PMID- 31650289
OWN - NLM
STAT- MEDLINE
DCOM- 20191217
LR  - 20191217
IS  - 1432-0584 (Electronic)
IS  - 0939-5555 (Linking)
VI  - 98
IP  - 12
DP  - 2019 Dec
TI  - Peripheral neuropathy following bortezomib therapy in multiple myeloma patients: 
      association with cumulative dose, heparanase, and TNF-alpha.
PG  - 2793-2803
LID - 10.1007/s00277-019-03816-6 [doi]
AB  - Multiple myeloma (MM) is a plasma cell neoplasm which constitutes about 10% of 
      all hematologic malignancies. Despite bortezomib is a promising new generation of 
      drugs for MM, its clinical use is limited by peripheral neurotoxicity in the vast 
      majority of patients, which can be severe and require a reduction of dose or even 
      treatment withdrawal. Tumor necrosis factor-alpha (TNF-alpha), as the most important 
      inflammatory factor, could induce the inflammatory response and expression of 
      heparanase (HPSE), which may play a crucial role in peripheral neuropathy after 
      chemotherapy. However, the role of TNF-alpha in bortezomib-induced peripheral 
      neuropathy (BIPN) has not been reported. In this study, treatment-emergent 
      neuropathy was assessed by total neuropathy score and electrophysiological 
      examination. The expression level of TNF-alpha and HPSE were evaluated by 
      enzyme-linked immunosorbent assay. The effects of anti-TNF-alpha on the evolution of 
      neuropathy were tested in rat models of neurotoxicity. The results indicated that 
      with the augment of cumulative dose of bortezomib, the incidence of neuropathy 
      was increased. Moreover, bortezomib administration induced the expression of 
      TNF-alpha. With the increased expression of TNF-alpha, neuropathy was exacerbated. 
      TNF-alpha-induced expression of HSPE was secondary to the development of neuropathy. 
      Co-administration of anti-TNF-alpha in bortezomib therapy has a potential 
      neuroprotective effect on BIPN in rats. TNF-alpha participates in the pathogenesis of 
      BIPN, which represents an attractive target for future therapeutic intervention.
FAU - Zhao, Weiwei
AU  - Zhao W
AD  - Department of Hematology, The Second Affiliated Hospital of Harbin Medical 
      University, No. 246 Xuefu Street, Nangang, Harbin, 150081, People's Republic of 
      China.
FAU - Wang, Wei
AU  - Wang W
AD  - Department of Hematology, The Second Affiliated Hospital of Harbin Medical 
      University, No. 246 Xuefu Street, Nangang, Harbin, 150081, People's Republic of 
      China. wangweihmu@qq.com.
FAU - Li, Xiaoyun
AU  - Li X
AD  - Department of Hematology, The Second Affiliated Hospital of Harbin Medical 
      University, No. 246 Xuefu Street, Nangang, Harbin, 150081, People's Republic of 
      China.
FAU - Liu, Yijun
AU  - Liu Y
AD  - Department of Hematology, The Second Affiliated Hospital of Harbin Medical 
      University, No. 246 Xuefu Street, Nangang, Harbin, 150081, People's Republic of 
      China.
FAU - Gao, Haiyan
AU  - Gao H
AD  - Department of Hematology, The Second Affiliated Hospital of Harbin Medical 
      University, No. 246 Xuefu Street, Nangang, Harbin, 150081, People's Republic of 
      China.
FAU - Jiang, Yongfang
AU  - Jiang Y
AD  - Department of Hematology, The Second Affiliated Hospital of Harbin Medical 
      University, No. 246 Xuefu Street, Nangang, Harbin, 150081, People's Republic of 
      China.
FAU - Wang, Ying
AU  - Wang Y
AD  - Department of Hematology, The Second Affiliated Hospital of Harbin Medical 
      University, No. 246 Xuefu Street, Nangang, Harbin, 150081, People's Republic of 
      China.
LA  - eng
GR  - 81001051/Youth Science Fund of the Natural Science Foundation of China/
GR  - 2015M580270/Postdoctoral Science Foundation of China/
GR  - LBH-Z15129/Postdoctoral Science Foundation of Heilongjiang Province/
GR  - KYCX2018-15/Young and Middle-Aged Science Foundation of Harbin Medical 
      University/
PT  - Clinical Trial
PT  - Journal Article
DEP - 20191025
PL  - Germany
TA  - Ann Hematol
JT  - Annals of hematology
JID - 9107334
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 69G8BD63PP (Bortezomib)
RN  - EC 3.2.1.- (heparanase)
RN  - EC 3.2.1.31 (Glucuronidase)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Bortezomib/*administration & dosage
MH  - Female
MH  - Glucuronidase/*blood
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Multiple Myeloma/blood/drug therapy
MH  - Neoplasm Proteins/*blood
MH  - *Peripheral Nervous System Diseases/blood/drug therapy
MH  - Rats
MH  - Rats, Wistar
MH  - Tumor Necrosis Factor-alpha/*blood
OTO - NOTNLM
OT  - Bortezomib
OT  - Heparanase
OT  - Multiple myeloma
OT  - Peripheral neuropathy
OT  - Tumor necrosis factor-alpha
EDAT- 2019/10/28 06:00
MHDA- 2019/12/18 06:00
CRDT- 2019/10/26 06:00
PHST- 2019/03/03 00:00 [received]
PHST- 2019/10/02 00:00 [accepted]
PHST- 2019/10/28 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2019/10/26 06:00 [entrez]
AID - 10.1007/s00277-019-03816-6 [pii]
AID - 10.1007/s00277-019-03816-6 [doi]
PST - ppublish
SO  - Ann Hematol. 2019 Dec;98(12):2793-2803. doi: 10.1007/s00277-019-03816-6. Epub 
      2019 Oct 25.