scholarly journals Identification and expression of MMSA-8, and its clinical significance in multiple myeloma

2017 ◽  
Vol 37 (6) ◽  
pp. 3235-3243 ◽  
Author(s):  
Rui He ◽  
Nan Yang ◽  
Pengyu Zhang ◽  
Jie Liu ◽  
Junhui Li ◽  
...  
Inflammation ◽  
2014 ◽  
Vol 38 (2) ◽  
pp. 705-709 ◽  
Author(s):  
Ping Feng ◽  
Ruhong Yan ◽  
Xiaoli Dai ◽  
Xiaofang Xie ◽  
Huiyan Wen ◽  
...  

Cancer ◽  
2002 ◽  
Vol 94 (8) ◽  
pp. 2232-2238 ◽  
Author(s):  
Motoaki Shiratsuchi ◽  
Koichiro Muta ◽  
Yasunobu Abe ◽  
Seiichi Motomura ◽  
Fumihiro Taguchi ◽  
...  

2007 ◽  
Vol 27 (6) ◽  
pp. 400-405 ◽  
Author(s):  
So Young Kang ◽  
Jae Jin Lee ◽  
Woo In Lee

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3086-3086
Author(s):  
Ruyi Xu ◽  
Yi Li ◽  
Haimeng Yan ◽  
Xi Huang ◽  
He Huang ◽  
...  

Background: Despite with the introduction of novel chemotherapy agents to multiple myeloma (MM), chemoresistance remains the major problem in clinical management. The interaction of MM cells with different cell components in the tumor microenvironment is important for tumor growth and chemoresistance, in which macrophages (Mφs) represent the prominent components. Mφs, who provide a favorable microenvironment for MM cells, protect them from drug-induced apoptosis. Mφs have great plasticity and can differentiate into different functional states according to microenvironmental signals. We previously found that the chemokine CCL2 is overexpressed in MM patients and CCL2 promoted Mφs'infiltration in the MM-BM microenvironment. The present study aims to further investigate the clinical significance of CCL2 and elucidate the mechanism how it participates in Mφs-mediated MM chemoresistance. Methods: Clinical significance of CCL2 were investigated by immunohistochemistry and Elisa. Flow cytometry, quantitative real-time PCR and Western blotting were conducted to evaluated the apoptosis of MM cells and Mφs' polarization. RNA sequencing was performed to determine the key molecular induced by CCL2 in Mφs. Genetically modified cells (e.g., exhibiting siRNA knockdown, generating deletion mutants through lentiviruses) were employed to evaluate the functional significance of MCPIP1. Proteome Profiler Human phosphor-kinase antibody array was used to determine the changes of protein phosphorylation in Mφs caused by CCL2. MM xenograft models were used to evaluated the role of CCL2 and MCPIP1 in vivo. Results: We found that CCL2 expression is tightly associated with MM patients' treatment status. When newly diagnosed patients received 4 courses of PCD combined therapy, CCL2 expression in their BM significantly decreased. MM cell lines and PBMCs barely expressed CCL2, while Mφs highly expressed CCL2. Mφs interacted with MM cells further upregulated their expression of CCL2. These increased CCL2 in the MM' BM microenvironment had little effect on MM cells' proliferation and their drug responses, but CCL2-treated Mφs were more effective at protecting MM cells from bortezomib- and melphalan- induced apoptosis. CCL2 could also effectively polarize Mφs toward M2-like Mφs, which possess a stronger ability to protect MM cells from chemotherapy drug-induced apoptosis. RNA sequencing revealed that CCL2 significantly induced the immunosuppressive molecular MCP-1-induced protein (MCPIP1) in Mφs and the result was verified both in mRNA and protein level. MM cells cocultured with MCPIP1-knock down Mφs were more sensitive to drug-induced apoptosis than those cocultured with control Mφs. Mφs transfected with D141N mutant MCPIP1 lost their protective effects because the mutation resulted in impaired RNase and DUB activities of MCPIP1. Mφs isolated from NSG mice' tumor masses showed MCPIP1-knock down Mφs displayed a more M1-like phenotype and in vitro experiments showed MCPIP1-knock down Mφs were more difficult to be polarized toward M2-like Mφs by MM cells. CCL2 significantly activated JAK2/STAT3 pathway in Mφs and inhibition of STAT3 hindered CCL2-induced MCPIP1 protein expression. Conclusion: Our study showed that increased CCL2 in MM' BM microenvironment polarizes Mφs towards M2-like phenotype and promotes Mφs to protect MM cells from chemotherapy drug-induced apoptosis. Mechanistically, CCL2 activated JAK2/STAT3 pathway to induce the expression of MCPIP1. MCPIP1, the critical negative regulator of inflammation, mediated Mφs 'polarization and protection effect via its dual catalytic activities. Key words: Multiple Myeloma, Macrophages-Associated Chemoresistance, Polarization, CCL2, MCPIP1 Disclosures No relevant conflicts of interest to declare.


2012 ◽  
Vol 91 (9) ◽  
pp. 1413-1418 ◽  
Author(s):  
M. Fragioudaki ◽  
A. Boula ◽  
G. Tsirakis ◽  
F. Psarakis ◽  
M. Spanoudakis ◽  
...  

2004 ◽  
Vol 349 (1-2) ◽  
pp. 39-43 ◽  
Author(s):  
Michael G. Alexandrakis ◽  
Freda H. Passam ◽  
Katerina Sfiridaki ◽  
Panayiotis Kafarakis ◽  
Elli Karydi ◽  
...  

2014 ◽  
Vol 45 (3) ◽  
pp. 1184-1192 ◽  
Author(s):  
SARA HUERTA-YEPEZ ◽  
HONG LIU ◽  
STAVROULA BARITAKI ◽  
MARIA DEL LOURDES CEBRERA-MUÑOZ ◽  
CLARA RIVERA-PAZOS ◽  
...  

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5631-5631
Author(s):  
Seo-Yeon Ahn ◽  
Sung-Hoon Jung ◽  
Hee Kyung Kim ◽  
Ho-Cheol Kang ◽  
Deok-Hwan Yang ◽  
...  

Abstract Background: Glucocorticoids has been a backbone of various treatment regimens for multiple myeloma (MM). The repeated and chronic use of high doses of glucocorticoids is associated with development of secondary adrenal insufficiency (AI), and AI could be a major problem in critically-ill patients. However, there has been no specialized data about incidence and clinical significance of secondary AI in hospitalized patients with MM. Purpose: The objective of this retrospective study is to evaluate incidence, predictive factors, and clinical significance of secondary AI in hospitalized patients with MM. Methods: We retrospectively evaluated medical records of MM patients who were hospitalized in Chonnam National University Hwasun Hospital, South Korea from December 2014 to December 2015. The definite AI was diagnosed when the peak cortisol concentration was less than < 500 nmol/L (18 mcg/dL) after ACTH administration. Results: Between December 2014 and December 2015, 77 patients were hospitalized, and 58 underwent rapid ACTH stimulation test. The most frequent cause of hospitalization was infection (70.7%), followed by weakness (24.1%), and the others (5.3%). The definite AI was confirmed in 19 patients (32.7%). To evaluate the predictive factors of AI, all variables including clinical characteristics, laboratory results, cumulative steroid dose, and treatment duration at hospitalization were analyzed, but there were no significant predictors for AI. In addition, the patients with AI had a significantly poor survival outcomes compared to those without AI (the median overall survival of 42.3 months vs. 82.7 months; P = 0.037) (Figure 1). Conclusions: This study showed that the secondary AI is not a rare condition among hospitalized patients with MM, and there was no specific predictable symptoms or signs. In addition, development of AI in the treatment period is associated with a poor prognosis. This study suggests that evaluation of AI is routinely needed in hospitalized patients with MM. Disclosures No relevant conflicts of interest to declare.


2014 ◽  
Vol 38 (9) ◽  
pp. 1130-1135 ◽  
Author(s):  
Yanjie Li ◽  
Depeng Li ◽  
Zhiling Yan ◽  
Kunming Qi ◽  
Lili Chen ◽  
...  

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