Background
Interleukin-6 (IL-6) has been demonstrated to be a critical factor for breast cancer malignancy. However, the molecular mechanisms by which IL-6 induce breast cancer cells epithelial–mesenchymal-transition (EMT) and stemness remain elusive.
Methods
Breast cancer cell lines T47D and MCF7 were exposed to IL-6, the expression of PIM1 was examined by quantitative real-time PCR (qRT-PCR) and western blot. Luciferase reporter assay was used to determine the transcriptional modulation of PIM1 by IL-6 and STAT3 inhibitor. Transwell assay was used to detect the invading ability of breast cancer cells induced by IL-6 or PIM1. The expressions of EMT and stemness markers were determined by qRT-PCR.
Results
IL-6 promoted PIM1 expression in a dose- and time-dependent manner, and this induction could be abrogated by inhibiting STAT3 activation, subsequently suppressing the transcriptional level of PIM1. Moreover, we noticed that knocking down of PIM1 in cells which was exposed to IL-6 significantly impaired the invasion ability and the expression of EMT and stemness markers. On the contrary, overexpression of PIM1 promoted cell invasion and upregulated the expression of EMT and stemness markers. In addition, we demonstrated that c-myc, the cofactor of PIM1, involved in the pro-oncogenic roles of PIM1. Knocking down of c-myc attenuated the PIM1-induced cell EMT and stemness.
Conclusion
This study proposed the upregulation of PIM1 by IL-6 contributed to breast cancer cell aggressiveness and targeting PIM1 or c-myc could be novel approaches for breast cancer treatment.
Aims
To evaluate the compliance of patients after gastrectomy in taking oral nutritional supplementation and to explore the promoting and hindering factors.
Design
A mixed‐methods design with an explanatory sequential approach was employed.
Methods
We conducted a 12‐week longitudinal study to evaluate the oral nutritional supplementation compliance of 122 patients after gastric cancer surgery and the factors that affected their compliance. After the quantitative phase, we selected the interview subjects and developed the interview outline based on the analysis of the quantitative results. In‐depth interviews (n = 15) were conducted to explain and supplement the quantitative phase results. Data were collected from October 2019 to May 2020.
Results
The average overall compliance rate of oral nutritional supplementation in patients with gastric cancer over 12 weeks was 30.59%. Adverse reactions to oral nutritional supplementation, the identity of the main caregivers and the patient's financial ability were independent factors that affected patient compliance. In subsequent interviews, we extracted four themes: social support plays an important role in patients taking oral nutritional supplementation, adverse reactions discourage patients from continuing to take oral nutritional supplementation, patients' attitudes affect their motivation to take oral nutritional supplementation, and the different needs of patients for oral nutritional supplementation affect patient compliance.
Conclusion
Patients' compliance with oral nutritional supplementation after gastric cancer surgery is very low. Health education should pay more attention to the management of adverse reactions and the role of patients' peers and family members. Oral nutritional supplementation products should be diversified to provide patients with more choices.
Impact
This study clarifies the factors that hinder and promote oral nutritional supplementation compliance and provides an important reference for the establishment and revision of health education strategies for patients after gastric cancer surgery.
Purpose
Mutation-specific T-cell response to epithelial cancers and T-cell-based immunotherapy has been successfully used to treat several human solid cancers. We aimed to investigate the anti-tumour effect of neo-antigen-reactive T(NRT) cells induced by RNA mutanome vaccine, which may serve as a feasible and effective therapeutic approach for lung cancer.
Methods
We predicted candidate neo-antigens according to the mutant gene analysis by sequencing the mouse Lewis cells and C57BL/6 mouse tail tissue. RNA vaccine was prepared with the neo-antigens as the template. We assessed antitumor efficacy, cytokine secretion and pathological changes after adoptive transfer of NRT cells in vitro and vivo experiments.
Results
We identified 10 non-synonymous somatic mutations and successfully generated NRT cells. The percentage of T-cell activation proportion was increased from 0.072% in conventional T cells to 9.96% in NRT cells. Interferon-γ secretion augmented from 17.8 to 24.2% as well. As an in vivo model, adoptive NRT cell infusion could promote active T-cell infiltration into the tumour tissue and could delay tumour progression.
Conclusion
NRT cells induced by RNA mutanome vaccine exert a significant anti-tumour effect in mouse lung cancer, and adoptive NRT cell therapy might be considered a feasible, effective therapeutic approach for lung cancer.
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