Publisher: BMC (Biomed Central)   (Total: 316 journals)

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Showing 201 - 316 of 316 Journals sorted by number of followers
Fisheries and Aquatic Sciences     Open Access   (Followers: 3, SJR: 0.199, CiteScore: 0)
Cancers of the Head & Neck     Open Access   (Followers: 3)
Clinical and Translational Allergy     Open Access   (Followers: 3, SJR: 1.425, CiteScore: 4)
J. of Clinical Movement Disorders     Open Access   (Followers: 3)
Advances in Rheumatology     Open Access   (Followers: 3)
J. of Animal Science and Technology     Open Access   (Followers: 3)
Flavour     Open Access   (Followers: 3)
Biomarker Research     Open Access   (Followers: 3)
Cancer Imaging     Open Access   (Followers: 3, SJR: 1.012, CiteScore: 3)
Inflammation and Regeneration     Open Access   (Followers: 2)
Asthma Research and Practice     Open Access   (Followers: 2)
Public Health Reviews     Open Access   (Followers: 2, SJR: 0.454, CiteScore: 1)
Intl. J. of Retina and Vitreous     Open Access   (Followers: 2)
Biology of Sex Differences     Open Access   (Followers: 2, SJR: 1.902, CiteScore: 4)
Tropical Diseases, Travel Medicine and Vaccines     Open Access   (Followers: 2)
J. of Angiogenesis Research     Open Access   (Followers: 2)
Animal Biotelemetry     Open Access   (Followers: 2, SJR: 1.067, CiteScore: 2)
BMC Materials     Open Access   (Followers: 2)
Urban Transformations     Open Access   (Followers: 2)
CABI Agriculture and Bioscience     Open Access   (Followers: 2)
J. of Biomedical Semantics     Open Access   (Followers: 2, SJR: 0.952, CiteScore: 2)
One Health Outlook     Open Access   (Followers: 2)
NeuroCommons     Open Access   (Followers: 2)
Signals     Open Access   (Followers: 2)
Contraception and Reproductive Medicine     Open Access   (Followers: 2)
Fertility Research and Practice     Open Access   (Followers: 2)
Chinese Medicine     Open Access   (Followers: 2, SJR: 0.57, CiteScore: 2)
J. of Inflammation     Open Access   (Followers: 2, SJR: 1.101, CiteScore: 3)
Molecular Neurodegeneration     Open Access   (Followers: 2, SJR: 3.418, CiteScore: 7)
Fluids and Barriers of the CNS     Open Access   (Followers: 2, SJR: 2.054, CiteScore: 5)
Cell Communication and Signaling     Open Access   (Followers: 2, SJR: 2.211, CiteScore: 4)
BMC Pharmacology     Open Access   (Followers: 2)
Cancer Nanotechnology     Open Access   (Followers: 2, SJR: 1.168, CiteScore: 4)
Neural Development     Open Access   (Followers: 2, SJR: 1.821, CiteScore: 2)
J. of Neuroinflammation     Open Access   (Followers: 2, SJR: 2.336, CiteScore: 5)
J. of Experimental & Clinical Cancer Research     Open Access   (Followers: 2, SJR: 2, CiteScore: 6)
Particle and Fibre Toxicology     Open Access   (Followers: 2, SJR: 2.253, CiteScore: 8)
Hereditary Cancer in Clinical Practice     Open Access   (Followers: 2, SJR: 0.848, CiteScore: 2)
BMC Proceedings     Full-text available via subscription   (Followers: 2, SJR: 0.302, CiteScore: 1)
Italian J. of Pediatrics     Open Access   (Followers: 2, SJR: 0.685, CiteScore: 2)
Reproductive Health     Open Access   (Followers: 2, SJR: 1.228, CiteScore: 2)
Plant Methods     Open Access   (Followers: 2, SJR: 1.885, CiteScore: 4)
Acta Neuropathologica Communications     Open Access   (Followers: 1, SJR: 2.683, CiteScore: 5)
Canine Genetics and Epidemiology     Open Access   (Followers: 1)
Cerebellum & Ataxias     Open Access   (Followers: 1)
Infectious Diseases of Poverty     Open Access   (Followers: 1, SJR: 1.212, CiteScore: 3)
Longevity & Healthspan     Open Access   (Followers: 1)
J. of Environmental Health Science & Engineering     Open Access   (Followers: 1, SJR: 0.802, CiteScore: 3)
Translational Neurodegeneration     Open Access   (Followers: 1, SJR: 1.901, CiteScore: 5)
Eye and Vision     Open Access   (Followers: 1)
Cancer Convergence     Open Access   (Followers: 1)
BMC Zoology     Open Access   (Followers: 1)
Bioelectronic Medicine     Open Access   (Followers: 1)
European J. of Medical Research     Open Access   (Followers: 1, SJR: 0.55, CiteScore: 1)
Scoliosis and Spinal Disorders     Open Access   (Followers: 1, SJR: 0.843, CiteScore: 2)
Women's Midlife Health     Open Access   (Followers: 1)
COPD Research and Practice     Open Access   (Followers: 1, SJR: 0.755, CiteScore: 2)
Genes and Environment     Open Access   (Followers: 1, SJR: 0.516, CiteScore: 1)
Gynecologic Oncology Research and Practice     Open Access   (Followers: 1)
Pilot and Feasibility Studies     Open Access   (Followers: 1)
Investigative Genetics     Open Access   (Followers: 1, SJR: 1.809, CiteScore: 3)
J. of Venomous Animals and Toxins including Tropical Diseases     Open Access   (Followers: 1, SJR: 0.573, CiteScore: 2)
Orphanet J. of Rare Diseases     Open Access   (Followers: 1, SJR: 1.413, CiteScore: 3)
Skeletal Muscle     Open Access   (Followers: 1, SJR: 2.32, CiteScore: 4)
J. of Medical Case Reports     Open Access   (Followers: 1, SJR: 0.331, CiteScore: 1)
Head & Face Medicine     Open Access   (Followers: 1, SJR: 0.62, CiteScore: 2)
BMC Ear, Nose and Throat Disorders     Open Access   (Followers: 1, SJR: 0.653, CiteScore: 2)
Cell Division     Open Access   (Followers: 1, SJR: 2.445, CiteScore: 4)
Respiratory Research     Open Access   (Followers: 1, SJR: 1.644, CiteScore: 4)
Proteome Science     Open Access   (Followers: 1, SJR: 0.792, CiteScore: 2)
Theoretical Biology and Medical Modelling     Open Access   (Followers: 1, SJR: 0.783, CiteScore: 2)
Biological Research     Open Access   (Followers: 1, SJR: 0.654, CiteScore: 2)
Hereditas     Open Access   (Followers: 1, SJR: 0.278, CiteScore: 1)
Thyroid Research     Open Access   (Followers: 1, SJR: 0.329, CiteScore: 1)
World Allergy Organization J.     Open Access   (Followers: 1, SJR: 1.936, CiteScore: 6)
World J. of Surgical Oncology     Open Access   (Followers: 1, SJR: 0.688, CiteScore: 2)
J. of Cardiovascular Magnetic Resonance     Open Access   (Followers: 1, SJR: 2.292, CiteScore: 5)
Molecular Cytogenetics     Open Access   (Followers: 1, SJR: 0.623, CiteScore: 1)
Measurement Instruments for the Social Sciences     Open Access  
BMC Energy     Open Access  
Sustainable Earth     Open Access  
BMC Biomedical Engineering     Open Access  
BMC Chemical Engineering     Open Access  
ExRNA     Open Access  
J. of Cotton Research     Open Access  
Biomedical Dermatology     Open Access  
Cancer Communications     Open Access  
Diagnostic and Prognostic Research     Open Access  
Porcine Health Management     Open Access  
Neurovascular Imaging     Open Access  
NeuroMetals     Open Access  
Chinese Neurosurgical J.     Open Access  
Cardio-Oncology     Open Access  
Neuropsychiatric Electrophysiology     Open Access  
Research Involvement and Engagement     Open Access  
J. of Biological Research - Thessaloniki     Open Access   (SJR: 0.32, CiteScore: 2)
J. of Therapeutic Ultrasound     Open Access   (SJR: 0.906, CiteScore: 3)
Cilia     Open Access   (SJR: 0.732, CiteScore: 1)
Israel J. of Health Policy Research     Open Access   (SJR: 0.488, CiteScore: 1)
Vascular Cell     Open Access   (SJR: 1.349, CiteScore: 4)
Clinical Sarcoma Research     Open Access  
Environmental Microbiome     Open Access   (SJR: 0.768, CiteScore: 2)
Mobile DNA     Open Access   (SJR: 3.783, CiteScore: 5)
J. of Neurodevelopmental Disorders     Open Access   (SJR: 1.71, CiteScore: 4)
Biological Procedures Online     Open Access   (SJR: 1.352, CiteScore: 4)
Basic and Clinical Andrology     Open Access   (SJR: 0.564, CiteScore: 2)
PMC Biophysics     Open Access  
Fibrogenesis & Tissue Repair     Open Access   (SJR: 1.531, CiteScore: 4)
J. of Ovarian Research     Open Access   (SJR: 1.008, CiteScore: 3)
Source Code for Biology and Medicine     Open Access   (SJR: 0.784, CiteScore: 2)
Retrovirology     Open Access   (SJR: 1.855, CiteScore: 3)
Lipids in Health and Disease     Open Access   (SJR: 0.915, CiteScore: 2)
J. of Negative Results in BioMedicine     Open Access   (SJR: 0.483, CiteScore: 1)
J. of Ethnobiology and Ethnomedicine     Open Access   (SJR: 0.693, CiteScore: 3)
Infectious Agents and Cancer     Open Access   (SJR: 0.855, CiteScore: 2)
Harm Reduction J.     Open Access   (SJR: 1.445, CiteScore: 3)

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Biomarker Research
Number of Followers: 3  

  This is an Open Access Journal Open Access journal
ISSN (Online) 2050-7771
Published by BMC (Biomed Central) Homepage  [316 journals]
  • Assessment of serum macrophage migration inhibitory factor (MIF),
           adiponectin, and other adipokines as potential markers of proteinuria and
           renal dysfunction in lupus nephritis: a cross-sectional study

    • Abstract: Background To date, the association of serum macrophage migration inhibitory factor (MIF) and serum adipokines with lupus nephritis is controversial. Objective To assess the utility of serum MIF, leptin, adiponectin and resistin levels as markers of proteinuria and renal dysfunction in lupus nephritis. Methods Cross-sectional study including 196 systemic lupus erythematosus (SLE) patients and 52 healthy controls (HCs). Disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Renal SLE involvement was investigated by renal-SLEDAI. MIF, adiponectin, leptin and resistin levels were quantified by ELISA. We assessed the correlations of quantitative variables by Spearman correlation (rs). Multivariable linear regression adjusted the variables associated with the severity of proteinuria. Results SLE patients had higher MIF (p = 0.02) and adiponectin (p < 0.001) than HCs. Patients with renal SLE involvement (n = 43) had higher adiponectin (19.0 vs 13.3 μg/mL, p = 0.002) and resistin (10.7 vs 8.9 ng/mL, p = 0.01) than patients with non-renal SLE (n = 153). Proteinuria correlated with high adiponectin (rs = 0.19, p < 0.009) and resistin (rs = 0.26, p < 0.001). MIF (rs = 0.27, p = 0.04). Resistin correlated with increased creatinine (rs = 0.18, p = 0.02). High renal-SLEDAI correlated with adiponectin (rs = 0.21, p = 0.004). Multiple linear regression showed that elevated adiponectin (p = 0.02), younger age (p = 0.04) and low MIF (p = 0.02) were associated with the severity of proteinuria. Low MIF and high adiponectin levels interacted to explain the association with the severity of proteinuria (R2 = 0.41). Conclusions High adiponectin combined with low MIF concentrations int+eract to explain the severity of proteinuria in renal SLE. These findings highlight the relevance of adiponectin, resistin and MIF as markers of LN.
      PubDate: 2020-10-28
       
  • CCR7 as a novel therapeutic target in t-cell PROLYMPHOCYTIC leukemia

    • Abstract: T-cell prolymphocytic leukemia (T-PLL) is a poor prognostic disease with very limited options of efficient therapies. Most patients are refractory to chemotherapies and despite high response rates after alemtuzumab, virtually all patients relapse. Therefore, there is an unmet medical need for novel therapies in T-PLL. As the chemokine receptor CCR7 is a molecule expressed in a wide range of malignancies and relevant in many tumor processes, the present study addressed the biologic role of this receptor in T-PLL. Furthermore, we elucidated the mechanisms of action mediated by an anti-CCR7 monoclonal antibody (mAb) and evaluated whether its anti-tumor activity would warrant development towards clinical applications in T-PLL. Our results demonstrate that CCR7 is a prognostic biomarker for overall survival in T-PLL patients and a functional receptor involved in the migration, invasion, and survival of leukemic cells. Targeting CCR7 with a mAb inhibited ligand-mediated signaling pathways and induced tumor cell killing in primary samples. In addition, directing antibodies against CCR7 was highly effective in T-cell leukemia xenograft models. Together, these findings make CCR7 an attractive molecule for novel mAb-based therapeutic applications in T-PLL, a disease where recent drug screen efforts and studies addressing new compounds have focused on chemotherapy or small molecules.
      PubDate: 2020-10-24
       
  • Long interspersed nuclear element 1 hypomethylation has novel prognostic
           value and potential utility in liquid biopsy for oral cavity cancer

    • Abstract: Background New biomarkers are urgently needed to improve personalized treatment approaches for head and neck squamous cell carcinoma (HNSCC). Global DNA hypomethylation has wide-ranging functions in multistep carcinogenesis, and the hypomethylation of long interspersed nucleotide element-1 (LINE-1) is related to increased retrotransposon activity and induced genome instability. However, little information is available regarding LINE-1 hypomethylation and its prognostic implications in HNSCC. Methods In this study, we analyzed LINE-1 hypomethylation levels in a well-characterized dataset of 317 primary HNSCC tissues and 225 matched pairs of normal mucosa tissues, along with five oral cavity cancer (OCC) circulating tumor DNA (ctDNA) samples using quantitative real-time methylation and unmethylation PCR. The analysis was performed according to various clinical characteristics and prognostic implications. Results The results demonstrated that LINE-1 hypomethylation levels were significantly higher in the HNSCC tissues than in corresponding normal tissues from the same individuals (P < 0.001). Univariate analysis revealed that high levels of LINE-1 hypomethylation were correlated with poor disease-free survival (DFS; log-rank test, P = 0.038), whereas multivariate analysis demonstrated that they were significant independent prognostic factor for DFS (hazard ratio: 2.10, 95% confidence interval: 1.02–4.36; P = 0.045). Moreover, samples with high LINE-1 hypomethylation levels exhibited the greatest decrease in 5-hydroxymethylcytosine (5-hmC) levels and increase in tumor-suppressor gene methylation index (P = 0.006 and P < 0.001, respectively). Further, ctDNA studies also showed that LINE-1 hypomethylation had high predictive ability in OCC. Conclusions LINE-1 hypomethylation is associated with a higher risk of early OCC relapse, and is hence, a potential predictive biomarker for OCC. Furthermore, 5-hmC levels also exhibited predictive potential in OCC, based on their inverse correlation with LINE-1 hypomethylation levels. LINE-1 hypomethylation analysis, therefore, has applications in determining patient prognosis and real-time surveillance of disease recurrence, and could serve as an alternative method for OCC screening.
      PubDate: 2020-10-23
       
  • Mechanisms of tRNA-derived fragments and tRNA halves in cancer treatment
           resistance

    • Abstract: The tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs) are newly discovered noncoding RNAs in recent years. They are derived from specific cleavage of mature and pre-tRNAs and expressed in various cancers. They enhance cell proliferation and metastasis or inhibit cancer progression. Many studies have investigated their roles in the diagnosis, progression, metastasis, and prognosis of various cancers, but the mechanisms through which they are involved in resistance to cancer treatment are unclear. This review outlines the classification of tRFs and tiRNAs and their mechanisms in cancer drug resistance, thus providing new ideas for cancer treatment.
      PubDate: 2020-10-15
       
  • Lymphocyte antigen 6 superfamily member D is a marker of urothelial and
           squamous differentiation: implications for risk stratification of bladder
           cancer

    • Abstract: Background Screening across a multitude of normal and malignant tissues revealed an enhanced expression of lymphocyte antigen 6 superfamily member D (LY6D) in squamous epithelium and urothelium, as well as in malignancies derived therefrom. The aim of this study was to further delineate the protein expression of LY6D in urothelial bladder cancer, with particular attention to its relationship with clinicopathological characteristics and patient outcome. Methods Immunohistochemical expression of LY6D was assessed in tissue microarrays with urothelial bladder cancer tumours from three independent patient cohorts; one with transurethral resection of the bladder (TURB) specimens of mixed tumour stages from 110 consecutive cases, one with tumours of mixed stages from 260 incident cases in a population-based cohort, and one with paired TURB specimens, resected tumours and a subset of lymph node metastases from 145 patients with muscle-invasive bladder cancer (MIBC). Chi-square and non-parametric tests were applied to examine associations of LY6D expression with clinicopathological characteristics. Kaplan-Meier and Cox regression analyses were applied to examine 5-year overall survival (OS) and recurrence free survival (RFS) in relation to LY6D expression. Results In the two cohorts with mixed stages, positive LY6D expression was denoted in 63 and 64% of the cases, respectively, and found to be significantly higher in low-grade and less invasive tumours. Negative LY6D expression was significantly associated with a reduced 5-year OS, although not independently of established prognostic factors. In the population-based cohort, LY6D expression was higher in tumours with squamous differentiation and lower in other variant histologies compared to pure urothelial tumours, and the association of LY6D expression with survival was somewhat enhanced after exclusion of the former. LY6D expression was generally lower in the MIBC cohort, and even more reduced in resected tumours compared to TURB specimens in patients who had not received neoadjuvant chemotherapy. There were no significant associations between LY6D expression and RFS, neither allover nor in relation to neoadjuvant chemotherapy. Conclusion LY6D is a marker of urothelial and squamous differentiation that may add useful diagnostic and prognostic information to better guide the clinical management of bladder cancer, given that the presence of variant histology is taken into account.
      PubDate: 2020-10-07
       
  • Novel insights on targeting ferroptosis in cancer therapy

    • Abstract: Ferroptosis belongs to a novel form of regulated cell death. It is characterized by iron dependence, destruction of intracellular redox balance and non-apoptosis. And cellular structure and molecules level changes also occur abnormally during ferroptosis. It has been proved that ferroptosis exist widespreadly in many diseases, such as heart disease, brain damage or alzheimer disease. At the same time, the role of ferroptosis in cancer cannot be underestimated. More and more indications have told that ferroptosis is becoming a powerful weapon against cancer. In addition, therapies rely on ferroptosis have been applied to the clinic. Therefore, it is necessary to understand this newly discovered form of cell death and its connection with cancer. This review summarizes the mechanism of ferroptosis, ferroptosis inducers based on different targets and inspection methods. At last, we analyzed the relationship between ferroptosis and malignancies, in order to provide a novel theory basis for cancer treatment.
      PubDate: 2020-10-02
       
  • Roles of IFN-γ in tumor progression and regression: a review

    • Abstract: Background Interferon-γ (IFN-γ) plays a key role in activation of cellular immunity and subsequently, stimulation of antitumor immune-response. Based on its cytostatic, pro-apoptotic and antiproliferative functions, IFN-γ is considered potentially useful for adjuvant immunotherapy for different types of cancer. Moreover, it IFN-γ may inhibit angiogenesis in tumor tissue, induce regulatory T-cell apoptosis, and/or stimulate the activity of M1 proinflammatory macrophages to overcome tumor progression. However, the current understanding of the roles of IFN-γ in the tumor microenvironment (TME) may be misleading in terms of its clinical application. Main body Some researchers believe it has anti-tumorigenic properties, while others suggest that it contributes to tumor growth and progression. In our recent work, we have shown that concentration of IFN-γ in the TME determines its function. Further, it was reported that tumors treated with low-dose IFN-γ acquired metastatic properties while those infused with high dose led to tumor regression. Pro-tumorigenic role may be described through IFN-γ signaling insensitivity, downregulation of major histocompatibility complexes, upregulation of indoleamine 2,3-dioxygenase, and checkpoint inhibitors such as programmed cell death ligand 1. Conclusion Significant research efforts are required to decipher IFN-γ-dependent pro- and anti-tumorigenic effects. This review discusses the current knowledge concerning the roles of IFN-γ in the TME as a part of the complex immune response to cancer and highlights the importance of identifying IFN-γ responsive patients to improve their sensitivity to immuno-therapies.
      PubDate: 2020-09-29
       
  • FibroBox: a novel noninvasive tool for predicting significant liver
           fibrosis and cirrhosis in HBV infected patients

    • Abstract: Background China is a highly endemic area of chronic hepatitis B (CHB). The accuracy of existed noninvasive biomarkers including TE, APRI and FIB-4 for staging fibrosis is not high enough in Chinese cohort. Methods Using liver biopsy as a gold standard, a novel noninvasive indicator was developed using laboratory tests, ultrasound measurements and liver stiffness measurements with machine learning techniques to predict significant fibrosis and cirrhosis in CHB patients in north and east part of China. We retrospectively evaluated the diagnostic performance of the novel indicator named FibroBox, Fibroscan, aspartate transaminase-to-platelet ratio index (APRI), and fibrosis-4 index (FIB-4) in CHB patients from Jilin and Huai’an (training sets) and also in Anhui and Beijing cohorts (validation sets). Results Of 1289 eligible HBV patients who had liver histological data, 63.2% had significant fibrosis and 22.5% had cirrhosis. In LASSO logistic regression and filter methods, fibroscan results, platelet count, alanine transaminase (ALT), prothrombin time (PT), type III procollagen aminoterminal peptide (PIIINP), type IV collagen, laminin, hyaluronic acid (HA) and diameter of spleen vein were finally selected as input variables in FibroBox. Consequently, FibroBox was developed of which the area under the receiver operating characteristic curve (AUROC) was significantly higher than that of TE, APRI and FIB-4 to predicting significant fibrosis and cirrhosis. In the Anhui and Beijing cohort, the AUROC of FibroBox was 0.88 (95% CI, 0.72–0.82) and 0.87 (95% CI, 0.83–0.91) for significant fibrosis and 0.87 (95% CI, 0.82–0.92) and 0.90 (95% CI, 0.85–0.94) for cirrhosis. In the validation cohorts, FibroBox accurately diagnosed 81% of significant fibrosis and 84% of cirrhosis. Conclusions FibroBox has a better performance in predicting liver fibrosis in Chinese cohorts with CHB, which may serve as a feasible alternative to liver biopsy.
      PubDate: 2020-09-25
       
  • A radiomics-based model on non-contrast CT for predicting cirrhosis: make
           the most of image data

    • Abstract: Background To establish and validate a radiomics-based model for predicting liver cirrhosis in patients with hepatitis B virus (HBV) by using non-contrast computed tomography (CT). Methods This retrospective study developed a radiomics-based model in a training cohort of 144 HBV-infected patients. Radiomic features were extracted from abdominal non-contrast CT scans. Features selection was performed with the least absolute shrinkage and operator (LASSO) method based on highly reproducible features. Support vector machine (SVM) was adopted to build a radiomics signature. Multivariate logistic regression analysis was used to establish a radiomics-based nomogram that integrated radiomics signature and other independent clinical predictors. Performance of models was evaluated through discrimination ability, calibration and clinical benefits. An internal validation was conducted in 150 consecutive patients. Results The radiomics signature comprised 25 cirrhosis-related features and showed significant differences between cirrhosis and non-cirrhosis cohorts (P < 0.001). A radiomics-based nomogram that integrates radiomics signature, alanine transaminase, aspartate aminotransferase, globulin and international normalized ratio showed great calibration and discrimination ability in the training cohort (area under the curve [AUC]: 0.915) and the validation cohort (AUC: 0.872). Decision curve analysis confirmed the most clinical benefits can be provided by the nomogram compared with other methods. Conclusions Our developed radiomics-based nomogram can successfully diagnose the status of cirrhosis in HBV-infected patients, that may help clinical decision-making.
      PubDate: 2020-09-17
       
  • Inducible transgene expression in PDX models in vivo identifies KLF4 as a
           therapeutic target for B-ALL

    • Abstract: Background Clinically relevant methods are not available that prioritize and validate potential therapeutic targets for individual tumors, from the vast amount of tumor descriptive expression data. Methods We established inducible transgene expression in clinically relevant patient-derived xenograft (PDX) models in vivo to fill this gap. Results With this technique at hand, we analyzed the role of the transcription factor Krüppel-like factor 4 (KLF4) in B-cell acute lymphoblastic leukemia (B-ALL) PDX models at different disease stages. In competitive preclinical in vivo trials, we found that re-expression of wild type KLF4 reduced the leukemia load in PDX models of B-ALL, with the strongest effects being observed after conventional chemotherapy in minimal residual disease (MRD). A nonfunctional KLF4 mutant had no effect on this model. The re-expression of KLF4 sensitized tumor cells in the PDX model towards systemic chemotherapy in vivo. It is of major translational relevance that azacitidine upregulated KLF4 levels in the PDX model and a KLF4 knockout reduced azacitidine-induced cell death, suggesting that azacitidine can regulate KLF4 re-expression. These results support the application of azacitidine in patients with B-ALL as a therapeutic option to regulate KLF4. Conclusion Genetic engineering of PDX models allows the examination of the function of dysregulated genes like KLF4 in a highly clinically relevant translational context, and it also enables the selection of therapeutic targets in individual tumors and links their functions to clinically available drugs, which will facilitate personalized treatment in the future.
      PubDate: 2020-09-16
       
  • Epigenetic based synthetic lethal strategies in human cancers

    • Abstract: Over the past decades, it is recognized that loss of DNA damage repair (DDR) pathways is an early and frequent event in tumorigenesis, occurring in 40-50% of many cancer types. The basis of synthetic lethality in cancer therapy is DDR deficient cancers dependent on backup DNA repair pathways. In cancer, the concept of synthetic lethality has been extended to pairs of genes, in which inactivation of one by deletion or mutation and pharmacological inhibition of the other leads to death of cancer cells whereas normal cells are spared the effect of the drug. The paradigm study is to induce cell death by inhibiting PARP in BRCA1/2 defective cells. Since the successful application of PARP inhibitor, a growing number of developed DDR inhibitors are ongoing in preclinical and clinical testing, including ATM, ATR, CHK1/2 and WEE1 inhibitors. Combination of PARP inhibitors and other DDR inhibitors, or combination of multiple components of the same pathway may have great potential synthetic lethality efficiency. As epigenetics joins Knudson’s two hit theory, silencing of DDR genes by aberrant epigenetic changes provide new opportunities for synthetic lethal therapy in cancer. Understanding the causative epigenetic changes of loss-of-function has led to the development of novel therapeutic agents in cancer. DDR and related genes were found frequently methylated in human cancers, including BRCA1/2, MGMT, WRN, MLH1, CHFR, P16 and APC. Both genetic and epigenetic alterations may serve as synthetic lethal therapeutic markers.
      PubDate: 2020-09-15
       
  • Expression of p52, a non-canonical NF-kappaB transcription factor, is
           associated with poor ovarian cancer prognosis

    • Abstract: Background The canonical and non-canonical nuclear factor-kappaB (NF-κB) signaling pathways have key roles in cancer, but studies have previously evaluated only the association of canonical transcription factors and ovarian cancer survival. Although a number of in vitro and in vivo studies have demonstrated mechanisms by which non-canonical NF-κB signaling potentially contributes to ovarian cancer progression, a prognostic association has yet to be shown in the clinical context. Methods We assayed p65 and p52 (major components of the canonical and non-canonical NF-κB pathways) by immunohistochemistry in epithelial ovarian tumor samples; nuclear and cytoplasmic staining were semi-quantified by H-scores and dichotomized at median values. Associations of p65 and p52 with progression-free survival (PFS) and overall survival (OS) were quantified by Hazard Ratios (HR) from proportional-hazards regression. Results Among 196 cases, median p52 and p65 H-scores were higher in high-grade serous cancers. Multivariable regression models indicated that higher p52 was associated with higher hazards of disease progression (cytoplasmic HR: 1.54; nuclear HR: 1.67) and death (cytoplasmic HR: 1.53; nuclear HR: 1.49), while higher nuclear p65 was associated with only a higher hazard of disease progression (HR: 1.40) in unadjusted models. When cytoplasmic and nuclear staining were combined, p52 remained significantly associated with increased hazards of disease progression (HR: 1.91, p = 0.004) and death (HR: 1.70, p = 0.021), even after adjustment for p65 and in analyses among only high-grade serous tumors. Conclusions This is the first study to demonstrate that p52, a major component of non-canonical NF-κB signaling, may be an independent prognostic factor for epithelial ovarian cancer, particularly high-grade serous ovarian cancer. Approaches to inhibit non-canonical NF-κB signaling should be explored as novel ovarian cancer therapies are needed.
      PubDate: 2020-09-15
       
  • Advances in RNA cytosine-5 methylation: detection, regulatory mechanisms,
           biological functions and links to cancer

    • Abstract: As an important posttranscriptional modification of RNA, 5-methylcytosine (m5C) has attracted increasing interest recently, with accumulating evidence suggesting the involvement of RNA m5C modification in multiple cellular processes as well as tumorigenesis. Cooperatively, advances in m5C detection techniques have enabled transcriptome mapping of RNA methylation at single-nucleotide resolution, thus stimulating m5C-based investigations. In this review, we summarize currently available approaches for detecting m5C distribution in RNA as well as the advantages and disadvantages of these techniques. Moreover, we elucidate the regulatory mechanisms of RNA m5C modification by introducing the molecular structure, catalytic substrates, cellular distributions and biological functions of RNA m5C regulators. The functional consequences of m5C modification on mRNAs, tRNAs, rRNAs and other RNA species, including viral RNAs and vault RNAs, are also discussed. Finally, we review the role of RNA m5C modification in cancer pathogenesis and progression, in hopes of providing new insights into cancer treatment.
      PubDate: 2020-09-14
       
  • Redox signaling and Alzheimer’s disease: from pathomechanism insights to
           biomarker discovery and therapy strategy

    • Abstract: Aging and average life expectancy have been increasing at a rapid rate, while there is an exponential risk to suffer from brain-related frailties and neurodegenerative diseases as the population ages. Alzheimer’s disease (AD) is the most common neurodegenerative disease worldwide with a projected expectation to blossom into the major challenge in elders and the cases are forecasted to increase about 3-fold in the next 40 years. Considering the etiological factors of AD are too complex to be completely understood, there is almost no effective cure to date, suggesting deeper pathomechanism insights are urgently needed. Metabolites are able to reflect the dynamic processes that are in progress or have happened, and metabolomic may therefore provide a more cost-effective and productive route to disease intervention, especially in the arena for pathomechanism exploration and new biomarker identification. In this review, we primarily focused on how redox signaling was involved in AD-related pathologies and the association between redox signaling and altered metabolic pathways. Moreover, we also expatiated the main redox signaling-associated mechanisms and their cross-talk that may be amenable to mechanism-based therapies. Five natural products with promising efficacy on AD inhibition and the benefit of AD intervention on its complications were highlighted as well. Graphical
      PubDate: 2020-09-11
       
  • LncRNA SNHG16 as a potential biomarker and therapeutic target in human
           cancers

    • Abstract: Long non-coding RNAs (lncRNAs) represent an important class of RNAs comprising more than 200 nucleotides, which are produced by RNA polymerase II. Although lacking an open reading framework and protein-encoding activity, lncRNAs can mediate endogenous gene expression by serving as chromatin remodeler, transcriptional or post-transcriptional modulator, and splicing regulator during gene modification. In recent years, increasing evidence shows the significance of lncRNAs in many malignancies, with vital roles in tumorigenesis and cancer progression. Moreover, lncRNAs were also considered potential diagnostic and prognostic markers in cancer. The lncRNA small nuclear RNA host gene 16 (SNHG16), found on chromosome 17q25.1, represents a novel tumor-associated lncRNA. SNHG16 was recently found to exhibit dysregulated expression in a variety of malignancies. There are growing evidence of SNHG16’s involvement in characteristics of cancer, including proliferation, apoptosis, together with its involvement in chemoresistance. In addition, SNHG16 has been described as a promising diagnostic and prognostic biomarker in cancer patients. The current review briefly summarizes recently reported findings about SNHG16 and discuss its expression, roles, mechanisms, and diagnostic and prognostic values in human cancers.
      PubDate: 2020-09-10
       
  • The role of estrogen receptor beta in breast cancer

    • Abstract: Breast cancer, a malignant tumor originating from mammary epithelial tissue, is the most common cancer among women worldwide. Challenges facing the diagnosis and treatment of breast cancer necessitate the search for new mechanisms and drugs to improve outcomes. Estrogen receptor (ER) is considered to be important for determining the diagnosis and treatment strategy. The discovery of the second estrogen receptor, ERβ, provides an opportunity to understand estrogen action. The emergence of ERβ can be traced back to 1996. Over the past 20 years, an increasing body of evidence has implicated the vital effect of ERβ in breast cancer. Although there is controversy among scholars, ERβ is generally thought to have antiproliferative effects in disease progression. This review summarizes available evidence regarding the involvement of ERβ in the clinical treatment and prognosis of breast cancer and describes signaling pathways associated with ERβ. We hope to highlight the potential of ERβ as a therapeutic target.
      PubDate: 2020-09-07
       
  • Recent progress of prognostic biomarkers and risk scoring systems in
           chronic lymphocytic leukemia

    • Abstract: Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia with high heterogeneity in the western world. Thus, investigators identified a number of prognostic biomarkers and scoring systems to guide treatment decisions and validated them in the context of immunochemotherapy. A better understanding of prognostic biomarkers, including serum markers, flow cytometry outcomes, IGHV mutation status, microRNAs, chromosome aberrations and gene mutations, have contributed to prognosis in CLL. Del17p/ TP53 mutation, NOTCH1 mutation, CD49d, IGHV mutation status, complex karyotypes and microRNAs were reported to be of predictive values to guide clinical decisions. Based on the biomarkers above, classic prognostic models, such as the Rai and Binet staging systems, MDACC nomogram, GCLLSG model and CLL-IPI, were developed to improve risk stratification and tailor treatment intensity. Considering the presence of novel agents, many investigators validated the conventional prognostic biomarkers in the setting of novel agents and only TP53 mutation status/del 17p and CD49d expression were reported to be of prognostic value. Whether other prognostic indicators and models can be used in the context of novel agents, further studies are required.
      PubDate: 2020-09-07
       
  • The biological function and clinical significance of SF3B1 mutations in
           cancer

    • Abstract: Spliceosome mutations have become the most interesting mutations detected in human cancer in recent years. The spliceosome, a large, dynamic multimegadalton small nuclear ribonucleoprotein composed of small nuclear RNAs associated with proteins, is responsible for removing introns from precursor mRNA (premRNA) and generating mature, spliced mRNAs. SF3B1 is the largest subunit of the spliceosome factor 3b (SF3B) complex, which is a core component of spliceosomes. Recurrent somatic mutations in SF3B1 have been detected in human cancers, including hematological malignancies and solid tumors, and indicated to be related to patient prognosis. This review summarizes the research progress of SF3B1 mutations in cancer, including SF3B1 mutations in the HEAT domain, the multiple roles and aberrant splicing events of SF3B1 mutations in the pathogenesis of tumors, and changes in mutated cancer cells regarding sensitivity to SF3B small-molecule inhibitors. In addition, the potential of SF3B1 or its mutations to serve as biomarkers or therapeutic targets in cancer is discussed. The accumulated knowledge about SF3B1 mutations in cancer provides critical insight into the integral role the SF3B1 protein plays in mRNA splicing and suggests new targets for anticancer therapy.
      PubDate: 2020-09-03
       
  • Secondary donor-derived humanized CD19-modified CAR-T cells induce
           remission in relapsed/refractory mixed phenotype acute leukemia after
           allogeneic hematopoietic stem cell transplantation: a case report

    • Abstract: Background Mixed phenotype acute leukemia (MPAL) is a rare leukemia and is regarded as a high-risk entity with a poor prognosis. Induction therapy of an acute lymphoblastic leukemia type or hybrid regimen and hematopoietic stem cell transplantation has been recommended for MPAL. However, the optimal therapies for relapsed or refractory MPAL remain unclear, especially for relapse after stem cell transplantation. Donor-derived chimeric antigen receptor T (CAR-T) cell therapy may be a promising therapeutic option for patients with MPAL who express target antigens and have relapsed after stem cell transplantation. However, recurrence remains a challenge, and reinfusion of CAR-T cells is not always effective. An infusion of secondary donor-derived humanized CD19-modified CAR-T cells may be effective in inducing remission. Case presentation We report a case of MPAL with CD19 expression. The patient was treated with acute lymphoblastic leukemia-like induction and consolidation therapies but remained positive for SET-NUP214 fusion gene transcript. He subsequently underwent a haploidentical stem cell transplantation but relapsed within 6 months. He then underwent donor-derived CD19-targeted CAR-T cell therapy and achieved a sustained, complete molecular remission. Unfortunately, he developed a CD19-positive relapse after 2 years. Donor-derived humanized CD19-directed CAR-T cells induced a second complete molecular remission without severe cytokine release syndrome or acute graft-versus-host disease. Conclusion This case demonstrated the efficacy and safety of humanized donor-derived CD19-modified CAR-T cell infusion for treating the recurrence of MPAL previously exposed to murine-derived CD19-directed CAR-T cells.
      PubDate: 2020-08-31
       
  • A meta-analysis of potential biomarkers associated with severity of
           coronavirus disease 2019 (COVID-19)

    • Abstract: Background Prognostic factors for the Coronavirus disease 2019 (COVID1–9) are not well established. This study aimed to summarize the available data on the association between the severity of COVID-19 and common hematological, inflammatory and biochemical parameters. Methods EMBASE, MEDLINE, Web of sciences were searched to identify all published studies providing relevant data. Random-effects meta-analysis was used to pool effect sizes. Results The bibliographic search yielded 287 citations, 31 of which were finally retained. Meta-analysis of standardized mean difference (SMD) between severe and non-severe COVID-19 cases showed that CK-MB (SMD = 0.68,95%CI: 0.48;0.87; P-value:< 0.001), troponin I (SMD = 0.71, 95%CI:0.42;1.00; P-value:< 0.001), D-dimer (SMD = 0.54,95%CI:0.31;0.77; P-value:< 0.001), prothrombin time (SMD = 0.48, 95%CI:0.23;0.73; P-value: < 0.001), procalcitonin (SMD = 0.72, 95%CI: 0.34;1,11; P-value:< 0.001), interleukin-6 (SMD = 0.93, 95%CI: 0.25;1.61;P-value: 0.007),C-reactive protein (CRP) (SMD = 1.34, 95%CI:0.83;1.86; P-value:< 0.001), ALAT (SMD = 0.53, 95%CI: 0.34;0,71; P-value:< 0.001), ASAT (SMD = 0.96, 95%CI: 0.58;1.34; P-value: < 0.001), LDH (SMD = 1.36, 95%CI: 0.75;1.98; P-value:< 0.001), CK (SMD = 0.48, 95%CI: 0.10;0.87; P-value:0.01), total bilirubin (SMD = 0.32, 95%CI: 0.18;0.47;P-value: < 0.001), γ-GT (SMD = 1.03, 95%CI: 0.83;1.22; P-value: < 0.001), myoglobin (SMD = 1.14, 95%CI: 0.81;1.47; P-value:< 0.001), blood urea nitrogen (SMD = 0.32, 95%CI: 0.18;0.47;P-value:< 0.001) and Creatininemia (SMD = 0.18, 95%CI: 0.01;0.35; P-value:0.04) were significantly more elevated in severe cases, in opposition to lymphocyte count (SMD = -0.57, 95%CI:-0.71; − 0.42; P-value: < 0.001) and proportion of lymphocytes (SMD = -0.81, 95%CI: − 1.12; − 0.49; P-value:< 0.001) which were found to be significantly lower in severe patients with other biomarker such as thrombocytes (SMD = -0.26, 95%CI: − 0.48; − 0.04; P-value:0.02), eosinophils (SMD = − 0.28, 95%CI:-0.50; − 0.06; P-value:0.01), haemoglobin (SMD = -0.20, 95%CI: − 0.37,-0.03; P-value:0.02), albuminemia (SMD-1.67,95%CI -2.40; − 0.94; P-value:< 0.001), which were also lower. Furthermore, severe COVID-19 cases had a higher risk to have lymphopenia (RR =1.66, 95%CI: 1.26;2.20; P-value:0.002), thrombocytopenia (RR = 1.86, 95%CI: 1.59;2.17; P-value: < 0.001), elevated procalcitonin level (RR = 2.94, 95%CI: 2.09–4.15; P-value:< 0.001), CRP (RR =1.41,95%CI: 1.17–1.70; P-value:0.003), ASAT(RR =2.27, 95%CI: 1.76;2.94; P-value:< 0.001), CK(RR = 2.61, 95%CI: 1.35;5.05; P-value: 0.01), Creatininemia (RR = 3.66, 95%CI: 1.53;8.81; P-value: 0.02) and LDH blood level (RR = 2.03, 95%CI: 1.42;290; P-value: 0.003). Conclusion Some inflammatory (procalcitonin, CRP), haematologic (lymphocyte, Thrombocytes), and biochemical (CK-MB, Troponin I, D-dimer, ASAT, ALAT, LDH, γ-GT) biomarkers are significantly associated with severe COVID-19. These biomarkers might help in prognostic risk stratification of patients with COVID-19.
      PubDate: 2020-08-31
       
 
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