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1.
Cancer Causes Control ; 31(12): 1069-1077, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32915323

RESUMO

PURPOSE: Diets with a high glycemic load (GL) or glycemic index (GI) may increase cancer risk. Findings from prior studies on the relationship between GL, GI, and lung cancer risk are inconsistent. We investigated this relationship in a large prospective cohort. METHODS: We analyzed data from the Southern Community Cohort Study, a prospective cohort that includes diverse racial groups predominantly low-income adults aged 40-79 in 12 southeastern states of the USA. We estimated dietary GL and GI values using data collected from food frequency questionnaires at baseline. Dietary GL and GI were energy adjusted by residual method and categorized into sex-specific quintiles. Cox proportional hazard regression was used to assess the associations between dietary GL, GI, and lung cancer risk. We further performed stratified analyses by various factors. RESULTS: Intakes of individual food items or food groups that commonly contribute to GL were similar between blacks and whites in the cohort. After excluding the first two years of follow-up, 947 incident lung cancers were ascertained among 55,068 participants. Neither dietary GL nor GI was significantly associated with incident lung cancer risk in the overall population (GL: Q5 vs. Q1, HR = 0.88, 95% CI 0.72-1.07, ptrend = 0.29; GI: Q5 vs. Q1, HR = 1.06, 95% CI 0.86-1.30, ptrend = 0.71), nor in subgroups of populations (ptrend > 0.05), in multivariable-adjusted analyses. CONCLUSION: Dietary GL and GI were not independently associated with incident lung cancer risk in a large understudied population.

2.
Parasitol Res ; 119(11): 3639-3648, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32930858

RESUMO

Due to its wide presence in apicomplexan parasites as well as high polymorphism and antigenic diversity, the variable merozoite surface antigen (VMSA) family in Babesia sp. has attracted increasing attention of researchers. Here, all the reported VMSA genes of Babesia spp. were obtained from GenBank, and multiple alignments were performed by using conserved regions to blast the Babesia orientalis genome database (unpublished data). Five MSA genes (named MSA-2a1, MSA-2a2, MSA-2c1, MSA-1, and MSA-2c2, respectively) were identified, sequenced, and cloned from B. orientalis, which were shown to encode proteins with open reading frames ranging in size from 266 (MSA-2c1) to 317 (MSA-1) amino acids. All the five proteins contain an MSA-2c superfamily conserved domain, with an identical signal peptide and glycosyl phosphatidyl inositol (GPI)-anchor for each of them. The five proteins were also predicted to contain B cell epitopes, with only three for BoMSA-2c1, the smallest protein in the BoVMSA family, while at least six for each of the others. Notably, BoMSA-2a1 has 2 identical copies, a specific phenomenon only present in B. orientalis. This research has determined the MSA genes of B. orientalis and provides a genetic basis for further research of functional genes in B. orientalis.

3.
Nat Commun ; 11(1): 3905, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32764609

RESUMO

It remains elusive whether some of the associations identified in genome-wide association studies of prostate cancer (PrCa) may be due to regulatory effects of genetic variants on CpG sites, which may further influence expression of PrCa target genes. To search for CpG sites associated with PrCa risk, here we establish genetic models to predict methylation (N = 1,595) and conduct association analyses with PrCa risk (79,194 cases and 61,112 controls). We identify 759 CpG sites showing an association, including 15 located at novel loci. Among those 759 CpG sites, methylation of 42 is associated with expression of 28 adjacent genes. Among 22 genes, 18 show an association with PrCa risk. Overall, 25 CpG sites show consistent association directions for the methylation-gene expression-PrCa pathway. We identify DNA methylation biomarkers associated with PrCa, and our findings suggest that specific CpG sites may influence PrCa via regulating expression of candidate PrCa target genes.


Assuntos
Biomarcadores Tumorais/genética , Metilação de DNA/genética , Neoplasias da Próstata/genética , Estudos de Casos e Controles , Ilhas de CpG , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Modelos Genéticos , Fatores de Risco
4.
Acta Pharmacol Sin ; 2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32647340

RESUMO

Sphingosine-1-phosphate (S1P), the backbone of most sphingolipids, activating S1P receptors (S1PRs) and the downstream G protein signaling has been implicated in chemoresistance. In this study we investigated the role of S1PR2 internalization in 5-fluorouracil (5-FU) resistance in human colorectal cancer (CRC). Clinical data of randomly selected 60 CRC specimens showed the correlation between S1PR2 internalization and increased intracellular uracil (P < 0.001). Then we explored the regulatory mechanisms in CRC model of villin-S1PR2-/- mice and CRC cell lines. We showed that co-administration of S1P promoted S1PR2 internalization from plasma membrane (PM) to endoplasmic reticulum (ER), thus blunted 5-FU efficacy against colorectal tumors in WT mice, compared to that in S1PR2-/- mice. In HCT116 and HT-29 cells, application of S1P (10 µM) empowered S1PR2 to internalize from PM to ER, thus inducing 5-FU resistance, whereas the specific S1PR2 inhibitor JTE-013 (10 µM) effectively inhibited S1P-induced S1PR2 internalization. Using Mag-Fluo-AM-labeling [Ca2+]ER and LC-ESI-MS/MS, we revealed that internalized S1PR2 triggered elevating [Ca2+]ER levels to activate PERK-eLF2α-ATF4 signaling in HCT116 cells. The activated ATF4 upregulated RNASET2-mediated uracil generation, which impaired exogenous 5-FU uptake to blunt 5-FU therapy. Overall, this study reveals a previously unrecognized mechanism of 5-FU resistance resulted from S1PR2 internalization-upregulated uracil generation in colorectal cancer, and provides the novel insight into the significance of S1PR2 localization in predicting the benefit of CRC patients from 5-FU-based chemotherapy.

6.
Parasitol Int ; 78: 102152, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32512049

RESUMO

Babesia orientalis (B. orientalis) is responsible for water buffalo babesiosis, which caused serious economic losses in the south of China. Although the invasion process has been roughly described, there are still some unknown molecules that have not yet been identified. Recently, an invasion-related protein BOV57 has been identified in the Babesia bovis. However, there is no report available about the gene in B. orientalis. B. orientalis P53 (BoP53) sequence was obtained by blast BOV57 sequence in B. orientalis genome database, and the full length of the BoP53 gene is 1599 bp. BoP53 gene was cloned into a pGEX-6P-1 expression vector and expressed as a GST-tag fusion protein. The tertiary structure of BoP53 was predicted with the I-TASSER software. The native BoP53 was identified from of B. orientalis lysate incubation with mouse antiserum against rBoP53. BoP53 as a novel identified protein promotes the study of B. orientalis, the reaction of rBoP53 with the serum of B. orientalis-infected water buffalo but not with healthy buffalo serum indicated its good antigenicity. It may be a candidate antigen for the diagnosis of B. orientalis infection.

7.
Oncogene ; 39(29): 5214-5227, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32546724

RESUMO

Aberrant sphingolipid metabolism has been implicated in chemoresistance, but the underlying mechanisms are still poorly understood. Herein we revealed a previously unrecognized mechanism of 5-fluorouracil (5-FU) resistance contributed by high SphK2-upregulated dihydropyrimidine dehydrogenase (DPD) in colorectal cancer (CRC), which is evidenced from human CRC specimens, animal models, and cancer cell lines. TMA samples from randomly selected 60 CRC specimens firstly identified the clinical correlation between high SphK2 and increased DPD (p < 0.001). Then the regulatory mechanism was explored in CRC models of villin-SphK2 Tg mice, SphK2-/-mice, and human CRC cells xenografted nude mice. Assays of ChIP-Seq and luciferase reporter gene demonstrated that high SphK2 upregulated DPD through promoting the HDAC1-mediated H3K56ac, leading to the degradation of intracellular 5-FU into inactive α-fluoro-ß-alanine (FBAL). Lastly, inhibition of SphK2 by SLR080811 exhibited excellent inhibition on DPD expression and potently reversed 5-FU resistance in colorectal tumors of villin-SphK2 Tg mice. Overall, this study manifests that SphK2high conferred 5-FU resistance through upregulating tumoral DPD, which highlights the strategies of blocking SphK2 to overcome 5-FU resistance in CRC.

8.
Cancer Epidemiol Biomarkers Prev ; 29(7): 1501-1508, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32439797

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with few known risk factors and biomarkers. Several blood protein biomarkers have been linked to PDAC in previous studies, but these studies have assessed only a limited number of biomarkers, usually in small samples. In this study, we evaluated associations of circulating protein levels and PDAC risk using genetic instruments. METHODS: To identify novel circulating protein biomarkers of PDAC, we studied 8,280 cases and 6,728 controls of European descent from the Pancreatic Cancer Cohort Consortium and the Pancreatic Cancer Case-Control Consortium, using genetic instruments of protein quantitative trait loci. RESULTS: We observed associations between predicted concentrations of 38 proteins and PDAC risk at an FDR of < 0.05, including 23 of those proteins that showed an association even after Bonferroni correction. These include the protein encoded by ABO, which has been implicated as a potential target gene of PDAC risk variant. Eight of the identified proteins (LMA2L, TM11D, IP-10, ADH1B, STOM, TENC1, DOCK9, and CRBB2) were associated with PDAC risk after adjusting for previously reported PDAC risk variants (OR ranged from 0.79 to 1.52). Pathway enrichment analysis showed that the encoding genes for implicated proteins were significantly enriched in cancer-related pathways, such as STAT3 and IL15 production. CONCLUSIONS: We identified 38 candidates of protein biomarkers for PDAC risk. IMPACT: This study identifies novel protein biomarker candidates for PDAC, which if validated by additional studies, may contribute to the etiologic understanding of PDAC development.

9.
J Asian Nat Prod Res ; : 1-7, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32189519

RESUMO

One new phenolic glycoside, methyl 3,4-dihydroxyphenylacetate-4-O-[2-O-ß-D-apisoyl-6-O-(2-hydroxybenzoyl)]-ß-D-glucopyranoside (1), together with 10 known compounds (2-11), were isolated from the roots of Datura metel. The structures of these compounds were elucidated on the basis of their spectroscopic data. Furthermore, the in vitro anti-inflammatory activities of compounds 1-11 were evaluated.

10.
Drug Deliv ; 27(1): 482-490, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32212952

RESUMO

A sodium N-lauryl amino acids (shortly silk sericin surfactant, SSS) is synthesized with lauryl chloride and sericin amino acids recovered from silk industrial waste. The purpose of this study is to explore whether the sericin surfactant can be used as a potential drug delivery carrier. By controlling the proportion of cationic drugs, cytarabine hydrochloride (CH) and anionic SSS, the aggregation behavior, slow release capability and toxicological effects of catanionic aggregates or vesicles, formed through CH and SSS, have been investigated in detail. Dynamic light scattering (DLS), transmission electron microscopy (TEM), and zeta potential analysis showed that the aggregate solution could form a stable vesicle structure when the mass fraction of CH is less than or equal to 0.3. The drug release results showed that the cumulative release rate of the catanionic aggregation solution with CH mass fraction of 0.2 reached a maximum at 18 h, being approximately 9 times greater than that of pure cytarabine. The CH/SSS aggregates had a significant sustained release effect compared with the control group. At the same time, vesicles formed by SSS and CH have better anti-tumor effects compared with the pure drug group. In summary, sericin surfactant from silk industrial waste has a potential use as a drug delivery carrier.

11.
Parasitol Int ; 77: 102106, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32179136

RESUMO

Babesiosis caused by Babesia orientalis is one of the most serious parasitic diseases of water buffalo in the central and south part of China. Rhoptry neck proteins (RONs) are very important protein components to form a complex moving junction (MJ) which mainly participate in the invasion processes in apicomplexan parasites. Aimed to the further investigation of the function of BoRON proteins in B. orientalis, in this study, BoRON5 was characterized. A truncated 921 bp fragment of BoRON5 with predicted antigenic epitopes was cloned and inserted into pSUMO expression vector. Recombinant protein rSUMO-BoRON5 was purified from Escherichia coli. and used to produce antisera in Kunming mice. rSUMO-BoRON5 showed strong immunosignals when blotted with the positive serum from B. orientalis-infected water buffalo. Antisera raised in Kunming mice against rSUMO-BoRON5 could detect the native BoRON5 in parasite lysates. Immuofluorescence assay showed that mice antisera of rSUMO-BoRON5 could detect merozoite in B. orientalis infected water buffalo erythrocytes. This study provides useful information for the further investigation of the BoRON5 function during B. orientalis invasion of water buffalo.

12.
Nat Commun ; 11(1): 1217, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32139696

RESUMO

Known risk variants explain only a small proportion of breast cancer heritability, particularly in Asian women. To search for additional genetic susceptibility loci for breast cancer, here we perform a meta-analysis of data from genome-wide association studies (GWAS) conducted in Asians (24,206 cases and 24,775 controls) and European descendants (122,977 cases and 105,974 controls). We identified 31 potential novel loci with the lead variant showing an association with breast cancer risk at P < 5 × 10-8. The associations for 10 of these loci were replicated in an independent sample of 16,787 cases and 16,680 controls of Asian women (P < 0.05). In addition, we replicated the associations for 78 of the 166 known risk variants at P < 0.05 in Asians. These findings improve our understanding of breast cancer genetics and etiology and extend previous findings from studies of European descendants to Asian women.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Neoplasias da Mama/genética , Grupo com Ancestrais do Continente Europeu/genética , Loci Gênicos , Predisposição Genética para Doença , Feminino , Humanos , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Receptores Estrogênicos/metabolismo , Fatores de Risco
13.
Int J Biol Sci ; 16(6): 935-946, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32140063

RESUMO

Lymphoma is a malignant disease of the hematopoietic system that typically affects B cells. The up-regulation of miR-148b is associated with radiosensitization in B-cell lymphoma (BCL). This study aimed to explore the role of miR-148b in regulating the radiosensitivity of BCL cells and to investigate the underlying mechanism. miR-148b directly targeted Bcl-w, decreased the cell viability and colony formation, while promoted apoptosis, in irradiated BCL cells. These changes were accompanied by decreased mitochondrial membrane potential, release of cytochrome C, increased levels of the cleaved caspase 9 and caspase 3, and increased expression of other proteins related to the mitochondrial apoptosis pathway. These effects of miR-148b were effectively inhibited by Bcl-w. In addition, miR-148b inhibited the growth of tumors in nude mice implanted with xenografts of irradiated Raji cells. In patients with BCL, levels of miR-148b were downregulated, while levels of Bcl-w were upregulated; a significant negative correlation between levels of miR-148b and Bcl-w was confirmed. Taken together, these experiments showed that miR-148b promoted radiation-induced apoptosis in BCL cells by targeting anti-apoptotic Bcl-w. miR-148b might be used as a marker to predict the radiosensitivity of BCL.

14.
J Vasc Access ; 21(5): 680-686, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31960762

RESUMO

OBJECTIVES: The purpose of this research is to describe and understand nurses' knowledge of drug-induced peripherally inserted central catheter obstruction management in developing countries. This research aims to identify the reasons why nurses lack knowledge of the management of drug-induced peripherally inserted central catheter obstruction and do not use the drug-induced peripherally inserted central catheter obstruction management techniques recommended by the Infusion Therapy Standards of Practice. METHODS: The descriptive phenomenological method was used to investigate nurses' knowledge of the management of drug-induced peripherally inserted central catheter obstruction. Semi-structured in-depth interviews with 17 nurses from three hospitals in northeast China were used in this qualitative study. Data collection and analysis were conducted simultaneously during the research. Nvivo software 12.0 was used to organize and code the data, and Colaizzi's seven phases of data analysis were used to form themes. FINDINGS: The findings showed that there is inconsistency in nurses' knowledge of drug-induced peripherally inserted central catheter obstruction and its management, and we suggest reasons for this phenomenon. CONCLUSION: This research has shown that inconsistent practice in the management of drug-induced peripherally inserted central catheter obstruction is a more complex issue than originally thought. These inconsistencies are related to time pressure on nurses, nurses' knowledge of peripherally inserted central catheter obstruction, and limitations of the clinical work model.


Assuntos
Atitude do Pessoal de Saúde , Obstrução do Cateter/etiologia , Cateterismo Venoso Central/efeitos adversos , Cateterismo Periférico/efeitos adversos , Cateteres de Demora , Cateteres Venosos Centrais , Conhecimentos, Atitudes e Prática em Saúde , Recursos Humanos de Enfermagem no Hospital/psicologia , Preparações Farmacêuticas/administração & dosagem , Adulto , Cateterismo Venoso Central/instrumentação , Cateterismo Periférico/instrumentação , China , Composição de Medicamentos , Feminino , Humanos , Infusões Intravenosas , Entrevistas como Assunto , Preparações Farmacêuticas/química , Padrões de Prática em Enfermagem , Pesquisa Qualitativa , Fatores de Risco , Fatores de Tempo , Viscosidade , Carga de Trabalho
15.
Int J Biol Macromol ; 150: 1061-1071, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31743716

RESUMO

The sericin protein from silk-processing waste added to the normal diet at 0.8% (g%) level was administered orally to type 2 diabetic (T2D) mice to investigate its hypoglycaemic effects and mechanism. The oral protein is in the form of silk sericin hydrolysate, obtained from a boiling treatment of 0.025% calcium hydroxide solution. The protein significantly decreased fasting blood glucose, fasting plasma insulin, and glycosylated serum protein levels; improved oral glucose tolerance and insulin tolerance, and enhanced antioxidative activities. The protein could ameliorate the pathological damage in pancreatic ß-cells and the liver tissue. It enhanced the expression of key proteins and enzymes, including insulin receptor, insulin receptor substrate, PI3K, phosphorylated-AKT, hepatic kinase, GLUT4, glycogen synthase, GSK3ß, GLK, PFK1, PKM2, and AMPKα, which are related to insulin metabolism and glycolysis. The protein also reduced the expression of G6Pase, PCK, and ACC, which are related to gluconeogenesis and lipid metabolism in the liver, and decreased the expression of TNF-α, IL-6, P65, and IKKß related to inflammation. In general, sericin could maintain normal glucose levels and regulate insulin secretion, insulin and lipid metabolism, and inhibition of inflammation. Therefore, sericin protein could be developed into a novel functional health food with significantly hypoglycaemic effect.

16.
Int J Cancer ; 146(8): 2130-2138, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-31265136

RESUMO

A small number of circulating proteins have been reported to be associated with breast cancer risk, with inconsistent results. Herein, we attempted to identify novel protein biomarkers for breast cancer via the integration of genomics and proteomics data. In the Breast Cancer Association Consortium (BCAC), with 122,977 cases and 105,974 controls of European descendants, we evaluated the associations of the genetically predicted concentrations of >1,400 circulating proteins with breast cancer risk. We used data from a large-scale protein quantitative trait loci (pQTL) analysis as our study instrument. Summary statistics for these pQTL variants related to breast cancer risk were obtained from the BCAC and used to estimate odds ratios (OR) for each protein using the inverse-variance weighted method. We identified 56 proteins significantly associated with breast cancer risk by instrumental analysis (false discovery rate <0.05). Of these, the concentrations of 32 were influenced by variants close to a breast cancer susceptibility locus (ABO, 9q34.2). Many of these proteins, such as insulin receptor, insulin-like growth factor receptor 1 and other membrane receptors (OR: 0.82-1.18, p values: 6.96 × 10-4 -3.28 × 10-8 ), are linked to insulin resistance and estrogen receptor signaling pathways. Proteins identified at other loci include those involved in biological processes such as alcohol and lipid metabolism, proteolysis, apoptosis, immune regulation and cell motility and proliferation. Consistent associations were observed for 22 proteins in the UK Biobank data (p < 0.05). The study identifies potential novel biomarkers for breast cancer, but further investigation is needed to replicate our findings.


Assuntos
Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Locos de Características Quantitativas
17.
J Natl Cancer Inst ; 112(3): 295-304, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31143935

RESUMO

BACKGROUND: DNA methylation plays a critical role in breast cancer development. Previous studies have identified DNA methylation marks in white blood cells as promising biomarkers for breast cancer. However, these studies were limited by low statistical power and potential biases. Using a new methodology, we investigated DNA methylation marks for their associations with breast cancer risk. METHODS: Statistical models were built to predict levels of DNA methylation marks using genetic data and DNA methylation data from HumanMethylation450 BeadChip from the Framingham Heart Study (n = 1595). The prediction models were validated using data from the Women's Health Initiative (n = 883). We applied these models to genomewide association study (GWAS) data of 122 977 breast cancer patients and 105 974 controls to evaluate if the genetically predicted DNA methylation levels at CpG sites (CpGs) are associated with breast cancer risk. All statistical tests were two-sided. RESULTS: Of the 62 938 CpG sites CpGs investigated, statistically significant associations with breast cancer risk were observed for 450 CpGs at a Bonferroni-corrected threshold of P less than 7.94 × 10-7, including 45 CpGs residing in 18 genomic regions, that have not previously been associated with breast cancer risk. Of the remaining 405 CpGs located within 500 kilobase flaking regions of 70 GWAS-identified breast cancer risk variants, the associations for 11 CpGs were independent of GWAS-identified variants. Integrative analyses of genetic, DNA methylation, and gene expression data found that 38 CpGs may affect breast cancer risk through regulating expression of 21 genes. CONCLUSION: Our new methodology can identify novel DNA methylation biomarkers for breast cancer risk and can be applied to other diseases.

18.
J Surg Res ; 245: 265-272, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31421372

RESUMO

BACKGROUND: Although insurance and race-based survival disparities in colon cancer are well studied, little is known regarding how these survival disparities are impacted by type of treating facility. MATERIALS AND METHODS: This is a retrospective cohort study of 433,997 patients diagnosed with colon adenocarcinoma using the National Cancer Database (NCDB). Using Cox proportional hazard analyses, we assessed overall survival (OS) as a function of race, insurance status, and treating facility, after adjusting for demographic and clinical factors. We also assessed differences in OS according to race and insurance status stratified by treating facility type. RESULTS: OS was significantly diminished for blacks (hazard ratio [HR], 1.09; 95% confidence interval [CI], 1.07-1.10; P < 0.001) and increased for patients of other race (primarily Asians; HR, 0.76; 95% CI, 0.74-0.78) compared with whites. Patients with private insurance had improved OS compared with uninsured (HR, 1.28; 95% CI, 1.25-1.31; P < 0.001), Medicaid (HR, 1.35; 95% CI, 1.33-1.38; P < 0.001) and Medicare (HR, 1.13, 95% CI, 1.12-1.15; P < 0.001) patients. Compared with patients treated at comprehensive community programs, patients treated at academic centers (ACs) had improved OS (HR, 0.86; 95% CI, 0.85-0.88; P < 0.001). When stratified by type of treating facility, racial disparities were not mitigated for patients treated at ACs compared with other facilities (P = 0.266 for interaction). At ACs, patients with Medicaid had persistent OS disparities compared with patients with private insurance (HR, 1.12; 95% CI, 1.09-1.15; P < 0.001), although these disparities were significantly diminished compared with patients treated at other facilities (HR, 1.41; 95% CI, 1.38-1.45; P < 0.001). CONCLUSIONS: Other race, private insurance, and treatment at AC were independently associated with improved OS in patients with colon cancer. Medicaid-based, but not race-based, survival disparities are reduced at ACs compared with other facilities.


Assuntos
Centros Médicos Acadêmicos/estatística & dados numéricos , Neoplasias do Colo/terapia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Cobertura do Seguro/estatística & dados numéricos , Medicaid/estatística & dados numéricos , Afro-Americanos/estatística & dados numéricos , Idoso , Neoplasias do Colo/mortalidade , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos/epidemiologia
19.
Anticancer Agents Med Chem ; 19(17): 2108-2119, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31642792

RESUMO

BACKGROUND: Laryngeal Squamous Cell Carcinoma (LSCC) is a malignant epithelial tumor with poor prognosis and its incidence rate increased recently. rLj-RGD3, a recombinant protein cloned from the buccal gland of Lampetra japonica, contains three RGD motifs that could bind to integrins on the tumor cells. METHODS: MTT assay was used to detect the inhibitory rate of viability. Giemsa's staining assay was used to observe the morphological changes of cells. Hoechst 33258 and TUNEL staining assay, DNA ladder assay were used to examine the apoptotic. Western blot assay was applied to detect the change of the integrin signal pathway. Wound-healing assay, migration, and invasion assay were used to detect the mobility of Hep2 cells. H&E staining assay was used to show the arrangement of the Hep2 cells in the solid tumor tissues. RESULTS: In the present study, rLj-RGD3 was shown to inhibit the viability of LSCC Hep2 cells in vitro by inducing apoptosis with an IC50 of 1.23µM. Western blot showed that the apoptosis of Hep2 cells induced by rLj- RGD3 was dependent on the integrin-FAK-Akt pathway. Wound healing, transwells, and western blot assays in vitro showed that rLj-RGD3 suppressed the migration and invasion of Hep2 cells by integrin-FAKpaxillin/ PLC pathway which could also affect the cytoskeleton arrangement in Hep2 cells. In in vivo studies, rLj-RGD3 inhibited the growth, tumor volume, and weight, as well as disturbed the tissue structure of the solid tumors in xenograft models of BALB/c nude mice without reducing their body weights. CONCLUSION: These results suggested that rLj-RGD3 is an effective and safe suppressor on the growth and metastasis of LSCC Hep2 cells from both in vitro and in vivo experiments. rLj-RGD3 might be expected to become a novel anti-tumor drug to treat LSCC patients in the near future.

20.
EBioMedicine ; 48: 203-211, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31629678

RESUMO

BACKGROUND: We previously conducted a systematic field synopsis of 1059 breast cancer candidate gene studies and investigated 279 genetic variants, 51 of which showed associations. The major limitation of this work was the small sample size, even pooling data from all 1059 studies. Thereafter, genome-wide association studies (GWAS) have accumulated data for hundreds of thousands of subjects. It's necessary to re-evaluate these variants in large GWAS datasets. METHODS: Of these 279 variants, data were obtained for 228 from GWAS conducted within the Asian Breast Cancer Consortium (24,206 cases and 24,775 controls) and the Breast Cancer Association Consortium (122,977 cases and 105,974 controls of European ancestry). Meta-analyses were conducted to combine the results from these two datasets. FINDINGS: Of those 228 variants, an association was observed for 12 variants in 10 genes at a Bonferroni-corrected threshold of P < 2·19 × 10-4. The associations for four variants reached P < 5 × 10-8 and have been reported by previous GWAS, including rs6435074 and rs6723097 (CASP8), rs17879961 (CHEK2) and rs2853669 (TERT). The remaining eight variants were rs676387 (HSD17B1), rs762551 (CYP1A2), rs1045485 (CASP8), rs9340799 (ESR1), rs7931342 (CHR11), rs1050450 (GPX1), rs13010627 (CASP10) and rs9344 (CCND1). Further investigating these 10 genes identified associations for two additional variants at P < 5 × 10-8, including rs4793090 (near HSD17B1), and rs9210 (near CYP1A2), which have not been identified by previous GWAS. INTERPRETATION: Though most candidate gene variants were not associated with breast cancer risk, we found 14 variants showing an association. Our findings warrant further functional investigation of these variants. FUND: National Institutes of Health.


Assuntos
Grupo com Ancestrais do Continente Asiático , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Grupo com Ancestrais do Continente Europeu , Predisposição Genética para Doença , Variação Genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Caspase 8 , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Genótipo , Humanos , Razão de Chances , Polimorfismo de Nucleotídeo Único , Vigilância da População , Risco
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