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  • 机译 METTL3通过稳定的整合素β1mRNA通过m6A-HuR依赖性机制增强前列腺癌的细胞粘附性
    摘要:
  • 机译 线粒体动力学在人类癌症中的作用
    摘要:Mitochondria are crucial cellular organelles. Under extracellular stimulations, mitochondria undergo constant fusion and fission dynamics to meet different cellular demands. Mitochondrial dynamics is regulated by specialized proteins and lipids. Dysregulated mitochondrial dynamics has been linked to the initiation and progression of diverse human cancers, affecting aspects such as cancer metastasis, drug resistance and cancer stem cell survival, suggesting that targeting mitochondrial dynamics is a potential therapeutic strategy. In the present review, we summarize the molecular mechanisms underlying fusion and fission dynamics and discuss the effects of mitochondrial dynamics on the development of human cancers.
  • 机译 癌症中慢性应激诱导的免疫失调:对起始,进展,转移和治疗的意义
    摘要:
  • 机译 大肠癌癌变前期的免疫战:关注免疫细胞组成,功能和细胞因子产物
    • 作者:Guanglin Cui
    • 刊名:American Journal of Cancer Research
    • 2020年第5期
    摘要:It is now widely accepted that most human cancers, including colorectal cancers (CRCs), develop from premalignant lesions through a long-term multistep process. Host immunity is a key determinant that maintains most premalignant lesions in a stable state via immunosurveillance. However, premalignant cells use diverse strategies to escape host immunosurveillance. A switch in the immune function from immunosurveillance to immunosuppression facilitates the progression of premalignant lesions to established CRCs. This review summarizes the recent progress in understanding alterations in the immune landscape, including immune cell compositions, functions and cytokine products, in the premalignant stage of CRC and provides an updated discussion on its translational significance along the colorectal adenoma-carcinoma sequence.
  • 机译 中低收入国家的乳腺癌:剪接异常和缺乏针对性的治疗选择
    摘要:Breast cancer is a common malignancy among women worldwide. Regardless of the economic status of a country, breast cancer poses a burden in prevention, diagnosis and treatment. Developed countries such as the U.S. have high incidence and mortality rates of breast cancer. Although low incidence rates are observed in developing countries, the mortality rate is on the rise implying that low- to middle-income countries lack the resources for preventative screening for early detection and adequate treatment resources. The differences in incidence between countries can be attributed to changes in exposure to environmental risk factors, behaviour and lifestyle factors of the different population groups. Genomic modifications are an important factor that significantly alters the risk profile of breast tumourigenesis. The incidence of early-onset breast cancer is increasing and evidence shows that early onset of breast cancer is far more aggressive than late onset of the disease; possibly due to the difference in genetic alterations or tumour biology. Alternative splicing is a pivotal factor in the progressions of breast cancer. It plays a significant role in tumour prognosis, survival and drug resistance; hence, it offers a valuable option as a therapeutic target. In this review, the differences in breast cancer incidence and mortality rates in developed countries will be compared to low- to middle-income countries. The review will also discuss environmental and lifestyle risk factors, and the underlying molecular mechanisms, genetic variations or mutations and alternative splicing that may contribute to the development and novel drug targets for breast cancer.
  • 机译 催乳素和雄激素R1881在三阴性和HER2 +乳腺癌中诱导生存前的羧肽酶D和EDD E3连接酶
    摘要:Plasma membrane carboxypeptidase-D (CPD) hydrolyzes C-terminal arginine (Arg) from extracellular substrates, and Arg is converted into nitric oxide (NO) in the cell. CPD is upregulated by prolactin (PRL) and androgens in breast cancer (BCa) cells, increasing NO production to promote cell survival. EDD E3 ubiquitin ligase, upregulated by PRL/androgens, is implicated in TORC1 signaling. This study investigated CPD and EDD in triple-negative (TNBC) and HER2+ BCa. Kaplan-Meier analysis showed a negative correlation between CPD or EDD mRNA expression in TNBC patients and relapse-free survival. Immunohistochemistry showed that benign and malignant breast tissues stained abundantly for the PRL receptor (PRLR) and androgen receptor (AR). CPD and EDD staining were elevated in TNBC and HER2+ tumors as compared to benign tissues. In TNBC/HER2+ cell lines, CPD and EDD protein expression were upregulated by PRL or synthetic androgen methyltrienolone (R1881) at 3-6 h. PRL/R1881-induced CPD in TNBC and HER2+ cells increased intracellular NO production, which was abolished by PRLR antagonist ∆1-9-G129R-hPRL and AR antagonist flutamide. In turn, treatment with NO increased viability and decreased apoptosis in Arg-deprived TNBC cells. Cell viability and apoptosis were also affected in HER2+ cells with CPD knockdown. Lastly, EDD knockdown decreased PRL/R1881-induced phosphorylation of initiation factor 4E binding protein-1 and decreased 4E release in TNBC cells. In summary, PRL/R1881-induced CPD promotes TNBC/HER2+ cell survival through production of NO, and EDD promotes TNBC cell survival by TORC1 activation. This study implicates CPD and EDD as useful therapeutic targets for TNBC/HER2+ tumors, and suggests that PRLR and AR blockade are also beneficial to these patients.
  • 机译 预测前列腺癌患者的长期多类别死亡原因:随机森林与多项式模型
    摘要:The majority of patients with prostate cancer die of non-cancer causes of death (COD). It is thus important to accurately predict multi-category COD in these patients. Random forest (RF), a popular machine learning model, has been shown useful for predicting binary cancer-specific deaths. However, its accuracy for predicting multi-category COD in cancer patients is unclear. We included patients in Surveillance, Epidemiology, and End Results-18 cancer registry-program with prostate cancer diagnosed in 2004 (followed-up through 2016). They were randomly divided into training and testing sets with equal sizes. We evaluated prediction accuracies of RF and conventional statistical/multinomial models for 6-category COD by data-encoding types using the 2-fold cross-validation approach. Among 49,864 prostate cancer patients, 29,611 (59.4%) were alive at the end of follow-up, and 5,448 (10.9%) died of cardiovascular disease, 4,607 (9.2%) of prostate cancer, 3,681 (7.4%) of non-prostate cancer, 717 (1.4%) of infection, and 5,800 (11.6%) of other causes. We predicted 6-category COD among these patients with a mean accuracy of 59.1% (n=240, 95% CI, 58.7%-59.4%) in RF models with one-hot encoding, and 50.4% (95% CI, 49.7%-51.0%) in multinomial models. Tumor characteristics, prostate-specific antigen level, and diagnosis confirmation-method were important in RF and multinomial models. In RF models, no statistical differences were found between the accuracies of training versus cross-validation phases, and those of categorical versus one-hot encoding. We here report that RF models can outperform multinomial logistic models (absolute accuracy-difference, 8.7%) in predicting long-term 6-category COD among prostate cancer patients, while pathology diagnosis itself and tumor pathology remain important factors.
  • 机译 具有抗人胰腺癌活性的新型小肽
    摘要:KTH-222 is a novel, 8-amino acid length peptide. It is derived from a motif identified in a group of peptides that are related to atrial natriuretic peptide and that are able to inhibit cancer cell growth. We report here that KTH-222 inhibits the attachment, proliferation, and development of an invasive morphology in cultured human pancreatic tumor cells (MIA PaCa-2 and HPAC). At a biochemical level, it inhibits tubulin polymerization which may underlie these cellular effects. We further report that KTH-222 reduces the rate of tumor growth and prolongs survival in mice implanted with MIA PaCa-2 cells. In this model system, KTH-222 is more effective than gemcitabine, a drug commonly used in the treatment of pancreatic cancer. Furthermore, KTH-222 does not decrease the rate of weight gain in the treated mice, suggesting the absence of gross toxicity. These activities of KTH-222 suggest that it may be useful in the treatment of pancreatic cancer.
  • 机译 COX7RP的过表达通过诱导肝癌细胞中ROS的产生来促进肿瘤生长和转移
    摘要:Cumulative evidence has indicated that mitochondrial respiration dysfunction plays important roles in tumorigenesis. However, the role of COX7RP, a critical regulator in the formation of mitochondrial respiratory supercomplex that has been suggested to be over-expressed in hepatocellular carcinoma (HCC) by our bioinformatic analysis of TCGA data, in tumor progression remains largely unclear. In this study, we found that COX7RP is frequently over-expressed in HCC mainly due to the down-regulation of miR-130a-3p and predicts poor prognosis of HCC patients. Functional experiments revealed that COX7RP promoted both growth and metastasis of HCC through induction of cell cycle progression and epithelial to mesenchymal transition (EMT), and suppression of cell apoptosis. Mechanistically, increased generation of reactive oxygen species (ROS) and subsequently activated nuclear transcription factor-κB (NF-κB) signaling was found to contribute to the promotion of HCC cell growth and metastasis by COX7RP. Collectively, COX7RP plays a critical oncogenic role in hepatocellular carcinogenesis, supporting COX7RP as a novel prognostic factor and therapeutic target in HCC.
  • 机译 抑制ULK1激酶可降低高级浆液性卵巢癌球体的自噬和细胞活力
    摘要:Metastasis in high-grade serous ovarian cancer (HGSOC) occurs through an unconventional route that involves exfoliation of cancer cells from primary tumors and peritoneal dissemination via multicellular clusters or spheroids. Previously, we demonstrated autophagy induction in HGSOC spheroids grown and in spheroids collected from ovarian cancer patient ascites; thus, we speculate that autophagy may contribute to spheroid cell survival and overall disease progression. Hence, in this study we sought to evaluate whether ULK1 (unc-51-like kinase-1), a serine-threonine kinase critical for stress-induced autophagy, is important for autophagy regulation in HGSOC spheroids. We demonstrate that HGSOC spheroids have increased ULK1 protein expression that parallels autophagy activation. knockdown increased p62 accumulation and decreased LC3-II/I ratio in HGSOC spheroids. In addition, knocking down ATG13, a protein that regulates ULK1 activity via complex formation, phenocopied our ULK1 knockdown results. HGSOC spheroids were blocked in autophagic flux due to and knockdown as determined by an mCherry-eGFP-LC3B fluorescence reporter. These observations were recapitulated when HGSOC spheroids were treated with an ULK1 kinase inhibitor, MRT68921. Autophagy regulation in normal human fallopian tube epithelial FT190 cells, however, may bypass ULK1, since MRT68921 reduced viability in HGSOC spheroids but not in FT190 cells. Interestingly, mRNA expression is negatively correlated with patient survival among stage III and stage IV serous ovarian cancer patients. As we observed using established HGSOC cell lines, cultured spheroids using our new, patient-derived HGSOC cells were also sensitive to ULK1 inhibition and demonstrated reduced cell viability to MRT68921 treatment. These results demonstrate the importance of ULK1 for autophagy induction in HGSOC spheroids and therefore justifies further evaluation of MRT68921, and other novel ULK1 inhibitors, as potential therapeutics against metastatic HGSOC.
  • 机译 CLIC4调节iNOS对γ射线照射后鼻咽癌的放射抵抗能力,但对碳离子照射不起作用
    摘要:Nasopharyngeal carcinoma (NPC) is a major health problem in the East and Southeast Asia, and the intensity modulated radiotherapy (IMRT) is the current preferred treatment method of NPC, but radioresistance-induced residual and recurrent tumors are the main cause of treatment failure. Till now, the mechanism of radioresistance and prognostic biomarkers of NPC are still unrevealed. In this study, we collected clinical NPC samples and established radioresistant NPC-R cell lines by irradiating NPC cells with fractionation doses of γ-rays. Using genechip assay between radioresistance and radiosensitive clinical samples and TMT assay between NPC and NPC-R cells, differential expressed genes were examined and the potential biomarker of radioresistance was screened. Immunohistochemical assay of NPC clinical specimens showed that CLIC4 was significantly up-regulated in radioresistance tumor tissues. In vitro studies confirmed that up-regulation of CLIC4 gene enhanced radioresistance in comparison with the alterations of intracellular oxidative metabolism of reactive oxygen species (ROS) and nitric oxide (NO) in an opposite way. Correspondingly, inhibition of CLIC4 sensitized NPC cells to irradiation and decreased nuclear translocation of iNOS and intracellular level of NO in NPC cells. Interestingly, the capacity for DNA repair had no difference between NPC and NPC-R cells. Moreover, because of great interests in using carbon ion irradiation to treat NPC effectively, we demonstrated that, after carbon ion irradiation, NPC-R and NPC cells had similar survival even under the status of up- or down-regulation of CLIC4. Conclusively, CLIC4 contributes to radioresistance of NPC to γ-rays but not carbon ions by regulating intracellular oxidative metabolism of nuclear translocation of iNOS.
  • 机译 携带胞嘧啶脱氨酶基因的间充质干细胞与5-氟胞嘧啶和替莫唑胺在原位神经胶质瘤模型中的联合作用
    摘要:
  • 机译 NQO1是细胞对抗肿瘤药物那巴布星的敏感性的决定因素
    摘要:Napabucasin (NAPA) is thought to be a potent cancer stemness inhibitor in different types of cancer cell lines. While it has shown promising activity in early phase clinical trials, two recent phase III NAPA clinical trials failed to meet the primary endpoint of overall survival. The reason for the failure is not clear, but a possible way to revive the clinical trial is to stratify patients with biomarkers that could predict NAPA response. Here, we report the identification of NAD(P)H dehydrogenase 1 (NQO1) as a major determinant of NAPA efficacy. A proteomic profiling of cancer cell lines revealed that NQO1 abundance is negatively correlated with IC ; in vitro assays showed that NAPA is a substrate for NQO1, which mediates the generation of ROS that leads to cell death. Furthermore, activation of an NQO1 transcription factor NRF2 by chemicals, including an FDA approved drug, can increase the NAPA cytotoxicity. Our findings suggest a potential use of NQO1 expression as a companion diagnostic test to identify patients in future NAPA trials and a combination strategy to expand the application of NAPA-based regimens for cancer therapy.
  • 机译 BAP1通过稳定DIDO1维持肾细胞癌的染色体稳定性
    摘要:
  • 机译 诊断时肝转移的发生率和预后:一项基于全癌人群的研究
    摘要:Metastasis is a major cause of cancer-related death and liver metastasis (LM) is a distinct type for its relatively good prognosis after timely treatment for selected patients. However, a generalizable estimation of incidence and prognosis of LM is lacking. Cancer patients with known LM status in the Surveillance, Epidemiology and End Results database were enrolled in the present study. The incidence and prognosis of LM were calculated by primary cancer type and clinicopathological factors. Among 1,630,725 cases, 105,329 (6.46%) cases present LM at diagnosis, with a median survival of 4 months. LM presents at diagnosis in 39.96% of pancreatic cancer, 16.00% of colorectal cancer (CRC) and 12.68% of lung cancer. Of all LM cases, 25.58% originated from lung cancer, with 24.76% from CRC and 17.55% from pancreatic cancer. LM originated from small intestine cancer shows the best prognosis (median survival: 30 months), followed by testis cancer (25 months) and breast cancer (15 months). Subgroup analyses demonstrated disparities in incidence and prognosis of LM, with higher incidence and poorer prognosis in the older population, African American, male, and patients with inferior socioeconomic status. The current study provides a generalizable data resource for the epidemiology of LM, which may help tailor screening protocol, design clinical trials and estimate disease burden.
  • 机译 患者应在COVID-19大流行期间停止放疗或化疗
    摘要:In the previous stage, there were too many patients with Corona virus disease 2019 (COVID-19) in Wuhan. Ordinary people, patients, even doctors, had a great sense of desperate. On the one hand, almost all doctors participated in the treatment of patients of COVID-19. On the other hand, the government restricted residents to go out, and the sick people were also afraid of being infected with COVID-19 when seeking medical treatment. Whether cancer patients seek medical treatment or not has become a contradiction for a long time. Our Viewpoint paper is to provide a positive signal to doctors and patients that patients with in the middle or advanced stage of cancer can receive radiotherapy and/or chemotherapy normally under protective measures.

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