Hepatoma-Derived Growth Factor: An Overview and Its Role as a Potential Therapeutic Target Molecule for Digestive Malignancies.

Hepatoma-derived growth factor (HDGF) was identified in research seeking to find a novel growth factor for hepatoma cells. Subsequently, four HDGF-related proteins were identified, and these proteins are considered to be members of a new gene family. HDGF has a growth-stimulating role, an angiogenesis-inducing role, and a probable anti-apoptotic role. HDGF is ubiquitously expressed in non-cancerous tissues, and participates in organ development and in the healing of damaged tissues. In addition, the high expression of HDGF was reported to be closely associated with unfavorable clinical outcomes in several malignant diseases. Thus, HDGF is considered to contribute to the development and progression of malignant disease. We herein provide a brief overview of the factor and its functions in relation to benign and malignant cells. We also describe its possible role as a target molecule for digestive malignancies.

Multicenter, randomized, controlled trial of S-1 monotherapy versus S-1 and interferon-α combination therapy for hepatocellular carcinoma with extrahepatic metastases.

AIM: No effective therapies for extrahepatic metastases from hepatocellular carcinoma (HCC) have yet been identified. Previous studies suggested a potentially promising antitumor effect of combination therapy of S-1, a novel oral dihydropyrimidine dehydrogenase inhibitor, and interferon (IFN)-α. The present study aimed to investigate the clinical efficacy of single agent S-1 and S-1/IFN-α for HCC patients with extrahepatic metastases in a randomized, open-label, multicenter trial. METHODS: A total of 103 patients with HCC with extrahepatic metastases were randomly assigned to the S-1/IFN-α group, receiving the combination of S-1 and IFN-α, or the S-1 group, receiving the single agent of S-1. Clinical efficacy and adverse events were compared between the two groups. RESULTS: A total of 49 patients in the S-1/IFN-α group and 51 patients in the S-1 group were included in the efficacy analysis. The response rate was 22.4% (11/49) in the S-1/IFN-α group and 13.7% (7/51) in the S-1 group; there was no significant difference. Overall and progression-free survival in the two groups were also not significantly different (1-year overall survival 50.8% vs. 72.4%, median progression-free survival 127 days vs. 157 days). The incidence of grade ≥3 adverse events in the S-1/IFN-α group was 62.7% (32/51), which tended to be higher than in the S-1 group (43.1% [22/51]). CONCLUSIONS: Oncological outcomes in both treatment groups were favorable compared with previous reports, though there was no significant beneficial effect of adding IFN-α to S-1 for the treatment of HCC patients with extrahepatic metastases.

Pancreatic juice cytology as sensitive test for detecting pancreatic malignancy in intraductal papillary mucinous neoplasm of the pancreas without mural nodule.

OBJECTIVE: Recent studies reported that mural nodule (MN) was the most associated with malignant intraductal papillary mucinous neoplasms (IPMNs). However, IPMNs without MN cannot be diagnosed as malignant if only MN is determined to be indicator of malignancy. This study aimed to investigate role of pancreatic juice cytology for IPMNs without MN. METHODS: Medical records of 50 patients with histologically proven malignant IPMNs were reviewed. Exclusively for non-invasive cancer, extent of high-grade dysplasia along the main pancreatic duct (MPD) was determined microscopically. RESULTS: Thirty-six percent IPMNs had no MN. Cyst and main MPD diameter were significantly smaller in IPMN without MN compared to those in IPMN with MN (23 ± 14.1 vs 35 ± 13.2 mm, p = 0.010; 6.6 ± 4.3 vs 10.9 ± 6.1 mm, p = 0.006). Sensitivity of pancreatic juice cytology was higher in IPMN without MN compared to that in IPMN with MN (94% vs 53%, p = 0.004) although it could be affected by selection bias of study patients. Absence of MN was determined to be an independent factor associated with true positive cytology (OR = 24.3, p = 0.005). Extent of high-grade dysplasia was significantly longer in IPMN with true positive cytology compared to that in IPMN with false negative cytology (46.8 ± 20.5 vs 26.4 ± 11.0 mm, p = 0.005), and tended to be longer in IPMN without MN compared to that in IPMN with MN (47.0 ± 19.0 vs 36.0 ± 20.1 mm, p = 0.16). CONCLUSIONS: Sensitivity of pancreatic juice cytology was excellent in IPMN without MN. Pancreatic juice cytology may be a sensitive test for detection of pancreatic malignancy in IPMN without MN compared to high-risk imaging features.

Clinical significance of serum Wisteria floribunda agglutinin positive Mac-2-binding protein level in non-alcoholic steatohepatitis.

AIM: To examine the relationship between the Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA+ -M2BP) level and histological findings for patients with non-alcoholic steatohepatitis (NASH). METHODS: A total of 134 NASH patients (mean age, 51.7 years) were analyzed. We examined the effect of WFA+ -M2BP level on severity of liver fibrosis comparing with other laboratory markers, including aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio, AST to platelet ratio index (APRI), FIB-4 index, platelet count and hyaluronic acid as serum liver fibrosis markers. Receiver-operator curve (ROC) analysis was performed for calculating the area under the ROC (AUROC). RESULTS: The WFA+ -M2B P-value ranged from 0.2 cut-off index (COI) to 9.6 COI (median, 0.9). The median values in each fibrosis stage were: 0.7 COI in F1, 0.7 COI in F2, 1.2 COI in F3 and 2.4 COI in F4 (P < 0.001). For predicting liver cirrhosis (F4), WFA+ -M2BP level had the AUROC of 0.854 (sensitivity, 69.2%; specificity, 88.4%) and for predicting advanced liver fibrosis (≥F3), WFA+ -M2BP level yielded the second highest AUROC with a level of 0.842 (sensitivity, 73.7%; specificity, 80.2%) and for predicting significant liver fibrosis (≥F2), WFA+ -M2BP level yielded the highest AUROC with a level of 0.663 (sensitivity, 47.2%; specificity, 78.6%) among six liver fibrosis markers. The median values in patients with ballooning scores 1 (n = 58) and 2 (n = 76) were 0.6 and 1.1 COI, respectively (P < 0.001). CONCLUSION: Serum WFA+ -M2BP level can be useful for assessing liver histological findings in patients with NASH.

Comparison of sleep disorders in chronic hepatitis C patients treated with interferon-based therapy and direct acting antivirals using actigraphy.

This study aimed to compare the severity of sleep problems between chronic hepatitis C (CHC) patients treated with interferon (IFN)-based triple therapy (pegylated [Peg]-IFN plus ribavirin [RBV] plus simeprevir [SMV]) and those who received IFN-free direct-acting antiviral (DAA) therapy. METHODS: Our study included 31 patients in group A (Peg-IFN/RBV/SMV combination therapy) and 41 patients in the group B (IFN-free DAA therapy). We prospectively compared the effect of each antiviral treatment regimen on sleep conditions between the two groups adding actigraphy data. Five parameters detected by actigraphy (objective assessment) and scores of the Pittsburgh Sleep Quality Index (subjective assessment, n = 30 [group A] and 35 [group B]) were estimated. The causal effect of each therapy on sleep disturbances was evaluated at baseline and at 4 weeks after commencement of therapy. RESULTS: In terms of baseline characteristics, no significant differences between groups were found, except for hepatitis C virus genotype. In group A, sustained virological response 12 rate was 83.9% (26/31), whereas in group B it was 95.1% (39/41). In group A, each score of waking after sleep onset, activity index, wake episodes, and Pittsburgh Sleep Quality Index at 4 weeks significantly increased compared to those evaluated at baseline. In group B, scores of all variables except for sleep episodes at 4 weeks did not significantly change compared to those at baseline. CONCLUSION: Interferon-based triple therapy in patients with CHC may cause significant sleep disturbances. Interferon-free DAA therapy is less likely to deteriorate sleep conditions in patients with CHC.

Hepatoma-Derived Growth Factor: Its Possible Involvement in the Progression of Hepatocellular Carcinoma.

The development of hepatocellular carcinoma (HCC) is an important complication of viral infection induced by hepatitis virus C, and our major research theme is to identify a new growth factor related to the progression of HCC. HDGF (hepatoma-derived growth factor) is a novel growth factor that belongs to a new gene family. HDGF was initially purified from the conditioned medium of a hepatoma cell line. HDGF promotes cellular proliferation as a DNA binding nuclear factor and a secreted protein acting via a receptor-mediated pathway. HDGF is a unique multi-functional protein that can function as a growth factor, angiogenic factor and anti-apoptotic factor and it participates in the development and progression of various malignant diseases. The expression level of HDGF may be an independent prognostic factor for predicting the disease-free and overall survival in patients with various malignancies, including HCC. Furthermore, the overexpression of HDGF promotes the proliferation of HCC cells, while a reduction in the HDGF expression inhibits the proliferation of HCC cells. This article provides an overview of the characteristics of HDGF and describes the potential role of HDGF as a growth-promoting factor for HCC.

Hepatitis C virus relapse was suppressed by long-term self-injection of low-dose interferon in patients with chronic hepatitis C after pegylated interferon plus ribavirin treatment.

AIM: The recommended treatment for chronic hepatitis C is a combination of pegylated interferon (PEG IFN) plus ribavirin (RBV). However, the sustained virological response (SVR) rate of PEG IFN-RBV therapy was approximately 50% in patients with genotype 1b and a high viral load. Thus, we compared the efficiencies and side-effects of PEG IFN-RBV and self-injected low-dose natural (n) IFN-α in patients with hepatitis C virus (HCV). METHODS: A prospective, multicenter, open-label study was conducted in 12 Japanese institutions. A total of 129 patients with chronic hepatitis C and no detectable HCV after 24-72 weeks of PEG IFN-RBV treatment were assigned to the control (n = 82) or treated (n = 47) group. Treated patients received 3 million units of nIFN-α 2-3 times/week over 96 weeks. The groups were compared regarding treatment efficiency and side-effects. RESULTS: Significant treatment success regarding virus negativation rates was found, with 89% and 73% for the treated and control groups, respectively (P = 0.039). In contrast, there was no difference in relapse rate between the groups 24 weeks after the 96-week nIFN-α treatment (P = 0.349). However, when early viral responders and late viral responders (LVR) were separated, LVR patients responded significantly to the treatment with 90% sustained virological response, compared to 53% for the control group (P = 0.044). The side-effects of nIFN-α were less than that of PEG IFN-RBV treatment. CONCLUSION: Self-injected nIFN-α has larger benefits than prolonged PEG IFN-RBV for chronic hepatitis C patients with high viral loads of genotype 1b who fail to achieve early viral response during initial combination treatment.

Study on the mechanism causing elevation of serum CA19-9 levels in diabetic patients.

Serum CA19-9 levels are often elevated in diabetic patients. To elucidate this mechanism, we investigated the metabolism of CA19-9 in diabetic patients without obvious cancer. Study 1 included 119 patients in whom HbA1c, glycated albumin (GA) and CA19-9 were measured at the time of hospital admission. Study 2 examined 6 patients with markedly elevated CA19-9 levels (≥100 U/mL). Their half-lives for HbA1c, GA, and serum CA19-9 were calculated using the data before and after diabetes treatment. Three diabetic patients with pancreatic cancer were also examined as controls. In Study 1, serum CA19-9 (logarithmically transformed value) was significantly correlated with fasting plasma glucose (FPG), HbA1c and GA. On multivariate analysis, GA and FPG, but not HbA1c, were significant explanatory variables for serum CA19-9. In Study 2, serum CA19-9 decreased together with HbA1c and GA after diabetes treatment. The calculated half-lives for HbA1c, GA, and serum CA19-9 were 33.8 days, 16.1 days, and 10.9 days, respectively. The half-life of serum CA19-9 was longer in the study patients than that reported in patients with malignant tumors. By contrast, in the diabetic patients with pancreatic cancer serum CA19-9 showed a marginal decrease after diabetes treatment. Taken all together, prolonged half-life of serum CA19-9 may contribute to the increase in serum CA19-9 levels in diabetic patients without obvious cancer.

Development of a new in situ hybridization method for the detection of global bacterial DNA to provide early evidence of a bacterial infection in spontaneous bacterial peritonitis.

BACKGROUND & AIMS: Despite the importance of identifying the causative pathogen(s), ascitic fluid cultures are occasionally negative in patients with spontaneous bacterial peritonitis (SBP). A novel strategy using the in situ hybridization (ISH) method was introduced to detect the bacterial genomic DNA phagocytized in the blood of patients with sepsis. In the present study, we developed a new ISH probe to detect global bacterial DNA (named as GB probe) and evaluated its utility for detecting the phagocytized bacterial DNA in SBP ascites. METHODS: Hybridization of bacterial DNA with the GB probe was examined by dot-blot and ISH tests. In addition, the utility of the ISH method to detect the bacterial DNA in the leukocytes of SBP ascites was evaluated. RESULTS: The GB probe hybridized with the genomic DNA of all 59 bacterial strains tested (59 species of 36 genus). Eleven of 51 patients with ascites (out of total 542 cirrhotic inpatients) were categorized as SBP. The ISH tests showed positive results in 10 of 11 SBP cases. However, the ISH tests all showed negative results in the 40 non-SBP ascitic samples. Therefore, the ISH tests yielded highly sensitive and specific results for detecting the phagocytized bacterial DNA in the leukocytes of SBP ascites. Moreover, all of the ISH test results were obtained within only one day. CONCLUSIONS: Our newly established ISH method was found to provide both a rapid and sensitive detection of bacterial DNA in SBP ascites, thus suggesting its utility for providing early and direct evidence of bacterial infection in SBP ascites.

Relationship between elevation of glycated albumin to glycated hemoglobin ratio in patients with a high bleeding risk of esophageal varices.

BACKGROUND/AIMS: Variceal hemorrhaging due to portal hypertension is a severe complication of liver cirrhosis. Although several biomarkers have been reported as predictors of the presence of varices, it is still difficult to assess the risk of variceal bleeding without esophagogastroduodenoscopy (EGD). The ratio of glycated albumin (GA) to glycated hemoglobin (HbA1c) was reported to increase with the progression of liver fibrosis. The aim of the study was to investigate whether the GA/HbA1c ratio is related to the severity and bleeding-risk of the varices. METHODOLOGY: We measured the GA/HbA1c ratio of HCV-related cirrhotic patients with Child-Pugh class A status and analyzed its relationship with the presence and bleeding risk of varices. RESULTS: The GA/HbA1c ratio was higher in the patients who had the varices with a high risk of hemorrhage than in the patients with a low risk of bleeding. In addition, the GA/HbA1c ratio was higher in patients with varices than that in patients without varices. Furthermore, the GA/HbA1c ratio was the most significantly different parameter of all the factors examined, including the platelet count, prothrombin activity and albumin level. CONCLUSIONS: The GA/HbA1c ratio is increased in patients with varices and with the bleeding risk of the varices.

Extraordinary pleiotropy of protein kinase CK2 revealed by weblogo phosphoproteome analysis.

A weblogo has been generated from the sequences surrounding 433 Ser/Thr protein residues whose phosphorylation by protein kinase CK2 had been previously validated ("bona fide" CK2 phosphosites). This has been compared to the weblogo extracted from 2275 putative CK2 phosphosites displaying the motif pS/pT-x1-x2-D/E/pS (where x1 not=P) present in the human phosphoElm database including 10899 naturally occurring phosphosites. The two weblogos are strikingly similar supporting the notion that indeed the 2275 putative sites (accounting for 20.9% of the whole phosphoproteome they belong to), or at least the great majority of these are generated by CK2. This conclusion has been corroborated by the random validation of 8 of such putative CK2 sites (belonging to 5 different proteins) as real targets of CK2 in vitro and/or in cells, leading to the inclusion into the repertoire of bona fide CK2 targets of 5 new entries, namely: oxidative stress-responsive kinase-1, anthrax toxin receptor 1, hepatoma derived growth factor, EpsinR and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like.

Hepatocellular Carcinoma-associated microRNAs Induced by Hepatoma-derived Growth Factor Stimulation.

BACKGROUND/AIM: Hepatoma-derived growth factor (HDGF) is involved in the progression of hepatocellular carcinoma (HCC). The present study assessed the epigenomic changes in hepatoma-derived cells through HDGF stimulation. MATERIALS AND METHODS: We used two hepatoma-derived cell lines (HepG2 and SK-Hep1) and searched for microRNAs whose expression commonly changed in response to HDGF administration. We further explored a genetic database to investigate the association of the candidate microRNAs with the survival of HCC patients. RESULTS: Despite both HepG2 and SK-Hep1 cells being categorized as hepatoma-derived cells, the microRNA profile differed between these two lines. However, HepG2 and SK-Hep1 cells shared 30 up-regulated and 2 down-regulated microRNAs. Of these, miR-6072 and miR-3137 were significantly associated with a poor prognosis in HCC patients. CONCLUSION: We identified two candidate microRNAs whose expression increased in response to HDGF stimulation. Both these molecules were associated with a poor prognosis of HCC patients.

Involvement of hepatoma-derived growth factor in the growth inhibition of hepatocellular carcinoma cells by vitamin K(2).

BACKGROUND: Vitamin K(2) has been reported to suppress the growth of human hepatocellular carcinoma (HCC) in vitro and hepatocarcinogenesis in hepatitis C virus (HCV)-related cirrhosis in vivo. Hepatoma-derived growth factor (HDGF) is a unique nuclear targeting growth factor that is highly expressed in HCC cells and is a possible prognostic factor for patients with HCC. We investigated the regulation of HDGF expression by vitamin K(2). METHODS: Three HCC-derived cell lines, HepG2, HuH-7, and SK-Hep-1, were used. Cell number was determined with the MTT assay. The expression levels of HDGF mRNA and protein were measured by the real-time reverse transcriptase-polymerase chain reaction (PCR) method and ELISA and Western blot analysis, respectively. The HDGF promoter activity was measured by a dual luciferase-reporter assay. RESULTS: Vitamin K(2) suppressed the growth of the three HCC cell lines in a dose-dependent manner. Vitamin K(2) significantly suppressed the expression of the HDGF protein and mRNA in three cell lines. By a luciferase assay, vitamin K(2) significantly suppressed the promoter activity of the HDGF protein. Based on some luciferase-reporter plasmids containing truncated promoter regions, the possible responsive site of vitamin K(2) seems to reside in the region -1 to -150 bp of the HDGF gene. CONCLUSIONS: These findings suggested that regulation of the HDGF gene expression is one of the crucial mechanisms of vitamin K(2)-induced cell growth suppression for HCC.

Hepatoma-derived growth factor is induced in liver regeneration.

AIM: Hepatoma-derived growth factor (HDGF) is a heparin-binding protein, which has been suggested to be involved in the development of kidneys, the cardiovascular system and the liver. We have shown that HDGF is highly expressed in parenchymal hepatocytes in the developing liver and promotes fetal hepatocyte proliferation. In the present study, we asked whether HDGF expression was related to liver regeneration. METHODS: We examined the mRNA and protein expressions of HDGF in two liver regeneration models. In addition, cellular distribution of HDGF in the regenerating liver was investigated by immunohistochemistry. RESULTS: In the carbon tetrachloride (CCl(4))-treated liver, HDGF expression was induced and the peak was detected at 24 h after the CCl(4 )injection. HDGF expression was also enhanced in the hepatectomy model and the peak was detected at 12 h after surgery. The increased expression of HDGF protein was also confirmed by western blotting. Expression of the HDGF gene in the regenerating liver was dominantly detected in parenchymal hepatocytes. CONCLUSION: These findings showed that HDGF expression was induced in parenchymal hepatocytes before the DNA synthesis in the regenerating liver, suggesting the possible involvement of HDGF in liver regeneration as an autocrine factor.

New chemotherapy for patients with advanced hepatocellular carcinoma: Pilot study of beta-interferon and doxorubicin one-shot intra-arterial chemotherapy.

BACKGROUND: Patients with advanced hepatocellular carcinoma (HCC) need an effective treatment modality because of the poor prognosis of the disease. From an in vitro study, beta-interferon (IFN-beta) has been reported to enhance the antiproliferative effects of doxorubicin on HCC cell lines. In the present study, we investigated the therapeutic effects of combined IFN-beta and doxorubicin intra-arterial injection therapy on patients with advanced HCC. METHODS: IFN-beta (3 MIU) and doxorubicin (10 mg/bodyweight) were given by one-shot intra-arterial injection through an arterial port to patients with advanced HCC. One treatment course consisted of three intra-arterial injections per week for 4 weeks. Three courses were conducted and evaluation was done monthly. RESULTS: Eleven patients with advanced HCC were treated with combined IFN-beta and doxorubicin. One patient enteredcomplete remission (CR), seven patients were evaluated as having stable disease (SD) and three as having progressive disease (PD). The mean overall survival was 10 months. The mean survival for CR and SD patients was 15 months, and that for PD patients was 6 months (P = 0.0464, log-rank test). Decrease of serum total bilirubin was observed for all patients. CONCLUSION: Combined IFN-beta and doxorubicin intra-arterial therapy offers an effective chemotherapy option for patients with advanced HCC by improving liver function and having tolerable side-effects.

Triple therapy of initial high-dose interferon with ribavirin and amantadine for patients with chronic hepatitis C.

AIMS: We previously reported the potential effect of combination therapy of an initial high-dose interferon (IFN) and amantadine on the eradication of HCV-RNA in patients with chronic hepatitis C. The additive effects of amantadine on interferon and ribavirin combination therapy remain controversial. In this study we investigated the efficacy of initial high-dose IFN with ribavirin and amantadine on the virological response in patients with chronic hepatitis C with a high viral load of genotype 1b. METHODS: Twenty-two patients with high viral loads of genotype 1b hepatitis C virus were enrolled in this pilot study. Patients were administered IFN-beta for four weeks and then IFN-alpha2b for 22 weeks with daily oral administration of ribavirin and amantadine. RESULTS: A sustained virological response (SVR) was shown in 31.8% (seven of 22 patients). With the naïve patients, the SVR rate was 21.4% (three of 14 patients). In patients who could not eradicate HCV-RNA by previous IFN monotherapy, the SVR rate was 50% (four of eight patients). CONCLUSION: Triple therapy with an initial high dose of IFN with ribavirin and amantadine may be effective, especially for chronic hepatitis C IFN-retreatment patients with a high viral load of genotype 1b.

Vitamin K2 inhibits the proliferation of HepG2 cells by up-regulating the transcription of p21 gene.

AIM: Vitamin K2 has been reported to inhibit the growth of human hepatocellular carcinoma (HCC) in vitro and suppress hepatocarcinogenesis in vivo. However, its inhibitory mechanism has not yet been clarified. METHODS: Different concentrations of vitamin K2 (30, 10, 1, 0.1 and 0.01 muM) were added to the HCC cell line HepG2 to assess effects on cell growth. The effect of vitamin K2 on cell cycle progression was determined by flow-cytometric analysis. The expression of cell cycle regulatory proteins p21 and p27 was then examined by Western blot. Whether vitamin K2 regulates the gene expression through action on the p21 promoter region was investigated by luciferase assay. RESULTS: Vitamin K2 inhibited the growth of HepG2 cells dose-dependently, and its inhibitory rate reached approximately 50% at the dose of 30 muM after 96 h treatment. After treatment with vitamin K2, the proportion of cells in G0-G1 phase increased, and in S phase decreased. Apoptotic cells were not detected. The expression of cell cycle regulatory protein p21 was induced by vitamin K2 treatment, but p27 was not. By the luciferase assay, vitamin K2 significantly activated the promoter of p21. Knock-down of p21 by siRNA reversed the growth inhibition of HepG2 cells by vitamin K2. CONCLUSIONS: The findings suggest that vitamin K2 suppresses the proliferation of HCC cells by blocking the cell cycle G1/S progression through the transcriptional induction of p21.

Expression of hepatoma-derived growth factor is correlated with lymph node metastasis and prognosis of gastric carcinoma.

PURPOSE: Hepatoma-derived growth factor (HDGF) is a unique nuclear/growth factor and might play an important role in the development and progression of carcinomas. In the present study, association of HDGF expression with recurrence and prognosis of gastric carcinoma was examined. PATIENTS AND METHODS: HDGF expression in 317 patients with gastric carcinoma (233 males and 84 females) with ages ranging from 26 to 81 years (median, 60 years) was analyzed by immunohistochemistry. Samples with >90% of tumor cells to express positive immunoreactivity similar to or stronger than that in endothelial cells both for nucleus and cytoplasm were regarded as HDGF index level 2, and others as HDGF index level 1. RESULTS: One hundred and eighty-two cases showed level 1 HDGF expression, whereas 135 cases showed level 2 HDGF expression. Patients with level 2 expression showed higher rates of proximal tumor location (P < 0.0001), large tumor size (P < 0.0001), infiltrative tumor growth (P < 0.0001), presence of vascular and lymphatic invasion (P < 0.0001 for both), presence of lymph node metastasis (P < 0.0001), deep tumor invasion (P < 0.0001), and poorer disease-free and overall survival (P < 0.0001 for both) compared to those with level 1 expression. Multivariate analysis revealed HDGF expression level as an independent prognosticator for disease-free and overall survival. CONCLUSION: HDGF expression level was shown to be a prognostic factor for gastric carcinoma.

Hepatoma-derived growth factor is a novel prognostic factor for patients with pancreatic cancer.

PURPOSE: Hepatoma-derived growth factor (HDGF) is a nucleus-targeted growth factor playing an important role in the development and progression of cancers. This study investigated the correlation of HDGF expression and prognosis in patients with pancreatic ductal carcinoma. PATIENTS AND METHODS: HDGF expression in pancreatic cancer cell lines was analyzed by Western blotting. HDGF expression was analyzed by immunohistochemistry for 50 patients with primary ductal carcinoma of the pancreas (33 male and 17 female) ranging in age from 48 to 80 years (median, 65 years) receiving surgical treatment. Cancer cells showing stronger staining than the noncancerous ducts were regarded as positive. Cases showing positive staining in < 90% and > 90% of tumor cells were regarded as HDGF labeling index (LI) levels 1 and 2, respectively. HDGF LI was determined separately for the nucleus and the cytoplasm. RESULTS: Western blotting showed HDGF expression in pancreatic cancer cells similar to that of hepatic cell lines. Twenty-three (46%) and 27 (54%) cases and 22 (44%) and 28 (56%) cases showed HDGF LI levels 1 and 2 for the nucleus and the cytoplasm, respectively. Patients with nuclear HDGF LI level 1 showed a significantly better 5-year survival rate (37.0%) than those with level 2 (6.8%; P = 0.023). No significant difference was observed in the cytoplasmic HDGF LI classification. Multivariate analysis revealed nuclear HDGF LI to be an independent prognosticator. CONCLUSIONS: These findings suggest that HDGF could be a novel prognostic factor for pancreatic ductal carcinoma.

Corrigendum to "An Increased Ratio of Glycated Albumin to HbA1c Is Associated with the Degree of Liver Fibrosis in Hepatitis B Virus-Positive Patients".

[This corrects the article DOI: 10.1155/2014/351396.].