Zhengzhi Liu, Zhongnan Xu, Zhenyue Gao, Qing Ren, Tianying Chang, Jinling Xue, Haimiao Yang
OBJECTIVE: Imnovid® is an immunomodulatory drug with antineoplastic activity. The aim of this study was to evaluate the bioequivalence and safety of the generic drug pomalidomide (Chia Tai Tianqing Pharmaceutical Group Co., Ltd) and its originator product Imnovid® (Celgene Europe Ltd) in the fasting and fed states, respectively. METHODS: The research consisted of two parts: one with a dose of 1 mg and the other with a dose of 4 mg. 48 healthy subjects were included in each study and were divided into two groups (fasting group and fed group) at a 1:1 ratio to administrate study drugs orally...
November 28, 2022: Investigational New Drugs
Limei Zhang, Shuzhao Chen, Mayan Huang, Weida Wang, Yang Liang, Yun Wang
The nutritional risk index (NRI), which is based on weight and albumin levels, is closely associated with the prognosis of many cancers. However, its prognostic value has not been investigated in patients with newly diagnosed multiple myeloma (NDMM). We aimed to assess the association between the NRI and survival outcomes in patients with NDMM. We retrospectively collected and analyzed clinical and laboratory data from patients with NDMM between 2005 and 2019 at our center. Patients were stratified into the high NRI (> 89) and low NRI (≤ 89) groups for prognostic analysis...
November 28, 2022: Annals of Hematology
Dipti Talaulikar, D Joshua, P J Ho, J Gibson, H Quach, S Gibbs, S Ling, C Ward, B Augustson, Judith Trotman, S J Harrison, Constantine S Tam
Waldenström Macroglobulinaemia (WM) is an indolent B-cell malignancy characterised by the presence of IgM paraprotein, bone marrow infiltration by clonal small B lymphocytes with plasmacytic differentiation, and the MYD88 L265P mutation in >90% of cases. Traditionally, WM has been treated with chemoimmunotherapy. Recent trials have demonstrated the efficacy and safety of Bruton's Tyrosine Kinase inhibitors (BTKi) in WM, both as monotherapy and in combination with other drugs. There is emerging evidence on use of other agents including BCL2 inhibitors and on treatment of rare presentations of WM...
November 28, 2022: Internal Medicine Journal
K C Eseonu, J R Panchmatia, Matthew J Streetly, Jonathan N Grauer, B Fakouri
BACKGROUND CONTEXT: Multiple myeloma (MM) is a systemic disorder characterised by proliferation of B-lymphocytes and plasma cells in the bone marrow. The primary aims of the management of spinal lesions in MM are pain control and fracture stabilisation. PURPOSE/METHODS: Vertebral augmentation procedures (VAP) can be subdivided into percutaneous vertebroplasty (VP) and balloon kyphoplasty (BKP). BKP involves the placement of orthopaedic balloons into the fractured vertebral body, creating a void into which polymethylmethacrylate bone cement is injected...
November 28, 2022: Hematological Oncology
Yinhuan Ding, Jingchen Hao, Zhangrui Zeng, Jinbo Liu
Vibrio cholerae is a bacterium ubiquitous in aquatic environments which can cause widespread infection worldwide. V. cholerae gradually became a rare species of bacteria in clinical microbiology laboratories with the control of the cholera epidemic. In this study, we isolated a V. cholerae strain, named VCHL017, from the blood of an elderly patient without gastrointestinal symptoms. The patient had a history of hookworm infection and multiple myeloma. Furthermore, she was immunocompromised, and received long-term chemotherapy and antimicrobial agents...
November 2022: Heliyon
Lucia Y Chen, Sarah Gooding
Resistance to immunomodulatory drugs (IMiDs® ) is a major cause of treatment failure, disease relapse and ultimately poorer outcomes in multiple myeloma (MM). In order to optimally deploy IMiDs and their newer derivates CRBN E3 ligase modulators (CELMoDs® ) into future myeloma therapeutic regimens, it is imperative to understand the mechanisms behind the inevitable emergence of IMiD resistance. IMiDs bind and modulate Cereblon (CRBN), the substrate receptor of the CUL4CRBN E3 ubiquitin ligase, to target novel substrate proteins for ubiquitination and degradation...
2022: Frontiers in Oncology
Shuxin Huang, Yujie Zhao, Pengjun Liao, Jinghua Wang, Zhiyan Li, Jiaxiong Tan, Xianfeng Zha, Shaohua Chen, Yangqiu Li, Liye Zhong
V-type immunoglobulin domain-containing suppressor of T cell activation (VISTA) is considered as an immunosuppressive factor and potential therapeutic target for anticancer therapy. However, little is known about VISTA expression and its role in immunosuppression in multiple myeloma (MM). In this study, VISTA expression and co-expression with programmed cell death receptor-1 (PD-1), T cell immunoglobulin mucin-domain-containing-3 (Tim-3), and T cell immunoglobulin and ITIM domain (TIGIT) in CD3+, CD4+, CD8+, and regulatory T (Treg) cells were analyzed in patients with MM by multi-color fluorescent flow cytometry of peripheral blood (PB) and bone marrow (BM) samples from 36 patients with MM and compared to 36 PB samples and 10 BM samples from healthy individuals (HIs), which served as controls...
2022: Frontiers in Oncology
Stephanos Vassilopoulos, Athanasios Vassilopoulos, Markos Kalligeros, Fadi Shehadeh, Eleftherios Mylonakis
BACKGROUND: Patients with multiple myeloma are at higher risk for infections due to disease pathogenesis and administered therapies. The purpose of this study was to estimate the risk for any grade and severe infections associated with the use of anti-CD38 monoclonal antibodies in patients with multiple myeloma. METHODS: We searched PubMed and EMBASE for randomized controlled trials (RCTs) that included patients with multiple myeloma who received CD38-targeting monoclonal antibody regimens and reported outcomes of infection and performed a random-effects meta-analysis to estimate the relative risk for infections...
November 2022: Open Forum Infectious Diseases
T V Tyrinova, E V Batorov, T A Aristova, G Yu Ushakova, S A Sizikova, V V Denisova, A A Ostanin, E R Chernykh
We studied suppressor potential of myeloid-derived suppressor cells (MDSC) in multiple myeloma patients, including before and after mobilization of hematopoietic stem cells (HSC), by evaluating the expression of arginase-1 (Arg1), indolamine-2,3-dioxygenase (IDO), and PD-L1 in MDSC subsets. The study included 20 multiple myeloma patients in remission, 5 patients with progression, as well as 10 sex-and age-matched healthy donors. The expression of Arg1, IDO, and PD-L1 in circulating granulocytic MDSC (G-MDSC, Lin- HLA-DR- CD33+ CD66b+ ), monocytic MDSC (M-MDSC, CD14+ HLA-DRlow/- ), and early-stage MDSC (E-MDSC, Lin- HLA-DR- CD33+ CD66b- ) was evaluated by flow cytometry...
November 28, 2022: Bulletin of Experimental Biology and Medicine
Amro Elshoury, Orla Maguire, Alexis Conway, Joseph Tario, Kah Teong Soh, Maureen Ross, Theresa Hahn, Joanne Becker, Paul Wallace, Philip L McCarthy, Hans Minderman, George L Chen
BACKGROUND: Hypoxic conditions preserve the multipotency and self-renewing capacity of murine bone marrow and human cord blood stem cells. Blood samples stored in sealed blood gas tubes become hypoxic as leukocytes metabolize and consume oxygen. Taken together, these observations suggest that peripheral blood stem cell samples stored under airtight conditions become hypoxic and that the stem cells contained may undergo qualitative or quantitative changes. OBJECTIVES: To determine the effect of storage for 8 hours in a sealed system on peripheral blood stem cell samples...
November 24, 2022: Transplantation and cellular therapy
Erling Håland, Ingrid Nyhus Moen, Esten N Vandsemb, Kristian K Starheim
OBJECTIVE: Multiple myeloma is a haematological malignancy characterized by proliferation of monoclonal plasma cells in the bone marrow. Development of resistance and minimal residual disease remain challenging in the treatment of multiple myeloma. Transforming growth factor-β activated kinase 1 (TAK1) has recently gained attention as a potential drug target in multiple myeloma. This study aimed at determining the in vivo effects of TAK1-inhibitors in a Vκ*MYC multiple myeloma mouse model...
November 26, 2022: BMC Research Notes
Kazutaka Sunami, Shin-Ichi Fuchida, Kenshi Suzuki, Masaki Ri, Morio Matsumoto, Chihiro Shimazaki, Hideki Asaoku, Hirohiko Shibayama, Kenichi Ishizawa, Hiroyuki Takamatsu, Takashi Ikeda, Dai Maruyama, Kazunori Imada, Michihiro Uchiyama, Toru Kiguchi, Satoshi Iyama, Hirokazu Murakami, Reiko Onishi, Keisuke Tada, Shinsuke Iida
The primary analysis of the phase 1/2 ISLANDs study in Japanese individuals with relapsed/refractory multiple myeloma (RRMM) showed that isatuximab monotherapy was well tolerated and effective, even in participants with high-risk cytogenetic abnormalities. Here, we report a prespecified second analysis conducted 20 months after the first dosing of the last participant ( identifier: NCT02812706). The primary objectives were to evaluate the safety and tolerability of isatuximab in phase 1 and to evaluate the efficacy of isatuximab, including assessment of overall response rate (ORR) at the recommended dose (RD), in phase 2...
November 26, 2022: Hematological Oncology
Patrick René Gerhard Eriksen, Elham Khakbaz, Erik Clasen-Linde, Peter de Nully Brown, Laura Haunstrup, Mette Christoffersen, Peter Asdahl, Troels Møller Thomsen, Jonas Gerner-Rasmussen, Steffen Heegaard, Christian von Buchwald
OBJECTIVES: Extraosseous plasmacytoma (EOP) is a rare plasma cell neoplasm that tends to convert to plasma cell myeloma (PCM) in about 11% to 35% of cases. It has a predilection for the upper respiratory tract, prototypically affecting the nasal cavity and paranasal sinuses. Contemporary first-line treatment is radiotherapy, with more recent studies showing an added benefit of combining radiation with surgery. In this cohort study, we aimed to examine clinical presentation, treatment, and prognosis for all patients nationwide from 1980 through 2017...
November 26, 2022: Annals of Otology, Rhinology, and Laryngology
Maurus Locher, Emina Jukic, Verena Vogi, Markus A Keller, Teresa Kröll, Simon Schwendinger, Klaus Oberhuber, Irmgard Verdorfer, Beatrix E Mühlegger, Martina Witsch-Baumgartner, David Nachbaur, Wolfgang Willenbacher, Eberhard Gunsilius, Dominik Wolf, Johannes Zschocke, Normann Steiner
Long-term disease control in multiple myeloma (MM) is typically an unmet medical need, and most patients experience multiple relapses. Fluorescence in situ hybridization (FISH) is the standard technique to detect chromosomal abnormalities (CAs), which are important to estimate the prognosis of MM and the allocation of risk adapted therapies. In advanced stages, the importance of CAs needs further investigation. From 148 MM patients, two or more paired samples, at least one of which was collected at relapse, were analyzed by FISH...
November 26, 2022: European Journal of Haematology
Gwendolyn N Y van Gorkom, Lara S Boerenkamp, Birgit L M G Gijsbers, Heidi H van Ojik, Will K W H Wodzig, Lotte Wieten, Catharina H M J Van Elssen, Gerard M J Bos
Vitamin C is an important micronutrient for various immune cells. It increases phagocytic cell function and is necessary for T and natural killer (NK) cell development. Patients in need of an autologous hematopoietic stem cell transplantation (HSCT) are often vitamin C-depleted. We therefore hypothesized that vitamin C supplementation could improve immune recovery in autologous HSCT patients. This blinded, placebo-controlled trial included 44 patients randomized to receive vitamin C or a placebo. The following outcome measures used were clinical and immunological parameters, among others: time to neutrophil recovery, serum, and intracellular vitamin C values...
November 11, 2022: Nutrients
Anastazja Poczta, Piotr Krzeczyński, Maksim Ionov, Aneta Rogalska, Udo S Gaipl, Agnieszka Marczak, Dorota Lubgan
Myeloablative therapy with highdoses of the cytostatic drug melphalan (MEL) in preparation for hematopoietic cell transplantation is the standard of care for multiple myeloma (MM) patients. Melphalan is a bifunctional alkylating agent that covalently binds to nucleophilic sites in the DNA and effective in the treatment, but unfortunately has limited therapeutic benefit. Therefore, new approaches are urgently needed for patients who are resistant to existing standard treatment with MEL. Regulating the pharmacological activity of drug molecules by modifying their structure is one method for improving their effectiveness...
November 17, 2022: International Journal of Molecular Sciences
Karin Jöhrer, Mayra Galarza Pérez, Brigitte Kircher, Serhat Sezai Çiçek
Phenolic plant constituents are well known for their health-promoting and cancer chemopreventive properties, and products containing such constituents are therefore readily consumed. In the present work, we isolated 13 phenolic constituents of four different compound classes from the aerial parts of the Moldavian dragonhead, an aromatic and medicinal plant with a high diversity on secondary metabolites. All compounds were tested for their apoptotic effect on myeloma (KMS-12-PE) and AML (Molm-13) cells, with the highest activity observed for the flavone and flavonol derivatives...
November 17, 2022: International Journal of Molecular Sciences
Rui Bergantim, Sara Peixoto da Silva, Bárbara Polónia, Mélanie A G Barbosa, André Albergaria, Jorge Lima, Hugo R Caires, José E Guimarães, M Helena Vasconcelos
Monitoring measurable residual disease (MRD) is crucial to assess treatment response in Multiple Myeloma (MM). Detection of MRD in peripheral blood (PB) by exploring Extracellular Vesicles (EVs), and their cargo, would allow frequent and minimally invasive monitoring of MM. This work aims to detect biomarkers of MRD in EVs isolated from MM patient samples at diagnosis and remission and compare the MRD-associated content between BM and PB EVs. EVs were isolated by size-exclusion chromatography, concentrated by ultrafiltration, and characterized according to their size and concentration, morphology, protein concentration, and the presence of EV-associated protein markers...
November 8, 2022: International Journal of Molecular Sciences
Chengcheng Liao, Srikanth Talluri, Jiangning Zhao, Shidai Mu, Subodh Kumar, Jialan Shi, Leutz Buon, Nikhil C Munshi, Masood A Shammas
BACKGROUND: In normal cells, homologous recombination (HR) is tightly regulated and plays an important role in the maintenance of genomic integrity and stability through precise repair of DNA damage. RAD51 is a recombinase that mediates homologous base pairing and strand exchange during DNA repair by HR. Our previous data in multiple myeloma and esophageal adenocarcinoma (EAC) show that dysregulated HR mediates genomic instability. Purpose of this study was to investigate role of HR in genomic instability, chemoresistance and immune dysregulation in solid tumors including colon and breast cancers...
November 20, 2022: Cancers
Samuel S Y Wang, Wee Joo Chng, Haiyan Liu, Sanjay de Mel
Multiple myeloma (MM) is the second-most common hematologic malignancy and remains incurable despite potent plasma cell directed therapeutics. The tumor microenvironment (TME) is a key player in the pathogenesis and progression of MM and is an active focus of research with a view to targeting immune dysregulation. Tumor-associated macrophages (TAM), myeloid derived suppressor cells (MDSC), and dendritic cells (DC) are known to drive progression and treatment resistance in many cancers. They have also been shown to promote MM progression and immune suppression in vitro, and there is growing evidence of their impact on clinical outcomes...
November 17, 2022: Cancers
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