Hepatoma-derived growth factor participates in concanavalin A-induced hepatitis.

Hepatitis is an important health problem worldwide. Novel molecular targets are in demand for detection and management of hepatitis. Hepatoma-derived growth factor (HDGF) has been delineated to participate in hepatic fibrosis and liver carcinogenesis. However, the relationship between hepatitis and HDGF remains unclear. This study aimed to elucidate the role of HDGF during hepatitis using concanavalin A (ConA)-induced hepatitis model. In cultured hepatocytes, ConA treatment-elicited HDGF upregulation at transcriptional level and promoted HDGF secretion while reducing intracellular HDGF protein level and cellular viability. Similarly, mice receiving ConA administration exhibited reduced hepatic HDGF expression and elevated circulating HDGF level, which was positively correlated with serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. By using HDGF knockout (KO) mice, it was found the ConA-evoked cell death was prominently alleviated in KO compared with control. Besides, it was delineated HDGF ablation conferred protection by suppressing the ConA-induced neutrophils recruitment in livers. Above all, the ConA-mediated activation of tumor necrosis factor-α (TNF-α)/interleukin-1ß (IL-1ß)/interleukin-6 (IL-6)/cyclooxygenase-2 (COX-2) inflammatory signaling was significantly abrogated in KO mice. Treatment with recombinant HDGF (rHDGF) dose-dependently stimulated the expression of TNF-α/IL-1ß/IL-6/COX-2 in hepatocytes, further supporting the pro-inflammatory function of HDGF. Finally, application of HDGF antibody not only attenuated the ConA-mediated inflammatory cascade in hepatocytes, but also ameliorated the ConA-induced hepatic necrosis and AST elevation in mice. In summary, HDGF participates in ConA-induced hepatitis via neutrophils recruitment and may constitute a therapeutic target for acute hepatitis.

Pembrolizumab for recurrent/metastatic head and neck squamous cell carcinoma in an Asian population.

Head and neck squamous cell carcinoma (HNSCC) has a high prevalence and is a major cause of cancer deaths in Taiwan. However, there is still no effective salvage therapy that prolongs the life expectancy of patients with recurrent/metastatic (R/M) HNSCC. Immune checkpoint therapy that targets the programmed cell death protein 1 (PD-1) may provide clinical benefit for these patients. We analyzed 22 R/M HNSCC patients who received pembrolizumab, a monoclonal antibody against PD-1, as salvage therapy. Intravenous pembrolizumab was given at a fixed dosage of 100 or 200 mg every 3 weeks. Three patients also received local palliative radiotherapy, but no patients received chemotherapy or targeted drugs. Seventeen patients (77.3%) received at least 3 cycles of pembrolizumab. Based on Response Evaluation Criteria in Solid Tumors criteria (ver. 1.1), 2 patients (9.1%) had complete response, 5 (22.7%) had partial response, and 6 (27.3%) had stable disease, corresponding to a disease control rate of 59.1%. Four patients had confirmed disease progression, 2 of whom had continuous progression over the target lesion after shrinkage of other metastases. One patient developed immune-related pneumonitis that resolved quickly after steroid treatment. Another patient developed itchy skin rashes immediately after administration of pembrolizumab, and this was controlled by an antihistamine. There were no other severe adverse effects. Pembrolizumab is beneficial and well-tolerated for some patients with refractory R/M HNSCC. However, it is important to identify biomarkers to identify the most responsive patients when designing future trials.

Pathologic response during chemo-radiotherapy and variation of serum VEGF levels could predict effects of chemo-radiotherapy in patients with esophageal cancer.

BACKGROUND: To investigate the relationship between pathologic tumor response to concurrent chemo- radiotherapy and variation of serum VEGF in patients with esophageal cancer. MATERIALS AND METHODS: Forty six patients with esophageal cancer who were treated with concurrent chemo-radiotherapy were enrolled. Endoscopic and pathologic examination was conducted before and four weeks afterwards. Serum level of VEGF was documented before, four weeks later and after chemo-radiotherapy. The relationship between pathologic response and the variation of serum level of VEGF and its influence on the prognosis were investigated. RESULTS: Serum level of VEGF decreased remarkably during and after chemo-radiotherapy in patients whose pathologic response was severe (F=5.393, 4.587, P(0.05). There were no statistical differences of serum VEGF level before, during and after chemo-radiotherapy for patients whose pathologic response was moderate or mild. There were 18 (85.7%), 7 (53.8%) and 6 patients (50.0%) whose serum VEGF level dropped in the severe, moderate and mild group, respectively, with significant differences among these groups (p=0.046). Two year survival rates of patients with severe, moderate and mild pathologic response were 61.9%, 53.8% and 33.3% respectively, and no statistically difference between severe and mild group regarding OS (p=0.245) was tested. CONCLUSIONS: Tumor pathologic response during chemo-radiotherapy and the changes of serum VEGF lever could predict curative effects of chemo-radiotherapy in patients with esophageal cancer.

[Expression of phosphatase and tensin homolog in lower rectal cancer on neoadjuvant chemoradiotherapy].

OBJECTIVE: To explore the expression of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in low rectal cancer on neoadjuvant chemoradiotherapy with capecitabine plus radiotherapy. METHODS: Sixty-six patients with low rectal cancer on therapy with capecitabine (1650 mg×m(-2)×d(-1) in 2 divided doses) for two course and concurrent radiotherapy (50 Gy, 2 Gy/day, 5 days a week). Then the investigators analyzed the relationship between the preoperative neoadjuvant chemoradiotherapy and prognosis and measured the expression of PTEN during neoadjuvant chemoradiotherapy. RESULTS: 92.4% (61/66) of patients received neoadjuvant chemoradiotherapy as planned. 87.9% (58/66) tumor stages were down-staged, tumor size decreased while the distance from anal edge increased. And curative resection with sphincter-sparing was carried out in all patients. The rate of sphincter preservation was 90.9% (60/66). Among which, 85.5% patients showed an excellent function of sphincter. The 2-year survival rate was 87.9% (58/66). The survival period was an average of 35.3 months (range: 25-60). The PTEN mRNA and protein expression in cancer tissues on neoadjuvant chemoradiotherapy were significantly higher than those before neoadjuvant chemoradiotherapy (P=0.0079, 0.0269). CONCLUSIONS: The preoperative neoadjuvant chemoradiotherapy in lower rectal cancer patients has shown its efficacy in down-staging cancer, enhancing resectability, offering sphincter preservation, up-regulating PTEN expression, promoting the apoptosis of cancer cell and achieving a better survival rate. Thus preoperative neoadjuvant chemoradiotherapy is an effective adjuvant measure.

XbaI polymorphisms of apolipoprotein B gene: another risk factor of gallstone formation after radical gastrectomy.

AIM: To prospectively investigate the association between the XbaI polymorphisms of apolipoprotein B (APOB) gene and gallstone formation following gastrectomy. METHODS: The study was conducted between January 2005 and December 2006. A total of 186 gastric cancer patients who had undergone radical gastrectomy were grouped according to XbaI polymorphisms of APOB gene (X(+)X(-) group, n = 24 and X(-)X(-) group, n = 162) and compared. The XbaI polymorphisms of APOB gene were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The incidence of gallstone was significantly higher in the X(+)X(-) group than in the X(-)X(-) group [54.2% vs 9.3%, RR = 5.85 (2.23-15.32), P < 0.001]. The serum levels of total cholesterol (TC) and low-density lipoprotein (LDL) were higher in the X(+)X(-) than in the X(-)X(-) group (4.02 +/- 1.12 vs 3.48 +/- 0.88, P = 0.004 before surgery and 3.88 +/- 1.09 vs 3.40 +/- 0.86, P = 0.008 after surgery). LDL was 2.21 +/- 0.96 vs 1.89 +/- 0.84 (P = 0.042) before surgery and 2.09 +/- 0.95 vs 1.72 +/- 0.85 (P = 0.029) after surgery in the two groups. No relationship was found between XbaI polymorphisms and gallbladder motility. CONCLUSION: In Chinese patients after radical gastrectomy, X(+) allele of APOB gene is another risk factor for the development of gallstone besides the gallbladder motility disorder after surgery.

[Relationship of gallstone formation after radical gastrectomy with the polymorphisms of apolipoprotein B Xba I and lipoprotein lipase Hind III gene].

OBJECTIVE: To investigate the relationship of gallstone formation after radical gastrectomy with the polymorphisms of apolipoprotein B (ApoB) Xba I gene and lipoprotein lipase (LPL) Hind III gene. METHODS: A total of 80 gastric cancer patients who underwent radical gastrectomy at our hospital between January 2006 and December 2006 were divided into different groups according to the polymorphisms of ApoB Xba I gene and LPL Hind III gene. The gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism. Gallstone formation 2 years after radical gastrectomy was compared among different genotype groups. RESULTS: Eight patients were lost to follow-up. According to the genotype detection, 72 patients were divided into X(+)X(-) group (10 cases), X(-)X(-) group (62 cases), H(-) group (27 cases) and H(-) deletion group (45 cases). The incidence of gallstone was significantly higher in X(+)X(-) group than that in X(-)X(-) group (60.0% vs 6.5%, P<0.01). The serum levels of total cholesterol TC and low density lipoprotein were significantly higher in X(+)X(-) group than those in X(-)X(-) group (P<0.05), but the level of ApoB was not significantly different between the two groups. The incidence of gallstone was not significantly different between H(-) group and H(-) deletion group (14.8% vs 13.3%). The level of triglyceride in H(-) group was significantly lower than that in H(-) deletion group before operation, however the difference disappeared after operation. CONCLUSION: X(+) allele may be associated with gallstone formation after radical gastrectomy, while H(-) may not.