Epithelial ovarian cancer (EOC) is a highly lethal gynecological malignancy since it could not be discovered until at late stage. Identifying the molecular phenotype alteration during the development and progression of ovarian cancer is an urgent demand for the targeted intervention therapy. Recently, inflammation and Integrin beta 1(ITGB1), a subunit of heterodimeric transmembrane receptors family, had been pointed out to be involved in promoting ovarian tumorigenesis and cancer progression, respectively. However, the relationship between ITGB1 and the inflammatory mediators in ovarian cancer progression remains obscure. In the present study, ITGB1 was observed to be frequently upregulated in ovarian cancer, overexpression of ITGB1 led to a more invasive and mesenchymal phenotype. Furthermore, our results also provided evidence concerning the role of inflammatory cytokines (IL-6, TGF-β1 and SDF-1) in ITGB1 expression as well as in the malignant potential of ovarian cancer cells. Consistently, sh-RNA mediated knocking down of ITGB1 evidently reduced tumor growth and peritoneal dissemination in in vivo Nod-scid SKOV3 orthotopic xenograft mice. Overall, the present data suggested that ITGB1 upregulation was involved in the regulation of tumorigenesis and disease exacerbation exerted by inflammatory cytokines as IL-6, TGF-β1 and SDF-1, and suggested that targeting ITGB1 and the underlying inflammatory modulator was an attractive strategy for therapeutic intervention during ovarian carcinogenesis.
Vγ2Vδ2 T cell-based immunotherapy has benefited some patients in clinical trials, but the overall efficacy is low for solid tumor patients. In this study, a bispecific antibody against both PD-L1 and CD3 (PD-L1 x CD3), Y111, could efficiently bridge T cells and PD-L1 expressing tumor cells. The Y111 prompted fresh CD8+ T cell-mediated lysis of H358 cells, but spared this effect on the fresh Vδ2+ T cells enriched from the same donors, which suggested that Y111 could bypass the anti-tumor capacity of the fresh Vγ2Vδ2 T cells. As the adoptive transfer of the expanded Vγ2Vδ2 T cells was approved to be safe and well-tolerated in clinical trials, we hypothesized that the combination of the expanded Vγ2Vδ2 T cells with the Y111 would provide an alternative approach of immunotherapy. Y111 induced the activation of the expanded Vγ2Vδ2 T cells in a dose-dependent fashion in the presence of PD-L1 positive tumor cells. Moreover, Y111 increased the cytotoxicity of the expanded Vγ2Vδ2 T cells against various NSCLC-derived tumor cell lines with the releases of granzyme B, IFNγ, and TNFα in vitro. Meanwhile, the adoptive transferred Vγ2Vδ2 T cells together with the Y111 inhibited the growth of the established xenografts in NPG mice. Taken together, our data suggested a clinical potential for the adoptive transferring the Vγ2Vδ2 T cells with the Y111 to treat PD-L1 positive solid tumors.
JAK-STAT signaling pathway shared by a variety of cytokines was discovered in recent years. It plays an important role in growth and development, cell apoptosis and immune response. In general, activated STAT dimer binds to a palindromic sequence (TTCN2-4GAA) located at the upstream promoter region to activate gene transcription. Some signal pathways including Toll and Imd in silkworm Bombyx mori, a model of Lepidopteran insect, have been well studied. However, little is known regarding JAK-STAT signal pathway. In the present study, the genes regulated by JAK-STAT signal pathway were predicted by bioinformatics analysis. 1000bp of upstream promoter sequence of the all predicted genes were downloaded from the silkworm genome database, and the STAT binding sequence TTCN2-4GAA were searched by scanning the promoter sequences, the results showed that 1 to 6 the target sequences could be found in the upstream promoter sequences of 9293 genes coding7271 non-redundant proteins. Go annotation results showed that these proteins were involved to cellular component, molecular function and biological process, suggesting JAK-STAT pathway play an important role in many way. More than 50% genes related to binding, about 40% genes related to cellular process, metabolic process and catalytic activity in the targeting genes. It is considered that JAK-STAT play a role in immune response.1-4 STAT binding sequences could be detected in promoter region of some genes related to anti-viral factors, cellular immune effector, and small antimicrobial peptide including defensin, attacin, moricin and gloverin3, implying that the expression of some anti-viral factors, cellular immune effectors and antimicrobial peptides related to antiviral activity might be regulated by JAK-STAT signal pathway.
With the development of the PCR technology, especially the improvement of its reagent and a method of pebrine detection by PCR in infected Bombyx mori eggs was established.With the 16sRNA gene of Nosema bombycis as target sequence, the results of extraction of genomic DNA from purified microspores showed that 1.3×10-7µg DNA can be extracted from each spore. The sensitivity detection showed the detection limit of Nosema bombycis DNA was 3.25×10-2pg, i.e. 4 spores. (PCR system volume is 25µl). The method of total DNA extraction from pebrine infected silkworm eggs just before hatching was created. The result showed that extracting total DNA from silkworm eggs after the eggs had been treated with 30% KOH met the PCR detection requirements. The result of application study showed the spores in the pebrine infected egg just before hatching can sensitively be found with PCR. The result of a group of eggs just before hatching detection showed that the maximum PCR detection level was of a pebrine infected eggs just before hatching in 300 healthy eggs when the total DNA extraction had been purified with Agarose electrophoresis. The probability of identifying groups of one pebrine spore in infected eggs just before hatching mixed with 100 healthy ones was about 80%.
Hippo kinase cascade shared by a variety of multicellular animals is appreciated as a signaling pathway which aims to inhibit the growth of cells and it is very conservative during evolution. Recent studies have confirmed that the Hippo signal pathway functions in cancer, tissue regeneration as well as stem cell regulation. The silkworm Bombyx mori is a model of Lepidopteran insect, little is known regarding genes related to Hippo kinase cascade. In the present study, the sequences of major genes related to Hippo pathway are obtained successfully in silkworm, B. mori, by in silico cloning or RT-PCR, including BmHop, BmSav, BmMats, BmWts and BmYki. The deduced amino acid sequences of the genes were aligned with those of other species, although the sequence identities of these proteins from different species were not high, the conserved domains were prominent, suggesting that the roles of Hippo pathway in the silkworm are similar to those in other species. These results has laid an important foundation for the further understanding and clarifying the function of the Hippo signaling pathway in silkworm.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.