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1.
BMC Cancer ; 24(1): 915, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39080554

RESUMO

AIMS: This investigation aims to elucidate the treatment status of advanced HR+/HER2- breast cancer patients in Hunan Province of Central Southern China from November 2021 to December 2022. METHODS: Data from 301 patients with advanced HR+/HER2- breast cancer were collected from the breast cancer investigation project in Hunan under the guidance of the Chinese Society of Clinical Oncolfogy (CSCO). The data included the clinical characteristics of patients and the status of first-line and second-line rescue treatment. RESULTS: First-line chemotherapy and endocrine therapy for mBC accounted for 40% (121/301) and 60% (180/301) of treatments, respectively. AI (21%), AI plus CDK4/6 inhibitor (28%), and fulvestrant (24%) or fulvestrant plus CDK4/6 inhibitor (18%) were the most common first-line endocrine therapies. Taxane-based chemotherapy was the most common first-line chemotherapy (59%). Second-line chemotherapy and endocrine therapy for mBC accounted for 43% (72/166) and 57% (94/166) of treatments, respectively. Fulvestrant (23%) or fulvestrant plus CDK4/6 inhibitor (29%) were the most common second-line endocrine therapies. The prevalences of AI and AI plus CDK4/6 inhibitor decreased to 19% and 11%, respectively. T (taxane)-based chemotherapy was still the most common chemotherapy regimen (46%). Third-line chemotherapy was more prevalent than endocrine therapy (57% vs. 41%). T (taxane)-based chemotherapy was still the most common chemotherapy regimen (46%). Fulvestrant plus CDK4/6 inhibitor was the most common endocrine therapy (33%). AI, AI plus CDK4/6 inhibitor, and fulvestrant accounted for 21%, 12% and 18% of third-line endocrine therapies, respectively. CONCLUSIONS: Compared to chemotherapy, endocrine therapy was a more favorable choice for first-line and second-line treatment for HR+/HER2- advanced breast cancer patients in Hunan Province.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Receptor ErbB-2 , Receptores de Estrogênio , Receptores de Progesterona , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , China/epidemiologia , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Pessoa de Meia-Idade , Estudos Transversais , Adulto , Receptores de Estrogênio/metabolismo , Idoso , Receptores de Progesterona/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
2.
Biochem Biophys Res Commun ; 520(1): 60-66, 2019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31570165

RESUMO

Human TRDMT1 is a transfer RNA (tRNA) methyltransferase for cytosine-5 methylation and has been suggested to be involved in the regulation of numerous developmental processes. However, little is known about the molecular mechanisms or their biological significance. In this study, we investigated the effects of CRISPR-based TRDMT1 knockdown on phenotypes, mRNA m5C modifications and gene expression changes in HEK293 cells. We found that knockdown of TRDMT1 significantly inhibited cell proliferation and migration but had no effect on clonogenic potential. The inhibitory effects could be attenuated by re-expression of TRDMT1 in HEK293 cells. RNA sequencing (RNA-Seq) and RNA bisulfite sequencing (RNA-BisSeq) were performed in TRDMT1 knockdown and wild-type HEK293 cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that the differentially expressed genes were associated with the cell cycle, RNA transport, and RNA degradation and were enriched in cancer and Notch signaling pathways. We also found that TRDMT1 knockdown could change mRNA methylation levels. For the first time, these findings clarify the role of TRDMT1 in regulating mRNA methylation and inhibiting the proliferation and migration of HEK293 cells. These results provide new insights into a new function of TRDMT1 and elucidate the molecular mechanisms of aberrant RNA m5C during tumorigenesis.


Assuntos
5-Metilcitosina/metabolismo , Movimento Celular , Proliferação de Células , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , RNA Mensageiro/metabolismo , Sistemas CRISPR-Cas , Carcinogênese , Biologia Computacional , Metilação de DNA , Perfilação da Expressão Gênica , Células HEK293 , Humanos , Fenótipo , RNA-Seq , Transdução de Sinais
3.
J Biol Chem ; 292(14): 5624-5633, 2017 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-28196870

RESUMO

The type II bacterial CRISPR/Cas9 system is a simple, convenient, and powerful tool for targeted gene editing. Here, we describe a CRISPR/Cas9-based approach for inserting a poly(A) transcriptional terminator into both alleles of a targeted gene to silence protein-coding and non-protein-coding genes, which often play key roles in gene regulation but are difficult to silence via insertion or deletion of short DNA fragments. The integration of 225 bp of bovine growth hormone poly(A) signals into either the first intron or the first exon or behind the promoter of target genes caused efficient termination of expression of PPP1R12C, NSUN2 (protein-coding genes), and MALAT1 (non-protein-coding gene). Both NeoR and PuroR were used as markers in the selection of clonal cell lines with biallelic integration of a poly(A) signal. Genotyping analysis indicated that the cell lines displayed the desired biallelic silencing after a brief selection period. These combined results indicate that this CRISPR/Cas9-based approach offers an easy, convenient, and efficient novel technique for gene silencing in cell lines, especially for those in which gene integration is difficult because of a low efficiency of homology-directed repair.


Assuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Inativação Gênica , Metiltransferases/biossíntese , Proteína Fosfatase 1/biossíntese , RNA Longo não Codificante/biossíntese , Regiões Terminadoras Genéticas , Animais , Bovinos , Células HEK293 , Humanos , Metiltransferases/genética , Proteína Fosfatase 1/genética , RNA Longo não Codificante/genética
4.
Arch Virol ; 163(3): 639-647, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29198037

RESUMO

Avian leukosis virus J (ALVJ) infection induces hematopoietic malignancy in myeloid leukemia and hemangioma in chickens. However, little is known about the mechanisms underpinning the unique pathogenesis of ALVJ. In this study, we investigated the gene expression profiles of ALVJ-infected chicken cells and performed a comprehensive analysis of the long non-coding RNAs (lncRNAs) in CEF cells using RNA-Seq. As a result, 36 differentially expressed lncRNAs and 91 genes (FC > 2 and q-values < 0.05) were identified. Bioinformatics analysis revealed that these differentially expressed genes are involved in the innate immune response. Target prediction analysis revealed that these lncRNAs may act in cis or trans and affect the expression of genes which are involved in the anti-viral innate immune responses. Toll-like receptor, RIG-I receptor, NOD-like receptor and JAK-STAT signaling pathways were enriched. Notably, the induced expression of innate immunity genes, including B2M, DHX58, IFI27L2, IFIH1, IRF10, ISG12(2), MX, OAS*A, RSAD2, STAT1, TLR3, IL4I1, and IRF1 (FC > 2 and correlation > 0.95), were highly correlated with the upregulation of several lncRNAs, including MG066618, MG066617, MG066601, MG066629, MG066609 and MG066616. These findings identify the expression profile of lncRNAs in chicken CEF cells infected by ALVJ virus and provide new insights into the molecular mechanisms of ALVJ infection.


Assuntos
Vírus da Leucose Aviária/genética , Fibroblastos/virologia , Interações Hospedeiro-Patógeno , RNA Longo não Codificante/genética , Transcriptoma/imunologia , Animais , Vírus da Leucose Aviária/crescimento & desenvolvimento , Vírus da Leucose Aviária/imunologia , Linhagem Celular , Embrião de Galinha , Biologia Computacional , Proteína DEAD-box 58/genética , Proteína DEAD-box 58/imunologia , Fibroblastos/imunologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Imunidade Inata , Janus Quinase 1/genética , Janus Quinase 1/imunologia , Proteínas NLR/genética , Proteínas NLR/imunologia , RNA Longo não Codificante/imunologia , Fatores de Transcrição STAT/genética , Fatores de Transcrição STAT/imunologia , Análise de Sequência de RNA , Transdução de Sinais , Receptores Toll-Like/genética , Receptores Toll-Like/imunologia
5.
Biotechnol Lett ; 40(11-12): 1507-1518, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30244429

RESUMO

OBJECTIVES: To investigate the effect of endogenous Cas9 on genome editing efficiency in transgenic zebrafish. RESULTS: Here we have constructed a transgenic zebrafish strain that can be screened by pigment deficiency. Compared with the traditional CRISPR injection method, the transgenic zebrafish can improve the efficiency of genome editing significantly. At the same time, we first observed that the phenotype of vertebral malformation in early embryonic development of zebrafish after ZFERV knockout. CONCLUSIONS: The transgenic zebrafish with expressed Cas9, is more efficient in genome editing. And the results of ZFERV knockout indicated that ERV may affect the vertebral development by Notch1/Delta D signal pathway.


Assuntos
Animais Geneticamente Modificados/genética , Sistemas CRISPR-Cas/genética , Retrovirus Endógenos/genética , Edição de Genes/métodos , Peixe-Zebra/genética , Animais , Feminino , Técnicas de Inativação de Genes , Masculino , Regiões Promotoras Genéticas/genética
6.
Arch Virol ; 162(1): 89-101, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27686071

RESUMO

Endogenous retroviruses (ERVs) are genomic elements that are present in a wide range of vertebrates and have been implicated in a variety of human diseases, including cancer. However, the characteristic expression patterns of ERVs, particularly in virus-induced tumours, is not fully clear. DNA methylation was analysed by bisulfite pyrosequencing, and gene expression was analysed by RT-qPCR. In this study, we first found that the endogenous avian retrovirus ALVE1 was highly expressed in some chicken tissues (including the heart, bursa, thymus, and spleen) at 2 days of age, but its expression was markedly decreased at 35 days of age. In contrast, the CpG methylation level of ALVE1 was significantly lower in heart and bursa at 2 days than at 35 days of age. Moreover, we found that the expression of ALVE1 was significantly inhibited in chicken embryo fibroblast cells (CEFs) and MSB1 cells infected with avian leukosis virus subgroup J (ALVJ) and reticuloendotheliosis virus (REV) at the early stages of infection. In contrast, the expression of the ALVE1 env gene was significantly induced in CEFs and MSB1 cells infected with Marek's disease virus (MDV). However, the methylation and expression levels of the ALVE1 long terminal repeat (LTR) did not show obvious alterations in response to viral infection. The present study revealed the expression patterns of ALVE1 in a variety of chicken organs and tissues and in chicken cells in response to avian tumour virus infection. These findings may be of significance for understanding the role and function of ERVs that are present in the host genome.


Assuntos
Coinfecção/veterinária , Retrovirus Endógenos/genética , Regulação Viral da Expressão Gênica , Interações Microbianas , Vírus Oncogênicos/genética , Infecções por Retroviridae/complicações , Infecções Tumorais por Vírus/veterinária , Estruturas Animais/virologia , Animais , Células Cultivadas , Embrião de Galinha , Galinhas , Coinfecção/virologia , Metilação de DNA , Retrovirus Endógenos/crescimento & desenvolvimento , Fibroblastos/virologia , Perfilação da Expressão Gênica , Vírus Oncogênicos/crescimento & desenvolvimento , Reação em Cadeia da Polimerase em Tempo Real , Infecções por Retroviridae/virologia , Análise de Sequência de DNA , Infecções Tumorais por Vírus/virologia
7.
Arch Virol ; 161(3): 521-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26597188

RESUMO

Toll-like receptor 3 (TLR3) is a critical component of the innate immune system against viral infection and controls the activation of adaptive immunity. The role of TLR3 in Marek's disease virus (MDV) infection is not clear. In this study, we found that the abundance of TLR3 mRNA was significantly higher in chicken embryo fibroblast cells (CEF) infected with MDV than in a control group. Activated TLR3 signaling via TLR3 ligand stimulation inhibited replication of the RB1B strain of MDV in CEF cells. In contrast, CEF cells transfected with TLR3 siRNA promoted RB1B infection and replication. However, treatment with other TLR ligands, whether stimulatory (LPS, imiquimod and CpG) or inhibitory (TLR2/4 inhibitor and/or MyD88 inhibitor), had little effect on RB1B infection and replication. In addition, we found that the expression trend of TLR3 mRNA in RB1B-infected CEF cells was similar to that of mdv1-mir-M4-5p (a functional ortholog of oncogenic miR-155 encoded by MDV). Inconsistent with this, the TLR3 protein level was sharply reduced in RB1B-infected CEF cells at 96 hpi, while there was an at least 200-fold increase in miR-M4-5p at the same time point. Additionally, CEF cells transfected with an mdv1-mir-M4-5p mimic promoted RB1B infection and replication, while an mdv1-mir-M4-5p inhibitor inhibited RB1B infection and replication. Similar results were observed in CEF cells transfected with a gga-miR-155 mimic or inhibitor. These findings suggest that TLR3 and MDV-encoded miRNAs might be involved in MDV infection.


Assuntos
Fibroblastos/imunologia , Fibroblastos/virologia , Herpesvirus Galináceo 2/imunologia , Receptor 3 Toll-Like/metabolismo , Animais , Embrião de Galinha , Herpesvirus Galináceo 2/fisiologia , Interações Hospedeiro-Patógeno , MicroRNAs/metabolismo , RNA Viral/metabolismo , Replicação Viral
8.
Arch Virol ; 161(6): 1623-32, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27016933

RESUMO

Endogenous retroviruses (ERVs) are important retroelements that reside in host genomes. However, ERV expression patterns and regulatory mechanisms are poorly understood. In this study, chicken embryo fibroblasts (CEFs) and MSB1 cells infected with Marek's disease virus (MDV) exhibited significantly increased expression of env from the endogenous retrovirus ALVE. In contrast, env expression was significantly lower in CEF and MSB1 cells infected with exogenous avian leukosis virus J (ALVJ) at the early infection stage. Furthermore, env was found to be ubiquitously expressed in various chicken tissues, with high expression in certain tissues at 2 days of age and low levels in most tissues, including immune organs (thymus, spleen and bursa) as well as the brain and heart, at 35 days of age. Sequence analysis revealed miR-155 target sites in env transcripts, which was verified using a firefly luciferase reporter assay, and treatment with miR-155 agomir significantly decreased levels of env transcripts in MSB1 and CEF cells. Together, these findings suggest that the env gene from the endogenous retrovirus ALVE is regulated by miR-155.


Assuntos
Retrovirus Endógenos/genética , Genes env , MicroRNAs/genética , Animais , Leucose Aviária/virologia , Vírus da Leucose Aviária/genética , Vírus da Leucose Aviária/patogenicidade , Células Cultivadas , Embrião de Galinha , Galinhas , Retrovirus Endógenos/classificação , Retrovirus Endógenos/patogenicidade , Regulação Viral da Expressão Gênica , Mardivirus/genética , Mardivirus/patogenicidade , Filogenia
9.
Intervirology ; 58(2): 95-105, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25677615

RESUMO

Marek's disease virus (MDV) is a cell-associated alpha-herpesvirus that causes T-cell lymphomas and nervous disorders in chickens. Different from other lymphoid organs, the thymus is the site of T-cell maturation and differentiation. However, the transcriptional response to MDV infection in the chicken thymus is still not known. In this study, we performed genome-wide expression analysis in thymus tissues of RB1B-infected chickens at different time points to investigate the molecular mechanisms of MDV pathogenesis. The number of differentially expressed genes with 2-fold or higher changes (>2) are as follows: 1,250 genes (7 dpi), 834 genes (14 dpi), 1,958 genes (21 dpi), and 2,306 genes (28 dpi). Gene ontology enrichment analysis revealed that the upregulated genes were involved in immune and inflammatory response at 7 dpi; angiogenesis, cytoskeleton organization, cell adhesion, and signal transduction showed different expressions at 21 and 28 dpi. The expression pattern of 18 randomly selected genes was confirmed by real-time RT-PCR. Several differently expressed host genes associated with tumor development are discussed. We identified the global host-gene expression pattern in the thymus of chickens that responded to MDV infection. The present data may provide groundwork for future investigation in the biology and pathogenesis of MDV.


Assuntos
Perfilação da Expressão Gênica , Mardivirus/imunologia , Doença de Marek/genética , Doença de Marek/imunologia , Timo/virologia , Animais , Galinhas , Biologia Computacional , Doença de Marek/virologia , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Aves Domésticas , Reação em Cadeia da Polimerase em Tempo Real , Timo/imunologia , Regulação para Cima
10.
Genes (Basel) ; 15(8)2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39202404

RESUMO

As a founding member of the Src family of kinases, Src has been confirmed to participate in the regulation of immune responses, integrin signaling, and motility. Ducks are usually asymptomatic carriers of RNA viruses such as Newcastle disease virus and avian influenza virus, which can be deadly to chickens. The beneficial role of Src in modulating the immune response remains largely unknown in ducks. Here, we characterized the duck Src and found that it contains a 192-base-pair 5' untranslated region, a 1602-base-pair coding region, and a 2541-base-pair 3' untranslated region, encoding 533 amino acid residues. Additionally, duSrc transcripts were significantly activated in duck tissues infected by Newcastle disease virus compared to controls. The duSrc transcripts were notably widespread in all tissues examined, and the expression level was higher in liver, blood, lung, pancreas, and thymus. Moreover, we found the expression levels of IFN-ß, NF-κB, IRF3, and Src were significantly increased in DEFs after infection with 5'ppp dsRNA, but there was no significant difference before and after treatment in DF1 cells. Furthermore, overexpression of duSrc followed by stimulation with 5'ppp dsRNA led to an elevation of IFN-ß levels. The SH3 and PTKc domains of duSrc contributed to promoting the activity of IFN-ß and NF-κB in DEFs stimulated by 5'ppp dsRNA.


Assuntos
Clonagem Molecular , Patos , Animais , Patos/genética , Patos/imunologia , Patos/virologia , Quinases da Família src/genética , Quinases da Família src/metabolismo , Vírus da Doença de Newcastle/imunologia , Vírus da Doença de Newcastle/genética , Proteínas Aviárias/genética , Proteínas Aviárias/imunologia , Proteínas Aviárias/metabolismo , Doença de Newcastle/imunologia , Doença de Newcastle/virologia , Doença de Newcastle/genética , Interferon beta/genética , Interferon beta/imunologia , Interferon beta/metabolismo , Distribuição Tecidual , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/genética
11.
Arch Virol ; 158(8): 1787-93, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23494227

RESUMO

In this study, 86 Marek's disease virus (MDV) transcripts were detected in chicken thymus infected with RB1B strain. Forty-seven of them, which were mainly involved in viral replication and immune escape, were detected at 7 days postinfection (dpi). Expression of most of the genes was increased at 21 and 28 dpi but reduced or shut down at 14 dpi. Unlike others tissues, we found that a latent infection was established at 14 dpi in infected thymus. Here, we show the kinetics of expression of MDV transcripts and their relative expression in infected thymus.


Assuntos
Genes Virais , Mardivirus/crescimento & desenvolvimento , Mardivirus/genética , Doença de Marek/virologia , Timo/virologia , Transcriptoma , Animais , Galinhas , Evasão da Resposta Imune , Mardivirus/imunologia , Mardivirus/fisiologia , Fatores de Tempo , Replicação Viral
12.
Vet Res Commun ; 47(2): 431-443, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35715584

RESUMO

Endogenous retroviruses (ERVs) are remnants of the historical retroviral infections, and their derived transcripts with viral signatures are important sources of long noncoding RNAs (lncRNAs). We have previously shown that the chicken ERV-derived lncRNA lnc-ALVE1-AS1 exerts antiviral innate immunity in chicken embryo fibroblasts. However, it is not clear whether this endogenous retroviral RNA has a similar function in immune cells. Here, we found that lnc-ALVE1-AS1 was persistently inhibited in chicken macrophages after avian leukosis virus subgroup J (ALV-J) infection. Furthermore, overexpression of lnc-ALVE1-AS1 significantly inhibited the replication of exogenous ALV-J, whereas knockdown of lnc-ALVE1-AS1 promoted the replication of ALV-J in chicken macrophages. This phenomenon is attributed to the induction of antiviral innate immunity by lnc-ALVE1-AS1 in macrophages, whereas knockdown of lnc-ALVE1-AS1 had the opposite effect. Mechanistically, lnc-ALVE1-AS1 can be sensed by the cytosolic pattern recognition receptor TLR3 and trigger the type I interferons response. The present study provides novel insights into the antiviral defense of ERV-derived lncRNAs in macrophages and offers new strategies for future antiviral solutions.


Assuntos
Vírus da Leucose Aviária , RNA Longo não Codificante , Embrião de Galinha , Animais , Galinhas , Vírus da Leucose Aviária/genética , Receptor 3 Toll-Like/genética , RNA Longo não Codificante/genética , Linhagem Celular , Macrófagos , Antivirais
13.
IEEE Trans Vis Comput Graph ; 29(6): 3121-3144, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35104221

RESUMO

Utilizing Visualization-oriented Natural Language Interfaces (V-NLI) as a complementary input modality to direct manipulation for visual analytics can provide an engaging user experience. It enables users to focus on their tasks rather than having to worry about how to operate visualization tools on the interface. In the past two decades, leveraging advanced natural language processing technologies, numerous V-NLI systems have been developed in academic research and commercial software, especially in recent years. In this article, we conduct a comprehensive review of the existing V-NLIs. In order to classify each article, we develop categorical dimensions based on a classic information visualization pipeline with the extension of a V-NLI layer. The following seven stages are used: query interpretation, data transformation, visual mapping, view transformation, human interaction, dialogue management, and presentation. Finally, we also shed light on several promising directions for future work in the V-NLI community.

14.
Front Microbiol ; 14: 1205143, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37333648

RESUMO

Interferon and chemokine-mediated immune responses are two general antiviral programs of the innate immune system in response to viral infections and have recently emerged as important players in systemic metabolism. This study found that the chemokine CCL4 is negatively regulated by glucose metabolism and avian leukosis virus subgroup J (ALV-J) infection in chicken macrophages. Low expression levels of CCL4 define this immune response to high glucose treatment or ALV-J infection. Moreover, the ALV-J envelope protein is responsible for CCL4 inhibition. We confirmed that CCL4 could inhibit glucose metabolism and ALV-J replication in chicken macrophages. The present study provides novel insights into the antiviral defense mechanism and metabolic regulation of the chemokine CCL4 in chicken macrophages.

15.
Breast ; 72: 103597, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37944341

RESUMO

BACKGROUND: Inetetamab is a novel recombinant humanized anti-HER2 monoclonal antibody. This study aimed to evaluate the efficacy and safety of inetetamab and predictive factors for response in HER2-positive metastatic breast cancer (MBC) patients. METHODS: A cohort of HER2-positive MBC patients who received inetetamab-based therapy between June 2020 and August 2021 was evaluated. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included objective response rate (ORR) and disease control rate (DCR). Adverse events (AEs) were graded according to the National Cancer Institute Common Toxicity Criteria. RESULTS: A total of 141 patients were included in the final analysis. The median PFS of the entire cohort was 7.1 months. The median number of treatment lines administered was three. The ORR was 36.9 %, and the DCR was 80.9 %. The most frequently employed treatment strategy was inetetamab + chemotherapy (49/141, 34.8 %), followed by inetetamab + HER2-tyrosine kinase inhibitors (HER2-TKIs) + chemotherapy, inetetamab + pertuzumab + chemotherapy, inetetamab + endocrine treatment and inetetamab + HER2-TKIs. Cox multivariate analysis revealed that PFS was associated with liver metastasis (hazard ratio [HR] 2.112, 95 % confidence interval [CI] 1.334-3.343, p = 0.001), previous HER2-TKI treatment (HR 2.019, 95 % CI 1.133-3.597, p = 0.017) and estrogen receptor positivity (HR 0.587, 95 % CI 0.370-0.934, p = 0.024). The toxicity was tolerable, with neutropenia being the most common treatment-related grade 3/4 AE (14.9 %). CONCLUSION: Inetetamab demonstrates effectiveness with a manageable safety profile, offering a promising therapeutic option for HER2-positive breast cancer patients who have shown resistance to prior anti-HER2 treatments.


Assuntos
Anticorpos Monoclonais , Antineoplásicos , Neoplasias da Mama , Receptor ErbB-2 , Feminino , Humanos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/secundário , População do Leste Asiático , Receptor ErbB-2/antagonistas & inibidores , Trastuzumab/uso terapêutico , Resultado do Tratamento , Anticorpos Monoclonais/uso terapêutico
16.
Virol J ; 9: 256, 2012 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-23116199

RESUMO

BACKGROUND: Marek's disease virus (MDV) is a highly cell-associated oncogenic α-herpesvirus that causes a disease characterised by T-cell lymphomas. The pathogenesis, or the nature of the interaction of the virus and the host, in the thymus are still unclear. RESULTS: In this study, we identified 119 differentially expressed proteins using two-dimensional electrophoresis and mass spectrometry from the thymuses of chickens infected with the RB1B strain of MDV. These differentially expressed proteins were found mainly at 21, 28 and 35 days post-infection. More than 20 of the differentially expressed proteins were directly associated with immunity, apoptosis, tumour development and viral infection and replication. Five of these proteins, ANXA1, MIF, NPM1, OP18 and VIM, were further confirmed using real-time PCR. The functional associations and roles in oncogenesis of these proteins are discussed. CONCLUSIONS: This work provides a proteomic profiling of host responses to MDV in the thymus of chickens and further characterises proteins related to the mechanisms of MDV oncogenesis and pathogenesis.


Assuntos
Mardivirus , Doença de Marek/metabolismo , Proteoma , Proteômica , Timo/metabolismo , Timo/virologia , Animais , Galinhas , Perfilação da Expressão Gênica , Doença de Marek/genética , Espectrometria de Massas , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , RNA Mensageiro/genética , Reprodutibilidade dos Testes , Timo/patologia , Fatores de Tempo
17.
Vet Sci ; 10(1)2022 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-36669017

RESUMO

Avian leukosis virus (ALV) has a tremendous adverse impact on the poultry industry. Since its discovery, research on different aspects of ALV have been published. Due to the vast academic emphasis and economic importance of the ALV infection in poultry worldwide, this bibliometric analysis explored the scientific output associated with ALV utilizing the Web of Science (Core Collection) database. The relevant data were collected using the search query "AVIAN LEUKOSIS VIRUS", further refined by document types (article, book chapter, and proceedings paper). Finally, 1060 items with full records were imported in Plaintext and tab-delimited formats. The data analysis was carried out using MS Excel, VOS viewer, and R (Biblioshiny) software. Chinese and American research institutions produced the majority of papers during study time period. The Journal of Virology and Avian Diseases appeared as the favorite journal/source for publications. Apart from the avian leukosis virus and the ALV-J, the important keywords mentioned included avian leukosis virus subgroup j, chicken, and retrovirus. The analysis revealed substantial findings on ALV research, with a strong research response from the USA and China.

18.
Rend Lincei Sci Fis Nat ; 33(3): 663-672, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35967085

RESUMO

Endogenous retrovirus (ERV) research amalgamates host-retroviral coevolutionary, phylogenomic, infection, immunity, and cellular studies in various hosts ranging from fish to humans. Henceforth, a bibliometric analysis of these publications may aid in the identification of trends in ERV research. It was the foremost bibliographic study, with the key aim to conduct the bibliometric network analysis (e.g. co-authorship, co-occurrence, citation, bibliographic coupling, and co-citation analysis) to find the most prolific authors, organizations, and countries in ERV research, based on the mapping of bibliographic data. Second, the mapping based on text data comprised to chalk out the research trend over the time. The global literature about endogenous retroviruses published between 1985 and Sep 2021 was searched in the Web of Science (Core Collection) database using the "ENDOGENOUS RETROVIRUS" keyword. The bibliometric analysis of this dataset was carried out using VOSviewer version 1.6.17. According to findings, English was the de facto language of these publications, and 2157 were original articles. Among 2939 published documents, "endogenous retrovirus" was the most frequent keyword. Moreover, it revealed the United States as a core contributor to studies on the ERV. The Journal of Virology published a substantial amount of manuscripts in ERV. Robert Koch Institute and Harvard University were leading organizations for research in this field. The application of ERV research from China could be the research hotspot to follow in the coming years. Current bibliometric analysis provides a comprehensive picture of ERV research progress and has highlighted the contribution of different stakeholders.

19.
J Poult Sci ; 58(4): 245-257, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34899020

RESUMO

Nutrition and energy are essential for poultry growth and production performance. Fasting and refeeding have been widely used to study the effects of nutrition, energy, and related mechanisms in chicken. Previous studies have shown that geese have a strong capacity for fat synthesis and storage; thus, changes in the goose liver transcriptome may be different from those in chicken assessed with a model of fasting and refeeding. However, the responses of the goose liver transcriptome to fasting and refeeding have not yet been addressed. In this study, 36 70-day-old Si Ji geese with similar body weight were randomly assigned to three groups: control (ad libitum feeding), fasting (fasted for 24 h), and refeeding (fast for 24 h followed by 2-h feeding) groups. After treatment, eight geese per group were sacrificed for sample collection. Liver samples from four geese in each group were subjected to transcriptome analysis, followed by validation of differentially expressed genes (DEGs) using quantitative polymerase chain reaction with the remaining samples. As a result, 155 DEGs (73 up-regulated) were identified between the control and fasting groups, and 651 DEGs (321 up-regulated) were identified between the fasting and refeeding groups. The enrichment analyses of Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways showed that fasting mainly influenced material metabolism in the liver, especially lipid metabolism; in contrast, refeeding affected not only lipid metabolism but also glucose and amino acid metabolism. In addition, the peroxisome proliferator-activated receptor (PPAR) signaling pathway may play an important role in lipid metabolism. In conclusion, fasting and refeeding have a strong effect on lipid metabolism in the goose liver; specifically, fasting promotes fatty acid oxidation and inhibits fatty acid synthesis, and refeeding has the opposite effect. The model of fasting and refeeding is suitable for goose nutrition studies.

20.
Front Microbiol ; 12: 788317, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34912323

RESUMO

Infection with the avian leukosis virus subgroup J (ALV-J) impairs host genes and facilitates the establishment of chronic infection and the viral life cycle. However, the involvement of long noncoding RNAs (lncRNAs) in ALV-J infection remains largely unknown. In this study, we identified a novel chicken lncRNA derived from LTR5B of the ERV-L family (namely lnc-LTR5B), which is significantly downregulated in ALV-J infected cells. lnc-LTR5B was localized in the cytoplasm and was relatively high expressed in the chicken lung and liver. Notably, the replication of ALV-J was inhibited by the overexpression of lnc-LTR5B but enhanced when lnc-LTR5B expression was knocked down. We further confirmed that lnc-LTR5B could bind to the binding immunoglobulin protein (BiP), a master regulator of endoplasmic reticulum (ER) function. Mechanistically, lnc-LTR5B serves as a competing endogenous RNA for BiP, restricting its physical availability. Upon ALV-J infection, the reduction of lnc-LTR5B released BiP, which facilitated its translocation to the cell surface. This is crucial for ALV-J entry as well as pro-survival signaling. In conclusion, we identified an endogenous retroviral LTR-activated lnc-LTR5B that is involved in regulating the cell surface translocation of BiP, and such regulatory machinery can be exploited by ALV-J to complete its life cycle and propagate.

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