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Monoclonal gammopathy of undetermined significance

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https://www.readbyqxmd.com/read/29910095/sporadic-late-onset-nemaline-myopathy-with-monoclonal-gammopathy-of-undetermined-significance-slonm-mgus-an-alternative-treatment-using-cyclophosphamide-thalidomide-dexamethasone-ctd-regimen
#1
Theerawat Kumutpongpanich, Weerapat Owattanapanich, Jantima Tanboon, Ichizo Nishino, Kanokwan Boonyapisit
Sporadic late-onset nemaline myopathy with monoclonal gammopathy of undetermined significance is a rare subacute adult-onset myopathy. Without appropriate treatment, the prognosis is unfavorable and can be fatal. Various efficacious treatment options have been reported. High dose melphalan followed by autologous stem cell transplantation is the most used option with favorable outcome. Nevertheless, potentially safer alternative regimens await exploration. Here, we report the case of sporadic late-onset nemaline myopathy with monoclonal gammopathy of undetermined significance in a 33-year-old man with significant clinical improvement and complete remission of monoclonal gammopathy after 5 cycles of cyclophosphamide, thalidomide, and dexamethasone regimen...
May 16, 2018: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/29884135/c3-glomerulonephritis-associated-with-monoclonal-gammopathy-of-renal-significance-case-report
#2
Juana Alonso-Titos, Lara Perea-Ortega, Eugenia Sola, Alvaro Torres-Rueda, Myriam León, Remedios Toledo, Ana D Duarte, Teresa Vazquez, Maria Dolores Martinez-Esteban, Alicia Bailen, Pedro Ruiz-Esteban, Domingo Hernandez
BACKGROUND: Morbidity associated with monoclonal gammopathy of renal significance is high due to the severe renal lesions and the associated systemic alterations. Accordingly, early diagnosis is fundamental, as is stopping the clonal production of immunoglobulins using specific chemotherapy. CASE PRESENTATION: A 75-year-old man with chronic renal disease of unknown origin since 2010 experienced rapid worsening of renal function over a period of 6 mos. Bone marrow biopsy showed monoclonal gammopathy of undetermined significance...
June 8, 2018: BMC Nephrology
https://www.readbyqxmd.com/read/29795248/immunoglobulin-light-chain-amyloidosis-diagnosis-and-treatment-algorithm-2018
#3
REVIEW
Morie A Gertz
Immunoglobulin light chain amyloidosis (AL) should be considered in any patient that presents to a cancer care provider with nephrotic range proteinuria, heart failure with preserved ejection fraction, non-diabetic peripheral neuropathy, unexplained hepatomegaly or diarrhea. More importantly, patients being monitored for smoldering multiple myeloma and a monoclonal gammopathy of undetermined significance (MGUS) are at risk for developing AL amyloidosis. MGUS and myeloma patients that have atypical features, including unexplained weight loss; lower extremity edema, early satiety, and dyspnea on exertion should be considered at risk for light chain amyloidosis...
May 23, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29766549/leukocytoclastic-vasculitis-associated-with-immunoglobulin-a-lambda-monoclonal-gammopathy-of-undetermined-significance-a-case-report-and-review-of-previously-reported-cases
#4
Hiroshi Umemura, Osamu Yamasaki, Keiji Iwatsuki
Leukocytoclastic vasculitis is often associated with immunoglobulin (Ig)A deposition on the vascular walls. IgA-associated leukocytoclastic vasculitis comprises various underlying diseases. Hematological disorders that can be minor triggers include multiple myeloma and monoclonal gammopathy of undetermined significance. Here, we present the case of a 78-year-old woman with leukocytoclastic vasculitis associated with monoclonal gammopathy of undetermined significance of the IgA lambda chain. Oral steroid administration initially showed remission of vasculitis; however, the condition recurred after four attempts of treatment withdrawal...
May 15, 2018: Journal of Dermatology
https://www.readbyqxmd.com/read/29755672/inhibition-of-mtor-complex-2-restrains-tumor-angiogenesis-in-multiple-myeloma
#5
Aurelia Lamanuzzi, Ilaria Saltarella, Vanessa Desantis, Maria Antonia Frassanito, Patrizia Leone, Vito Racanelli, Beatrice Nico, Domenico Ribatti, Paolo Ditonno, Marcella Prete, Antonio Giovanni Solimando, Francesco Dammacco, Angelo Vacca, Roberto Ria
The mammalian Target of Rapamycin (mTOR) is an intracellular serine/threonine kinase that mediates intracellular metabolism, cell survival and actin rearrangement. mTOR is made of two independent complexes, mTORC1 and mTORC2, activated by the scaffold proteins RAPTOR and RICTOR, respectively. The activation of mTORC1 triggers protein synthesis and autophagy inhibition, while mTORC2 activation promotes progression, survival, actin reorganization, and drug resistance through AKT hyper-phosphorylation on Ser473...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29740794/focal-segmental-glomerulosclerosis-with-heterozygous-apolipoprotein-e5-glu3lys
#6
Masaru Sasaki, Tetsuhiko Yasuno, Kenji Ito, Akira Matsunaga, Satoshi Hisano, Yasuhiro Abe, Katsuhisa Miyake, Kosuke Masutani, Hitoshi Nakashima, Takao Saito
Apolipoprotein (apo) E5 is a rare apoE isoform. The apoE5 (Glu3Lys) variant, which is caused by the substitution of lysine with glutamic acid at codon 3, has a relative frequency of 0.1% in Japan. Previous studies have reported that apoE5 (Glu3Lys) is associated with hyperlipidemia and cardiovascular diseases, but this isoform has higher LDL receptor-binding activity than that of normal apoE3. Nephropathy associated with apoE5 (Glu3Lys) alone has not yet been reported. We present a case of a 51-year-old man with nephrotic syndrome...
May 8, 2018: CEN Case Reports
https://www.readbyqxmd.com/read/29725501/the-untold-stories-of-the-speech-gene-the-foxp2-cancer-gene
#7
REVIEW
Maria Jesus Herrero, Yorick Gitton
FOXP2 encodes a transcription factor involved in speech and language acquisition. Growing evidence now suggests that dysregulated FOXP2 activity may also be instrumental in human oncogenesis, along the lines of other cardinal developmental transcription factors such as DLX5 and DLX6 [1-4]. Several FOXP familymembers are directly involved during cancer initiation, maintenance and progression in the adult [5-8]. This may comprise either a pro-oncogenic activity or a deficient tumor-suppressor role, depending upon cell types and associated signaling pathways...
January 2018: Genes & Cancer
https://www.readbyqxmd.com/read/29721239/meningitis-spondylodiscitis-pneumonia-and-septic-shock-with-streptococcus-pneumoniae-in-a-previously-healthy-woman-with-isolated-igg2-igg3-iga-deficiency-and-monoclonal-gammopathy-of-undetermined-significance
#8
Shahin Gaini, David Gudnason, Bjarni Á Steig, Jenny Jónsdóttir Nielsen
A 66 years old Caucasian woman with pneumococcal meningitis was treated and discharged after an uncomplicated course. Five months later she was readmitted with fever and right side abdominal pain and diagnosed with pneumococcal spondylodiscitis. One year later she was treated for a severe chest X-ray confirmed left lobar pneumonia. Two years later she was diagnosed with a pneumococcal pneumonia in her left lung with septic shock. An immune deficiency screen revealed slightly reduced IgA levels, low IgG2 levels, low IgG3 levels and high IgG1 levels...
March 29, 2018: Infectious Disease Reports
https://www.readbyqxmd.com/read/29710195/multiple-myeloma-and-its-precursor-disease-among-firefighters-exposed-to-the-world-trade-center-disaster
#9
Ola Landgren, Rachel Zeig-Owens, Orsolya Giricz, David Goldfarb, Kaznouri Murata, Katie Thoren, Lakshmi Ramanathan, Malin Hultcrantz, Ahmet Dogan, George Nwankwo, Ulrich Steidl, Kith Pradhan, Charles B Hall, Hillel W Cohen, Nadia Jaber, Theresa Schwartz, Laura Crowley, Michael Crane, Shani Irby, Mayris P Webber, Amit Verma, David J Prezant
Importance: The World Trade Center (WTC) attacks on September 11, 2001, created an unprecedented environmental exposure to known and suspected carcinogens suggested to increase the risk of multiple myeloma. Multiple myeloma is consistently preceded by the precursor states of monoclonal gammopathy of undetermined significance (MGUS) and light-chain MGUS, detectable in peripheral blood. Objective: To characterize WTC-exposed firefighters with a diagnosis of multiple myeloma and to conduct a screening study for MGUS and light-chain MGUS...
April 26, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29703722/-myd88-l265p-mutation-in-lymphoid-malignancies
#10
REVIEW
Xinfang Yu, Wei Li, Qipan Deng, Ling Li, Eric D Hsi, Ken H Young, Mingzhi Zhang, Yong Li
Next-generation sequencing has revealed cancer genomic landscapes, in which over 100 driver genes that, when altered by intragenic mutations, can promote oncogenesis. MYD88 is a driver gene found in hematologic B-cell malignancies. A missense mutation (L265P) changing leucine at position 265 to proline in MYD88 is found in ∼90% of Waldenström macroglobulinemia (WM) cases and in significant portions of activated B-cell diffuse large B-cell lymphomas and IgM monoclonal gammopathy of undetermined significance...
May 15, 2018: Cancer Research
https://www.readbyqxmd.com/read/29703720/from-mgus-to-multiple-myeloma-a-paradigm-for-clonal-evolution-of-premalignant-cells
#11
REVIEW
Niels van Nieuwenhuijzen, Ingrid Spaan, Reinier Raymakers, Victor Peperzak
Multiple myeloma (MM) is a treatable, but incurable, malignancy of plasma cells (PC) in the bone marrow (BM). It represents the final stage in a continuum of PC dyscrasias and is consistently preceded by a premalignant phase termed monoclonal gammopathy of undetermined significance (MGUS). The existence of this well-defined premalignant phase provides the opportunity to study clonal evolution of a premalignant condition into overt cancer. Unraveling the mechanisms of malignant transformation of PC could enable early identification of MGUS patients at high risk of progression and may point to novel therapeutic targets, thereby possibly delaying or preventing malignant transformation...
April 27, 2018: Cancer Research
https://www.readbyqxmd.com/read/29696302/-long-term-follow-up-of-monoclonal-gammopathies-of-undetermined-significance-mgus
#12
H Goldschmidt, S Nitschmann
No abstract text is available yet for this article.
June 2018: Der Internist
https://www.readbyqxmd.com/read/29686421/the-multiple-myelomas-current-concepts-in-cytogenetic-classification-and-therapy
#13
REVIEW
Shaji K Kumar, S Vincent Rajkumar
Multiple myeloma (MM) is a plasma cell neoplasm that accounts for 2% of all haematological malignancies and predominantly affects older individuals (with a median age at diagnosis of 65-70 years). MM is consistently preceded by the clinically recognized precancerous stages monoclonal gammopathy of undetermined significance and smouldering MM. Thus far, MM has been considered as a single disease entity, but the clinical presentation, response to treatment, and survival outcomes of patients with MM are quite heterogeneous and highly dependent on a set of chromosomal abnormalities that can be identified in nearly all of them...
April 23, 2018: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29685422/circulating-soluble-receptor-activator-of-nuclear-factor-kappa-b-ligand-and-c-c-motif-ligand-3-correlate-with-survival-in-patients-with-waldenstr%C3%A3-m-macroglobulinemia
#14
Evangelos Eleutherakis-Papaiakovou, Efstathios Kastritis, Maria Gavriatopoulou, Dimitrios Christoulas, Maria Roussou, Ioannis Ntanasis-Stathopoulos, Nikolaos Kanellias, Athanasios Papatheodorou, Meletios A Dimopoulos, Evangelos Terpos
BACKGROUND: Serum receptor activator of nuclear factor κB ligand (sRANKL) and chemokine (C-C) motif ligand 3 (CCL-3) have been reported to be elevated in Waldenström macroglobulinemia (WM) patients. However, there are no published data regarding the prognostic value of these molecules in WM regarding progression-free and overall survival. METHODS: To evaluate the effect of these markers of bone remodeling on survival parameters, we prospectively evaluated serum cytokines and biological markers in 55 patients with symptomatic WM before they received any kind of treatment...
June 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29669929/antigen-mediated-regulation-in-monoclonal-gammopathies-and-myeloma
#15
Shiny Nair, Joel Sng, Chandra Sekhar Boddupalli, Anja Seckinger, Marta Chesi, Mariateresa Fulciniti, Lin Zhang, Navin Rauniyar, Michael Lopez, Natalia Neparidze, Terri Parker, Nikhil C Munshi, Rachael Sexton, Bart Barlogie, Robert Orlowski, Leif Bergsagel, Dirk Hose, Richard A Flavell, Pramod K Mistry, Eric Meffre, Madhav V Dhodapkar
A role for antigen-driven stimulation has been proposed in the pathogenesis of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) based largely on the binding properties of monoclonal Ig. However, insights into antigen binding to clonal B cell receptors and in vivo responsiveness of the malignant clone to antigen-mediated stimulation are needed to understand the role of antigenic stimulation in tumor growth. Lysolipid-reactive clonal Ig were detected in Gaucher disease (GD) and some sporadic gammopathies...
April 19, 2018: JCI Insight
https://www.readbyqxmd.com/read/29656787/fifty-year-incidence-of-waldenstr%C3%A3-m-macroglobulinemia-in-olmsted-county-minnesota-from-1961-through-2010-a-population-based-study-with-complete-case-capture-and-hematopathologic-review
#16
Robert A Kyle, Dirk R Larson, Ellen D McPhail, Terry M Therneau, Angela Dispenzieri, Shaji Kumar, Prashant Kapoor, James R Cerhan, S Vincent Rajkumar
OBJECTIVE: To determine the incidence of Waldenström macroglobulinemia (WM) in a strictly defined geographic area over a 50-year period. PATIENTS AND METHODS: All residents of Olmsted County with a diagnosis of WM, consisting of a monoclonal IgM protein of any size and/or 10% or more lymphoplasmacytic infiltration of the bone marrow along with anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or hepatosplenomegaly requiring therapy, were identified from January 1, 1961, to December 31, 2010...
June 2018: Mayo Clinic Proceedings
https://www.readbyqxmd.com/read/29651353/a-rare-case-of-systemic-al-amyloidosis-with-muscle-involvement-a-misleading-diagnosis
#17
Fabrizio Accardi, Valentina Papa, Anna Rita Capozzi, Gian Luca Capello, Laura Verga, Cristina Mancini, Eugenia Martella, Roberta Costa, Laura Notarfranchi, Benedetta Dalla Palma, Franco Aversa, Vladimiro Pietrini, Giovanna Cenacchi, Nicola Giuliani
Muscle involvement in AL amyloidosis is a rare condition, and the diagnosis of amyloid myopathy is often delayed and underdiagnosed. Amyloid myopathy may be the initial manifestation and may precede the diagnosis of systemic AL amyloidosis. Here, we report the case of a 73-year-old man who was referred to our center for a monoclonal gammopathy of undetermined significance (MGUS) diagnosed since 1999. He reported a progressive weakness of proximal muscles of the legs with onset six months previously. Muscle biopsy showed mild histopathology featuring alterations of nonspecific type with a mixed myopathic and neurogenic involvement, and the diagnostic turning point was the demonstration of characteristic green birefringence under cross-polarized light following Congo red staining of perimysial vessels...
2018: Case Reports in Hematology
https://www.readbyqxmd.com/read/29629484/light-chain-monoclonal-gammopathy-of-undetermined-significance-is-characterized-by-a-high-disappearance-rate-and-low-risk-of-progression-on-longitudinal-analysis
#18
Benedikt W Pelzer, Marina Arendt, Susanne Moebus, Lewin Eisele, Karl-Heinz Jöckel, Ulrich Dührsen, Jan Dürig
We determined the 10-year progression rate of light chain monoclonal gammopathy of undetermined significance (LCMGUS) and investigated potential associations with cancer utilizing the German population-based Heinz Nixdorf Recall Study. The Heinz Nixdorf Recall Study comprises 4814 men and women aged 45-75 years. Serum samples from baseline (2000-2003) and five-year (2006-2008) and 10-year (2011-2015) follow-up examinations were screened for monoclonal free light chains (FLC). LCMGUS was defined as abnormal FLC ratio, increase of involved FLC with complete loss of immunoglobulin heavy chain, and absence of a history of lymphoproliferative disease (LPD)...
April 9, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29616856/oncogene-induced-senescence-a-potential-breakpoint-mechanism-against-malignant-transformation-in-plasma-cell-disorders
#19
Nicola Lehners, Elena Ellert, Jing Xu, Jens Hillengass, Jonas Leichsenring, Albrecht Stenzinger, Hartmut Goldschmidt, Mindaugas Andrulis, Marc S Raab
Oncogene-induced senescence (OIS) is a cellular tumor-suppressive mechanism present in several premalignant conditions. Here, we analyze the possible impact of OIS on malignant transformation in plasma cell disorders. Tumor samples from 125 patients with different disease stages were analyzed immunohistochemically for expression of senescence markers. Protein expression of cyclin-dependent kinase inhibitor p21Cip1/Waf1 was significantly higher in smoldering multiple myeloma (SMM) compared to monoclonal gammopathy of undetermined significance (MGUS) (p = ...
April 4, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29589107/rhu-epo-down-regulates-pro-tumorigenic-activity-of-cancer-associated-fibroblasts-in-multiple-myeloma
#20
Vanessa Desantis, Maria Antonia Frassanito, Roberto Tamma, Ilaria Saltarella, Lucia Di Marzo, Aurelia Lamanuzzi, Antonio Giovanni Solimando, Simona Ruggieri, Tiziana Annese, Beatrice Nico, Angelo Vacca, Domenico Ribatti
We have previously demonstrated that recombinant human erythropoietin (rHuEpo) is involved in the regulation of the angiogenic response in multiple myeloma (MM) through a direct effect on macrophages and endothelial cells isolated from the bone marrow of patients with MM. The aim of the present study was designed to determine the effects of rHuEpo on cancer-associated fibroblasts (CAFs) from monoclonal gammopathy of undetermined significance (MGUS) and MM patients by means of in vitro and in vivo assays. rHuEpo treatment reduces the expression of mRNA levels of fibroblast activation markers, namely alpha smooth actin (αSMA) and fibroblast activation protein (FAP) in MGUS and MM CAFs, and of pro-inflammatory and pro-angiogenic cytokines, including interleukin (IL)-6 and IL-8, vascular endothelial growth factor-A (VEGF-A), fibroblast growth factor-2 (FGF-2), and hepatocyte growth factor (HGF) in MM CAFs...
March 28, 2018: Annals of Hematology
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