scholarly journals A Potential Mechanism of Tumor Progression during Systemic Infections Via the Hepatocyte Growth Factor (HGF)/c-Met Signaling Pathway

2020 ◽  
Vol 9 (7) ◽  
pp. 2074 ◽  
Author(s):  
Hironori Tsujimoto ◽  
Hiroyuki Horiguchi ◽  
Yusuke Matsumoto ◽  
Risa Takahata ◽  
Nariyoshi Shinomiya ◽  
...  
Keyword(s):  
Growth Factor ◽  
Liver Metastasis ◽  
Hepatocyte Growth Factor ◽  
Liver Metastases ◽  
Signaling Pathway ◽  
Tumor Cells ◽  
High Serum ◽  
Term Survival ◽  
Hepatocyte Growth

Background: Increasing evidence has demonstrated that postoperative infectious complications (PICs) after digestive surgery are significantly associated with negative long-term outcomes; however, precise mechanisms of how PICs affect the poor long-term survival remain unclear. Here, we focused on the hepatocyte growth factor (HGF)/c-Met signaling pathway as one of those mechanisms. Methods: In the clinical setting, serum HGF levels were measured in the patients with sepsis and those with PICs after undergoing esophagectomy. Using a liver metastasis mouse model with cecal ligation and puncture (CLP), expressions of HGF and the roles of the HGF/c-Met pathway in the progression of tumor cells were examined. Results: Serum HGF levels were very high in the patients with intra-abdominal infection on postoperative days (PODs) 1, 3, and 5; similarly, compared to the patients without PICs, those with PICs had significantly higher serum HGF levels on 1, 3, and 5 days after esophagectomy. The patients with PICs showed poorer overall survival than those without PICs, and the patients with high serum HGF levels on POD 3 showed poorer prognosis than those with low HGF levels. Similarly, at 24 and 72 h after operation, serum levels of HGF in CLP mice were significantly higher than those in sham-operated mice. Intraperitoneal injection of mouse recombinant HGF significantly promoted liver metastases in sham-operated mice on 14 days after surgery. Knocking down c-Met expression on NL17 tumor cells by RNAi technology significantly inhibited the promotion of CLP-induced liver metastases. Conclusions: Infections after surgery increased serum HGF levels in the clinical as well as experimental settings. Induction of high serum HGF levels by CLP promoted liver metastases in a murine liver metastasis model, suggesting the involvement of the HGF/c-Met signaling pathway in tumor promotion mechanisms. Thus, targeting the HGF/c-Met signaling pathway may be a promising approach for malignant tumors, particularly in the patients with PICs.

Serum Levels of Hepatocyte Growth Factor/Scatter Factor in Patients with Liver Metastases from Breast Cancer

Tumor Biology ◽  
2007 ◽  
Vol 28 (1) ◽  
pp. 36-44 ◽  
Author(s):  
Michael H.R. Eichbaum ◽  
Thomas M. de Rossi ◽  
Sepp Kaul ◽  
Thomas Bruckner ◽  
Andreas Schneeweiss ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Liver Metastases ◽  
Serum Levels ◽  
Scatter Factor ◽  
Hepatocyte Growth

Increased Engraftment of Hepatic Progenitors After Activation of the Hepatocyte Growth Factor Signaling Pathway by Protein Transduction

2009 ◽  
Vol 234 (9) ◽  
pp. 1102-1108 ◽  
Author(s):  
Guillaume Kellermann ◽  
Lyes Boudechiche ◽  
Anne Weber ◽  
Michelle Hadchouel
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Signaling Pathway ◽  
Cell Types ◽  
Cell Surface Receptor ◽  
Migration And Invasion ◽  
Protein Transduction ◽  
Growth Factor Signaling ◽  
Hepatocyte Growth

Cell transplantation has become a major focus in biomedical research. However, efficient engraftment in solid tissues remains a challenge. Hepatocyte growth factor (HGF) signaling increases survival, proliferation, migration, and invasion of many cell types through Met, its cell surface receptor. Therefore, activation of this signaling pathway may improve the ability of many cells to be transplanted. We constructed a constitutively activated form of Met (Tpr-Met) fused to the protein transduction domain of HIV-TAT to activate the HGF/Met pathway for a few hours following cell injection. Matrix-assisted refolding was used to renature TAT-Tpr-Met protein, which was efficiently delivered into cells and recapitulated several biological functions of Met in vitro. Furthermore, treatment of hepatic progenitors with this molecule for one hour before transplantation significantly improved engraftment efficiency (31% untreated cells, 58% treated cells). These findings suggest that the transient transfer of Tpr-Met may provide a new approach to increase the proportion of successfully engrafted cells.

Loss of Hepatocyte Growth Factor/c-Met Signaling Pathway Accelerates Early Stages of N-nitrosodiethylamine–Induced Hepatocarcinogenesis

2007 ◽  
Vol 67 (20) ◽  
pp. 9844-9851 ◽  
Author(s):  
Taro Takami ◽  
Pal Kaposi-Novak ◽  
Koichi Uchida ◽  
Luis E. Gomez-Quiroz ◽  
Elizabeth A. Conner ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Signaling Pathway ◽  
Early Stages ◽  
Factor C ◽  
Hepatocyte Growth

High Serum Hepatocyte Growth Factor Levels in the Acute Stage of Community-acquired Infectious Diseases

2002 ◽  
Vol 34 (2) ◽  
pp. 127-130 ◽  
Author(s):  
F. Nayeri ◽  
I. Nilsson ◽  
L. Brudin ◽  
A. Fryden ◽  
C. Söderström ◽  
...  
Keyword(s):  
Growth Factor ◽  
Infectious Diseases ◽  
Hepatocyte Growth Factor ◽  
High Serum ◽  
Acute Stage ◽  
Hepatocyte Growth

scholarly journals Long-term effects of hepatocyte growth factor gene therapy in rat myocardial infarct model

Gene Therapy ◽  
2011 ◽  
Vol 19 (8) ◽  
pp. 836-843 ◽  
Author(s):  
Y-N Jin ◽  
M Inubushi ◽  
K Masamoto ◽  
K Odaka ◽  
I Aoki ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Myocardial Infarct ◽  
Long Term Effects ◽  
Factor Gene ◽  
Growth Factor Gene ◽  
Myocardial Infarct Model ◽  
Hepatocyte Growth

scholarly journals A metastatic colorectal carcinoma: A curative approach?

2014 ◽  
Vol 61 (2) ◽  
pp. 47-49
Author(s):  
Nadezda Basara
Keyword(s):  
Liver Metastasis ◽  
Liver Metastases ◽  
Colorectal Liver Metastasis ◽  
Randomised Trial ◽  
Increase Response Rate ◽  
Term Survival ◽  
Exon 2 ◽  
Long Term Survival ◽  
Response To Chemotherapy

Background: Unresectable colorectal liver metastases can be resected after response to chemotherapy. The use of neoadjuvant chemotherapy with or without targeted monoclonal antibodies increases the proportion of resectable liver metastasis and conferred a long term survival of 40%. Methods: The current ongoing studies regarding neodjuvant treatment strategies aiming to increase a proportion of patients with resectable liver metastases is going to be presented. Results: Perioperative chemotherapy with FOLFOX4 is compatible with major liver surgery and reduces the risk of events of progression free survival in resected patients. The results of the CELIM study confirm a favourable long-term survival for patients with initially suboptimal or unresectable colorectal liver metastasis who respond to conversion therapy and undergo secondary resection. The New EPOC randomised trial does not support the addition of cetuximab to chemotherapy and surgery for operable colorectal liver metastasis in KRAS exon 2 wild-type patients. Conclusion: The ability of anti-epidermal growth factor receptor agents to increase response rate and resection when added to chemotherapy has been clearly shown in a number of trials. The resection rates are higher with chemotherapy plus Cetuximab, in general, a conversion is contributes to the better overall survival.

scholarly journals Progress of Gene Therapy in Cardiovascular Disease

Hypertension ◽  
2020 ◽  
Vol 76 (4) ◽  
pp. 1038-1044
Author(s):  
Munehisa Shimamura ◽  
Hironori Nakagami ◽  
Fumihiro Sanada ◽  
Ryuichi Morishita
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Dna Vaccine ◽  
Critical Limb Ischemia ◽  
Dna Vaccines ◽  
Limb Ischemia ◽  
Hepatocyte Growth

Gene therapy has been extensively studied in peripheral and cardiac ischemia, heart and vein graft failure, and dyslipidemia, but most clinical trials failed to show their efficacies despite good outcomes in preclinical studies. So far, 2 gene therapies for dyslipidemia and one for critical limb ischemia in peripheral artery disease have been approved. In critical limb ischemia, gene therapy using proangiogenic factors has emerged as a novel therapeutic modality for promoting angiogenesis. Initial researches mainly focused on vascular endothelial growth factor, fibroblast growth factor, or hepatocyte growth factor. After the favorable results of basic research, several phase I and II clinical trials of these proangiogenic factors have shown promising results. However, only a phase III clinical trial of the intramuscular injection of hepatocyte growth factor plasmid DNA has shown successful outcomes, and it was recently approved in Japan for treating patients with critical limb ischemia who have ulcers and for whom no alternative therapeutic options are available. DNA vaccine is another promising modality of gene therapy. An antitumor vaccine suppressing angiogenesis through the inhibition of proangiogenic factors and an antihypertensive vaccine inhibiting the renin–angiotensin system are representative DNA vaccines. The advantage of DNA vaccine is its long-term effectiveness with a few vaccinations; however, the benefits and risks, such as adverse T-cell reaction against self-antigen or long-term side effects, of DNA vaccines should be carefully evaluated. In this review, we discuss the recent advances in proangiogenic gene therapy for critical limb ischemia and DNA vaccine for hypertension.

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