Polo-like kinase 1 suppresses lung adenocarcinoma immunity through necroptosis.

Polo-like kinase 1 (PLK1) plays a crucial role in cell mitosis and has been associated with necroptosis. However, the role of PLK1 and necroptosis in lung adenocarcinoma (LA) remains unclear. In this study, we analyzed The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression databases to evaluate the prognostic value and mechanistic role of PLK1 in LA. PLK1 was found to be highly expressed in LA and was positively associated with advanced disease staging and poor survival outcomes. Functional enrichment analysis showed that PLK1 was involved in cell mitosis, neurotransmitter transmission, and drug metabolism. Further analysis using single-sample gene set enrichment analysis and ESTIMATE algorithm revealed a correlation between PLK1 expression and immune infiltration in LA. Silencing of PLK1 using miRNA transfection in LA cells reduced cell proliferation and increased apoptosis, as well as upregulating the expression of necroptosis-related proteins, such as RIPK1, RIPK3, and MLKL. Additionally, nude mouse transplantation tumor experiments demonstrated that silencing PLK1 reduced the growth capacity of LA cells. These findings suggest that PLK1 plays a critical role in LA progression by regulating necroptosis and immune infiltration, and may serve as a potential therapeutic target for immunotherapy. Furthermore, PLK1 expression can be used as a prognostic biomarker for LA patients.

The best strategy for metastatic colorectal cancer (mCRC) patients in second-line treatment: A network meta-analysis.

BACKGROUND: Varieties of systemic treatments in second-line treatment for metastatic colorectal cancer (mCRC) patients have showed an improvement on survival. In this study, we performed a systematic review with a pairwise and bayesian network meta-analysis to rank the best strategy for mCRC patients in second-line treatment. METHODS: A systematic literature search through 2007 was performed to evaluate the association between several treatment combinations and overall survival (OS), progression-free survival (PFS) and disease control rate (DCR) in mCRC patients. Data were carried out and pooled into a statistical indirect comparison with Bayesian network meta-analysis (NMA). RESULTS: 10 trials totally comprised 4183 patients were included in our study. In NMA, For PFS, Doublet+Bev showed benefits in comparing with Doublet, Doulblet+placebo and Doublet+Ramucirumab. Also, Doublet+Aflibercept demonstrated its superiority in comparing with Doulblet+placebo. For OS, Doublet+Bev represented its superiority when comparing with Double and Doublet+placebo. Doublet+Aflibercept and Doublet+Ramucirumab also done well when opposed to Doublet+placebo. For DCR, Doublet+bev showed unique superiority when compared with Doublet, And Doublet+targeted agent did not represent benefits to each other in DCR. Doublet+bev ranked highest in terms of PFS, OS and DCR followed by Doublet+panitumumab, Doublet+placebo was the lowest in terms of PFS and OS. CONCLUSIONS: Our study shows that Doublet+Bev has the major probability to provide an improvement of survival in patients with mCRC.

Identifications of Candidate Genes Significantly Associated With Rectal Cancer by Integrated Bioinformatics Analysis.

INTRODUCTION: Rectal cancer ranks as the eighth in cancer-related morbidity and the tenth in the cancer-related mortality. A few studies have explored several biomarkers for colorectal cancer. However, there is still a great need for us to excavate novel biomarkers with effective and efficient diagnostic and prognostic values to discover the etiology and pathogenesis of rectal cancer separately. Therefore, we aimed to identify more novel candidate genes that were significantly associated with rectal cancer through integrated bioinformatics analysis. METHODS: We analyzed the gene expression profiles of GSE15781 and GSE20842 from Gene Expression Omnibus database to identify differentially expressed genes between normal rectal tissue and rectal cancer tissue. RESULTS: We searched for core genes, carried out survival analysis and analyzed the expressions of core genes. We found that 142 genes were significantly upregulated, and 229 genes were significantly downregulated in all 3 independent studies. In KEGG analysis, the upregulated genes were significantly enriched in cytokine-cytokine receptor interaction, IL-17 signaling pathway, cell cycle, etc. The downregulated genes were primarily enriched in nitrogen metabolism, mineral absorption and pentose and glucuronate interconversions. Inhibin subunit beta B (INHBB) expressed markedly higher in rectal cancer tissues compared with normal tissues, and claudins (CLDN) 23 expressed significantly lower in rectal cancer tissues. CONCLUSION: In conclusion, we discovered that INHBB could provide a great significant diagnostic and prognostic values for rectal cancer.

Solanine Inhibits Immune Escape Mediated by Hepatoma Treg Cells via the TGFß/Smad Signaling Pathway.

OBJECTIVE: To observe the inhibitory effect of solanine on regulatory T cells (Treg) in transplanted hepatoma mice and to study the mechanism of solanine inhibiting tumor growth. METHODS: The levels of Treg cells and IL-2, IL-10, and TGFß in the blood of patients with liver cancer were detected by flow cytometry and ELISA, respectively. A mouse hepatocellular carcinoma (HCC) graft model was established and randomly divided into four groups: control group, solanine group, TGFß inhibitor group (SB-431542), and solanine +TGFß inhibitor combined group. Tumor volume of each group was recorded, tumor inhibition rate was calculated, and tumor metastasis was counted. The proportion of CD4+CD25+Foxp3+ Treg in transplanted tumor tissues was detected by flow cytometry. The expression levels of Foxp3 and TGFß in transplanted tumor tissues were detected by quantitative fluorescence PCR. RESULTS: Compared with healthy people, Treg cells and IL-2, IL-10, and TGFß contents in peripheral blood of liver cancer patients were increased. The results of the transplanted tumor model in mice showed that the tumor volume of the transplanted mice in the solanine group and the TGFß inhibitor mice was reduced compared with the control group. The combined group had the smallest tumor volume. The proportion of CD4+CD25+Foxp3+ Treg in the transplanted tumor tissues of mice in the solanine treatment group was significantly lower than that in the control group. The expressions of Foxp3 and TGFß in the transplanted tumor tissues of mice in the solanine group were significantly lower than those in the control group. CONCLUSION: Solanine may enhance the antitumor immune response by downregulating the proportion of CD4+CD25+ Treg and the expression of Foxp3 and TGFß in tumor tissues.

Certain interleukin polymorphisms might influence predisposition to lung cancer: A meta-analysis of 35 published studies.

Interleukin polymorphisms might influence predisposition to lung cancer (LC), but the results of already published studies regarding the relationship between interleukin polymorphisms and LC were still controversial and ambiguous. So the authors designed this meta-analysis to more precisely estimate relationship between interleukin polymorphisms and LC by pooling the results of already published related studies. The authors searched Pubmed, Embase, Web of Science, and CNKI for already published studies. Thirty-five already published studies were pooled and analyzed in this meta-analysis. The pooled meta-analyses results showed that distributions of IL-4 rs2243250 polymorphism among patients and controls from Asian countries differed significantly (dominant comparison: OR = 1.29, 95% CI 1.07-1.55; overdominant comparison: OR = 0.83, 95% CI 0.73-0.95; allele comparison: OR = 1.26, 95% CI 1.03-1.54), and distributions of IL-10 rs1800872 polymorphism among patients and controls from Caucasian countries also differed significantly (recessive comparison: OR = 0.54, 95% CI 0.35-0.83; overdominant comparison: OR = 1.26, 95% CI 1.05.1.51). No genotypic distribution differences were observed for IL-4 rs2070874, IL-6 rs1800795, IL-6 rs1800796, IL-8 rs4073, IL-10 rs1800871, and IL-10 rs1800896 polymorphisms in pooled meta-analyses. This meta-analysis suggested that IL-4 rs2243250 might influence predisposition to LC in Asians, whereas IL-10 rs1800872 polymorphism might influence predisposition to LC in Caucasians.

[Research progress on nonspecific immune microenvironment in breast cancer].

The immune microenvironment plays an important role in the occurrence and development of breast cancer. The infiltrating immune cells and the produced inflammatory cytokines in the tumor microenvironment regulate the growth, proliferation and metastasis of breast cancer. In this article, the roles and related mechanisms of nonspecific immune microenvironment in breast cancer are summarized, focusing on the natural killer cells, dendritic cells, myeloid derived suppressor cells, tumor associated macrophages, interleukins, chemokines, tumor necrosis factor-α, transforming growth factor-ß and so on.

[Fibromyalgia syndrome after comprehensive treatment of breast cancer: a case report].

Fibromyalgia syndrome after comprehensive treatment of breast cancer is rare and seldom reported. Here we present a case of a 50-year-old female patient,who was admitted to the hospital because of generalized fibromyalgia for 3 months and brain metastasis after the right breast carcinoma surgery for 1 month, and the clinical diagnosis was brain metastasis from breast carcinoma combined with fibromyalgia syndrome. The fibromyalgia were relieved with proper symptomatic treatment but the patient eventually died of tumor progression.