Type of Necrosis Influences Prognosis in Hepatocellular Carcinoma After the First Transarterial Chemoembolization.

BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common tumors. Transarterial chemoembolization (TACE) is the first choice of treatment for intermediate HCC and an important treatment option for advanced HCC. This retrospective study compared the prognosis between patients showing coagulative necrosis and patients showing liquefactive necrosis after the first TACE procedure. MATERIAL AND METHODS We divided 171 patients with Barcelona Clinic Liver Cancer (BCLC) Stage B or C HCC into 2 groups; a coagulative necrosis group (79 patients) and a liquefactive necrosis group (92 patients). The coagulative and liquefactive necroses were identified by computed tomography after the first TACE procedure. Kaplan-Meier analysis was used to identify the differences in the overall survival (OS) and progression-free survival (PFS) between the 2 groups, and the associated risk factors and safety of TACE were analyzed. RESULTS The median OS durations were 23.27±1.40 months and 8.83±2.15 months (P=0.004) and the median PFS durations were 9.33±0.96 months and 3.70±0.44 months (P=0.002) in the coagulative necrosis and liquefactive necrosis groups, respectively. Intrahepatic in situ progression, new intrahepatic metastasis, and extrahepatic progression occurred significantly earlier in the liquefactive necrosis group (P<0.05). Univariate analysis and multivariate analyses showed liquefactive necrosis was the main risk factor for OS. There was no significant difference in the hepatic function impairment or post-embolism syndrome after TACE. CONCLUSIONS After the first TACE procedure, the patients with liquefactive necrosis experienced recurrence and metastasis earlier and had a worse prognosis. Therefore, these patients should be considered for earlier administration of targeted therapies or immunotherapies after TACE.

The programmed cell death 6 interacting protein insertion/deletion polymorphism is associated with non-small cell lung cancer risk in a Chinese Han population.

It has been proposed that genetic factors contribute to the susceptibility of non-small cell lung cancer (NSCLC). The programmed cell death 6 interacting protein (PDCD6IP) encodes for a protein that has been known to bind to the products of the PDCD6 gene, a required protein in apoptosis. The aim of this study is to investigate the relationship between PDCD6IP insertion/deletion (I/D) polymorphism (rs28381975) and NSCLC risk in a Chinese population. A population-based case-control study was conducted in 449 NSCLC patients and 512 cancer-free controls. The genotype of the PDCD6IP gene was determined by using a polymerase chain reaction assay. The promoter activity was analyzed by luciferase reporter assay in A549 and H1299 cells. Statistically significant difference was observed when the patients and controls were compared according to ID + II versus DD (OR = 1.72, 95 % CI 1.29-2.31, P < 0.01). The I allele was significantly associated with NSCLC risk (OR = 1.41, 95 % CI 1.18-1.69, P < 0.01). Compared to TNM stage I + II, PDCD6IP I/D polymorphism significantly increased advanced NSCLC risk (OR = 2.06, 95 % CI 1.30-3.26, P < 0.01). Promoter reporter structures carrying the I allele displayed significantly higher promoter activity than the D allele in A549 and H1299 cells (P = 0.001). The results from this study suggested that PDCD6IP I/D polymorphism was potentially related to NSCLC susceptibility in Chinese Han population.

[Inhibitory effect of compound cantharides capsule on the proliferation of xenografts of human hepatocellular carcinoma HepG(2)215 in mice].

OBJECTIVE: To investigate the inhibitory effect of compound cantharides capsules on the proliferation of xenografts of human hepatocellular carcinoma HepG(2215) in mice and their mechanism of action. METHODS: One hundred healthy Balb/c mice (5-week old, male:female 1:1) were used in this study. Mouse models of human HepG(2215) hepatocarcinoma were established. The tumor-bearing mice were divided into five groups randomly. The control group A received daily intragastric administration of physiologic saline. The intervention groups B1, B2 and B3 were treated with compound cantharides capsule in a dose of 12.5 mg×kg(-1)×d(-1), 25 mg×kg(-1)×d(-1) and 37.5 mg×kg(-1)×d(-1), respectively, for 10 consecutive days. The group C had intraperitoneal injection of cyclophosphamide (25 mg×kg(-1)×d(-1)) for 10 consecutive days. The mice were sacrificed after the completion of administration. The tumors were taken out, the tumor volume was measured, the inhibitory rate of body weight was calculated, and the serum AFP concentration and the level of HBV DNA were determined. The survival of each group mice was analyzed. The levels of mRNA expression of apoptosis-related genes were assayed by quantitative RT-PCR. Apoptosis in the tumor cells was assayed with TUNEL staining. Flow cytometry was used to detect the levels of CD3(+), CD19(+), CD4(+) and CD8(+), and microvessel density (MVD) of the tumors was assessed by immunohistochemistry. RESULTS: After completion of the treatment, the inhibition rate of tumor growth of the groups B1, B2 and B3 was 29.8%, 38.7% and 48.1%, respectively, and that of the group C was 52.4%, with a significant difference among the groups (P < 0.05). The median survival time of the groups A, B1, B2, B3 and C was (30.0 ± 3.2) days, (49.0 ± 5.1) days, (50.0 ± 5.2) days, (57.5 ± 6.5) days and (49.0 ± 4.7) days, respectively. The median survival time of the group B3 was significantly longer than that of other groups (P < 0.05). The serum AFP level in the groups A, B1, B2, B3 and C was (492.7 ± 48.5) ng/ml, (281.2 ± 25.6) ng/ml, (194.3 ± 18.7) ng/ml, (170.1 ± 15.8) ng/ml and (138.7 ± 12.5) ng/ml, respectively, indicating that it was significantly inhibited in the group C. The inhibition rate of HBV DNA replication of the groups B1, B2, B3 and C was (46.0 ± 5.1)%, (65.5 ± 6.9)%, (81.3 ± 7.8)% and (19.5 ± 2.1)%, respectively, showing that compound cantharides capsules inhibited HBV DNA replication in a dose-dependent manner. The apoptosis rate of the groups A, B1, B2, B3 and C was (0.27 ± 0.03)%, (7.18 ± 2.12)%, (9.17 ± 2.42)%, (11.27 ± 3.03)% and (5.44 ± 2.45)%, respectively, and that of the group B3 was significantly higher than that of the groups A, B1, B2 and C (P < 0.05). The expression level of bax mRNA was significantly higher than that of the group C (P < 0.05). The drug could significantly decrease the bcl-2 mRNA expression level, more remarkably along with the increasing dose of cantharides, and it was significantly lower than that in the group C (P < 0.05). The levels of CD4(+), CD8(+), CD3(+) and CD19(+) were significantly higher than that in the groups A and C (P < 0.05). The value of MVD of the group B3 was significantly lower that that of groups A and C (P < 0.05). CONCLUSION: Compound cantharides capsules may inhibit the replication of HBV DNA in HepG(2215) cells, inducing apoptosis in the tumor cells, enhancing the immune function to inhibit the growth of liver cancer cells in mice, and significantly prolong the median survival time of tumor-bearing mice.

Amplification and overexpression of PPFIA1, a putative 11q13 invasion suppressor gene, in head and neck squamous cell carcinoma.

Chromosomal amplifications of the 11q13 genomic region are frequent in head and neck squamous cell carcinoma (HNSCC). To identify novel 11q13 amplification targets, we integrated high-resolution array-based comparative genomic hybridization and Affymetrix gene-expression profiling of eight HNSCC cell lines. We found that PPFIA1 was the highest upregulated gene in the 11q13 amplicon of HNSCC cell lines when compared with HNSCC lines without 11q13 amplification and confirmed the upregulation of PPFIA1 in primary HNSCCs by real-time PCR. Using siRNA knockdown, we investigated PPFIA1 function in three HNSCC lines using both in vitro invasion assays and wound-healing assays. Surprisingly, we found that cancer cells become more invasive when the PPFIA1 protein levels were reduced, suggesting that PPFIA1 may act as an invasion inhibitor in HNSCC. This unexpected result suggests that the 11q13 amplicon may comprise both positive and negative regulators involved in HNSCC. Our study is the first to evaluate the role of PPFIA1 in head and neck carcinogenesis and suggests a potential link between PPFIA1 activity and cell-extracellular matrix interactions. This article contains supplementary material available via the Internet at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.

Efficacy of radiofrequency ablation and microwave ablation in the treatment of thoracic cancer: A systematic review and meta-analysis.

BACKGROUND: Radiofrequency ablation and microwave ablation are frequently prescribed for thoracic cancer. However, few writers have been able to draw on any systematic research into the differences between the two ablation methods. METHODS: A literature search was carried out using Embase, PUBMED, Web of Science, Cochrane Library, and CNKI databases, with additional searches carried out manually using terms associated with thoracic cancer and thermal ablation. Then we used Google Scholar for a complementary search. Data were extracted from studies of patients that underwent radiofrequency ablation or microwave ablation, and the investigator carried out efficacy evaluation and follow up. The data obtained from the literature were summarized and analyzed using Cochrane Revman software Version 5.3 and SPSS 22.0. RESULTS: There were seven comparative studies, but no randomized studies identified for data extraction; 246 patients received radiofrequency ablation therapy and 319 controls received microwave ablation. There was no significant difference in the six-month, one-year, two-year, and three-year survival rates, and adverse reactions were found in the two treatments. For patients' long-term survival rate, the two treatments can achieve a similar survival time. CONCLUSION: In the treatment of thoracic cancer, microwave ablation can achieve the same efficacy as radiofrequency ablation.

Di-µ(2)-chlorido-bis-[aqua-(2,2'-bipyridine-4,4'-dicarboxylic acid-κN,N')(nitrato-κO)copper(II)].

In the title compound, [Cu(2)Cl(2)(NO(3))(2)(C(12)H(8)N(2)O(4))(2)(H(2)O)(2)], which consists of a chloride-bridged Cu(II) dimer, the Cu atom is in a distorted octa-hedral environment defined by two N atoms from the 2,2'-bipyridine-4,4'-dicarboxylic acid ligand (H(2)bpdca), two bridging chlorido ligands, and two O atoms from an equatorial water mol-ecule and an axial nitrate anion, respectively. The two halves of the dimeric unit are related by an inversion centre at the midpoint between the two Cu atoms. Both carboxylic acid groups in the H(2)bpdca ligand remain protonated, as confirmed by the two sets of C-O bond lengths. The dinuclear mol-ecules are linked into a three-dimensional network via inter-molecular hydrogen bonds.

The Clinical Research of Serum VEGF, TGF-ß1, and Endostatin in Non-small Cell Lung Cancer.

The aim of the study was to analyze the expressions of vascular endothelial growth factor (VEGF), transforming growth factor ß1 (TGF-ß1) and endostatin in non-small cell lung caner (NSCLC), and to explore their correlations with NSCLC. 80 NSCLC patients during January 2013 to June 2014 were selected. The expression levels of VEGF, TGF-ß1, and endostatin before surgeries were detected, and compared with 40 healthy individuals and 40 patients with benign pulmonary diseases. Serum VEGF, TGF-ß1, and endostatin levels were (573.6 ± 25.4) pg/mL, (36.2 ± 10.5) ng/mL, and (20.3 ± 7.8) ng/mL, respectively, in NSCLC group, which were obviously higher than those in healthy individuals and patients with benign pulmonary diseases, and the difference was statistically significant (p < 0.05); there was no statistical difference of the VEGF, TGF-ß1, and endostatin levels between the healthy individuals and patients with benign pulmonary diseases (p > 0.05), or among patients with different physiological characteristics such as gender, age, and smoking history in NSCLC group (p > 0.05). Serum VEGF, TGF-ß1, and endostatin levels also showed no statistical difference among patients with different pathological characteristics such as histological types, with or without lymphatic metastasis (p > 0.05). However, the three indicators were significantly different among patients with different TNM stages, with or without distant metastasis and different cell differentiation degrees (p < 0.05). Serum VEGF and TGF-ß1 were positively related (r = 0.479, p < 0.05), endostatin was negatively related to both VEGF and TGF-ß1 (r = -0.392, -0.354, p < 0.05 in both comparisons). The expression levels of VEGF, TGF-ß1, and endostatin significantly contributed to the poor cell differentiation in NSCLC. They had important effects on the occurrence, development, and metastasis of NSCLC, which could be applied as the indicators to predict the malignancy of NSCLC.

Induction of apoptosis by IGFBP3 overexpression in hepatocellular carcinoma cells.

BACKGROUND: The insulin-like growth factor (IGF) system comprises a group of proteins that play key roles in regulating cell growth, differentiation, and apoptosis in a variety of cellular systems. The aim of this study was to investigate the role of insulin-like growth factor binding protein 3 (IGFBP3) in hepatocellular carcinoma. MATERIALS AND METHODS: Expression of IGF2, IGFBP3, and PTEN was analyzed by qRT-PCR. Lentivirus vectors were used to overexpress IGFBP3 in hepatocellular carcinoma cell (HCC) lines. The effect of IGFBP3 on proliferation was investigated by MTT and colony formation assays. RESULTS: Expression of IGF2, IGFBP3, and PTEN in several HCC cell lines was lower than in normal cell lines. After 5-aza-2'-deoxycytidine/trichostatin A treatment, significant demethylation of the promoter region of IGFBP3 was observed in HCC cells. Overexpression of IGFBP3 induced apoptosis and reduced colony formation in HUH7 cells. CONCLUSIONS: Expression of IGF2, IGFBP3, and PTEN in several HCC cell lines was lower than in normal cell lines. After 5-aza-2'-deoxycytidine/ trichostatin A treatment, significant demethylation of the promoter region of IGFBP3 was observed in HCC cells. Overexpression of IGFBP3 induced apoptosis and reduced colony formation in HUH7 cells.