Prognostic Impact of Surgical Complications and Preoperative Serum Hepatocyte Growth Factor in Hepatocellular Carcinoma Patients After Initial Hepatectomy

Mizuguchi, Toru; Nagayama, Masatoshi; Meguro, Makoto; Shibata, Toshihito; Kaji, Shinsuke; Nobuoka, Takayuki; Kimura, Yasutoshi; Furuhata, Tomohisa; Hirata, Koichi

doi:10.1007/s11605-008-0711-8

Cited by 41 publications

(35 citation statements)

References 25 publications

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“…HGF in serum is an indicator of ovarian carcinoma in females with a pelvic mass, and with poor prognosis in advanced ovarian cancer. Similar results have been demonstrated in studies evaluating HGF in gastric carcinoma, colorectal cancer and hepatocellular carcinoma (17)(18)(19). However, there has been no study evaluating HGF in NPC.…”

Section: Discussionsupporting

confidence: 83%

HGF stimulates proliferation through the HGF/c-Met pathway in nasopharyngeal carcinoma cells

et al. 2012

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Abstract. Hepatocyte growth factor (HGF) and its receptor c-Met are important in the development and homeostasis of a variety of human malignancies. However, the role of the HGF/c-Met signaling pathway in nasopharyngeal carcinoma (NPC) has not been clearly elucidated. This study examined the effect of HGF/c-Met on proliferation and migration in several NPC cell lines. RT-PCR was used to detect the HGF gene in CNE-1, CNE-2, HK-1, HONE-1 and SUNE-1 NPC cells. However, HGF gene expression was not detected in any of these cells. Using immunoblotting analysis, the Met25 protein was identified in HONE-1, HK-1 and CNE-1 cells. Results from fluorescence-activated cell sorting (FACS) analysis revealed that anti-Met25 mAb specifically bound Met-expressing HONE-1, HK-1 and CNE-1 cells. It was further demonstrated that exogenous HGF was able to stimulate the proliferation of HONE-1 and HK-1 cells and the healing of scrape wounds in HONE-1 NPC cells. Our results reveal the potential therapeutic applications of combination therapy with antibodies targeting HGF in NPC patients. IntroductionNasopharyngeal carcinoma (NPC) is one of the most common types of cancer in South East Asia, and remains a cause of high morbidity in Southern China (1). In addition to its ability for rapid growth, NPC has a tendency to invade the adjacent regions and metastasize to the regional lymph nodes and distant organs. Despite the sequela of radiation, radiotherapy remains the standard treatment for NPC (2,3). However, only early stage NPC cases are able to obtain effective results, including good prognosis and function. The combination of radiotherapy and chemotherapy is crucial in the therapy of locoregional advanced cases of NPC (4). Although over 95% of biopsies belong to the WHO type Ⅱ or Ⅲ classification, which are sensitive to radiotherapy and chemotherapy, there are many treatment-failure cases (5). Thus, there is a requirement for new therapeutic targets and a better understanding of the mechanisms involved in the metastasis of NPC.The Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), are overexpressed and/or activated in a variety of human malignancies. The hepatocyte growth factor/ scatter factor (HGF/SF) and its receptor Met are important in the development, homeostasis, tumorigenesis, angiogenesis, invasion and metastasis of human malignancies (6). However, the mechanisms of the HGF/c-Met signaling pathway that contribute to the invasiveness of malignancies remain unknown. The Met receptor is frequently overexpressed in NPC patients, and high expression is associated with short patient survival (7). The availability of the Met receptor has been shown to modify NPC cell response to HGF. This finding enhanced our understanding of the mechanisms of signaling transduction in the HGF-induced progression of NPC. However, the role of the HGF/c-Met signaling pathway in NPC has not been clearly elucidated. In this study, we detected the effect of HGF/c-Met on proliferation and migration in several NPC cell lines. Our r...

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Section: Discussionsupporting

confidence: 83%

HGF stimulates proliferation through the HGF/c-Met pathway in nasopharyngeal carcinoma cells

et al. 2012

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“…Previous studies showed that high serum levels of HGF in patients with HCC negatively associated with OS and outcome [104][105][106] . In the recent SHARP study biomarkers analysis, patients treated with sorafenib experienced a decrease in a mean plasma level of HGF although; patients treated with placebo have mean HGF concentration increase [63] .…”

Section: Hepatocyte Growth Factormentioning

confidence: 98%

“…Mizuguchi et al [106] systemic therapies for patients with advanced HCC, no association between baseline AFP levels and prognosis was observed [66] . More interestingly, some authors evaluated the kinetics of AFP during treatment in HCC as a predictive marker of response or outcome.…”

Section: Poorer Prognosismentioning

confidence: 99%

Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging

Bouattour

Payancé

Wassermann

2015

WJH

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Many years after therapeutic wilderness, sorafenib finally showed a clinical benefit in patients with advanced hepatocellular carcinoma. After the primary general enthusiasm worldwide, some disappointments emerged particularly since no new treatment could exceed or at least match sorafenib in this setting. Without these new drugs, research focused on optimi zing care of patients treated with sorafenib. One challenging research approach deals with identifying prognostic and predictive biomarkers of sorafenib in this population. The task still seems difficult; however appropriate investigations could resolve this dilemma, as observed for some malignancies where other drugs were used.

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“…[22][23][24][25], but these studies-conducted on tumor tissue (22)(23)(24) and hepatic vein (25) markers-have involved small numbers of patients. Biomarker evaluations in larger HCC patient populations, especially as part of randomized, placebo-controlled trials, may provide additional insight into the predictive and/or prognostic utility of specific markers.…”

Section: Introductionmentioning

confidence: 99%

Plasma Biomarkers as Predictors of Outcome in Patients with Advanced Hepatocellular Carcinoma

Llovet

Peña

Lathia

et al. 2012

Clinical Cancer Research

511

461

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Purpose: Validated biomarkers of prognosis and response to drug have not been identified for patients with hepatocellular carcinoma (HCC). One of the objectives of the phase III, randomized, controlled Sorafenib HCC Assessment Randomized Protocol (SHARP) trial was to explore the ability of plasma biomarkers to predict prognosis and therapeutic efficacy. Experimental Design: In SHARP, 602 patients with advanced HCC were randomized to receive either oral sorafenib 400 mg twice a day per os or matching placebo daily on a continuous basis. Ten plasma biomarkers implicated in the pathogenesis of HCC were measured in 491 patients at baseline and in 305 after 12 weeks of treatment. The candidate biomarkers were analyzed to identify correlates of prognosis or predictors of response to sorafenib. Results: In both the entire patient population and the placebo cohort, baseline angiopoietin 2 (Ang2) and VEGF concentrations independently predicted survival. Clinical variables such as macroscopic vascular invasion, Eastern Cooperative Oncology Group (ECOG) performance status, and baseline α-fetoprotein and alkaline phosphatase concentrations also independently predicted survival in these groups. In the sorafenib cohort, trends toward enhanced survival benefit from sorafenib were observed in patients with high s-c-KIT or low hepatocyte growth factor concentration at baseline (P of interaction = 0.081 and 0.073, respectively). Conclusions: The angiogenesis biomarkers Ang2 and VEGF were independent predictors of survival in patients with advanced HCC. In contrast, none of the biomarkers tested significantly predicted response to sorafenib. Clin Cancer Res; 18(8); 2290–300. ©2012 AACR.

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Prognostic Impact of Surgical Complications and Preoperative Serum Hepatocyte Growth Factor in Hepatocellular Carcinoma Patients After Initial Hepatectomy

Abstract: Postoperative surgical complications could have a prognostic impact on overall survival in HCC patients after initial hepatectomy. Serum HGF could be a factor connected to complications and survival in this group.

Cited by 41 publications

References 25 publications

HGF stimulates proliferation through the HGF/c-Met pathway in nasopharyngeal carcinoma cells

HGF stimulates proliferation through the HGF/c-Met pathway in nasopharyngeal carcinoma cells

Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging

Plasma Biomarkers as Predictors of Outcome in Patients with Advanced Hepatocellular Carcinoma

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