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To investigate the effects of tamoxifen (TAM) and toremifene (TOR) on hepatic function and serum lipid levels in breast cancer patients receiving adjuvant endocrine therapy. The clinical data of 597 early breast cancer patients treated at the First Affiliated Hospital of Nanjing Medical University between January 2016 and December 2022 were collected. All the patients received standard adjuvant endocrine therapy with TAM or TOR after chemotherapy. Hepatic function and serum lipid data of all patients before and at 6 months and 1, 2, and 3 years after the treatment were collected retrospectively and analyzed statistically. There: no negative effect on hepatic function was observed in patients treated with either TAM or TOR. The triglyceride levels in both groups increased during treatment, and the effect of TAM on improving total cholesterol levels was stronger. Total cholesterol levels were not affected by time or treatment regimen. The low-density lipoprotein cholesterol levels decreased in both groups, and the effect was similar between groups. TAM can decrease the high-density lipoprotein cholesterol levels, whereas TOR can increase the high-density lipoprotein cholesterol levels, and there was a significant difference between groups. In the postoperative adjuvant endocrine therapy, TOR and TAM will not negatively impact the hepatic function of breast cancer patients, and TOR is better than TAM in the management of serum lipids; therefore, it may be a better choice for clinical medication.
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Neoplasias da Mama , Toremifeno , Humanos , Feminino , Toremifeno/uso terapêutico , Toremifeno/farmacologia , Tamoxifeno/farmacologia , Estudos Retrospectivos , Antineoplásicos Hormonais/efeitos adversos , Quimioterapia Adjuvante , Adjuvantes Imunológicos , Lipídeos/uso terapêutico , Colesterol , Lipoproteínas HDL/uso terapêuticoRESUMO
BACKGROUND: Triple-negative breast cancer (TNBC) is a type of highly invasive breast cancer with a poor prognosis. According to new research, long noncoding RNAs (lncRNAs) play a significant role in the progression of cancer. Although the role of lncRNAs in breast cancer has been well reported, few studies have focused on TNBC. This study aimed to explore the biological function and clinical significance of forkhead box C1 promoter upstream transcript (FOXCUT) in triple-negative breast cancer. METHODS: Based on a bioinformatic analysis of the cancer genome atlas (TCGA) database, we detected that the lncRNA FOXCUT was overexpressed in TNBC tissues, which was further validated in an external cohort of tissues from the General Surgery Department of the First Affiliated Hospital of Nanjing Medical University. The functions of FOXCUT in proliferation, migration, and invasion were detected in vitro or in vivo. Luciferase assays and RNA immunoprecipitation (RIP) were performed to reveal that FOXCUT acted as a competitive endogenous RNA (ceRNA) for the microRNA miR-24-3p and consequently inhibited the degradation of p38. RESULTS: lncRNA FOXCUT was markedly highly expressed in breast cancer, which was associated with poor prognosis in some cases. Knockdown of FOXCUT significantly inhibited cancer growth and metastasis in vitro or in vivo. Mechanistically, FOXCUT competitively bounded to miR-24-3p to prevent the degradation of p38, which might act as an oncogene in breast cancer. CONCLUSION: Collectively, this research revealed a novel FOXCUT/miR-24-3p/p38 axis that affected breast cancer progression and suggested that the lncRNA FOXCUT could be a diagnostic marker and therapeutic target for breast cancer.
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MicroRNAs , RNA Longo não Codificante , Neoplasias de Mama Triplo Negativas , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Sistema de Sinalização das MAP Quinases , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
OBJECTIVE: To establish a nomogram for predicting the pathologic complete response (pCR) in breast cancer (BC) patients after NAC by applying magnetic resonance imaging (MRI) and ultrasound (US). METHODS: A total of 607 LABC women who underwent NAC before surgery between January 2016 and June 2022 were retrospectively enrolled, and then were randomly divided into the training (n = 425) and test set (n = 182) with the ratio of 7:3. MRI and US variables were collected before and after NAC, as well as the clinicopathologic features. Univariate and multivariate logistic regression analyses were applied to confirm the potentially associated predictors of pCR. Finally, a nomogram was developed in the training set with its performance evaluated by the area under the receiver operating characteristics curve (ROC) and validated in the test set. RESULTS: Of the 607 patients, 108 (25.4%) achieved pCR. Hormone receptor negativity (odds ratio [OR], 0.3; P < .001), human epidermal growth factor receptor 2 positivity (OR, 2.7; P = .001), small tumour size at post-NAC US (OR, 1.0; P = .031), tumour size reduction ≥50% at MRI (OR, 9.8; P < .001), absence of enhancement in the tumour bed at post-NAC MRI (OR, 8.1; P = .003), and the increase of ADC value after NAC (OR, 0.3; P = .035) were all significantly associated with pCR. Incorporating the above variables, the nomogram showed a satisfactory performance with an AUC of 0.884. CONCLUSION: A nomogram including clinicopathologic variables and MRI and US characteristics shows preferable performance in predicting pCR. ADVANCES IN KNOWLEDGE: A nomogram incorporating MRI and US with clinicopathologic variables was developed to provide a brief and concise approach in predicting pCR to assist clinicians in making treatment decisions early.
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Neoplasias da Mama , Feminino , Humanos , Imageamento por Ressonância Magnética , Terapia Neoadjuvante , Nomogramas , Estudos RetrospectivosRESUMO
INTRODUCTION: Coronary heart disease (CHD) is one of the common cardiovascular diseases that seriously jeopardise human health, and endothelial inflammation and dyslipidaemia are the initiating links leading to its occurrence. Percutaneous coronary intervention (PCI) is one of the most effective surgical treatments for CHD with narrowed or blocked blood vessels, which can quickly unblock the blocked vessels and restore coronary blood supply. However, most patients may experience coronary microcirculation disorders (CMDs) and decreased cardiac function after PCI treatment, which directly affects the efficacy of PCI and the prognosis of patients. Preprotein converting enzyme subtilisin/Kexin 9 (PCSK9) inhibitors are novel pleiotropy lipid-lowering drug with dual anti-inflammation and lipid-lowering effects, and represent a new clinical pathway for rapid correction of dyslipidaemia. Therefore, we designed this protocol to systematically evaluate the effects of PCSK9 inhibitors on coronary microcirculation and cardiac function in patients with CHD after PCI, and to provide high-quality evidence-based evidence for the clinical application of PCSK9 inhibitors. METHODS AND ANALYSIS: This protocol is reported strictly in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols Guidelines. We will search PubMed, EMBASE, Web of Science and three Chinese databases (CNKI, Wanfang and VIP database) according to preset search strategies, without language and publication data restrictions. We will work with manual retrieval to screen references that have been included in the literature. Google Scholar will be used to search for grey literature. The final included literature must meet the established inclusion criteria. Titles, abstracts and full text will be extracted independently by two reviewers, and disagreements will be resolved through discussion or the involvement of a third reviewer. Extracted data will be analysed using Review Manager V.5.3. The Cochrane Risk of Bias Tool will be used to evaluate the risk of bias. Publication bias will be assessed by funnel plots. Heterogeneity will be assessed by I2 test and subgroup analyses will be used to further investigate potential sources of heterogeneity. The quality of the literature will be assessed by GRADE score. This protocol will start in January 2026 and end in December 2030. ETHICS AND DISSEMINATION: This study is a systematic review of published literature data and no special ethical approval was required. PROSPERO REGISTRATION NUMBER: CRD42022346189.
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Doença das Coronárias , Intervenção Coronária Percutânea , Humanos , Subtilisina , Inibidores de PCSK9 , Pró-Proteína Convertase 9 , Microcirculação , Revisões Sistemáticas como Assunto , Metanálise como Assunto , Inflamação , Inibidores Enzimáticos , LipídeosRESUMO
OBJECTIVE: Immunogenic cell death (ICD) of tumor cells is characterized by the induction of adaptive and innate immune responses, which in turn activates the immune surveillance and improves the efficacy of immunotherapy. In this study, we aimed to investigate the effect of ICD on the prognosis and the efficacy of immunotherapy in patients with triple-negative breast cancer (TNBC). METHODS: TNBC samples from The Cancer Genome Atlas-Breast Cancer (TCGA-BRCA) dataset were divided into two subtypes (ICD-high and ICD-low) based on the ICD status by using the consensus clustering method, and their genomic landscape and immune landscape were delineated. Furthermore, we established an ICD-related prognostic model to predict the efficacy of immunotherapy and the survival of TNBC. RESULTS: Our study showed that a poor prognosis of TNBC was associated with ICD-high subtype, while a favorable outcome was associated with ICD-low subtype. The immune landscape profiling results revealed that ICD-high subtype presented an immune-hot phenotype, whereas ICD-low subtype was associated with an immune-cold phenotype. Furthermore, our prognostic model predicted that the high-risk score group had a poor overall survival (OS), which was consistent with the actual data in the Gene Expression Omnibus (GEO) dataset. We also used tumor immune dysfunction and exclusion (TIDE) to determine the predictive significance of our ICD risk signature in immunotherapy efficacy, and found that ICD high-risk group had the highest response rate to immunotherapy in the immunotherapy response group. CONCLUSION: Our results reveal a correlation between ICD status and alterations in the tumor immune microenvironment in patients with TNBC. This finding might help guide clinicians in immunotherapy application for TNBC patients.
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PURPOSE: To develop a combined nomogram by incorporating the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram and ultrasound (US)-based radiomics score (Radscore) for predicting sentinel lymph node (SLN) metastasis in invasive breast cancer. MATERIALS AND METHODS: This retrospective study was approved by the ethics committee of our institution, and written informed consent was waived. A total of 452 patients with invasive breast cancer who received SLN Biopsy in a single center were included between January 2016 and December 2019. The patients were divided into a training set (n = 318) and a validation set (n = 134). A total of 1216 features were extracted from the regions of interest (ROIs) of the tumors on conventional ultrasound. The maximum relevance minimum redundancy (mRMR) and the least absolute shrinkage and selection operator (LASSO) algorithm were used to build the Radscore. Afterward, the diagnostic performance was assessed and validated. Comparison of receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were performed to evaluate the incremental value of the combined model. RESULTS: Obtained from 18 features, the Radscore indicated a favorable discriminatory capability in the training set with an area under the curve (AUC) of 0.834, whereas a value of 0.770 was observed in the validation set. The AUC of the combined model was 0.901 (95 % confidence interval (95 % CI): 0.865-0.938) in the training set and 0.833 (95 % CI: 0.788-0.878) in the validation set. Both of them were superior to MSKCC or imaging Radscore alone (P < 0.05). DCA demonstrated that the combined model was superior to the others in terms of clinical practicability. CONCLUSION: Preoperative US-based Radscore can improve the accuracy of clinical MSKCC nomogram for SLN metastasis prediction in breast cancer.
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Neoplasias da Mama , Nomogramas , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Humanos , Linfonodos/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Curva ROC , Estudos Retrospectivos , Biópsia de Linfonodo SentinelaRESUMO
A Gram-stain-positive, aerobic, non-motile and coccoid-shaped bacterium, designated XNB-1T, was isolated from farmland soil in Taian, Shandong province, China. Strain XNB-1T contained iso-C15â:â0 and iso-C16â:â0 as the predominant fatty acids. The diagnostic diamino acid of the peptidoglycan was ornithine, and the interpeptide bridge was l-OrnâGly(1, 2)âd-Glu. The polar lipid profile of strain XNB-1T consisted of diphosphatidylglycerol, phosphatidylglycerol, an unidentified phosphoglycolipid and three unidentified phospholipids. The predominant menaquinone of strain XNB-1T was MK-8(H4) and the DNA G+C content was 70.1 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain XNB-1T belonged to the genus Ornithinicoccus, and shared the highest similarity with Ornithinicoccus hortensis HKI 0125T (96.0â%), followed by Ornithinicoccus halotolerans EGI 80423T (95.5â%). Genome-based analysis of average nucleotide identity of strain XNB-1T with O. hortensis HKI 0125T and O. halotolerans EGI 80423T yielded values of 73.1 and 73.3â%, respectively, while the digital DNA-DNA hybridization values were 19.5 and 19.9â%, respectively. On the basis of phenotypic, chemotaxonomic and phylogenetic data, strain XNB-1T is considered to represent a novel species of the genus Ornithinicoccus, for which the name Ornithinicoccus soli sp. nov. is proposed. The type strain is XNB-1T (=CCTCC AB 2019099T=KCTC 49259T).
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Actinobacteria/classificação , Fazendas , Filogenia , Microbiologia do Solo , Actinobacteria/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Hibridização de Ácido Nucleico , Peptidoglicano/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMO
A Gram-stain-positive, strictly aerobic, non-motile, non-spore-forming and rod-shaped bacterium, designated as strain G-1T, was isolated from farmland soil sampled in in Fuyang, Anhui Province, PR China. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain G-1T was closely related to Cumulibacter manganitolerans 2-36T (97.7â% similarity). Strain G-1T contained iso-C16â:â0, C17â:â1ω6c, iso-C15â:â0 and iso-C14â:â0 as the predominant fatty acids. The polar lipids of strain G-1T were diphosphatidylglycerol, phosphatidylethanolamine, an unidentified phospholipid, an unidentified lipid and two unidentified glycolipids. The predominant respiratory quinone of strain G-1T was MK-9(H4). The cell wall contained meso-diaminopimelic acid as the diagnostic diamino acid. The G+C content of the genomic DNA based on genome calculations was 64.2 mol%. Average nucleotide identity and the digital DNA-DNA hybridization values for the draft genomes between strain G-1T and strain 2-36T were 75.7 and 20.2 %, respectively. On the basis of phenotypic and phylogenetic data, strain G-1T is considered to represent a novel species of the genus Cumulibacter, for which the name Cumulibacter soli sp. nov. is proposed. The type strain is G-1T (=CCTCC AB2019021T=KCTC 49258T).
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Actinobacteria/classificação , Fazendas , Filogenia , Microbiologia do Solo , Actinobacteria/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Glicolipídeos/química , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMO
Abstracts Purpose: Pirfenidone is mostly used in antifibrotic and anti-inflammatory therapies. We have previously demonstrated that pirfenidone had antifibrotic and anti-inflammatory effects on the wound healing process after glaucoma filtration surgery in vitro and in vivo. Since the wound healing and reactive scarring process simultaneously involves inflammation, fibrosis, and angiogenesis, and angiogenesis plays a more important role in chronic or prolonged wound healing, we tried to explore the antiangiogenesis effect in pirfenidone and its potential multitarget function in regulating excessive scarring. The aim of the present study was to investigate the antiangiogenesis effect of pirfenidone. METHODS: The proliferation of human umbilical vein endothelial cells (HUVECs) and human Tenon's fibroblasts (HTFs) were detected by WST-1 assay. The cell viability of HUVECs was measured by Trypan Blue together with lactate dehydrogenase, Annexin 5 experiment, and Ki-67 immunofluorescence assay. The functions of HUVECs and HTFs were demonstrated using cell migration assay, transwell invasion assay, and tube formation assay. The expression levels of vascular endothelial growth factor-A (VEGF-A), VEGF receptor-2 (VEGFR-2), neuropilin-1(NRP-1), and their downstream signaling proteins p-PI3K, PI3K, p-AKT, AKT, p-mTOR, and mechanistic target of rapamycin (mTOR) were indicated by western blot assay. The secretion of VEGF-A was detected by enzyme-linked immunosorbent assay. RESULTS: Pirfenidone inhibited proliferation, migration, invasion, and tube formation of HUVECs in vitro, and had an equivalent antiangiogenesis effect when compared with Ranibizumab in HUVECs and HTFs. Pirfenidone downregulated VEGF-A/VEGFR-2, VEGF-A/NRP-1, and its downstream signaling pathway protein expression. CONCLUSIONS: Pirfenidone has an antiangiogenesis effect in the wound healing process and may become an ideal multitarget antiscarring agent after glaucoma filtration surgery.
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Inibidores da Angiogênese/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Piridonas/farmacologia , Cicatrização/efeitos dos fármacos , Anexina A5/metabolismo , Western Blotting , Movimento Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Fibroblastos/efeitos dos fármacos , Citometria de Fluxo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Antígeno Ki-67/metabolismo , L-Lactato Desidrogenase/metabolismo , Neurofisinas/metabolismo , Cápsula de Tenon/citologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
PURPOSE: To investigate the pharmacologic effect of tetramethylpyrazine (TMP) on human Tenon's fibroblasts (HTFs), the cells implicated in scarring after filtration surgery. METHODS: Transforming growth factor-ß2 (TGF-ß2) was used to stimulate a fibrotic phenotype in primary HTFs, and the influence of TMP on the fibrotic phenotype was assessed. Cell proliferation and cell cycle regulation were profiled. Immunofluorescence staining tracked proliferating cell nuclear antigen (PCNA) expression. Transwell assays monitored cell migration. Flow cytometry measured TMP toxicity. In addition, in TGF-ß2-treated HTFs, Western blot and immunofluorescence were employed to assess the expression of α-smooth muscle actin (α-SMA). The TMP-mediated activity on cytoskeletal arrangements and extracellular matrix (ECM) accumulation in HTFs was evaluated using actin polymerization and Western blot assays. Moreover, TGF-ß-dependent activation of Smad3 and p38 was examined by Western blot analysis. RESULTS: In TGF-ß2-treated HTFs, TMP reduced proliferation and migration but did not induce apoptosis. Moreover, TMP attenuated expression of α-SMA and suppressed stress fiber formation stimulated by profibrotic cytokine; it also counteracted TGF-ß2-induced cytoskeletal rearrangements, morphologic changes, and ECM accumulation. Smad3 and p38 mitogen-activated protein kinase (MAPK) signaling were downstream of the TMP-sensitive effect. CONCLUSIONS: Tetramethylpyrazine counteracts TGF-ß2-mediated myofibroblast transdifferentiation and attenuates ECM component deposition and cell proliferation in HTFs, implicating TMP as a potential antifibrosis agent in glaucoma filtration surgery.
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Pirazinas/farmacologia , Cápsula de Tenon/patologia , Fator de Crescimento Transformador beta2/farmacologia , Western Blotting , Proliferação de Células , Transdiferenciação Celular/efeitos dos fármacos , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Cirurgia Filtrante , Citometria de Fluxo , Glaucoma/cirurgia , Humanos , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/metabolismo , Complicações Pós-Operatórias/patologia , Cápsula de Tenon/efeitos dos fármacos , Vasodilatadores/farmacologiaRESUMO
The aim of this article was to evaluate whether genetic variants in autophagy-related genes affect the overall survival (OS) of non-small cell lung cancer (NSCLC) patients. We analyzed 14 single nucleotide polymorphisms (SNPs) in core autophagy-related genes for OS in 1,001 NSCLC patients. Three promising SNPs in ATG10 were subsequently annotated by the expression quantitative trait loci (eQTL) and methylation quantitative trait loci (meQTL) analyses based on Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets. We observed that the variants of rs10514231, rs1864182 and rs1864183 were associated with poor lung cancer survival (HR = 1.33, 95% CI = 1.07-1.65; HR = 1.43, 95% CI = 1.13-1.81; HR = 1.38, 95% CI = 1.14-1.68, respectively) and positively correlated with ATG10 expression (all p < 0.05) from GTEx and TCGA datasets. The elevated expression of ATG10 may predict shorter survival time in lung cancer patients in TCGA dataset (HR = 2.10, 95% CI = 1.33-3.29). Moreover, the variants of rs10514231 and rs1864182 were associated with the increased methylation levels of cg17942617 (meQTL), which in turn contributed to the elevated ATG10 expression and decreased survival time. Further functional assays revealed that ATG10 facilitated lung cancer cell proliferation and migration. Our findings suggest that eQTL/meQTL variations of ATG10 could influence lung cancer survival through regulating ATG10 expression.
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Proteínas Relacionadas à Autofagia/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Locos de Características Quantitativas , Proteínas de Transporte Vesicular/genética , Autofagia/genética , Proteínas Relacionadas à Autofagia/biossíntese , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Linhagem Celular Tumoral , Metilação de DNA , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Polimorfismo de Nucleotídeo Único , Prognóstico , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Taxa de Sobrevida , Proteínas de Transporte Vesicular/biossínteseRESUMO
The Vav3 oncogene is overexpressed and has a significant role in the tumorigenesis of prostate cancer and glioblastoma. In the present study, the expression status and prognostic value of Vav3 expression was investigated in breast cancer. Vav3 protein levels were analyzed by immunoblotting in human breast cancer and epithelial cell lines. Immunohistochemistry was used to detect Vav3 in a tissue microarray of 173 breast cancers and 19 benign breast lesions. Statistical analysis was performed to reveal the association between Vav3 expression and clinicopathological parameters. Disease-free survival (DFS) and overall survival (OS) were calculated by Kaplan-Meier analysis and the Cox regression model. The Vav3 protein level was higher in the breast cancer cell lines than in the normal human breast cells. Vav3 was expressed in 86.1% of breast cancer patients, but in only 15.6% patients with benign breast disease. Patients with negative estrogen receptor expression, axillary lymph node involvement and a high tumor-node-metastasis stage demonstrated a higher positive rate of Vav3 expression. The Kaplan-Meier survival analysis revealed that patients with higher Vav3 expression exhibited shorter DFS and OS times. The multivariate Cox analysis revealed that Vav3 was a prognostic factor of survival. Overall, Vav3 was overexpressed in human breast cancer cells and this correlated with a shorter survival time, indicating that Vav3 is a biomarker of a poor prognosis for breast cancer patients.
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AIM: Blood group is an important risk factor for some malignancies, including pancreatic and stomach cancer. However, it is unclear whether the risk of breast cancer is higher in any specific ABO blood type. METHODS: We searched the electronic database of PubMed, EMBASE, China National Knowledge Infrastructure and the VIP Chinese Journal of Science and Technology for case-control studies about blood type and breast cancer incidence, and a meta-analysis was conducted. RESULTS: Fourteen studies were eligible for assessment on the association of breast cancer with different blood types, including 9665 breast cancer patients and 244,768 controls. Relative to blood type O, women with blood type A (odds ratio (OR) = 1.115, 95% confidence interval (CI) 0.992-1.254), B (OR = 0.983, 95% CI 0.915-1.056) and AB (OR = 1.042, 95% CI 0.881-1.231) had the same breast cancer risk. The risk for women with Rhesus-positive (Rh+) was the same as those with Rh-negative (Rh-) (OR = 0.948, 95% CI 0.667-1.348). Among Caucasians, the OR of blood type A was 1.066 (95% CI, 1.001-1.134, P = 0.522 for heterogeneity). CONCLUSION: This meta-analysis suggests Caucasians with blood type A may have a higher risk of breast cancer than other Caucasians. No association was found in any other blood type or any other population. Similarly, the Rh factor had no association with the risk of breast cancer.
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Sistema ABO de Grupos Sanguíneos , Neoplasias da Mama/sangue , Sistema do Grupo Sanguíneo Rh-Hr , Neoplasias da Mama/etnologia , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Humanos , Fatores de Risco , População Branca/estatística & dados numéricosRESUMO
Autophagy is a cellular process directed at recycling of cellular proteins and removal of intracellular microorganisms, which is important for balancing sources of energy at critical times in development and in response to nutrient stress. It has been reported to be a critical process in cancer initiation and progression. We hypothesized that genetic variants in critical genes of autophagy may be involve in the development of breast cancer. Thus, we systematically screened 14 potentially functional polymorphisms in six autophagy-related genes (ATG3, ATG5, ATG7, ATG10, and ATG12 and LC3) that are core components in autophagosome formation. We conducted a case-control study including 1064 breast cancer cases and 1073 cancer-free controls to evaluate the associations of these variants with breast cancer risk. We found that rs1864182 and rs10514231 in ATG10 were significantly associated with a decreased risk of breast cancer [odds ratios (OR)=0.77, 95% confidence interval (CI): 0.61-0.96, P=0.023; and OR=0.75, 95% CI: 0.59-0.93, P=0.010, respectively]. Similar protective effects for both loci were observed between subgroups stratified by ages at diagnosis/recruitment, menarche and first live birth, and status of menopause, estrogen receptor (ER) and progesterone receptor (PR). These results suggest that genetic variants in ATG10 may implicate with breast cancer susceptibility in Chinese population. Further large and functional studies are needed to confirm our findings.
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Neoplasias da Mama/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Enzimas de Conjugação de Ubiquitina/genética , Adulto , Proteínas Relacionadas à Autofagia , China , Feminino , Humanos , Pessoa de Meia-Idade , Proteínas de Transporte VesicularRESUMO
MicroRNAs (miRNA) are a class of small, noncoding RNA molecules involved in a diversity of cellular functions. Single nucleotide polymorphisms (SNPs) in miRNA biosynthesis genes may affect the biogenesis of miRNAs and consequently affect the miRNAs regulation. In this study, we systematically selected 24 functional SNPs located in eight key biosynthesis genes of miRNA (DROSHA, DGCR8, RAN, DICER, AGO2, GEMIN3, GEMIN4 and HIWI) and investigated the association between these SNPs and the risk of breast cancer in a Chinese population. All 24 SNPs were firstly genotyped in stage 1 (878 cases and 900 controls) and three promising SNPs (DROSHA rs2291109, RAN rs7301722 and DGCR8 rs417309) were selected for further validation in stage 2 (914 cases and 967 controls). We found that only one SNP (rs417309) located in the 3'-UTR of DGCR8 was consistently associated with an increased breast cancer risk in two stages with a combined odds ratio (OR) of 1.50 [95% confidence interval (CI) = 1.16-1.93]. Based on the bioinformatics prediction, rs417309 is located at the binding sites of miR-106b and miR-579 in the 3'-UTR of DGCR8. To evaluate whether rs417309 variant affects the binding capacity of miRNAs, we cotransfected luciferase reporter plasmids of DGCR8 3'-UTR and miR-106b/miR-579 in three cell lines. Luciferase activity assay showed a higher expression level with rs417309 A allele compared with G allele in MCF-7 cell lines (p = 3.31 × 10(-7) , 9.29 × 10(-7) for miR-106b and miR-579, respectively). Our findings suggested that DGCR8 rs417309 G > A might affect breast cancer risk through the interruption of miRNA binding.
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Regiões 3' não Traduzidas/genética , Povo Asiático/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas/genética , Estudos de Casos e Controles , Feminino , Seguimentos , Genótipo , Humanos , Luciferases/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Prognóstico , Proteínas de Ligação a RNARESUMO
Genetic variants may influence miRNA-mRNA interaction through modulate binding affinity, creating or destroying miRNA-binding sites. Twenty-four single nucleotide polymorphisms (SNPs) that were predicted to affect the binding affinity of breast cancer-related miRNAs to 3'-untranslated regions (UTR) of known genes were genotyped in 878 breast cancer cases and 900 controls in Chinese women. Three promising SNPs (rs10494836, rs10857748 and rs7963551) were further validated in additional 914 breast cancer cases and 967 controls. The variant allele (C) of rs7963551 at 3'-UTR of RAD52 showed a consistently reduced breast cancer risk in two stages with a combined odds ratio (OR) of 0.84 [95% confidence interval (CI) = 0.75-0.95], which was more prominent among women with early age at first live birth (OR = 0.71, 95% CI = 0.58-0.87). A significant interaction was observed between rs7963551 and age at first live birth on breast cancer risk (P for interaction = 0.04). Luciferase activity assay showed a higher expression level for rs7963551 C allele as compared with A allele (P = 5.19 × 10(-3) for MCF-7 cell lines), which might be due to a reduced inhibition from a weakened binding capacity of miRNA to 3'-UTR of RAD52 harboring C allele. These findings indicate that rs7963551 located at hsa-let-7 binding site may alter expression of RAD52 through modulating miRNA-mRNA interaction and contribute to the development of breast cancer in Chinese women.
Assuntos
Neoplasias da Mama/genética , MicroRNAs/fisiologia , Polimorfismo de Nucleotídeo Único , Proteína Rad52 de Recombinação e Reparo de DNA/genética , Regiões 3' não Traduzidas , Sítios de Ligação , Estudos de Casos e Controles , Linhagem Celular , China , Feminino , Regulação Neoplásica da Expressão Gênica , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Ligação Proteica , Interferência de RNA , Proteína Rad52 de Recombinação e Reparo de DNA/metabolismo , RiscoRESUMO
BACKGROUND: The relationship between postmenopausal hormone therapy (HT) and invasive breast cancer has been extensively investigated, but that with breast carcinoma in situ (BCIS) has received relatively little attention. The aim of our present study was to review and summarize the evidence provided by longitudinal studies on the association between postmenopausal HT use and BCIS risk. METHODS: A comprehensive literature search for articles published up to May 2012 was performed. Prior to performing a meta-analysis, the studies were evaluated for publication bias and heterogeneity. Relative risk (RR) or odds ratio (OR) values were calculated using 14 reports (8 case-control studies and 6 cohort studies), published between 1986 and 2012. RESULTS: There was evidence of an association between ever postmenopausal estrogen use and BCIS based on a random-effects model (RR = 1.25, 95% confidence interval (CI) = 1.01, 1.55). However, we found no strong evidence of an association between ever postmenopausal estrogen combined with progesterone use and BCIS using a random- effects model (RR = 1.55, 95% CI = 0.95, 2.51). Furthermore, our analysis showed a strong association between " > 5 years duration" of estrogen or estrogen combined with progesterone use and BCIS. Furthermore, current use of any HT is associated with increased risk of BCIS in cohort studies. Additional well-designed large studies are now required to validate this association in different populations.
Assuntos
Neoplasias da Mama/etiologia , Carcinoma Ductal de Mama/etiologia , Carcinoma Intraductal não Infiltrante/etiologia , Terapia de Reposição de Estrogênios/efeitos adversos , Pós-Menopausa , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Fatores de RiscoRESUMO
Mouse models play an irreplaceable role in the in vivo research of human gastric cancer. In this study, we developed a novel human Gastric tissue-derived Orthotopic and Metastatic (GOM) mouse model of human gastric cancer, in which the human normal gastric tissues were implanted subcutaneously into immunodeficient mice to create a human gastric microenvironment. Then, human gastric cancer cells were injected into the implants. GOM model could mimic the interactions between human gastric microenvironment and human gastric cancer cells, which help exhibit the real characteristics of tumor cells, and finally mimic the clinical-like tumor proliferation and metastases of human beings.
Assuntos
Modelos Animais de Doenças , Neoplasias Gástricas/patologia , Microambiente Tumoral/fisiologia , Animais , Apoptose/fisiologia , Processos de Crescimento Celular/fisiologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Humanos , Camundongos , Camundongos SCID , Invasividade Neoplásica , Metástase Neoplásica , Transplante de Neoplasias/métodosRESUMO
A genome-wide association study, conducted among women of European ancestry, has identified two single-nucleotide polymorphisms (SNPs) rs4415084 (T>C) and rs10941679 (A>G) at chromosome 5p12 were associated with risk of breast cancer, suggesting that genetic variants in this region may have a role in the development of breast cancer. To investigate the associations between SNPs at 5p12 and risk of breast cancer in the Chinese population, we conducted a fine-mapping in 5p12 using a haplotype-tagging SNP approach and genotyped these SNPs with a case-control study consisting of 878 cases and 900 controls. We found that the two risk SNPs reported in the European population were neither associated with breast cancer risk in our Chinese population, nor did the fine-mapping SNPs after controlling multiple comparison.
Assuntos
Povo Asiático/genética , Neoplasias da Mama/genética , Cromossomos Humanos Par 5/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Povo Asiático/etnologia , Neoplasias da Mama/etnologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Testes Genéticos/métodos , Estudo de Associação Genômica Ampla , Projeto HapMap , Haplótipos , Humanos , Desequilíbrio de Ligação , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Cancer/testis antigen (CTA) SSX2, which is silent in most normal adult tissues and expressed in various malignant tumors, has been identified for decades. Expression of SSX in tumors has been associated with advanced stages and worse patient prognosis. However, little is known about its role in breast cancer. The SSX2 expression plasmid constructed was stably transfected into the breast cancer cell line MCF-7. The influence of SSX2 on MCF-7 cells was assessed using MTT assay, flow cytometry, transwell invasion assay and in vivo tumorigenicity assay. A comparative proteomic approach was performed to identify and clarify the underlying molecular mechanisms. SSX2 expression was more pronounced in ERα-negative breast cancer cells compared with the positive ones. Overexpression of SSX2 induced cell growth and prompted cell invasion. Both ERα and E-cadherin expression were suppressed in the SSX2 overexpressing MCF-7 cells. Eleven known proteins were identified with significant differential expression. Among these, five were decreased, while other six were increased in the SSX2 overexpressing MCF-7 cells. These results suggested SSX2 may enhance invasiveness in MCF-7 cells both in vivo and in vitro. The regulation of ERα signaling by target proteins of SSX2 may explain the metastatic potential of breast cancer cells.