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1.
Cancer Cell Int ; 22(1): 369, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36424596

RESUMO

Renal cell carcinoma (RCC) is one of the most common malignant tumors with a poor response to radiotherapy and chemotherapy. The advent of molecular targeted drugs has initiated great breakthroughs in the treatment of RCC. However, drug resistance to targeted drugs has become an urgent problem. Various studies across the decades have confirmed the involvement of circular RNAs (circRNAs) in multiple pathophysiological processes and its abnormal expression in many malignant tumors. This review speculated that circRNAs can provide a new solution to drug resistance in RCC and perhaps be used as essential markers for the early diagnosis and prognosis of RCC. Through the analysis and discussion of relevant recent research, this review explored the relationship of circRNAs to and their regulatory mechanisms in drug resistance in RCC. The results indicate an association between the expression of circRNAs and the development of RCC, as well as the involvement of circRNAs in drug resistance in RCC.

2.
Neoplasma ; 69(1): 1-15, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34704451

RESUMO

Papillary thyroid carcinoma (PTC) is the most prevalent form of thyroid cancer (TC). There is increasing evidence that circular RNAs play a role in the tumorigenesis of PTC. The aim of our study was to evaluate the potential function of circ_0067934 in PTC and the underlying molecular mechanism. In our study, cell viability assay, quantitative real-time PCR (qRT-PCR), colony formation assay, flow cytometry, wound-healing assay, Transwell invasion assay, western blot, soft agar assay, RNA immunoprecipitation (RIP), dual-luciferase reporter assay, immunohistochemical (IHC) staining, and tumor xenograft formation were conducted to evaluate the effects of circ_0067934 in PTC cells. We found that circ_0067934 was upregulated in PTC tissues and cell lines. Knockdown of circ_0067934 inhibited growth, colony formation, migration, invasion, EMT, and tumor xenograft growth, and induced apoptosis of PTC cells. Moreover, circ_0067934 acted as a molecular sponge for miR-1301-3p, and depletion of miR-1301-3p abrogated the effects of circ_0067934 knockdown in PTC cells. In addition, HMGB1 was a target of miR-1301-3p, and miR-1301-3p overexpression inhibited the malignant effects of PTC cells via suppressing HMGB1. Furthermore, knockdown of circ_0067934 suppressed HMGB1 expression, PI3K/Akt, and MAPK activation by sponging miR-1301-3p. In nude mice, circ_0067934 depletion repressed tumor xenograft growth of PTC cells. In conclusion, our results provided a novel insight into circ_0067934 in the tumorigenesis and progression of PTC. circ_0067934 might be a prognostic marker or therapeutic target for PTC treatment.


Assuntos
Proteína HMGB1 , MicroRNAs , RNA Circular/genética , Neoplasias da Glândula Tireoide , Animais , Linhagem Celular Tumoral , Proliferação de Células , Proteína HMGB1/genética , Humanos , Camundongos , Camundongos Nus , MicroRNAs/genética , Fosfatidilinositol 3-Quinases , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética
3.
Zhongguo Zhong Yao Za Zhi ; 47(22): 5978-5990, 2022 Nov.
Artigo em Zh | MEDLINE | ID: mdl-36471923

RESUMO

Peptide is a compound consisting of 2-50 amino acids, which is intermediate between small molecule and protein. It is characterized by a variety of biological activities, easy absorption, strong specific targeting, and few side effects and has become one of the hotspots in biomedical research in recent years. Chinese medicine contains a large number of peptides. The traditional processing methods such as decocting and boiling can effectively boost peptides to exert their due biological activities. At present, however, the research on Chinese medicinal components in laboratory generally employs high-concentration alcohol extraction method, which may cause the peptides to be ignored in many natural Chinese medicines. Substantial studies have revealed that the peptides in Chinese medicine are important material basis responsible for the traditional efficacy. Based on years of research and literature retrieval, this study put forward the concept of "traditional Chinese medicine(TCM)-peptides", referring to the components consisting of two or more amino acids with molecular weight between small molecules and proteins that can express the efficacy of Chinese medicine. Furthermore, this study also summarized the extraction and separation of TCM-peptides, and structure determination methods and routes, predicted the research prospect of modern research methods of TCM-peptides based on "holistic view" and big data. The artificial intelligence prediction was combined with high-throughput screening technology to improve the discovery efficiency and accuracy of TCM-peptides, and holographic images between TCM-peptides and biological targets were established to provide references for the innovative drug design and related health product development of TCM-peptides based on TCM theories.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Inteligência Artificial , Medicamentos de Ervas Chinesas/química , Projetos de Pesquisa , Peptídeos , Proteínas , Aminoácidos
4.
Gynecol Endocrinol ; 37(6): 541-545, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34027789

RESUMO

OBJECTIVE: To assess possible risk factors for female sexual dysfunction (FSD), aiming especially at smoking in China. METHODS: Female Sexual Function Index (FSFI) for assessing FSD; 621 women (24-75 years) divided into 'group FSD' (FSFI≤ 26.55) and 'group No FSD' (FSFI > 26.55). Univariate and multivariate analysis to detect potential risk factors for FSD. RESULTS: Active smoking was the strongest risk factor after multiple adjustments (OR= 6.226, 95%CI = 1.561 ∼ 24.822), but passive smoking also was significantly associated with a risk of FSD (OR = 1.887, 95%CI = 1.092 ∼ 3.260) (p < .05). Other risk factors included age (OR = 1.040, 95%CI = 1.005 ∼ 1.076), medical comorbidities (OR= 1.688, 95%CI =1.044 ∼ 2.729), postmenopausal stage (OR= 2.021, 95%CI = 1.073 ∼ 5.717), and dissatisfied marital relations (OR= 3.771, 95%CI = 1.768 ∼ 8.045). The prevalence of FSD for smokers regarding disorders of sexual arousal, orgasm and sexual satisfaction increased in active smokers; sexual desire disorder, sexual arousal disorder and pain in secondhand smokers (p < .05). CONCLUSION: The risk of FSD was closely related to depletion of ovarian function. Active smokers had the highest risk, but passive smoking also had a significant relationship to FSD. Although female smokers are rare in China, 'husband smoking' is frequent. Thus, our results should have significant healthcare consequences.


Assuntos
Disfunções Sexuais Fisiológicas/epidemiologia , Disfunções Sexuais Psicogênicas/epidemiologia , Fumar/epidemiologia , Poluição por Fumaça de Tabaco/estatística & dados numéricos , Adulto , Idoso , China/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Disfunções Sexuais Fisiológicas/etiologia , Disfunções Sexuais Psicogênicas/etiologia , Fumar/efeitos adversos , Inquéritos e Questionários , Poluição por Fumaça de Tabaco/efeitos adversos , Adulto Jovem
5.
Gynecol Endocrinol ; 37(3): 264-268, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33084429

RESUMO

OBJECTIVE: To investigate the correlation between abdominal adipose tissue and lumbar bone mineral density (BMD) in different menopausal periods of Chinese women. METHODS: 230 women were included in this cross-sectional study. Subjects were divided into a perimenopausal and postmenopausal group. Lumbar BMD was measured by QCT to assess total adipose tissue (TAT), visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). The concomitant variables age, body mass index (BMI), and endocrine hormones were also considered. Multiple linear regression was used to assess the relationship between abdominal adipose tissue and BMD. RESULTS: In the perimenopausal group, Spearman correlation analysis showed that there was no significant association among TAT, SAT, VAT, and BMD (all p > .05). In the postmenopausal group, BMD was negatively correlated with TAT, SAT, and VAT. In both groups, after adjustment for age and BMI, multiple linear regression analysis showed that VAT was negatively correlated with BMD (p < .05). In contrast, there was no significant correlation with TAT, SAT, and BMD. CONCLUSIONS: High VAT volume is associated with low lumbar BMD in both perimenopausal and postmenopausal women. TAT and SAT have no significant correlation with lumbar trabecular BMD.


Assuntos
Gordura Abdominal/diagnóstico por imagem , Densidade Óssea , Menopausa/fisiologia , Tomografia Computadorizada por Raios X/métodos , Gordura Abdominal/patologia , Adiposidade/fisiologia , Adulto , Idoso , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Pessoa de Meia-Idade
6.
Eur J Contracept Reprod Health Care ; 26(3): 246-254, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33539254

RESUMO

OBJECTIVES: The aims of the study were to investigate female sexual dysfunction (FSD) at different reproductive stages and the effect on FSD of hormone replacement therapy (HRT). METHODS: Participants (N = 524) were divided into six groups according to the Stages of Reproductive Aging Workshop (STRAW + 10): reproductive age (R), early (ET)/late (LT) menopausal transition, early (EP)/late (LP) postmenopause and early postmenopause in women using HRT (EP-HRT; oestradiol sequentially combined with dydrogesterone). The Female Sexual Function Index (FSFI) was used to assess FSD. Univariate and multivariate logistic regression analysis was carried out to predict FSD risk factors. RESULTS: There was an increase in FSD in groups EP and LP, but not in groups R, ET and LT; most FSFI scores were lower in groups EP and LP than in groups R, ET and LT (p < .05). There was no difference in FSD between groups EP and LP, but lubrication and pain scores were higher in group EP (p < .05). The prevalence of FSD was lower in group EP-HRT; most FSFI scores were higher in group EP-HRT compared with group EP as control (p < .05). Further risk factors for FSD were identified as neutral and dissatisfied marital relations, lower educational level and smoking (p < .05). CONCLUSION: We report a clear association between deteriorating sexual function and increasing STRAW + 10 classification, suggesting the consequence of decreasing ovarian function. HRT containing 'natural hormones' was shown to have a beneficial effect on FSD. The results are reported here for the first time in Chinese women.


Assuntos
Terapia de Reposição Hormonal/efeitos adversos , Disfunções Sexuais Fisiológicas/tratamento farmacológico , Disfunções Sexuais Psicogênicas/psicologia , Idoso , China/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Prevalência , Disfunções Sexuais Fisiológicas/epidemiologia , Disfunções Sexuais Fisiológicas/etnologia , Disfunções Sexuais Psicogênicas/epidemiologia , Inquéritos e Questionários
7.
Pharmazie ; 76(4): 172-174, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33849703

RESUMO

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancers. Chemotherapy is the most important therapeutic option for TNBC, and chemotherapy-induced nausea and vomiting (CINV) is inevitable. Metoclopramide is a good and cost-effective therapeutic option for chemotherapy-induced nausea and vomiting. However, it is not commonly used in breast cancer because it can increase serum prolactin levels by blocking dopamine D2 receptor. This study aimed at elucidating the effect of metoclopramide on triple-negative breast cancer, MDA-MB-231 cells were treated with various concentrations of metoclopramide, the cell proliferation was detected by MTT method, the apoptosis rate was detected by Annexin V/PI double staining method, the expression change of death-related protein was detected by Western Blot. We found that metoclopramide inhibits cell proliferation and induces cell apoptosis of MDA-MB-231 in a concentration-dependent manner, and the Bcl family was involved in this process.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Metoclopramida/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral , Antagonistas dos Receptores de Dopamina D2/administração & dosagem , Antagonistas dos Receptores de Dopamina D2/farmacologia , Relação Dose-Resposta a Droga , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Metoclopramida/administração & dosagem , Neoplasias de Mama Triplo Negativas/patologia
8.
Clin Immunol ; 218: 108516, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32574709

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is posing a huge threat to human health worldwide. We aim to investigate the immune status of CD8+ T and NK cells in COVID-19 patients. METHODS: The count and immune status of lymphocytes were detected by flow cytometry in 32 COVID-19 patients and 18 healthy individuals. RESULTS: As the disease progression in COVID-19 patients, CD8+ T and NK cells were significantly decreased in absolute number but highly activated. After patients' condition improved, the count and immune status of CD8+ T and NK cells restored to some extent. GrA+CD8+ T and perforin+ NK cells had good sensitivity and specificity for assisting diagnosis of COVID-19. CONCLUSIONS: As the disease progression, the declined lymphocytes in COVID-19 patients might lead to compensatory activation of CD8+ T and NK cells. GrA+CD8+ T and perforin+ NK cells might be used as meaningful indicators for assisting diagnosis of COVID-19.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Granzimas/genética , Células Matadoras Naturais/imunologia , Perforina/genética , Pneumonia Viral/diagnóstico , Linfócitos T Citotóxicos/imunologia , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/imunologia , Biomarcadores/sangue , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD4-Positivos/virologia , COVID-19 , Teste para COVID-19 , Estudos de Casos e Controles , China , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Progressão da Doença , Feminino , Expressão Gênica , Granzimas/sangue , Granzimas/imunologia , Humanos , Células Matadoras Naturais/patologia , Células Matadoras Naturais/virologia , Ativação Linfocitária , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Perforina/sangue , Perforina/imunologia , Pneumonia Viral/sangue , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Prognóstico , Curva ROC , SARS-CoV-2 , Índice de Gravidade de Doença , Linfócitos T Citotóxicos/patologia , Linfócitos T Citotóxicos/virologia
9.
BMC Womens Health ; 20(1): 75, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32316946

RESUMO

BACKGROUND: Diverticulum, one of the long-term sequelae of cesarean section, can cause abnormal uterine bleeding, dysmenorrhea and chronic pelvic pain. Hysteroscopic resection of diverticula is thought to reduce abnormal uterine bleeding and chronic pelvic pain. In this study, we aim to describe the improvement after hysteroscopic resection of cesarean section diverticula (CSD) in women without childbearing intention, and to explore the variables associated with poor prognosis. METHODS: A retrospective cohort study of women aged 25-48 with CSD diagnosis by transvaginal ultrasonography (TVS) and hysteroscopy that were enrolled at Guangzhou Women and Children's Medical Center between June 2017 and December 2018. A total of 124 women met the inclusion criteria and all patients had undergone hysteroscopic resection and accepted a follow-up interview at the 3rd and 6th months postoperatively to record symptom improvement. RESULT: The mean of intraoperative blood loss and operative time of hysteroscopic resection were (12.94 ± 12.63) ml and (33.63 ± 6.87) min in 124 patients. Overall observed improvement rates of CSD symptom were 47.2 and 65.6% in the first 3 and 6 months, respectively. Multivariable logistic regression models revealed that timing of surgery < 14 days was a good prognostic factor associated with both 3-month improvement (OR, 16.59; 95% CI, 2.62-104.90; P = 0.003) and 6-month improvement (OR, 15.51; 95%CI, 1.63-148.00; P = 0.02); Patients with numbers of cesarean section (CS) ≥2 had a lower rate of improvement after 6 months of CSD repair surgery compared with patients who underwent one CS (OR, 8.29; 95%CI, 1.05-65.75; P = 0.04). CONCLUSIONS: A hysteroscopic repair might be an appropriate method for CSD in women who no childbearing intentions. The timing of surgery and the number of CS seems to be factors influencing the postoperative improvement of CSD.


Assuntos
Cesárea/efeitos adversos , Divertículo/cirurgia , Histeroscopia/métodos , Histeroscopia/estatística & dados numéricos , Doenças Uterinas/cirurgia , Adulto , Criança , China , Cicatriz/cirurgia , Feminino , Procedimentos Cirúrgicos em Ginecologia/métodos , Humanos , Histeroscopia/efeitos adversos , Pessoa de Meia-Idade , Gravidez , Procedimentos de Cirurgia Plástica/métodos , Estudos Retrospectivos , Resultado do Tratamento
10.
Ann Hum Biol ; 47(7-8): 610-619, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33050724

RESUMO

BACKGROUND: Cognitive decline can develop into mild cognitive impairment, a high-risk factor in the progression of Alzheimer's disease. The antioxidant micronutrient selenium may have some effect on preventing cognitive decline, but the association between whole blood selenium concentration and cognitive function remains controversial. AIM: To investigate the association between whole blood selenium concentration and cognitive function score in elderly Americans. SUBJECTS AND METHODS: Data was obtained from the national health and nutrition survey between 2011 and 2014. A general linear model was used to adjust for possible risk factors to analyse the association between blood selenium concentration and cognitive function. RESULTS: 2068 participants were included in our study, and the average blood selenium concentration was high at 195.08 µg/L. The risk of lower cognitive scores was higher in people with lower blood selenium concentration (p < 0.05). The lower cognition may also be associated with one or more of the following characteristics: older, male, had a low poverty-income ratio, low education level, and consumed less alcohol. Related conditions such as stroke, diabetes and high blood pressure may also affect cognitive scores. CONCLUSIONS: Higher blood selenium is associated with higher cognitive scores in elderly Americans.


Assuntos
Cognição , Inquéritos Nutricionais , Selênio/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Estados Unidos
11.
Mol Cancer ; 18(1): 155, 2019 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-31690319

RESUMO

The emergence of immune checkpoint inhibitors (ICIs), mainly including anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) and anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) monoclonal antibodies (mAbs), has shaped therapeutic landscape of some type of cancers. Despite some ICIs have manifested compelling clinical effectiveness in certain tumor types, the majority of patients still showed de novo or adaptive resistance. At present, the overall efficiency of immune checkpoint therapy remains unsatisfactory. Exploring additional immune checkpoint molecules is a hot research topic. Recent studies have identified several new immune checkpoint targets, like lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), T cell immunoglobulin and ITIM domain (TIGIT), V-domain Ig suppressor of T cell activation (VISTA), and so on. The investigations about these molecules have generated promising results in preclinical studies and/or clinical trials. In this review, we discussed the structure and expression of these newly-characterized immune checkpoints molecules, presented the current progress and understanding of them. Moreover, we summarized the clinical data pertinent to these recent immune checkpoint molecules as well as their application prospects.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Biomarcadores Tumorais , Imunomodulação/efeitos dos fármacos , Neoplasias/etiologia , Neoplasias/metabolismo , Animais , Antineoplásicos Imunológicos/uso terapêutico , Antígeno CTLA-4/antagonistas & inibidores , Ensaios Clínicos como Assunto , Humanos , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Resultado do Tratamento
12.
Mol Cancer ; 18(1): 125, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429760

RESUMO

Chimeric antigen receptor T (CAR-T) cell therapy is an emerging and effective cancer immunotherapy. Especially in hematological malignancies, CAR-T cells have achieved exciting results. Two Anti-CD19 CAR-T therapies have been approved for the treatment of CD19-positive leukemia or lymphoma. However, the application of CAR-T cells is obviously hampered by the adverse effects, such as cytokines release syndrome and on-target off-tumor toxicity. In some clinical trials, patients quitted the treatment of CAR-T cells due to life-threatening toxicity. Seeking to alleviate these toxicities or prevent the occurrence, researchers have developed a number of safety strategies of CAR-T cells, including suicide genes, synthetic Notch receptor, on-switch CAR, combinatorial target-antigen recognition, bispecific T cell engager and inhibitory CAR. This review summarized the preclinical studies and clinical trials of the safety strategies of CAR-T cells and their respective strengths and weaknesses.


Assuntos
Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos Quiméricos/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Animais , Humanos , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/normas , Modelos Biológicos , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/terapia , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos Quiméricos/genética , Receptores Notch , Transgenes
13.
Mol Cancer ; 18(1): 60, 2019 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-30925919

RESUMO

Immune checkpoint inhibitor (ICI) activates host's anti-tumor immune response by blocking negative regulatory immune signals. A series of clinical trials showed that ICI could effectively induce tumor regression in a subset of advanced cancer patients. In clinical practice, a main concerning for choosing ICI is the low response rate. Even though multiple predictive biomarkers such as PD-L1 expression, mismatch-repair deficiency, and status of tumor infiltrating lymphocytes have been adopted for patient selection, frequent resistance to ICI monotherapy has not been completely resolved. However, some recent studies indicated that ICI resistance could be alleviated by combination therapy with anti-angiogenesis treatment. Actually, anti-angiogenesis therapy not only prunes blood vessel which is essential to cancer growth and metastasis, but also reprograms the tumor immune microenvironment. Preclinical studies demonstrated that the efficacy of combination therapy of ICI and anti-angiogenesis was superior to monotherapy. In mice model, combination therapy could effectively increase the ratio of anti-tumor/pro-tumor immune cell and decrease the expression of multiple immune checkpoints more than PD-1. Based on exciting results from preclinical studies, many clinical trials were deployed to investigate the synergistic effect of the combination therapy and acquired promising outcome. This review summarized the latest understanding of ICI combined anti-angiogenesis therapy and highlighted the advances of relevant clinical trials.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Sinergismo Farmacológico , Imunoterapia , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Animais , Antígeno B7-H1/antagonistas & inibidores , Humanos , Neoplasias/patologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores
14.
Histochem Cell Biol ; 152(4): 281-291, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31352515

RESUMO

Breast cancer is one of the most prevalent cancers in women. Chemoresistance is a major obstacle for the treatment of breast cancer. We investigated the role of long noncoding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) in paclitaxel (PTX) resistance in breast cancer. CASC2 expression was increased in PTX-resistant clinical samples and cell lines. PTX induced CASC2 expression in a concentration-dependent manner. Downregulation of CASC2 increased PTX toxicity and decreased IC50 value, while upregulation of CASC2 decreased PTX toxicity and increased IC50 value in MCF-7/PTX and MDA-MB-231/PTX cells. Moreover, downregulation of CASC2 decreased tumor growth in xenograft mice implanted with MCF-7/PTX cells. miR-18a-5p possessed a putative binding site in 3'-UTR of CASC2 and cyclin-dependent kinase 19 (CDK19). In PTX-resistant breast cancer cells, miR-18a-5p expression was decreased. CASC2 and miR-18a-5p could negatively regulate the expression of each other. CDK19 expression could be negatively regulated by miR-18a-5p, but positively regulated by CASC2. miR-18a-5p mimics or downregulation of CDK19 decreased tumor growth in xenograft mice implanted with MCF-7/PTX cells. In summary, we identified that CASC2 activated PTX resistance in breast cancer through regulation of miR-18a-5p/CDK19. We highlight the importance of CASC2/miR-18a-5p/CDK19 axis in the chemoresistance of breast cancer and provide potential targets for the improving chemotherapy of breast cancer.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Quinases Ciclina-Dependentes/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , MicroRNAs/metabolismo , Paclitaxel/farmacologia , RNA Longo não Codificante/genética , Animais , Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/genética , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética
15.
Soft Matter ; 15(11): 2311-2314, 2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30672575

RESUMO

Polymers responsive to external stimuli (e.g., electric field, chemical vapor, light) are of great interest for smart materials such as sensors and soft robotics. A vapor-driven multilayer polymer actuator, capable of fast and large-scale actuation, is described here. This Janus-like actuator is prepared with two polyelectrolyte multilayer systems (polyethylenimine (PEI)/poly(acrylic acid) (PAA) and polyurethane (PU)/poly(acrylic acid) (PAA)) using layer-by-layer assembly (LbL). The differing hydrophilicity of these two nanocoatings results in different swelling behavior in water and organic solvents, which leads to vapor-responsive mechanical motion. The bending/curling degree of this polymeric actuator can be precisely controlled by changing the thickness ratio of the two layers. A vapor sensor was constructed to demonstrate the environmental detection ability of this unique actuator.

16.
Sheng Li Xue Bao ; 71(4): 613-624, 2019 Aug 25.
Artigo em Zh | MEDLINE | ID: mdl-31440759

RESUMO

Circular RNAs (circRNAs) are a class of endogenous, covalently closed, single-stranded RNA without 3'-poly(A) and 5'-cap structures. CircRNAs are characterized by universality, diversity, stability and conservation, and have been found to regulate mammalian transcription and be translated into proteins. In this review, we summarized the biogenesis, classification, expression, distribution, biological functions and regulation of circRNAs. In addition, we discussed the association of circRNAs with diseases and the methods for identification and characterization of circRNAs. Finally, we speculated the application prospect and research direction of circRNAs.


Assuntos
RNA/genética , Animais , RNA Circular , Pesquisa/tendências
17.
Mol Cancer ; 17(1): 53, 2018 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-29455669

RESUMO

Tyrosine kinase inhibitors (TKIs)-treatments bring significant benefit for patients harboring epidermal growth factor receptor (EGFR) mutations, especially for those with lung cancer. Unfortunately, the majority of these patients ultimately develop to the acquired resistance after a period of treatment. Two central mechanisms are involved in the resistant process: EGFR secondary mutations and bypass signaling activations. In an EGFR-dependent manner, acquired mutations, such as T790 M, interferes the interaction between TKIs and the kinase domain of EGFR. While in an EGFR-independent manner, dysregulation of other receptor tyrosine kinases (RTKs) or abnormal activation of downstream compounds both have compensatory functions against the inhibition of EGFR through triggering phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) signaling axes. Nowadays, many clinical trials aiming to overcome and prevent TKIs resistance in various cancers are ongoing or completed. EGFR-TKIs in accompany with the targeted agents for resistance-related factors afford a promising first-line strategy to further clinical application.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Biomarcadores Tumorais , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Mutação , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Inibidores de Proteínas Quinases/uso terapêutico
18.
Mod Pathol ; 31(9): 1391-1399, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29752477

RESUMO

Invasive adenocarcinoma intraoperatively misdiagnosed as adenocarcinoma in situ or minimally invasive adenocarcinoma is more likely to undergo potentially insufficient resection. The purpose of our study was to evaluate the diagnostic accuracy of frozen section. We retrospectively reviewed 1,111 lung adenocarcinomas from January to March 2016 to evaluate the diagnostic performance of frozen section. A derivation cohort consisting of 436 cases of adenocarcinoma in situ or minimally invasive adenocarcinoma diagnosed by frozen section in the same period were analyzed to find predictive factors for invasive adenocarcinoma as the final diagnosis. Validation cohorts (first: April to June 2016, second: January to March 2015) were included to confirm the results. The overall concordance rate between frozen section and final diagnosis was 92%. Most frozen section errors were underestimation. The sensitivity of frozen section diagnosis for minimally invasive adenocarcinoma (74%) was significantly lower than others. Intraoperatively measured tumor size was the only independent factor for invasive adenocarcinoma as the final diagnosis (<1 cm: 2%, reference; 1-1.4 cm: 15%, odds ratio, 5.678; > 1.5 cm: 18%, odds ratio, 5.878; P = 0.001) in the derivation cohort, and was confirmed by validation cohorts. Fifty-nine misdiagnosed invasive adenocarcinomas in the three cohorts consisted of 54 lepidic predominant type, 1 papillary and 4 acinar predominant type. There were no positive N1, N2 node, pleural, lymphatic and vascular invasion cases found. Thirty-seven (37/59, 63%) cases of misdiagnosis were attributed to sampling error, which was the main reason. Our study suggests that adenocarcinoma in situ or minimally invasive adenocarcinoma ≥1 cm by frozen section were more likely to be invasive adenocarcinoma because of sampling error. Frozen section diagnosis of adenocarcinoma in situ or minimally invasive adenocarcinoma should be considered cautiously for tumors ≥1 cm to avoid potentially insufficient resection.


Assuntos
Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/patologia , Adenocarcinoma de Pulmão/cirurgia , Feminino , Secções Congeladas , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Retrospectivos , Sensibilidade e Especificidade , Carga Tumoral
19.
Reprod Biomed Online ; 36(3): 361-368, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29352649

RESUMO

The aim of this study was to improve clinical decision-making for the identification of persistent ectopic pregnancy after linear salpingostomy. The study identified 854 laparoscopic salpingostomies performed between 2011 and 2016; 794 had a human chorionic gonadotrophin (HCG) <10 mIU/ml documented in the electronic medical record within 1 month after surgery ('successes'). Sixty (7%) received either methotrexate or repeat surgery for persistent ectopic pregnancy ('failures'). Five hundred and seventeen, including 46 'failures', had two or more immediate post-operative HCG measurements available. The most clinically useful prediction rule was calculated by dividing the difference between the first and second post-operative HCG values by the first post-operative HCG value (i.e. [HCG1 - HCG2]/HCG1). When this ratio exceeded 0.75, it reliably ruled out persistent ectopic with a negative predictive value = 99%. When this ratio was less than 0.2, it identified persistent ectopics with a positive predictive value = 88%. It appears that this simple arithmetic calculation involving two early post-operative HCG values may allow for efficient triage of patients before post-operative day 5. If validated in prospective studies, this could help minimize the risk, inconvenience and expense of requiring several weeks of frequent follow up to rule in/rule out persistent ectopic pregnancy.


Assuntos
Biomarcadores/sangue , Gonadotropina Coriônica/sangue , Laparoscopia/efeitos adversos , Gravidez Ectópica/diagnóstico , Salpingostomia/efeitos adversos , Adulto , Tomada de Decisão Clínica , Feminino , Humanos , Gravidez , Gravidez Ectópica/sangue , Gravidez Ectópica/etiologia , Estudos Retrospectivos
20.
Zhongguo Zhong Yao Za Zhi ; 43(11): 2216-2223, 2018 Jun.
Artigo em Zh | MEDLINE | ID: mdl-29945370

RESUMO

Spatholobi Caulis, the vine stem of Spatholobus suberectus and widely used in China and Southeast Asian nations, has the effects on nourishing the blood and promoting blood flow, regulating menstruation and relieving pain, and invigorating the nerves. Through consulting the herbal textual and local chronicles, we summarized the original textual research and medicinal evolution on Spatholobi Caulis to analyze the changes of varieties in different historical periods. Further, the major active ingredient in Spatholobi Caulis was discussed. According to the literature to date, 60 flavonoids compounds have been isolated and could be divided into isoflavones, dihydroflavones, flavanols, dihydroflavonols, procyaninides, chalcones, pterocarpans, isoflavanols, isoflavanones and aurone according to their molecular structures. These indicative ingredients in Spatholobi Caulis showed pharmacological activities on regulation of the blood system, anti-tumor, anti-oxidation, anti-virus, anti-bacteria and inhibition of melanin deposition. This review will provide reference and basis for the sustainable use of resources and industry development on Spatholobi Caulis.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Fabaceae/química , Flavonoides/análise , China , Humanos , Caules de Planta/química
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