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  • 1
    Online Resource
    Online Resource
    The Anti-Non-Small Cell Lung Cancer Cell Activity by a mTOR Kinase Inhibitor PQR620
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-6-10)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-6-10)
    Abstract: In non-small-cell lung carcinoma (NSCLC), aberrant activation of mammalian target of rapamycin (mTOR) contributes to tumorigenesis and cancer progression. PQR620 is a novel and highly-potent mTOR kinase inhibitor. We here tested its potential activity in NSCLC cells. In primary human NSCLC cells and established cell lines (A549 and NCI-H1944), PQR620 inhibited cell growth, proliferation, and cell cycle progression, as well as cell migration and invasion, while inducing significant apoptosis activation. PQR620 disrupted assembles of mTOR complex 1 (mTOR-Raptor) and mTOR complex 2 (mTOR-Rictor-Sin1), and blocked Akt, S6K1, and S6 phosphorylations in NSCLC cells. Restoring Akt-mTOR activation by a constitutively-active Akt1 (S473D) only partially inhibited PQR620-induced cytotoxicity in NSCLC cells. PQR620 was yet cytotoxic in Akt1/2-silenced NSCLC cells, supporting the existence of Akt-mTOR-independent mechanisms. Indeed, PQR620 induced sphingosine kinase 1 (SphK1) inhibition, ceramide production and oxidative stress in primary NSCLC cells. In vivo studies demonstrated that daily oral administration of a single dose of PQR620 potently inhibited primary NSCLC xenograft growth in severe combined immune deficient mice. In PQR620-treated xenograft tissues, Akt-mTOR inactivation, apoptosis induction, SphK1 inhibition and oxidative stress were detected. In conclusion, PQR620 exerted potent anti-NSCLC cell activity via mTOR-dependent and -independent mechanisms.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    DOI: 10.3389/fonc.2021.669518
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 2
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    Table1.DOCX
    Frontiers Media SA ; 2021
    In:  Frontiers in Molecular Biosciences Vol. 8 ( 2021-7-30)
    Details
    In: Frontiers in Molecular Biosciences, Frontiers Media SA, Vol. 8 ( 2021-7-30)
    Abstract: This study aims to evaluate the association between free triiodothyronine (FT3) and outcomes of coronary artery disease (CAD) patients, as well as to assess the predictive power of FT3 and related functional markers from the perspective of potential mechanism. A total of 5104 CAD patients with an average follow-up of three years were enrolled into our study. Multivariate Cox regression was used to evaluate the associations between FT3, FT4 (free thyroxin), FT3/FT4 and death, MACE. We developed and validated an age, biomarker, and clinical history (ABC) model based on FT3 indicators to predict the prognosis of patients with CAD. In the multivariable Cox proportional hazards model, FT3 and FT3/FT4 were independent predictors of mortality (Adjusted HR = 0.624, 95% CI = 0.486–0.801; adjusted HR = 0.011, 95% CI = 0.002–0.07, respectively). Meanwhile, emerging markers pre-brain natriuretic peptide, fibrinogen, and albumin levels are significantly associated with low FT3 ( p & lt; 0.001). The new risk death score based on biomarkers can be used to well predict the outcomes of CAD patients (C index of 0.764, 95% CI = 0.731–0.797). Overall, our findings suggest that low levels of FT3 and FT3/FT4 are independent predictors of death and MACE risk in CAD patients. Besides, the prognostic model based on FT3 provides a useful tool for the death risk stratification of CAD patients.
    Type of Medium: Online Resource
    ISSN: 2296-889X
    URL: Article
    URL: Article
    DOI: 10.3389/fmolb.2021.681955
    DOI: 10.3389/fmolb.2021.681955.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2814330-9
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  • 3
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    Table1.DOCX
    Frontiers Media SA ; 2023
    In:  Frontiers in Pharmacology Vol. 14 ( 2023-4-21)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 14 ( 2023-4-21)
    Abstract: Background: Evidence of efficacy and safety of programmed cell death 1 (PD-1) and programmed death ligand-1 (PD-L1) checkpoint inhibitors in oesophageal cancer (EC), gastric cancer (GC) and colorectal cancer (CRC) was inconsistent, obscuring their clinical application and decision-making. The aim of this study was to comprehensively evaluate the value of PD-1/PD-L1 inhibitors in EC, GC and CRC to select valuable PD-1/PD-L1 inhibitors, and to assess the association between the value and cost of PD-1/PD-L1 inhibitors. Methods: A comprehensive search of trials of PD-1/PD-L1 inhibitors in EC, GC and CRC was performed in Chinese and English medical databases with a cut-off date of 1 July 2022. Two authors independently applied the ASCO-VF and ESMO-MCBS to assess the value of PD-1/PD-L1 inhibitors. A receiver operating characteristic (ROC) curve was generated to establish the predictive value of the ASCO-VF score to meet the threshold of the ESMO-MCBS grade. Spearman’s correlation was used to calculate the relationship between the cost and value of drugs. Results: Twenty-three randomized controlled trials were identified: ten (43.48%) in EC, five (21.74%) in CRC, and eight (34.78%) in GC or gastroesophageal junction cancer (GEJC). For advanced diseases, ASCO-VF scores ranged from −12.5 to 69, with a mean score of 26.5 (95% CI 18.4–34.6). Six (42.9%) therapeutic regimens met the ESMO-MCBS benefit threshold grade. The area under the ROC curve was 1.0 ( p = 0.002). ASCO-VF scores and incremental monthly cost were negatively correlated (Spearman’s ρ = −0.465, p = 0.034). ESMO-MCBS grades and incremental monthly cost were negatively correlated (Spearman’s ρ = −0.211, p = 0.489). Conclusion: PD-1/PD-L1 inhibitors did not meet valuable threshold in GC/GEJC. Pembrolizumab met valuable threshold in advanced microsatellite instability–high CRC. The value of camrelizumab and toripalimab may be more worth paying in EC.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2023.1106961
    DOI: 10.3389/fphar.2023.1106961.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2587355-6
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  • 4
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    Table_3.xlsx
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-6-8)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-6-8)
    Abstract: This study aims to compare the efficacy and safety of different poly (ADP-ribose) polymerase (PARP) inhibitors in patients with ovarian cancer through a network meta-analysis to support clinical treatment choices. Methods The Cochrane Library, PubMed, Embase, Science Citation Index, China National Knowledge Infrastructure (CNKI), Wanfang Data, Chongqing VIP (CQVIP), and Chinese BioMedical Literature Database (CBM) were searched with a cutoff date of 14 January 2021. ClinicalTrials.gov was also checked for supplementary data. Phase II or III randomized controlled trials that compared a PARP inhibitor with a placebo in patients with relapsed or newly diagnosed advanced ovarian cancer were included. The hazard ratios (HRs) for progression-free survival and overall survival and odds ratios (ORs) for grade 3 or higher adverse events were analyzed. The network meta-analysis was conducted in a Bayesian framework based on the Markov Chain Monte Carlo model in the R gemtc package (version 4.0.3). Results Eight eligible articles reporting six trials with a total of 2,801 patients were incorporated in this network meta-analysis. Three trials compared olaparib with placebo. Two trials compared niraparib with placebo. One trial compared rucaparib with placebo. The network meta-analysis failed to show significant differences in progression-free survival among the three PARP inhibitors: HR of 0.64, 95% confidence interval of 0.3 to 1.42 for olaparib versus niraparib, and olaparib versus rucaparib (0.86; 0.33 to 2.33). The comparison between niraparib and rucaparib also did not express a statistical difference (1.34; 0.47 to 3.72). Subgroup analysis bybreast cancer susceptibility gene (BRCA) status showed no obvious difference in progression-free survival among the three PARP inhibitors regardless of BRCA mutation status. Olaparib had fewer grade 3 or higher adverse events than niraparib (OR, 0.27; 95% confidence interval, 0.13 to 0.55) and rucaparib (0.34; 0.14 to 0.86). However, the analysis failed to show a significant difference between niraparib and rucaparib (1.27; 0.49 to 3.27). Conclusion Current evidence indicates that there is no significant difference observed in efficacy among olaparib, niraparib, and rucaparib. However, olaparib might have fewer grade 3 or higher adverse events.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    URL: Article
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    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2022.815265
    DOI: 10.3389/fonc.2022.815265.s001
    DOI: 10.3389/fonc.2022.815265.s002
    DOI: 10.3389/fonc.2022.815265.s003
    DOI: 10.3389/fonc.2022.815265.s004
    DOI: 10.3389/fonc.2022.815265.s005
    DOI: 10.3389/fonc.2022.815265.s006
    DOI: 10.3389/fonc.2022.815265.s007
    DOI: 10.3389/fonc.2022.815265.s008
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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  • 5
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    Table_5.xlsx
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-7-13)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-7-13)
    Abstract: An influx of systematic reviews (SRs) of programmed cell death 1 (PD-1) and programmed death ligand-1 (PD-L1) checkpoint inhibitors in cancer treatment with or without meta-analysis and with different methodological quality and inconsistent results have been published, confusing clinical decision making. The aim of this study was to comprehensively evaluate and summarize the current evidence of PD-(L)1 inhibitors in the treatment of cancer. Methods A comprehensive search of SRs, which included meta-analyses of PD-(L)1 inhibitors on cancer, was performed on eight databases with a cutoff date of 1 January 2022. Two authors independently identified SRs, extracted data, assessed the report quality according to the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement, evaluated the methodological quality by the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2), and appraised the quality of evidence by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Results A total of 172 SRs with meta-analysis met the inclusion criteria. The report quality of included SRs was quite good, with 128 (74.42%) SRs of high quality and 44 (25.58%) of moderate quality. The methodological quality was alarming, as only one (0.58%) SR had high quality, five (2.91%) SRs had low quality, and the other 166 (96.51%) SRs had critically low quality. For GRADE, 38 (3.77%) outcomes had high-quality evidence, 288 (28.57%) moderate, 545 (54.07%) low, and 137 (13.59%) critically low-quality evidence. Current evidence indicated that treatment with PD-(L)1 inhibitors were significantly effective in non-small cell lung cancer, small cell lung cancer, hepatocellular carcinoma, malignant melanoma, renal cell carcinoma, and urothelial carcinoma, breast cancer, and head and neck squamous cell carcinoma with PD-L1 expression level≥1%, whereas the evidence in gastroesophageal and colorectal tumors is still controversial. Monotherapy with PD-(L)1 inhibitors was associated with a lower frequency of any grade and high-grade adverse events (AEs). The incidence of any grade and high-grade AEs caused by PD-(L)1 inhibitors in combination with other therapies was no lower than the controls. However, PD-(L)1 inhibitors were associated with a higher frequency of any grade and high-grade immune-related AEs. Conclusions PD-(L)1 inhibitors appeared to be effective and safe for cancer treatment, except for gastrointestinal tumors; however, the quality of the evidence is not convincing. Future studies should improve methodological quality and focus on the sequential trial analysis of subgroups and safety. Systematic Review Registration http://www.crd.york.ac.uk/prospero , identifier CRD42020194260.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.953761
    DOI: 10.3389/fimmu.2022.953761.s001
    DOI: 10.3389/fimmu.2022.953761.s002
    DOI: 10.3389/fimmu.2022.953761.s003
    DOI: 10.3389/fimmu.2022.953761.s004
    DOI: 10.3389/fimmu.2022.953761.s005
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 6
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    Table_1.DOCX
    Frontiers Media SA ; 2023
    In:  Frontiers in Public Health Vol. 11 ( 2023-2-24)
    Details
    In: Frontiers in Public Health, Frontiers Media SA, Vol. 11 ( 2023-2-24)
    Abstract: Whether the high cost of cancer drugs is commensurate with their value to patients, which has become the focus of public concern. We aimed to assess the value of new cancer drugs approved for solid cancer in China and to explore the association between price and value of drugs. Methods We identified all new drugs for solid tumor that approved by the China's National Medical Products Administration (NMPA) between 2016 and 2020. The value of these drugs was assessed according to the American Society of Clinical Oncology Value Framework (ASCO-VF) and the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). We calculated Cohen's κ statistic to describe agreement between the two frameworks. Spearman's correlation coefficient was used to evaluate the correlation between price and value of drugs. Results Between 2016 and 2020, 37 new drugs were approved by the NMPA for solid tumor and we could evaluate the value of 28 drugs (76%). Eight (29%) of drugs were approved for non-small-cell lung cancer and 6 (21%) for breast cancer. ASCO-VF scores had a range of −20 to 110.1, and the median score was 43.3 (inter-quartile range 27.1–58.35). Only seven drugs (25%) met the ASCO-VF cutoff score. By the ESMO-MCBS, 13 drugs showed a meaningful value. Agreement between these two frameworks thresholds was only fair (κ = 0.515, P & lt; 0.05). We found no statistically significant correlation between launch price of drugs and clinical benefit according to both frameworks. Conclusions Not all NMPA-approved new cancer drugs had meaningful value as measured by ASCO-VF or ESMO-MCBS. There was no significant correlation between drug price and the level of clinical benefit.
    Type of Medium: Online Resource
    ISSN: 2296-2565
    URL: Article
    URL: Article
    DOI: 10.3389/fpubh.2023.1109668
    DOI: 10.3389/fpubh.2023.1109668.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2711781-9
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  • 7
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    Table_2.xlsx
    Frontiers Media SA ; 2023
    In:  Frontiers in Oncology Vol. 13 ( 2023-2-23)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-2-23)
    Abstract: We evaluated he effects of molecular guided-targeted therapy for intractable cancer. Also, the epidemiology of druggable gene alterations in Chinese population was investigated. Materials and methods The Long March Pathway (ClinicalTrials.gov identifier: NCT03239015) is a non-randomized, open-label, phase II trial consisting of several basket studies examining the molecular profiles of intractable cancers in the Chinese population. The trial aimed to 1) evaluate the efficacy of targeted therapy for intractable cancer and 2) identify the molecular epidemiology of the tier II gene alterations among Chinese pan-cancer patients. Results In the first stage, molecular profiles of 520 intractable pan-cancer patients were identified, and 115 patients were identified to have tier II gene alterations. Then, 27 of these 115 patients received targeted therapy based on molecular profiles. The overall response rate (ORR) was 29.6% (8/27), and the disease control rate (DCR) was 44.4% (12/27). The median duration of response (DOR) was 4.80 months (95% CI, 3.33−27.2), and median progression-free survival (PFS) was 4.67 months (95% CI, 2.33−9.50). In the second stage, molecular epidemiology of 17,841 Chinese pan-cancer patients demonstrated that the frequency of tier II gene alterations across cancer types is 17.7%. Bladder cancer had the most tier-II alterations (26.1%), followed by breast cancer (22.4%), and non-small cell lung cancer (NSCLC; 20.2%). Conclusion The Long March Pathway trial demonstrated a significant clinical benefit for intractable cancer from molecular-guided targeted therapy in the Chinese population. The frequency of tier II gene alterations across cancer types supports the feasibility of molecular-guided targeted therapy under basket trials.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2023.860711
    DOI: 10.3389/fonc.2023.860711.s001
    DOI: 10.3389/fonc.2023.860711.s002
    DOI: 10.3389/fonc.2023.860711.s003
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
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  • 8
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    Table_4.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Nutrition Vol. 8 ( 2022-2-7)
    Details
    In: Frontiers in Nutrition, Frontiers Media SA, Vol. 8 ( 2022-2-7)
    Abstract: Systemic inflammation and malnutrition are correlated with cancer sarcopenia and have deleterious effects on oncological outcomes. However, the combined effect of inflammation and malnutrition in patients with cancer sarcopenia remains unclear. Methods We prospectively collected information on 1,204 patients diagnosed with cancer sarcopenia. the mean (SD) age was 64.5 (11.4%) years, and 705 (58.60%) of the patients were male. The patients were categorized into the high advanced lung cancer inflammation index (ALI) group (≥18.39) and the low ALI group ( & lt;18.39) according to the optimal survival cut-off curve. We selected the optimal inflammation marker using the C-index, decision curve analysis (DCA), and a prognostic receiver operating characteristic curve. Univariate and multivariate survival analyses were performed to determine the prognostic value of the optimal inflammation indicator. We also analyzed the association between inflammation and malnutrition in patients with cancer. Results The C-index, DCA, and prognostic area under the curve of ALI in patients with cancer sarcopenia were higher or better than those of neutrophil-lymphocyte ratio (NLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and platelet-lymphocyte ratio (PLR). The prognosis for patients in the low ALI group was worse than that of patients in the high ALI group [HR (95%CI) = 1.584 (1.280–1.959), P & lt; 0.001]. When the ALI was divided into quartiles, we observed that decreased ALI scores strongly correlated with decreased overall survival (OS). Patients with both a low ALI and severe malnutrition (vs. patients with high ALI and well-nourished) had a 2.262-fold death risk ( P & lt; 0.001). Subgroup analysis showed a significant interactive association between the ALI and death risk in terms of TNM stage ( P for interaction = 0.030). Conclusions The inflammation indicator of the ALI was better than those of the NLR, PNI, SII, and PLR in patients with cancer sarcopenia. Inflammation combined with severe malnutrition has a nearly 3-fold death risk in patients with cancer sarcopenia, suggesting that reducing systemic inflammation, strengthening nutritional intervention, and improving skeletal muscle mass are necessary.
    Type of Medium: Online Resource
    ISSN: 2296-861X
    URL: Article
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    URL: Article
    DOI: 10.3389/fnut.2021.811288
    DOI: 10.3389/fnut.2021.811288.s001
    DOI: 10.3389/fnut.2021.811288.s002
    DOI: 10.3389/fnut.2021.811288.s003
    DOI: 10.3389/fnut.2021.811288.s004
    DOI: 10.3389/fnut.2021.811288.s005
    DOI: 10.3389/fnut.2021.811288.s006
    DOI: 10.3389/fnut.2021.811288.s007
    DOI: 10.3389/fnut.2021.811288.s008
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2776676-7
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  • 9
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    Data_Sheet_1.docx
    Frontiers Media SA ; 2020
    In:  Frontiers in Neurology Vol. 11 ( 2020-7-10)
    Details
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 11 ( 2020-7-10)
    Type of Medium: Online Resource
    ISSN: 1664-2295
    URL: Article
    URL: Article
    DOI: 10.3389/fneur.2020.00806
    DOI: 10.3389/fneur.2020.00806.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2564214-5
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  • 10
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    Image_2.pdf
    Frontiers Media SA ; 2023
    In:  Frontiers in Oncology Vol. 12 ( 2023-2-16)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2023-2-16)
    Abstract: The impact of hospital volume on the long-term survival of esophageal squamous cell carcinoma (ESCC) has not been well assessed in China, especially for stage I–III stage ESCC. We performed a large sample size study to assess the relationships between hospital volume and the effectiveness of ESCC treatment and the hospital volume value at the lowest risk of all-cause mortality after esophagectomy in China. Aim To investigate the prognostic value of hospital volume for assessing postoperative long-term survival of ESCC patients in China. Methods The date of 158,618 patients with ESCC were collected from a database (1973–2020) established by the State Key Laboratory for Esophageal Cancer Prevention and Treatment, the database includes 500,000 patients with detailed clinical information of pathological diagnosis and staging, treatment approaches and survival follow-up for esophageal and gastric cardia cancers. Intergroup comparisons of patient and treatment characteristics were conducted with the X 2 test and analysis of variance. The Kaplan-Meier method with the log-rank test was used to draw the survival curves for the variables tested. A Multivariate Cox proportional hazards regression model was used to analyze the independent prognostic factors for overall survival. The relationship between hospital volume and all-cause mortality was assessed using restricted cubic splines from Cox proportional hazards models. The primary outcome was all-cause mortality. Results In both 1973-1996 and 1997-2020, patients with stage I-III stage ESCC who underwent surgery in high volume hospitals had better survival than those who underwent surgery in low volume hospitals (both P & lt;0.05). And high volume hospital was an independent factor for better prognosis in ESCC patients. The relationship between hospital volume and the risk of all-cause mortality was half-U-shaped, but overall, hospital volume was a protective factor for esophageal cancer patients after surgery (HR & lt;1). The concentration of hospital volume associated with the lowest risk of all-cause mortality was 1027 cases/year in the overall enrolled patients. Conclusion Hospital volume can be used as an indicator to predict the postoperative survival of ESCC patients. Our results suggest that the centralized management of esophageal cancer surgery is meaningful to improve the survival of ESCC patients in China, but the hospital volume should preferably not be higher than 1027 cases/year. Core tip Hospital volume is considered to be a prognostic factor for many complex diseases. However, the impact of hospital volume on long-term survival after esophagectomy has not been well evaluated in China. Based on a large sample size of 158,618 ESCC patients in China spanning 47 years (1973-2020), We found that hospital volume can be used as a predictor of postoperative survival in patients with ESCC, and identified hospital volume thresholds with the lowest risk of death from all causes. This may provide an important basis for patients to choose hospitals and have a significant impact on the centralized management of hospital surgery.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2022.1056086
    DOI: 10.3389/fonc.2022.1056086.s001
    DOI: 10.3389/fonc.2022.1056086.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2649216-7
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