Impaired liver regeneration with humoral and genetic disturbances in urinary trypsin inhibitor‐deficient mice

Nobuoka, Takayuki; Mizuguchi, Toru; Oshima, Hideki; Shibata, Toshihito; Kaji, Shinsuke; Nagayama, Masatoshi; Meguro, Makoto; Mitaka, Toshihiro; Hirata, Koichi

doi:10.1111/j.1478-3231.2009.01990.x

Cited by 10 publications

(5 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Impairment of liver regeneration was observed in UTI −/− mice with high cytokine and chemokine levels [47]. Multiple pharmacological properties that may contribute to inhibition of MMPs during advanced stages of liver regeneration, and there may be a dynamic inhibition-promoting balance that is regulated by inflammatory mediators.…”

Section: Discussionmentioning

confidence: 99%

Ulinastatin Reduces Cancer Recurrence after Resection of Hepatic Metastases from Colon Cancer by Inhibiting MMP-9 Activation via the Antifibrinolytic Pathway

Shen

et al. 2013

BioMed Research International

View full text Add to dashboard Cite

High recurrence of colon cancer liver metastasis is observed in patients after hepatic surgery, and the cause is believed to be mostly due to the growth of residual microscopic metastatic lesions within the residual liver. Therefore, triggering the progression of occult metastatic foci may be a novel strategy for improving survival from colon cancer liver metastases. In the present study, we identified an anti-recurrence effect of ulinastatin on colon cancer liver metastasis in mice after hepatectomy. Transwell cell invasion assays demonstrated that ulinastatin significantly inhibited the in vitro invasive ability of colon cancer HCT116 cells. Moreover, gelatin zymography and ELISA analysis showed that MMP-9 activity and plasmin activity of colon cancer HCT116 cells were inhibited by ulinastatin, respectively. Furthermore, in vivo BALB/C nu/nu mice model indicated that ulinastatin effectively reduced recurrence after resection of hepatic metastases from colon cancer. The optimum timing for ulinastatin administration was one week after hepatectomy. Taken together, our findings point to the potential of ulinastatin as an effective approach in controlling recurrence of hepatic metastases from colon cancer after hepatectomy via its anti-plasmin activity.

show abstract

Section: Discussionmentioning

confidence: 99%

Ulinastatin Reduces Cancer Recurrence after Resection of Hepatic Metastases from Colon Cancer by Inhibiting MMP-9 Activation via the Antifibrinolytic Pathway

Shen

et al. 2013

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…Ulinastatin or urinary trypsin inhibitor (UTI) is a Kunitz-type serine protease inhibitor that plays an antiinflammatory effect by inhibiting several proteases such as trypsin, plasmin, cathepsin G, chymotrypsin, and neutrophil elastase (6). Animal studies (7)(8)(9)(10) and human studies (11,12) showed that UTI administration suppressed acute inflammatory responses after hepatectomy. Since there was no systematic review or meta-analysis of randomized controlled trials (RCTs) to assess the benefits of UTI in hepatectomy, whether perioperatively UTI using has a protective effect on liver function remained unclear.…”

Section: Original Articlementioning

confidence: 99%

Perioperation ulinastatin intervention protects liver function in hepatectomy: a systematic review of randomized controlled trials and meta-analysis

Gao¹,

Lyu²,

Yang³

et al. 2020

Ann Palliat Med

View full text Add to dashboard Cite

Background: Vascular occlusion during hepatectomy accompanies ischemia-reperfusion (IR) injury, which can cause liver dysfunction and affect patients' outcome. Ulinastatin or urinary trypsin inhibitor (UTI), a polyvalent inhibitor of various enzymes, has been confirmed of anti-IR injury effect in recent studies. Here we performed a systematic review and meta-analysis to assess the benefits of perioperation UTI using to protect liver function in hepatectomy.Methods: Randomized controlled trials (RCTs) evaluating UTI in hepatectomy were identified. Two independent reviewers extracted data on basic characteristics and risk of bias in the studies, and on outcomes such as alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin (TBIL) from 1 to 7 days after operation.Results: A total of 9 RCTs including 408 UTI and 372 control participants were identified. There was no significant difference in basic characteristics such as age or sex. The majority of the patients who underwent hepatectomy had primary liver carcinoma, liver metastases and benign liver lesions. A significant improvement in liver function was associated with UTI use not only at 1 and 3 days postoperatively, but also at 7 days (all P≤0.01). However, significant heterogeneity existed between the pooled studies (all P<0.01).Conclusions: UTI has positive protective effects against IR injury in hepatectomy. However, further highquality RCTs are needed to confirm this conclusion.

show abstract

“…On the other hand, a large number of in vivo reports have provided evidence that UTI protects against pathological traits related to septic shock induced by gram-negative bacteria: UTI reduces LPS-induced hypoten- using UTI (-/-) mice via the regulation of systemic (serum) levels of cytokines such as IL-6 and IL-10 and chemokines such as MCP-1 and MIP-1α 73 .…”

Section: Anti-inflammatory Property Of Utimentioning

confidence: 99%

Urinary trypsin inhibitor as a therapeutic option for inflammatory disorders

Inoue¹,

Takano²

2013

OA Biotechnology

View full text Add to dashboard Cite

Introduction Urinary trypsin inhibitor, a serine protease inhibitor, has been widely used, particularly in Japan, as a drug for patients with acute inflammatory disorders such as pancreatitis, shock and disseminated intravascular coagulation. Previous in vitro studies have demonstrated that serine protease inhibitors may have anti-inflammatory properties beyond their inhibition of neutrophil elastase at sites of inflammation. However, the therapeutic effects of urinary trypsin inhibitor in vivo remain unclarified. In this review, we introduce the roles of urinary trypsin inhibitor in experimental systemic inflammatory responses induced by both the intraperitoneal and intratracheal administration of lipopolysaccharide using urinary trypsin inhibitor-deficient (-/-) and corresponding wild-type mice. Conclusion Urinary trypsin inhibitor may provide an attractive 'rescue' therapeutic option for systemic inflammatory response syndromes such as disseminated intravascular coagulation, acute lung injury and acute liver injury.

show abstract

Impaired liver regeneration with humoral and genetic disturbances in urinary trypsin inhibitor‐deficient mice

Abstract: UTI appears to important cytokine and chemokine regulation in normal liver regeneration.

Cited by 10 publications

References 38 publications

Ulinastatin Reduces Cancer Recurrence after Resection of Hepatic Metastases from Colon Cancer by Inhibiting MMP-9 Activation via the Antifibrinolytic Pathway

Ulinastatin Reduces Cancer Recurrence after Resection of Hepatic Metastases from Colon Cancer by Inhibiting MMP-9 Activation via the Antifibrinolytic Pathway

Perioperation ulinastatin intervention protects liver function in hepatectomy: a systematic review of randomized controlled trials and meta-analysis

Urinary trypsin inhibitor as a therapeutic option for inflammatory disorders

Contact Info

Product

Resources

About