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MEDICAL SCIENCES (2415 journals)            First | 1 2 3 4 5 6 7 8 | Last

Showing 201 - 400 of 3562 Journals sorted alphabetically
Asian Biomedicine     Open Access   (Followers: 2)
Asian Journal of Cell Biology     Open Access   (Followers: 6)
Asian Journal of Health     Open Access   (Followers: 3)
Asian Journal of Medical and Biological Research     Open Access   (Followers: 5)
Asian Journal of Medical and Pharmaceutical Researches     Open Access   (Followers: 2)
Asian Journal of Medical Sciences     Open Access   (Followers: 2)
Asian Journal of Medicine and Health     Open Access   (Followers: 1)
Asian Journal of Research in Medical and Pharmaceutical Sciences     Open Access   (Followers: 1)
Asian Journal of Scientific Research     Open Access   (Followers: 3)
Asian Journal of Transfusion Science     Open Access   (Followers: 1)
Asian Medicine     Hybrid Journal   (Followers: 5)
Asian Pacific Journal of Cancer Prevention     Open Access  
Asian Pacific Journal of Health Sciences     Open Access   (Followers: 17)
ASPIRATOR : Journal of Vector-borne Disease Studies     Open Access  
Astrocyte     Open Access  
Atención Familiar     Open Access  
Atención Primaria     Open Access   (Followers: 2)
Atención Primaria Práctica     Open Access   (Followers: 1)
Atti della Accademia Peloritana dei Pericolanti - Classe di Scienze Medico-Biologiche     Open Access  
Audiology - Communication Research     Open Access   (Followers: 10)
AUP Advances     Open Access   (Followers: 14)
Auris Nasus Larynx     Full-text available via subscription  
Australasian Journal of Ultrasound in Medicine (AJUM)     Hybrid Journal   (Followers: 1)
Australian Coeliac     Full-text available via subscription   (Followers: 2)
Australian Family Physician     Full-text available via subscription   (Followers: 3)
Australian Journal of Medical Science     Full-text available via subscription   (Followers: 2)
Autopsy and Case Reports     Open Access  
Avicenna     Open Access   (Followers: 3)
Avicenna Journal of Clinical Medicine     Open Access  
Avicenna Journal of Medicine     Open Access   (Followers: 1)
Bangabandhu Sheikh Mujib Medical University Journal     Open Access   (Followers: 1)
Bangladesh Journal of Anatomy     Open Access   (Followers: 2)
Bangladesh Journal of Bioethics     Open Access  
Bangladesh Journal of Medical Biochemistry     Open Access   (Followers: 4)
Bangladesh Journal of Medical Education     Open Access   (Followers: 2)
Bangladesh Journal of Medical Microbiology     Open Access   (Followers: 4)
Bangladesh Journal of Medical Physics     Open Access   (Followers: 1)
Bangladesh Journal of Medical Science     Open Access  
Bangladesh Journal of Medicine     Open Access   (Followers: 1)
Bangladesh Journal of Physiology and Pharmacology     Open Access  
Bangladesh Journal of Scientific Research     Open Access   (Followers: 1)
Bangladesh Medical Journal     Open Access  
Bangladesh Medical Journal Khulna     Open Access  
Basal Ganglia     Hybrid Journal  
Basic Sciences of Medicine     Open Access   (Followers: 1)
Batı Karadeniz Tıp Dergisi / Medical Journal of Western Black Sea     Open Access  
Baylor University Medical Center Proceedings     Hybrid Journal  
BBA Clinical     Open Access  
BC Medical Journal     Free  
Benha Medical Journal     Open Access  
Beni-Suef University Journal of Basic and Applied Sciences     Open Access   (Followers: 3)
Bijblijven     Hybrid Journal  
Bijzijn     Hybrid Journal   (Followers: 1)
Bijzijn XL     Hybrid Journal  
Bio-Algorithms and Med-Systems     Hybrid Journal   (Followers: 2)
BioDiscovery     Open Access   (Followers: 2)
Bioelectromagnetics     Hybrid Journal   (Followers: 2)
Bioelectronic Medicine     Open Access   (Followers: 1)
Bioengineering & Translational Medicine     Open Access  
Bioethics     Hybrid Journal   (Followers: 21)
Bioethics Research Notes     Full-text available via subscription   (Followers: 15)
Biologics in Therapy     Open Access  
Biology of Sex Differences     Open Access   (Followers: 2)
Biomarker Research     Open Access   (Followers: 3)
Biomarkers in Medicine     Hybrid Journal   (Followers: 2)
BioMed Research International     Open Access   (Followers: 5)
Biomédica     Open Access  
Biomedical & Life Sciences Collection     Full-text available via subscription   (Followers: 3)
Biomedical and Biotechnology Research Journal     Open Access   (Followers: 1)
Biomedical Engineering     Hybrid Journal   (Followers: 16)
Biomedical Engineering and Computational Biology     Open Access   (Followers: 13)
Biomedical Engineering Letters     Hybrid Journal   (Followers: 6)
Biomedical Engineering Research     Open Access   (Followers: 7)
Biomedical Informatics Insights     Open Access   (Followers: 9)
Biomedical Journal     Open Access   (Followers: 4)
Biomedical Materials     Hybrid Journal   (Followers: 7)
Biomedical Microdevices     Hybrid Journal   (Followers: 9)
Biomedical Optics Express     Open Access   (Followers: 6)
Biomedical Photonics     Open Access  
Biomedical Reports     Full-text available via subscription  
Biomedical Research Reports     Full-text available via subscription   (Followers: 2)
Biomedical Safety & Standards     Full-text available via subscription   (Followers: 9)
Biomedical Science and Engineering     Open Access   (Followers: 7)
BioMedicine     Open Access  
Biomedicine Hub     Open Access  
Biomedicines     Open Access   (Followers: 1)
Biomedika     Open Access  
Biomolecular and Health Science Journal     Open Access   (Followers: 1)
Biophysics Reports     Open Access  
BioPsychoSocial Medicine     Open Access   (Followers: 8)
Biosafety and Health     Open Access   (Followers: 4)
Biosalud     Open Access   (Followers: 1)
Biostatistics & Epidemiology     Hybrid Journal   (Followers: 2)
Birat Journal of Health Sciences     Open Access  
BIRDEM Medical Journal     Open Access   (Followers: 1)
Birth Defects Research     Hybrid Journal  
Birth Defects Research Part A : Clinical and Molecular Teratology     Hybrid Journal   (Followers: 3)
Birth Defects Research Part C : Embryo Today : Reviews     Hybrid Journal  
BJR|Open     Open Access   (Followers: 1)
BJS Open     Open Access   (Followers: 1)
Black Sea Journal of Health Science     Open Access  
BLDE University Journal of Health Sciences     Open Access  
Blickpunkt Medizin     Hybrid Journal  
BMC Biomedical Engineering     Open Access  
BMC Medical Ethics     Open Access   (Followers: 23)
BMC Medical Research Methodology     Open Access   (Followers: 9)
BMC Medicine     Open Access   (Followers: 14)
BMC Obesity     Open Access   (Followers: 8)
BMC Proceedings     Full-text available via subscription   (Followers: 2)
BMC Research Notes     Open Access   (Followers: 4)
BMC Sports Science, Medicine and Rehabilitation     Open Access   (Followers: 35)
BMH Medical Journal     Open Access   (Followers: 2)
BMI Journal : Bariátrica & Metabólica Iberoamericana     Open Access  
BMJ     Hybrid Journal   (Followers: 1936)
BMJ Case Reports     Hybrid Journal   (Followers: 28)
BMJ Evidence-Based Medicine     Hybrid Journal   (Followers: 4)
BMJ Global Health     Open Access   (Followers: 3)
BMJ Innovations     Hybrid Journal   (Followers: 6)
BMJ Leader     Hybrid Journal  
BMJ Open     Open Access   (Followers: 44)
BMJ Open Quality     Open Access   (Followers: 19)
BMJ Open Science     Open Access   (Followers: 1)
BMJ Sexual & Reproductive Health     Hybrid Journal   (Followers: 2)
BMJ Surgery, Interventions, & Health Technologies     Open Access  
Bodine Journal     Open Access  
Boletín del Consejo Académico de Ética en Medicina     Open Access  
Boletín del ECEMC     Open Access  
Boletin Médico de Postgrado     Open Access  
Boletín Médico del Hospital Infantil de México     Open Access  
Bone     Hybrid Journal   (Followers: 17)
Bone and Tissue Regeneration Insights     Open Access   (Followers: 2)
Bone Marrow Research     Open Access   (Followers: 2)
Bone Reports     Open Access  
Bosnian Journal of Basic Medical Sciences     Open Access  
Bozok Tıp Dergisi / Bozok Medical Journal     Open Access  
Brachytherapy     Full-text available via subscription   (Followers: 6)
Brain and Development     Full-text available via subscription   (Followers: 5)
Brain Communications     Open Access   (Followers: 4)
Brain Connectivity     Hybrid Journal   (Followers: 5)
Brain Impairment     Full-text available via subscription   (Followers: 2)
Brazilian Journal of Medical and Biological Research     Open Access  
Brazilian Journal of Medicine and Human Health     Open Access  
Brazilian Journal of Pain (BrJP)     Open Access  
Brazilian Journal of Physical Therapy     Open Access   (Followers: 2)
Breastfeeding Review     Full-text available via subscription   (Followers: 21)
British Journal of Biomedical Science     Full-text available via subscription   (Followers: 7)
British Journal of General Practice     Full-text available via subscription   (Followers: 40)
British Journal of Hospital Medicine     Full-text available via subscription   (Followers: 16)
British Medical Bulletin     Hybrid Journal   (Followers: 6)
Buddhachinaraj Medical Journal     Open Access  
Bulletin Amades     Open Access  
Bulletin de la Société de pathologie exotique     Hybrid Journal   (Followers: 1)
Bulletin of Legal Medicine     Open Access  
Bulletin of Medical Sciences     Open Access  
Bulletin of the History of Medicine     Full-text available via subscription   (Followers: 21)
Bulletin of the Menninger Clinic     Full-text available via subscription  
Bulletin of The Royal College of Surgeons of England     Free  
Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products     Open Access  
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz     Hybrid Journal   (Followers: 6)
Burapha Journal of Medicine     Open Access  
Burns     Hybrid Journal   (Followers: 10)
Cadernos de Naturologia e Terapias Complementares     Open Access   (Followers: 1)
Calcified Tissue International     Hybrid Journal   (Followers: 2)
Canadian Bulletin of Medical History     Hybrid Journal   (Followers: 1)
Canadian Family Physician     Partially Free   (Followers: 13)
Canadian Journal of Pain     Open Access   (Followers: 2)
Canadian Journal of Rural Medicine     Full-text available via subscription   (Followers: 1)
Canadian Medical Association Journal     Open Access   (Followers: 18)
Canadian Medical Education Journal     Open Access   (Followers: 10)
Canadian Prosthetics & Orthotics Journal     Open Access  
Cannabis and Cannabinoid Research     Hybrid Journal   (Followers: 2)
Cardiac Electrophysiology Clinics     Full-text available via subscription   (Followers: 1)
Care Management Journals     Hybrid Journal   (Followers: 5)
Case Reports     Open Access  
Case Reports in Acute Medicine     Open Access   (Followers: 2)
Case Reports in Clinical Medicine     Open Access   (Followers: 2)
Case Reports in Clinical Nutrition     Open Access   (Followers: 1)
Case Reports in Clinical Pathology     Open Access   (Followers: 1)
Case Reports in Medicine     Open Access   (Followers: 3)
Case Reports in Transplantation     Open Access  
Case Reports in Vascular Medicine     Open Access  
Case Reports in Women's Health     Open Access   (Followers: 4)
Case Study and Case Report     Open Access   (Followers: 5)
CASUS : Revista de Investigación y Casos en Salud     Open Access   (Followers: 1)
CBU International Conference Proceedings     Open Access   (Followers: 3)
Cell & Bioscience     Open Access   (Followers: 6)
Cell Adhesion & Migration     Open Access   (Followers: 9)
Cell and Molecular Response to Stress     Full-text available via subscription   (Followers: 2)
Cell and Tissue Transplantation and Therapy     Open Access   (Followers: 2)
Cell Cycle     Full-text available via subscription   (Followers: 6)
Cell Death and Differentiation     Hybrid Journal   (Followers: 8)
Cell Death Discovery     Open Access   (Followers: 1)
Cell Health and Cytoskeleton     Open Access   (Followers: 1)
Cell Medicine     Open Access   (Followers: 6)
Cell Research     Hybrid Journal   (Followers: 9)
Cell Transplantation     Open Access   (Followers: 4)
CEN Case Reports     Hybrid Journal  
Central African Journal of Medicine     Full-text available via subscription  
Cephalalgia Reports     Open Access   (Followers: 5)
Ceylon Journal of Medical Science     Open Access  

  First | 1 2 3 4 5 6 7 8 | Last

Similar Journals
Journal Cover
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]
  • 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: 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: 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: 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: 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: 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: 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
       
  • Resistance to PD-1/PD-L1 blockade cancer immunotherapy: mechanisms,
           predictive factors, and future perspectives

    • Abstract: Abstract PD-1/PD-L1 blockade therapy is a promising cancer treatment strategy, which has revolutionized the treatment landscape of malignancies. Over the last decade, PD-1/PD-L1 blockade therapy has been trialed in a broad range of malignancies and achieved clinical success. Despite the potentially cure-like survival benefit, only a minority of patients are estimated to experience a positive response to PD-1/PD-L1 blockade therapy, and the primary or acquired resistance might eventually lead to cancer progression in patients with clinical responses. Accordingly, the resistance to PD-1/PD-L1 blockade remains a significant challenge hindering its further application. To overcome the limitation in therapy resistance, substantial effort has been made to improve or develop novel anti-PD-1/PD-L1 based immunotherapy strategies with better clinical response and reduced immune-mediated toxicity. In this review, we provide an overview on the resistance to PD-1/PD-L1 blockade and briefly introduce the mechanisms underlying therapy resistance. Moreover, we summarize potential predictive factors for the resistance to PD-1/PD-L1 blockade. Furthermore, we give an insight into the possible solutions to improve efficacy and clinical response. In the following research, combined efforts of basic researchers and clinicians are required to address the limitation of therapy resistance.
      PubDate: 2020-08-26
       
  • Predictive biomarkers for cancer immunotherapy with immune checkpoint
           inhibitors

    • Abstract: Abstract Although the clinical development of immune checkpoint inhibitors (ICIs) therapy has ushered in a new era of anti-tumor therapy, with sustained responses and significant survival advantages observed in multiple tumors, most patients do not benefit. Therefore, more and more attention has been paid to the identification and development of predictive biomarkers for the response of ICIs, and more in-depth and comprehensive understanding has been continuously explored in recent years. Predictive markers of ICIs efficacy have been gradually explored from the expression of intermolecular interactions within tumor cells to the expression of various molecules and cells in tumor microenvironment, and been extended to the exploration of circulating and host systemic markers. With the development of high-throughput sequencing and microarray technology, a variety of biomarker strategies have been deeply explored and gradually achieved the process from the identification of single marker to the development of multifactorial synergistic predictive markers. Comprehensive predictive-models developed by integrating different types of data based on different components of tumor-host interactions is the direction of future research and will have a profound impact in the field of precision immuno-oncology. In this review, we deeply analyze the exploration course and research progress of predictive biomarkers as an adjunctive tool to tumor immunotherapy in effectively identifying the efficacy of ICIs, and discuss their future directions in achieving precision immuno-oncology.
      PubDate: 2020-08-26
       
  • A genetic predictive model for precision treatment of diffuse large B-cell
           lymphoma with early progression

    • Abstract: Background Early progression after the first-line R-CHOP treatment leads to a very dismal outcome and necessitates alternative treatment for patients with diffuse large B-cell lymphoma (DLBCL). This study aimed to develop a genetic predictive model for early progression and evaluate its potential in advancing alternative treatment. Methods Thirty-two hotspot driver genes were examined in 145 DLBCL patients and 5 DLBCL cell lines using next-generation sequencing. The association of clinical features, cell-of-origin, double expression, positive p53 protein, and gene alterations with early progression was analyzed, and the genetic predictive model was developed based on the related independent variables and assessed by the area under receiver operating characteristic. The potential of novel treatment based on the modeling was investigated in in-vitro DLBCL cell lines and in vivo xenograft mouse models. Results The frequency of CD79B (42.86% vs 9.38%, p = 0.000) and PIM1 mutations (38.78% vs 17.71%, p = 0.005) showed a significant increase in patients with early progression. CD79B and PIM1 mutations were associated with complex genetic events, double expression, non-GCB subtype, advance stage and unfavorable prognosis. A powerful genetic predictive model (AUROC = 0.771, 95% CI: 0.689–0.853) incorporating lactate dehydrogenase levels (OR = 2.990, p = 0.018), CD79B mutations (OR = 5.970, p = 0.001), and PIM1 mutations (OR = 3.021, p = 0.026) was created and verified in the other cohort. This modeling for early progression outperformed the prediction accuracy of conventional International Prognostic Index, and new molecular subtypes of MCD and Cluster 5. CD79B and PIM1 mutations indicated a better response to inhibitors of BTK (ibrutinib) and pan-PIM kinase (AZD 1208) through repressing activated oncogenic signaling. Since the two inhibitors failed to decrease BCL2 level, BCL2 inhibitor (venetoclax) was added and demonstrated to enhance their apoptosis-inducing activity in mutant cells with double expression. Conclusions The genetic predictive model provides a robust tool to identify early progression and determine precision treatment. These findings warrant the development of optimal alternative treatment in clinical trials.
      PubDate: 2020-08-26
       
  • Application of pharmacogenetics in oncology

    • Abstract: Abstract The term “pharmacogenetics” is used to describe the study of variability in drug response due to heredity. It is associated with “gene – drug interactions”. Later on, the term “pharmacogenomics” has been introduced and it comprises all genes in the genome that can define drug response. The application of pharmacogenetics in oncology is of a great significance because of the narrow therapeutic index of chemotherapeutic drugs and the risk for life-threatening adverse effects. Many cancer genomics studies have been focused on the acquired, somatic mutations; however, increasing evidence shows that inherited germline genetic variations play a key role in cancer risk and treatment outcome. The aim of this review is to summarize the state of pharmacogenomics in oncology, focusing only on germline mutations. Genetic polymorphisms can be found in the genes that code for the metabolic enzymes and cellular targets for most of the chemotherapy drugs. Nevertheless, predicting treatment outcome is still not possible for the majority of regimens. In this review, we discuss the most comprehensively studied drug-gene pairs – present knowledge and current limitations. However, further studies in larger groups of cancer patients are necessary to be conducted with precise validation of pharmacogenetic biomarkers before these markers could be routinely applied in clinical diagnosis and treatment.
      PubDate: 2020-08-17
       
  • Bidirectional interaction between intestinal microbiome and cancer:
           opportunities for therapeutic interventions

    • Abstract: Abstract Gut microbiota composition influences the balance between human health and disease. Increasing evidence suggests the involvement of microbial factors in regulating cancer development, progression, and therapeutic response. Distinct microbial species have been implicated in modulating gut environment and architecture that affects cancer therapy outcomes. While some microbial species offer enhanced cancer therapy response, others diminish cancer treatment efficacy. In addition, use of antibiotics, often to minimize infection risks in cancer, causes intestinal dysbiosis and proves detrimental. In this review we discuss the role of gut microbiota in cancer development and therapy. We also provide insights into future strategies to manipulate the microbiome and gut epithelial barrier to augment therapeutic responses while minimizing toxicity or infection risks.
      PubDate: 2020-08-12
       
  • AML risk stratification models utilizing ELN-2017 guidelines and
           additional prognostic factors: a SWOG report

    • Abstract: Background The recently updated European LeukemiaNet risk stratification guidelines combine cytogenetic abnormalities and genetic mutations to provide the means to triage patients with acute myeloid leukemia for optimal therapies. Despite the identification of many prognostic factors, relatively few have made their way into clinical practice. Methods In order to assess and improve the performance of the European LeukemiaNet guidelines, we developed novel prognostic models using the biomarkers from the guidelines, age, performance status and select transcript biomarkers. The models were developed separately for mononuclear cells and viable leukemic blasts from previously untreated acute myeloid leukemia patients (discovery cohort, N = 185) who received intensive chemotherapy. Models were validated in an independent set of similarly treated patients (validation cohort, N = 166). Results Models using European LeukemiaNet guidelines were significantly associated with clinical outcomes and, therefore, utilized as a baseline for comparisons. Models incorporating age and expression of select transcripts with biomarkers from European LeukemiaNet guidelines demonstrated higher area under the curve and C-statistics but did not show a substantial improvement in performance in the validation cohort. Subset analyses demonstrated that models using only the European LeukemiaNet guidelines were a better fit for younger patients (age < 55) than for older patients. Models integrating age and European LeukemiaNet guidelines visually showed more separation between risk groups in older patients. Models excluding results for ASXL1, CEBPA, RUNX1 and TP53, demonstrated that these mutations provide a limited overall contribution to risk stratification across the entire population, given the low frequency of mutations and confounding risk factors. Conclusions While European LeukemiaNet guidelines remain a critical tool for triaging patients with acute myeloid leukemia, the findings illustrate the need for additional prognostic factors, including age, to improve risk stratification.
      PubDate: 2020-08-12
       
  • Development of a highly sensitive method for detection of FLT3D835Y

    • Abstract: Background Acute myeloid leukemia (AML) is a malignant hematological neoplasm of myeloid progenitor cells. Mutations of FLT3 in its tyrosine kinase domain (FLT3-TKD) are found in ~ 8% of patients with AML, with D835Y as the most common substitution. This mutation activates survival signals that drives the disease and is resistant to the first generation FLT3 inhibitors. Development of a highly sensitive method to detect FLT3D835Y is important to direct therapeutic options, predict prognosis, and monitor minimal residual disease in patients with AML. Methods and results In the present study, we developed a highly sensitive FLT3D835Y detection method by using the restriction fragment nested allele-specific PCR technique. The method consists of three steps: 1) initial amplification of DNA samples with PCR primers surrounding the FLT3D835Y mutation site, 2) digestion of the PCR products with restriction enzyme EcoRV that only cleaves the wild type allele, and 3) detection of FLT3D835Y by allele-specific PCR with nested primers. We were able to detect FLT3D835Y with a sensitivity of 0.001% by using purified plasmid DNAs and blood cell DNAs containing known proportions of FLT3D835Y. We analyzed blood cell DNA samples from 64 patients with AML and found six FLT3D835Y-positive cases, two of which could not be detected by conventional DNA sequencing methods. Importantly, the method was able to detect FLT3D835Y in a sample collected from a relapsed patient while the patient was in complete remission with negative MRD determined by flow cytometry. Therefore, our RFN-AS-PCR detected MRD after treatment that was missed by flow cytometry and Sanger DNA sequencing, by conventional methods. Conclusions We have developed a simple and highly sensitive method that will allow for detection of FLT3D835Y at a very low level. This method may have major clinical implications for treatment of AML.
      PubDate: 2020-08-12
       
  • Role of platelet biomarkers in inflammatory response

    • Abstract: Abstract Beyond hemostasis, thrombosis and wound healing, it is becoming increasingly clear that platelets play an integral role in inflammatory response and immune regulation. Platelets recognize pathogenic microorganisms and secrete various immunoregulatory cytokines and chemokines, thus facilitating a variety of immune effects and regulatory functions. In this review, we discuss recent advances in signaling of platelet activation-related biomarkers in inflammatory settings and application prospects to apply for disease diagnosis and treatment.
      PubDate: 2020-08-02
       
 
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