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Oncology research.
Tech Science Press,
Oncology research.

Tech Science Press,

0965-0407

Oncology research./Journal Oncology research.
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    MYCN Directly Targets NeuroD1 to Promote Cellular Proliferation in Neuroblastoma

    Lu, FangjinMu, BinJin, GeZhu, Lin...
    10页
    查看更多>>摘要：NeuroD1 is a neuronal differentiation factor that contains a basic helix???loop???helix (bHLH) motif。 Recently， NeuroD1 was found to be associated with tumorigenesis in neuroblastoma (NB) and is known to promote cell proliferation and migration in these cells。 Here we found that MYCN regulates the expression of NeuroD1 in NB cells and that the downregulation of MYCN using short hairpin RNAs (shRNA) results in the inhibition of cellular proliferation in NB cells。 Moreover， the phenotype induced by MYCN shRNA was rescued by the exogenous expression of NeuroD1。 Chromatin immunoprecipitation (ChIP) assay showed that MYCN directly binds to the E-box element in the NeuroD1 promoter region。 In addition， our evaluation of two clinical databases showed that there was a positive correlation between the expression of MYCN and NeuroD1 in NB patients， which supports our in vitro data。 In conclusion， this study demonstrates that MYCN-regulated NeuroD1 expression is one of the important mechanisms underlying enhanced cellular proliferation induced by the increase in MYCN expression in NB， and our results provide an important therapeutic target for NB in the future。
      原文链接:
    • NSTL
    • Cognizant Communication Corp

    STAT3 Polymorphism Associates With mTOR Inhibitor-Induced Interstitial Lung Disease in Patients With Renal Cell Carcinoma

    Yamamoto, KazuhiroIoroi, TakeshiShinomiya, KazuakiYoshida, Ayaka...
    13页
    查看更多>>摘要：We evaluated the association of signal transducer and activator of transcription 3 (STAT3) polymorphisms with the incidence of mammalian target of rapamycin (mTOR) inhibitor-induced interstitial lung disease (ILD) in patients with renal cell carcinoma (RCC)。 We also used lung-derived cell lines to investigate the mechanisms of this association。 Japanese patients with metastatic RCC who were treated with mTOR inhibitors were genotyped for the STAT3 polymorphism， rs4796793 (???1697C/G)。 We evaluated the association of the STAT3 genotype with the incidence of ILD and therapeutic outcome。 In the 57 patients included in the primary analysis， the ILD rate within 140 days was significantly higher in patients with the GG genotype compared with those with other genotypes (77。8% vs。 23。1%， odds ratio = 11。67， 95% confidential interval = 3。06???44。46)。 There were no significant differences in progression-free survival or time-to-treatment failure between the patients with the GG genotype and those with other genotypes。 An in vitro study demonstrated that some lung-derived cell lines carrying the GG genotype exhibited an increase in the expression of mesenchymal markers， such as fibronectin， N-cadherin， and vimentin， and decreases in E-cadherin， which is an epithelial marker associated with exposure to everolimus， although STAT3 expression and activity were not related to the genotype。 In conclusion， the GG genotype of the STAT3 rs4796793 polymorphism increases the risk of mTOR inhibitor-induced ILD， supporting its use as a predictive marker for RCC。
      原文链接:
    • NSTL
    • Cognizant Communication Corp

    Real-World Data: Fruquintinib in Treating Metastatic Colorectal Cancer

    Liu, ShuaiLu, LuPan, FengYang, Chunsheng...
    7页
    查看更多>>摘要：Fruquintinib， also called HMPL-013， was first discovered by Hutchison Whampoa Pharmaceuticals Co。 Ltd。， Shanghai， China， and it is an oral vascular endothelial growth factor receptor (VEGFR) inhibitor。 In clinical trials， fruquintinib has demonstrated a survival benefit in metastatic colorectal cancer (mCRC) patients。 The purpose of this study was to retrospectively evaluate the efficacy and toxicity of fruquintinib in real-world patients。 We collected data from patients with mCRC treated with oral fruquintinib from 2018 to 2020 in six different institutions。 Patients with mCRC initially received 5 mg of oral fruquintinib daily for 3 weeks。 Progression-free survival (PFS) was evaluated using the Kaplan???Meier method。 The efficacy and safety of fruquintinib were also assessed。 Seventy-five patients were involved in our study， and 29。3% of patients achieved stable disease (SD)。 Median PFS was 5。4 months (95% CI: 4。841???5。959)。 The treatment-emergent adverse events (TEAEs) with fruquintinib were acceptable with grade 3 TEAEs of 6%。 The grade 3 TEAEs were hand???foot skin reaction (HFSR)， fatigue， and stomatitis。 The ECOG performance status was associated with PFS。 In this real-world study， the clinical activity of fruquintinib was consistent with what has been reported in previous clinical trials。 The level of safety was acceptable， and the side effects were manageable。
      原文链接:
    • NSTL
    • Tech Science Press

    Lactate Maintains BCR/Abl Expression and Signaling in Chronic Myeloid Leukemia Cells Under Nutrient Restriction

    Silvano, AngelaMenegazzi, GiulioPeppicelli, SilviaMancini, Caterina...
    14页
    查看更多>>摘要：This study was directed to deepen the effects of nutrient shortage on BCR/Abl(protein )expression and signaling in chronic myeloid leukemia (CML) cells。 The backbone of the study was cell culture in medium lacking glucose， the consumption of which we had previously shown to drive BCR/Abl(protein) suppression， and glutamine， the other main nutrient besides glucose。 In this context， we focused on the role of lactate， the main by-product of glucose metabolism under conditions of rapid cell growth， in particular as a modulator of the maintenance of CML stem/progenitor cell potential， a crucial determinant of disease course and relapse of disease。 The results obtained indicated that lactate is a powerful surrogate of glucose to prevent the suppression of BCR/Abl signaling and is therefore capable to maintain BCR/Abl-dependent CML stem/progenitor cell potential。 A number of metabolism-related functional and phenotypical features of CML cells were also determined。 Among these， we focused on the effect of lactate on oxygen consumption rate， the dependence of this effect on the cell surface lactate carrier MCT-1， and the relationship of the lactate effect to pyruvate and to the activity of mitochondrial pyruvate carrier。
      原文链接:
    • NSTL
    • Cognizant Communication Corp

    Comparison of UGT1A1 Polymorphism as Guidance of Irinotecan Dose Escalation in RAS Wild-Type Metastatic Colorectal Cancer Patients Treated With Cetuximab or Bevacizumab Plus FOLFIRI as the First-Line Therapy

    Tsai, Hsiang-LinChen, Yen-ChengYin, Tzu-ChiehSu, Wei-Chih...
    15页
    查看更多>>摘要：Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) polymorphism plays a crucial role in the increased susceptibility and toxicity of patients to irinotecan。 This retrospective， observational study compared the clinical outcomes and adverse events (AEs) in RAS wild-type metastatic colorectal cancer (mCRC) patients treated with cetuximab or bevacizumab plus FOLFIRI with UGT1A1 genotyping and irinotecan dose escalation as the first-line therapy。 In total， 173 patients with mCRC with RAS wild-type were enrolled。 Among them， 98 patients were treated with cetuximab， whereas 75 patients were treated with bevacizumab。 All patients received irinotecan dose escalation based on UGT1A1 genotyping。 We compared the progression-free survival (PFS)， overall survival (OS)， objective response rates (ORRs)， disease control rates (DCRs)， metastatectomy， and severe adverse events (SAEs) between the two groups。 The clinical effects of primary tumor sidedness and target therapy crossover were further analyzed。 Over a median follow-up of 23。0 months [interquartile range (IQR)， 15。0???32。5 months]， no significant differences were observed between the cetuximab and bevacizumab groups in PFS [18。0 months vs。 14。0 months; 95% confidence interval (CI)， 0。517???1。027; hazard ratio (HR)， 0。729; p = 0。071]， OS (40。0 months vs。 30。0 months; 95% CI， 0。410???1。008; HR， 0。643; p = 0。054)， ORR (65。3% vs。 62。7%; p = 0。720)， DCR (92。8% vs。 86。7%; p = 0。175)， metastatectomy (36。7% vs。 29。3%; p = 0。307)， and SAEs (p = 0。685)。 Regardless of primary tumor sidedness and target therapy crossover， no significant differences were noted in efficacy and safety between the two groups (all p > 0。05)。 Our results revealed that patients with wild-type RAS mCRC， regardless of biologics， with UGT1A1 genotyping can tolerate escalated doses of irinotecan and potentially achieve a more favorable clinical outcome without significantly increased toxicity。
      原文链接:
    • NSTL
    • Cognizant Communication Corp

    Research Progress in Immunotherapy of NSCLC With EGFR-Sensitive Mutations

    Yang, YudieZhang, XiaGao, YajieDong, Yan...
    12页
    查看更多>>摘要：Lung cancer is a malignant tumor with high incidence and mortality across the world。 The use of immune checkpoint inhibitors for lung cancer has improved the prognosis of some lung cancer patients to a greater extent and provided a new direction for the clinical treatment of lung cancer。 Immunotherapy still has limitations in terms of its appropriate population and adverse reactions。 Particularly for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation， there has been no major breakthrough in current immunotherapy。 Whether immunotherapy can bring new benefits after drug resistance is induced by tyrosine kinase inhibitor-targeted therapy and whether the combination of immunotherapy with other treatments can improve the prognosis remain to be studied in depth。 In this article， we provide a detailed review of the relevant characteristics of the tumor microenvironment of NSCLC with EGFR mutation and the current research on immunotherapy for NSCLC with EGFR mutation。
      原文链接:
    • NSTL
    • Tech Science Press

    Long Noncoding RNA LINC01133 Functions as an miR-422a Sponge to Aggravate the Tumorigenesis of Human Osteosarcoma (Retraction of Vol 26, Pg 335, 2018)

    Zeng, Hai-FengQiu, Hai-YanFeng, Fa-Bo
    1页
      原文链接:
    • NSTL
    • Cognizant Communication Corp

    Targeted Silencing of Kim-1 Inhibits the Growth of Clear Cell Renal Cell Carcinoma Cell Line 786-0 In Vitro and In Vivo (Retraction of Vol 26, Pg 997, 2018)

    Xu, JianpingSun, LiguoSun, WeiTian, Jianhai...
    1页
      原文链接:
    • NSTL
    • Cognizant Communication Corp

    Downregulation of MicroRNA-147 Inhibits Cell Proliferation and Increases the Chemosensitivity of Gastric Cancer Cells to 5-Fluorouracil by Directly Targeting PTEN (Retraction of Vol 26, Pg 901, 2018)

    Shen, JianjunNiu, WeinaZhang, HongboJun, Ma...
    1页
      原文链接:
    • NSTL
    • Cognizant Communication Corp