Decreased expression of ApoF associates with poor prognosis in human hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is frequently associated with metabolism dysfunction. Increasing evidence has demonstrated the crucial role of lipid metabolism in HCC progression. The function of apolipoprotein F (ApoF), a lipid transfer inhibitor protein, in HCC is incompletely understood. We aimed to evaluate the functional role of ApoF in HCC in this study. METHODS: We used quantitative reverse-transcription polymerase chain reaction (qRT-PCR) to detect ApoF mRNA expression in HCC tissues and hepatoma cell lines (SMMC-7721, HepG2, and Huh7). Immunohistochemistry was performed to detect the expression of ApoF in HCC tissues. The associations between ApoF expression and clinicopathological features as well as HCC prognosis were analyzed. The effect of ApoF on cellular proliferation and growth of SMMC-7721 and Huh7 cells was examined in vitro and in vivo. RESULTS: ApoF expression was significantly down-regulated at both mRNA and protein levels in HCC tissues as compared with adjacent tissues. In SMMC-7721 and Huh7 HCC cells, ApoF overexpression inhibited cell proliferation and migration. In a xenograft nude mouse model, ApoF overexpression effectively controlled HCC growth. Kaplan-Meier analysis results showed that the recurrence-free survival rate of HCC patients with low ApoF expression was significantly lower than that of other HCC patients. Low ApoF expression was associated with several clinicopathological features such as liver cirrhosis, Barcelona Clinic Liver Cancer stage and tumor-node-metastasis stage. CONCLUSIONS: ApoF expression was down-regulated in HCC, which was associated with low recurrence-free survival rate. ApoF may serve as a tumor suppressor in HCC and be a potential application for the treatment of this disease.

KCNK levels are prognostic and diagnostic markers for hepatocellular carcinoma.

Two-pore-domain (KCNK, K2P) K+ channels are transmembrane protein complexes that control the flow of ions across biofilms, which underlie many essential cellular functions. Because KCNK family members are known to contribute to tumorigenesis in various types of cancer, we hypothesized that they might be differentially expressed in hepatocellular carcinoma (HCC) cells as compared to healthy tissue and serve as diagnostic or prognostic biomarkers. We tested this hypothesis through bioinformatic analyses of publicly available data for the expression of various KCNK subunits in HCC. We observed reduced expression of KCNK2, KCNK15, and KCNK17 in liver cancer, as well as overexpression of KCNK9, all of which correlated with a better prognosis for HCC patients per survival analyses. Moreover, ROC curves indicated that KCNK2, KCNK9, KCNK15, and KCNK17 levels could be used as a diagnostic biomarker for HCC. Finally, our western blot and qRT-PCR results were consistent with those obtained from bioinformatic analyses. Taken together, these results suggest that KCNK2, KCNK9, KCNK15, and KCNK17 could serve as potential diagnostic and prognostic biomarkers of HCC.

Efficacy and Safety of Willis Covered Stent for Treatment of Complex Vascular Diseases of the Internal Carotid Artery.

BACKGROUND: Willis covered stents are used in clinical practice for some complex cerebrovascular diseases. However, the performance of the Willis covered stent requires further investigation. In this study, we investigate the safety and efficacy of Willis covered stents for the treatment of complex vascular diseases of the internal carotid artery (ICA). METHODS: Thirteen patients with complex ICA diseases treated with the Willis covered stent system at our institution from October 2016 to January 2018 were analyzed retrospectively. Follow-up observation and digital subtraction angiography (DSA) examination were conducted at about 6-10 months after the treatment. RESULTS: The complex vascular diseases of the ICA were successfully treated in 12 patients. The technical success rate was 92.3%. Pathologically, 13 lesions included blood blister-like aneurysm (n = 7), traumatic pseudoaneurysm (n = 1), traumatic carotid artery rupture (n = 1), and aneurysm with arteriovenous fistula (n = 4). Thirteen patients with complex vascular diseases of the ICA were treated with 15 Willis covered stents. The release sites of Willis covered stents were the C7 (n = 2), C6 (n = 1), C5 and/or C4 (n = 9), and the C2 (n = 3) segment of the ICA. DSA performed immediately after stent deployment revealed that complete occlusion of the lesion was achieved in 11 patients and endoleak was observed in 2 patients. Of the 11 patients, postoperative DSA examination indicated that the lesions were occluded completely. Among 2 patients, who had a second stent implantation at the break of the ICA, the traumatic ICA rupture was essentially completely obstructed in 1 patient. The endoleak remained in 1 patient with carotid cavernous sinus fistula because the placement of the second stent system was difficult with his ICA tortuosity. No recurrence of aneurysms, hemorrhagia, and other lesions was observed, and the patients' parent arteries were patent without stenosis. No procedure-related complications or deaths occurred during follow-up. CONCLUSIONS: For the treatment of complex vascular diseases in the ICA, Willis covered stent implantation is safe and effective. However, longer follow-up, large-sample controlled studies, and multicenter studies are needed for further confirmation.

Characteristics and prognostic factors of age-stratified high-grade intracranial glioma patients: A population-based analysis.

We evaluated characteristics and different prognostic factors for survival in age-stratified high-grade glioma in a U.S. cohort. Eligible patients were identified in the Surveillance, Epidemiology, and End Results (SEER) registries and stratified into 3 age groups: 20-39 years old (1,043 patients), 40-59 years old (4,503 patients), and >60 years old (5,045 patients). Overall and cancer-related survival data were obtained. Cox models were built to analyze the outcomes and risk factors. It showed that race was a prognostic factor for survival in patients 40 to 59 years old and in patients ≥60 years old. Partial resection was associated with lower overall survival and cause-specific survival in all age groups (overall survival: 20-39 yr: HR = 6.41; 40-59 yr: HR = 4.84; >60 yr: HR = 5.06; cause-specific survival: 20-39 yr: HR = 5.87; 40-59 yr: HR = 4.01; >60 yr: HR = 3.36). The study highlights that, while some prognostic factors are universal, others are age-dependent. The effectiveness of treatment approaches differs for patients in different age groups. Results of this study may help to develop personalized treatment protocols for glioma patients of different ages.

MicroRNA-34a-5p enhances sensitivity to chemotherapy by targeting AXL in hepatocellular carcinoma MHCC-97L cells.

Mature microRNA (miRNA) 34a-5p, which is a well-known tumor suppressor in hepatitis virus-associated hepatocellular carcinoma (HCC), plays an important role in cell processes, such as cell proliferation and apoptosis, and is therefore an optimal biomarker for future clinical use. However, the role of miRNA-34a-5p in chemoresistance has yet to be identified. In the present study, the expression of miRNA-34a-5p was assessed by an in situ hybridization assay in HCC tissues and was found to be significantly decreased compared with the pericarcinomatous areas of the tissue specimens, which consisted of samples obtained from 114 patients with HCC. High expression of miRNA-34a-5p was found to be associated with a favorable overall survival time in HCC patients. Functional tests performed by transfecting miRNA-34a-5p mimics or inhibitors into MHCC-97L cells illustrated that miRNA-34a-5p inhibited proliferation, elevated apoptosis and decreased chemoresistance to cisplatin in HCC cells. AXL is the direct target of miRNA-34a-5p, as confirmed by sequence analysis and luciferase assay. Transfection of the cells with small interfering RNA for AXL (siAXL) increased the apoptosis ratio of the MHCC-97L cell line. Transfection with siAXL led to similar biological behaviors in the MHCC-97L cells to those induced by ectopic expression of miRNA-34a-5p. Thus, it was concluded that miRNA-34a-5p enhanced the sensitivity of the cells to chemotherapy by targeting AXL in hepatocellular carcinoma. In addition, low expression of miRNA-34a-5p in HCC tissues yielded an unfavorable prognosis for patients with HCC that received radical surgery, due to the promotion of proliferation and an increase in chemoresistance in HCC cells.

Dendritic cell-based vaccine for the treatment of malignant glioma: a systematic review.

OBJECTIVE: Glioblastoma multiforme (GBM) has a poor prognosis. The purpose of this systematic review and meta-analysis was to analyze the outcomes of clinical trials which compared immunotherapy with conventional therapy for the treatment of malignant gliomas. METHODS: PubMed, Cochrane and Google Scholar databases were searched for relevant studies. The 2-year survival rate was used to evaluate effectiveness of immunotherapy. RESULTS: Of 171 studies identified, six comparative trials were included in the systematic review. Immunotherapy was associated with a significantly longer OS and 2-year survival compared to conventional therapy. CONCLUSION: Immunotherapy may improve the survival of patients with GBM.

Human IP10-scFv and DC-induced CTL synergistically inhibit the growth of glioma in a xenograft model.

The epidermal growth factor receptor (EGFR) mutant of EGFRvIII is highly expressed in glioma cells, and the EGFRvIII-specific dendritic cell (DC)-induced tumor antigen-specific CD8(+) cytotoxic T lymphocytes (CTLs) may hold promise in cancer immunotherapy. Interferon (IFN)-γ-inducible protein (IP)-10 (IP-10) is a potent inhibitor of angiogenesis and can recruit CXCR3(+) T cells, including CD8(+) T cells, which are important for the control of tumor growth. In this study, we assessed if the combination of IP10-EGFRvIIIscFv with DC-induced CTLs would improve the therapeutic antitumor efficacy. IP10-scFv was generated by linking the human IP-10 gene with the DNA fragment for anti-EGFRvIIIscFv with a (Gly4Ser)3 flexible linker, purified by affinity chromatography, and characterized for its anti-EGFRvIII immunoreactivity and chemotactic activity. DCs were isolated from human peripheral blood monocyte cells and pulsed with EGFRvIII-peptide, then co-cultured with autologous CD8(+) T cells. BALB/c-nu mice were inoculated with human glioma U87-EGFRvIII cells in the brain and treated intracranially with IP10-scFv and/or intravenously with DC-induced CTLs for evaluating the therapeutic effect. Treatment with both IP10-scFv and EGFRvIII peptide-pulsed, DC-induced CTL synergistically inhibited the growth of glioma and prolonged the survival of tumor-bearing mice, which was accompanied by the inhibition of tumor angiogenesis and enhancement of cytotoxicity, thereby increasing the numbers of brain-infiltrating lymphocytes (BILs) and prolonging the residence time of CTLs in the tumor.

Complement C5a is detrimental to histological and functional locomotor recovery after spinal cord injury in mice.

Based on the studies on the role of complements C3, C1q and factor B, we hypothesized that complement C5a is detrimental to locomotor recovery at the early stage of secondary injury after spinal cord injury (SCI). To test this hypothesis, we investigated the effect of inhibition of complement C5a receptor (C5aR) by using C5aR antagonist PMX53 (C5aRA) and deficiency of complement C5a receptor (C5aR-/- mice) on histological and locomotor recovery after SCI in mice. We demonstrated that the Basso Mouse Scale scores in the mice injected with C5aRA (C5aRA-mice) at 45min before and 24h after SCI and the C5aR-/- mice were markedly higher than those in the mice treated with saline (Saline-mice) and the C5aR+/+ mice respectively between 7 and 28days after SCI. Also, expression of TNF-α and IL-1ß in C5aRA-mice was significantly lower than that in Saline-mice from 1 to 24h after SCI. In addition, the percentage of microglia/macrophage in C5aRA mice and C5aR-/- mice was significantly lower than those in their corresponding control groups from 1 to 14days after SCI. Furthermore, C5aRA mice and C5aR-/- mice had less GFAP expression in the injured spinal cord epicenter as compared to Saline mice and C5aR+/+ mice at day 28 after SCI. These findings provided evidence that inhibition or deficiency of C5aR could significantly improve histological and functional locomotor recovery after SCI in mice.

Diaqua-bis-(1H-imidazole-4-carboxyl-ato-κ(2) N (3),O (4))manganese(II).

In the title compound, [Mn(C4H3N2O2)2(H2O)2], the Mn(II) ion is located on a twofold rotation axis and displays a distorted octa-hedral coordination environment, defined by two N,O-bidentate 1H-imidazole-4-carboxyl-ate ligands in the equatorial plane and two water mol-ecules in axial positions. In the crystal, O-H⋯O and N-H⋯O hydrogen bonds link the mol-ecules into a three-dimensional supra-molecular network. π-π stacking inter-actions between the imidazole rings [centroid-centroid distances = 3.5188 (15) and 3.6687 (15) Å] further stabilize the structure.

Health-related quality-of-life after traumatic brain injury: a 2-year follow-up study in Wuhan, China.

OBJECTIVE: To assess health-related quality-of-life (HRQoL) 2 years after traumatic brain injury (TBI) among a group of Chinese. METHODS: A total of 358 adult patients with moderate-to-severe TBI based on Glasgow Coma Scale score were recruited in a large trauma centre in Wuhan, China during May 2005 to April 2008. They were followed up for 2 years and the Medical Outcome Short Form 36 was used to measure HRQoL. RESULTS: After a 2-year follow-up, there were 312 (87.2%) survivors. All domains of HRQoL had the lowest scores at discharge, greatly improved over the first 6 months and showed continued improvement. Patients with TBI still had significantly lower scores in every domain than the reference group 2 years after discharge. Female patients had lower MCS scores than the males (OR = 1.8, 95% CI: 1.1-2.9). Patients older than 30 had lower scores in PCS (OR = 1.7, 95% CI: 1.1-2.6). Patients with severe TBI had lower scores in both PCS (OR = 1.9, 95% CI: 1.2-3.1) and MCS (OR = 1.6, 95% CI: 1.0-2.6) compared with those with moderate TBI. CONCLUSIONS: HRQoL of a group of Chinese patients with TBI improved during 2 years after discharge. Age, sex and severity of TBI were significantly associated with physical or mental HRQoL after discharge.

Polymorphisms in DNA repair gene XRCC1 and increased genetic susceptibility to glioma.

BACKGROUND: The XRCC1 gene encodes the XRCC1 protein, which complexes with three other DNA repair enzymes involved in the base-excision repair (BER) pathways. Different XRCC1 polymorphisms may increase the risk of cancers by impairing interaction with other enzymatic proteins and consequently altering DNA repair activity, and result in carcinogenesis. Our study aimed to investigate any association between three polymorphisms of the XRCC1 gene at codon 194, 280 and 399 and potential glioma risk. METHODS: We collected 127 patients with primary glioma and 249 controls who requested general health examinations from Union Hospital of Tongji Medical College hospital from March 2007 to September 2010. A total of 5 ml venous blood was drawn from each subject. The polymorphisms of XRCC1 gene at codons 194, 280 and 399 were analyzed based on duplex polymerase-chain-reactions with the confronting-two-pair primer (PCR-CTPP) method. RESULTS: The homozygous Trp/Trp and heterozygotes Arg/Trp variants of codon 194 had a 2.12 fold and 1.46 fold increased risk of glioma compared to the homozygous Arg/Arg wide genotypes. The same effect was found in codon 399, the codon 399 Gln/Gln and Arg/Gln genotypes being associated with a 2.24 fold and 1.67 fold increased risk in glioma. When comparing the codon 194 Arg/Arg and 399 Arg/Arg genotypes, the combination of codon 194 Trp allele and 399 Gln allele had a heavy increase in glioma risk (OR=2.87, 95%CI=1.56-6.73). CONCLUSION: The present study provided evidence of a potential role for XRCC1 codon 194 and 399 polymorphisms in genetic predisposition to glioma among the Chinese population. This analysis of correlation of DNA repair genes and glioma may provide a deeper insight into the genetic and environment factors for cancer risk.

Cytogenetic comparisons between A and G genomes in Oryza using genomic in situ hybridization.

The genomic structures of Oryza sativa (A genome) and O. meyeriana (G genome) were comparatively studied using bicolor genomic in situ hybridization (GISH). GISH was clearly able to discriminate between the chromosomes of O. sativa and O. meyeriana in the interspecific F1 hybrids without blocking DNA, and co-hybridization was hardly detected. The average mitotic chromosome length of O. meyeriana was found to be 1.69 times that of O. sativa. A comparison of 4,6-diamidino-2-phenylindole staining showed that the chromosomes of O. meyeriana were more extensively labelled, suggesting that the G genome is amplified with more repetitive sequences than the A genome. In interphase nuclei, 9-12 chromocenters were normally detected and nearly all the chromocenters constituted the G genome-specific DNA. More and larger chromocenters formed by chromatin compaction corresponding to the G genome were detected in the hybrid compared with its parents. During pachytene of the F1 hybrid, most chromosomes of A and G did not synapse each other except for 1-2 chromosomes paired at the end of their arms. At meiotic metaphase I, three types of chromosomal associations, i.e. O. sativa-O. sativa (A-A), O. sativa-O. meyeriana (A-G) and O. meyeriana-O. meyeriana (G-G), were observed in the F1 hybrid. The A-G chromosome pairing configurations included bivalents and trivalents. The results provided a foundation toward studying genome organization and evolution of O. meyeriana.

FISH analysis of pachytene chromosome and DNA fiber of telomere sequence in rice (Oryza sativa L. indica).

Telomere sequences were analyzed by using pachytene chromosome and extended DNA fiber FISH in rice (Oryza, sativa ssp. indica cv. -Guangluai No.4). Pachytene FISH results showed that most of chromosome ends possess the telomere tandem repeats, but the signals on different chromosomes were not the same in intensity. Fiber FISH results indicated that the longest string of beads was 6.55 microm, while the shortest one was 1.82 microm long,which were equal to 16.44 and 4.56 kb correspondingly based on a stretching factor of 2.51 kb/microm. The average value of signal length was 3.62 +/- 1.32 microm, i.e. 9.09 +/- 3.31 kb. It could be estimated that the longest and the shortest as well as the average value were equal to 2,349,651 and 1298 +/- 473 of copy number respectively.

A new chromosome fluorescence banding technique combining DAPI staining with image analysis in plants.

In this study, a new chromosome fluorescence banding technique was developed in plants. The technique combined 4',6-diamidino-2-phenylindole (DAPI) staining with software analysis including three-dimensional imaging after deconvolution. Clear multiple and adjacent DAPI bands like G-bands were obtained by this technique in the tested species including Hordeum vulgare L., Oryza officinalis, Wall & Watt, Triticum aestivum L., Lilium brownii, Brown, and Vicia faba L. During mitotic metaphase, the numbers of bands for the haploid genomes of these species were about 185, 141, 309, 456 and 194, respectively. Reproducibility analysis demonstrated that banding patterns within a species were stable at the same mitotic stage and they could be used for identifying specific chromosomes and chromosome regions. The band number fluctuated: the earlier the mitotic stage, the greater the number of bands. The technique enables genes to be mapped onto specific band regions of the chromosomes by only one fluorescence in situ hybridisation (FISH) step with no chemical banding treatments. In this study, the 45S and 5S rDNAs of some tested species were located on specific band regions of specific chromosomes and they were all positioned at the interbands with the new technique. Because no chemical banding treatment was used, the banding patterns displayed by the technique should reflect the natural conformational features of chromatin. Thus it could be expected that this technique should be suitable for all eukaryotes and would have widespread utility in chromosomal structure analysis and physical mapping of genes.