scholarly journals Elevated Serum Concentrations of Hepatocyte Growth Factor in Patients With Multiple Myeloma

Blood ◽  
1998 ◽  
Vol 91 (3) ◽  
pp. 806-812 ◽  
Author(s):  
Carina Seidel ◽  
Magne Børset ◽  
Ingemar Turesson ◽  
Niels Abildgaard ◽  
Anders Sundan ◽  
...  

Abstract Serum from 398 myeloma patients at diagnosis and serial samples from 29 patients were analysed for hepatocyte growth factor (HGF). HGF was elevated at diagnosis in 43% of myeloma patients compared with healthy controls (median 1.00 ng/mL and 0.44 ng/mL, respectively;P < .00001). In the group with elevated HGF levels 46% of the patients reached plateau phase, as compared with 60% of the patients with low HGF levels (P = .005), and the median survival time was 21 and 32 months, respectively (P = .002). In a univariate Cox regression analysis, HGF was a significant predictor of mortality (P = .02). In the subgroup of patients with β2-microglobulin levels less than or equal to 6 mg/L, high versus low HGF was a prognostic factor when a multivariate Cox regression analysis was performed. In serial samples HGF was higher at the time of diagnosis and relapse (median 0.57 ng/mL and 0.52 ng/mL, respectively; P = .0018) than at response (median 0.24 ng/mL, P = .008). We conclude that HGF may be a useful follow-up parameter in myeloma patients. Measurement of HGF may identify a group of patients with poor response to melphalan-prednisone treatment and short survival. HGF was a prognostic factor in patients with high levels of β2-microglobulin.

Blood ◽  
1998 ◽  
Vol 91 (3) ◽  
pp. 806-812 ◽  
Author(s):  
Carina Seidel ◽  
Magne Børset ◽  
Ingemar Turesson ◽  
Niels Abildgaard ◽  
Anders Sundan ◽  
...  

Serum from 398 myeloma patients at diagnosis and serial samples from 29 patients were analysed for hepatocyte growth factor (HGF). HGF was elevated at diagnosis in 43% of myeloma patients compared with healthy controls (median 1.00 ng/mL and 0.44 ng/mL, respectively;P < .00001). In the group with elevated HGF levels 46% of the patients reached plateau phase, as compared with 60% of the patients with low HGF levels (P = .005), and the median survival time was 21 and 32 months, respectively (P = .002). In a univariate Cox regression analysis, HGF was a significant predictor of mortality (P = .02). In the subgroup of patients with β2-microglobulin levels less than or equal to 6 mg/L, high versus low HGF was a prognostic factor when a multivariate Cox regression analysis was performed. In serial samples HGF was higher at the time of diagnosis and relapse (median 0.57 ng/mL and 0.52 ng/mL, respectively; P = .0018) than at response (median 0.24 ng/mL, P = .008). We conclude that HGF may be a useful follow-up parameter in myeloma patients. Measurement of HGF may identify a group of patients with poor response to melphalan-prednisone treatment and short survival. HGF was a prognostic factor in patients with high levels of β2-microglobulin.


Author(s):  
Philip J. Johnson ◽  
Sofi Dhanaraj ◽  
Sarah Berhane ◽  
Laura Bonnett ◽  
Yuk Ting Ma

Abstract Background The neutrophil–lymphocyte ratio (NLR), a presumed measure of the balance between neutrophil-associated pro-tumour inflammation and lymphocyte-dependent antitumour immune function, has been suggested as a prognostic factor for several cancers, including hepatocellular carcinoma (HCC). Methods In this study, a prospectively accrued cohort of 781 patients (493 HCC and 288 chronic liver disease (CLD) without HCC) were followed-up for more than 6 years. NLR levels between HCC and CLD patients were compared, and the effect of baseline NLR on overall survival amongst HCC patients was assessed via multivariable Cox regression analysis. Results On entry into the study (‘baseline’), there was no clinically significant difference in the NLR values between CLD and HCC patients. Amongst HCC patients, NLR levels closest to last visit/death were significantly higher compared to baseline. Multivariable Cox regression analysis showed that NLR was an independent prognostic factor, even after adjustment for the HCC stage. Conclusion NLR is a significant independent factor influencing survival in HCC patients, hence offering an additional dimension in prognostic models.


1995 ◽  
Vol 268 (2) ◽  
pp. G380-G386 ◽  
Author(s):  
F. Roos ◽  
A. M. Ryan ◽  
S. M. Chamow ◽  
G. L. Bennett ◽  
R. H. Schwall

Hepatocyte growth factor/scatter factor (HGF/SF) is a potent stimulator of DNA synthesis in a variety of epithelial cells, including hepatocytes, and has been implicated in liver regeneration. We show here that combining dextran sulfate with HGF/SF markedly increases the plasma concentrations of HGF/SF that are achieved during intraperitoneal infusion. Three days of administration of HGF/SF by this mechanism caused a dose-dependent increase in liver wet weight. Mitotic figures were rarely observed in control livers but were abundant in livers exposed to HGF/SF, and liver DNA content was elevated. Serum levels of triglycerides, cholesterol, total protein, and albumin were also dose dependently increased, whereas alkaline phosphatase was reduced. From these data we conclude 1) that combining HGF/SF with dextran sulfate provides a novel method for delivering HGF/SF in a continuous manner, 2) that HGF/SF can induce liver growth in an intact animal, and 3) that HGF/SF-induced liver enlargement is associated with changes in serum biochemistry.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4983-4983
Author(s):  
Ida Bruun Kristensen ◽  
Jacob Haaber Christensen ◽  
Maria Lyng ◽  
Tobias W Klausen ◽  
Lene Meldgaard Knudsen ◽  
...  

Abstract Abstract 4983 Background: Full length Hepatocyte growth Factor (HGF) (consisting of four “kringle”-domains) is known to be produced by multiple myeloma plasma cells (MM PC) in vivo and HGF is among the 70 most up regulated genes in MM. Elevated serum levels of HGF are known to be an adverse prognostic factor and recently, MM PC expression of the HGF receptor cMET has been shown to be an adverse prognostic factor. Functionally, HGF inhibits osteoblastogenesis in vitro and promotes migration of MM PC. So far, studies on HGF and its impact in MM have focused on measuring full-length or all isoforms of HGF expression. However, naturally occurring shorter isoforms of HGF (known as NK1 and NK2) are known to work as partial inhibitors of full-length HGF (Otsuka et al, Mol and Cell Biol, 2000). We examined the HGF isoforms and cMET expression at the mRNA level in isolated MM PC of >150 newly diagnosed patients with MM, 18 MGUS patients and 8 healthy volunteers (HV) and associated it to overall survival (OS) and degree of osteolytic bone disease (OBD). Methods: Aberrant MM PCs (CD38++/CD19-/CD45-/i/CD56-/+/++) were sorted directly into PCR tubes by fluorescence activated cell sorting (FACS) using a FACS Aria (BDIS). In all cases a PC-purity above 98% was obtained. A cDNA archive was generated by global reverse transcription. By using a polyadenylating step 5x-oligo(dT)-transcript-poly(A)-3xcDNA were generated and finally amplified by PCR using a sequence independent X-(dT)24 primer. The conditions of the reverse transcriptase reaction is designed to limit the size of the first strand cDNA to 300–700 bases, which leads to a more uniform and unbiased amplification. Isoform specific primers were designed using the Primer Express program and experimentally tested. The HGF version covered full-length HGF (transcript variant 1 and 3), HGF2 covered the 2 kringle domain versions (transcript variant 2 and 4) and HGF5 covered the 1 kringle domain version (transcript variant 5). cMET only exists in one isoform. Quantitative PCR was performed using β-actin as internal reference gene, using the δCt method. Determination of positivity or negativity was made from a cut-off-value at 10E-05. OBD was evaluated by standard radiographic methods. The MM patients were treated with either high-dose melphalan with ASCT or melphalan-prednisone according to age recommendations. Results: At least one of the HGF isoforms were found to be expressed in PCxs from 43% of MM patients compared to 32% of MGUS patients, and 0% of HV. Full length HGF was expressed in 17 %, HGF2 in 29%, and HGF5 in 26% of the MM patients. Expression of any HGF variant was associated to an adverse OS (p=0.04) (Fig. 1). The quantitative expression of the transcript variant 5 associated negatively to OS (p=0.02), while expression of the other specific isoforms showed no association to OS. Thus, somehow surprisingly, MM PC expression of the shorter isoform of HGF (HGF5) was more predictive of poor prognosis. A tendency towards elevated expression of full-length HGF in patients with no OBD compared to limited or advanced was observed but did not reach statistically significance (p=0.13). Pre-liminary analysis of cMET expression data showed no correlation between MM PC cMet expression and degree of OBD. Further data on cMet will be presented at the meeting. Disclosures: No relevant conflicts of interest to declare.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 56-56
Author(s):  
Chan-Young Ock ◽  
Ah-Rong Nam ◽  
Ju-Hee Bang ◽  
Tae-Yong Kim ◽  
Kyung-Hun Lee ◽  
...  

56 Background: Anti-angiogenic strategy in gastric cancer (GC) has been highlighted again due to the recent success of ramucirumab and apatinib. Therefore, the comprehensive network of VEGF, soluble VEGF receptor-2 (sVEGFR2) and cytokines and other angiogenic factors (CAF) in GC and their prognostic impact would be of importance, although they have been poorly understood. We aimed to find out the CAF signature associated with VEGF and sVEGFR2, and to explore their prognostic implication in GC. Methods: We measured pretreatment serum levels of 52 CAFs, including VEGF and sVEGFR2, using multiplex bead immunoassays and ELISA, in 70 patients who were diagnosed with GC in Seoul National University Hospital, and treated with palliative chemotherapy. Linear regression analysis for correlating CAFs with VEGF and sVEGFR2, and survival analysis by log rank test and Cox regression analysis were performed. Results: The VEGF signature was shown to be associated with seven CAFs (interluekin [IL]-7, IL-12p70, IL-2Ra, IL-10, stem cell factor, Fibroblast growth factor-basic, IL-3). The sVEGFR2 signature was associated with IL-4 and platelet-derived growth factor beta, but VEGF and sVEGFR2 showed no association with each other. Patients with high VEGF had a tendency to have worse overall survival (OS) than those with low VEGF (11.2 months versus 16.7 months; P = 0.061). However, among patients with high-sVEGFR2, OS was not different according to VEGF (12.1 months, high-VEGF versus 15.1 months, low-VEGF; P = 0.546). Interestingly, the poor prognostic impact of high-VEGF was far significant in patients with low-sVEGFR2 (10.9 months versus 16.8 months; P = 0.036). With this perspective, VEGF/sVEGFR2 ratio was significantly correlated with worse OS in univariate as well as multivariate analysis (HR 1.78 [95% CI 1.08-2.94], P= 0.024). Conclusions: Based on the comprehensive network analysis of CAF, VEGF and sVEGFR2 had distinct CAF signatures in GC. Consideration of both VEGF and sVEGFR2 confers more accurate prognostic implication compared with VEGF alone in GC. Regarding the angiogenic aspect, VEGF/sVEGFR2 ratio is significantly correlated with survival outcome in GC.


2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Vladan Zivaljevic ◽  
Katarina Tausanovic ◽  
Ivan Paunovic ◽  
Aleksandar Diklic ◽  
Nevena Kalezic ◽  
...  

Background.Anaplastic thyroid cancer (ATC) is one of the tumors with the shortest survival in human medicine.Aim.The aim was to determine the importance of age in survival of patients with ATC.Material and Methods. We analyzed the data on 150 patients diagnosed with ATC in the period from 1995 to 2006. The Kaplan-Meier method and log-rank test were used to determine overall survival. Prognostic factors were identified by univariate and multivariate Cox regression analysis.Results.The youngest patient was 35 years old and the oldest was 89 years old. According to univariate regression analysis, age was significantly associated with longer survival in patients with ATC. In multivariate regression analysis, patients age, presence of longstanding goiter, whether surgical treatment is carried out or not, type of surgery, tumor multicentricity, presence of distant metastases, histologically proven preexistent papillary carcinoma, radioiodine therapy, and postoperative radiotherapy were included. According to multivariate analysis, besides surgery (P=0.000, OR = 0.43, 95% CI = 0.29–0.63), only patients age (P=0.023, OR = 0.68, 95% CI = 0.49–0.95) was independent prognostic factor of favorable survival in patients with ATC.Conclusion. Age is a factor that was independently associated with survival time in ATC. Anaplastic thyroid cancer has the best prognosis in patients younger than 50 years.


2009 ◽  
Vol 62 (2) ◽  
pp. 129-134 ◽  
Author(s):  
H. Hjorth-Hansen ◽  
C. Seidel ◽  
J. Lamvik ◽  
M. Börset ◽  
A. Sundan ◽  
...  

2020 ◽  
Vol 27 (4) ◽  
pp. 199-208 ◽  
Author(s):  
Xinyue Wang ◽  
Xiwen Bi ◽  
Zhangzan Huang ◽  
Jiajia Huang ◽  
Wen Xia ◽  
...  

The significance of androgen receptor (AR) in metastatic breast cancer (MBC) remains unclear, and it is still largely unknown how AR expression level influences HER2-positive tumors. This study aimed to investigate the prognostic and predictive value of AR in HER2-enriched MBC. Primary and/or paired metastatic tumors of 304 patients with pathologically confirmed HER2-enriched MBC were collected and immunohistochemically assessed for AR expression. The associations of AR and other clinicopathological characteristics were compared using the Chi-square test. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan–Meier method and log-rank test. Cox regression analysis was used to determine independent prognostic factors. AR-positivity with a cut-off value of 10% was observed in 237 (78.0%) cases and was associated with longer PFS, 13.2 months, as compared to that of 8.2 months (P = 0.004) in patients with AR-negativity. Moreover, a significant increase in the 5-year OS rate (65.3% vs 36.2%, P < 0.001) was also observed for patients with AR-positive tumors. Cox regression analysis identified AR-positivity as an independent prognostic factor of both PFS (hazard ratio = 0.71, P = 0.039) and OS (HR = 0.53, P = 0.013). Additionally, for those who received first-line Trastuzumab therapies, prolonged PFS (15.8 months vs 8.2 months, P = 0.005) and 5-year OS rate (66.2% vs 26.2%, P = 0.009) were observed in AR-positive tumors compared to AR-negative ones. In conclusion, AR was identified as an independent prognostic factor for favorable PFS and OS and could also predict the efficacy of first-line Trastuzumab treatment in patients with HER2-enriched MBC.


2020 ◽  
Vol 52 (1) ◽  
pp. 86-92 ◽  
Author(s):  
Jiliang Chen ◽  
Zhiping Xie ◽  
Zou Bin

Abstract Objective Cardiovascular diseases (CVDs) are important complications for patients with rheumatoid arthritis (RA). The study aimed to explore whether serum leptin is associated with a increased risk of cardiovascular (CV) events in patients with RA. Methods Two hundred twenty-three patients with RA were followed for a mean of 40 (range = 8-42) months. Serum leptin levels were measured at baseline. Cox regression analysis was performed to assess the association between leptin levels and the risk of CV events. Results The univariate analysis showed that patients with RA with higher serum leptin levels had higher rates of CV events and CV mortality, respectively (P &lt;.001). The logistic regression model showed that leptin was independently related to CVD history (odds ratio = 1.603, 95% confidence interval [CI], 1.329–2.195; P =.005) after adjusting for confounding factors in patients with RA at baseline. The multivariate Cox proportional hazard model suggested that leptin was an independent prognostic factor for CV events in patients with RA after adjustments were made for clinical confounding factors (hazard ratio = 2.467, 95% CI, 2.019–4.495; P &lt;.001). The Kaplan-Meier analysis showed that compared with patients with RA with leptin levels below the median value (≤15.4 mg/L), patients with leptin above the median value (&gt;15.4 μg/L) had a higher rate of CV events (P &lt;.001). Conclusion Leptin was significantly associated with CV events in patients with RA. Elevated serum leptin levels may be a reliable prognostic factor for predicting CV complications in patients with RA.


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