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Showing 201 - 400 of 3562 Journals sorted alphabetically
Audiology - Communication Research     Open Access   (Followers: 10)
Auris Nasus Larynx     Full-text available via subscription  
Australasian Journal of Ultrasound in Medicine (AJUM)     Hybrid Journal  
Australian Coeliac     Full-text available via subscription   (Followers: 1)
Australian Family Physician     Full-text available via subscription   (Followers: 3)
Australian Journal of Medical Science     Full-text available via subscription   (Followers: 1)
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: 2)
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: 4)
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: 17)
Bioethics Research Notes     Full-text available via subscription   (Followers: 14)
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: 4)
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: 17)
Biomedical Engineering and Computational Biology     Open Access   (Followers: 12)
Biomedical Engineering Letters     Hybrid Journal   (Followers: 6)
Biomedical Engineering Research     Open Access   (Followers: 7)
Biomedical Informatics Insights     Open Access   (Followers: 8)
Biomedical Journal     Open Access   (Followers: 3)
Biomedical Materials     Hybrid Journal   (Followers: 7)
Biomedical Microdevices     Hybrid Journal   (Followers: 8)
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: 8)
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)
Biostatistics & Epidemiology     Hybrid Journal   (Followers: 1)
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  
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: 21)
BMC Medical Research Methodology     Open Access   (Followers: 9)
BMC Medicine     Open Access   (Followers: 13)
BMC Obesity     Open Access   (Followers: 8)
BMC Proceedings     Full-text available via subscription   (Followers: 1)
BMC Research Notes     Open Access   (Followers: 4)
BMC Sports Science, Medicine and Rehabilitation     Open Access   (Followers: 34)
BMH Medical Journal     Open Access   (Followers: 2)
BMI Journal : Bariátrica & Metabólica Iberoamericana     Open Access  
BMJ     Hybrid Journal   (Followers: 1725)
BMJ Case Reports     Hybrid Journal   (Followers: 27)
BMJ Evidence-Based Medicine     Hybrid Journal  
BMJ Global Health     Open Access   (Followers: 3)
BMJ Innovations     Hybrid Journal   (Followers: 6)
BMJ Leader     Hybrid Journal  
BMJ Open     Open Access   (Followers: 42)
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: 18)
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 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: 1)
Breastfeeding Review     Full-text available via subscription   (Followers: 18)
British Journal of Biomedical Science     Full-text available via subscription   (Followers: 7)
British Journal of General Practice     Full-text available via subscription   (Followers: 38)
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: 18)
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  
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   (Followers: 1)
Cannabis and Cannabinoid Research     Hybrid Journal   (Followers: 1)
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  
Case Reports in Clinical Medicine     Open Access   (Followers: 1)
Case Reports in Clinical Nutrition     Open Access   (Followers: 1)
Case Reports in Medicine     Open Access   (Followers: 2)
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)
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: 7)
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: 8)
Cell Transplantation     Open Access   (Followers: 4)
CEN Case Reports     Hybrid Journal  
Central African Journal of Medicine     Full-text available via subscription  
Ceylon Journal of Medical Science     Open Access  
Ceylon Medical Journal     Open Access  
Chattagram Maa-O-Shishu Hospital Medical College Journal     Open Access  
Chiang Mai Medical Journal     Open Access  
ChiangRai Medical Journal     Open Access  
Chimerism     Full-text available via subscription  
Chinese Journal of Integrative Medicine     Hybrid Journal   (Followers: 3)
Chinese Journal of Natural Medicines     Full-text available via subscription   (Followers: 1)
Chinese Medical Journal     Open Access   (Followers: 10)
Chinese Medical Record English Edition     Hybrid Journal  
Chinese Medical Sciences Journal     Full-text available via subscription   (Followers: 2)
Chinese Medicine     Open Access   (Followers: 2)
Chinese Medicine     Open Access   (Followers: 4)
Chisholm Health Ethics Bulletin     Full-text available via subscription   (Followers: 1)
CHRISMED Journal of Health and Research     Open Access   (Followers: 2)
Christian Journal for Global Health     Open Access  
Chronic Diseases and Translational Medicine     Open Access  
Chronic Illness     Hybrid Journal   (Followers: 6)
Chronic Wound Care Management and Research     Open Access   (Followers: 4)
Chronobiology International     Hybrid Journal   (Followers: 3)
ChronoPhysiology and Therapy     Open Access  
Chulalongkorn Medical Bulletin     Open Access  
Chulalongkorn Medical Journal     Open Access  
Ciencia e Innovación en Salud     Open Access  
Ciencia e Investigación Medico Estudiantil Latinoamericana     Open Access  
Ciencias Clínicas     Open Access  
CienciaUAT     Open Access   (Followers: 1)

  First | 1 2 3 4 5 6 7 8 | Last

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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  [311 journals]
  • Impact of MET alterations on targeted therapy with EGFR-tyrosine kinase
           inhibitors for EGFR-mutant lung cancer

    • Abstract: Abstract EGFR-tyrosine kinase inhibitors (EGFR-TKIs) have achieved remarkable outcomes in the treatment of patients with EGFR-mutant non-small-cell lung cancer, but acquired resistance is still the main factor restricting their long-term use. In addition to the T790 M mutation of EGFR, amplification of the MET (or c-MET) gene has long been recognized as an important resistance mechanism for first- or second-generation EGFR-TKIs. Recent studies suggest that a key mechanism of acquired resistance to third-generation EGFR-TKIs (such as osimertinib) may be MET amplification and/or protein overactivation, especially when they are used as a first-line treatment. Therefore, in patients resistant to first-generation EGFR-TKIs caused by MET amplification and/or protein overactivation, the combination of osimertinib with MET or MEK inhibitors may be considered.
      PubDate: 2019-11-21
  • Clinical significance of stromal ER and PR expression in periampullary

    • Abstract: Background Tamoxifen treatment has previously been reported to confer life-prolonging effects in patients with advanced pancreatic cancer, and most evidently so in women. None of these trials did however include biomarkers, and the relevance of female hormone signaling in pancreatic or other periampullary adenocarcinoma remains largely unexplored. The aim of this study was to examine the extent and potential clinical significance of estrogen receptor-α (ER) and progesterone receptor (PR) expression in pancreatic and other periampullary cancers. Methods ER and PR expression was examined using immunohistochemistry on tissue microarrays with primary tumors from a retrospective consecutive cohort of 175 patients with resected periampullary adenocarcinoma, with long-term clinical follow-up. Non-parametric and Chi square tests were applied to examine the associations of stromal ER and PR expression with patient and tumor characteristics. Kaplan-Meier analysis and log rank test were applied to illustrate survival differences in relation to ER and PR expression. Cox regression proportional hazards models were applied to examine the associations between investigative factors and risk of death and recurrence, and to test for interactions between KRAS mutation status and hormone receptor expression in relation to survival. Results Expression of both ER and PR was more frequent in the tumor-associated stroma than in the epithelium. A significant prognostic interaction, independent of tumor morphology, was found between stromal PR expression and KRAS mutation status in relation to both overall and recurrence-free survival (pinteraction = 0.026 and pinteraction = 0.005), in particular in women (pinteraction = 0.002 and pinteraction = 0.005). Specifically, stromal PR expression was associated with a prolonged survival in patients with KRAS-mutated tumors, whereas the opposite was seen for KRAS wild-type tumors. The prognostic value of ER positivity was limited to the subgroup of women with tumors of pancreatic origin. Conclusions These results demonstrate that stromal PR rather than ER expression, together with KRAS mutation status, provides long-term prognostic information in patients with periampullary adenocarcinoma. Further study into the mechanistic basis for these observations may unveil important clues to the pathogenesis of these cancers and open up for the discovery of novel treatment options.
      PubDate: 2019-11-19
  • Cancer biomarkers for targeted therapy

    • Abstract: Abstract Tumor-associated antigens (TAA) or cancer biomarkers are major targets for cancer therapies. Antibody- based agents targeting the cancer biomarkers include monoclonal antibodies (MoAbs), radiolabeled MoAbs, bispecific T cell engagers, and antibody-drug conjugates. Antibodies targeting CD19, CD20, CD22, CD30, CD33, CD38, CD79B and SLAMF7 are in clinical applications for hematological malignancies. CD123, CLL-1, B cell maturation antigen, and CD138 are targets for cancer immunotherapeutic agents, including the chimeric antigen receptor - engineered T cells. Immune checkpoint inhibitors (ICIs) against PD-1, PD-L1, and CTLA-4 have led to the revolution of cancer immunotherapy. More ICIs targeting IDO, LAG3, TIM-3, TIGIT, SIGLECs, VISTA and CD47 are being explored. Small molecule inhibitors (SMIs) against tyrosine kinase oncoproteins such as BCR-ABL, JAK2, Bruton tyrosine kinase, FLT3, EGFR, ALK, HER2, VEGFR, FGFR, MEK, and MET have fundamentally changed the landscape of cancer therapy. SMIs against BCL-2, IDHs, BRAF, PI3 kinase, mTOR, PARP, and CDKs have become the mainstay in the treatment of a variety of cancer types. To reduce and avoid off-tumor toxicities, cancer-specific TAAs such as CD33 are being manufactured through systems biology approach. Search for novel biomarkers and new designs as well as delivery methods of targeted agents are fueling the next wave of advances in cancer therapy.
      PubDate: 2019-11-15
  • Epigenetic heterogeneity in cancer

    • Abstract: Abstract Phenotypic and functional heterogeneity is one of the hallmarks of human cancers. Tumor genotype variations among tumors within different patients are known as interpatient heterogeneity, and variability among multiple tumors of the same type arising in the same patient is referred to as intra-patient heterogeneity. Subpopulations of cancer cells with distinct phenotypic and molecular features within a tumor are called intratumor heterogeneity (ITH). Since Nowell proposed the clonal evolution of tumor cell populations in 1976, tumor heterogeneity, especially ITH, was actively studied. Research has focused on the genetic basis of cancer, particularly mutational activation of oncogenes or inactivation of tumor-suppressor genes (TSGs). The phenomenon of ITH is commonly explained by Darwinian-like clonal evolution of a single tumor. Despite the monoclonal origin of most cancers, new clones arise during tumor progression due to the continuous acquisition of mutations. It is clear that disruption of the "epigenetic machinery" plays an important role in cancer development. Aberrant epigenetic changes occur more frequently than gene mutations in human cancers. The epigenome is at the intersection of the environment and genome. Epigenetic dysregulation occurs in the earliest stage of cancer. The current trend of epigenetic therapy is to use epigenetic drugs to reverse and/or delay future resistance to cancer therapies. A majority of cancer therapies fail to achieve durable responses, which is often attributed to ITH. Epigenetic therapy may reverse drug resistance in heterogeneous cancer. Complete understanding of genetic and epigenetic heterogeneity may assist in designing combinations of targeted therapies based on molecular information extracted from individual tumors.
      PubDate: 2019-10-31
  • Gemtuzumab ozogamicin and novel antibody-drug conjugates in clinical
           trials for acute myeloid leukemia

    • Abstract: Abstract Targeted agents are increasingly used for the therapy of acute myeloid leukemia (AML). Gemtuzumab ozogamicin (GO) is the first antibody-drug conjugate (ADC) approved for induction therapy of AML. When used in fractionated doses, GO combined with the conventional cytarabine/anthracycline-based induction chemotherapy significantly improves the outcome of previously untreated AML patients. Single-agent GO is effective and safe for AML patient ineligible for intensive chemotherapy. Multiple combination regimens incorporating GO have also been recommended as potential alternative options. In addition, several novel ADCs targeting CD33, CD123 and CLL-1 are currently undergoing preclinical or early clinical investigations. In this review, we summarized the efficacy and limitations of GO as well as novel ADCs for adult AML patients.
      PubDate: 2019-10-31
  • Isocitrate dehydrogenase inhibitors in acute myeloid leukemia

    • Abstract: Abstract Isocitrate dehydrogenase (IDH) is a key enzyme involved in the conversion of isocitrate to α-ketoglutarate (α-KG) in the tricarboxylic acid (TCA) cycle. IDH mutation produces a neomorphic enzyme, which can lead to the abnormal accumulation of R-2-HG and promotes leukemogenesis. IDH mutation occurs in 20% of acute myeloid leukemia (AML) patients, mainly including IDH1 R132, IDH2 R140, and IDH2 R172. Different mutant isoforms have different prognostic values. In recent years, IDH inhibitors have shown good clinical response in AML patients. Hence, enasidenib and ivosidenib, the IDH2 and IDH1 inhibitors developed by Agios Pharmaceuticals, have been approved by the Food and Drug Administration on 1 August 2017 and 20 July 2018 for the treatment of adult relapsed or refractory (R/R) AML with IDH2 and IDH1 mutations, respectively. IDH inhibitor monotherapy for R/R AML is efficacious and safe; however, there are problems, such as primary or acquired resistance. Clinical trials of IDH inhibitors combined with hypomethylating agents or standard chemotherapy for the treatment of R/R AML or newly diagnosed AML, as well as in post hematopoietic stem cell transplantation as maintenance therapy, are ongoing. This article summarizes the use of IDH inhibitors in AML with IDH mutations.
      PubDate: 2019-10-22
  • Correction to: Gilteritinib: a novel FLT3 inhibitor for acute myeloid

    • Abstract: The original article [1] contains an error in the legend of Fig. 1 whereby it is incorrectly stated that MEC stands for ‘mitoprostate cancer using magnetic resonance imagingxantrone, etoposide, cyclophosphamide’. Correction to: Biomark Res (2019) 7:19.
      PubDate: 2019-10-17
  • Gilteritinib: a novel FLT3 inhibitor for acute myeloid leukemia

    • Abstract: Abstract FMS-like tyrosine kinase 3- internal tandem duplication (FLT3-ITD) remains as one of the most frequently mutated genes in acute myeloid leukemia (AML), especially in those with normal cytogenetics. The FLT3-ITD and FLT3-TKD (tyrosine kinase domain) mutations are biomarkers for high risk AML and are associated with drug resistance and high risk of relapse. Multiple FLT3 inhibitors are in clinical development, including lestaurtinib, tandutinib, quizartinib, midostaurin, gilteritinib, and crenolanib. Midostaurin and gilteritinib have been approved by FDA for Flt3 mutated AML. Gilteritinib (ASP2215, Xospata) is a small molecule dual inhibitor of FLT3/AXL. The ADMIRAL study showed that longer overall survival and higher response rate are associated with gilteritinib in comparison with salvage chemotherapy for relapse /refractory (R/R) AML. These data from the ADMIRAL study may lead to the therapy paradigm shift and establish gilteritinib as the new standard therapy for R/R FLT3-mutated AML. Currently, multiple clinical trials are ongoing to evaluate the combination of gilteritinib with other agents and regimens. This study summarized clinical trials of gilteritinib for AML.
      PubDate: 2019-09-11
  • Evaluation of breast stiffness measured by ultrasound and breast density
           measured by MRI using a prone-supine deformation model

    • Abstract: Background This study evaluated breast tissue stiffness measured by ultrasound elastography and the percent breast density measured by magnetic resonance imaging to understand their relationship. Methods Magnetic resonance imaging and whole breast ultrasound were performed in 20 patients with suspicious lesions. Only the contralateral normal breasts were analyzed. Breast tissue stiffness was measured from the echogenic homogeneous fibroglandular tissues in the central breast area underneath the nipple. An automatic, computer algorithm-based, segmentation method was used to segment the whole breast and fibroglandular tissues on three dimensional magnetic resonanceimaging. A finite element model was applied to deform the prone magnetic resonance imaging to match the supine ultrasound images, by using the inversed gravity loaded transformation. After deformation, the tissue level used in ultrasound elastography measurement could be estimated on the deformed supine magnetic resonance imaging to measure the breast density in the corresponding tissue region. Results The mean breast tissue stiffness was 2.3 ± 0.8 m/s. The stiffness was not correlated with age (r = 0.29). Overall, there was no positive correlation between breast stiffness and breast volume (r = − 0.14), or the whole breast percent density (r = − 0.09). There was also no correlation between breast stiffness and the local percent density measured from the corresponding region (r = − 0.12). Conclusions The lack of correlation between breast stiffness measured by ultrasound and the whole breast or local percent density measured by magnetic resonance imaging suggests that breast stiffness is not solely related to the amount of fibroglandular tissue. Further studies are needed to investigate whether they are dependent or independent cancer risk factors.
      PubDate: 2019-09-11
  • Mesothelin as a biomarker for targeted therapy

    • Abstract: Abstract CAR-T cell therapy targeting CD19 has achieved remarkable success in the treatment of B cell malignancies, while various solid malignancies are still refractory for lack of suitable target. In recent years, a large number of studies have sought to find suitable targets with low “on target, off tumor” concern for the treatment of solid tumors. Mesothelin (MSLN), a tumor-associated antigen broadly overexpressed on various malignant tumor cells, while its expression is generally limited to normal mesothelial cells, is an attractive candidate for targeted therapy. Strategies targeting MSLN, including antibody-based drugs, vaccines and CAR-T therapies, have been assessed in a large number of preclinical investigations and clinical trials. In particular, the development of CAR-T therapy has shown great promise as a treatment for various types of cancers. The safety, efficacy, doses, and pharmacokinetics of relevant strategies have been evaluated in many clinical trials. This review is intended to provide a brief overview of the characteristics of mesothelin and the development of strategies targeting MSLN for solid tumors. Further, we discussed the challenges and proposed potential strategies to improve the efficacy of MSLN targeted immunotherapy.
      PubDate: 2019-08-23
  • Seeking biomarkers for acute graft-versus-host disease: where we are and
           where we are heading'

    • Abstract: Abstract Acute graft-versus-host disease (aGVHD) is one of the most important complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which would seriously affect the clinical outcomes of patients. Early diagnosis and early intervention are keys for improving its curative efficacy. Thus, seeking the biomarkers of aGVHD that can accurately identify and diagnose aGVHD is very important to guiding the intervention and treatment of aGVHD. For the past decades, many studies have focused on searching for aGVHD-related biological markers to assist in diagnosis, early warning, and risk stratification. Unfortunately, until now, no reliable aGVHD biomarker is available that is recognized and widely used in clinical practice. With the continuous development of biological technology, as well as our in-depth understanding of the pathophysiologic mechanism of aGVHD, the selection, examination and application of biological markers have changed much. In this review, we summarized the progress of aGVHD biological marker screening, identification, preliminary clinical application, and look forward to a promising development direction in the future.
      PubDate: 2019-08-07
  • Comprehensive analysis of peroxiredoxins expression profiles and
           prognostic values in breast cancer

    • Abstract: Background The peroxiredoxins (PRDXs) gene family has been demonstrated to participate in carcinogenesis and development of numerous cancers and the prognostic values in several cancers have been evaluated already. Purpose of our research is to explore the expression profiles and prognostic values of PRDXs in breast cancer (BrCa). Methods The transcriptional levels of PDRX family members in primary BrCa tissues and their association with intrinsic subclasses were analyzed using UALCAN database. Then, the genetic alterations of PDRXs were examined by cBioPortal database. Moreover, the prognostic values of PRDXs in BrCa patients were investigated via the Kaplan-Meier plotter. Results The transcriptional levels of most PRDXs family members in BrCa tissues were significantly elevated compared with normal breast tissues. Meanwhile, dysregulated PRDXs expression was associated with intrinsic subclasses of BrCa. Besides, copy number alterations (CNA) of PRDXs positively regulated their mRNA expressions. Furthermore, high mRNA expression of PRDX4/6 was significantly associated with poor overall survival (OS) in BrCa patients, while high mRNA expression of PRDX3 was notably related to favorable OS. Simultaneously, high mRNA expression of PRDX1/2/4/5/6 was significantly associated with shorter relapse-free survival (RFS) in BrCa patients, while high mRNA expression of PRDX3 was notably related to favorable RFS. In addition, the prognostic value of PRDXs in the different clinicopathological features based on intrinsic subclasses and chemotherapeutic treatment of BrCa patients was further assessed in the KM plotter database. Conclusion Our findings systematically elucidate the expression profiles and distinct prognostic values of PRDXs in BrCa, which might provide novel therapeutic targets and potential prognostic biomarkers for BrCa patients.
      PubDate: 2019-08-06
  • Targeted therapies for myeloproliferative neoplasms

    • Abstract: Abstract The discovery of JAK2V617F and the demonstration that BCR-ABL-negative myeloproliferative neoplasms (MPNs) are driven by abnormal JAK2 activation have led to advances in diagnostic algorithms, prognosis and ultimately also treatment strategies. The JAK 1/2 inhibitor ruxolitinib was a pivotal moment in the treatment of MPNs, representing the first targeted treatment in this field. Despite a weak effect on the cause of the disease itself in MPNs, ruxolitinib improves the clinical state of patients and increases survival in myelofibrosis. In parallel, other JAK inhibitors with potential for pathologic and molecular remissions, less myelosuppression, and with greater selectivity for JAK1 or JAK2, and the ability to overcome JAK inhibitor persistence are in various stages of development. Moreover, many novel classes of targeted agents continue to be investigated in efforts to build on the progress made with ruxolitinib. This article will discuss some of the advances in the targeted therapy in this field in recent years and explore in greater detail some of the most advanced emerging agents as well as those with greatest potential.
      PubDate: 2019-07-16
  • A preliminary analysis of interleukin-1 ligands as potential predictive
           biomarkers of response to cetuximab

    • Abstract: Background The epidermal growth factor receptor (EGFR) monoclonal IgG1 antibody cetuximab is approved for first-line treatment of recurrent and metastatic (R/M) HNSCC as a part of the standard of care EXTREME regimen (platinum/5-fluorouracil/cetuximab). This regimen has relatively high response and disease control rates but is generally not curative and many patients will experience recurrent disease and/or metastasis. Therefore, there is a great need to identify predictive biomarkers for recurrence and disease progression in cetuximab-treated HNSCC patients to facilitate patient management and allow for treatment modification. The goal of this work is to assess the potential of activating interleukin-1 (IL-1) ligands (IL-1 alpha [IL-1α], IL-1 beta [IL-1β]) as predictive biomarkers of survival outcomes in HNSCC patients treated with cetuximab-based chemotherapy. Methods Baseline gene, serum and tumor expression of interleukin-1 (IL-1) ligands were analyzed from The Cancer Genome Atlas (TCGA) database or clinical trials of cetuximab-based therapies and interrogated for associations with clinical outcome data. Results High tumor gene expression of IL-1β was associated with a more favorable overall survival in cetuximab-treated HNSCC patients but not in non-cetuximab-treated patients. In HNSCC patients treated with cetuximab-based chemotherapy, higher gene and circulating levels of IL-1α and IL-1β were correlated with a more favorable progression free survival compared to patients with low or undetectable levels of IL-1 ligands. Conclusions These findings suggest that IL-1 ligands may function as predictive biomarkers for tumor response to cetuximab-based chemotherapy in HNSCC patients and warrants further investigation and validation in larger clinical studies.
      PubDate: 2019-07-16
  • DLGAP1 directs megakaryocytic growth and differentiation in an MPL
           dependent manner in hematopoietic cells

    • Abstract: Background The MPL protein is a major regulator of megakaryopoiesis and platelet formation as well as stem cell regulation. Aberrant MPL and downstream Jak/STAT signaling results in the development of the Myeloproliferative Neoplasms (MPN). The pathogenetic and phenotypic features of the classical MPNs cannot be explained by the known mutations and genetic variants associated with the disease. Methods In order to identify potential pathways involved in MPN development, we have performed a functional screen using retroviral insertional mutagenesis in cells dependent on MPL activation. We have used viral transduction and plasmid transfections to test the effects of candidate gene overexpression on growth and differentiation of megakaryocytic cells. The shRNA approach was used to test for the effects of candidate gene downregulation in cells. All effects were tested with candidate gene alone or in presence of hematopoietic relevant kinases in the growth medium. We assayed the candidate gene cellular localization in varying growth conditions by immunofluorescence. Flow Cytometry was used for testing of transduction efficiency and for sorting of positive cells. Results We have identified the DLGAP1 gene, a member of the Scribble cell polarity complex, as one of the most prominent positive candidates. Analyses in hematopoietic cell lines revealed DLGAP1 centrosomal and cytoplasmic localization. The centrosomal localization of DLGAP1 was cell cycle dependent and hematopoietic relevant tyrosine kinases: Jak2, SRC and MAPK as well as the CDK1 kinase promoted DLGAP1 dissociation from centrosomes. DLGAP1 negatively affected the growth rate of MPL dependent hematopoietic cells and supported megakaryocytic cells polyploidization, which was correlated with its dissociation from centrosomes. Conclusions Our data support the conclusion that DLGAP1 is a novel, potent factor in MPL signaling, affecting megakaryocytic growth and differentiation, relevant to be investigated further as a prominent candidate in MPN development.
      PubDate: 2019-07-08
  • Identification of TCR Vβ 11-2- Dβ 1- Jβ 1-1 T cell clone specific for
           WT1 peptides using high-throughput TCRβ gene sequencing

    • Abstract: Abstract We previously identified a TCR Vβ21 T cell clone which was specific to CML patients, and demonstrated that TCR Vα13/β21 gene-modified CD3+ T cells had specific cytotoxicity for HLA-A11+ K562 cells. However, it remains unclear which antigen is specifically recognized by the TCR Vβ21 T cell clone. In this study, CD3+ T cells from healthy donor peripheral blood were stimulated with the WT1 peptide or mixed BCR-ABL peptides in the presence or absence of IL-2 and IL-7. The distribution of the TCR Vβ repertoire was analyzed after different stimulations. We found that the mixed BCR-ABL peptides induced clonally expanded Vβ7–9-Dβ2-Jβ2–7 T cells while the Wilms Tumor 1 peptide induced clonally expanded Vβ11–2-Dβ1-Jβ1–1 T cells by high-throughput TCRβ sequencing and GeneScan. Interestingly, the sequence and CDR3 motif of Vβ11–2 T cell clone are similar to the TCR Vβ21 (a different TCR V region naming system) T cell clone that we previously found in CML patients. Thus, our findings suggest that the TCR Vβ21 T cell clone found in CML patients might be a T cell clone that specifically recognizes WT1.
      PubDate: 2019-06-14
  • Cyclin D1 + large B-cell lymphoma with altered CCND1 and BCL-6
           rearrangements: a diagnostic challenge

    • Abstract: Background A subset of diffuse large B-cell lymphoma may show aberrant cyclin D1 expression, which may be confused with blastoid mantle cell lymphoma. These cases usually lack of CCND1 gene rearrangement. Duplication of CCND1 gene was attributed to some of the cases with cyclin D1 expression. The mechanism of overexpression of CCND1 in other cases was not well documented. Case presentation We report a case of diffuse large B-cell lymphoma with cyclin D1 expression. The underlying mechanism for cyclin D1 expression was due to an abnormal gene rearrangement involving BCL-6 and CCND1, which was different from most reported cases. Rare cases with similar genetic profile were reported and were classified as diffuse large B-cell lymphoma. Conclusion The phenotype and genetic abnormalities of DLBCL with cyclin D1 overexpression can be complex and may be difficult to differentiate from blastoid and pleomorphic variants of mantle cell lymphoma.
      PubDate: 2019-06-03
  • Longitudinal study of leukocyte DNA methylation and biomarkers for cancer
           risk in older adults

    • Abstract: Background Changes in DNA methylation over the course of life may provide an indicator of risk for cancer. We explored longitudinal changes in CpG methylation from blood leukocytes, and likelihood of future cancer diagnosis. Methods Peripheral blood samples were obtained at baseline and at follow-up visit from 20 participants in the Health, Aging and Body Composition prospective cohort study. Genome-wide CpG methylation was assayed using the Illumina Infinium Human MethylationEPIC (HM850K) microarray. Results Global patterns in DNA methylation from CpG-based analyses showed extensive changes in cell composition over time in participants who developed cancer. By visit year 6, the proportion of CD8+ T-cells decreased (p-value = 0.02), while granulocytes cell levels increased (p-value = 0.04) among participants diagnosed with cancer compared to those who remained cancer-free (cancer-free vs. cancer-present: 0.03 ± 0.02 vs. 0.003 ± 0.005 for CD8+ T-cells; 0.52 ± 0.14 vs. 0.66 ± 0.09 for granulocytes). Epigenome-wide analysis identified three CpGs with suggestive p-values ≤10− 5 for differential methylation between cancer-free and cancer-present groups, including a CpG located in MTA3, a gene linked with metastasis. At a lenient statistical threshold (p-value ≤3 × 10− 5), the top 10 cancer-associated CpGs included a site near RPTOR that is involved in the mTOR pathway, and the candidate tumor suppressor genes REC8, KCNQ1, and ZSWIM5. However, only the CpG in RPTOR (cg08129331) was replicated in an independent data set. Analysis of within-individual change from baseline to Year 6 found significant correlations between the rates of change in methylation in RPTOR, REC8 and ZSWIM5, and time to cancer diagnosis. Conclusion The results show that changes in cellular composition explains much of the cross-sectional and longitudinal variation in CpG methylation. Additionally, differential methylation and longitudinal dynamics at specific CpGs could provide powerful indicators of cancer development and/or progression. In particular, we highlight CpG methylation in the RPTOR gene as a potential biomarker of cancer that awaits further validation.
      PubDate: 2019-05-28
  • Inotuzumab ozogamicin in clinical development for acute lymphoblastic
           leukemia and non-Hodgkin lymphoma

    • Abstract: Abstract B cell acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) frequently express CD19, CD20 and CD22 on the cell surfaces. Immunotherapeutic agents including antibodies and chimeric antigen receptor T cells are widely studied in clinical trials. Several antibody-drug conjugates (ADC) have been approved for clinical use (gemtuzumab ozogamicin in acute myeloid leukemia and brentuximab vedotin in Hodgkin lymphoma as well as CD30+ anaplastic large cell lymphoma). Inotuzumab ozogamicin (INO), a CD22 antibody conjugated with calicheamicin is one of the newest ADCs. INO has been approved for treatment of relapsed /refractory B cell precursor ALL. Multiple ongoing trials are evaluating its role in the relapsed /refractory B cell NHL. This review summarized recent development in INO applications for ALL and NHL.
      PubDate: 2019-04-11
  • Exosomes from mesenchymal stem/stromal cells: a new therapeutic paradigm

    • Abstract: Abstract Mesenchymal stem/stromal cells (MSCs) have been demonstrated to hold great potential for the treatment of several diseases. Their therapeutic effects are largely mediated by paracrine factors including exosomes, which are nanometer-sized membrane-bound vesicles with functions as mediators of cell-cell communication. MSC-derived exosomes contain cytokines and growth factors, signaling lipids, mRNAs, and regulatory miRNAs. Increasing evidence suggests that MSC-derived exosomes might represent a novel cell-free therapy with compelling advantages over parent MSCs such as no risk of tumor formation and lower immunogenicity. This paper reviews the characteristics of MSC exosomes and their fate after in vivo administration, and highlights the therapeutic potential of MSC-derived exosomes in liver, kidney, cardiovascular and neurological disease. Particularly, we summarize the recent clinical trials performed to evaluate the safety and efficacy of MSC exosomes. Overall, this paper provides a general overview of MSC-exosomes as a new cell-free therapeutic paradigm.
      PubDate: 2019-04-04
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Heriot-Watt University
Edinburgh, EH14 4AS, UK
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