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BACKGROUND Breast cancer (BC), a prevalent and heterogeneous disease of glandular breast tissue, is the most common cancer in women. The interaction between Kaempferol and IQ motif containing GTPase-activating protein 3 (IQGAP3) in BC and its underlying mechanism are poorly defined. MATERIAL AND METHODS After natural phytochemicals treatment, the expression of IQGAP3 in BC cells (ZR-75-30 and BT474) was detected by real-time PCR. Then, the proliferation and apoptosis in BC cells with different gradient concentrations (10, 25, 50, and 100 µmol/l) of Kaempferol treatment were detected. After treatment with Kaempferol or epidermal growth factor (EGF), we assessed apoptosis and expression of related genes. RESULTS We found that natural phytochemicals, especially Kaempferol, decreased IQGAP3 expression in BC cells. Kaempferol significantly induced proliferation inhibition and apoptosis in BC cells, concurrent with decreased IQGAP3 expression. Upregulation of IQGAP3 inhibited apoptosis in BC cells, along with increased expression of phosphorylated extracellular signal-regulated kinases 1/2 (p-ERK1/2) and B cell lymphoma 2 (Bcl2) and decreased Bcl-2-associated X protein (Bax) expression, which was counteracted by Kaempferol treatment. EGF markedly inhibited Kaempferol-induced apoptosis in BC cells, and ERK1/2 inhibitor PD98059 had an effect similar to that of Kaempferol. CONCLUSIONS IQGAP3 may be a potential target gene for Kaempferol in the treatment of BC, and upregulation of IQGAP3 inhibits Kaempferol-induced apoptosis in BC cells by ERK1/2 signaling activation. Targeting IQGAP3 may contribute to the study of natural phytochemicals as anti-tumor drugs in BC.
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Apoptosis/efectos de los fármacos , Neoplasias de la Mama/enzimología , Neoplasias de la Mama/patología , Proteínas Activadoras de GTPasa/metabolismo , Quempferoles/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Proteínas Activadoras de GTPasa/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Fitoquímicos/farmacología , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Background: LINC01207 expression is associated with colorectal cancer progression. However, the exact role of LINC01207 in colorectal cancer (CRC) is not clear, and further exploration is needed. Methods: Gene expression data of the GSE34053 database were used to explore the differential expressed genes (DEGs) between colon cancer cells and normal cells. The gene expression profiling interactive analysis (GEPIA) was used to determine the differential expression of LINC01207 between CRC and normal tissues and the association between the expression of LINC01207 and survival in patients with CRC. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis were performed to obtain the biological processes and pathways associated with DEGs and LINC01207 coexpressed genes in CRC. The qRT-PCR was used to determine the LINC01207 level in CRC cell lines and tissue samples. CCK-8 assay was employed to measure cell viability and Transwell assay to assess cell invasion and migration. Results: In this study, a total of 954 DEGs were identified, including 282 upregulated and 672 downregulated genes. LINC01207 was significantly upregulated in CRC samples with a poor prognosis. LINC01207 was also associated with pathways such as ECM-receptor interaction, O-glycan processing, and TNF signaling pathway in CRC. Knockdown of LINC01207 inhibited the migration, invasion, and proliferation of CRC cells. Conclusion: LINC01207 might act as an oncogene and promote the progression of CRC. Our study suggested that LINC01207 had the potential to be a novel biomarker for CRC detection and a therapeutic target for CRC treatment.
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PURPOSE: Colorectal cancer (CRC) is a common human cancer along with higher incidence and mortality, and this study aimed to identify the effect of cincumol on CRC and its potential mechanisms. METHODS: CRC cell line HCT116 was used as the material. Cell proliferation was evaluated by CCK-8 assay, and cell migration was detected by scratch test and Transwell assay. TUNEL staining assay was used to evaluate cell apoptosis. The expression of target genes was detected by qualitative real-time polymerase chain reaction and western blot assays. RESULTS: Cincumol significantly reduced the proliferative and migratory rate and enhanced apoptotic rate of HCT116 cells. Meanwhile, the elevated levels of RBUsuh, Nicd and Tace was also observed in cincumol-treated HCT116 cells. Moreover, our findings revealed that additional cincumol inhibited the expression of p-PI3K and p-AKT, suggesting the inhibition of PI3K/AKT signaling might be involved in the protective role of cincumol on the malignant phenotypes of CRC cells in vitro. CONCLUSIONS: Cincumol inhibited the malignant phenotypes of CRC cells in vitro through inactivating PI3K/AKT signaling, suggesting that cincumol might be a potential anti-CRC agent.
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Neoplasias Colorrectales , Proteínas Proto-Oncogénicas c-akt , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Células HCT116 , Apoptosis , Neoplasias Colorrectales/tratamiento farmacológico , Fenotipo , Proliferación Celular , Línea Celular TumoralRESUMEN
Tripartite motif-containing 14 (TRIM14) is abnormally expressed in several human cancers. However, the function and expression of TRIM14 in human breast cancer are still largely unknown. To understand the biological function of TRIM14 in breast cancer, we measured the expression level of TRIM14. Cell proliferation and cell apoptosis were measured after TRIM14 overexpression or knockdown. Upregulation of TRIM14 was found in human breast cancer specimens and cell lines. Reduction of TRIM14 inhibited cell proliferation but increased cell apoptosis in the BT474 and MDA-MB-231 cell lines. Further study showed that knockdown of TRIM14 upregulated the expression of BAX while downregulating the expression of BCL2. In addition, the expression of SHP-1 was increased, and the phosphorylation of STAT3 (p-STAT3) was inhibited. Conversely, overexpression of TRIM14 had the opposite effects. Additionally, cryptotanshinone, a STAT3 inhibitor, inhibited cell proliferation but increased cell apoptosis in the BT474 and MDA-MB-231 cell lines. In conclusion, TRIM14 may act as an oncogene in human breast cancer and may be a novel strategy for human breast cancer.
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Apoptosis/genética , Neoplasias de la Mama/genética , Proteínas Portadoras/genética , Línea Celular Tumoral , Proliferación Celular , Femenino , Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Péptidos y Proteínas de Señalización Intracelular , Factor de Transcripción STAT3/metabolismo , Proteínas de Motivos TripartitosRESUMEN
BACKGROUND: We evaluated the influence of different debridement methods on the prognosis of elderly patients with diabetic foot ulcers complicated with sepsis. METHODS: Retrospective study was adopted to study 65 hospitalized elderly patients with Wagner Grade-4 diabetic foot ulcer and sepsis in Vascular Disease Department of Shanghai TCM-Integrated Hospital. Thirty-two cases were included in the thorough debridement group and the other 33 were included in the minor debridement group. We compared the mortality rates on the 7th day and 14th day after debridement, and monitored changes of sepsis-related organ failure assessment (SOFA) Score as well as C-reactive protein (CRP), procalcitonin (PCT) and D-Dimer (D-D) levels. Cox regression analysis and Kaplan-Meier analysis were used to analyze the mortality rates. Binary logistic regression analysis was employed to screen relevant prognostic factors to see the prognostic value of SOFA Score, PCT and D-D. RESULTS: Fatality rates of the thorough debridement group on the 7th day and 14th day of the debridement were higher than those in the minor debridement group and such a difference has statistical significance. The CRP, PCT, and D-D of patients within seven days after thorough debridement were obviously higher than those of patients after minor debridement. CONCLUSIONS: Damage control should be provided for elderly patients with diabetic foot ulcers and sepsis when debridement is being performed. Palliative debridement methods such as small-scale incision and drainage are less likely to affect systematic inflammatory response and coagulation function, and thus can buy time for further treatment to improve clinical effect.
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Envejecimiento , Bacteriemia/cirugía , Desbridamiento , Pie Diabético/cirugía , Anciano , Anciano de 80 o más Años , Bacteriemia/complicaciones , Bacteriemia/mortalidad , China , Desbridamiento/métodos , Pie Diabético/complicaciones , Pie Diabético/mortalidad , Humanos , Estimación de Kaplan-Meier , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Breast cancer is a highly prevalent disease affecting women. The association of IQ motif containing GTPase-activating protein 3 (IQGAP3) and breast cancer is poorly defined. Here we reported that IQGAP3 is a key regulator of cell proliferation and metastasis during breast cancer progression. The expression of IQGAP3 was significantly increased in breast tissues compared to nontumor tissues at both protein and mRNA levels. Furthermore, IQGAP3 had a high expression level in ZR-75-30 and BT474 compared to other breast cancer cell lines. Depletion of IQGAP3 through RNA interference in ZR-75-30 and BT474 significantly inhibited cell proliferation. More importantly, IQGAP3 silencing in breast cancer cells notably repressed cell migration and invasion. Further analysis suggested that inhibition of cell proliferation and metastasis was associated with some proteins, including p53, MMP9, Snail, CDC42, p-ERK1/2, KIF2C, KIF4A, PCNA, and Twist. Since expression of IQGAP3 seems to be associated with the pathogenesis of breast cancer and suppression of it can inhibit cancer cell growth and metastasis, IQGAP3 may be a potential therapeutic target in human breast cancer.
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Neoplasias de la Mama/genética , Carcinoma/genética , Proliferación Celular/genética , Proteínas Activadoras de GTPasa/genética , Invasividad Neoplásica/genética , Interferencia de ARN/fisiología , Neoplasias de la Mama/patología , Carcinoma/patología , Línea Celular Tumoral , Movimiento Celular/genética , Femenino , Humanos , Invasividad Neoplásica/patología , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Proteína p53 Supresora de Tumor/genéticaRESUMEN
BACKGROUND: Plugged ducts are a common, painful condition in lactating women, but no standard treatment is currently available. OBJECTIVE: This study aimed to evaluate the clinical efficacy of a newly established 6-step recanalization manual therapy (SSRMT) for treating plugged ducts. METHODS: This observational study included 3497 lactating women with plugged ducts. The SSRMT comprised the following well-defined steps: (1) preparation, (2) clearing the plugged duct outlets, (3) nipple manipulation, (4) pushing and pressing the areola, (5) pushing and kneading the breast, and (6) checking for residual milk stasis. The response to the treatment was graded as I (complete resolution), II (marked improvement), III (improvement), or IV (no response). RESULTS: Of the 3497 patients, the mean age was 26.7 years and 3284 (93.9%) patients were primiparas. Fever was present in 1231 (35.2%) patients. After a single SSRMT treatment, 3189 (91.2%), 173 (4.9%), and 83 (2.4%) patients achieved grade I, II, and III responses, respectively, with only 52 (1.5%) showing unresponsiveness. For the 308 (8.8% of total) non-grade I patients, a second SSRMT given 3 days later resulted in grade I, II, and III responses in 267 (7.6% of total), 28 (0.8% of total), and 13 (0.4% of total) patients, respectively, and none were absolutely unresponsive. No complications with clinical significance were observed. CONCLUSION: Based on this large-scale clinical observation, SSRMT appears to be a useful, safe, low-cost treatment for postpartum plugged milk ducts.