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Topic Review
Diffuse Large B-Cell Lymphoma and Its Tumor Microenvironment
Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma. It is a clinically and morphologically heterogeneous entity that has continued to resist complete subtyping. Molecular subtyping efforts emerged in earnest with the advent of gene expression profiling (GEP). This molecular subtyping approach has continued to evolve simultaneously with others including immunohistochemistry and more modern genomic approaches. The veritable explosion of genomic data availability and evolving computational methodologies have provided additional avenues, by which further understanding and subclassification of DBLCLs is possible.
  • 1.2K
  • 23 May 2022
Topic Review
Treatment Strategies in Chronic Myeloid Leukaemia
Chronic myeloid leukaemia (CML) is a type of blood cancer that is currently well-managed with drugs that target cancer-causing proteins. However, a significant proportion of CML patients do not respond to those drug treatments or relapse when they stop those drugs because the cancer cells in those patients stop relying on that protein and instead develop a new way to survive. Therefore, new treatment strategies may be necessary for those patients.
  • 1.2K
  • 21 Jul 2022
Topic Review
Venous Thromboembolism Prevention in Multiple Myeloma
Multiple myeloma (MM) is associated with an increased risk of thrombotic complications, which remains substantial despite the implementation of thromboprophylaxis. The procoagulant state that characterizes the disease is multifactorial, and a greater understanding of the underlying pathophysiology is required to inform appropriate thrombosis prevention. There is a shift towards using direct oral anticoagulants (DOACs) in this setting; head-to-head comparisons in the context of controlled clinical trials between class agents are still missing. MM-specific venous thromboembolism (VTE) risk assessment scores have been developed to optimize management and minimize the associated mortality/morbidity. Their clinical utility remains to be evaluated. 
  • 1.2K
  • 29 Dec 2022
Topic Review
Aptamer-Mediated Precision Therapy for Hematologic Malignancy
Hematologic malignancies, including leukemia, lymphoma, myeloproliferative disorder and plasma cell neoplasia, are genetically heterogeneous and characterized by an uncontrolled proliferation of their corresponding cell lineages in the bone marrow, peripheral blood, tissues or plasma. Although there are many types of therapeutic drugs available for the treatment of different malignancies, the relapse, drug resistance and severe side effects due to the lack of selectivity seriously limit their clinical application. Aptamers are ssDNA or RNA oligonucleotides that can also precisely deliver therapeutic agents into cancer cells through specifically recognizing the membrane protein on cancer cells, which is similar to the capabilities of monoclonal antibodies. Aptamers exhibit higher binding affinity, lower immunogenicity and higher thermal stability than antibodies.
  • 1.1K
  • 20 Dec 2022
Topic Review
Venetoclax Combination Therapies in Pediatric Hematological Malignancies
Venetoclax is a strongly effective B-cell lymphoma-2 inhibitor (BCL-2) with an ability to selectively restore the apoptotic potential of cancerous cells. It has been proven that in combination with immunotherapy, targeted therapies, and lower-intensity therapies such as hypomethylating agents (HMAs) or low-dose cytarabine (LDAC), the drug can improve overall outcomes for adult patients with acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and multiple myeloma (MM), amongst other hematological malignancies.
  • 1.1K
  • 07 Feb 2024
Topic Review
Role of Immune Targets in Acute Myeloid Leukemia
It is now well known that the bone marrow (BM) cell niche contributes to leukemogenesis, but emerging data support the role of the complex crosstalk between AML cells and the BM microenvironment to induce a permissive immune setting that protects leukemic stem cells (LSCs) from therapy-induced death, thus favoring disease persistence and eventual relapse. The identification of potential immune targets on acute myeloid leukemia (AML) cells and the modulation of the BM environment could lead to enhanced anti-leukemic effects of drugs, immune system reactivation, and the restoration of AML surveillance. Potential targets and effectors of this immune-based therapy could be monoclonal antibodies directed against LSC antigens such as CD33, CD123, and CLL-1 (either as direct targets or via several bispecific T-cell engagers), immune checkpoint inhibitors acting on different co-inhibitory axes (alone or in combination with conventional AML drugs), and novel cellular therapies such as chimeric antigen receptor (CAR) T-cells designed against AML-specific antigens. 
  • 1.1K
  • 09 Mar 2023
Topic Review
COVID-19 Adenoviral Vaccine-Induced Immune Thrombotic Thrombocytopenia
Adenoviral-based vaccines such as ChadoX1 CoV-19 (AstraZeneca) and Ad26.COV2.S (J&J) were developed to prevent infection and reduce hospitalization or death in Coronavirus Disease 2019 (COVID-19) patients. These vaccines passed safety and efficacy trials with excellent neutralizing capabilities against SARS-CoV-2, very rare reports of acute thrombotic thrombocytopenic events following administration emerged in certain populations, which triggered a series of clinical investigations that gave rise to a novel phenomenon called vaccine-induced immune thrombotic thrombocytopenia (VITT).
  • 1.1K
  • 14 Dec 2022
Topic Review
Metabolic Vulnerabilities in Multiple Myeloma
Multiple myeloma (MM) remains an incurable malignancy with eventual emergence of refractory disease. Metabolic shifts, which ensure the availability of sufficient energy to support hyperproliferation of malignant cells, are a hallmark of cancer. Deregulated metabolic pathways have implications for the tumor microenvironment, immune cell function, prognostic significance in MM and anti-myeloma drug resistance.
  • 1.1K
  • 18 Apr 2022
Topic Review
Mechanisms of Immunothrombosis by SARS-CoV-2
During COVID-19 infection, SARS-Cov-2 interacts with Angiotensin-Converting Enzyme 2 (ACE2), NRP1, endothelial cells, platelets, neutrophil extracellular traps (NETs), thrombin, extracellular DNA (eDNA), and histones, inducing heterogeneous clinical manifestations characterized by endothelial damage, microthrombosis, and inflammation.
  • 1.1K
  • 22 Nov 2021
Topic Review
Syndromes Predisposing to Haematological Malignancies
The past decade, with large-scale genomic analyses, gave a possibility for better understanding of genetic disorders with predisposition to paediatric cancer. Interactions between germline and somatic mutations are a key determinant of cancer development. Cancer predisposition syndrome (CPS) is inherited when a germline mutation is present in the cancer predisposition gene. The early recognition of genetic predispositions for childhood cancers may provide an opportunity of early detection of neoplasms, followed by presymptomatic genetic testing of relatives, implementation of appropriate clinical procedures (e.g., avoiding radiotherapy), prophylactic surgical resection of organs at risk, or searching for donors of hematopoietic stem cells. 
  • 1.1K
  • 08 Aug 2022
Topic Review
Mature T-Cell Lymphomas
The most recent WHO 2016 classification of lymphoid tumors now recognizes 29 discrete types of mature T-cell lymphomas (MTCLs). According to the initial site of involvement, MTCLs can clinically be broadly classified into one of four categories, including (1) leukemic disease; (2) nodal disease; (3) extranodal disease; and (4) cutaneous disease. The most common MTCLs subtypes include PTCL, not otherwise specified (NOS) and angioimmunoblastic T-cell lymphoma (AITL), other subtypes include hepatosplenic gamma delta T-cell lymphoma (HSTCL), anaplastic large-cell lymphoma (ALCL), and subcutaneous panniculitis-like T-cell lymphoma (SPTCL), the primary T-cell lymphoma of the intestine.
  • 1.1K
  • 04 Nov 2021
Topic Review
Paraneoplastic Leukocytosis in Cervical Cancer
Tumor-associated leukocytosis has been associated with poor prognosis in cervical cancer. Leukemoid reaction (i.e., white blood cell count > 40,000/μL) is defined paraneoplastic (PLR) when it occurs in the presence of a cytokine-secreting tumor (CST) without neoplastic bone marrow infiltration. Cervical cancers displaying PLR represent a peculiar entity characterized by a rapidly progressive behavior typically associated with chemo-radioresistance.
  • 1.1K
  • 30 Aug 2022
Topic Review
Venetoclax in Relapsed/Refractory Acute Myeloid Leukemia
Relapsed and/or refractory (R/R) acute myeloid leukemia (AML) represents one of the most challenging scenarios in hematology, with a 5-year survival of only 10%. Venetoclax is a small molecule that acts as a potent, selective inhibitor of BCL-2. Given its satisfactory safety profile, VEN-based combinations are increasingly being investigated as a part of the therapeutic strategy for R/R AML. On the other hand, the issue of overcoming resistance is one of the most important fields to be addressed in upcoming clinical research.
  • 1.1K
  • 22 May 2023
Topic Review
Immune Status of Chronic Myelogenous Leukemia Patients
During the diagnosis of chronic myelogenous leukemia(CML), patients’ immune cells are derived from leukemic stem cells, and aberrations of both innate and acquired immunity are observed. The following treatment with tyrosine kinase inhibitors (TKIs) not only suppress leukemic cell growth, but also alter immune functions, which may affect prognosis of CML patients.
  • 1.1K
  • 10 Nov 2021
Topic Review
Richter Syndrome
Richter syndrome (RS) represents the occurrence of an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL), in patients with chronic lymphocytic leukemia (CLL).
  • 1.1K
  • 03 Feb 2023
Topic Review
Monoclonal Gammopathies of Clinical Significance
Monoclonal gammopathy of clinical significance (MGCS) refers to a recently coined term describing a complex and heterogeneous group of nonmalignant monoclonal gammopathies. These patients are characterized by the presence of a commonly small clone and the occurrence of symptoms that may be associated with the clone or with the monoclonal protein through diverse mechanisms. This is an evolving, challenging, and rapidly changing field. Patients are classified according to the key organ or system involved, with kidneys, skin, nerves, and eyes being the most frequently affected. However, multiorgan involvement may be the most relevant clinical feature at the presentation or during the course. 
  • 1.1K
  • 07 Nov 2022
Topic Review
Multiple Myeloma Therapy
Multiple myeloma (MM) is a complex hematologic malignancy characterized by the uncontrolled proliferation of clonal plasma cells in the bone marrow that secrete large amounts of immunoglobulins and other non-functional proteins. Despite decades of progress and several landmark therapeutic advancements, MM remains incurable in most cases. Standard of care frontline therapies have limited durable efficacy, with the majority of patients eventually relapsing, either early or later. Induced drug resistance via up-modulations of signaling cascades that circumvent the effect of drugs and the emergence of genetically heterogeneous sub-clones are the major causes of the relapsed-refractory state of MM. Cytopenias from cumulative treatment toxicity and disease refractoriness limit therapeutic options, hence creating an urgent need for innovative approaches effective against highly heterogeneous myeloma cell populations. 
  • 1.1K
  • 09 Sep 2022
Topic Review
Myelodysplastic Syndromes (MDS)
Myelodysplastic syndromes (MDS) comprise a group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, one or more peripheral cytopenias, single or multilineage dysplasia in the bone marrow (BM), and an increased risk of progressing to acute myeloid leukemia (AML), occurring eventually in approximately 30% of the cases, more rapidly in higher risk patients.
  • 1.0K
  • 05 May 2021
Topic Review
Clonal Behavior of Hematopoietic Stem Cells
Hematopoietic stem cells (HSCs) are the only cell population that possesses both a self-renewing capacity and multipotency, and can give rise to all lineages of blood cells throughout an organism’s life. However, the self-renewal capacity of HSCs is not infinite, and cumulative evidence suggests that HSCs alter their function and become less active during organismal aging, leading ultimately to the disruption of hematopoietic homeostasis, such as anemia, perturbed immunity and increased propensity to hematological malignancies. Thus, understanding how HSCs alter their function during aging is a matter of critical importance to prevent or overcome these age-related changes in the blood system. Recent advances in clonal analysis have revealed the functional heterogeneity of murine HSC pools that is established upon development and skewed toward the clonal expansion of functionally poised HSCs during aging. In humans, next-generation sequencing has revealed age-related clonal hematopoiesis that originates from HSC subsets with acquired somatic mutations, and has highlighted it as a significant risk factor for hematological malignancies and cardiovascular diseases. 
  • 1.0K
  • 11 Mar 2022
Topic Review
Belantamab Mafodotin
Belantamab Mafodotin, a first-in-class anti-B cell maturation antigen (BCMA) antibody–drug conjugate, demonstrated good efficacy and safety profile in triple-refractory patients in the phase 2 DREAMM-2 trial, and it was approved for the treatment of MM triple-exposed patients with >4 prior lines of therapy. 
  • 1.0K
  • 31 May 2023
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