. He took concurrently apatinib with a dose of 500mg daily from 1 to 10 days per cycle. He was confirmed as partial response (PR) by the Response Evaluation Criteria in Solid Tumors (RECIST). The level of serum alpha-fetoprotein (AFP) decreased from 60500 ng/ml to 12.7 ng/ml, and the progression free survival (PFS) time was more than eight months. It indicated that apatinib may be a superior choice for HCC patients.