ABSTRACT
Evans syndrome (ES) is rare and mostly treated on a "case-by-case" basis and no guidelines are available. With the aim of assessing disease awareness and current management of adult ES, a structured survey was administered to 64 clinicians from 50 Italian participating centers. Clinicians had to be involved in the management of autoimmune cytopenias and were enrolled into the ITP-NET initiative. The survey included domains on epidemiology, diagnosis, and therapy of ES and was designed to capture current practice and suggested work-up and management. Thirty clinicians who had followed a median of 5 patients (1-45)/15 years responded. The combination of AIHA plus ITP was more common than the ITP/AIHA with neutropenia (p < .001) and 25% of patients had an associated condition, including lymphoproliferative syndromes, autoimmune diseases, or primary immunodeficiencies. The agreement of clinicians for each diagnostic test is depicted (i.e., 100% for blood count and DAT; only 40% for anti-platelets and anti-neutrophils; 77% for bone marrow evaluation). Most clinicians reported that ES requires a specific approach compared to isolated autoimmune cytopenias, due to either a more complex pathogenesis and a higher risk of relapse and thrombotic and infectious complications. The heterogeneity of treatment choices among different physicians suggests the need for broader harmonization.
ABSTRACT
BACKGROUND: Gaucher disease (GD) is a rare autosomal recessive inherited disorder caused by the lysosomal enzyme acid ß-glucosidase deficiency. Many patients experience a critical delay in the diagnosis of up to 8-10 years due to its rarity and variability in signs and symptoms, with the consultation of several specialists. PATIENTS AND METHODS: This prospective observational study analyzed the prevalence of GD in 600 patients with monoclonal gammopathy of uncertain significance (MGUS) from January 2018 until February 2022. RESULTS: The mean age of participants was 66 years, with a mean monoclonal component of 0.58 g/dL. In 433 MGUS patients with available data, anemia (hemoglobin level < 10 g/dL) was present in 31 patients (7%), and thrombocytopenia (platelet count <100.000/mm3 ) in 24 (5.5%). Of 600 MGUS patients tested for acid ß-glucosidase enzyme activity, 7 patients (1.2%) had activity below 2.5 nmol/h/mL. In comparison, GBA gene analysis was executed in 110 patients. It revealed 4 patients (0.7%) affected by GD (3 patients with compound heterozygous mutation and 1 with homozygous mutation), with a prevalence of 1 every 150 MGUS patients. Furthermore, 12 out of the remaining 106 evaluated patients (11%) were carriers of a single heterozygous mutation while having regular enzyme activity. CONCLUSIONS: The clinical heterogeneity of GD and frequent lack of awareness among physicians often lead to diagnostic delays and severe clinical manifestations. The role of MGUS in the presence of at least one clinical sign, such as low platelet count, organomegaly, bone pain, or bleeding tendency, could aid in initiating GD screening with DBS, thus reducing the period between symptom onset and the diagnosis of this rare disease.
Subject(s)
Anemia , Gaucher Disease , Monoclonal Gammopathy of Undetermined Significance , Paraproteinemias , Humans , Aged , Monoclonal Gammopathy of Undetermined Significance/complications , Monoclonal Gammopathy of Undetermined Significance/diagnosis , Monoclonal Gammopathy of Undetermined Significance/epidemiology , Gaucher Disease/complications , Gaucher Disease/diagnosis , Gaucher Disease/epidemiology , PrevalenceABSTRACT
Vitamin D is a steroid hormone that is essential for bone mineral metabolism and it has several other effects in the body, including anti-cancer actions. Vitamin D causes a reduction in cell growth by interrupting the cell cycle. Moreover, the active form of vitamin D, i.e., 1,25-dihydroxyvitamin D, exerts various effects via its interaction with the vitamin D receptor on the innate and adaptive immune system, which could be relevant in the onset of tumors. Multiple myeloma is a treatable but incurable malignancy characterized by the growth of clonal plasma cells in protective niches in the bone marrow. In patients affected by multiple myeloma, vitamin D deficiency is commonly correlated with an advanced stage of the disease, greater risk of progression, the development of pathological fractures, and a worse prognosis. Changes in the vitamin D receptor often contribute to the occurrence and progress of deficiencies, which can be overcome by supplementation with vitamin D or analogues. However, in spite of the findings available in the literature, there is no clear standard of care and clinical practice varies. Further research is needed to better understand how vitamin D influences outcomes in patients with monoclonal gammopathies.
Subject(s)
Paraproteinemias/drug therapy , Vitamin D/therapeutic use , Animals , Disease Progression , Humans , Immune System/pathology , Models, Biological , Paraproteinemias/pathology , Risk FactorsABSTRACT
Bortezomib-melphalan-prednisone (VMP) and continuous lenalidomide-dexamethasone (Rd) represent the standard treatment of transplant-ineligible patients with newly diagnosed multiple myeloma (MM). To date, no randomized trial has compared VMP to Rd, and there is no evidence of the optimal treatment for newly diagnosed MM, particularly in patients with high-risk cytogenetics [del(17p), t(4;14) or t(14;16)]. We pooled together data from patients with newly diagnosed MM treated with VMP or Rd induction followed by lenalidomide maintenance 10 mg (Rd-R) enrolled in the GIMEMA-MM-03-05 and EMN01 trials, to evaluate the efficacy of these treatments in different subgroups of patients, focusing on those with standard- and high-risk cytogenetics. Overall, 474 patients were analyzed (VMP: 257 patients; Rd-R: 217 patients). No differences in progression-free survival (hazard ratio=0.96) and overall survival (hazard ratio=1.08) were observed between standard-risk patients treated with VMP or Rd-R, whereas among the high-risk patients, the probabilities of progression (hazard ratio=0.54) and death (hazard ratio=0.73) were lower in the patients treated with VMP than in those treated with Rd-R. In particular, standard-risk patients >75 years benefited less from VMP than from Rd-R (hazard ratio for progression-free survival=0.96; hazard ratio for overall survival=1.81). In this non-randomized analysis, VMP and Rd-R were equally effective in younger (≤75 years), standard-risk patients, while older ones (>75 years) benefited more from Rd-R. In high-risk patients, VMP improved progression-free survival and overall survival irrespective of age. The source trials are registered at ClinicalTrials.gov (NCT01063179 and NCT01093196).
Subject(s)
Bortezomib , Dexamethasone , Lenalidomide , Melphalan , Multiple Myeloma , Prednisone , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bortezomib/therapeutic use , Dexamethasone/therapeutic use , Humans , Lenalidomide/therapeutic use , Melphalan/therapeutic use , Multiple Myeloma/diagnosis , Multiple Myeloma/drug therapy , Prednisone/therapeutic use , Treatment OutcomeABSTRACT
In October 2019, a viral infectious disease appeared in the city of Wuhan in China. A new betacoronavirus, SARS-CoV-2, has been recognized as the responsible pathogen in this infection. Although coronavirus disease is principally expressed as a pulmonary infection, critical SARS-CoV-2 infection is frequently complicated with coagulopathy, and thromboembolic events are recognizable in several patients. Dehydration, acute inflammatory condition, protracted immobilization during disease, existence of multiple cardiovascular risk factors such as diabetes, obesity or hypertension, previous coronary artery disease, ischemic stroke, peripheral artery disease are frequent comorbidities in SARS-CoV-2 hospitalized subjects, which possibly augment thrombo-embolic risk. However, other causal factors can still be identified such as unrestricted angiotensin II action, the use of immunoglobulins, an increased production of adhesion molecules able to induce vascular inflammation and endothelial activation, complement stimulation, excessive production of neutrophil extracellular traps (NETs), and increased platelet count. Low-molecular-weight heparin should be chosen as early treatment because of its anti-inflammatory action and its ability to antagonize histones and so defend the endothelium. However, several therapeutic possibilities have also been proposed such as fibrinolytic treatment, drugs that target NETs, and complement inhibition. Nevertheless, although the violence of the pandemic may suggest the use of heroic treatments to reduce the frightening mortality that accompanies SARS-CoV-2 infection, we believe that experimental treatments should only be used within approved and controlled protocols, the only ones that can provide useful and specify information on the validity of the treatments.
Subject(s)
Betacoronavirus , Blood Coagulation Disorders/blood , Coronavirus Infections/blood , Disease Management , Pneumonia, Viral/blood , Thromboembolism/blood , Anti-Inflammatory Agents/therapeutic use , Anticoagulants/therapeutic use , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/etiology , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Humans , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , SARS-CoV-2 , Thromboembolism/drug therapy , Thromboembolism/etiologyABSTRACT
G-CSF administration after high-dose chemotherapy and autologous stem cell transplantation (ASCT) has been shown to expedite neutrophil recovery. Several studies comparing filgrastim and pegfilgrastim in the post-ASCT setting concluded that the two are at least equally effective. Lipegfilgrastim (LIP) is a new long-acting, once-per-cycle G-CSF. This multicentric, prospective study aimed to describe the use of LIP in multiple myeloma patients receiving high-dose melphalan and autologous stem cell transplantation (ASCT) and compare LIP with historic controls of patients who received short-acting agent (filgrastim [FIL]). Overall, 125 patients with a median age of 60 years received G-CSF after ASCT (80 patients LIP on day 1 post-ASCT and 45 patients FIL on day 5 post-ASCT). The median duration of grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 × 10 [9]/L) was 5 days in both LIP and FIL groups, whereas the median number of days to reach ANC ≥ 0.5 × 10 [9]/L was 10% lower in the LIP than in the FIL group (10 vs 11 days), respectively. Male sex was significantly associated with a faster ANC ≥ 0.5 × 10 [9] L response (p = 0.015). The incidence of FN was significantly lower in the LIP than in the FIL group (29% vs 49%, respectively, p = 0.024). The days to discharge after ASCT infusion were greater in patients with FN (p < 0.001). The study indicates that LIP had a shorter time to ANC recovery and is more effective than FIL for the prevention of FN in the ASCT setting.
Subject(s)
Filgrastim/administration & dosage , Melphalan/administration & dosage , Multiple Myeloma/therapy , Polyethylene Glycols/administration & dosage , Stem Cell Transplantation , Aged , Autografts , Female , Filgrastim/adverse effects , Humans , Male , Melphalan/adverse effects , Middle Aged , Multiple Myeloma/mortality , Polyethylene Glycols/adverse effects , Prospective Studies , Sex FactorsABSTRACT
BACKGROUND: The importance of the role of MicroRNAs (or miRNAs) has been emphasised by the large number of studies in human tumour cells, underlining the high impact of post-transcriptional processes in cancer onset, progression, invasion and metastatisation. Currently known as oncomiR, real databases are collecting all the smaller fragments of RNA capable of participating in the oncogenesis. AIMS: With the aim to collect for the first time the most important acquisitions in literature about antagomiRs in oncology, our narrative review is born with the purpose of showing that specific antisense oligonucleotides, capable to bind and antagonise single or multiple miRNAs, are effective as therapeutic compounds. RESULTS: Peptide or locked nucleic acids, miRNA sponges or antagomiRs attached to plasmid or lentiviral vectors carrying miRNA sequences to its target are objects of our analysis, demonstrating their effectiveness in a large number and types of tumours. We have also tried how to overcome their high immunogenicity, which remains its greatest limit for clinical use. CONCLUSIONS: They are ambitious but fascinating promise to alter the promotion of the tumour growth by binding specific molecular targets, with high precision and low toxicity, leaving the scientists the chance of development as anti-cancer drugs and not just.
Subject(s)
Antagomirs/therapeutic use , MicroRNAs/genetics , Neoplasms/drug therapy , Hematologic Neoplasms/drug therapy , Hematologic Neoplasms/genetics , Humans , Neoplasms/geneticsABSTRACT
Microbiota is considered an independent organ with the capability to modulate tumor growth and response to therapies. In the chemo-free era, the use of new immunotherapies, more selective and effective and less toxic, led to the extension of overall survival of patients, subject to their ability to not stop treatment. This has focused scientists' attention to optimize responses by understanding and changing microbiota composition. While we have obtained abundant data from studies in oncologic and hematologic patients receiving conventional chemotherapy, we have less data about alterations in intestinal flora in those undergoing immunotherapy, especially based on Chimeric Antigen Receptor (CAR) T-cells. Actually, we know that the efficacy of Programmed Cell Death 1 (PD-1), PD-1 ligand, and Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is improved by probiotics rich in Bifidobacterium spp., while compounds of Bacteroidales and Burkholderiales protect from the development of the anti-CTLA-4-induced colitis in mouse models. CAR T-cell therapy seems to not be interfering with microbiota; however, the numerous previous therapies may have caused permanent damage, thus obscuring the data we might have obtained. Therefore, this review opens a new chapter to transfer known acquisitions to a typology of patients destined to grow.
Subject(s)
Gastrointestinal Microbiome/drug effects , Immune Checkpoint Inhibitors/therapeutic use , Immunotherapy , Neoplasms/therapy , B7-H1 Antigen/antagonists & inhibitors , CTLA-4 Antigen/antagonists & inhibitors , Humans , Immunotherapy, Adoptive , Neoplasms/immunology , Neoplasms/microbiology , Programmed Cell Death 1 Receptor/antagonists & inhibitorsABSTRACT
Medication-related osteonecrosis of the jaw (MRONJ) is a condition of exposed bone in the maxillofacial region, which occurs among subjects treated with antiresorptive agents or anti-angiogenesis drugs, despite the lack of a history of head or neck radiation treatment. Although there are still many points to be clarified about the mechanism of MRONJ, it is possible to hypothesize a common pathogenetic mechanism for two different classes of drugs: antiresorptive and anti-angiogenetic drugs. These drugs can inhibit angiogenesis by interfering with endothelial cell proliferation and survival, leading to loss of blood vessels and avascular necrosis. This hypothesis could be of immediate translational interest. Targeting the anti-angiogenetic effect of the antiresorptive agents could provide a new possibility for the prevention of treatment of MRONJ.
Subject(s)
Angiogenesis Inhibitors/adverse effects , Bisphosphonate-Associated Osteonecrosis of the Jaw/etiology , Bone Density Conservation Agents/adverse effects , Bisphosphonate-Associated Osteonecrosis of the Jaw/blood , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Humans , Interleukin-17/bloodABSTRACT
Interleukin (IL)-33 is a chromatin-related nuclear interleukin that is a component of IL-1 family. IL-33 production augments the course of inflammation after cell damage or death. It is discharged into the extracellular space. IL-33 is regarded as an "alarmin" able to stimulate several effectors of the immune system, regulating numerous immune responses comprising cancer immune reactions. IL-33 has been demonstrated to influence tumorigenesis. However, as far as this cytokine is concerned, we are faced with what has sometimes been defined as the IL-33 paradox. Several studies have demonstrated a relevant role of IL-33 to numerous malignancies, where it may have pro- and-less frequently-antitumorigenic actions. In the field of hematological malignancies, the role of IL-33 seems even more complex. Although we can affirm the existence of a negative role of IL-33 in Chronic myelogenos leukemia (CML) and in lymphoproliferative diseases and a positive role in pathologies such as Acute myeloid leukemia (AML), the action of IL-33 seems to be multiple and sometimes contradictory within the same pathology. In the future, we will have to learn to govern the negative aspects of activating the IL-33/ST2 axis and exploit the positive ones.
Subject(s)
Hematologic Neoplasms/metabolism , Interleukin-1 Receptor-Like 1 Protein/metabolism , Interleukin-33/metabolism , Animals , Hematologic Neoplasms/genetics , Humans , Interleukin-1 Receptor-Like 1 Protein/genetics , Interleukin-33/genetics , Signal TransductionABSTRACT
Almost all multiple myeloma (MM) cases have been demonstrated to be linked to earlier monoclonal gammopathy of undetermined significance (MGUS). Nevertheless, there are no identified characteristics in the diagnosis of MGUS that have been helpful in differentiating subjects whose cancer may progress to a malignant situation. Regarding malignancy, the role of lymphocyte subsets and cytokines at the beginning of neoplastic diseases is now incontestable. In this review, we have concentrated our attention on the equilibrium between the diverse lymphocyte subsets and the cytokine system and summarized the current state of knowledge, providing an overview of the condition of the entire system in MGUS and MM. In an age where the therapy of neoplastic monoclonal gammopathies largely relies on drugs capable of acting on the immune system (immunomodulants, immunological checkpoint inhibitors, CAR-T), detailed knowledge of the the differences existing in benign and neoplastic forms of gammopathy is the main foundation for the adequate and optimal use of new drugs.
Subject(s)
Cytokines/blood , Lymphocyte Subsets/immunology , Monoclonal Gammopathy of Undetermined Significance/blood , Multiple Myeloma/blood , Humans , Monitoring, Immunologic , Monoclonal Gammopathy of Undetermined Significance/immunology , Multiple Myeloma/immunologyABSTRACT
Background and objective: The aim of the present study was to evaluate associations between cumulative and peak formaldehyde exposure and occurrence of acute myeloid leukemia. Material and Methods: A comprehensive search was performed using the PubMed and Embase databases. We included studies presenting information about the role of formaldehyde in leukemic occurrence and mortality risk. Then, full texts of the selected references were assessed, and references of included studies were checked to identify additional articles. Result: The information was then summarized and organized in the present review. A total of 81 articles were obtained from the search. Conclusion: Findings from the review of the literature do not support the hypothesis that formaldehyde is a cause of acute myeloid leukemia.
Subject(s)
Formaldehyde/adverse effects , Hematologic Neoplasms/chemically induced , Leukemia, Myeloid, Acute/chemically induced , Occupational Diseases/chemically induced , Occupational Exposure/adverse effects , Formaldehyde/toxicity , Hematologic Neoplasms/mortality , Humans , Leukemia, Myeloid, Acute/mortality , Occupational Diseases/mortalityABSTRACT
Reducing the dimension of antigen-binding proteins to an only immunoglobulin domain has been one of the objectives of antibody manufacturing. Heavy chain antibodies were encountered while attempting to separate the blood serum proteins of dromedaries. Later the term "nanobodies" (Nbs) was introduced. The advantageous features of Nbs comprise little immunogenicity, stability at low/high pH, capacity to target antigens that are less antigenic, and, lastly, easy capability to be used for therapy against tumor cells. Presently, Nbs have been used for several medical and biotechnological purposes. Numerous Nb-derived formats have been positively proved useful for targeting drug delivery, and bioimaging.
Subject(s)
Neoplasms/drug therapy , Single-Domain Antibodies/administration & dosage , Animals , Antibodies, Monoclonal/administration & dosage , HumansABSTRACT
Bisphosphonates are formidable inhibitors of osteoclast-mediated bone resorption employed for therapy of multiple myeloma (MM) subjects with osteolytic lesions. Osteonecrosis of the jaw (ONJ) is an uncommon drug-induced adverse event of these agents. MicroRNAs (miRNAs) are a group of small, noncoding RNAs nucleotides, which are essential post-transcriptional controllers of gene expression. They have a central role in the normal bone development. The goal of our study was to investigate 18 miRNAs, whose targets were previously validated and described in MM subjects without ONJ, in peripheral lymphocytes of MM subjects with bisphosphonate-induced ONJ. Utilizing reverse transcription quantitative polymerase chain reaction, we evaluated miRNAs in five healthy subjects and in five MM patients with ONJ. Our experimental data revealed that a diverse miRNA signature for ONJ subjects emerged with respect to control subjects. Using the filter for in silico analysis, among the 18 miRNAs, we recognized 14 dysregulated miRNAs. All these miRNAs were significantly over-expressed in patients vs controls (MIR-16-1, MIR-21, MIR-23A, MIR-28, MIR-101-1, MIR-124-1, MIR-129, MIR-139, MIR-145, MIR-149, MIR-202, MIR-221, MIR-424, MIR-520). Among them, six were strongly upregulated (fourfold upregulated and more). These miRNAs target numerous pathways and genes implicated in calcium ion binding, bone resorption, mineralization of bone matrix, and differentiation and maintenance of bone tissue. A modified microRNA expression profile after zoledronate therapy could participate to the onset of ONJ. Targeting these miRNAs could provide a new opportunity for the prevention or treatment of ONJ.
Subject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw/genetics , Bone Density Conservation Agents/adverse effects , Diphosphonates/adverse effects , Gene Expression Regulation, Neoplastic , Imidazoles/adverse effects , Lymphocytes/metabolism , MicroRNAs/biosynthesis , Monocytes/metabolism , Multiple Myeloma/genetics , RNA, Neoplasm/biosynthesis , Aged , Bisphosphonate-Associated Osteonecrosis of the Jaw/blood , Bisphosphonate-Associated Osteonecrosis of the Jaw/etiology , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic/drug effects , Gene Ontology , Humans , Male , MicroRNAs/blood , MicroRNAs/genetics , Middle Aged , Multiple Myeloma/blood , Multiple Myeloma/complications , Osteoclasts/metabolism , Osteolysis/blood , Osteolysis/drug therapy , Osteolysis/etiology , RNA, Neoplasm/blood , RNA, Neoplasm/genetics , Reverse Transcriptase Polymerase Chain Reaction , Zoledronic AcidABSTRACT
Curcumin has been shown to have a wide variety of therapeutic effects, ranging from anti-inflammatory, chemopreventive, anti-proliferative, and anti-metastatic. This review provides an overview of the recent research conducted to overcome the problems with the bioavailability of curcumin, and of the preclinical and clinical studies that have reported success in combinatorial strategies coupling curcumin with other treatments. Research on the signaling pathways that curcumin treatment targets shows that it potently acts on major intracellular components involved in key processes such as genomic modulations, cell invasion and cell death pathways. Curcumin is a promising molecule for the prevention and treatment of cancer.
Subject(s)
Antineoplastic Agents/pharmacokinetics , Curcumin/analogs & derivatives , Curcumin/pharmacokinetics , Neoplasms/drug therapy , Animals , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biological Availability , Cell Proliferation/drug effects , Cell Survival/drug effects , Clinical Trials as Topic , Curcumin/therapeutic use , Gene Expression Regulation, Neoplastic/drug effects , Humans , Neoplasm Invasiveness , Neoplasms/genetics , Neoplasms/metabolism , Neoplasms/prevention & control , Signal Transduction/drug effectsABSTRACT
Multiple myeloma (MM) is typically exemplified by a desynchronized cytokine system with increased levels of inflammatory cytokines. We focused on the contrast between inflammatory and anti-inflammatory systems by assessing the role of cytokines and their influence on MM. The aim of this review is to summarize the available information to date concerning this equilibrium to provide an overview of the research exploring the roles of serum cytokines in MM. However, the association between MM and inflammatory cytokines appears to be inadequate, and other functions, such as pro-proliferative or antiproliferative effects, can assume the role of cytokines in the genesis and progression of MM. It is possible that inflammation, when guided by cancer-specific Th1 cells, may inhibit tumour onset and progression. In a Th1 microenvironment, proinflammatory cytokines (e.g., IL-6 and IL-1) may contribute to tumour eradication by attracting leucocytes from the circulation and by increasing CD4 + T cell activity. Hence, caution should be used when considering therapies that target factors with pro- or anti-inflammatory activity. Drugs that may reduce the tumour-suppressive Th1-driven inflammatory immune response should be avoided. A better understanding of the relationship between inflammation and myeloma will ensure more effective therapeutic interventions.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Cytokines/metabolism , Inflammation/drug therapy , Multiple Myeloma/drug therapy , Animals , Cytokines/immunology , Humans , Inflammation/immunology , Interleukin-12/metabolism , Interleukin-15/metabolism , Interleukin-2/metabolism , Interleukin-6/metabolism , Multiple Myeloma/immunologyABSTRACT
Hematological malignancies frequently express cancer-associated antigens that are shared with normal cells. Such tumor cells elude the host immune system because several T cells targeted against self-antigens are removed during thymic development, and those that persist are eliminated by a regulatory population of T cells. Chimeric antigen receptor-modified T cells (CAR-Ts) have emerged as a novel modality for tumor immunotherapy due to their powerful efficacy against tumor cells. These cells are created by transducing genes-coding fusion proteins of tumor antigen-recognition single-chain Fv connected to the intracellular signaling domains of T cell receptors, and are classed as first-, second- and third-generation, differing on the intracellular signaling domain number of T cell receptors. CAR-T treatment has emerged as a promising approach for patients with hematological malignancies, and there are several works reporting clinical trials of the use of CAR-modified T-cells in acute lymphoblastic leukemia, chronic lymphoblastic leukemia, multiple myeloma, lymphoma, and in acute myeloid leukemia by targeting different antigens. This review reports the history of adoptive immunotherapy using CAR-Ts, the CAR-T manufacturing process, and T cell therapies in development for hematological malignancies.
Subject(s)
Hematologic Neoplasms/therapy , Immunotherapy, Adoptive/methods , Antigens, Neoplasm/immunology , History, 21st Century , Humans , Immunotherapy, Adoptive/history , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/immunology , Recombinant Fusion Proteins/genetics , Single-Chain Antibodies/genetics , Single-Chain Antibodies/immunology , T-Lymphocytes/immunologyABSTRACT
Plasma cell tumors are lymphoid neoplastic proliferations of B cells. Multiple myeloma is the disseminated type of this disorder, while localized forms of plasma cell neoplasms are solitary plasmacytoma of bone that is observed as centrally localized in bones, and extramedullar plasmacytoma (EMP) that develops in soft tissues. EMP of the head and neck region is a rare malignant tumor comprising approximately 3% of all plasma cell tumors, and approximately 0.4% of all head and neck malignancies; among them, plasmacytoma of the maxilla is extremely rare. The authors present a case of a patient affected by an EMP of the maxilla simulating a maxillary radicular cyst comparing our results with the recent literature. EMP entity requires a meticulous overview of the patient by the specialist and overall the control of any signs or symptoms of systemic diseases, a fact that would mark a dramatic change in the treatment and prognosis for the patient.
Subject(s)
Maxillary Neoplasms/diagnosis , Osteotomy/methods , Plasmacytoma/diagnosis , Radicular Cyst/diagnosis , Adult , Biopsy , Diagnosis, Differential , Humans , Imaging, Three-Dimensional , Male , Maxilla/diagnostic imaging , Maxilla/surgery , Maxillary Neoplasms/surgery , Plasmacytoma/surgery , Radiography, Panoramic , Tomography, X-Ray ComputedABSTRACT
Common cancer theories hold that tumor is an uncontrolled somatic cell proliferation caused by the progressive addition of random mutations in critical genes that control cell growth. Nevertheless, various contradictions related to the mutation theory have been reported previously. These events may be elucidated by the persistence of residual tumor cells, called Cancer Stem Cells (CSCs) responsible for tumorigenesis, tumor maintenance, tumor spread, and tumor relapse. Herein, we summarize the current understanding of CSCs, with a focus on the possibility to identify specific markers of CSCs, and discuss the clinical application of targeting CSCs for cancer treatment.