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Pediatrics and Neonatology Jul 2022Respiratory distress syndrome (RDS) is the major cause of respiratory failure in preterm infants due to immature lung development and surfactant deficiency. Although the... (Review)
Review
Respiratory distress syndrome (RDS) is the major cause of respiratory failure in preterm infants due to immature lung development and surfactant deficiency. Although the concepts and methods of managing respiratory problems in neonates have changed continuously, determining appropriate respiratory treatment with minimal ventilation-induced lung injury and complications is crucially important. This review summarizes neonatal respiratory therapy's advances and available strategies (i.e., exogenous surfactant therapy, noninvasive ventilation, and different ventilation modes), focusing on RDS management.
Topics: Humans; Infant; Infant, Newborn; Infant, Premature; Interactive Ventilatory Support; Noninvasive Ventilation; Respiratory Distress Syndrome, Newborn; Surface-Active Agents
PubMed: 35382987
DOI: 10.1016/j.pedneo.2022.02.002 -
Nature Reviews. Immunology Mar 2020Cellular therapies using regulatory T (T) cells are currently undergoing clinical trials for the treatment of autoimmune diseases, transplant rejection and... (Review)
Review
Cellular therapies using regulatory T (T) cells are currently undergoing clinical trials for the treatment of autoimmune diseases, transplant rejection and graft-versus-host disease. In this Review, we discuss the biology of T cells and describe new efforts in T cell engineering to enhance specificity, stability, functional activity and delivery. Finally, we envision that the success of T cell therapy in autoimmunity and transplantation will encourage the clinical use of adoptive T cell therapy for non-immune diseases, such as neurological disorders and tissue repair.
Topics: Animals; Autoimmune Diseases; Cell- and Tissue-Based Therapy; Graft Rejection; Humans; Immunotherapy, Adoptive; T-Lymphocytes, Regulatory
PubMed: 31811270
DOI: 10.1038/s41577-019-0232-6 -
Frontiers in Endocrinology 2020Thyroid cancer is the most common endocrine cancer. The discovery of new biomarkers for thyroid cancer has significantly improved the understanding of the molecular... (Review)
Review
Thyroid cancer is the most common endocrine cancer. The discovery of new biomarkers for thyroid cancer has significantly improved the understanding of the molecular pathogenesis of thyroid cancer, thus allowing more personalized treatments for patients with thyroid cancer. Most of the recently discovered targeted therapies inhibit the known oncogenic mechanisms in thyroid cancer initiation and progression such as MAPK pathway, PI3K/Akt-mTOR pathways, or VEGF. Despite the significant advances in molecular testing and the discoveries of new and promising therapeutics, effective treatments for advanced and metastatic, iodine-refractory thyroid cancer are still lacking. Here, we aim to summarize the current understanding of the genetic alterations and the dysregulated pathways in thyroid cancer and to discuss the most recent targeted therapies and immunotherapy for advanced thyroid cancer with a promising anti-tumor activity and clinical benefit.
Topics: History, 21st Century; Humans; Immunotherapy; Molecular Targeted Therapy; Mutation; Signal Transduction; Therapies, Investigational; Thyroid Neoplasms
PubMed: 32528402
DOI: 10.3389/fendo.2020.00082 -
Nature Reviews. Immunology Dec 2021Several non-redundant features of the tumour microenvironment facilitate immunosuppression and limit anticancer immune responses. These include physical barriers to... (Review)
Review
Several non-redundant features of the tumour microenvironment facilitate immunosuppression and limit anticancer immune responses. These include physical barriers to immune infiltration, the recruitment of suppressive immune cells and the upregulation of ligands on tumour cells that bind to inhibitory receptors on immune cells. Recent insights into the importance of the metabolic restrictions imposed by the tumour microenvironment on antitumour T cells have begun to inform immunotherapeutic anticancer strategies. Therapeutics that target metabolic restrictions, such as low glucose levels, a low pH, hypoxia and the generation of suppressive metabolites, have shown promise as combination therapies for different types of cancer. In this Review, we discuss the metabolic aspects of the antitumour T cell response in the context of immune checkpoint blockade, adoptive cell therapy and treatment with oncolytic viruses, and discuss emerging combination strategies.
Topics: Animals; Glucose; Humans; Hydrogen-Ion Concentration; Hypoxia; Immunotherapy; Immunotherapy, Adoptive; Neoplasms; Oncolytic Viruses; Tumor Microenvironment
PubMed: 33927375
DOI: 10.1038/s41577-021-00541-y -
Cell Apr 2020Cell therapies present an entirely new paradigm in drug development. Within this class, immune cell therapies are among the most advanced, having already demonstrated... (Review)
Review
Cell therapies present an entirely new paradigm in drug development. Within this class, immune cell therapies are among the most advanced, having already demonstrated definitive evidence of clinical benefits in cancer and infectious disease. Numerous features distinguish these "living therapies" from traditional medicines, including their ability to expand and contract in proportion to need and to mediate therapeutic benefits for months or years following a single application. Continued advances in fundamental immunology, genetic engineering, gene editing, and synthetic biology exponentially expand opportunities to enhance the sophistication of immune cell therapies, increasing potency and safety and broadening their potential for treatment of disease. This perspective will summarize the current status of immune cell therapies for cancer, infectious disease, and autoimmunity, and discuss advances in cellular engineering to overcome barriers to progress.
Topics: Autoimmune Diseases; Cell Engineering; Cell- and Tissue-Based Therapy; Gene Editing; Genetic Engineering; Humans; Immunotherapy; Neoplasms; Synthetic Biology; Virus Diseases
PubMed: 32243795
DOI: 10.1016/j.cell.2020.03.001 -
Molecular Therapy : the Journal of the... Feb 2021Hereditary diseases are caused by mutations in genes, and more than 7,000 rare diseases affect over 30 million Americans. For more than 30 years, hundreds of researchers... (Review)
Review
Hereditary diseases are caused by mutations in genes, and more than 7,000 rare diseases affect over 30 million Americans. For more than 30 years, hundreds of researchers have maintained that genetic modifications would provide effective treatments for many inherited human diseases, offering durable and possibly curative clinical benefit with a single treatment. This review is limited to gene therapy using adeno-associated virus (AAV) because the gene delivered by this vector does not integrate into the patient genome and has a low immunogenicity. There are now five treatments approved for commercialization and currently available, i.e., Luxturna, Zolgensma, the two chimeric antigen receptor T cell (CAR-T) therapies (Yescarta and Kymriah), and Strimvelis (the gammaretrovirus approved for adenosine deaminase-severe combined immunodeficiency [ADA-SCID] in Europe). Dozens of other treatments are under clinical trials. The review article presents a broad overview of the field of therapy by in vivo gene transfer. We review gene therapy for neuromuscular disorders (spinal muscular atrophy [SMA]; Duchenne muscular dystrophy [DMD]; X-linked myotubular myopathy [XLMTM]; and diseases of the central nervous system, including Alzheimer's disease, Parkinson's disease, Canavan disease, aromatic l-amino acid decarboxylase [AADC] deficiency, and giant axonal neuropathy), ocular disorders (Leber congenital amaurosis, age-related macular degeneration [AMD], choroideremia, achromatopsia, retinitis pigmentosa, and X-linked retinoschisis), the bleeding disorder hemophilia, and lysosomal storage disorders.
Topics: Animals; Clinical Studies as Topic; Combined Modality Therapy; Dependovirus; Gene Expression; Genetic Diseases, Inborn; Genetic Therapy; Genetic Vectors; Humans; Organ Specificity; Treatment Outcome
PubMed: 33309881
DOI: 10.1016/j.ymthe.2020.12.007 -
Circulation Research May 2021Acute decompensated heart failure (ADHF) is one of the leading admission diagnoses worldwide, yet it is an entity with incompletely understood pathophysiology and... (Review)
Review
Acute decompensated heart failure (ADHF) is one of the leading admission diagnoses worldwide, yet it is an entity with incompletely understood pathophysiology and limited therapeutic options. Patients admitted for ADHF have high in-hospital morbidity and mortality, as well as frequent rehospitalizations and subsequent cardiovascular death. This devastating clinical course is partly due to suboptimal medical management of ADHF with persistent congestion upon hospital discharge and inadequate predischarge initiation of life-saving guideline-directed therapies. While new drugs for the treatment of chronic HF continue to be approved, there has been no new therapy approved for ADHF in decades. This review will focus on the current limited understanding of ADHF pathophysiology, possible therapeutic targets, and current limitations in expanding available therapies in light of the unmet need among these high-risk patients.
Topics: Acute Disease; Body Fluids; Cardio-Renal Syndrome; Cardiotoxins; Comorbidity; Heart Failure; Hospitalization; Humans; Inflammation Mediators; Myocardial Contraction; Natriuretic Peptide, Brain; Patient Discharge; Patient Readmission; Renin-Angiotensin System; Symptom Assessment; Vascular Resistance; Vasoconstriction; Vasodilator Agents
PubMed: 33983837
DOI: 10.1161/CIRCRESAHA.121.318186 -
Journal of Hematology & Oncology Sep 2021Immunotherapies such as immune checkpoint blockade (ICB) and adoptive cell therapy (ACT) have revolutionized cancer treatment, especially in patients whose disease was... (Review)
Review
Immunotherapies such as immune checkpoint blockade (ICB) and adoptive cell therapy (ACT) have revolutionized cancer treatment, especially in patients whose disease was otherwise considered incurable. However, primary and secondary resistance to single agent immunotherapy often results in treatment failure, and only a minority of patients experience long-term benefits. This review article will discuss the relationship between cancer immune response and mechanisms of resistance to immunotherapy. It will also provide a comprehensive review on the latest clinical status of combination therapies (e.g., immunotherapy with chemotherapy, radiation therapy and targeted therapy), and discuss combination therapies approved by the US Food and Drug Administration. It will provide an overview of therapies targeting cytokines and other soluble immunoregulatory factors, ACT, virotherapy, innate immune modifiers and cancer vaccines, as well as combination therapies that exploit alternative immune targets and other therapeutic modalities. Finally, this review will include the stimulating insights from the 2020 China Immuno-Oncology Workshop co-organized by the Chinese American Hematologist and Oncologist Network (CAHON), the China National Medical Product Administration (NMPA) and Tsinghua University School of Medicine.
Topics: Animals; Cancer Vaccines; Combined Modality Therapy; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Neoplasms; Oncolytic Virotherapy
PubMed: 34579759
DOI: 10.1186/s13045-021-01164-5 -
Nature Cancer Apr 2022Hepatocellular carcinoma (HCC) remains one of the most prevalent and deadliest cancers. The poor outcome associated with HCC is dramatically changing due to the advent... (Review)
Review
Hepatocellular carcinoma (HCC) remains one of the most prevalent and deadliest cancers. The poor outcome associated with HCC is dramatically changing due to the advent of effective systemic therapies. Here we discuss the molecular pathogenesis of HCC, molecular classes and determinants of heterogeneity. In addition, effective single-agent and combination systemic therapies involving immunotherapies as standard of care are analyzed. Finally, we propose a flowchart of sequential therapies, explore mechanisms of resistance and address the need for predictive biomarkers.
Topics: Carcinoma, Hepatocellular; Combined Modality Therapy; Humans; Immunotherapy; Liver Neoplasms; Molecular Targeted Therapy
PubMed: 35484418
DOI: 10.1038/s43018-022-00357-2 -
Genes May 2022"The story of cancer is the story of human ingenuity, resilience, and perseverance, but also of hubris, paternalism, and misperception" (Siddhartha Mukherjee). The... (Review)
Review
"The story of cancer is the story of human ingenuity, resilience, and perseverance, but also of hubris, paternalism, and misperception" (Siddhartha Mukherjee). The present review discusses the evolution of early breast cancer (BC) treatment philosophy in the last 50 years and the shift from an emphasis on local therapy to an emphasis on systemic precision treatment options.
Topics: Breast Neoplasms; Female; Humans; Immunotherapy
PubMed: 35741721
DOI: 10.3390/genes13060960