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1.
Am J Physiol Cell Physiol ; 325(4): C833-C848, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37642235

RESUMO

Breast cancer has become the malignant disease with the highest morbidity and mortality among female cancer patients. The prognosis of metastatic breast cancer is very poor, and the therapeutic effects still need to be improved. The molecular mechanism of breast cancer has not been fully clarified. Bioinformatics analysis was used to find the differentially expressed gene that affects the occurrence and development of breast cancer. Furthermore, scratch assays, Transwell assays, immunofluorescence, and Western blotting were used to determine the biological behavior of breast cancer cells affected by DEP domain-containing protein 1B (DEPDC1B). The molecular mechanism was investigated by mass spectrometry analysis, coimmunoprecipitation, and ubiquitin assays. Here, we found that DEPDC1B was highly expressed in breast cancer cells and tissues and was associated with lower overall survival (OS) in patients. We found that DEPDC1B interference significantly inhibited tumor invasion and migration in vitro and tumor metastasis in vivo. Mechanistically, DEPDC1B was first shown to activate the wnt/ß-catenin signaling pathway as an oncogene in breast cancer cells. In addition, we also confirmed the interaction between DEPDC1B, ubiquitin-specific protease 5 (USP5), and ß-catenin. Then, we found that DEPDC1B mediates the deubiquitination of ß-catenin via USP5, which promotes cell invasion and migration. Our findings provide new insights into the carcinogenic mechanism of DEPDC1B, suggesting that DEPDC1B can be considered a potential therapeutic target for breast cancer.NEW & NOTEWORTHY By using bioinformatics analysis and the experimental techniques of cell biology and molecular biology, we found that DEP domain-containing protein 1B (DEPDC1B) can promote the invasion and migration of breast cancer cells and that DEPDC1B mediates the deubiquitination of ß-catenin by ubiquitin-specific protease 5 (USP5), thus activating the wnt/ß-catenin pathway. Our findings provide new insights into the carcinogenic mechanism of DEPDC1B, suggesting that DEPDC1B can be used as a potential therapeutic target for breast cancer.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , beta Catenina/genética , Via de Sinalização Wnt , Proteases Específicas de Ubiquitina/genética , Proteínas Ativadoras de GTPase , Melanoma Maligno Cutâneo
2.
Mol Med ; 29(1): 15, 2023 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-36717782

RESUMO

BACKGROUND: Osteosarcoma is a malignant bone tumor that usually affects adolescents aged 15-19 y. The DNA damage response (DDR) is significantly enhanced in osteosarcoma, impairing the effect of systemic chemotherapy. Targeting the DDR process was considered a feasible strategy benefitting osteosarcoma patients. However, the clinical application of DDR inhibitors is not impressive because of their side effects. Chinese herbal medicines with high anti-tumor effects and low toxicity in the human body have gradually gained attention. 2-Hydroxy-3-methylanthraquinone (HMA), a Chinese medicine monomer found in the extract of Oldenlandia diffusa, exerts significant inhibitory effects on various tumors. However, its anti-osteosarcoma effects and defined molecular mechanisms have not been reported. METHODS: After HMA treatment, the proliferation and metastasis capacity of osteosarcoma cells was detected by CCK-8, colony formation, transwell assays and Annexin V-fluorescein isothiocyanate/propidium iodide staining. RNA-sequence, plasmid infection, RNA interference, Western blotting and immunofluorescence assay were used to investigate the molecular mechanism and effects of HMA inhibiting osteosarcoma. Rescue assay and CHIP assay was used to further verified the relationship between MYC, CHK1 and RAD51. RESULTS: HMA regulate MYC to inhibit osteosarcoma proliferation and DNA damage repair through PI3K/AKT signaling pathway. The results of RNA-seq, IHC, Western boltting etc. showed relationship between MYC, CHK1 and RAD51. Rescue assay and CHIP assay further verified HMA can impair homologous recombination repair through the MYC-CHK1-RAD51 pathway. CONCLUSION: HMA significantly inhibits osteosarcoma proliferation and homologous recombination repair through the MYC-CHK1-RAD51 pathway, which is mediated by the PI3K-AKT signaling pathway. This study investigated the exact mechanism of the anti-osteosarcoma effect of HMA and provided a potential feasible strategy for the clinical treatment of human osteosarcoma.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Adolescente , Reparo de DNA por Recombinação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Rad51 Recombinase/genética , Rad51 Recombinase/metabolismo , Rad51 Recombinase/farmacologia , Osteossarcoma/tratamento farmacológico , Osteossarcoma/genética , Osteossarcoma/metabolismo , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células
3.
Ann Surg Oncol ; 30(9): 5912-5922, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37389655

RESUMO

BACKGROUND: Small pulmonary nodules (<3 cm) can sometimes be unrecognizable and nonpalpable in video-assisted thoracoscopic surgery (VATS). Near-infrared fluorescence (NIF) VATS after indocyanine green (ICG) inhalation may effectively guide surgeons to locate the nodules. OBJECTIVE: This study aimed to investigate the safety, feasibility, and efficacy of ICG inhalation-based NIF imaging for guiding small pulmonary nodule resections. METHODS: Between February and May 2021, the first-stage, non-randomized trial enrolled 21 patients with different nodule depth, ICG inhalation doses, post-inhalation surgery times, and nodule types at a tertiary referral hospital. Between May 2021 and May 2022, the second-stage randomized trial enrolled 56 patients, who were randomly assigned to the fluorescence VATS (FLVATS) or the white-light VATS (WLVATS) group. The ratio of effective guidance and the time consumption for nodule localization were compared. RESULTS: The first-stage trial proved this new method is safe and feasible, and established a standardized protocol with optimized nodule depth (≤1 cm), ICG dose (0.20-0.25 mg/kg), and surgery window (50-90 min after ICG inhalation). In the second-stage trial, the FLVATS achieved 87.1% helpful nodule localization guidance, which was significantly higher than the WLVATS (59.1%, p < 0.05). The mean nodule locating time (standard deviation) was 1.8 [0.9] and 3.3 [2.3] min, respectively. Surgeons adopting FLVATS were significantly faster (p < 0.01), especially when locating small ground-glass opacities (1.3 [0.6] min vs. 7.0 [3.5] min, p < 0.05). Five of 31 nodules (16.1%) were only detectable by FLVATS, whereas both white light and palpation failed. CONCLUSIONS: This new method is safe and feasible for small pulmonary nodule resection. It significantly improves nodule localization rates with less time consumption, and hence is highly worthy for clinical promotion. Clinical Trial Registration Chinese Clinical Trial Registry Identifier: ChiCTR2100047326.


Assuntos
Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Nódulo Pulmonar Solitário , Humanos , Verde de Indocianina , Cirurgia Torácica Vídeoassistida/métodos , Neoplasias Pulmonares/cirurgia , Tomografia Computadorizada por Raios X/métodos , Pulmão , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/cirurgia , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/cirurgia
4.
Environ Sci Technol ; 57(11): 4434-4442, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36883325

RESUMO

Fe(III) and carboxylic acids are common compositions in atmospheric microdroplet systems like clouds, fogs, and aerosols. Although photochemical processes of Fe(III)-carboxylate complexes have been extensively studied in bulk aqueous solution, relevant information on the dynamic microdroplet system, which may be largely different from the bulk phase, is rare. With the help of the custom-made ultrasonic-based dynamic microdroplet photochemical system, this study examines the photochemical process of Fe(III)-citric acid complexes in microdroplets for the first time. We find that when the degradation extent of citric acid is similar between the microdroplet system and the bulk solution, the significantly lower Fe(II) ratio is present in microdroplet samples due to the rapider reoxidation of photogenerated Fe(II). However, by replacing citric acid with benzoic acid, no much difference in the Fe(II) ratio between microdroplets and bulk solution is observed, which indicates distinct reoxidation pathways of Fe(II). Moreover, the presence of •OH scavenger, namely, methanol, greatly accelerates the reoxidation of photogenerated Fe(II) in both citric acid and benzoic acid situations. Further experiments reveal that the high availability of O2 and the citric acid- or methanol-derived carbon-centered radicals are responsible for the rapider reoxidation of Fe(II) in iron-citric acid microdroplets by prolonging the length of HO2•- and H2O2-involved radical reaction chains. The results in this study may provide a new understanding about iron-citric acid photochemistry in atmospheric liquid particles, which can further influence the photoactivity of particles and the formation of secondary organic aerosols.


Assuntos
Ácido Cítrico , Ferro , Ferro/química , Ácido Cítrico/química , Peróxido de Hidrogênio/química , Fotoquímica , Metanol , Oxirredução , Ácidos Carboxílicos/química , Compostos Ferrosos , Aerossóis , Benzoatos , Compostos Férricos/química
5.
Altern Ther Health Med ; 29(1): 130-136, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35986740

RESUMO

Context: Lung cancer is one of the most common forms of cancer. Autophagy and apoptosis play an important role in the development of lung cancer. Researchers have found upregulation of GRP78 expression in cancer cells of various types. Objective: The study intended to explore the mechanism of G protein-coupled receptor 78(GPR78) in regulating autophagy and drug resistance in non-small cell lung cancer (NSCLC). Design: The research team performed a laboratory study. Setting: The study took place in the Department of Thoracic Surgery at Hainan General Hospital of the Hainan Affiliated Hospital of Hainan Medical University in Haikou, Hainan, China. Intervention: The research team cultured immortalized, normal, human bronchial epithelial cells C3 (HBEC3) lines and HBEC4 lines in a serum medium without keratinocytes and infected the expression of GPR78 in knockdown A549 cells using lentiviral agents. The team divided the cells into a control group and a shRNA-GPR78 group, the intervention group. The lentiviral silencing vector expressing shRNA targets human GPR78#1 and GPR78 #2aadam10. Outcome Measures: The research team analyzed the mRNA expression of GPR78 in the NSCLC cell lines H1975, H1299, and A549 and in HBEC3 and HBEC4 using a real time-polymerase chain reaction (RT-PCR) and measured the proliferation of A549 cells at 0h, 24h, 48h, 72h, and 96h using yellow tetrazolium salt (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The team also analyzed the migration and invasion ability of cells using wound healing and Transwell tests as well as measured the protein expression of the autophagy-related factors Beclin-1, microtubule-associated protein light chain 3-I/II (LC3-I/LC3-II), ubiquitin-binding protein p62 and c-Jun N-terminal kinase (JNK) using a Western blot test. The team also analyzed the protein expressions of caspase-9, caspase-3, and caspase-12 related to apoptosis using a Western blot. To detect the cell viability induced by cisplatin, the team used a Cell Counting Kit 8 (CCK-8) at the concentrations of 1µM, 3µM and 10µM. Results: The mRNA expression of GPR78 in the H1975, H1299, and A549 cell lines was significantly higher than that in the HBEC3 and HBEC4 cell lines (P < .05). At 48h, 72h, and 96h, the A549 cell proliferation in the shRNA-GPR78 group was significantly lower than that of the control group (P < .05). The cell migration and invasion of cells in the shRNA-GPR78 group was significantly lower than that in the control group (P < .05), and the cell viability of the shRNA-GPR78 group was significantly lower than that of control group (P < .05). The expression of Beclin-1 and JNK protein in shRNA-GPR78 group was significantly higher than that in the control group (P < .05), and the expression of LC3-I/LC3-II and p62 protein in shRNA-GPR78 group was significantly lower than that in the control group (P < .05). The protein expressions of caspase-9, caspase-3, and caspase-12 in the shRNA-GPR78 group were significantly higher than those of the control group (P < .05), and the protein activities of RhoA and Rac1 in the shRNA-GPR78 group were significantly lower than those in the control group (P < .05). Conclusion: NSCLC upregulated GPR78. The knockdown of GPR78 can attenuate the proliferation, migration, and invasion of NSCLC cells and increase the apoptosis and autophagy of NSCLC cells that cisplatin has induced. Therefore, targeting GPR78 may be a promising treatment strategy for NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Caspase 3/uso terapêutico , Caspase 9 , Proteína Beclina-1 , Caspase 12/uso terapêutico , Linhagem Celular Tumoral , Apoptose , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/uso terapêutico , Proliferação de Células , Autofagia , Resistência a Medicamentos , RNA Mensageiro
6.
Pharmacol Res ; 182: 106287, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35671921

RESUMO

Osteosarcoma (OS) is a malignant solid tumor prone to lung metastasis that occurs in adolescents aged 15-19 years. Neoadjuvant chemotherapy and surgical treatment aimed at curing OS have gained limited progress over the last 30 years. Exploring new effective second-line therapies for OS patients is a serious challenge for researchers. Quercetin, a multiple biologically active polyphenolic flavonoid, has been used in tumor therapy. However, the exact mechanism of quercetin is still unknown, which limits the application of quercetin. In the current study, we found that quercetin could inhibit JAK2 through the JH2 domain in a non-covalent manner, resulting in the inhibition of OS proliferation and immune escape via the JAK2-STAT3-PD-L1 signaling axis. More importantly, to overcome the shortcomings of quercetin, including low water solubility and low oral availability, we encapsulated it with folic acid-modified liposomes. The transportation of quercetin by folic acid-modified liposomes may provide a feasible strategy to cure OS.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Adolescente , Antígeno B7-H1/metabolismo , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Ácido Fólico , Humanos , Janus Quinase 2/metabolismo , Lipossomos/farmacologia , Lipossomos/uso terapêutico , Osteossarcoma/tratamento farmacológico , Osteossarcoma/metabolismo , Quercetina/farmacologia , Quercetina/uso terapêutico , Fator de Transcrição STAT3/metabolismo
7.
J Cell Mol Med ; 25(21): 10279-10290, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34658138

RESUMO

Tumour-derived DNA found in the plasma of cancer patients provides the probability to detect somatic mutations from circulating cell-free DNA (cfDNA) in plasma samples. However, clonal hematopoiesis (CH) mutations affect the accuracy of liquid biopsy for cancer diagnosis and treatment. Here, we integrated landscape of CH mutations in 11,725 pan-cancer patients of Chinese and explored effects of CH on liquid biopsies in real-world. We first identified 5933 CHs based on panel sequencing of matched DNA of white blood cell and cfDNA on 301 genes for 5100 patients, in which CH number of patients had positive correlation with their diagnosis age. We observed that canonical genes related to CH, including DNMT3A, TET2, ASXL1, TP53, ATM, CHEK2 and SF3B1, were dominant in the Chinese cohort and 13.29% of CH mutations only appeared in the Chinese cohort compared with the Western cohort. Analysis of CH gene distribution bias indicated that CH tended to appear in genes with functions of tyrosine kinase regulation, PI3K-Akt signalling and TP53 activity, suggesting unfavourable effects of CH mutations in cancer patients. We further confirmed effect of driver genes carried by CH on somatic mutations in liquid biopsy of cancer patients. Forty-eight actionable somatic mutations in 17 driver genes were considered CH genes in 92 patients (1.80%) of the Chinese cohort, implying potential impacts of CH on clinical decision-making. Taken together, this study exhibits strong evidence that gene mutations from CH interfere accuracy of liquid biopsies using cfDNA in cancer diagnosis and treatment in real-world.


Assuntos
Biomarcadores Tumorais , Ácidos Nucleicos Livres , Hematopoiese Clonal/genética , Biópsia Líquida , Mutação , China/epidemiologia , Estudos de Coortes , Biologia Computacional/métodos , Biblioteca Gênica , Ontologia Genética , Mutação em Linhagem Germinativa , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Biópsia Líquida/métodos , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/genética
8.
BMC Cancer ; 21(1): 244, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33685397

RESUMO

BACKGROUND: RNA-binding proteins (RBPs) play crucial and multifaceted roles in post-transcriptional regulation. While RBPs dysregulation is involved in tumorigenesis and progression, little is known about the role of RBPs in bladder cancer (BLCA) prognosis. This study aimed to establish a prognostic model based on the prognosis-related RBPs to predict the survival of BLCA patients. METHODS: We downloaded BLCA RNA sequence data from The Cancer Genome Atlas (TCGA) database and identified RBPs differentially expressed between tumour and normal tissues. Then, functional enrichment analysis of these differentially expressed RBPs was conducted. Independent prognosis-associated RBPs were identified by univariable and multivariable Cox regression analyses to construct a risk score model. Subsequently, Kaplan-Meier and receiver operating characteristic curves were plotted to assess the performance of this prognostic model. Finally, a nomogram was established followed by the validation of its prognostic value and expression of the hub RBPs. RESULTS: The 385 differentially expressed RBPs were identified included 218 and 167 upregulated and downregulated RBPs, respectively. The eight independent prognosis-associated RBPs (EFTUD2, GEMIN7, OAS1, APOBEC3H, TRIM71, DARS2, YTHDC1, and RBMS3) were then used to construct a prognostic prediction model. An in-depth analysis showed lower overall survival (OS) in patients in the high-risk subgroup compared to that in patients in the low-risk subgroup according to the prognostic model. The area under the curve of the time-dependent receiver operator characteristic (ROC) curve were 0.795 and 0.669 for the TCGA training and test datasets, respectively, showing a moderate predictive discrimination of the prognostic model. A nomogram was established, which showed a favourable predictive value for the prognosis of BLCA. CONCLUSIONS: We developed and validated the performance of a prognostic model for BLCA that might facilitate the development of new biomarkers for the prognostic assessment of BLCA patients.


Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Nomogramas , Proteínas de Ligação a RNA/genética , Neoplasias da Bexiga Urinária/mortalidade , Biologia Computacional , Conjuntos de Dados como Assunto , Humanos , Estimativa de Kaplan-Meier , Valor Preditivo dos Testes , Prognóstico , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas/genética , RNA-Seq , Curva ROC , Medição de Risco/métodos , Fatores de Risco , Taxa de Sobrevida , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
9.
Eur Spine J ; 26(Suppl 1): 95-99, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27900552

RESUMO

STUDY DESIGN: Case report. PURPOSE: We present a rare case of a giant chordoma in the thoracolumbar spine and review the current literature. We describe its complicated clinical progression, hoping to shed light on the clinical management of this complex tumor. METHODS: We present a previously healthy 41-year-old man who experienced progressive low back pain at T10-L2 for the past 2 years. A giant tumor was detected on magnetic resonance imaging, and aspiration biopsy was used to obtain a definite pathological diagnosis. The postoperative pathology confirmed that it was a chordoma. He underwent complete resection of the tumor and internal fixation of the vertebral bodies, which is a good way to control recurrence and preserve stability. RESULTS: Histopathology confirmed the tumor was a chordoma via immunohistochemical study of both the biopsy sample and the surgically resected tissues. There has been no recurrence or metastasis at the 30-month postsurgery radiographic examination. The internal fixation has remained stable. CONCLUSION: Primary chordoma in the thoracolumbar spine is extremely rare. The treatment is difficult because the current literature is sparse and patients are rare. Complete resection and internal fixation are effective for reducing recurrences and metastasis.


Assuntos
Cordoma/cirurgia , Vértebras Lombares/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Vértebras Torácicas/cirurgia , Adulto , Biópsia por Agulha , Cordoma/complicações , Cordoma/diagnóstico por imagem , Cordoma/patologia , Humanos , Dor Lombar/etiologia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/patologia , Imageamento por Ressonância Magnética , Masculino , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/patologia , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/patologia
10.
Tumour Biol ; 2016 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-27730542

RESUMO

MicroRNAs are a group of small non-coding RNAs that play a complex role in post-transcriptional gene expression and can be used for diagnosis, prognosis, and targeted treatment. Despite advances in diagnosis and treatment of chondrosarcoma, its underpinning molecular mechanisms still remain elusive. Given the recent increasing knowledge base of micro RNA (miRNA) roles in neoplasia, both as oncogenes and tumor suppressor genes, this review will focus on discussing the available data on expression profiles and potential roles of miRNA in chondrosarcoma. Accumulating evidence suggests that microRNAs have the potential to be used in the future for clinical management of chondrosarcoma.

11.
Biomarkers ; 19(5): 417-23, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24893701

RESUMO

Considering the role of variants in the 3' untranslated region (3'UTR) of GPR30 gene remains unclear, we analyzed the association between the variants at the GPR30 gene 3'UTR miRNA binding sites and their mRNA expression using the data from the HapMap online database. Nine single nucleotide polymorphisms (SNPs) in GPR30 gene 3'UTR had available minor allele frequency (MAF) values which were obtained. And the frequency distribution of all the selected GPR30 gene 3'UTR variants genotypes among the different populations and pairwise linkage disequilibrium (LD) values were calculated. In addition, correlation analysis of the selected GPR30 variants genotypes and their mRNA expression in the lymphoblastoid cell lines was performed, which showed that only rs10235056 was significantly associated with GPR30 mRNA expression (p = 0.028), but rs4266553 (p = 0.304), rs3808353 (p = 0.900), rs3808354 (p = 0.739) and rs1133043 (p = 0.913) were insignificant. Taken together, the present study provides the first evidences that the GPR30 rs10235056 A > G polymorphism could be a putative variant mediating its post-transcriptional regulation, which might support its use as markers of cancer risk and individualized treatment.


Assuntos
Regulação da Expressão Gênica , Linfócitos/metabolismo , Polimorfismo de Nucleotídeo Único , Receptores de Estrogênio/genética , Receptores Acoplados a Proteínas G/genética , Regiões 3' não Traduzidas/genética , Sítios de Ligação/genética , Linhagem Celular , Frequência do Gene , Genótipo , Humanos , Desequilíbrio de Ligação , Linfócitos/citologia , MicroRNAs/genética , MicroRNAs/metabolismo , Fenótipo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
12.
Eur J Clin Pharmacol ; 70(5): 531-8, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24562632

RESUMO

PURPOSE: We undertook a meta-analysis of randomized trials to evaluate the efficacy of multitargeted antiangiogenic tyrosine kinase inhibitors (MATKIs) in addition to chemotherapy in metastatic breast cancer. METHODS: PubMed, Web of Knowledge databases and the ASCO meeting abstracts were searched for eligible literature published up to August 30, 2013. The endpoints included progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and toxicities. Pooled hazard ratios (HRs) for survival outcomes and odds ratio (ORs) for dichotomous data with 95 % confidence intervals (CIs) were derived. RESULTS: Eight studies including 2,077 participants were analyzed. Compared to chemotherapy alone, adding MATKIs to chemotherapy resulted in a 14 % risk reduction of PFS events. However, the benefit did not reach statistical significance (HR 0.86; 95 % CI 0.70-1.04, P=0.126). Also, no OS benefit was observed (HR 1.03; 95 % CI 0.89-1.18, P=0.724). The addition of MATKIs significantly increased the ORR (OR 1.57; 95 % CI 1.30-1.91, P=0.000). Subgroup analysis revealed that sorafinib showed a significantly greater effect on PFS in patients with HER2 negative metastatic breast cancer (HR 0.67; 95 % CI 0.55-0.82, P=0.000) in comparison to chemotherapy alone. Additionally, sunitinib seemed to have no substantial efficacy for metastatic breast cancer. Toxicities were more frequent in patients receiving MATKIs. CONCLUSION: Overall, regimens consisting of MATKIs seemed not to be superior to chemotherapy alone in terms of PFS and OS, although significant improvement in ORR was observed. However, the addition of sorafenib significantly improved PFS. Further studies are needed to corroborate this finding.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Proteínas Tirosina Quinases/antagonistas & inibidores , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Terapia de Alvo Molecular , Metástase Neoplásica , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Artigo em Inglês | MEDLINE | ID: mdl-39194057

RESUMO

This study aimed to explore the relationship between preoperative baseline perfusion index (PI) and intraoperative hypothermia during general anesthesia. PI reflects the peripheral perfusion status, which may be associated with the decrease of core temperature during general anesthesia, as the redistribution of temperature from the core compartment to the peripheral compartment depends on the peripheral perfusion status. A total of 68 patients underwent radical surgery for urological malignancies in this study. The baseline PI value was measured upon entering the operating room. Core temperature was continuously monitored using a nasal pharyngeal probe from anesthesia induction to the end of surgery, with temperature data recorded every 15 minutes. Univariate and multivariate logistic regression analyses were used to identify risk factors for intraoperative hypothermia. Intraoperative hypothermia occurred in 26 patients, whose baseline PI (2.70 ± 0.73) was significantly lower than that of the normothermic group (3.65 ± 1.05), with P<0.05. The baseline PI was independently associated with intraoperative hypothermia (PI: [OR] 0.375, 95% confidence interval [CI]: 1.584-6.876, p = 0.001). This study suggests that low baseline PI is an independent factor associated with intraoperative hypothermia. In future studies, PI value could be considered as a predictor for the treatment of intraoperative hypothermia.

14.
Artigo em Inglês | MEDLINE | ID: mdl-39054959

RESUMO

The study aimed to explore the effect of the temperature chain management scheme on preventing hypothermia in patients undergoing robot-assisted radical prostatectomy (RARP). The patients were randomized to receive either intraoperative warming only (control group, Group C) or the temperature chain management (experimental group, Group T). We compared the core temperature, inadvertent perioperative hypothermia (IPH) rates, the incidence of shivering, and thermal comfort between the two groups. The perioperative core temperature of the Group T was higher than that of the Group C, and the incidence of IPH, the incidence of shivering in the postanesthesia care unit (PACU), and the length of stay in PACU were lower than those of the control group. The thermal comfort of Group T scored higher than that of Group C when leaving the PACU, all above have a statistically significant difference (p < 0.05). The temperature chain management scheme could decrease the IPH rates and reduce postoperative complications in RARP patients. The Clinical Trials Registration number is 2023IIT034.

15.
Heliyon ; 10(1): e23208, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38170064

RESUMO

Objective: This study aimed to analyze the effect of modular nursing model for typical issues on enteral nutrition status, immune function, and quality of life in patients with colon cancer. Methods: The clinical data of 106 colorectal cancer patients who came to our hospital from January 2020 to January 2022 were retrospectively analyzed. The patients were randomized into the control and observation group based on the different nursing models, with 53 cases in each group. The patients in the control group received a simple enteral nutrition nursing model, while these in the observation group were administrated with a modular nursing model for typical issues on the basis of the control group. The differences in enteral nutrition status, immune function, and quality of life indicators of patients before and after nursing were counted and compared between the two groups. Results: After the nursing, the contents of albumin, serum albumin, and transferrin were all elevated in both two groups compared with these before the nursing (P < 0.001), and these contents in observation group was markedly higher than these in the control group after the nursing (P < 0.001). The expressions of immune function indicators, including CD3+, CD4+, CD4+/CD8+, and SIgA of the two groups after the nursing, were much higher than these before the nursing (P < 0.05), while the contents of CD8+ and IgG were sharply decreased in comparison with these before the nursing (P < 0.05). The improvement of immune indicators in the observation group after the nursing was strongly better than that in the control (P < 0.01). The proportion of the total nursing satisfaction was significantly higher in the observation group than that in the control (P < 0.05). After the nursing, the life quality scores of two groups were both strongly elevated (P < 0.05), and the improvement of life quality scores were memorably better in the observation group after nursing than these in the control (P < 0.01). Conclusion: For patients undergoing radical colon cancer resection, modular nursing model for typical issues in the early postoperative period is not only safe, but also improves enteral nutrition, can better maintain immune function in the early postoperative period, improve nursing satisfaction, improve patient prognosis, and promote the improvement of the condition, which is worthy of popularization and application.

16.
Sci Total Environ ; 932: 173069, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38723974

RESUMO

The exposure to cooking organic aerosols (COA) is closely related to people's daily lives. Despite extensive investigations into COA's model compounds like oleic acid, the intricacies of heterogeneous ozonolysis of real COA and the effects of ambient conditions like humidity remain elusive. In this work, the ozonolysis of COA proxies from heated peanut oil emissions was investigated using diffuse reflectance infrared Fourier transform (DRIFTS) spectroscopy, and proton transfer reaction time-of-flight mass spectrometer (PTR-ToF-MS). We found that humidity hinders the reaction between ozone and CC double bonds due to the competitive adsorption of water and ozone on COA. Although visible light has little influence on the ozonolysis of COA in the absence of humidity, the ozonolytic CO production is significantly promoted by visible light in the presence of humidity. It may be attributed to the formation of water-derived reactive oxygen species (ROS, mainly HO•) from the photosensitization of polycyclic aromatic hydrocarbons (PAHs) in COA. We also found that humidity can enhance the depolymerization of carboxylic acid dimers and hydrolysis of intrinsic acetals in the COA. Moreover, humidity promotes the release of VOCs during both the dark and light ozonolysis of COA. This work reveals the important roles of humidity-responsive and photo-responsive components in COA during its ozonolysis, and the change in VOC release may guide the control of human VOC exposure in indoor air.

17.
Crit Rev Eukaryot Gene Expr ; 23(4): 309-16, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24266846

RESUMO

Studies on the association between the TCF7L2 rs12255372 polymorphism and breast cancer risk have reported conflicting results. To characterize the relationship between this polymorphism and breast cancer risk, we conducted a comprehensive literature search for relevant studies and performed a meta-analysis. A total of four studies including 5280 cases and 6026 controls were eligible for our analysis. Overall, we did find that this polymorphism correlates with breast cancer risk [TT versus GG: odds ratio (OR)=1.19, 95% confidence interval (CI)=1.02-1.40; GT versus GG: OR=1.10, 95% CI=1.01-1.19; T versus G: OR=1.12, 95% CI=1.05-1.19]. Furthermore, in the subgroup analysis by ethnicity, we did also find that this polymorphism associated with an increased breast cancer risk in white individuals (T versus G: OR=1.11, 95% CI=1.04-1.18). In summary, this meta-analysis suggests that the rs12255372 T allele is a low-penetrant risk factor for breast carcinogenesis. In the future, larger-scale and more well-designed studies based on homogeneous breast cancer patients are needed to validate our findings, especially in Asians.


Assuntos
Neoplasias da Mama/genética , Carcinogênese/genética , Polimorfismo de Nucleotídeo Único , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética , Feminino , Predisposição Genética para Doença , Humanos
18.
Artigo em Inglês | MEDLINE | ID: mdl-37751189

RESUMO

To explore the effect of the temperature chain management scheme on inadvertent perioperative hypothermia (IPH) during robot-assisted radical resection of urological tumors. Fifty male patients who underwent elective robot-assisted radical prostatectomy (RARP) or robot-assisted radical cystectomy (RARC) surgery from February 2022 to March 2023 in a teaching hospital were enrolled and randomized to receive either intraoperative warming, including forced-air warming blanket and prewarming fluid (group C) or the temperature chain management involving an active warming bunch covering the whole perioperative period (group T). Comparing the core temperature, IPH rates, the incidence of shivering, recovery from anesthesia, and thermal between the two groups. Perioperative core temperature of group T was higher compared with group C (p < 0.05); IPH rates and the incidence of shivering in postanesthesia care unit (PACU) of group T were lower compared with group C (p < 0.05); group T scored higher in thermal comfort compared with group C after PACU 15 minutes, after PACU 30 minutes, and when leaving the PACU (p < 0.05); group T took shorter time on recovering from anesthesia (p < 0.05). Temperature chain management could reduce IPH and postoperative complications during RARP and RARC.

19.
Artigo em Inglês | MEDLINE | ID: mdl-37948541

RESUMO

The study aimed to explore the effect of the training scheme guided by Knowles' adult learning theory model on perioperative hypothermia prevention-related knowledge, practice, and behavior in operating room nurses. Operating room nurses of a teaching hospital were included from February to May 2023. Under the guideline of the adult learning theory, we accessed the score of the knowledge, attitude, and practice in operating room nurses about the prevention of the inadvertent perioperative hypothermia (IPH) before and after trainings through qualitative interviews and questionnaire surveys. There were statistically significant differences in scores of knowledge, attitude, and practice of IPH prevention in operating room nurses before and after training. The training program guided by adult learning theory could significantly increase the scores of IPH prevention-related knowledge of operating room nurses, improve the attitude of perioperative hypothermia prevention, and advance the compliance with IPH prevention interventions. Clinical Trial Registration number: 2023IIT109.

20.
Environ Sci Pollut Res Int ; 30(21): 60294-60302, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37022551

RESUMO

The COVID-19 lockdown had a positive control effect on urban air quality. However, this effect remains uncertain after the epidemic enters regular management, and furthermore, only limited data are available regarding urban PM2.5 (aerodynamic diameter ≤ 2.5µm) under the impact of the epidemic. We used daily ambient PM2.5 concentration data in Beijing to compare and analyze the changes in urban PM2.5 concentrations before and after the COVID-19 epidemic and to estimate the healthy effects and economic burden associated with PM2.5 before and after the epidemic. The study found that COVID-19 has a significant impact on the urban environmental PM2.5 concentration, which is manifested by the decrease in the PM2.5 concentration in Beijing during the epidemic by 27.8%. Exposure-response models estimated 56.443 (95% CI: 43.084-69.893) thousand people die prematurely in Beijing during the COVID-19 epidemic attributed to long-term PM2.5 exposure, with a 13.3% decrease in the number of premature deaths year-on-year. The total healthy economic losses attributable to PM2.5 in Beijing during the COVID-19 epidemic were 35.76 (95% CI: 28.41-42.44) billion yuan, with a per capita loss of 816.8 yuan. Strict control measures throughout the COVID-19 epidemic had a positive impact on air quality in Beijing, with a decrease in both premature deaths and economic healthy losses attributable to fine particles. This paper helps to enrich and expand the research on the impact of COVID-19 on the urban environment and provides a basis for formulating policies related to air quality improvement in the post-epidemic era.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , COVID-19 , Humanos , Pequim/epidemiologia , Poluentes Atmosféricos/análise , Material Particulado/análise , Estresse Financeiro , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Poluição do Ar/análise , China/epidemiologia
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