scholarly journals Diagnostic and Therapeutic Biomarkers in Glioblastoma: Current Status and Future Perspectives

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Wojciech Szopa ◽  
Thomas A. Burley ◽  
Gabriela Kramer-Marek ◽  
Wojciech Kaspera
Keyword(s):  
Clinical Practice ◽  
Predictive Biomarkers ◽  
Current Status ◽  
Immune Checkpoints ◽  
Molecular Heterogeneity ◽  
Treatment Standards ◽  
Drug Conjugates ◽  
Idh Mutations ◽  
The Central Nervous System ◽  
New Generation

Glioblastoma (GBM) is a primary neuroepithelial tumor of the central nervous system, characterized by an extremely aggressive clinical phenotype. Patients with GBM have a poor prognosis and only 3–5% of them survive for more than 5 years. The current GBM treatment standards include maximal resection followed by radiotherapy with concomitant and adjuvant therapies. Despite these aggressive therapeutic regimens, the majority of patients suffer recurrence due to molecular heterogeneity of GBM. Consequently, a number of potential diagnostic, prognostic, and predictive biomarkers have been investigated. Some of them, such as IDH mutations, 1p19q deletion, MGMT promoter methylation, and EGFRvIII amplification are frequently tested in routine clinical practice. With the development of sequencing technology, detailed characterization of GBM molecular signatures has facilitated a more personalized therapeutic approach and contributed to the development of a new generation of anti-GBM therapies such as molecular inhibitors targeting growth factor receptors, vaccines, antibody-based drug conjugates, and more recently inhibitors blocking the immune checkpoints. In this article, we review the exciting progress towards elucidating the potential of current and novel GBM biomarkers and discuss their implications for clinical practice.

scholarly journals Contemporary Mouse Models in Glioma Research

2021 ◽  
Author(s):  
William Hicks ◽  
Cylaina Bird ◽  
Kalil Abdullah
Keyword(s):  
Disease Modeling ◽  
Treatment Strategies ◽  
Genetically Engineered ◽  
Current Status ◽  
Molecular Heterogeneity ◽  
Lower Grade ◽  
Idh Mutations ◽  
Novel Treatment Strategies ◽  
Murine Glioma

Despite advances in understanding of the molecular pathogenesis of glioma, outcomes remain dismal. Developing successful treatments for glioma requires faithful in vivo disease modeling and rigorous preclinical testing. Murine models, including xenograft, syngeneic, and genetically engineered models, are used to study gliomagenesis, identify methods of tumor progression, and test novel treatment strategies. Since the discovery of highly recurrent isocitrate dehydrogenase (IDH) mutations in lower-grade gliomas, there is increasing emphasis on effective modeling of IDH mutant brain tumors. Improvements in preclinical models that capture the phenotypic and molecular heterogeneity of gliomas are critical for the development of effective new therapies. Herein, we explore the current status, advancements, and challenges with contemporary murine glioma models.

scholarly journals Clinical Applications of Molecular Biomarkers in Prostate Cancer

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1550 ◽  
Author(s):  
Felipe Couñago ◽  
Fernando López-Campos ◽  
Ana Aurora Díaz-Gavela ◽  
Elena Almagro ◽  
Esaú Fenández-Pascual ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Practice ◽  
Biological Diversity ◽  
Predictive Biomarkers ◽  
Current Data ◽  
Molecular Biomarkers ◽  
Molecular Heterogeneity ◽  
Minimal Impact ◽  
Clinical Scenarios ◽  
Gene Panels

There is clinically relevant molecular heterogeneity in prostate cancer (PCa), but this biological diversity has had only a minimal impact on clinical practice. Treatment outcomes in patients with localised PCa are often highly variable, even among patients stratified to the same risk group or disease state based on standard clinical and pathological parameters. In recent years, the development of gene panels has provided valuable data on the differential expression of genes in patients with PCa. Nevertheless, there is an urgent need to identify and validate prognostic and predictive biomarkers that can be applied across clinical scenarios, ranging from localised disease to metastatic castration-resistant PCa. The availability of such tools would allow for precision medicine to finally reach PCa patients. In this review, we evaluate current data on molecular biomarkers for PCa, with an emphasis on the biomarkers and gene panels with the most robust evidence to support their application in routine clinical practice.

scholarly journals Genetic and Epigenetic Biomarkers of Immune Checkpoint Blockade Response

2020 ◽  
Vol 9 (1) ◽  
pp. 286 ◽  
Author(s):  
Qingyang Xiao ◽  
André Nobre ◽  
Pilar Piñeiro ◽  
Miguel-Ángel Berciano-Guerrero ◽  
Emilio Alba ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Current Status ◽  
Immune Checkpoints ◽  
Current Response ◽  
Epigenetic Biomarkers

Checkpoint inhibitor therapy constitutes a promising cancer treatment strategy that targets the immune checkpoints to re-activate silenced T cell cytotoxicity. In recent pivotal trials, immune checkpoint blockade (ICB) demonstrated durable responses and acceptable toxicity, resulting in the regulatory approval of 8 checkpoint inhibitors to date for 15 cancer indications. However, up to ~85% of patients present with innate or acquired resistance to ICB, limiting its clinical utility. Current response biomarker candidates, including DNA mutation and neoantigen load, immune profiles, as well as programmed death-ligand 1 (PD-L1) expression, are only weak predictors of ICB response. Thus, identification of novel, more predictive biomarkers that could identify patients who would benefit from ICB constitutes one of the most important areas of immunotherapy research. Aberrant DNA methylation (5mC) and hydroxymethylation (5hmC) were discovered in multiple cancers, and dynamic changes of the epigenomic landscape have been identified during T cell differentiation and activation. While their role in cancer immunosuppression remains to be elucidated, recent evidence suggests that 5mC and 5hmC may serve as prognostic and predictive biomarkers of ICB-sensitive cancers. In this review, we describe the role of epigenetic phenomena in tumor immunoediting and other immune evasion related processes, provide a comprehensive update of the current status of ICB-response biomarkers, and highlight promising epigenomic biomarker candidates.

scholarly journals Contemporary Mouse Models in Glioma Research

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 712
Author(s):  
William H. Hicks ◽  
Cylaina E. Bird ◽  
Jeffrey I. Traylor ◽  
Diana D. Shi ◽  
Tarek Y. El Ahmadieh ◽  
...  
Keyword(s):  
Disease Modeling ◽  
Treatment Strategies ◽  
Genetically Engineered ◽  
Current Status ◽  
Molecular Heterogeneity ◽  
Lower Grade ◽  
Idh Mutations ◽  
Novel Treatment Strategies ◽  
Murine Glioma

Despite advances in understanding of the molecular pathogenesis of glioma, outcomes remain dismal. Developing successful treatments for glioma requires faithful in vivo disease modeling and rigorous preclinical testing. Murine models, including xenograft, syngeneic, and genetically engineered models, are used to study glioma-genesis, identify methods of tumor progression, and test novel treatment strategies. Since the discovery of highly recurrent isocitrate dehydrogenase (IDH) mutations in lower-grade gliomas, there is increasing emphasis on effective modeling of IDH mutant brain tumors. Improvements in preclinical models that capture the phenotypic and molecular heterogeneity of gliomas are critical for the development of effective new therapies. Herein, we explore the current status, advancements, and challenges with contemporary murine glioma models.

Comprehensive assessment of drug consumption as a basis for pharmacotherapy optimization

2019 ◽  
pp. 22-31
Author(s):  
Olga Vyacheslavovna Zhukova
Keyword(s):  
Clinical Practice ◽  
Treatment Options ◽  
Comprehensive Assessment ◽  
Drug Consumption ◽  
Treatment Standards ◽  
Disease Epidemiology ◽  
Efficacy Analysis ◽  
Epidemiological Monitoring ◽  
Guidelines Development ◽  
Real Clinical Practice

This article describes the rationale for methodology of comprehensive assessment of drug consumption in real clinical practice. The proposed methodology includes three stages: 1) epidemiological monitoring – disease epidemiology assessment; assessment of the role of factors leading to the disease; 2) pharmacoepidemiological monitoring – assessment of pharmacotherapy in real clinical practice; clinical efficacy analysis of drugs; cost-effectiveness analysis; 3) long-term clinical and economical evaluation of various treatment options. Comprehensive assessment of drug consumption should result in optimal pharmacotherapy regimens, decrease of the drug load, increasing of the therapy effectiveness and cost reduction. The scheme of comprehensive assessment of drug consumption is universal and can be used for clinical guidelines development, treatment standards, for the optimal formation of drugs lists at the federal level. Separate stages and sub-steps of an integrated assessment also can be used at the territorial and local levels, medical institution, to optimize pharmacotherapy.

ANTIBODY-DRUG CONJUGATES FOR TARGETED CANCER THERAPY

2019 ◽  
Vol 65 (6) ◽  
pp. 777-784
Author(s):  
David Korman
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Gemtuzumab Ozogamicin ◽  
Brentuximab Vedotin ◽  
Cytostatic Agent ◽  
Cytostatic Agents ◽  
Drug Conjugates ◽  
Natural Substances ◽  
Intracellular Release ◽  
High Antitumor Activity

Monoclonal antibody (MAB) conjugates with cytostatic agents (ADC) are intended for selective delivery of a cytostatic agent to a tumor cell. Three ADC have been approved for clinical use (gemtuzumab ozogamicin, brentuximab vedotin, trastuzumab-DM1); a few dozens of other ADC are undergoing clinical trials. Several derivatives of natural substances (antibiotics and inhibitors of microtubules) having a high antitumor activity are used as cytostatic agents included in ADC. They are inapplicable in clinical practice as self-sustained drugs due to their considerable toxicity. Of great importance for the implementation of the ADC effect is the character of a linker connecting MAB with a cytostatic agent and ensuring selective intracellular release after ADC internalization. The structure, mechanisms of action, and the results of clinical trials of a number of ADC are considered here as an illustration (by way of example). The development of ADC can help introduce new effective cytostatic agents into clinical practice.

Therapeutic Monoclonal Antibodies in Clinical Practice against Cancer

2020 ◽  
Vol 20 (16) ◽  
pp. 1895-1907
Author(s):  
Navgeet Kaur ◽  
Anju Goyal ◽  
Rakesh K. Sindhu
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Clinical Practice ◽  
Therapeutic Agent ◽  
Hematologic Malignancies ◽  
Immune Checkpoints ◽  
Malignant Cells ◽  
Main Target ◽  
Therapeutic Monoclonal Antibodies ◽  
Cancerous Cells

The importance of monoclonal antibodies in oncology has increased drastically following the discovery of Milstein and Kohler. Since the first approval of the monoclonal antibody, i.e. Rituximab in 1997 by the FDA, there was a decline in further applications but this number has significantly increased over the last three decades for various therapeutic applications due to the lesser side effects in comparison to the traditional chemotherapy methods. Presently, numerous monoclonal antibodies have been approved and many are in queue for approval as a strong therapeutic agent for treating hematologic malignancies and solid tumors. The main target checkpoints for the monoclonal antibodies against cancer cells include EGFR, VEGF, CD and tyrosine kinase which are overexpressed in malignant cells. Other immune checkpoints like CTLA-4, PD-1 and PD-1 receptors targeted by the recently developed antibodies increase the capability of the immune system in destroying the cancerous cells. Here, in this review, the mechanism of action, uses and target points of the approved mAbs against cancer have been summarized.

Anatomy for Dental Students

2013 ◽  
Author(s):  
Martin E. Atkinson
Keyword(s):  
Clinical Practice ◽  
Dental Students ◽  
Multiple Choice Questions ◽  
Developmental Anatomy ◽  
Form And Function ◽  
Full Color ◽  
Online Resource ◽  
The Central Nervous System ◽  
And Function ◽  
Key Resources

Anatomy for Dental Students, Fourth Edition, demonstrates and explains all the anatomy needed for a modern dentistry undergraduate course. This text covers developmental anatomy, the thorax, the central nervous system, and the head and neck with an emphasis on the practical application of anatomical knowledge. This new edition has been extensively revised and updated in line with contemporary teaching and dental practice. Over 300 new full color diagrams map all the anatomical regions that dental students need to know, while the lively and accesible text guides the reader's learning. Throughout Clinical Application Boxes demonstrate how the form and function of anatomy have consequences for clinical practice. Sidelines boxes contain additional descriptions for key anatomical structures. This text is supported by an Online Resource Centre with multiple choice questions, drag and drop figure exercises, and links to key resources to help readers to consolidate and extend their knowledge of anatomy. Anatomy for Dental Students brings together anatomical structure, function, and their relationship to clinical practice, making it ideal for dental students.

scholarly journals A novel gene signature based on five immune checkpoint genes predicts the survival of glioma

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Wei Zhang ◽  
You Zhai ◽  
Guanzhang Li ◽  
Tao Jiang
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Immune Response ◽  
Nervous System ◽  
Cox Regression ◽  
Gene Signature ◽  
Immune Checkpoints ◽  
The Novel ◽  
The Central Nervous System ◽  
Checkpoint Genes

Abstract Background Glioma is the most common and fatal type of nerve neoplasm in the central nervous system. Several biomarkers have been considered for prognosis prediction, which is not accurate enough. We aimed to carry out a gene signature related to the expression of immune checkpoints which was enough for its performance in prediction. Methods Gene expression of immune checkpoints in TGGA database was filtrated. The 5 selected genes underwent verification by COX and Lasso-COX regression. Next, the selected genes were included to build a novel signature for further analysis. Results Patients were sub-grouped into high and low risk according to the novel signature. Immune response, clinicopathologic characters, and survival showed significant differences between those 2 groups. Terms including “naive,” “effector,” and “IL-4” were screened out by GSEA. The results showed strong relevance between the signature and immune response. Conclusions We constructed a gene signature with 5 immune checkpoints. The signature predicted survival effectively. The novel signature performed more functional than previous biomarkers.

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