Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 3 de 3
Filter
Add more filters










Database
Language
Publication year range
1.
Cancer Sci ; 113(10): 3618-3632, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35946078

ABSTRACT

Osteosarcoma (OS) is the most common bone malignancy without a reliable therapeutic target. Glypican-3 (GPC3) mutation and upregulation have been detected in multidrug resistant OS, and anti-GPC3 immunotherapy can effectively suppress the growth of organoids. Further profiling of GPC3 mutations and expression patterns in OS is of clinical significance. To address these issues, fresh OS specimens were collected from 24 patients for cancer-targeted next-generation sequencing (NGS) and three-dimensional patient-derived organoid (PDO) culture. A tumor microarray was prepared using 37 archived OS specimens. Immunohistochemical (IHC) staining was performed on OS specimens and microarrays to profile GPC3 and CD133 expression as well as intratumoral distribution patterns. RT-PCR was conducted to semiquantify GPC3 and CD133 expression levels in the OS tissues. Anti-GPC3 immunotherapy was performed on OS organoids with or without GPC3 expression and its efficacy was analyzed using multiple experimental approaches. No OS cases with GPC3 mutations were found, except for the positive control (OS-08). IHC staining revealed GPC3 expression in 73.77% (45/61) of OSs in weak (+; 29/45), moderate (++; 8/45), and strong (+++; 8/45) immunolabeling densities. The intratumoral distribution of GPC3-positive cells was variable in the focal (+; 10%-30%; 8/45), partial (++; 31%-70%; 22/45), and the most positive patterns (+++; >71%; 15/45), which coincided with CD133 immunolabeling (P = 9.89 × 10-10 ). The anti-GPC3 antibody efficiently inhibits Wnt/ß-catenin signaling and induces apoptosis in GPC3-positive PDOs and PDXs, as opposed to GPC3-negative PDOs and PDXs. The high frequency of GPC3 and CD133 co-expression and the effectiveness of anti-wild-type GPC3-Ab therapy in GPC3-positive OS models suggest that GPC3 is a novel prognostic parameter and a promising therapeutic target for osteosarcoma.


Subject(s)
Bone Neoplasms , Carcinoma, Hepatocellular , Liver Neoplasms , Osteosarcoma , Bone Neoplasms/drug therapy , Bone Neoplasms/genetics , Carcinoma, Hepatocellular/pathology , Glypicans/metabolism , Humans , Liver Neoplasms/pathology , Osteosarcoma/drug therapy , Osteosarcoma/genetics , beta Catenin
2.
Environ Pollut ; 246: 597-607, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30605815

ABSTRACT

Di(n-butyl) phthalate (DBP) is extensively used in industrial applications as plasticizer and stabilizer and its presence in the environment may present health risks for human. Previous studies have demonstrated its mutagenic, teratogenic, and carcinogenic ability. However, its effect on mammalian oocyte maturation remains unknown. In this study, we examined the effect of DBP on oocyte maturation both in vitro and in vivo. Our results showed that DBP could significantly reduce mice oocyte germinal vesicle breakdown (GVBD) and polar body extrusion (PBE) rates. In addition, oocyte cytoskeleton was damaged and cortical granule-free domains (CGFDs) were also disrupted. Finally, DBP induced early apoptosis of oocyte and granulosa cells (GCs). Collectively, these data demonstrate that DBP could reduce meiosis competence and mouse oocyte development.


Subject(s)
Apoptosis/drug effects , Dibutyl Phthalate/toxicity , Environmental Pollutants/toxicity , Meiosis/drug effects , Oocytes/drug effects , Animals , Female , Granulosa Cells/drug effects , Granulosa Cells/pathology , Humans , Mice , Mice, Inbred ICR , Oocytes/growth & development , Oocytes/pathology
3.
Microb Pathog ; 112: 295-302, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28970171

ABSTRACT

To monitor the genetic variation of PRRSV, the ORF5 gene of the PRRSV-SN strain found in Suining City, Sichuan Province, was cloned and sequenced. The results showed that the PRRSV-SN strain was a highly pathogenic PRRSV (HP-PRRSV) variant strain with the North American (NA) genotype. Homology analysis showed that the ORF5 gene of the PRRSV-SN isolate shared 89.4% (86.5%) nucleotide (amino acid) sequence similarity with the North American strain VR-2332, 98.8% (96%) similarity with JXA1, and 63.8% (57.7%) similarity with the European type representative strain Lelystad virus. Phylogenetic analysis showed that PRRSV-SN belongs to the NA genotype and has the same subtype as other highly pathogenic PRRSV strains. Amino acid sequence analysis showed that compared with the VR2332 strain, PRRSV-SN has different degrees of variation in the signal peptide, transmembrane region (TM), primary neutralizing epitope (PNE), non-neutral epitopes and N-glycosylation sites. Antigenicity analysis showed that the PRRSV-SN ORF5 gene products and JXA1 have similar antigenic characteristics, and the antigenic epitopes are mainly located in aa30-39, aa50-60, aa128-141, aa146-155 and aa161-183 regions. In contrast, the antigenic characteristics of PRRSV-SN are quite different from those of the VR2332 strain. The main differences were that the PRRSV-SN strain was significantly narrower than the VR2332 strain in the aa30-39 and the aa50-60 regions but was significantly wider in the aa136-141 region. The results of this study showed that the epidemic strains that cause PRRSV outbreaks in the farm are still mainly JXA1 variants, but due to the more frequent use of live vaccine immunizations, the genes of the PRRSV epidemic strain still show constant variation. Vaccination with live PRRSV should be reduced, and surveillance of PRRSV strains should be enhanced.


Subject(s)
Genes, Viral/genetics , Genetic Variation , Porcine Reproductive and Respiratory Syndrome/virology , Porcine respiratory and reproductive syndrome virus/classification , Porcine respiratory and reproductive syndrome virus/genetics , Porcine respiratory and reproductive syndrome virus/isolation & purification , Viral Envelope Proteins/genetics , Amino Acid Sequence , Animals , Antigens, Viral/genetics , Antigens, Viral/immunology , Base Sequence , China , Genetic Vectors , Genotype , Molecular Epidemiology , Phylogeny , Porcine Reproductive and Respiratory Syndrome/epidemiology , Porcine respiratory and reproductive syndrome virus/immunology , Porcine respiratory and reproductive syndrome virus/pathogenicity , RNA, Viral/genetics , RNA-Binding Proteins/genetics , Sequence Alignment , Sequence Analysis , Sequence Homology, Amino Acid , Sequence Homology, Nucleic Acid , Swine , Vaccination , Viral Nonstructural Proteins/genetics , Viral Proteins/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...