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共1477条结果
  • 1.

    【2hr】Small molecule TSC01682 inhibits osteosarcoma cell growth by specifically disrupting the CUL4B-DDB1 interaction and decreasing the ubiquitination of CRL4B E3 ligase substrates

    包量

    机译 小分子TSC01682通过特异性破坏CUL4B-DDB1相互作用并降低CRL4B E3连接酶底物的泛素化作用来抑制骨肉瘤细胞的生长
    摘要：The direct interaction between Cullin 4B (CUL4B) and DNA damage-binding protein 1 (DDB1) is required for the assembly of Cullin4B-RING E3 ligase complex (CRL4B), which are involved in the tumorigenesis of osteosarcoma through ubiquitinating and degrading multiple tumor suppressors and cell cycle regulators. Thus, targeting CUL4B-DDB1 interaction to prevent the assembly of CRL4B may be a potent approach to inhibit osteosarcoma cell growth. In the present study, we identified six naturally-sourced small molecules that can specifically disrupt the CUL4B-DDB1 interaction using an in vitro high-throughput screening (HTS) system in yeast. We focused our investigation on revealing the molecular effects of , the most active compound capable of inhibiting osteosarcoma cell growth. Biochemically, significantly repressed the CUL4B-DDB1 interaction in both yeast cells and osteosarcoma cells. Moreover, treatment in osteosarcoma cells also caused a decrease of other CRL4B components including CUL4-associated factor 11 (DCAF11) and DCAF13, but an increase of two CRL4B substrates including cyclin-dependent kinase inhibitor 1A (CDKN1A, also known as p21) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) through inhibiting their ubiquitination. Consistent with these molecular changes, treatment significantly inhibited cell proliferation, colony formation, invasion, and in vivo tumor growth. Collectively, our results suggest that is a potent compound capable of disrupting the CUL4B-DDB1 interaction, and it may be developed as a chemotherapeutic drug for osteosarcoma treatment.
  • 2.

    【2hr】Promising new treatments for pancreatic cancer in the era of targeted and immune therapies

    包量

    机译 靶向和免疫疗法时代的胰腺癌有望成为新疗法
    摘要：Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer mortality among men and women in the United States. Its incidence has been on the rise, with a projected two-fold increase by 2030. PDAC carries a poor prognosis due to a lack of effective screening tools, limited understanding of pathophysiology, and ineffective treatment modalities. Recently, there has been a revolution in the world of oncology with the advent of novel treatments to combat this disease. However, the 5-year survival of PDAC remains unchanged at a dismal 8%. The aim of this review is to bring together several studies and identify various recent modalities that have been promising in treating PDAC.
  • 3.

    【2hr】Therapeutic targeting of the crosstalk between cancer-associated fibroblasts and cancer stem cells

    包量

    机译 靶向治疗癌症相关成纤维细胞与癌症干细胞之间的串扰
    摘要：Cancer-associated fibroblasts (CAFs) play critical roles in cancer progression and treatment failure. CAFs display extreme phenotypic heterogeneity and functional diversity. Some subpopulations of CAFs have the ability to reconstitute cancer stemness by promoting the expansion of cancer stem cells (CSCs) or by inducing the generation of CSCs from differentiated cancer cells. CAFs regulate cancer stemness in different types of solid tumors by activating a wide array of CSC-related signaling by secreting proteins and exosomes. As feedback, the CSCs can also induce the proliferation and further activation of CAFs to promote their CSC-supporting activities, thus completing the loop of CAF-CSC crosstalk. Current research on targeting CAF-CSC crosstalk could be classified into (i) specific depletion of CAF subpopulations that have CSC-supporting activities and (ii) targeting molecular signaling in CAF-CSC crosstalk, such as the IL6/STAT3, TGF-β/SDF-1/PI3K, WNT/β-catenin, HGF/cMET and SHH/Hh pathways. Strategies targeting CAF-CSC crosstalk may open new avenues for overcoming cancer progression and therapeutic resistance.
  • 4.

    【2hr】PDE3A inhibitor anagrelide activates death signaling pathway genes and synergizes with cell death-inducing cytokines to selectively inhibit cancer cell growth

    包量

    机译 PDE3A抑制剂阿那格雷可激活死亡信号通路基因并与诱导细胞死亡的细胞因子协同作用，从而选择性抑制癌细胞的生长
    摘要：We performed a drug repurposing screening of a US Food and Drug Administration (FDA)-approved drug compound library and identified Anagrelide (ANA), a known phosphodiesterase 3A (PDE3A) inhibitor, that selectively and potently inhibited the growth of cancer cells. However, inactivation of PDE3A or knocking-down its gene expression did not inhibit cancer cell growth. It was the interaction of ANA with PDE3A that created a new function of PDE3A to alter the activities of another unknown function protein SLFN12 to cause the inhibition of cancer cell growth. The expressions of both PDE3A and SLFN12 were required for ANA to inhibit cancer cell growth. Depletion of PDE3A or SLFN12 led to ANA resistance. Furthermore, the effects of ANA on different cancer cells were different depending on the expression levels of PDE3A and SLFN12, causing G0/G1 cell cycle arrest in the cells expressing lower levels of SLFN12, but apoptosis in the cells expressing higher levels of the two proteins. Further investigation into the molecular mechanisms of the ANA-induced cell cycle arrest and apoptosis identified a set of cell cycle and apoptosis-related genes whose expressions were altered by ANA treatment. ANA also synergized with the cell death-inducing cytokines IFN-α, IFN-γ, TNF-α, or TRAIL, which regulated the same set of genes as ANA did, to induce apoptosis of the cancer cells. Our study uncovered new activities, functions, and mechanisms of ANA and SLFN12 and provided a diagnosis method to precisely use ANA as an anti-cancer drug. It also revealed PDE3A and SLFN12 as new anti-cancer drug targets for developing novel anti-cancer therapies.
  • 5.

    【2hr】A low dose of AZD8055 enhances radiosensitivity of nasopharyngeal carcinoma cells by activating autophagy and apoptosis

    包量

    机译 低剂量的AZD8055可通过激活自噬和凋亡增强鼻咽癌细胞的放射敏感性
    摘要：Activation of the PI3K/mTOR pathways is significantly correlated with a poor prognosis in nasopharyngeal carcinoma (NPC). Inhibition of these pathways was reported to be effective in restoring radiosensitivity. In this study, the activity of the novel ATP-competitive, orally bioavailable mTOR inhibitor AZD8055 was found to inhibit the phosphorylated mTOR and NPC cells proliferation. The IC50 doses in CNE1 and CNE2 cell lines were 60 and 100 nanomolar, respectively. AZD8055 significantly enhanced the inhibitions of cell growth and colony formation induced by irradiation (P < 0.05 for all). AZD8055 at the IC50 doses prolonged G2/M arrest (P < 0.05) and promoted the apoptosis (P < 0.01) induced by irradiation and autophagy in NPC cells. Blocking autophagy weaken the cell growth inhibition and decreased apoptosis induced by AZD8055 combined with irradiation. Treatment with AZD8055 at 5, 10 and 20 mg/kg/d significantly enhanced NPC cell radiosensitivity in vivo and significantly induced apoptosis and autophagy in tumor tissues, Neither 5 nor 20 mg/kg/d AZD8055 induced significantly pro-apoptosis bax expressions in mouse livers and kidneys. 5 mg/kg/d produced good radiosensitivity but had little impact on body weight. We concluded that AZD8055 was a promising candidate radiosensitizer for NPC.
  • 6.

    【2hr】MYCN-mediated regulation of the HES1 promoter enhances the chemoresistance of small-cell lung cancer by modulating apoptosis

    包量

    机译 MYCN介导的HES1启动子调控通过调节细胞凋亡增强小细胞肺癌的化学耐药性
    摘要：MYCN, a member of the MYC family, is correlated with tumorigenesis, metastasis and therapy in many malignancies; however, its role in small-cell lung cancer (SCLC) remains unclear. In this study, we sought to identify the function of MYCN in SCLC chemoresistance and found that MYCN is overexpressed in chemoresistant SCLC cells. We used MYCN gain- and loss-of- function experiments to demonstrate that MYCN promotes in vitro and in vivo chemoresistance in SCLC by inhibiting apoptosis. Mechanistic investigations showed that MYCN binds to the HES1 promoter and exhibits transcriptional activity. Furthermore, MYCN mediated SCLC chemoresistance through HES1. Accordingly, the NOTCH inhibitor FLI-60 derepressed HES1 and diminished MYCN-induced chemoresistance in SCLC. Finally, the positive correlation between HES1 and MYCN was confirmed in SCLC patients. Chemoresistant SCLC patients had higher expression levels of MYCN and HES1 than patients without chemoresistant SCLC. MYCN overexpression was related to advanced clinical stage and shorter survival in SCLC. In conclusion, our study revealed that MYCN and HES1 may be potential therapeutic targets and promising predictors for SCLC.
  • 7.

    【2hr】Tumor-associated macrophages (TAMs) depend on Shp2 for their anti-tumor roles in colorectal cancer

    包量

    机译 肿瘤相关巨噬细胞（TAM）依赖Shp2在大肠癌中的抗肿瘤作用
    摘要：Tumor associated macrophages (TAMs) in tumor microenvironment can interact with tumor cells and are related to tumor progression. However, the mechanisms that drive the anti-tumor functions of TAMs are not fully understood. The Src homology 2 domain-containing tyrosine phosphatase 2 (Shp2) has been reported to have tumor-suppressing roles in colorectal cancer (CRC). However, a role for Shp2 on TAMs in CRC has not been studied. Here we report that in CRC, Shp2 expression on TAMs is negatively associated with liver metastasis. TAMs require Shp2 for their anti-tumor functions in a cell-cell co-culture system and a mouse model of CRC. Mechanistically, absence of Shp2 on TAMs induces their polarization toward M2 phenotype through the activation of p-STAT3 and inhibition of p-NF-κB p65. The findings of our study imply that Shp2 is a key factor in the tumor microenvironment to facilitate the TAMs’ tumor-suppressing functions in colorectal cancer.
  • 8.

    【2hr】UCHL3 promotes pancreatic cancer progression and chemo-resistance through FOXM1 stabilization

    包量

    机译 UCHL3通过FOXM1稳定化促进胰腺癌的进展和耐药性
    摘要：The dysregulation of deubiquitinating enzymes has been reported to be important in the development of many human cancers, including pancreatic cancer. However, the precise role and potential mechanism of action of the deubiquitinating enzyme UCHL3 in pancreatic cancer progression and chemo-resistance, are poorly elucidated. In the current study, the consequences of UCHL3 knockdown in pancreatic cancer cells were evaluated via cell viability and colony formation assays. In vivo experiments were also conducted to confirm the effect of UCHL3 and FOXM1 depletion on tumor growth in nude mouse xenograft models. Cell migration and invasion were assessed by wound-healing and transwell assays, respectively. Co-immunoprecipitation (co-IP) and in vitro deubiquitination assays were performed to investigate the interactions between UCHL3 and FOXM1. Immunohistochemical (IHC) staining was utilized to examine the expression of UCHL3 and FOXM1 in pancreatic cancer tissues. Our results demonstrate that UCHL3 deubiquitinated and stabilized FOXM1, thereby potentiating proliferation, migration, and invasion of pancreatic cancer cells. Furthermore, knockdown of UCHL3 increased FOXM1 ubiquitination, which enhanced FOXM1 turnover and promoted pancreatic cancer cells’ sensitivity to gemcitabine. High UCHL3 expression was positively associated with FOXM1 expression level in pancreatic cancer patient samples. Collectively, our study established the UCHL3-FOXM1 axis as a pivotal driver of pancreatic cancer progression and gemcitabine resistance and provided evidence for the potential therapeutic benefit of targeting the UCHL3-FOXM1 axis for pancreatic cancer treatment.
  • 9.

    【2hr】DWI and DCE-MRI approaches for differentiating reversibly electroporated penumbra from irreversibly electroporated ablation zones in a rabbit liver model

    包量

    机译 DWI和DCE-MRI方法用于区分兔肝模型中可逆电穿孔半影与不可逆电穿孔消融区
    摘要：The purpose of our study was to investigate the hypothesis that DWI-MRI and DCE-MRI cab be used to distinguish between IRE and RE zones of IRE treatment in a rabbit liver model. 6 rabbits underwent baseline and post-procedure MR imaging with DWI and DCE-MRI as well as IRE (10 pulses, 2000 V, 10 µs/pulse, 10 ms between pulses). Rabbits were euthanized immediately after post-procedure MRI to acquire liver tissue for histology. Liver tissues were fixed and then stained with HE and TUNEL. T1w and T2w intensities in different treatment zones were calculated and normalized to paraspinal muscle signal. ADC maps were generated from DWI. AUC, PE, TTP, WIS, Ktrans, Kep, and VE were calculated from DCE-MRI. Apoptosis index was calculated from TUNEL stained tissues. P<0.05 was considered statistically significant. Entire IRE treated region was hyperintense compared with untreated tissues on T1w, with the RE zone having a higher signal intensity. On DWI, IRE treated tissue had decreased ΔADC. The IRE zone has a lower ΔADC than the RE zone within the treated region. On DCE-MRI, IRE zone demonstrated the highest TTP and the lowest PE, WIS, Ktrans, Kep, and VE, followed by the RE zone then the untreated tissue. TUNEL staining of liver tissues showed that the IRE zone had the highest apoptosis index, followed by the RE zone and then untreated tissue. In conclusion, DCE-MRI and DWI parameters allow differentiation between RE and IRE zones in a rabbit liver model.
  • 10.

    【2hr】Protease activated receptor 2 mediates tryptase-induced cell migration through MYO10 in colorectal cancer

    包量

    机译 蛋白酶激活受体2通过大肠癌中的MYO10介导类胰蛋白酶诱导的细胞迁移
    摘要：MYO10 is an actin-based motor protein and correlates with cancer metastasis. However, the regulation of MYO10 by tumor microenvironment is unknown. In the current study, we found that the expression of protease activated receptor 2 (PAR2) was highly correlated with that of MYO10 in colorectal carcinoma (CRC) specimens. Both MYO10 and PAR2 were up-regulated in lymph node metastasis group compared with non-metastasis group. Activation of PAR2 significantly induced cell migration through the up-regulation of MYO10, which was mediated by repression of miR-204 in multiple cell lines. Interestingly, it was observed that tryptase was highly expressed in adjacent tissue around primary tumor of CRC. Furthermore, tryptase stimulated cell migration and up-regulated MYO10 expression through a PAR2-dependent manner. Taken together, our findings showed that PAR2 enhanced the expression of MYO10 through the repression of miR-204. PAR2 mediated tryptase-induced cell migration and might contribute to the invasion of cancer cells at the edge of tumor.
  • 11.

    【2hr】Decursin inhibits tumor growth, migration, and invasion in gastric cancer by down-regulating CXCR7 expression

    包量

    机译 地精蛋白通过下调CXCR7表达来抑制胃癌中的肿瘤生长，迁移和侵袭
    摘要：CXC chemokine receptor 7 (CXCR7) is highly expressed in various type of cancers and promotes cancer progression and metastasis. However, the biological role and regulation of CXCR7 in gastric cancer remains unclear, and little is known about compounds that modulate CXCR7. Here, we investigated the role of CXCR7 in gastric tumorigenesis, and the effects of decursin, which is derived from Angelica gigas Nakai, on CXCR7. Our results showed that CXCR7 significantly promoted growth of gastric cancer cells and increased migration and invasion, which was mediated by the STAT3/c-Myc pathway. We also confirmed that decursin had an antitumor effect through down-regulating the expression of CXCR7 in gastric cancer. Furthermore, apoptotic cell death was induced through the reduction of anti-apoptotic factors such as Bcl-2 in vitro and in vivo. Our findings show that CXCR7 in gastric cancer promotes cancer progression through the STAT3/c-Myc pathway and that decursin is a natural compound that may target CXCR7 in gastric cancer treatment.
  • 12.

    【2hr】TRIM11 promotes tumor angiogenesis via activation of STAT3/VEGFA signaling in lung adenocarcinoma

    包量

    机译 TRIM11通过激活STAT3 / VEGFA信号激活肺腺癌促进肿瘤血管生成
    摘要：Tripartite motif containing 11 (TRIM11) plays important roles in the regulation of lung cancer behaviors. However, the mechanisms of action of TRIM11 in tumor angiogenesis remain unclear. In this study, we found that TRIM11 expression is higher in lung adenocarcinoma (ADC) than in normal lung tissues. High TRIM11 expression was found to be associated with advanced progression and a poor prognosis of lung ADCs. Functional assays demonstrated that TRIM11 promoted tumor growth and angiogenesis in vivo and enhanced migration of (and tube formation by) human umbilical vein endothelial cells (HUVECs). Mechanistically, TRIM11 was found to regulate angiogenesis through the signal transducer and activator of transcription 3 (STAT3)/vascular endothelial growth factor A (VEGFA) pathway. Moreover, in clinical samples, VEGFA expression was much higher in cancer tissue samples and positively correlated with TRIM11 expression. TRIM11-overexpressing samples showed higher CD31 staining and microvessel density. Thus, we provide evidence that TRIM11 is a proangiogenic factor in lung ADC and may serve as a therapeutic target for lung ADC treatment.
  • 13.

    【2hr】Endoplasmic reticulum-targeting sequence enhanced the cellular immunity of a tumor-associated antigen L6-based DNA vaccine

    包量

    机译 内质网靶向序列增强了基于肿瘤的基于抗原L6的DNA疫苗的细胞免疫
    摘要：Cancer vaccine design to effectively eliminate tumors requires triggering strong immune reactions to elicit long-lasting humoral and cellular immunity and DNA vaccines have been demonstrated to be an attractive immunotherapeutic approach. The tumor-associated antigen L6 (TAL6) is overexpressed on the surface of different cancer cells and promotes cancer progression; therefore, it could be a potential target for cancer treatment. We have revealed that a synthetic peptide containing HLA-A2-restricted cytotoxic T lymphocyte (CTL) and B cell epitope can induce cellular and humoral immunity against TAL6-expressing cancer. To enhance the efficacy of immunotherapy, in this report, we designed an endoplasmic reticulum (ER)-targeting sequence (adenovirus E3/19K protein) at the N-terminus of TAL6 to facilitate MHC class I antigen presentation to CD8+ T cells. Transfection of mammalian cells with the plasmid containing TAL6 fused with the ER-targeting sequence (pEKL6) resulted in higher levels of TAL6 antigens in the ER than transfection with the full-length TAL6 (pL6). The plasmid pEKL6 induced both TAL6-specific CTL responses and antibody titers after intramuscular (IM) immunization with electroporation and it elicited higher levels of antigen-specific CTLs in HLA-A2 transgenic mice. Immunization with pEKL6 induced higher levels of protective antitumor immunity against tumor growth than pL6 immunization in thymoma and melanoma tumor animal models. Notably, pEKL6 elicited long-term anti-tumor immunity against the recurrence of cancers. We found that CD4+ T, CD8+ T, and NK cells are all important for the effector mechanisms of pEKL6 immunization. Thus, cancer therapy using an ER-targeting sequence linked to a tumor antigen holds promise for treating tumors by triggering strong immune reactions.
  • 14.

    【2hr】Immuno-PET imaging of VEGFR-2 expression in prostate cancer with 89Zr-labeled ramucirumab

    包量

    机译 89Zr标记的ramucirumab在前列腺癌中VEGFR-2表达的免疫PET成像
    摘要：The detection and monitoring of prostate cancer (PrCa) malignancies using most of the conventional strategies is challenging. As an over-expressed biomarker of PrCa, the vascular endothelial growth factor receptor 2 (VEGFR-2) can be delineated by non-invasive imaging to address such issue. Herein, we report the positron emission tomography (PET) of VEGFR-2 expression in a PrCa mice models by composing a novel tracer, [89Zr]zirconium-labeled clinical VEGFR-2 antibody (Ramucirumab), i.e. 89Zr-Df-R. The VEGFR-2 expression levels among three different PrCa cell lines (PC-3, LNCAP and LAPC-4) were confirmed by flow cytometry. The immuno-PET imaging and bio-distribution (Bio-D) study were conducted in subcutaneous PrCa mice models via the 89Zr-Df-R. The regions of interest (ROI) data showed that the uptake of 89Zr-Df-R in the positive PC-3 (9.5±3 %ID/g) tumors are obviously higher than those ones in the negative LNCAP (6.0±1.7 %ID/g) or LAPC-4 (4.3±0.7 %ID/g) tumors at 120 hours post-injection, while the accumulation of 89Zr-Df-R in PC-3 tumors (4.3±1.2 %ID/g)) could be significantly reduced by the blockade of unlabeled Ramucirumab. These quantitative data coincide with the Bio-D data and proves the specificity. Additionally, the immuno-fluorescent staining results confirmed the expression pattern of VEGFR-2 among various PrCa tumors. Finally, the flow cytometry of PC-3 tumor tissue further proved that the binding of 89Zr-Df-R to VEGFR-2 primarily occurs on the PC-3 tumor cells. In summary, the description of the VEGFR-2 expression in PrCa by in-vivo PET with 89Zr-Df-R is feasible and it may shed light on the early detection of foci and dynamic monitoring of anti-VEGFR-2 therapy in PrCa.
  • 15.

    【2hr】The characterization of lung microbiome in lung cancer patients with different clinicopathology

    包量

    机译 不同临床病理特征的肺癌患者肺微生物组的特征
    摘要：There were few knowledge concerned correlation between lung microbiome and different clinicopathology of lung cancer. Bronchial washing fluid (BWF) and sputum are commonly used sample types but there was no study comparing difference of microbiome between these two in lung cancer. In this study, we aimed to compare difference of microbiome between these two sample types and characterize lung microbiome in squamous cell lung carcinoma with (SCC_M1) or without distant metastasis (SCC_M0) and lung adenocarcinoma with (AD_M1) or without distant metastasis (AD_M0). We collected 40 BWF samples and 52 sputum samples from newly diagnosed lung cancer patients. Bacterial species were sequenced via 16S rRNA sequencing. Phylum Proteobacteria in BWF samples were significantly higher than sputum samples (Wilcoxon test, P = 0.003). At phylum level, microbiome of BWF samples was more similar to that of lung cancer tissues reported in the previous literature. LEFse analysis showed that in BWF group, genera Veillonell, Megasphaera, Actinomyces and Arthrobacter in AD_M0 were significantly higher than those in SCC_M0, and genera Capnocytophaga and Rothia in AD_M1 were significantly lower than that in SCC_M1. Compared with AD_M0, genus Streptococcus of AD_M1 was significantly lower, and genera Veillonella and Rothia in SCC_M1 were significantly higher than that in SCC_M1. Our study suggested that BWF samples might better reflect the microbiome of lung cancer tissues. In different metastatic states of lung cancer, differential genera between squamous cell carcinoma and adenocarcinoma were different. And in different histologic types of lung cancer, distant metastasis-related genera were not the same.
  • 16.

    【2hr】Targeting snoRNAs as an emerging method of therapeutic development for cancer

    包量

    机译 靶向snoRNAs作为治疗癌症的新兴方法
    摘要：The relevance of the dysregulation of snoRNAs in human cancer has been widely investigated and has challenged the view that snoRNAs merely function as house-keeping genes for the posttranscriptional modification of rRNAs. Accumulating evidence has shown the intimate connection between snoRNAs and proliferation, apoptosis, invasion and migration of tumor cells via manual intervention patterns of snoRNA expression. In this review, we focused on how snoRNAs are dysregulated and its regulation of the formation and development of cancer. We summarized the non-classical functions of snoRNAs in the context of their regulations of the signaling pathways involving PI3K-AKT and K-Ras and p53-dependant manner. Under these novel functions and characteristics, snoRNAs can act as potential and feasible biomarkers for diagnosis. Simultaneously, these promising therapeutic strategies should be considered to counteract the perturbations of snoRNAs.
  • 17.

    【2hr】Chemopreventive and anticancer activity of flavonoids and its possibility for clinical use by combining with conventional chemotherapeutic agents

    包量

    机译 黄酮类化合物的化学预防和抗癌活性及其与常规化学治疗剂合用的临床应用可能性
    摘要：Cancer is a diverse class of diseases characterized by uncontrolled cell growth with the potential to invade and spread to other parts of the body, and continues to be one of the leading causes of death worldwide. Conventional cancer treatment modalities include antitumor drugs, surgical resection, locally targeted therapies such as radiation therapy. Along with improved understanding of the molecular pathogenesis of various cancers, generation and the use of smart targeted anti-cancer drugs have been challenged. The need for novel therapeutic strategies remains paramount given the sustained development of drug resistance, tumor recurrence, and metastasis. Development of new strategies aimed at improving chemotherapy sensitivity and minimizing the adverse side effects is thus essential for obtaining satisfied therapeutic outcomes for patients and enhancing their quality of life. Emerging evidence has reported that many cancer patients use either herbs employed in complementary therapies or dietary agents that influence cellular signaling worldwide. Numerous components of edible plants, collectively termed phytochemicals that have beneficial effects for health, are being reported increasingly in the scientific literature. Of those, flavonoids have attracted much attention by virtue of its wide variety of biological functions including antioxidant, anti-inflammatory, and anticancer activity. In this review, we highlight the molecular mechanisms underlying its multiple pharmacological effects, especially focusing on cancer chemoprevention. We further discuss possible strategies to develop anticancer therapy by combining flavonoids nutraceuticals and conventional chemotherapeutic agents. We also highlight numerous pharmacokinetic challenges such as bioavailability, drug-drug interactions, which are still fundamental questions concerning its future clinical application.
  • 18.

    【2hr】Trends in the treatment of advanced hepatocellular carcinoma: immune checkpoint blockade immunotherapy and related combination therapies

    包量

    机译 晚期肝细胞癌的治疗趋势：免疫检查点封锁免疫疗法及相关联合疗法
    摘要：Hepatocellular carcinoma (HCC) is the most common liver cancer with high morbidity and mortality worldwide. Systemic treatments with several multi-targeted tyrosine kinase inhibitors (TKIs), including sorafenib, lenvatinib, regorafenib and cabozantinib, have been widely utilized int the treatment of HCC. However, with tolerable adverse events and relative low survival time, neo or optimized therapies for advanced HCC are still urgently needed. New developed immune checkpoint inhibitors therapy have been first demonstrated effective in metastatic melanoma through against CTLA-4 or PD-1/PD-L1 to renew T cell effector function. Preclinical data indicated that interference with immune checkpoint molecules results in HCC growth suppression, suggesting it may bring hope to the HCC treatment. Several clinical trials applying monoclonal antibodies to immune checkpoint molecules demonstrated that immune checkpoint inhibitors are safe and enable durable antitumor activity in advanced HCC patients. Several published immunotherapy trials in HCC using Anti-CTLA-4 agents (tremelimumab) or anit-PD-1 agents (Nivolumab) have showed promising results, in which have similar response rate (15%-30%) and disease control rate with TKIs therapies. This article will review the on-going clinical trials associated with immune checkpoint molecules monotherapy or co, and then discuss the optimal scheme of immune checkpoint therapy for advanced HCC.
  • 19.

    【2hr】How to differentiate pseudoprogression from true progression in cancer patients treated with immunotherapy

    包量

    机译 在免疫疗法治疗的癌症患者中如何区分假进展与真实进展
    摘要：Immunotherapy has achieved unprecedented clinical efficacy in patients with various types of advanced tumors; however, some patients experience delayed tumor shrinkage following an increase in tumor burden after such a therapeutic method. This phenomenon is called pseudoprogression and can lead to premature cessation of efficacious immunotherapeutic agents. Consequently, we summarized the available data on methods to differentiate pseudoprogression from true progression in patients who have been treated with immunotherapy including biomarkers, medical imaging techniques and biopsy. We also introduce hyperprogression and special pseudoprogression for improved evaluation of immunotherapy.
  • 20.

    【2hr】Focus on exosomes: novel pathogenic components of leukemia

    包量

    机译 专注于外泌体：白血病的新型致病成分
    摘要：Exosomes are released membrane vesicles derived from late endosomes, which share structural and biochemical characteristics with proteasomes. Exosomes are responsible for trafficking proteins, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) among cells and regulating various cellular processes, such as differentiation, proliferation, migration, invasion, and apoptosis. Although our knowledge of the roles of exosomes in the initiation and progression of leukemia is limited, some studies have indicated that exosomes can encompass many functional factors with an appropriate sorting signal, thereby supporting the metastasis, drug resistance, and immune escape of leukemia cells. This review initially focuses on the biogenesis and composition of exosomes and then summarizes the application of exosomes as a screening biomarker and a potential therapeutic target in leukemia. Many recent reports on the functions of exosomes released from leukemia cells are also discussed, including drug resistance, immune dysfunction, and microenvironment manipulation. Given the critical roles of exosomes in leukemia, understanding the mechanisms regulating the compositions and levels of exosomes, as well as defining exosome functions, will ultimately provide additional insights into the use of exosomes as therapeutic agents for leukemia treatment.
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