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Multiple myeloma

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https://www.readbyqxmd.com/read/28944848/cmip-is-oncogenic-in-human-gastric-cancer-cells
#1
Jianlin Zhang, Jin Huang, Xingyu Wang, Weidong Chen, Qinqing Tang, Maoyong Fang, Yeben Qian
Gastric cancer is one of the most common cancers and the second leading cause of cancer‑associated mortality worldwide. Recurrence, metastasis and resistance to drug treatment are the main barrier to survival of patients with advanced stage gastric cancer. Further study of the molecular mechanisms involved will improve the therapeutic options for gastric cancer. In a previous study, c‑Maf was discovered as an oncogene transduced in the avian AS42 retrovirus, and was found to be overexpressed in multiple myeloma and angioimmunoblastic T‑cell lymphoma...
September 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28943951/recurrent-alterations-of-the-ww-domain-containing-oxidoreductase-gene-spanning-the-common-fragile-site-fra16d-in-multiple-myeloma-and-monoclonal-gammopathy-of-undetermined-significance
#2
Hiroshi Handa, Yoshiko Sasaki, Hikaru Hattori, Lobna Alkebsi, Tetsuhiro Kasamatsu, Takayuki Saitoh, Takeki Mitsui, Akihiko Yokohama, Norifumi Tsukamoto, Morio Matsumoto, Hirokazu Murakami
The putative tumor suppressor gene WW domain containing oxidoreductase (WWOX) spans a common fragile site (CFS) on chromosome 16q23.3. CFSs are regions of profound genomic instability and sites for genomic deletions in cancer cells. Therefore, WWOX is structurally altered in diverse nonhematological cancer types. However, the function of WWOX in hematological tumor types, including multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) remains unclear. WWOX expression and methylation in patients with MM, MGUS, or noninvasive lymphoma (control) were analyzed using reverse transcription- and methylation specific-polymerase chain reaction analysis...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28943924/network-based-analysis-of-the-molecular-mechanisms-of-multiple-myeloma-and-monoclonal-gammopathy-of-undetermined-significance
#3
Zhi Liu, Jing Huang, Qi Zhong, Yanling She, Ruimin Ou, Cheng Li, Rui Chen, Mengdong Yao, Qing Zhang, Shuang Liu
The present study aimed to reveal the molecular mechanisms of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). This was a secondary study on microarray dataset GSE80608, downloaded from the Gene Expression Omnibus database, which included 10 control samples, 10 MGUS samples and 10 MM samples. Differentially expressed genes (DEGs) were identified between control and MGUS samples, and between control and MM samples. A protein-protein interaction (PPI) network was built for studying the interactions between the DEGs...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28943850/withanolide-d-exhibits-similar-cytostatic-effect-in-drug-resistant-and-drug-sensitive-multiple-myeloma-cells
#4
Mark E Issa, E M K Wijeratne, A A L Gunatilaka, Muriel Cuendet
In spite of recent therapeutic advances, multiple myeloma (MM) remains a malignancy with very low curability. This has been partly attributed to the existence of a drug-resistant subpopulation known as cancer stem cells (CSCs). MM-CSCs are equipped with the necessary tools that render them highly resistant to virtually all conventional therapies. In this study, the growth inhibitory effects of withanolide D (WND), a steroidal lactone isolated from Withania somnifera, on drug-sensitive tumoral plasma cells and drug-resistant MM cells have been investigated...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28943545/amyloid-angiopathy-related-severe-hemorrhage-with-multiple-myeloma
#5
Seiichiro Katagiri, Daigo Akahane, Yuko Tanaka, Kazuma Ohyashiki
No abstract text is available yet for this article.
September 25, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28941591/ige-monoclonal-gammopathy-a-case-report-and-literature-review
#6
REVIEW
C Hejl, R Mestiri, T Carmoi, S Bugier, D Chianea, C Renard, P Vest
Immunoglobulin E (IgE) gammopathy is a rare disorder, accounting for just 0.1% of all patients with multiple myeloma (MM). Herein, we report a case of IgE monoclonal gammopathy without any biological and clinical symptoms, and we review 63 published cases in the literature. Demographic, biological and clinical presentations and features appear to be similar to those of other subtypes of MM, with a median age of diagnosis of 67years. There is a slight excess of male patients, and incidence seems to increase with age...
September 20, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/28940410/mechanisms-of-bone-destruction-in-multiple-myeloma
#7
REVIEW
E Terpos, D Christoulas, M Gavriatopoulou, M A Dimopoulos
Osteolytic bone disease is a frequent complication of multiple myeloma, resulting in skeletal complications that are a significant cause of morbidity and mortality. It is the result of an increased activity of osteoclasts, which is not followed by reactive bone formation by osteoblasts. Recent studies have revealed novel molecules and pathways that are implicated in osteoclast activation and osteoblast inhibition. Among them, the most important include the receptor activator of nuclear factor-kappa B ligand/osteoprotegerin pathway, the macrophage inflammatory proteins and the activin-A that play a crucial role in osteoclast stimulation in myeloma, while the wingless-type (Wnt) signalling inhibitors (sclerostin and dickkopf-1) along with the growth factor independence-1 are considered the most important factors for the osteoblast dysfunction of myeloma patients...
September 21, 2017: European Journal of Cancer Care
https://www.readbyqxmd.com/read/28938651/positive-transcription-elongation-factor-b-p-tefb-is-a-therapeutic-target-in-human-multiple-myeloma
#8
Yu Zhang, Liang Zhou, Yun Leng, Yun Dai, Robert Z Orlowski, Steven Grant
The role of the positive RNA Pol II regulator, P-TEFb (positive transcription elongation factor b), in maintenance of the anti-apoptotic protein Mcl-1 and bortezomib (btz) resistance was investigated in human multiple myeloma (MM) cells. Mcl-1 was up-regulated in all MM lines tested, including bortezomib-resistant lines, human MM xenograft mouse models, and primary CD138(+) MM cells. Mcl-1 over-expression significantly reduced bortezomib lethality, indicating a functional role for Mcl-1 in bortezomib resistance...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938542/the-immune-checkpoint-molecule-v-set-ig-domain-containing-4-is-an-independent-prognostic-factor-for-multiple-myeloma
#9
Jin Roh, Youkyoung Jeon, A-Neum Lee, Sang Min Lee, YeonMee Kim, Chang Ohk Sung, Chan-Jeoung Park, Jung Yong Hong, Dok Hyun Yoon, Cheolwon Suh, Jooryung Huh, Inhak Choi, Chan-Sik Park
Multiple myeloma (MM) remains as an incurable disease, despite recent substantial improvements in treatment. Therefore, development of novel biomarkers for risk stratification and new therapeutic targets are imperative. One of the emerging treatments for MM is the immune checkpoint blockades. V-set Ig domain-containing 4 (VSIG4) is a lately studied B7-related immune checkpoint modulator. We assessed the VSIG4 expression in patients with MM and its prognostic impact. We analyzed 81 bone marrow and 66 extramedullary biopsy samples of MM patients using immunohistochemistry...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28937974/high-somatic-mutation-and-neoantigen-burden-are-correlated-with-decreased-progression-free-survival-in-multiple-myeloma
#10
A Miller, Y Asmann, L Cattaneo, E Braggio, J Keats, D Auclair, S Lonial, S J Russell, A K Stewart
Tumor-specific mutations can result in immunogenic neoantigens, both of which have been correlated with responsiveness to immune checkpoint inhibitors in highly mutagenic cancers. However, early results of single-agent checkpoint inhibitors in multiple myeloma (MM) have been underwhelming. Therefore, we sought to understand the relationship between mutation and neoantigen landscape of MM patients and responsiveness to therapies. Somatic mutation burden, neoantigen load, and response to therapy were determined using interim data from the MMRF CoMMpass study (NCT01454297) on 664 MM patients...
September 22, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28937327/carfilzomib-dexamethasone-versus-subcutaneous-or-intravenous-bortezomib-in-relapsed-or-refractory-multiple-myeloma-secondary-analysis-of-the-phase-3-endeavor-study
#11
Hartmut Goldschmidt, Philippe Moreau, Heinz Ludwig, Ruben Niesvizky, Wee-Joo Chng, Douglas Joshua, Katja Weisel, Andrew Spencer, Robert Z Orlowski, Shibao Feng, Karim S Iskander, Meletios A Dimopoulos
This is a secondary analysis of the phase 3 ENDEAVOR study comparing relapsed and/or refractory multiple myeloma (RRMM) patients receiving carfilzomib-dexamethasone (Kd) with those receiving subcutaneous (SC) bortezomib with dexamethasone (Vd) or intravenous (IV) Vd. Of Kd-treated patients, 356 Kd were pre-selected (by physician prior to randomization if to be randomized to Vd) for SC Vd (Kd [SC Vd]) and 108 for IV Vd (Kd [IV Vd], respectively. Of Vd-treated patients, 360 received SC Vd and 75 IV Vd. Kd (SC Vd) median PFS was not reached; SC Vd was 9...
September 22, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28935772/the-european-medicines-agency-review-of-carfilzomib-for-the-treatment-of-adult-patients-with-multiple-myeloma-who-have-received-at-least-one-prior-therapy
#12
Kyriaki Tzogani, Jorge Camarero Jiménez, Isabel Garcia, Arantxa Sancho-López, Marc Martin, Alexandre Moreau, Pierre Demolis, Tomas Salmonson, Jonas Bergh, Edward Laane, Heinz Ludwig, Christian Gisselbrecht, Francesco Pignatti
On November 19, 2015, a marketing authorization valid through the European Union was issued for carfilzomib in combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma (MM) who have received at least one prior therapy.In a phase III trial in patients with relapsed MM, median progression-free survival (PFS) for patients treated with carfilzomib in combination with lenalidomide and dexamethasone (CRd) was 26.3 months versus 17.6 months for those receiving lenalidomide and dexamethasone alone (hazard ratio = 0...
September 21, 2017: Oncologist
https://www.readbyqxmd.com/read/28933784/inhibition-of-the-deubiquitinase-usp5-leads-to-c-maf-protein-degradation-and-myeloma-cell-apoptosis
#13
Siyu Wang, Jiaxiang Juan, Zubin Zhang, Yanyun Du, Yujia Xu, Jiefei Tong, Biyin Cao, Michael F Moran, Yuanying Zeng, Xinliang Mao
The deubiquitinase USP5 stabilizes c-Maf, a key transcription factor in multiple myeloma (MM), but the mechanisms and significance are unclear. In the present study, USP5 was found to interact with c-Maf and prevented it from degradation by decreasing its polyubiquitination level. Specifically, the 308th and 347th lysine residues in c-Maf were critical for USP5-mediated deubiquitination and stability. There are five key domains in the USP5 protein and subsequent studies revealed that the cryptic ZnF domain and the C-box domain interacted with c-Maf but the UBA1/UBA2 domain partly increased its stability...
September 21, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28933361/lysosomal-storage-disorders-and-malignancy
#14
REVIEW
Gregory M Pastores, Derralynn A Hughes
Lysosomal storage disorders (LSDs) are infrequent to rare conditions caused by mutations that lead to a disruption in the usual sequential degradation of macromolecules or their transit within the cell. Gaucher disease (GD), a lipidosis, is among the most common LSD, with an estimated incidence of 1 in 40,000 among the Caucasian, non-Jewish population. Studies have indicated an increased frequency of polyclonal and monoclonal gammopathy among patients with GD. It has been shown that two major sphingolipids that accumulate in GD, namely, β-glucosylceramide 22:0 (βGL1-22) and glucosylsphingosine (LGL1), can be recognized by a distinct subset of CD1d-restricted human and murine type II natural killer T (NKT) cells...
February 27, 2017: Diseases (Basel)
https://www.readbyqxmd.com/read/28933264/from-a-better-understanding-of-the-mechanisms-of-action-of-histone-deacetylases-inhibitors-to-the-progress-of-the-treatment-of-malignant-lymphomas-and-plasma-cell-myeloma
#15
Romeo-Gabriel Mihăilă
BACKGROUND: Notable progress has been made in chemo- and immunotherapy of B-cell lymphomas, but less in the treatment of T-cell lymphomas. OBJECTIVE: Histone deacetylases inhibitors are a potentially useful therapeutic mean, as an epigenetic dysregulation is present in lymphomas, and especially in T-cell types. We aimed to study the progress made in this area. METHOD: A minireview was achieved using the articles published in PubMed in the last two years and the new patents made in this field...
September 19, 2017: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/28932638/the-anti-slamf7-antibody-elotuzumab-mediates-nk-cell-activation-through-both-cd16-dependent-and-independent-mechanisms
#16
Tatiana Pazina, Ashley M James, Alexander W MacFarlane, Natalie A Bezman, Karla A Henning, Christine Bee, Robert F Graziano, Michael D Robbins, Adam D Cohen, Kerry S Campbell
Elotuzumab is a humanized therapeutic monoclonal antibody directed to the surface glycoprotein SLAMF7 (CS1, CRACC, CD319), which is highly expressed on multiple myeloma (MM) tumor cells. Improved clinical outcomes have been observed following treatment of MM patients with elotuzumab in combination with lenalidomide or bortezomib. Previous work showed that elotuzumab stimulates NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC), via Fc-domain engagement with FcγRIIIa (CD16). SLAMF7 is also expressed on NK cells, where it can transmit stimulatory signals...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932581/catch-me-if-you-can-how-to-make-the-best-use-of-pleural-effusion
#17
Lianjun Lin, Qian Han, Zhonghui Liu, Huiying Xu, Yanping Wu, Jixin Zhang, Xinmin Liu
Etiology diagnosis of pleural effusion is a commonly encountered yet challenging problem. How to make the best use of pleural effusion evokes thinking. Myelomatous pleural effusion (MPE) is a rare condition and has been reported sporadically. We report an extremely rare case of multiple myeloma (MM) [IgD-lambda (λ) type, stage III B] with MPE as initial presentation and complicated with massive pericardial effusions during the progression of the disease. Cytological identification of malignant plasma cells in pleural effusion is the most direct method to diagnose MPE...
August 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28931820/the-non-canonical-poly-a-polymerase-fam46c-acts-as-an-onco-suppressor-in-multiple-myeloma
#18
Seweryn Mroczek, Justyna Chlebowska, Tomasz M Kuliński, Olga Gewartowska, Jakub Gruchota, Dominik Cysewski, Vladyslava Liudkovska, Ewa Borsuk, Dominika Nowis, Andrzej Dziembowski
FAM46C is one of the most frequently mutated genes in multiple myeloma. Here, using a combination of in vitro and in vivo approaches, we demonstrate that FAM46C encodes an active non-canonical poly(A) polymerase which enhances mRNA stability and gene expression. Reintroduction of active FAM46C into multiple myeloma cell lines, but not its catalytically-inactive mutant, leads to broad polyadenylation and stabilization of mRNAs strongly enriched with those encoding endoplasmic reticulum-targeted proteins and induces cell death...
September 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28930776/a-phase1b-dose-escalation-study-of-recombinant-circularly-permuted-trail-in-patients-with-relapsed-or-refractory-multiple-myeloma
#19
Jian Hou, Lugui Qiu, Yaozhong Zhao, Xuejun Zhang, Yan Liu, Zhao Wang, Fang Zhou, Yun Leng, Shifang Yang, Hao Xi, Fuxu Wang, Bing Zhu, Wenming Chen, Peng Wei, Xiangjun Zheng
OBJECTIVES: Circularly permuted tumor necrosis factor-related apoptosis-inducing ligand (CPT), or CPT, is a novel antitumor drug candidate. This phase 1b study evaluated the safety, tolerability, pharmacokinetics (PK), and efficacy of single-agent CPT in patients with relapsed or refractory multiple myeloma (RRMM), and aimed to identify the recommended dose for the phase 2 study. MATERIALS AND METHODS: Patients received single or multiple doses (once daily for 5 consecutive days per 21-d cycle) of CPT intravenous infusion at doses of 5, 6...
September 19, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28928810/characteristics-of-baff-and-april-factor-expression-in-multiple-myeloma-and-clinical-significance
#20
Jing Pan, Yuanyuan Sun, Ning Zhang, Jianming Li, Fangxin Ta, Wei Wei, Shanshan Yu, Limei Ai
The characteristics of the proliferation of B-cell activating factor (BAFF) and the proliferation-inducing ligand (APRIL) mRNA expression in mononuclear cell in multiple myeloma patients were detected, and the correlation was analyzed between the BAFF and APRIL concentrations in plasma and tumor burden parameters of multiple myeloma. Bone marrow samples from 60 patients with multiple myeloma and 20 healthy persons taken as controls, were collected. Bone marrow mononuclear cells (BMMCs) were harvested, and plasma was extracted...
September 2017: Oncology Letters
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