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Cancer: Myeloma

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Total 122 results found since Jan 2013.

One siRNA pool targeting the {lambda} constant region stops {lambda} light-chain production and causes terminal endoplasmic reticulum stress
In systemic light-chain amyloidosis, light chains produced by clonal plasma cells cause organ damage and early death. In pursuit of novel therapy, we developed 1 pool of short interfering RNA (siRNA) targeting the constant region of light chains that substantially and promptly reduces -light-chain production and secretion by human plasma cells regardless of sequence diversity. In clones producing intact immunoglobulin G (IgG) antibodies (containing paired heavy and light chains), the secretion of intact antibodies is reduced, and all 3 branches of the unfolded protein response are activated by accumulation of unpaired IgG ...
Source: Blood - May 29, 2014 Category: Hematology Authors: Zhou, P., Ma, X., Iyer, L., Chaulagain, C., Comenzo, R. L. Tags: Multiple Myeloma, Lymphoid Neoplasia Source Type: research

Anacardic acid induces cell apoptosis associated with induction of ATF4-dependent endoplasmic reticulum stress.
Abstract Anacardic acid (6-pentadecylsalicylic acid, AA), a natural compound isolated from the traditional medicine Amphipterygium adstringens, has been reported to possess antitumor activities. However, its molecular targets have not been thoroughly studied. Here, we report that AA is a potent inducer of endoplasmic reticulum (ER) stress, leading to apoptosis in hepatoma HepG2 and myeloma U266 cells. Induction of ER stress by AA was supported by a dose- and time-dependent increase in expression of the ER signaling downstream molecules, such as GRP78/BiP, phosphorylated eIF2α, ATF4 and CHOP in both HepG2 and U266...
Source: Toxicology Letters - May 19, 2014 Category: Toxicology Authors: Huang H, Hua X, Liu N, Li X, Liu S, Chen X, Zhao C, Lan X, Yang C, Dou QP, Liu J Tags: Toxicol Lett Source Type: research

The natural killer-activating receptor, NKG2D, on CD3+CD8+ T cells plays a critical role in identifying and killing autologous myeloma cells.
CONCLUSION: Clinical trials are ongoing to determine a correlation with the number and function of NKG2D+CD3+CD8+ T cells and clinical outcomes in transplanted myeloma patients, including lymphocyte recovery following transplant and overall survival. PMID: 24446786 [PubMed - as supplied by publisher]
Source: Transfusion - January 22, 2014 Category: Hematology Authors: Talebian L, Fischer DA, Wu J, Channon JY, Sentman CL, Ernstoff MS, Meehan KR Tags: Transfusion Source Type: research

Interferon-¿-induced upregulation of immunoproteasome subunit assembly overcomes bortezomib resistance in human hematological cell lines
Conclusion: Downregulation of β5i subunit expression is a major determinant in acquisition of bortezomib-resistance and enhancement of its proteasomal assembly after induction by interferon-γ facilitates restoration of sensitivity in bortezomib-resistant leukemia cells towards bortezomib and next generation (immuno) proteasome inhibitors.
Source: Journal of Hematology and Oncology - January 13, 2014 Category: Hematology Authors: Denise NiewerthGertjan KaspersYehuda AssarafJohan van MeerlooChristopher KirkJanet AnderlJonathan BlankPeter van de VenSonja ZweegmanGerrit JansenJacqueline Cloos Source Type: research

Interferon-gamma-induced upregulation of immunoproteasome subunit assembly overcomes bortezomib resistance in human hematological cell lines
Conclusion: Downregulation of beta5i subunit expression is a major determinant in acquisition of bortezomib-resistance and enhancement of its proteasomal assembly after induction by interferon-gamma facilitates restoration of sensitivity in bortezomib-resistant leukemia cells towards bortezomib and next generation (immuno) proteasome inhibitors.
Source: Journal of Hematology and Oncology - January 13, 2014 Category: Hematology Authors: Denise NiewerthGertjan KaspersYehuda AssarafJohan van MeerlooChristopher KirkJanet AnderlJonathan BlankPeter van de VenSonja ZweegmanGerrit JansenJacqueline Cloos Source Type: research

Unfolded protein response inducers tunicamycin and dithiothreitol promote myeloma cell differentiation mediated by XBP-1.
Abstract The unfolded protein response (UPR) is an essential pathway for both normal and malignant plasma cells to maintain endoplasmic reticulum (ER) homeostasis in response to the large amount of immunoglobulin (Ig) output. The inositol-requiring enzyme 1-X-box binding protein-1 (IRE1-XBP-1) arm of the UPR pathway has been shown to play crucial roles not only in relieving the ER stress by up-regulating a series of genes favoring ER-associated protein degradation and protein folding, but in mediating terminal plasmacytic differentiation and maturation. Myeloma cells comprise various subsets arrested in diverse di...
Source: Clinical Lymphoma and Myeloma - December 20, 2013 Category: Cancer & Oncology Authors: Jiang H, Zou J, Zhang H, Fu W, Zeng T, Huang H, Zhou F, Hou J Tags: Clin Exp Med Source Type: research

A role for activator of G-protein signaling 3 (AGS3) in multiple myeloma.
In this report, we delineate the anti-apoptotic role of AGS3 in multiple myeloma (MM). To do this, we developed a cell apoptotic model induced by doxorubicin in MM. Our data indicate that decreased expression of AGS3 is correlated with reduced levels of p-CREB in the apoptotic model. The negative role of AGS3 in cell apoptosis was further confirmed by knocking down AGS3. The microenvironment has been shown to influence tumor cell phenotype in response to chemotherapy. Since cell adhesion-mediated drug resistance remains a major obstacle for successful treatment of MM, we constructed a cell adhesion model in MM and detected...
Source: International Journal of Hematology - December 5, 2013 Category: Hematology Authors: Shao S, Huang X, Wang Y, He S, Xu X, Zhu X, Yang X, Ding Z, Yao L, Huang Y, Wang C Tags: Int J Hematol Source Type: research

HIF-1α of bone marrow endothelial cells implies relapse and drug resistance in patients with multiple myeloma and may act as a therapeutic target.
CONCLUSIONS: The HIF-1α protein in MMECs may induce angiogenesis and resistance to bortezomib and lenalidomide and be a plausible target for the antiangiogenic management of well defined relapsed/refractory MM patients. It may also have prognostic significance. PMID: 24297864 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - December 2, 2013 Category: Cancer & Oncology Authors: Ria R, Catacchio I, Berardi S, De Luisi A, Caivano A, Piccoli C, Ruggieri V, Frassanito MA, Ribatti D, Nico B, Annese T, Ruggieri S, Guarini A, Minoia C, Ditonno P, Angelucci E, Derudas D, Moschetta M, Dammacco F, Vacca A Tags: Clin Cancer Res Source Type: research

Adhesion to fibronectin induces p27(Kip1) nuclear accumulation through down-regulation of Jab1 and contributes to cell adhesion-mediated drug resistance (CAM-DR) in RPMI 8,226 cells.
In conclusion, our data suggest that Jab1 plays an important role in CAM-DR, which depends on pSer10-p27(Kip1)-mediated subcellular localization of p27(Kip1). The understanding of this novel molecular mechanism may prove valuable in designing new therapeutic approaches for CAM-DR in Multiple myeloma. PMID: 24170542 [PubMed - as supplied by publisher]
Source: Molecular and Cellular Biochemistry - October 30, 2013 Category: Biochemistry Authors: Fei M, Hang Q, Hou S, He S, Ruan C Tags: Mol Cell Biochem Source Type: research

Syntaxin-4 is implicated in the secretion of antibodies by human plasma cells.
Abstract PCs are responsible for the production and secretion of antibodies, the effector molecules of the humoral immune response. The molecular mechanisms responsible for vesicle docking and secretion implicated in the antibody-secretion process are not well-known, as they have not been studied, but it is known that SNARE proteins are responsible for many membrane-fusion processes in the cell. We show here that freshly isolated human colon LP-PCs and T-PCs from MM-PC patients and the U266 cell line, as a model for PC secretion, contain a set of these proteins. SNAP23, STX3, and STX4 were localized mainly in the ...
Source: Journal of Leukocyte Biology - October 21, 2013 Category: Hematology Authors: Gómez-Jaramillo L, Delgado-Pérez L, Reales E, Mora-López F, Mateos RM, García-Poley A, Brieva JA, Campos-Caro A Tags: J Leukoc Biol Source Type: research

Chemotherapy stimulates syndecan-1 shedding: A potentially negative effect of treatment that may promote tumor relapse.
Abstract In patients with multiple myeloma, the heparan sulfate proteoglycan syndecan-1 (CD138) is shed from the surface of tumor cells and accumulates in the serum and within the extracellular matrix of the bone marrow where it promotes tumor growth and metastasis. In the present study we discovered that commonly used anti-myeloma drugs stimulate syndecan-1 shedding both in vitro and in animals bearing myeloma tumors. Enhanced shedding is accompanied by increased syndecan-1 synthesis prior to drug induced tumor cell death. Addition of a caspase inhibitor blocks the drug-induced shedding of syndecan-1 in vitro ind...
Source: Matrix Biology - October 18, 2013 Category: Molecular Biology Authors: Ramani VC, Sanderson RD Tags: Matrix Biol Source Type: research

CD147 regulates the expression of MCT1 and lactate export in multiple myeloma cells.
Abstract Increased use of the glycolytic pathway, even in the presence of oxygen, has recently been recognized as a key characteristic of malignant cells. However, the glycolytic phenotype results in increased lactic acid production and, in order to prevent cellular acidosis tumor cells, must increase proton efflux via upregulation of pH regulators such as proton-pumps, sodium-proton exchangers, and/or monocarboxylate transporters (MCT) (e.g., MCT1, MCT4). Interestingly, expression of MCT1 and MCT4 has been previously shown to be dependent upon expression of the transmembrane glycoprotein CD147. Recently, we demon...
Source: Cell Cycle - September 3, 2013 Category: Cytology Authors: Walters DK, Arendt BK, Jelinek DF Tags: Cell Cycle Source Type: research

Regulation of cellular processes by interleukin‐16 in homeostasis and cancer
This article will review the cellular process for generating IL‐16, the biological activities for both the pro‐ and secreted forms of the protein, and then the mechanism by which these forms contribute to cancer progression. As a soluble cytokine the ability to reduce or eliminate IL‐16 synthesis through siRNA approaches or bioactivity through the use of neutralizing antibody treatment may represent a novel therapeutic approach. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc.
Source: Journal of Cellular Physiology - July 29, 2013 Category: Cytology Authors: Jillian Richmond, Marina Tuzova, William Cruikshank, David Center Tags: Mini‐Review Source Type: research

β‐Caryophyllene oxide Inhibits Constitutive and Inducible STAT3 Signaling Pathway Through Induction of the SHP‐1 Protein Tyrosine Phosphatase
Abstract Constitutive activation of STAT3 is frequently observed and closely linked with proliferation, survival, invasion, metastasis and angiogenesis in tumor cells. In the present study, we investigated whether β‐caryophyllene oxide (CPO), a sesquiterpene isolated primarily from the essential oils of medicinal plants such as guava (Psidium guajava), and oregano (Origanum vulgare L.), can mediate its effect through interference with the STAT3 activation pathway in cancer cells. The effect of CPO on STAT3 activation, associated protein kinases and phosphatase, STAT3‐regulated gene products and apoptosis was investiga...
Source: Molecular Carcinogenesis - June 13, 2013 Category: Molecular Biology Authors: Chulwon Kim, Somi K. Cho, Shweta Kapoor, Ansu Kumar, Shireen Vali, Taher Abbasi, Sung‐Hoon Kim, Gautam Sethi, Kwang Seok Ahn Tags: Research Article Source Type: research

Down-regulation of the cancer/testis antigen 45 (CT45) is associated with altered tumor cell morphology, adhesion and migration
Conclusions: Providing first evidence of a cell biological function of CT45, we suggest that this cancer/testis antigen is involved in the modulation of cell morphology, cell adherence and cell motility. Enhanced motility and/or invasiveness of CT45-positive cells could contribute to the more severe disease progression that is correlated to CT45-positivity in several malignancies.
Source: Cell Communication and Signaling - June 10, 2013 Category: Molecular Biology Authors: Anja KoopNadia SellamiSabine Adam-KlagesMarcus LettauDieter KabelitzOttmar JanssenHans-Jürgen Heidebrecht Source Type: research