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1.
BMC Cancer ; 23(1): 816, 2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37653504

RESUMO

BACKGROUND: This network meta-analysis aimed to assess the comparative efficacy and safety of combinations involving three cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and endocrine therapies (ETs) in patients with metastatic or advanced breast cancer (BC) who are hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-). METHODS: We initially identified relevant studies from previous meta-analyses and then conducted a comprehensive search of PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases to locate additional studies published between February 2020 and September 2021. Essential data were extracted, and a network meta-analysis was performed using R 4.1.1 software with a random-effects model. Furthermore, we assigned rankings to all available treatment combinations by calculating their cumulative probability. RESULTS: Data analysis included ten reports from nine studies. Pooled results demonstrated that each treatment combination significantly reduced the hazard risk of progression-free survival (PFS) compared to treatment with an aromatase inhibitor (AI) or fulvestrant alone. However, there were no differences observed in PFS or overall survival (OS) among the different treatment combinations. Additionally, patients receiving palbociclib plus AI and abemaciclib plus AI or fulvestrant experienced more severe adverse events (AEs), with hazard ratios (HRs) of 10.83 (95% confidence interval [CI] = 2.3 to 52.51) and 4.8 (95%CI = 1.41 to 16.21), respectively. The HR for ribociclib plus AI was 9.45 (95%CI = 2.02 to 43.61), and the HR for palbociclib plus fulvestrant was 6.33 (95%CI = 1.03 to 39.86). Based on the ranking probabilities, palbociclib plus fulvestrant had the highest probability of achieving superior PFS (37.65%), followed by abemaciclib plus fulvestrant (28.76%). For OS, ribociclib plus fulvestrant ranked first (34.11%), with abemaciclib plus fulvestrant in second place (25.75%). In terms of safety, palbociclib plus AI (53.98%) or fulvestrant (51.37%) had the highest probabilities of being associated with adverse events. CONCLUSIONS: Abemaciclib plus fulvestrant or ribociclib plus AI appear to be effective and relatively safe for the treatment of HR+/HER2- metastatic or advanced BC patients. However, given the reliance on limited evidence, our findings require further validation through additional studies.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Fulvestranto , Metanálise em Rede , Inibidores da Aromatase , Quinase 4 Dependente de Ciclina
2.
Front Oncol ; 13: 1104531, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36910665

RESUMO

Purpose: We used bibliometric methods to evaluate the global scientific output of palliative care breast cancer research and to explore the current status and further research directions in the field over the past decade. Methods: All relevant publications from the year 2012 to 2022 were retrieved from Web of Science. We applied VOSviewer and Bibliometrix R v4.2.1 to obtain information on subject domains, annual publication output and citations, countries and authors with the highest productivity, influential journals and articles, and popular keywords. Results: In total, 1529 publications were included in the final analysis. Health services and supportive care, pain and symptom management were the focus of the research in the field. From the year 2017 to 2021, the annual publication output was abundant and peaked in 2018. The systematic review by Fitzmaurice et al. in 2017 was the most-cited publication. The United States was the leading country with the maximum number of publications, citations, and link strengths with other countries. The most contributing institution was University of Toronto. E. Bruera was the most prolific author, ranking first among the authors in both the H and M index. The journal with the most publications was Palliative & Supportive Care. Keywords analysis indicated that exploring the significant degree of palliative care to reduce anxiety and depression in breast cancer patients may be a good research direction. In addition, how to assess the optimal timing of palliative care interventions and further exploring the specific contradiction between insufficient medical resources and palliative care are also possible research directions. Conclusion: Palliative care plays an important role in the treatment of breast cancer. With the help of a scientometric analysis in this field, researchers can clarify the current research status and hotspots worth fully exploring.

3.
World J Clin Cases ; 10(31): 11338-11348, 2022 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-36387832

RESUMO

BACKGROUND: There are few nomograms for the prognosis of Chinese patients with triple-negative breast cancer (TNBC). AIM: To construct and validate a nomogram for overall survival (OS) of Chinese TNBC patients after surgery. METHODS: This study used the data of SEER*stat 8.3.5 and selected Chinese patients with TNBC operated on between 2010 and 2015. Univariate and multivariate Cox proportional hazard regression models were used. The identified variables were integrated to form a predictive nomogram and risk stratification model; it was assessed with C-indexes and calibration curves. RESULTS: The median and maximal OS of the 336 patients was 39 and 83 mo, respectively. The multivariate analysis showed that age (P = 0.043), marital status (P = 0.040), tumor localization (P = 0.030), grade (P = 0.035), T classification (P = 0.012), and N classification (P = 0.002) were independent prognostic factors. The six variables were combined to construct a 1-, 3- and 5-year OS nomogram. The C-indexes of the nomogram to predict OS were 0.766 and compared to the seventh edition staging system, which was higher (0.766 vs 0.707, P < 0.001). In order to categorize patients into different prognostic groups, a risk stratification model was created. There was a significant difference between the Kaplan-Meier curves of the entire cohort and each disease stage according to the nomogram. CONCLUSION: The nomogram provided prognostic superiority over the traditional tumor, node and metastasis system. It could help clinicians make individual OS or risk predictions for Chinese TNBC patients after surgery.

4.
World J Clin Cases ; 10(26): 9493-9501, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36159419

RESUMO

BACKGROUND: The bone is the second most common site of thyroid cancer metastasis, after the lung. Treatment options for bone metastasis of thyroid cancer include surgery, radioiodine therapy (RAIT), external radiation therapy, thyroid-stimulating hormone (TSH) inhibition, bisphosphonates, and small-molecule targeted therapies. In most cases, thyroid carcinoma is found in the thyroid tissue; reports of follicular thyroid carcinoma with a single metastasis to the lumbar spine are rare. CASE SUMMARY: We report a case of bone metastasis as the only clinical manifestation of thyroid cancer. The patient was a 67-year-old woman with lumbar pain for 7 years and aggravation with intermittent claudication who had previously undergone partial thyroidectomy of a benign thyroid lesion. No abnormal nodules were found in the bilateral thyroid glands. However, imaging studies were consistent with a spinal tumor, and the lesion was diagnosed as a metastatic follicular carcinoma of thyroid origin. We adopted a multidisciplinary collaboration and comprehensive treatment approach. The patient underwent lumbar spine surgery, total resection of the thyroid, postoperative TSH suppression therapy, and RAIT. There were no complications associated with the operation, and the patient had good postoperative recovery. She has experienced no recurrence. CONCLUSION: Follicular thyroid carcinoma is associated with early hematogenous metastasis, and the bone is a typical site of metastasis. Single bone metastasis is not a contraindication to medical procedures, and providing the appropriate therapy can result in better outcomes and quality of life for these patients.

5.
Front Endocrinol (Lausanne) ; 13: 939048, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35957836

RESUMO

Background and Objective: Previous studies determined the therapeutic effects of capecitabine-based chemotherapy regimens on early-stage triple-negative breast cancer (TNBC). However, the optimal strategy of capecitabine-based chemotherapy remains uncertain. We conducted this network meta-analysis to address this issue. Methods: We systematically searched PubMed, Embase, and the Cochrane Registry of Controlled Trials (CENTRAL) to retrieve eligible studies published before September 2021. Two independent reviewers extracted information from eligible studies using a pre-designed data extraction sheet. The primary outcome included disease-free survival, and the second outcome showed overall survival and adverse events. Direct meta-analysis was performed using RevMan 5.4, and Bayesian network analysis was performed using R version 3.6.1 with the "gemtc" and "rjags" packages. Results: Nine studies involving 3661 TNBC patients met the selection criteria. The network meta-analysis suggested that the addition of capecitabine to adjuvant chemotherapy achieved a significantly longer disease-free (HR = 0.66, 95% CrI = 0.49 to 0.86) and overall survival time (HR = 0.60, 95% CrI = 0.43 to 0.83) than standard chemotherapy. All comparisons did not achieve statistical significance. The addition of capecitabine to adjuvant chemotherapy was the most effective treatment for improving disease-free (81.24%) and overall survival (78.46%) times, and the replacement of capecitabine to adjuvant chemotherapy was the safest regime. Conclusions: Based on available evidence, capecitabine-based chemotherapy benefits TNBC patients, and the addition of capecitabine with adjuvant chemotherapy was the most effective regime. In contrast, the replacement of capecitabine to adjuvant chemotherapy was the safest regime. More studies of high quality and large scale are needed to confirm our findings.


Assuntos
Capecitabina , Neoplasias de Mama Triplo Negativas , Teorema de Bayes , Capecitabina/efeitos adversos , Capecitabina/uso terapêutico , Quimioterapia Adjuvante , Humanos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
6.
Front Endocrinol (Lausanne) ; 13: 887612, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35800434

RESUMO

Recently, the androgen receptor has been found as a potential prognostic index and therapeutic target for breast cancer. To reveal the current research status and hotspots in this area, we analyzed the characteristics of related publications from 2011 to 2020. All related publications from 2011 to 2020 were retrieved from the Web of Science. Biblioshiny, VOSviewer, and CiteSpace V were applied to obtain the information on annual publications and citations, the highest yielding countries and authors, influential journals and articles, as well as hot keywords. In total, 2,118 documents, including 1,584 original articles and 534 reviews, were retrieved. Annual publication output was rich from 2014 to 2018, reaching the top in 2017. A systematic review written by Lehman et al. in 2011 was the most-cited document and reference. The United States was the leading country with the maximum number of publications, citations, and link strengths with other countries. The journal publishing the most was Oncotarget. Lehmann was the author who had the highest link strengths with other authors. The most highlighted keywords were "androgen receptor" (n = 1,209), "breast cancer" (n = 690), "expression" (n = 545), "breast cancer" (n = 410), "prostate cancer" (n = 290), and so on, revealing the trend from molecular mechanism level to therapeutic use level. The androgen receptor plays a significant role in the development of breast cancers, whereas its therapeutic value seems to be controversial and needs further study. With the help of a scientometric analysis in this field, researchers can clarify the current research status and hotspots worth fully exploring.


Assuntos
Bibliometria , Neoplasias da Mama , Androgênios , Feminino , Humanos , Estados Unidos
7.
Genetica ; 150(5): 299-316, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35536451

RESUMO

Breast cancer is a devastating malignancy, among which the luminal A (LumA) breast cancer is the most common subtype. In the present study, we used a comprehensive bioinformatics approach in the hope of identifying novel prognostic biomarkers for LumA breast cancer patients. Transcriptomic profiling of 611 LumA breast cancer patients was downloaded from TCGA database. Differentially expressed genes (DEGs) between tumor samples and controls were first identified by differential expression analysis, before being used for the weighted gene co-expression network analysis. The subsequent univariate Cox regression and LASSO algorithm were used to uncover key prognostic genes for constructing multivariate Cox regression model. Patients were stratified into high-risk and low-risk groups according to the risk score, and subjected to multiple downstream analyses including survival analysis, gene set enrichment analysis (GSEA), inference on immune cell infiltration and analysis of mutation burden. Receiving operator curve analysis was also performed. A total of 7071 DEGs were first identified by edgeR package, pink module was found significantly associated with invasive lobular carcinoma (ILC). 105 prognostic genes and 9 predictors were identified, allowing the identification of a 5-key prognostic genes (LRRC77P, CA3, BAMBI, CABP1, ATP8A2) after intersection. These 5 genes, and the resulting Cox model, displayed good prognostic performance. Furthermore, distinct differences existed between two risk-score stratified groups at various levels. The identified 5-gene prognostic model will help deepen the understanding of the molecular and immunological mechanisms that affect the survival of LumA-ILC patients and guide and proper monitoring of these patients.


Assuntos
Neoplasias da Mama , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Biologia Computacional , Feminino , Perfilação da Expressão Gênica , Humanos , Fatores de Risco
8.
Front Oncol ; 12: 1002667, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36713507

RESUMO

In recent years, anti-PD-1/anti-PD-L1 has been considered to be a valuable therapeutic target and prognostic indicator for triple-negative breast cancer. We analyzed all publications published in the field from their inception until the present day in order to determine the current research status and hotspots. All related publications were searched on the Web of Science. Our research used R-studio (bibliometrix package), VOSviewer, and CiteSpace to analyze and obtain annual publications and citation information, articles, highest publication countries and affiliations, influential journals and authors, keyword analysis, and keyword bursts. In total, 851 documents were retrieved including 628 articles and 223 review articles. The output of publications increased year by year from 2013 to 2021. However, the average article citation times reached the top in 2014 but generally showed a downward trend from 2014 to 2021. It was an article written by Schmid et al. in 2018 that received the most citations. With regard to publications, citations, and link strength, among the top countries was the United States. Cancers was the most published journal. Schmid and Loi ranked top in total citations and h-index. Schmid has the largest M-index and Loi has the most publication. The keywords that received the most attention were "Immunotherapy", "PD-L1", "Triple-negative breast cancer", "Tumor-infiltrating lymphocytes", and "Expression". According to the report, this current research focuses on immunotherapy for triple-negative breast cancer and the expression of PD-L1 and tumor-infiltrating lymphocytes (TILs). Pembrolizumab and Atezolizumab plus chemotherapy have completed the Phase 3 clinical trial. However, the biomarkers were limited in predicting the treatment prognosis. Through the scientometric analysis, we can understand the current research status and potential research points in this filed and provide research direction for researchers.

9.
World J Clin Cases ; 9(33): 10345-10354, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34904109

RESUMO

BACKGROUND: Studies have shown that patients with chronic renal failure (CRF) are more likely to suffer from breast cancer and other malignant tumors. To our knowledge, CRF can reduce drug excretion, thereby increase drug exposure and lead to increased toxicity, which will limit drug treatment and lead to tumor progression. Currently, there are few successful reports on the combination of docetaxel, trastuzumab, and pertuzumab (THP) as a neoadjuvant treatment regimen for breast cancer patients with CRF. CASE SUMMARY: We report a breast cancer (cT2N2M0, Her-2+/HR-) patient with CRF. It was a clinical stage IIIA tumor on the left breast. The patient had suffered from uremia for 2 years, and her heart function was normal. Based on the pathological type, molecular type, and clinical stage of breast cancer, and the patient's renal function, the clinician analyzed the pharmacological and pharmacokinetic characteristics of the antitumor drugs after consulting the relevant literature, and prescribed the neoadjuvant regimen of THP (docetaxel 80 mg/m², trastuzumab 8 mg/kg for the first dose, and 6 mg/kg for the maintenance dose with pertuzumab 840 mg for the first dose and 420 mg for the maintenance dose), once every 3 wk, for a total of 6 courses. The neoadjuvant treatment had a good effect, and the patient then underwent surgery which was uneventful. CONCLUSION: CRF is not a contraindication for systemic treatment and surgery of breast cancer. The THP regimen without dose adjustment may be a safe and effective neoadjuvant treatment for HER-2 positive breast cancer patients with CRF.

10.
Front Genet ; 12: 710412, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34737762

RESUMO

Thyroid cancer (THCA) is a common endocrine malignancy. With increasing incidence and low mortality, balancing the therapeutic approach is an inevitable issue. This study aimed to confirm the role of miR-222-3p and its target genes in THCA survival and immune infiltration. From different expression analyses based on the GEO and TCGA databases, we predicted and subsequently identified the key target genes of miR-222-3p. We then explored the expression, enrichment, pairwise correlation, protein expression, survival analysis, principal component analysis, and immune significance of the critical genes using bioinformatics analysis. The present study demonstrated that NEGR1, NTNG1, XPNPEP2, NTNG2, CD109, OPCML, and PRND are critical genes. The miR-222-3p was highly expressed, probably leading to low NEGR1 and high PRND expression in THCA tissues. Low NEGR1 expression indicated favorable prognosis in THCA patients, and high PRND expression indicated poor prognosis. Seven critical genes were significantly related to gender, age, race, tumor stage, and lymph node metastasis. In addition, the seven-gene biomarker exhibited a certain diagnostic value. Finally, CD109 expression was closely correlated with immune cells, especially B cells and CD4+ T cells. The miR-222-3p and its critical target genes could be promising biomarkers for the prognosis of THCA and may emerge as key regulators of immune infiltration in THCA.

11.
Front Cell Dev Biol ; 9: 703537, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650968

RESUMO

Tumor-derived exosomes, containing multiple nucleic acids and proteins, have been implicated to participate in the interaction between tumor cells and microenvironment. However, the functional involvement of phosphatases in tumor-derived exosomes is not fully understood. We and others previously demonstrated that protein tyrosine phosphatase receptor type O (PTPRO) acts as a tumor suppressor in multiple cancer types. In addition, its role in tumor immune microenvironment remains elusive. Bioinformatical analyses revealed that PTPRO was closely associated with immune infiltration, and positively correlated to M1-like macrophages, but negatively correlated to M2-like macrophages in breast cancer tissues. Co-cultured with PTPRO-overexpressing breast cancer cells increased the proportion of M1-like tumor-associated macrophages (TAMs) while decreased that of M2-like TAMs. Further, we observed that tumor-derived exosomal PTPRO induced M1-like macrophage polarization, and regulated the corresponding functional phenotypes. Moreover, tumor cell-derived exosomal PTPRO inhibited breast cancer cell invasion and migration, and inactivated STAT signaling in macrophages. Our data suggested that exosomal PTPRO inhibited breast cancer invasion and migration by modulating macrophage polarization. Anti-tumoral effect of exosomal PTPRO was mediated by inactivating STAT family in macrophages. These findings highlight a novel mechanism of tumor invasion regulated by tumor-derived exosomal tyrosine phosphatase, which is of translational potential for the therapeutic strategy against breast cancer.

12.
Front Oncol ; 11: 689562, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34094989

RESUMO

BACKGROUND: The burden of breast cancer has been increasing globally. The epidemiology burden and trends need to be updated. This study aimed to update the burden and trends of breast cancer incidences, deaths, and disability-adjusted life-years (DALYs) from 1990 to 2019, using the Global Burden of Disease 2019 study. METHODS: The data of incidences, deaths, DALYs, and age-standardized rates were extracted. Estimated annual percentage changes were used to quantify the trends of age-standardized rates. Besides, the population attributable fractions of the risk factors of breast cancer were also estimated. RESULTS: Globally, the incidences of breast cancer increased to 2,002,354 in 2019. High social-development index (SDI) quintiles had the highest incidence cases with a declining trend in age-standardized incidence rate. In 2019, the global deaths and DALYs of breast cancer increased to 700,660 and 20,625,313, respectively. From 1990 to 2019, the age-standardized mortality rates and age-standardized DALY rates declined globally, especially in high and high-middle SDI quintiles. Besides, the trends varied from different regions and countries. The proportion of the patients in the 70+ years age group increased globally. Deaths of breast cancer attributable to high fasting plasma glucose and high body mass index increased globally, and high fasting plasma glucose was the greatest contributor to the global breast cancer deaths. CONCLUSION: The burden of breast cancer in higher SDI quintiles had gone down while the burden was still on the rise in lower SDI quintiles. It is necessary to appeal to the public to decrease the exposure of the risk factors.

13.
Biosci Rep ; 41(2)2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33554245

RESUMO

OBJECTIVE: To identify immune-related long non-coding RNAs (lncRNAs) in papillary thyroid cancer (PTC). METHODS: The Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to obtain the gene expression profile. Immune-related lncRNAs were screened from the Molecular Signatures Database v4.0 (MsigDB). We performed a survival analysis of critical lncRNAs. Further, the function of prognostic lncRNAs was inferred using the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) to clarify the possible mechanisms underlying their predictive ability. The assessment was performed in clinical samples and PTC cells. RESULTS: We obtained 4 immune-related lncRNAs, 15 microRNAs (miRNAs), and 375 mRNAs as the key mediators in the pathophysiological processes of PTC from the GEO database. Further, Lasso regression analysis identified seven prognostic markers (LINC02550, SLC26A4-AS1, ACVR2B-AS1, AC005479.2, LINC02454, and AL136366.1), most of which were related to tumor development. The KEGG pathway enrichment analysis showed different, changed genes mainly enriched in the cancer-related pathways, PI3K-Akt signaling pathway, and focal adhesion. Only SLC26A4-AS1 had an intersection in the results of the two databases. CONCLUSION: LncRNA SLC26A4-AS1, which is the most associated with prognosis, may play an oncogenic role in the development of PTC.


Assuntos
RNA Longo não Codificante/análise , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Proliferação de Células/genética , Progressão da Doença , Humanos , Prognóstico , RNA/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/imunologia
14.
Cell Cycle ; 19(21): 2811-2825, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33054543

RESUMO

Circular RNAs (circRNAs) are a class of widely expressed noncoding RNA with significant regulatory potential discovered in recent years. The purpose of this study was to investigate the effects of hsa_circ_0001785 on the proliferation, migration and invasion of breast cancer (BC) cells in vivo and in vitro and the potential underlying molecular mechanism. In the present study, the expressions of hsa_circ_0001785 in five BC cells (T47D, MCF-7, MDA-MB-453, MDA-MB-231 and BT-549) and one normal breast cell (MCF-10A) were the first to examined by qRT-PCR. Then, we studied the biological function of hsa_circ_0001785 in BC by in vivo and in vitro experiments. CCK-8, clone formation, wound-healing and Transwell assays were performed to analyze the cellular proliferation, migration and invasion in vitro. The subcutaneous tumor model of nude mice was used for in vivo experiment. In addition, we determined that hsa_circ_0001785 acted as competing endogenous RNAs (ceRNAs) in BC by RNA immunoprecipitation (RIP) and dual-luciferase reporter assays. Results showed that the expressions of hsa_circ_0001785 were decreased in BC cells. Hsa_circ_0001785 overexpression inhibited the proliferation, migration, invasion of BC cells and tumor growth in nude mice. RIP and dual-luciferase reporter assay demonstrated that hsa_circ_0001785 could regulate the SOCS3 by sponging miR-942. In general, circular RNA hsa_circ_0001785 inhibits the proliferation, migration and invasion of BC cells by modulating the miR-942/SOCS3 signaling axis.


Assuntos
Neoplasias da Mama/genética , Movimento Celular/genética , Proliferação de Células/genética , MicroRNAs/genética , RNA Circular/genética , Proteína 3 Supressora da Sinalização de Citocinas/genética , Regulação para Cima/genética , Animais , Apoptose/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais/genética
15.
Gastroenterol Res Pract ; 2020: 4043871, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32454814

RESUMO

AIM: A lower ratio of creatinine to body weight (Cr/BW) is considered the independent risk factor for incident nonalcoholic fatty liver disease (NAFLD). However, the relationship between the Cr/BW ratio and NAFLD among individuals without obesity and dyslipidemia and how this relationship is impacted by age are still ambiguous. Therefore, we explored the effect of the Cr/BW ratio on the incident NAFLD among Chinese without obesity and dyslipidemia of different age groups. METHODS: A total of 9756 participants without NAFLD at baseline were included and grouped by the median value (1.32) of the Cr/BW ratio. Then, a further analysis was stratified by age (60 years old). The primary outcome was new-onset NAFLD. RESULTS: After a median follow-up of 2.76 years, 844 (8.7%) participants developed NAFLD. The elderly had a higher person-years incidence rate and cumulative incidence rate than the nonelderly. A high Cr/BW ratio showed a lower cumulative incidence compared to a low Cr/BW ratio for the whole population (P = 0.039) and the nonelderly group (P = 0.008). After being adjusted for multivariate variables, the lower Cr/BW ratio was the independent risk factor for incident NAFLD in the nonelderly (HR 0.718, 95% CI 0.548-0.942), instead of the elderly. CONCLUSIONS: The Cr/BW ratio has a negative relationship with incident NAFLD among nonobese Chinese without dyslipidemia before the age of 60.

16.
J Nanobiotechnology ; 17(1): 123, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31847857

RESUMO

BACKGROUND: Nanomedicine is a promising new approach to cancer treatment that avoids the disadvantages of traditional chemotherapy and improves therapeutic indices. However, the lack of a real-time visualization imaging technology to monitor drug distribution greatly limits its clinical application. Image-tracked drug delivery is of great clinical interest; it is useful for identifying those patients for whom the therapy is more likely to be beneficial. This paper discusses a novel nanomedicine that displays features of nanoparticles and facilitates functional magnetic resonance imaging but is challenging to prepare. RESULTS: To achieve this goal, we synthesized an acylamino-containing amphiphilic block copolymer (polyethylene glycol-polyacrylamide-polyacetonitrile, PEG-b-P(AM-co-AN)) by reversible addition-fragmentation chain transfer (RAFT) polymerization. The PEG-b-P(AM-co-AN) has chemical exchange saturation transfer (CEST) effects, which enable the use of CEST imaging for monitoring nanocarrier accumulation and providing molecular information of pathological tissues. Based on PEG-b-P(AM-co-AN), a new nanomedicine PEG-PAM-PAN@DOX was constructed by nano-precipitation. The self-assembling nature of PEG-PAM-PAN@DOX made the synthesis effective, straightforward, and biocompatible. In vitro studies demonstrate decreased cytotoxicity of PEG-PAM-PAN@DOX compared to free doxorubicin (half-maximal inhibitory concentration (IC50), mean ~ 0.62 µg/mL vs. ~ 5 µg/mL), and the nanomedicine more efficiently entered the cytoplasm and nucleus of cancer cells to kill them. Further, in vivo animal experiments showed that the nanomedicine developed was not only effective against breast cancer, but also displayed an excellent sensitive CEST effect for monitoring drug accumulation (at about 0.5 ppm) in tumor areas. The CEST signal of post-injection 2 h was significantly higher than that of pre-injection (2.17 ± 0.88% vs. 0. 09 ± 0.75%, p < 0.01). CONCLUSIONS: The nanomedicine with CEST imaging reflects the characterization of tumors and therapeutic functions has great potential medical applications.


Assuntos
Acrilamidas/síntese química , Antineoplásicos/química , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/química , Nanocápsulas/química , Polímeros/síntese química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Sobrevivência Celular , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Feminino , Corantes Fluorescentes/química , Humanos , Imageamento por Ressonância Magnética/métodos , Camundongos , Camundongos Nus , Imagem Óptica/métodos , Distribuição Tecidual
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