RESUMO
Colorectal cancer (CRC) is a heterogeneous disease of the intestinal epithelium and ranks the third largest diagnosed malignancy in the world. Many studies have shown that the high risk of CRC is believed to be related to the formation of biofilms. To prove causation, it will be significant to decipher which specific bacteria in biofilms initiate and maintain CRC and fully describe their underlying mechanisms. Here we introduce a bacterial driver-passenger model. This model added a novel and compelling angle to the role of microorganisms, putting more emphasis on the transformation of bacterial composition in biofilms which play different roles in the development of CRC. In this model, bacterial drivers can initiate the formation of CRC through genotoxicity, while bacterial passengers maintain the CRC process through metabolites. On the basis of these pathogens, we further turned our attention to strategies that can inhibit and eradicate these pathogenic biofilms, with the aim of finding new ways to hinder colorectal carcinogenesis.
Assuntos
Neoplasias Colorretais , Microbioma Gastrointestinal , Bactérias , Biofilmes , Carcinogênese/patologia , Neoplasias Colorretais/patologia , HumanosRESUMO
PURPOSE: The current study aims to explore the effects of CDKN2A on cell proliferation and cycle, and investigate the underlying mechanisms. METHODS: Expression of CDKN2A in cervical cancer cell lines was evaluated by real-time quantitative PCR (RT-qPCR) and western blotting. Apoptotic rate was detected by Annexin V assay. MTT assay, Transwell assay and cell cycle assay kit were applied to examine the effect of CDKN2A on cell viability, invasion and cell cycle. Co-immunoprecipitation and western blotting were devoted to explore the mechanism by which CDKN2A contributes to cell function. RESULTS: CDKN2A was expressed at a low level in cervical cancer cell lines. Overexpression of CDKN2A inhibited cell proliferation and invasion, and caused cell cycle arrest in the G1 phase. CDKN2A mediates the AKT-mTOR signaling pathway by suppressing lactate dehydrogenase (LDHA). Taken together, our data revealed that CDKN2A can be applied as a therapeutic target for the treatment of cervical cancer in future. CONCLUSIONS: CDKN2A inhibits cell proliferation and invasion in cervical cancer through LDHA-mediated AKT-mTOR pathway.
Assuntos
Proliferação de Células/fisiologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , L-Lactato Desidrogenase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Neoplasias do Colo do Útero/metabolismo , Apoptose/fisiologia , Linhagem Celular Tumoral , Sobrevivência Celular/fisiologia , Regulação para Baixo/fisiologia , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular , Células HeLa , Humanos , Imunoprecipitação , Invasividade Neoplásica , Neoplasias do Colo do Útero/patologiaRESUMO
PURPOSE: Our study aimed to explore the programmed death 1 (PD-1) expression on tumor-associated macrophage (TAM) in T cell non-Hodgkin lymphoma (T-NHL) and its relationship with lymphoma prognosis. The effect of PD-1 expression on the function of macrophages was also studied. METHODS: Multispectral image quantitative analysis was applied for detecting PD-1 expression on macrophages in T cell lymphoma tissues. The Kaplan-Meier analysis was performed to evaluate the value of PD-1 expression of TAM in predicting the overall survival of T-NHL. PD-1 overexpression THP-1-derived macrophage was constructed and was cocultured with Jurkat cells to explore the effect of PD-1 on macrophage function. RESULTS: In 17 T cell lymphoma cases, the 1-year overall survival rate was significantly lower in patients with higher PD-1 expression on TAMs (0.25 vs 0.86, p < 0.05). After co-cultured with Jurkat cells, classically activated (M1)-related markers on PD-1 overexpressed macrophages were significantly lower than those on controls, while the expressions of alternatively activated (M2) related markers were similar. The PD-1 overexpressed macrophages showed inhibited phagocytosis (4.42% vs 40.7%, p < 0.001) and increased IL-10 secretion (144.48 pg/ml vs 32.32 pg/ml, p < 0.001). CONCLUSION: High PD-1 expression on TAMs in T-NHL may predict poor prognosis. The PD-1 overexpression of macrophages significantly inhibited polarization of M1 macrophages and phagocytosis, and more IL-10 was excreted. These changes may enhance the pro-tumor effects of tumor microenvironment.
Assuntos
Linfoma de Células T/metabolismo , Receptor de Morte Celular Programada 1/biossíntese , Macrófagos Associados a Tumor/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Células Tumorais CultivadasRESUMO
PURPOSE: Cetuximab (CTX) has been used to treat metastatic colorectal cancer (mCRC) with wild-type (wt) RAS and BRAF genes. Meanwhile HER2 amplification reportedly denoted CTX-resistant mCRC tumors. We investigated whether monitoring of HER2 amplification in circulating DNA allowed early detection of mCRC progression and CTX resistance. METHODS: We analyzed HER2 amplification in circulating DNA at 8-week intervals using ddPCR from 36 patients with RASwt/BRAFwt mCRC, who progressed after CTX treatments between July 2015 and January 2018. RESULTS: Of the 36 patients, 5 (13.9%) exhibited dynamic fluctuations of HER2 amplification in plasma in the course of CTX treatment, of whom 2 were positive for HER2 amplification in matched tumor specimens at baseline (per FISH). All 5 primary sites were left side: 3 rectums and 2 descending colon. HER2 ratio fluctuations in circulating DNA not only reflected changes in tumor volume, but their obvious increases presaged CT-documented progress by an average lead time of 2 months. Interestingly, progression-free survival did not significantly differ between these 5 patients and those without HER2 amplification (HR 1.06, 95% CI 0.40-2.77, P = 0.909). CONCLUSION: Plasma HER2 amplification detected by ddPCR changed over time and predicted resistance to CTX, by an average lead time of 2 months. Further study is needed to validate our findings.
Assuntos
Ácidos Nucleicos Livres/sangue , Cetuximab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Receptor ErbB-2/genética , Adulto , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Amplificação de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Resultado do TratamentoRESUMO
Circulating tumor cells (CTCs), as cells shed from solid tumor into the vasculature, play a significant role in tumor metastasis. In the peripheral blood, immune cells and stromal cells can interact with CTCs and influence their biological behaviors of survival, proliferation, dissemination, and immune evasion. These peripheral blood cells can evolve synergistically with CTCs to constitute the liquid microenvironment which is essential for tumor progression. Here, we review the mechanisms of peripheral blood cells interacting with CTCs and uncover their effects on both CTCs and tumor metastasis. Then, we introduce the applications of these CTC-associated peripheral blood cells in the clinical setting. Besides, some peripheral blood cell subsets are of additional clinical values to CTCs in cancer diagnosis and prognosis. To improve the clinical utility of CTCs, an integrative analysis of CTCs and associated peripheral blood cells should be advocated for, which could provide a novel insight into tumor biology and offer comprehensive information in cancer diagnosis, prognosis, and therapy efficacy evaluation.
Assuntos
Biomarcadores Tumorais/sangue , Células Sanguíneas/patologia , Neoplasias/diagnóstico , Células Neoplásicas Circulantes/patologia , Microambiente Tumoral , Humanos , Biópsia Líquida , Neoplasias/sangue , PrognósticoRESUMO
Circular RNAs (CircRNAs) are a type of non-coding RNAs (NcRNAs) with a closed annular structure. Until next-generation sequencing (NGS) is developed, the misunderstanding of circRNAs 'splicing error' has changed, and the mysterious veil of circRNAs has been revealed. NGS provides an approach to investigate circRNAs. Many scholars point out that circRNAs may play an important role in many diseases, especially cancer. At the same time, exosomes, as a kind of extracellular vesicles loaded with many contents, are a hotspot in recent years. They can act as 'messengers' between cells, especially in cancer. Lately, it is interesting circRNAs are enriched and stable in exosomes, also called exo-circRNAs, and there have been several articles on circRNAs associated with exosomes. In this review, we summarize the characteristics of circRNAs, especially its main functions. Then, we briefly introduce exosomes and their function in cancer. Finally, the known relation between circRNAs and exosomes is discussed. With further researches, exo-circRNAs may be a novel pathway for cancer diagnosis and targeted therapy.
Assuntos
Exossomos/fisiologia , Neoplasias/genética , RNA/fisiologia , Humanos , Sistema Imunitário/fisiologia , MicroRNAs/fisiologia , Metástase Neoplásica , RNA CircularRESUMO
Newcastle disease is a highly contagious disease responsible for major outbreaks and considerable economic losses in the poultry industry in China. There is still little information available regarding gene characterization of the NDV, especially in ducks and pigeons. Therefore, the aim of this study was to investigate NDV isolated from ducks and pigeons in Hubei, China. In this study, three NDVs from ducks and pigeons were isolated between 2013 and 2015.The fusion protein (F) gene of the NDV isolates was sequenced and phylogenetically analyzed. The clinical signs and gross histopathological lesions were examined. Phylogenetic analysis of these strains indicated that all the sequences are classified as genotype II. The isolates shared a 112 G-R-Q-G-R-L 117motif at the F protein cleavage site, indicating that these three isolates strains are lentogenic. Necropsy and histopathology showed the typical pathological changes. It was concluded that commercial ducks and pigeons in Hubei province carry lentogenic NDV strains with regular genetic divergence, indicating that these species may act as the main reservoirs of NDV in poultry. Therefore, strategies and surveillance should be undertaken to reduce the risk of ND outbreaks.
Assuntos
Animais , Columbidae/genética , Columbidae/virologia , Patos/genética , Patos/virologia , Vírus da Doença de Newcastle/classificação , Vírus da Doença de Newcastle/genéticaRESUMO
Newcastle disease is a highly contagious disease responsible for major outbreaks and considerable economic losses in the poultry industry in China. There is still little information available regarding gene characterization of the NDV, especially in ducks and pigeons. Therefore, the aim of this study was to investigate NDV isolated from ducks and pigeons in Hubei, China. In this study, three NDVs from ducks and pigeons were isolated between 2013 and 2015.The fusion protein (F) gene of the NDV isolates was sequenced and phylogenetically analyzed. The clinical signs and gross histopathological lesions were examined. Phylogenetic analysis of these strains indicated that all the sequences are classified as genotype II. The isolates shared a 112 G-R-Q-G-R-L 117motif at the F protein cleavage site, indicating that these three isolates strains are lentogenic. Necropsy and histopathology showed the typical pathological changes. It was concluded that commercial ducks and pigeons in Hubei province carry lentogenic NDV strains with regular genetic divergence, indicating that these species may act as the main reservoirs of NDV in poultry. Therefore, strategies and surveillance should be undertaken to reduce the risk of ND outbreaks.(AU)
Assuntos
Animais , Vírus da Doença de Newcastle/classificação , Vírus da Doença de Newcastle/genética , Patos/genética , Patos/virologia , Columbidae/genética , Columbidae/virologiaRESUMO
PURPOSE: Aspirin could reduce the risk of cancer metastasis. Circulating tumor cells (CTCs) are a key factor of cancer metastasis, but no evidence has revealed how aspirin affects CTCs and its epithelial-mesenchymal transition (EMT). Here, we conducted a clinical trial to investigate how aspirin affects CTCs in metastatic colorectal cancer (MCC) and breast cancer patients (MBC). METHODS: The trial is retrospective registered at clinicaltrials.gov (NCT02602938). The eligible patients are given 100 mg aspirin q.d. for 8 weeks, and CTCs are evaluated at baseline, 4 and 8 weeks for absolute number, phenotype (epithelial type, E+, mesenchymal type, M+, and biophenotypic type, B+), and vimentin expression. RESULTS: Data on 21 MCC and 19 MBC patients are analyzed, and it revealed that the CTC numbers decreased with aspirin treatment in MCC (p < 0.001) but not MBC (p = 0.0532); besides, ratio of E+ CTCs increased (p = 0.037) and M+ CTCs decreased at 2 months in MCC (p = 0.013), but neither the ratio of E+ or M+ CTCs changes significantly in MBC; vimentin expression of M+ CTCs is higher than E+ and B+ CTCs either in MBC or MCC patients at baseline (p < 0.01); and aspirin suppresses the vimentin expression in M+ (p = 0.002)and B+ (p = 0.006) CTCs of MCC and M+ CTCs of MBC (p = 0.004); besides it find vimentin expression in B+ (p = 0.004) or M+ (p < 0.001), CTCs are markedly decreased in patients with total CTC numbers declined. CONCLUSION: Aspirin could decrease CTCs numbers and block EMT transition in MCC patients and part of MBC patients.
Assuntos
Aspirina/administração & dosagem , Neoplasias da Mama/patologia , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Células Neoplásicas Circulantes/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/administração & dosagem , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Neoplasias Colorretais/sangue , Neoplasias Colorretais/tratamento farmacológico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Células Neoplásicas Circulantes/efeitos dos fármacos , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Vimentina/metabolismo , Adulto JovemRESUMO
PURPOSE: Transcatheter arterial embolization (TAE) has been widely used in treating non-curative hepatocellular carcinoma (HCC). However, it is noticed that TAE may cause invasion of some cancer cells into circulation, resulting in distal metastasis and poor therapeutic outcome. Here, we aimed to reduce the side effects of TAE using the inhibitors for epidermal growth factor receptor (EGFR). METHODS: Transient hepatic artery ligation (HAL) was used as a mouse model for TAE. EGFR inhibitors were applied. Tumor size, presence of tumor cells in circulation, distal tumor formation, and activation of genes associated with tumor cell invasion and metastasis were analyzed. RESULTS: Inhibitors for EGFR significantly reduced the size of primary tumor, presence of tumor cells in circulation, and distal tumor formation after HAL. Further studies showed that EGFR inhibition suppressed several genes associated with tumor cell invasion and metastasis, such as vascular endothelial growth factor-A, stromal cell-derived factor 1, and Slug. CONCLUSION: EGFR inhibitor application may reduce circulating cancer cells during TAE and thus improve the therapy for advanced HCC.