Morio Matsumoto, Kenshi Suzuki, Junya Kuroda, Masafumi Taniwaki, Kazutaka Sunami, Hiroshi Kosugi, Kiyoshi Ando, Dai Maruyama, Kensei Tobinai, Uma Kher, Mohammed Farooqui, Jason Liao, Patricia Marinello, Kenji Matsuda, Yasuhiro Koh, Takashi Shimamoto, Shinsuke Iida
The global, randomized, open-label KEYNOTE-183 phase 3 study was closed early after an interim analysis showed unfavorable risk-benefit when pembrolizumab was added to pomalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma (MM). This subgroup analysis reported outcomes in 27 Japanese patients randomly assigned to receive pembrolizumab plus pomalidomide and dexamethasone (n = 15) or pomalidomide and dexamethasone alone (n = 12). Co-primary endpoints were progression-free survival (PFS) and overall survival (OS)...
April 15, 2021: International Journal of Hematology
A Russell Moore, R Adam Harris, Christina Jeffries, Laura Ashton, Paul R Avery
BACKGROUND: The diagnostic performance of routine electrophoresis (agarose gel electrophoresis [AGE] and capillary zone electrophoresis [CZE]) and species-specific immunofixation (IF) for the detection of immunoglobulin paraproteins (M-proteins) and diagnosis of secretory myeloma-related disorders (sMRD) can be improved. Available canine IF targets were IgG-FC, IgA, IgM, light chain (LC), IgG4, and free LC (fLC) antibodies. OBJECTIVE: We aimed to review specific features associated with the presence of M-proteins in canine serum samples and the common features causing inaccurate reporting of M-proteins to improve the diagnostic performance of routine electrophoresis and IF for the detection of M-proteins...
April 14, 2021: Veterinary Clinical Pathology
Zhongqing Zou, Tingting Guo, Jian Cui, Wenjiao Tang, Yan Li, Fangfang Wang, Tian Dong, Yunfan Yang, Yan Feng, Matthew Ho, Li Zhang, Ling Pan, Ting Niu
Multiple myeloma (MM) is a heterogeneous disease that remains incurable with significant interpatient variability in outcomes. Regulatory B cells (Bregs) were observed to be involved into specific defects in MM. Here, we provide our risk-adapted approach to newly diagnosed MM (NDMM), combining with the fundamental dysfunction of Bregs. We reported one hundred consecutive patients with NDMM from South-Western China, primarily treated with bortezomib plus dexamethasone with or without a 3rd agent, were enrolled from 2017...
2021: Journal of Cancer
Yixin Wang, Jing Xiu, Chune Ren, Zhenhai Yu
PIM2 (proviral integration site for Moloney murine leukemia virus 2) kinase plays an important role as an oncogene in multiple cancers, such as leukemia, liver, lung, myeloma, prostate and breast cancers. PIM2 is largely expressed in both leukemia and solid tumors, and it promotes the transcriptional activation of genes involved in cell survival, cell proliferation, and cell-cycle progression. Many tumorigenic signaling molecules have been identified as substrates for PIM2 kinase, and a variety of inhibitors have been developed for its kinase activity, including SMI-4a, SMI-16a, SGI-1776, JP11646 and DHPCC-9...
2021: Journal of Cancer
Ji Young Lee, Daeun Ryu, Sung Won Lim, Kyung Ju Ryu, Myung Eun Choi, Sang Eun Yoon, Kihyun Kim, Chaehwa Park, Seok Jin Kim
Background: Exosomes have emerged as important mediators of tumor progression, and a prognostic role for serum exosomal miRNAs has been suggested in multiple myeloma (MM). Given the association of hypoxia with tumor aggressiveness, including cancer stem cell-like phenotypes, we explored exosomal miRNAs from MM cells under hypoxic conditions and analyzed their diverse roles both in promoting oncogenic activity and in predicting prognosis. Methods: The human MM cell line, RPMI 8226, was cultured under hypoxic conditions and their exosome production and exosomal miRNA profiles were compared with those of normoxic parental cells...
2021: Journal of Cancer
Kelsey B Nusbaum, Abraham M Korman, Kelly H Tyler, Jessica A Kaffenberger, John C Trinidad, Steven Dean, Spero Cataland, Benjamin H Kaffenberger
The skin often provides initial clues of hypercoagulability with features such as livedo reticularis and racemosa, retiform purpura, necrosis and ulcerations. As these cutaneous manifestations are nonspecific, laboratory testing is often needed to evaluate for underlying causes of hypercoagulability. Importantly, these disorders are reported to be the most common mimicker resulting in erroneous diagnosis of pyoderma gangrenosum. Understanding inherent properties of and indications for available tests is necessary for appropriate ordering and interpretation of results...
April 11, 2021: Journal of the American Academy of Dermatology
Lorenzo D'Elia, Antonella Barreca, Martina Ferraresi, Antonio Marciello, Antonietta Rizzuto, Luisa Sandri, Paolo Maurizio Perosa
Multiple myeloma represents one of the main universal oncological diseases. Due to its clinical characteristics, it is often diagnosed only too late, when it has already determined systemic effects; this results in greater therapeutic difficulty and worse prognostic results. Through the clinical case discussed in this article, we want to focus on the often aspecific manifestations of this pathology and on the need for a correct clinical and diagnostic framework. The main renal manifestations secondary to the deposition of immunoglobulins in both the glomerular and tubular areas will also be examined...
April 14, 2021: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
Viral Bhanvadia, Tanuja Shet, Vidya Rao, Sridhar Epari, Sumeet Gujral, Hasmukh Jain, Bhausaheb Bagal, Manju Sengar
Background and Aim: Multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder manifesting as multiple lymphadenopathy, multiorgan involvement, and inflammatory symptoms. This study aims at highlighting some unique features of MCD in Indian patients. Materials and Methods: These 17 patients from review of 78 cases of Castleman's disease (CD) diagnosed. Besides routine tissue sections were stained for Human Herpes Virus 8 latency associated nuclear antigen (HHV8-LANA) by immunohistochemistry (IHC) and Epstein Barr virus latent membrane protein (EBV-LMP) or Epstein Barr Virus by in situ hybridization (EBER-ISH)...
April 2021: Indian Journal of Pathology & Microbiology
Priyanka Maity, Saugat Dasgupta, Keya Basu, Moumita Sengupta, Arpita Roy Chowdhury, Manimoy Bandopadhyay
Background: Proliferative glomerulonephritis with monoclonal immunoglobulin deposit (PGNMID) is an entity with a variable clinical and histological spectrum, which mimics immune-complex mediated glomerulonephritis on light microscopy. In this article, we aim to describe the clinical and pathological features of six cases of PGNMID that we encountered during our routine practice. Materials and Methods: The study was of the prospective type carried out from February 2018 to August 2019...
April 2021: Indian Journal of Pathology & Microbiology
Phuong Nhat Nguyen, Ngoc T B Tran, Truong P X Nguyen, Tam N M Ngo, Doan Van Lai, Chelsey D Deel, Lewis A Hassell, Huy Gia Vuong
BACKGROUND: Studies have recently shown that RHOA mutations play a crucial role in angioimmunoblastic T-cell lymphoma (AITL) pathogenesis. We aimed to pool data from these studies to provide a comparison of clinicopathological features between the RHOA mutant and RHOA wild-type groups in the AITL population. METHODS: We searched PubMed and Web of Science for the keywords "RHOA AND lymphoma" and selected only studies reporting the clinical significance of RHOA mutations in AITL...
March 19, 2021: Clinical Lymphoma, Myeloma & Leukemia
Juncheng He, Qifeng Zhou, Xianchao Jia, Peng Zhou, Lin Chen
Objective: To investigate the immune cellular and genomic profiles of bisphosphonates-related osteonecrosis (BRONJ) of the jaw and excavate potential small molecule drugs. Methods and materials: The genomic profile of a multiple myeloma (MM) patient with BRONJ was downloaded from Gene Expression Omnibus (GEO). The 22 immune cell subsets infiltration in the patient were predicted by cell-type identification by estimating relative subsets of RNA transcripts. In addition, the differently expressed immune-related genes (DEMGs) of BRONJ were identified, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses for functional annotation...
April 1, 2021: Die Pharmazie
Xiangyu Tian, Miaomiao Sun, Han Wu, Chao Chen, Hui Li, Sen Qiu, Tong Wang, Junya Han, Qiankun Xiao, Kuisheng Chen
Angiogenesis is an integral part of the multiple myeloma (MM) microenvironment, and affects tumorigenesis, progression, invasion, and metastasis. Exosomes are essential for cell-cell communication and help in regulating the bone marrow microenvironment. Herein, we investigated macrophage polarization and angiogenesis in MM in vitro via exosome-derived miR-let-7c. We observed that exosomal miR-let-7c secreted by mesenchymal stem cells promoted M2 macrophage polarization, thereby enhancing angiogenesis in the bone marrow microenvironment...
March 31, 2021: Leukemia Research
Tanya R Porras-Yakushi, Justin M Reitsma, Michael J Sweredoski, Raymond J Deshaies, Sonja Hess
Proteasome inhibitors are an important class of chemotherapeutic drugs. In this study, we performed a large-scale ubiquitylome analysis of the three proteasome inhibitors MG132, bortezomib and carfilzomib. Although carfilzomib is currently being used for the treatment of multiple myeloma, it has not yet been subjected to a global ubiquitylome analysis. In this study, we identified more than 14,000 unique sites of ubiquitylation in more than 4400 protein groups. We introduced stringent criteria to determine the correct ubiquitylation site ratios and used five biological replicates to achieve increased statistical power...
April 10, 2021: Journal of Proteomics
Osman Mert Topkar, Bülent Erol
OBJECTIVE: This study aimed to assess the pain and functional status of patients who underwent various surgical interventions for the stabilization of selected multiple myeloma (MM) lesions in the extremities and pelvis and to investigate the rate of complications requiring reintervention. METHODS: Patients with MM who underwent various surgical interventions for the extremity or pelvic lesions were retrospectively reviewed. Change in the pain intensity was assessed using visual analogous scale (VAS) preoperatively, at the time of discharge, and at the final follow-up...
March 2021: Acta Orthopaedica et Traumatologica Turcica
A Russell Moore, R Adam Harris, Christina Jeffries, Laura Ashton, Paul R Avery
BACKGROUND: Routine electrophoresis [agarose gel electrophoresis (AGE) and capillary zone electrophoresis (CZE)] and species-specific immunofixation (IF) can be used alone or in combination to detect immunoglobulin paraprotein (M-protein) and diagnose secretory myeloma-related disorders (sMRD). OBJECTIVE: We aimed to evaluate the performance of AGE, CZE, CZE plus IF (CZE-IF), and AGE plus IF (AGE-IF) for detecting canine serum M-proteins. METHODS: One hundred canine cases that had AGE, CZE, and routine IF performed on serum, and where B-cell lineage neoplasia (such as B-cell lymphoma and plasma cell tumors) had been diagnosed or excluded, were evaluated...
April 13, 2021: Veterinary Clinical Pathology
Soon Kyu Lee, Pil Soo Sung, Sung-Soo Park, Chang-Ki Min, Heechul Nam, Jeong Won Jang, Jong Young Choi, Seung Kew Yoon
The risk of reactivation of resolved HBV in HBsAg-negative multiple myeloma patients after daratumumab has not been reported. Among 93 patients with daratumumab treatment, reactivation occurred in 6 patients (6.5%) with one hepatic failure. This is the first report demonstrating a considerable risk of reactivation of resolved HBV after daratumumab.
April 13, 2021: Clinical Infectious Diseases
Sabrina Prommersberger, Michael Reiser, Julia Beckmann, Sophia Danhof, Maximilian Amberger, Patricia Quade-Lyssy, Hermann Einsele, Michael Hudecek, Halvard Bonig, Zoltán Ivics
Clinical development of chimeric antigen receptor (CAR)-T-cell therapy has been enabled by advances in synthetic biology, genetic engineering, clinical-grade manufacturing, and complex logistics to distribute the drug product to treatment sites. A key ambition of the CARAMBA project is to provide clinical proof-of-concept for virus-free CAR gene transfer using advanced Sleeping Beauty (SB) transposon technology. SB transposition in CAR-T engineering is attractive due to the high rate of stable CAR gene transfer enabled by optimized hyperactive SB100X transposase and transposon combinations, encoded by mRNA and minicircle DNA, respectively, as preferred vector embodiments...
April 13, 2021: Gene Therapy
Azka Latif, Vikas Kapoor, Noman Lateef, Muhammad Junaid Ahsan, Rana Mohammad Usman, Saad Ullah Malik, Naqib Ahmad, Nathaniel Rosko, Joslyn Rudoni, Preethi William, Jack Khouri, Faiz Anwer
BACKGROUND: The ASPIRE and ENDEAVOUR trials have shown cardiovascular adverse effects in patients treated with carfilzomib-based regimens. Therefore, we conducted this meta-analysis of published clinical trials to identify the cumulative incidence and risk of cardiovascular adverse effects due to carfilzomib. METHODS: A systematic search of PubMed, Embase, Web of Science, and Cochrane library was performed, and we identified 45 prospective trials of carfilzomib with data on 5583 patients...
April 11, 2021: Cardiovascular & Hematological Disorders Drug Targets
Carlo Sozzi, Mirko Trentadue, Lisa Nicolì, Federica Tavani, Enrico Piovan
PURPOSE: To demonstrate the utility of a biopsy performed just before vertebroplasty in patients with diagnosis of vertebral compression fracture (VCF) and no history of neoplastic or hematologic diseases. BACKGROUND: Osteoporosis is the most frequent cause of vertebral compression fracture, with trauma and pathologic vertebral weakening being other common causes. Since secondary fractures at imaging investigation can present as simple compression fractures, it is important to identify an underlying pathology...
April 12, 2021: La Radiologia Medica
Vasileios Lazaris, Aikaterini Hatziri, Argiris Symeonidis, Kyriakos E Kypreos
Multiple myeloma (MM) is an incurable neoplastic hematologic disorder characterized by malignant plasma cells, mainly in the bone marrow. MM is associated with multiple factors, such as lipid metabolism, obesity, and age-associated disease development. Although, the precise pathogenetic mechanisms remain unknown, abnormal lipid and lipoprotein levels have been reported in patients with MM. Interestingly, patients with higher APOA1 levels, the major apolipoprotein of high density lipoprotein (HDL), have better overall survival...
2021: Frontiers in Oncology
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