PMID- 22876791
OWN - NLM
STAT- MEDLINE
DCOM- 20130206
LR  - 20211021
IS  - 1472-6882 (Electronic)
IS  - 1472-6882 (Linking)
VI  - 12
DP  - 2012 Aug 9
TI  - Protective effect of the Japanese traditional medicine juzentaihoto on 
      myelosuppression induced by the anticancer drug TS-1 and identification of a 
      potential biomarker of this effect.
PG  - 118
LID - 10.1186/1472-6882-12-118 [doi]
AB  - BACKGROUND: TS-1 is an oral anticancer drug containing a 5-fluorouracil 
      derivative (Tegafur) that is widely used in Japan for the treatment of cancer, 
      especially gastrointestinal tumors. Frequently, however, TS-1 therapy has to be 
      discontinued because of leukopenia. If it were possible to predict the 
      development of bone marrow suppression before the white blood cell (WBC) count 
      had actually decreased, treatment could be improved by strict dosage control 
      and/or the prophylactic administration of hematopoietic drugs. Juzentaihoto 
      (JTT), a traditional Japanese medicine (Kampo), has been reported to activate 
      hematopoiesis and reduce the side effects associated with chemotherapy and 
      radiotherapy. Here, we 1) evaluate the efficacy of JTT in alleviating 
      myelosuppression induced by TS-1 therapy in mice, and 2) explore biomarkers that 
      reflect both induction by TS-1 and alleviation by JTT of bone marrow suppression 
      using a proteomics approach. METHODS: Ten mg/kg of TS-1 was administered to 
      Balb/c mice with or without 1 g/kg of oral JTT for 3, 5 and 7 days. WBC count and 
      ratio of CD34+ bone marrow cells (BMCs) were estimated by flow cytometry. Plasma 
      samples were analyzed using surface-enhanced laser desorption/ionization 
      time-of-flight mass spectrometry (SELDI TOF-MS). A biomarker candidate from SELDI 
      profiling was identified using a combination of cation exchange spin column 
      purification, SDS-PAGE, enzymatic digestion and LC-MS/MS. RESULTS: After 
      administration of TS-1, a significant decrease in WBC count and CD34+ BMC ratio 
      were observed at days 5 and 3, respectively. JTT treatment improved WBC count on 
      day 7 and CD34+ BMC ratio on days 5 and 7. SELDI analysis highlighted three 
      protein peaks that had increased on day 3 after treatment with TS-1 but remained 
      unchanged in mice co-treated with JTT. One of the three peaks, m/z 4223.1, was 
      further investigated and identified as a specific C-terminal fragment of albumin. 
      CONCLUSION: This study indicates that bone marrow suppression by treatment with 
      TS-1 in mice might be improved by coadministration of JTT. A C-terminal fragment 
      of albumin was identified as a candidate biomarker for predicting TS-1-induced 
      myelosuppression. However, the sensitivity and specificity of the biomarker 
      candidate must be validated in future clinical studies.
FAU - Ogawa, Kazuo
AU  - Ogawa K
AD  - TSUMURA Research Laboratories, TSUMURA & CO, 3586 Yoshiwara, Ami-machi, 
      Inashiki-gun, Ibaraki 300-1192, Japan. ogawa_kazuo@mail.tsumura.co.jp
FAU - Omatsu, Tatsushi
AU  - Omatsu T
FAU - Matsumoto, Chinami
AU  - Matsumoto C
FAU - Tsuchiya, Naoko
AU  - Tsuchiya N
FAU - Yamamoto, Masahiro
AU  - Yamamoto M
FAU - Naito, Yuji
AU  - Naito Y
FAU - Yoshikawa, Toshikazu
AU  - Yoshikawa T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120809
PL  - England
TA  - BMC Complement Altern Med
JT  - BMC complementary and alternative medicine
JID - 101088661
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Drugs, Chinese Herbal)
RN  - 0 (Protective Agents)
RN  - 0 (juzentaihoto)
RN  - 1548R74NSZ (Tegafur)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*adverse effects
MH  - Biomarkers/*blood
MH  - Blood Cell Count
MH  - Bone Marrow/drug effects/physiology
MH  - Drugs, Chinese Herbal/*administration & dosage
MH  - Female
MH  - Hematopoiesis/*drug effects
MH  - Humans
MH  - Japan
MH  - Leukopenia/*drug therapy/etiology/metabolism
MH  - Mass Spectrometry
MH  - *Medicine, Kampo
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Protective Agents/*administration & dosage
MH  - Proteomics
MH  - Tegafur/*adverse effects
PMC - PMC3478231
EDAT- 2012/08/11 06:00
MHDA- 2013/02/07 06:00
PMCR- 2012/08/09
CRDT- 2012/08/11 06:00
PHST- 2012/02/10 00:00 [received]
PHST- 2012/08/05 00:00 [accepted]
PHST- 2012/08/11 06:00 [entrez]
PHST- 2012/08/11 06:00 [pubmed]
PHST- 2013/02/07 06:00 [medline]
PHST- 2012/08/09 00:00 [pmc-release]
AID - 1472-6882-12-118 [pii]
AID - 10.1186/1472-6882-12-118 [doi]
PST - epublish
SO  - BMC Complement Altern Med. 2012 Aug 9;12:118. doi: 10.1186/1472-6882-12-118.