Repeat hepatectomy for recurrent hepatocellular carcinoma: a local experience and a systematic review

Background: This study aimed to assess the efficacy and safety of repeat hepatectomy for recurrent hepatocellular carcinoma (HCC). Methods: Thirty-seven patients who underwent a curative repeat hepatectomy in our hospital were retrospectively studied. An extensive database literature search was performed to obtain for all relevant studies. Results: In our series, there were no perioperative deaths during repeat hepatectomy for recurrent HCC. Patients survival after repeat hepatectomy were similar to 429 patients undergoing initial hepatectomy. A computerized search of the Medline and PubMed databases found 29 retrospective studies providing relevant data in 1149 patients were included for appraisal and data extraction. After the repeat hepatectomy, postoperative morbidity ranged from 6.2% to 68.2% with a median per cohort of 23.5 per cent. There were 7 perioperative deaths (0.7 per cent of 993 for whom mortality data were provided). The overall median survival ranged from 21 to 61.5 months, with 1 -, 3 -, and 5-year survival of 69.0% to 100%, 21.0% to 87.0%, and 25.0% to 87.0%, respectively. Conclusions: Repeat hepatectomy can be performed safely and is associated with long-term survival in a subset of patients with recurrent HCC. However, the findings have to be carefully interpreted due to the lower level of evidence. A randomized controlled study is needed to compare repeat hepatectomy and other modalities for recurrent HCC

Sphere-forming cell subpopulations with cancer stem cell properties in human hepatoma cell lines

<p>Abstract</p> <p>Background</p> <p>Cancer stem cells (CSCs) are regarded as the cause of tumor formation and recurrence. The isolation and identification of CSCs could help to develop novel therapeutic strategies specifically targeting CSCs.</p> <p>Methods</p> <p>Human hepatoma cell lines were plated in stem cell conditioned culture system allowed for sphere forming. To evaluate the stemness characteristics of spheres, the self-renewal, proliferation, chemoresistance, tumorigenicity of the PLC/PRF/5 sphere-forming cells, and the expression levels of stem cell related proteins in the PLC/PRF/5 sphere-forming cells were assessed, comparing with the parental cells. The stem cell RT-PCR array was performed to further explore the biological properties of liver CSCs.</p> <p>Results</p> <p>The PLC/PRF/5, MHCC97H and HepG2 cells could form clonal nonadherent 3-D spheres and be serially passaged. The PLC/PRF/5 sphere-forming cells possessed a key criteria that define CSCs: persistent self-renewal, extensive proliferation, drug resistance, overexpression of liver CSCs related proteins (Oct3/4, OV6, EpCAM, CD133 and CD44). Even 500 sphere-forming cells were able to form tumors in NOD/SCID mice, and the tumor initiating capability was not decreased when spheres were passaged. Besides, downstream proteins DTX1 and Ep300 of the CSL (CBF1 in humans, Suppressor of hairless in Drosophila and LAG1 in C. elegans) -independent Notch signaling pathway were highly expressed in the spheres, and a gamma-secretase inhibitor MRK003 could significantly inhibit the sphere formation ability.</p> <p>Conclusions</p> <p>Nonadherent tumor spheres from hepatoma cell lines cultured in stem cell conditioned medium possess liver CSC properties, and the CSL-independent Notch signaling pathway may play a role in liver CSCs.</p

The Epitope Study on the SARS-CoV Nucleocapsid Protein

The nucleocapsid protein (N protein) has been found to be an antigenic protein in a number of coronaviruses. Whether the N protein in severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is antigenic remains to be elucidated. Using Western blot and Enzyme-linked Immunosorbent Assay (ELISA), the recombinant N proteins and the synthesized peptides derived from the N protein were screened in sera from SARS patients. All patient sera in this study displayed strong positive immunoreactivities against the recombinant N proteins, whereas normal sera gave negative immunoresponses to these proteins, indicating that the N protein of SARS-CoV is an antigenic protein. Furthermore, the epitope sites in the N protein were determined by competition experiments, in which the recombinant proteins or the synthesized peptides competed against the SARS-CoV proteins to bind to the antibodies raised in SARS sera. One epitope site located at the C-terminus was confirmed as the most antigenic region in this protein. A detailed screening of peptide with ELISA demonstrated that the amino sequence from Codons 371 to 407 was the epitope site at the C-terminus of the N protein. Understanding of the epitope sites could be very significant for developing an effective diagnostic approach to SARS

Meta-analysis of radiofrequency ablation versus hepatic resection for small hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>There is no clear consensus on the better therapy [radiofrequency ablation (RFA) versus hepatic resection (HR)] for small hepatocellular carcinoma (HCC) eligible for surgical treatments. This study is a meta-analysis of the available evidence.</p> <p>Methods</p> <p>Systematic review and meta-analysis of trials comparing RFA with HR for small HCC published from 1997 to 2009 in PubMed and Medline. Pooled odds ratios (OR) with 95% confidence intervals (95% CI) were calculated using either the fixed effects model or random effects model.</p> <p>Results</p> <p>One randomized controlled trial, and 9 nonrandomized controlled trials studies were included in this analysis. These studies included a total of 1411 patients: 744 treated with RFA and 667 treated with HR. The overall survival was significantly higher in patients treated with HR than in those treated with RFA at 3 years (OR: 0.56, 95% CI: 0.44-0.71), and at 5 year (OR: 0.60, 95% CI: 0.36-1.01). RFA has a higher rates of local intrahepatic recurrence compared to HR (OR: 4.50, 95% CI: 2.45-8.27). In the HR group the 1, 3, and 5 years disease -free survival rates were significantly better than in the HR-treated patients (respectively: OR: 0.54, 95% CI: 0.35-0.84; OR: 0.44, 95% CI: 0.28-0.68; OR: 0.64, 95% CI: 0.42-0.99). The postoperative morbidity was higher with HR (OR: 0.29, 95% CI: 0.13-0.65), but no significant differences were found concerning mortality. For tumors ≤ 3 cm HR did not differ significantly from RFA for survival, as reported in three NRCTs .</p> <p>Conclusions</p> <p>HR was superior to RFA in the treatment of patients with small HCC eligible for surgical treatments, particularly for tumors > 3 cm. However, the findings have to be carefully interpreted due to the lower level of evidence.</p

Homogeneous and heterogeneous catalysts for multicomponent reactions

[EN] Organic synthesis performed through multicomponent reactions is an attractive area of research in organic chemistry. Multicomponent reactions involve more than two starting reagents that couple in an exclusive ordered mode under the same reaction conditions to form a single product which contains the essential parts of the starting materials. Multicomponent reactions are powerful tools in modern drug discovery processes, because they are an important source of molecular diversity, allowing rapid, automated and high throughput generation of organic compounds. This review aims to illustrate progress in a large variety of catalyzed multicomponent reactions performed with acid, base and metal heterogeneous and homogeneous catalysts. Within each type of multicomponent approach, relevant products that can be obtained and their interest for industrial applications are presented.The authors wish to gratefully acknowledge the Generalitat Valenciana for the financial support in the project CONSOLIDER-INGENIO 2010 (CSD2009-00050)Climent Olmedo, MJ.; Corma Canós, A.; Iborra Chornet, S. (2012). Homogeneous and heterogeneous catalysts for multicomponent reactions. RSC Advances. 2(1):16-58. https://doi.org/10.1039/c1ra00807bS16582

Resistance Distance and Kirchhoff Index for a Class of Graphs

Let G[F,Vk,Hv] be the graph with k pockets, where F is a simple graph of order n≥1, Vk={v1,v2,…,vk} is a subset of the vertex set of F, Hv is a simple graph of order m≥2, and v is a specified vertex of Hv. Also let G[F,Ek,Huv] be the graph with k edge pockets, where F is a simple graph of order n≥2, Ek={e1,e2,…ek} is a subset of the edge set of F, Huv is a simple graph of order m≥3, and uv is a specified edge of Huv such that Huv-u is isomorphic to Huv-v. In this paper, we derive closed-form formulas for resistance distance and Kirchhoff index of G[F,Vk,Hv] and G[F,Ek,Huv] in terms of the resistance distance and Kirchhoff index F, Hv and F, Huv, respectively

Homozygous lethality and heterozygous spotting due to a novel missense mutation in the mouse Kit gene

N-ethyl-N-nitrosourea (ENU) mutagenesis in mice can be used to study gene function in vivo and to establish genetic mouse models of human disease. In this study, a white spotted mouse (named KitW-1Bao) was obtained by ENU-induced mutagenesis. Inheritance testing showed a single-gene dominant mutation and lethality in the KitW-1Bao homozygous mice. The mutation was mapped to Chromosome 5 between markers D5Mit356 and D5Mit308. The region contains the Kit gene, whose mutations are known to lead to pigmentation defects in mice. Sequence analysis of the Kit cDNA from KitW-1Bao heterozygotes revealed an A to T missense mutation resulting in an amino acid substitution of Asp (D) by Val (V) at amino acid position 849 within a highly conserved tyrosine kinase domain. The combined phenotype displayed by the KitW-1Bao heterozygous and homozygous mutant mice demonstrates the critical function of the highly conserved aspartic acid residue at position 849 in the Kit gene product [Current Zoology 55 (6): 430–434, 2009]