Preoperative administration of polysaccharide Kureha and reduced plasma transforming growth factor-β in patients with advanced gastric cancer: A randomized clinical trial

Yamashita,Keishi; Sakuramoto,Shinichi; Mieno,Hiroaki; Nemoto,Masayuki; Shibata,Tomotaka; Katada,Natsuya; Ohtsuki,Shigeaki; Sakamoto,Yasutoshi; Hoshi,Keika; Wang,Guoqin; Hemmi,Osamu; Satoh,Toshihiko; Kikuchi,Shiro; Watanabe,Masahiko

doi:10.3892/mco.2015.488

Preoperative administration of polysaccharide Kureha and reduced plasma transforming growth factor-β in patients with advanced gastric cancer: A randomized clinical trial

Authors:
- Keishi Yamashita
- Shinichi Sakuramoto
- Hiroaki Mieno
- Masayuki Nemoto
- Tomotaka Shibata
- Natsuya Katada
- Shigeaki Ohtsuki
- Yasutoshi Sakamoto
- Keika Hoshi
- Guoqin Wang
- Osamu Hemmi
- Toshihiko Satoh
- Shiro Kikuchi
- Masahiko Watanabe
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Affiliations: Department of Surgery, Kitasato University School of Medicine, Minami-ku, Sagamihara, Kanagawa 252‑0374, Japan, Statistic Division, Kureha Special Laboratory Co., Ltd., Fukushima 974-8232, Japan, Kitasato Clinical Research Center, Kitasato University School of Medicine, Minami-ku, Sagamihara, Kanagawa 252‑0374, Japan, Department of Preventive Medicine, Kitasato University School of Medicine, Minami-ku, Sagamihara, Kanagawa 252‑0374, Japan
Published online on: January 19, 2015 https://doi.org/10.3892/mco.2015.488
Pages: 471-478

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Abstract

Systemic abrogation of TGF‑β signaling results in tumor reduction through cytotoxic T lymphocytes activity in a mouse model. The administration of polysaccharide‑Kureha (PSK) into tumor‑bearing mice also showed tumor regression with reduced TGF‑β. However, there have been no studies regarding the PSK administration to cancer patients and the association with plasma TGF‑β. PSK (3 g/day) was administered as a neoadjuvant therapy for 2 weeks before surgery. In total, 31 advanced gastric cancer (AGC) patients were randomly assigned to group A (no neoadjuvant PSK; n=14) or B (neoadjuvant PSK therapy; n=17). Plasma TGF‑β was measured pre‑ and postoperatively. The allocation factors were clinical stage (cStage) and gender. Plasma TGF‑β ranged from 1.85‑43.5 ng/ml (average, 9.50 ng/ml) in AGC, and 12 patients (38.7%) had a high value, >7.0 ng/ml. These patients were largely composed of poorly‑differentiated adenocarcinoma with pathological stage III/IV. All the six elevated cases in group B showed a significant reduction of plasma TGF‑β (from 21.6 to 4.5 ng/ml, on average), whereas this was not exhibited in group A. The cases within the normal limits of TGF‑β remained unchanged irrespective of PSK treatment. Analysis of variance showed a statistically significant reduction in the difference of plasma TGF‑β between groups A and B (P=0.019). PSK reduced the plasma TGF‑β in AGC patients when the levels were initially high. The clinical advantage of PSK may, however, be restricted to specific histological types of AGC. Perioperative suppression of TGF‑β by PSK may antagonize cancer immune evasion and improve patient prognosis in cases of AGC.

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