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  • 1
    Language: English
    In: International journal of molecular sciences, 2021-01-12, Vol.22 (2), p.705
    Description: Bone marrow failure (BMF) syndromes are a heterogenous group of non-malignant hematologic diseases characterized by single- or multi-lineage cytopenia(s) with either inherited or acquired pathogenesis. Aberrant T or B cells or innate immune responses are variously involved in the pathophysiology of BMF, and hematological improvement after standard immunosuppressive or anti-complement therapies is the main indirect evidence of the central role of the immune system in BMF development. As part of this immune derangement, pro-inflammatory cytokines play an important role in shaping the immune responses and in sustaining inflammation during marrow failure. In this review, we summarize current knowledge of cytokine signatures in BMF syndromes.
    Subject(s): Inflammation - pathology ; Cytokines - metabolism ; Humans ; Immunosuppressive Agents - therapeutic use ; Bone Marrow Failure Disorders - pathology ; Bone Marrow Failure Disorders - metabolism ; Immunity - drug effects ; Immunity - physiology ; Inflammation - metabolism ; Animals ; Inflammation - drug therapy ; Bone Marrow Failure Disorders - drug therapy ; Immunosuppressive Agents - pharmacology ; Index Medicus ; aplastic anemia ; cytokines ; Review ; bone marrow failure syndromes ; myelodysplastic syndromes
    ISSN: 1661-6596
    E-ISSN: 1422-0067
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: Directory of Open Access Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 2
    Language: English
    In: Current pharmaceutical design, 2017-09, Vol.23 (32), p.4745-4757
    Description: The 67 kDa high affinity laminin receptor (67LR) is a non-integrin cell surface receptor for laminin, the major component of basement membranes. Interactions between 67LR and laminin play a major role in mediating cell adhesion, migration, proliferation and survival. 67LR derives from homo- or hetero-dimerization of a 37 kDa cytosolic precursor (37LRP), most probably by fatty acid acylation. Interestingly, 37LRP, also called p40 or OFA/iLR (oncofetal antigen/immature laminin receptor), is a multifunctional protein with a dual activity in the cytoplasm and in the nucleus. In the cytoplasm, 37LRP it is associated with the 40S subunit of ribosome, playing a critical role in protein translation and ribosome biogenesis while in the nucleus it is tightly associated with nuclear structures, and bound to components of the cytoskeleton, such as tubulin and actin. 67LR is mainly localized in the cell membrane, concentrated in lipid rafts. Acting as a receptor for laminin is not the only function of 67LR; indeed, it also acts as a receptor for viruses, bacteria and prions. 67LR expression is increased in neoplastic cells and correlates with an enhanced invasive and metastatic potential. The primary function of 67LR in cancer is to promote tumor cell adhesion to basement membranes, the first step in the invasion-metastasis cascade. Thus, 67LR is overexpressed in neoplastic cells as compared to their normal counterparts and its overexpression is considered a molecular marker of metastatic aggressiveness in cancer of many tissues, including breast, lung, ovary, prostate, stomach, thyroid and also in leukemia and lymphoma. Thus, inhibiting 67LR binding to laminin could be a feasible approach to block cancer progression. Here, we review the current understanding of the structure and function of this molecule, highlighting its role in cancer invasion and metastasis and reviewing the various therapeutic options targeting this receptor that could have a promising future application.
    Subject(s): Receptors, Laminin - metabolism ; Neoplasm Metastasis ; Neoplasms - therapy ; Animals ; Cell Adhesion - physiology ; Humans ; Cell Proliferation - physiology ; Molecular Targeted Therapy ; Neoplasms - pathology ; Cell Movement - physiology ; Cell Survival - physiology ; Precision Medicine - methods ; Index Medicus
    ISSN: 1381-6128
    E-ISSN: 1873-4286
    Source: Bentham Science:Eduserv:Complete Collection:2015-2017
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 3
    Language: English
    In: Hepatology (Baltimore, Md.), 2018-01, Vol.67 (1), p.48-55
    Description: The association of hepatitis C virus (HCV) with non‐Hodgkin's lymphoma (NHL) has been demonstrated throughout the world. The new interferon‐free direct antiviral agents (DAAs) showed high efficacy and safety, and preliminary data seem to confirm their activity on low‐grade NHL. The question arises as whether or not—and how—to treat the HCV‐positive patients suffering from diffuse large B‐cell lymphomas (DLBCLs). The aim of this observational study was to evaluate whether DAA antiviral treatment of DLBCL/HCV‐infected patients in concomitance with chemotherapy is a safe and effective option. Twenty (13 males and 7 females) HCV genotype 1b‐positive subjects, undergoing chemotherapy for DLBCL, were enrolled between June 2015 and December 2015. After informed consent, all patients underwent antiviral therapy (AVT) with sofosbuvir/ledipasvir and chemotherapy (14 rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone and 6 cyclophosphamide, doxorubicin, vincristine, and prednisone) for DLBCL. Complete hematological (Revised European‐American Lymphoma classification, Ann Arbor, and International Prognostic Index [IPI] scores) and hepatological (viral markers, liver stiffness, and biochemical parameters) evaluations were made. A historical retrospective cohort of 101 DLBCL/HCV‐positive patients not undergoing AVT was enrolled for comparison. DAA‐treated and untreated patients were similar for sex distribution, IPI score, and NHL stage, and differed for age (older in treated), chemotherapy and use of AVT. Overall survival (OS) and disease‐free survival (DFS) were evaluated among a 52‐week of follow‐up. No statistical difference was found in OS after 52 weeks (P = 0.122), whereas a statistically significant higher DFS was achieved in treated patients (P = 0.036). At the multivariate analysis, only IPI score and AVT were independently correlated with a better DFS. No differences in adverse events were reported. Conclusion: DAA treatment in concomitance with chemotherapy was shown to be safe and effective in influencing remission of aggressive lymphomas in HCV patients. (Hepatology 2018;67:48‐55).
    Subject(s): Prospective Studies ; Humans ; Middle Aged ; Male ; Case-Control Studies ; Patient Safety ; Adult ; Female ; Hepatitis C, Chronic - epidemiology ; Liver Function Tests ; Severity of Illness Index ; Antiviral Agents - pharmacology ; Lymphoma, Large B-Cell, Diffuse - drug therapy ; Lymphoma, Large B-Cell, Diffuse - pathology ; Risk Assessment ; Antiviral Agents - therapeutic use ; Comorbidity ; Kaplan-Meier Estimate ; Proportional Hazards Models ; Treatment Outcome ; Hepatitis C, Chronic - diagnosis ; Hepatitis C, Chronic - drug therapy ; Disease-Free Survival ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Lymphoma, Large B-Cell, Diffuse - epidemiology ; Survival Analysis ; Aged ; Cohort Studies ; Index Medicus
    ISSN: 0270-9139
    E-ISSN: 1527-3350
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 4
    Language: English
    In: The New England journal of medicine, 2016-01-07, Vol.374 (1), p.43-53
    Description: Antilymphocyte globulin (ATG) added to the conditioning regimen before allogeneic hematopoietic stem-cell transplantation resulted in a lower rate of chronic graft-versus-host disease at 2 years than the rate without ATG (32% vs. 68%), with no apparent increased risk of relapse. Chronic graft-versus-host disease (GVHD) is a major complication of allogeneic stem-cell transplantation that results in later illness and death and a reduction in quality of life. 1 , 2 Risk factors for chronic GVHD are the use of peripheral blood as a source of stem cells, a history of acute GVHD, and the use of donated stem cells with high numbers of T cells. 3 – 7 In a meta-analysis, the Stem Cell Trialists’ Collaborative Group reported an incidence of extensive chronic GVHD of 47% after peripheral-blood stem-cell transplantation from an HLA-identical sibling. 4 In 2012, more than 70% of the stem-cell transplantations performed in . . .
    Subject(s): Graft vs Host Disease - epidemiology ; Prospective Studies ; Humans ; Immunosuppressive Agents - therapeutic use ; Middle Aged ; Proportional Hazards Models ; Child, Preschool ; Male ; Survival Rate ; Transplantation, Homologous ; Incidence ; Young Adult ; Disease-Free Survival ; Graft vs Host Disease - mortality ; Adolescent ; Antilymphocyte Serum - therapeutic use ; Adult ; Female ; Graft vs Host Disease - prevention & control ; T-Lymphocytes - immunology ; Child ; Chronic Disease ; Prevention ; Treatment outcome ; Graft versus host reaction ; Immunoglobulins ; Dosage and administration ; Analysis ; Graft-versus-host reaction ; Transplants & implants ; Leukemia ; Stem cell transplantation ; Lymphocytes T ; Preventive medicine ; Hemopoiesis ; Globulins ; Risk assessment ; Peripheral blood ; Stem cells ; Bone marrow ; Histocompatibility antigen HLA ; Index Medicus ; Abridged Index Medicus
    ISSN: 0028-4793
    E-ISSN: 1533-4406
    Source: Single Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 5
    Language: English
    In: International journal of molecular sciences, 2020-05-04, Vol.21 (9), p.3252
    Description: Aptamers or chemical antibodies are single-stranded DNA or RNA oligonucleotides that bind proteins and small molecules with high affinity and specificity by recognizing tertiary or quaternary structures as antibodies. Aptamers can be easily produced in vitro through a process known as systemic evolution of ligands by exponential enrichment (SELEX) or a cell-based SELEX procedure. Aptamers and modified aptamers, such as slow, off-rate, modified aptamers (SOMAmers), can bind to target molecules with less polar and more hydrophobic interactions showing slower dissociation rates, higher stability, and resistance to nuclease degradation. Aptamers and SOMAmers are largely employed for multiplex high-throughput proteomics analysis with high reproducibility and reliability, for tumor cell detection by flow cytometry or microscopy for research and clinical purposes. In addition, aptamers are increasingly used for novel drug delivery systems specifically targeting tumor cells, and as new anticancer molecules. In this review, we summarize current preclinical and clinical applications of aptamers in malignant and non-malignant hematological diseases.
    Subject(s): Oligonucleotides, Antisense ; Humans ; Treatment Outcome ; Clinical Trials as Topic ; Hematologic Diseases - mortality ; Hematologic Diseases - diagnosis ; Hematologic Diseases - therapy ; Molecular Diagnostic Techniques ; Animals ; Aptamers, Nucleotide ; Hematologic Diseases - etiology ; SELEX Aptamer Technique ; Disease Management ; Drug Evaluation, Preclinical ; Genetic Therapy - methods ; Index Medicus ; treatment ; diagnosis ; hematology ; Review ; aptamers ; antisense oligonucleotides
    ISSN: 1422-0067
    ISSN: 1661-6596
    E-ISSN: 1422-0067
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: Directory of Open Access Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 6
    Language: English
    In: Life (Basel, Switzerland), 2020-12-11, Vol.10 (12), p.344
    Description: Chemotherapy-related cardiac dysfunction, also known as cardiotoxicity, is a group of drug-related adverse events negatively affecting myocardial structure and functions in patients who received chemotherapy for cancer treatment. Clinical manifestations can vary from life-threatening arrythmias to chronic conditions, such as heart failure or hypertension, which dramatically reduce quality of life of cancer survivors. Standard chemotherapy exerts its toxic effect mainly by inducing oxidative stress and genomic instability, while new targeted therapies work by interfering with signaling pathways important not only in cancer cells but also in myocytes. For example, Bruton's tyrosine kinase (BTK) inhibitors interfere with class I phosphoinositide 3-kinase isoforms involved in cardiac hypertrophy, contractility, and regulation of various channel forming proteins; thus, off-target effects of BTK inhibitors are associated with increased frequency of arrhythmias, such as atrial fibrillation, compared to standard chemotherapy. In this review, we summarize current knowledge of cardiotoxic effects of targeted therapies used in hematology.
    Subject(s): targeted therapy ; cardiotoxicity ; hematology ; Review ; adverse reactions
    ISSN: 2075-1729
    E-ISSN: 2075-1729
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: Directory of Open Access Journals
    Source: ProQuest Central
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 7
    Language: English
    In: Frontiers in pharmacology, 2020-06-05, Vol.11, p.857-857
    Description: To date, there are no specific therapeutic strategies for treatment of COVID-19. Based on the hypothesis that complement and coagulation cascades are activated by viral infection, and might trigger an acute respiratory distress syndrome (ARDS), we report clinical outcomes of 17 consecutive cases of SARS-CoV-2-related ARDS treated (N = 7) with the novel combination of ruxolitinib, a JAK1/2 inhibitor, 10 mg/twice daily for 14 days and eculizumab, an anti-C5a complement monoclonal antibody, 900 mg IV/weekly for a maximum of three weeks, or with the best available therapy (N = 10). Patients treated with the combination showed significant improvements in respiratory symptoms and radiographic pulmonary lesions and decrease in circulating D-dimer levels compared to the best available therapy group. Our results support the use of combined ruxolitinib and eculizumab for treatment of severe SARS-CoV-2-related ARDS by simultaneously turning off abnormal innate and adaptive immune responses.
    Subject(s): COVID-19 ; JAK inhibitor ; SARS-CoV-2 ; Pharmacology ; eculizumab ; ARDS (acute respiratory distress syndrome)
    ISSN: 1663-9812
    E-ISSN: 1663-9812
    Source: PubMed Central
    Source: Directory of Open Access Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 8
    Language: English
    In: International journal of molecular sciences, 2020-08-17, Vol.21 (16), p.5905
    Description: Mesenchymal stem cells derived from human bone marrow (hBM-MSCs) are utilized in tendon tissue-engineering protocols while extra-embryonic cord-derived, including from Wharton's Jelly (hWJ-MSCs), are emerging as useful alternatives. To explore the tenogenic responsiveness of hBM-MSCs and hWJ-MSCs to human Growth Differentiation Factor 5 (hGDF-5) we supplemented each at doses of 1, 10, and 100 ng/mL of hGDF-5 and determined proliferation, morphology and time-dependent expression of tenogenic markers. We evaluated the expression of collagen types 1 (COL1A1) and 3 (COL3A1), Decorin (DCN), Scleraxis-A (SCX-A), Tenascin-C (TNC) and Tenomodulin (TNMD) noting the earliest and largest increase with 100 ng/mL. With 100 ng/mL, hBM-MSCs showed up-regulation of SCX-A (1.7-fold) at Day 1, TNC (1.3-fold) and TNMD (12-fold) at Day 8. hWJ-MSCs, at the same dose, showed up-regulation of COL1A1 (3-fold), DCN (2.7-fold), SCX-A (3.8-fold) and TNC (2.3-fold) after three days of culture. hWJ-MSCs also showed larger proliferation rate and marked aggregation into a tubular-shaped system at Day 7 (with 100 ng/mL of hGDF-5). Simultaneous to this, we explored the expression of pro-inflammatory (IL-6, TNF, IL-12A, IL-1β) and anti-inflammatory (IL-10, TGF-β1) cytokines across for both cell types. hBM-MSCs exhibited a better balance of pro-inflammatory and anti-inflammatory cytokines up-regulating IL-1β (11-fold) and IL-10 (10-fold) at Day 8; hWJ-MSCs, had a slight expression of IL-12A (1.5-fold), but a greater up-regulation of IL-10 (2.5-fold). Type 1 collagen and tenomodulin proteins, detected by immunofluorescence, confirming the greater protein expression when 100 ng/mL were supplemented. In the same conditions, both cell types showed specific alignment and shape modification with a length/width ratio increase, suggesting their response in activating tenogenic commitment events, and they both potential use in 3D in vitro tissue-engineering protocols.
    Subject(s): Tenascin - genetics ; Tenocytes - cytology ; Humans ; Umbilical Cord - cytology ; Male ; Tenascin - metabolism ; Interleukins - metabolism ; Interleukins - genetics ; Basic Helix-Loop-Helix Transcription Factors - metabolism ; Mesenchymal Stem Cells - cytology ; Mesenchymal Stem Cells - drug effects ; Adult ; Bone Marrow Cells - drug effects ; Female ; Cell Differentiation ; Collagen - genetics ; Membrane Proteins - metabolism ; Mesenchymal Stem Cells - metabolism ; Decorin - genetics ; Basic Helix-Loop-Helix Transcription Factors - genetics ; Bone Marrow Cells - cytology ; Membrane Proteins - genetics ; Cells, Cultured ; Tenocytes - metabolism ; Growth Differentiation Factor 5 - pharmacology ; Collagen - metabolism ; Bone Marrow Cells - metabolism ; Decorin - metabolism ; Index Medicus ; tenogenic commitment ; Growth Differentiation Factor-5 ; Wharton’s Jelly human umbilical cord mesenchymal stem cells (hWJ-MSCs) ; human bone marrow Mesenchymal Stem Cells (hBM-MSCs) ; gene expression ; immunofluorescence assay
    ISSN: 1422-0067
    ISSN: 1661-6596
    E-ISSN: 1422-0067
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: Directory of Open Access Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 9
    Language: English
    In: Diagnostic cytopathology, 2020-03, Vol.48 (3), p.211-216
    Description: Background The phenotypical identification of diagnostic cells is crucial for the diagnosis of Hodgkin's lymphoma (HL) on fine‐needle aspiration cytology (FNAC). The aim of this study is to evaluate the immunocytochemical (ICC) expression of CD30, CD15, and PAX5 in Hodgkin's cells (HC) and Reed‐Sternberg cells (RSC) on smears and cell‐blocks (CB) of HL and to compare the performance of each antibody on smears and CB. Methods In 21 FNAC cases of histologically confirmed classical HL, ICC identification of HC and RSC was performed using CD15, CD30, and PAX5 on smears and CB, respectively. Results CD30 was positive in 19/21 cases (90.5%; 11/11 smears and 8/10 CB), CD15 was positive in 14/21 cases (66.7%; 5/11 smears and 9/10 CB), and PAX5 was positive in 13/21 cases (61.9%; 9/11 smears and 4/10CB). Conclusions CD15, CD30, and PAX5 are useful to the FNAC identification of HC and RSC. CD30 is the most sensitive, followed by CD15 and PAX5, which are more effective on CB and smears, respectively.
    Subject(s): CD30 ; CD15 ; fine‐needle aspiration cytology ; PAX5 ; Hodgkin lymphoma ; Cellular biology ; Lymphoma ; Index Medicus
    ISSN: 8755-1039
    E-ISSN: 1097-0339
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 10
    Language: English
    In: Cytopathology (Oxford), 2019-07, Vol.30 (4), p.348-362
    Description: The 2016 World Health Organisation revised classification of lymphoma has sub‐classified well‐defined entities and added a number of provisional entities on the basis of new knowledge on genetic, epigenetics and phenotypical data; prognostic and predictive features are also part of this classification. New knowledge on well‐defined entities further enlightens the mechanisms of lymphomagenesis, which are more complex and multifactorial than once believed. Therapies are also more complex because traditional clinical trials have been integrated with new drugs and compounds with unique mechanisms of actions against distinct molecular targets. As lymphoma acquires additional genetic and phenotypic features over the time, pathological assessment is also necessary. Histological evaluation and tissue collection by surgical biopsies are necessary for phenotypical and molecular purposes; however, these are demanding procedures for both the patient and the health care system. At the same time, the choice of the best treatment for a specific entity, in different phases and different patients requires information that may not be available when the biopsy is performed. Fine needle aspiration cytology (FNAC) is successfully used in lymph nodes (LNs) in combination with different ancillary techniques and might be used to assess the phenotypic and genetic profile of specific targets and to get key information for therapy, in different phases and stages of the disease, with the option to re‐check the same target over time, without surgical excision. This brief review describes LN‐FNAC diagnostic criteria, current therapies for lymphomas and the potential role of LN‐FNAC in selecting non‐Hodgkin lymphomas patients for specific targeted treatments. Traditional therapies for lymphoma have been integrated with new drugs and compounds with unique mechanisms of actions against distinct molecular targets. Lymph node fine‐needle aspiration cytology might be used to evaluate the phenotypic and genetic profiles, identify specific targets and get useful information for therapeutic planning in different phases of the disease with the option to re‐check the same target over time.
    Subject(s): fine‐needle cytology ; lymphoma ; target therapy ; Lymphomas ; Index Medicus
    ISSN: 0956-5507
    E-ISSN: 1365-2303
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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