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Article ; Online: Pleural Effusion in Multiple Myeloma: A Liquid State.

Magen, Hila

2017 Volume 138, Issue 2, Page(s) 67–68

MeSH term(s)	Humans ; Multiple Myeloma ; Plasma Cells ; Pleural Effusion
Language	English
Publishing date	2017
Publishing country	Switzerland
Document type	Journal Article ; Comment
ZDB-ID	80008-9
ISSN	1421-9662 ; 0001-5792
ISSN (online)	1421-9662
ISSN	0001-5792
DOI	10.1159/000478888
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Article: Pleural Effusion in Multiple Myeloma: A Liquid State

Magen, Hila

Acta Haematologica

2017 Volume 138, Issue 2, Page(s) 67–68

Institution	Institute of Hematology, Davidoff Cancer Center, Beilinson Hospital, Rabin Medical Center, Petah Tikva, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Language	English
Publishing date	2017-08-10
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	Editorial Comment
ZDB-ID	80008-9
ISSN	1421-9662 ; 0001-5792
ISSN (online)	1421-9662
ISSN	0001-5792
DOI	10.1159/000478888
Database	Karger publisher's database

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Article: Diagnosis and management of multiple myeloma during pregnancy: case report, review of the literature, and an update on current treatments.

Magen, Hila / Simchen, Michal J / Erman, Shira / Avigdor, Abraham

Therapeutic advances in hematology

2022 Volume 13, Page(s) 20406207211066173

Abstract: The simultaneous occurrence of pregnancy and multiple myeloma (MM) is rare. The challenge of diagnosing MM during pregnancy is demonstrated in the case presented here. Despite the rarity of concurrent MM and pregnancy, this possibility should be ... ...

Abstract	The simultaneous occurrence of pregnancy and multiple myeloma (MM) is rare. The challenge of diagnosing MM during pregnancy is demonstrated in the case presented here. Despite the rarity of concurrent MM and pregnancy, this possibility should be considered in patients with signs and symptoms that may be attributed to MM so as not to delay the diagnosis and decision about pregnancy continuation and initiation of an appropriate and safe therapy to the mother and fetus. Treating physicians should be aware of the potential effects of MM therapies on the fetus and pregnancy outcomes.
Language	English
Publishing date	2022-01-21
Publishing country	England
Document type	Case Reports
ZDB-ID	2585183-4
ISSN	2040-6215 ; 2040-6207
ISSN (online)	2040-6215
ISSN	2040-6207
DOI	10.1177/20406207211066173
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Article: Amyloid Typing in Cardiac Amyloidosis Using Western Blotting.

Kaplan, Batia / Goldis, Rivka / Ziv, Tamar / Dori, Amir / Magen, Hila / Simon, Amos J / Volkov, Alexander / Maor, Elad / Arad, Michael

The Israel Medical Association journal : IMAJ

2024 Volume 26, Issue 3, Page(s) 149–156

Abstract: Background: Cardiac amyloidosis (CA) is characterized by the extracellular deposition of misfolded protein in the heart. Precise identification of the amyloid type is often challenging, but critical, since the treatment and prognosis depend on the ... ...

Abstract	Background: Cardiac amyloidosis (CA) is characterized by the extracellular deposition of misfolded protein in the heart. Precise identification of the amyloid type is often challenging, but critical, since the treatment and prognosis depend on the disease form and the type of deposited amyloid. Coexistence of clinical conditions such as old age, monoclonal gammopathy, chronic inflammation, or peripheral neuropathy in a patient with cardiomyopathy creates a differential diagnosis between the major types of CA: amyloidosis light chains (AL), amyloidosis transthyretin (ATTR) and amyloidosis A (AA). Objectives: To demonstrate the utility of the Western blotting (WB)-based amyloid typing method in patients diagnosed with cardiac amyloidosis where the type of amyloid was not obvious based on the clinical context. Methods: Congo red positive endomyocardial biopsy specimens were studied in patients where the type of amyloid was uncertain. Amyloid proteins were extracted and identified by WB. Mass spectrometry (MS) of the electrophoretically resolved protein-in-gel bands was used for confirmation of WB data. Results: WB analysis allowed differentiation between AL, AA, and ATTR in cardiac biopsies based on specific immunoreactivity of the electrophoretically separated proteins and their characteristic molecular weight. The obtained results were confirmed by MS. Conclusions: WB-based amyloid typing method is cheaper and more readily available than the complex and expensive gold standard techniques such as MS analysis or immunoelectron microscopy. Notably, it is more sensitive and specific than the commonly used immunohistochemical techniques and may provide an accessible diagnostic service to patients with amyloidosis in Israel.
MeSH term(s)	Humans ; Amyloidosis/diagnosis ; Amyloid/analysis ; Amyloid/metabolism ; Amyloidogenic Proteins ; Cardiomyopathies/diagnosis ; Blotting, Western ; Amyloid Neuropathies, Familial/pathology ; Prealbumin
Chemical Substances	Amyloid ; Amyloidogenic Proteins ; Prealbumin
Language	English
Publishing date	2024-03-16
Publishing country	Israel
Document type	Journal Article
ZDB-ID	2008291-5
ISSN	1565-1088 ; 0021-2180
ISSN	1565-1088 ; 0021-2180
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Article ; Online: Diagnostic Challenges and Solutions in Systemic Amyloidosis.

Goldis, Rivka / Kaplan, Batia / Kukuy, Olga Lesya / Arad, Michael / Magen, Hila / Shavit-Stein, Efrat / Dori, Amir / Livneh, Avi

International journal of molecular sciences

2023 Volume 24, Issue 5

Abstract: Amyloidosis refers to a clinically heterogeneous group of disorders characterized by the extracellular deposition of amyloid proteins in various tissues of the body. To date, 42 different amyloid proteins that originate from normal precursor proteins and ...

Abstract	Amyloidosis refers to a clinically heterogeneous group of disorders characterized by the extracellular deposition of amyloid proteins in various tissues of the body. To date, 42 different amyloid proteins that originate from normal precursor proteins and are associated with distinct clinical forms of amyloidosis have been described. Identification of the amyloid type is essential in clinical practice, since prognosis and treatment regimens both vary according to the particular amyloid disease. However, typing of amyloid protein is often challenging, especially in the two most common forms of amyloidosis, i.e., the immunoglobulin light chain amyloidosis and transthyretin amyloidosis. Diagnostic methodology is based on tissue examinations as well as on noninvasive techniques including serological and imaging studies. Tissue examinations vary depending on the tissue preparation mode, i.e., whether it is fresh-frozen or fixed, and they can be carried out by ample methodologies including immunohistochemistry, immunofluorescence, immunoelectron microscopy, Western blotting, and proteomic analysis. In this review, we summarize current methodological approaches used for the diagnosis of amyloidosis and discusses their utility, advantages, and limitations. Special attention is paid to the simplicity of the procedures and their availability in clinical diagnostic laboratories. Finally, we describe new methods recently developed by our team to overcome limitations existing in the standard assays used in common practice.
MeSH term(s)	Humans ; Immunoglobulin Light-chain Amyloidosis ; Proteomics/methods ; Amyloid/metabolism ; Amyloid Neuropathies, Familial ; Amyloidogenic Proteins
Chemical Substances	Amyloid ; Amyloidogenic Proteins
Language	English
Publishing date	2023-02-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24054655
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Article ; Online: Effect of HPSE and HPSE2 SNPs on the Risk of Developing Primary Paraskeletal Multiple Myeloma.

Ostrovsky, Olga / Beider, Katia / Magen, Hila / Leiba, Merav / Sanderson, Ralph D / Vlodavsky, Israel / Nagler, Arnon

Cells

2023 Volume 12, Issue 6

Abstract: Multiple myeloma (MM) is a plasma cell malignancy that is accompanied by hypercalcemia, renal failure, anemia, and lytic bone lesions. Heparanase (HPSE) plays an important role in supporting and promoting myeloma progression, maintenance of plasma cell ... ...

Abstract	Multiple myeloma (MM) is a plasma cell malignancy that is accompanied by hypercalcemia, renal failure, anemia, and lytic bone lesions. Heparanase (HPSE) plays an important role in supporting and promoting myeloma progression, maintenance of plasma cell stemness, and resistance to therapy. Previous studies identified functional single nucleotide polymorphisms (SNPs) located in the HPSE gene. In the present study, 5 functional HPSE SNPs and 11 novel HPSE2 SNPs were examined. A very significant association between two enhancer (rs4693608 and rs4693084), and two insulator (rs4364254 and rs4426765) HPSE SNPs and primary paraskeletal disease (PS) was observed. SNP rs657442, located in intron 9 of the HPSE2 gene, revealed a significant protective association with primary paraskeletal disease and lytic bone lesions. The present study demonstrates a promoting (HPSE gene) and protective (HPSE2 gene) role of gene regulatory elements in the development of paraskeletal disease and bone morbidity. The effect of signal discrepancy between myeloma cells and normal cells of the tumor microenvironment is proposed as a mechanism for the involvement of heparanase in primary PS. We suggest that an increase in heparanase-2 expression can lead to effective suppression of heparanase activity in multiple myeloma accompanied by extramedullary and osteolytic bone disease.
MeSH term(s)	Humans ; Bone Diseases/genetics ; Glucuronidase/genetics ; Introns ; Multiple Myeloma/genetics ; Polymorphism, Single Nucleotide/genetics ; Tumor Microenvironment
Chemical Substances	Glucuronidase (EC 3.2.1.31) ; heparanase (EC 3.2.1.-)
Language	English
Publishing date	2023-03-16
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12060913
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Article ; Online: Anti-RBD IgG antibodies and neutralizing antibody levels after the second BNT162b2 dose in patients with plasma cell disorders.

Magen, Hila / Avigdor, Abraham / Nevo, Lee / Fried, Shalev / Gibori, Amit / Levin, Einav G / Lustig, Yaniv / Shkury, Eden / Rahav, Galia

PloS one

2023 Volume 18, Issue 5, Page(s) e0284925

Abstract: Patients with plasma cell disorders (PCD) are at an increased risk for severe morbidity and mortality due to COVID-19. Recent data have suggested that patients with hematological malignancies, including those with PCD, have suboptimal antibody response ... ...

Abstract	Patients with plasma cell disorders (PCD) are at an increased risk for severe morbidity and mortality due to COVID-19. Recent data have suggested that patients with hematological malignancies, including those with PCD, have suboptimal antibody response to COVID-19 vaccination. We compared the antibody titers of 213 patients with PCD to those of 213 immunocompetent healthcare workers after the second vaccine dose of the BNT162b2 mRNA vaccine. Blood samples were taken 2-4 weeks after the second vaccination and analyzed for anti-receptor binding-domain immunoglobulin G (RBD-IgG) antibodies and neutralizing antibodies (NA). At a median of 20 days after the second vaccine dose, 172 patients (80.8%) developed anti-RBD-IgG antibodies with a geometric mean titer (GMT) of 2.7 (95% confidence interval [CI], 2.4-3.1). In the control group 210 (98.9%) developed anti-RBD-IgG antibodies after a median of 21 days, with a GMT of 5.17 (95%CI, 4.8-5.6), p<0.0001. NA were observed in 151 patients with MM (70.9%) and in 210 controls (98.9%). The GMT of NA in patients with MM and controls was 84.4 (95% CI, 59.0-120.6), and 420.2 (95% CI, 341.4-517.1), respectively (p<0.0001). Multivariable logistic regression revealed that the number of prior therapy lines and age were significant predictors of poor humoral response among patients with MM. Injection site reaction, headache and fatigue were the most common adverse events after vaccination. Adverse events were less common in patients with MM than in controls. In conclusion, a significant percentage of patients with MM developed protecting NA to the BNT162b2 mRNA vaccine, which appears to be safe in this patient population.
MeSH term(s)	Humans ; Antibodies, Neutralizing ; BNT162 Vaccine ; COVID-19 Vaccines ; Plasma Cells ; COVID-19 ; Paraproteinemias ; Immunoglobulin G ; Antibodies, Viral ; Vaccination
Chemical Substances	Antibodies, Neutralizing ; BNT162 Vaccine ; COVID-19 Vaccines ; Immunoglobulin G ; Antibodies, Viral
Language	English
Publishing date	2023-05-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0284925
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Article ; Online: Selinexor, Bortezomib, and Dexamethasone for Heavily Pretreated Multiple Myeloma: A Case Series.

Magen, Hila / Geva, Mika / Volchik, Yulia / Avigdor, Abraham / Nagler, Arnon

Clinical lymphoma, myeloma & leukemia

2020 Volume 20, Issue 12, Page(s) e947–e955

MeSH term(s)	Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bortezomib/pharmacology ; Bortezomib/therapeutic use ; Dexamethasone/pharmacology ; Dexamethasone/therapeutic use ; Humans ; Hydrazines/pharmacology ; Hydrazines/therapeutic use ; Middle Aged ; Multiple Myeloma/drug therapy ; Triazoles/pharmacology ; Triazoles/therapeutic use
Chemical Substances	Hydrazines ; Triazoles ; selinexor (31TZ62FO8F) ; Bortezomib (69G8BD63PP) ; Dexamethasone (7S5I7G3JQL)
Language	English
Publishing date	2020-07-29
Publishing country	United States
Document type	Case Reports ; Research Support, Non-U.S. Gov't
ZDB-ID	2540992-X
ISSN	2152-2669 ; 2152-2650
ISSN (online)	2152-2669
ISSN	2152-2650
DOI	10.1016/j.clml.2020.07.016
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Article: Elotuzumab: the first approved monoclonal antibody for multiple myeloma treatment.

Magen, Hila / Muchtar, Eli

Therapeutic advances in hematology

2016 Volume 7, Issue 4, Page(s) 187–195

Abstract: Elotuzumab is a monoclonal antibody directed against the SLAMF7 receptor, expressed on normal and malignant plasma cells with a lower expression on other lymphoid cells such as natural killer (NK) cells. Elotuzumab has no significant antimyeloma activity ...

Abstract	Elotuzumab is a monoclonal antibody directed against the SLAMF7 receptor, expressed on normal and malignant plasma cells with a lower expression on other lymphoid cells such as natural killer (NK) cells. Elotuzumab has no significant antimyeloma activity when given as a single agent to patients with relapsed or refractory multiple myeloma (RRMM). However, when combined with other antimyeloma agents, it results in improved response and outcome. Owing to the results from the landmark ELOQUENT-2 phase III clinical trial, which compared lenalidomide and dexamethasone with or without elotuzumab in patients with RRMM, elotuzumab in combination with lenalidomide and dexamethasone was approved by the American Food and Drug Administration (FDA) in November 2015 for multiple myeloma (MM) patients who received one to three prior lines of therapy. This review will give a brief description of the signaling lymphocytic activation molecule (SLAM) family receptors, the unique SLAMF7 receptor and the mechanism of action of elotuzumab. Thereafter, we will give an overview on its antimyeloma activity in preclinical and clinical trials, including its toxicity profile and management thereof.
Language	English
Publishing date	2016-06-10
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2585183-4
ISSN	2040-6215 ; 2040-6207
ISSN (online)	2040-6215
ISSN	2040-6207
DOI	10.1177/2040620716652862
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Article: Venetoclax in Relapse/Refractory AL Amyloidosis-A Multicenter International Retrospective Real-World Study.

Lebel, Eyal / Kastritis, Efstathios / Palladini, Giovanni / Milani, Paolo / Theodorakakou, Foteini / Aumann, Shlomzion / Lavi, Noa / Shargian, Liat / Magen, Hila / Cohen, Yael / Gatt, Moshe E / Vaxman, Iuliana

Cancers

2023 Volume 15, Issue 6

Abstract: Therapeutic options in relapsed refractory (R/R) light-chain (AL) amyloidosis patients are limited. Given the encouraging results in t(11;14) multiple myeloma and the high prevalence of t(11;14) in AL amyloidosis, venetoclax is an attractive treatment ... ...

Abstract	Therapeutic options in relapsed refractory (R/R) light-chain (AL) amyloidosis patients are limited. Given the encouraging results in t(11;14) multiple myeloma and the high prevalence of t(11;14) in AL amyloidosis, venetoclax is an attractive treatment option in this setting. We report here the results of a multi-center retrospective study on 26 R/R AL amyloidosis patients treated off-label with venetoclax. The median lines of therapy prior to venetoclax was 3.5 (range 1-7), and 88% of our cohort had t (11;14). Twenty-two patients (85%) were previously treated with daratumumab. The overall hematologic response rate was 88%, 35% achieved a CR, and 35% achieved VGPR. The median event-free survival was 25 months (m) (95% CI 9.7 m-not reached), and the median overall survival was 33 m (95% CI 25.9-39.2 m). Most of the patients in this cohort are in ongoing deep responses and continuing venetoclax therapy. The treatment was relatively safe. One patient died due to infection, and there were two grade 3 infections in our cohort. Tumor lysis syndrome (TLS) was not seen in any patient. Dose reductions were frequent but did not affect the efficacy. These promising results require confirmation in a randomized controlled trial.
Language	English
Publishing date	2023-03-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15061710
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