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1.
J Gene Med ; 26(1): e3572, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37525871

RESUMO

BACKGROUND: The physiological and immunological characteristics of the tumor microenvironment (TME) have a profound impact on the effectiveness of immunotherapy. The present study aimed to define the TME subtype of osteosarcoma according to the signatures representing the global TME of the tumor, as well as create a new prognostic assessment tool to monitor the prognosis, TME activity and immunotherapy response of patients with osteosarcoma. METHODS: The enrichment scores of 29 functional gene expression signatures in osteosarcoma samples were calculated by single sample gene set enrichment analysis (ssGSEA). TME classification of osteosarcoma was performed and a prognostic assessment tool was created based on 29 ssGSEA scores to comprehensively correlate them with TME components, immunotherapy efficacy and prognosis of osteosarcoma. RESULTS: Three TME subtypes were generated that differed in survival, TME activity and immunotherapeutic response. Four differentially expressed genes between TME subtypes were involved in the development of prognostic assessment tools. The established prognosis assessment tool had strong performance in both training and verification cohorts, could be effectively applied to the survival prediction of samples of different ages, genders and transfer states, and could well distinguish the TME status of different samples. CONCLUSIONS: The present study describes three different TME phenotypes in osteosarcoma, provides a risk stratification tool for osteosarcoma prognosis and TME status assessment, and provides additional information for clinical decision-making of immunotherapy.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Feminino , Masculino , Prognóstico , Microambiente Tumoral/genética , Osteossarcoma/diagnóstico , Osteossarcoma/genética , Osteossarcoma/terapia , Fenótipo , Imunoterapia , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/genética , Neoplasias Ósseas/terapia
2.
J Transl Med ; 22(1): 32, 2024 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-38184596

RESUMO

BACKGROUND: Chimeric antigen receptor (CAR) T cells have shown significant activity in B-lineage malignancies. However, their efficacy in myeloid leukemia has not been successful due to unclear molecular mechanisms. METHODS: We conducted in vitro and in vivo experiments to investigate whether myeloid leukemia cells directly induce CAR down-regulation. Furthermore, we designed a CD33 CARKR in which all lysines in the cytoplasmic domain of CAR were mutated to arginine and verified through in vitro experiments that it could reduce the down-regulation of surface CARs and enhance the killing ability. Transcriptome sequencing was performed on various AML and ALL cell lines and primary samples, and the galectin-1-specific inhibitory peptide (anginex) successfully rescued the killing defect and T-cell activation in in vitro assays. RESULTS: CAR down-regulation induced by myeloid leukemia cells under conditions of low effector-to-tumor ratio, which in turn impairs the cytotoxicity of CAR T cells. In contrast, lysosomal degradation or actin polymerization inhibitors can effectively alleviate CAR down-regulation and restore CAR T cell-mediated anti-tumor functions. In addition, this study identified galectin-1 as a critical factor used by myeloid leukemia cells to induce CAR down-regulation, resulting in impaired T-cell activation. CONCLUSION: The discovery of the role of galectin-1 in cell surface CAR down-regulation provides important insights for developing strategies to restore anti-tumor functions.


Assuntos
Galectina 1 , Leucemia Mieloide , Humanos , Galectina 1/genética , Galectinas , Linhagem Celular , Linfócitos T
3.
BMC Musculoskelet Disord ; 22(1): 6, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397328

RESUMO

BACKGROUND: To explore the influencing factors of perioperative hidden blood loss in intertrochanteric fractures. METHOD: We undertook a retrospective analysis from January 2016 to October 2019. Clinical data of 118 patients with intertrochanteric fractures were included. Hidden blood loss was calculated from the haematocrit changes before and after surgery using the Gross equation based on height, weight, and haematocrit (HCT) changes before and after surgery. Patients' gender, age, presence of underlying diseases, fracture types, anaesthesia methods, time from injury to surgery, administration of antiplatelet drugs within 6 months before surgery, use of anticoagulant drugs after surgery, and bone density were statistically analysed. Factors having an effect on hidden blood loss were screened out. Then, hidden blood loss was used as the dependent variable, and each influencing factor was used in turn as the independent variable. Multivariate linear regression analysis was employed to analyse the related risk factors that affect hidden blood loss during the perioperative period of patients with intertrochanteric fractures. RESULT: The apparent blood loss during the operation was 203.81 ±105. 51 ml, and the hidden blood loss was 517.55±191.47 ml. There were significant differences in the hidden blood loss of patients with different fracture types (stable vs unstable), anaesthesia methods (general anaesthesia vs intraspinal anaesthesia), antiplatelet or postoperative anticoagulant drugs, and bone densities (P< 0.05). 05). Multiple linear regression analysis showed that internal fixation, age, fracture type, anaesthesia method, anticoagulant application, and bone density were related risk factors that affected hidden blood loss during the surgical treatment of intertrochanteric fractures. CONCLUSION: Hidden blood loss is the main cause of perioperative blood loss in intertrochanteric fractures, and the risk factors for hidden blood loss include internal fixation, fracture type (e.g., unstable), anaesthesia (e.g., intraspinal), and use of anticoagulant drugs. Specifically, we found that low bone density was a risk factor for hidden blood loss. It is not reliable to use apparent blood loss as the basis for fluid replacement and transfusion. We must fully consider the existence of hidden blood loss and intervene as soon as possible to prevent complications. LEVEL OF EVIDENCE: III.


Assuntos
Fraturas do Fêmur , Fraturas do Quadril , Perda Sanguínea Cirúrgica/prevenção & controle , Densidade Óssea , Pinos Ortopédicos , Fraturas do Quadril/diagnóstico por imagem , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/cirurgia , Humanos , Lactente , Estudos Retrospectivos , Resultado do Tratamento
4.
BMC Public Health ; 19(1): 116, 2019 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-30691418

RESUMO

BACKGROUND: The epidemiological characteristics of sudden cardiac death (SCD) in the autonomous region of Xinjiang Uygur have been largely unknown. This study aimed to evaluate the incidence and demographic risk factors of SCD in Xinjiang, China. METHODS: This retrospective study reviewed medical records from 11 regions in Xinjiang with different geography (north and south of the Tian Shan mountain range), gross domestic product, and ethnicity (Han, Uyghur, Kazakh, and Hui). SCD was defined as unexpected death due to cardiac reasons within 1 hour after the onset of acute symptoms, including sudden death, unexpected death, and nonviolent death. Monitoring was conducted throughout 2015. Demographic and mortality data were recorded and age-adjusted standardized risk ratio (SRR) was analyzed. RESULTS: Among 3,224,103 residents, there were 13,308 all-cause deaths and 1244 events of SCD (784 men and 460 women; overall incidence 38.6 per 100,000 residents). SCD was associated with age (χ2 = 2105.3), but not geography. Men had an increased risk of SCD compared with women (SRR: 1.75, 95% CI: 1.10-2.79). The risk of SCD was highest in residents of the Uyghur (SRR: 1.59, 95% CI: 1.05-2.42) and Kazakh (SRR: 1.92, 95% CI: 1.29-2.87) compared with those of the Han. Poor economic development was associated with elevated risk of SCD (SRR: 1.55, 95% CI: 1.02-2.38). CONCLUSION: SCD is an important public health issue in China. Our understanding of the demographic differences on SCD in Xinjiang, China may improve the risk stratification and management to reduce the incidence and lethality of SCD.


Assuntos
Diversidade Cultural , Morte Súbita Cardíaca/etnologia , Etnicidade/estatística & dados numéricos , Adolescente , Adulto , Causas de Morte/tendências , China/epidemiologia , Desenvolvimento Econômico/estatística & dados numéricos , Feminino , Produto Interno Bruto/estatística & dados numéricos , Humanos , Incidência , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
5.
Front Bioeng Biotechnol ; 12: 1382845, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38803846

RESUMO

Background: The treatment of unstable femoral neck fractures (FNFs) remains a challenge. In this study, a new cannulated screw for unstable FNFs was designed to provide a new approach for the clinical treatment of these injuries, and its biomechanical stability was analyzed using finite element analysis and mechanical tests. Methods: An unstable FNF model was established. An internal fixation model with parallel inverted triangular cannulated screws (CSs) and a configuration with two superior cannulated screws and one inferior new cannulated screw (NCS) were used. The biomechanical properties of the two fixation methods were compared and analyzed by using finite element analysis and mechanical tests. Results: The NCS model outperformed the CSs model in terms of strain and stress distribution in computer-simulated reconstruction of the inverted triangular cannulated screw fixation model for unstable FNFs. In the biomechanical test, the NCS group showed significantly smaller average femoral deformation (1.08 ± 0.15 mm vs. 1.50 ± 0.37 mm) and fracture line displacement (1.43 ± 0.30 mm vs. 2.01 ± 0.47 mm). In the NCS group, the mean stiffness was significantly higher than that in the CSs group (729.37 ± 82.20 N/mm vs. 544.83 ± 116.07 N/mm), and the mean compression distance was significantly lower than that in the CSs group (2.87 ± 0.30 mm vs. 4.04 ± 1.09 mm). Conclusion: The NCS combined with two ordinary cannulated screws in an inverted triangle structure to fix unstable FNFs can provide better biomechanical stability than CSs and exhibit a length- and angle-stable construct to prevent significant femoral neck shortening.

6.
Eur J Surg Oncol ; 49(11): 106970, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37365055

RESUMO

BACKGROUND: The interest in breast cancer with low HER2 expression as a distinct subtype is increasing. We aimed to explore the differences between HER2-low and HER2-zero breast cancer in their prognosis and rate of pathological complete response (pCR) after neoadjuvant therapy. METHODS: The National Cancer Database (NCDB) was used to select patients with breast cancer who received neoadjuvant therapy from 2004 to 2017. Logistic regression model was constructed for analysis of pCR. Cox proportional hazards regression model and Kaplan-Meier method were used for survival analysis. RESULTS: A total of 41500 breast cancer patients were included, among which 14814 (35.7%) had HER2-zero tumors and 26686 (64.3%) had HER2-low. HER2-low tumors were more commonly HR-positive in comparison with HER2-zero (66.3% versus 47.1%, P < 0.001). A lower rate of pCR was observed in HER2-low tumors than in HER2-zero tumors after neoadjuvant therapy in the total cohort (OR = 0.90; 95% CI [0.86-0.95]; P < 0.001) and in the subset of HR-positive (OR = 0.87; 95% CI [0.81-0.94]; P < 0.001). Patients with HER2-low tumors had a significantly superior survival than those with HER2-zero tumors (HR = 0.90; 95% CI [0.86-0.94]; P < 0.001), regardless of the HR status. Additionally, a marginal survival difference was also observed between HER2 IHC1+ and HER2 IHC2+/ISH-negative (HR = 0.91; 95% CI [0.85-0.97]; P = 0.003) cohorts. CONCLUSION: HER2-low tumors are a clinically relevant breast cancer subtype that is distinct from HER2-zero tumors. These findings may provide clues to appropriate therapeutic strategies for this subtype in the future.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Terapia Neoadjuvante , Receptor ErbB-2/metabolismo , Quimioterapia Adjuvante , Prognóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
7.
Zhongguo Gu Shang ; 34(7): 601-4, 2021 Jul 25.
Artigo em Zh | MEDLINE | ID: mdl-34318633

RESUMO

OBJECTIVE: To investigate the application of tranexamic acid in the treatment of intertrochanteric fracture. METHODS: From January 2017 to October 2019, 100 patients with intertrochanteric fracture were randomly divided into observation group (48 cases) and control group(52 cases). All patients received the same surgical treatment. The control group was given tranexamic acid 20 minutes before operation, and 15 mg/kg diluted in 250 ml sodium chloride injection, intravenous drip;the observation group was given tranexamic acid 0.5 g dissolved in 20 ml normal saline injected into femoral bone marrow cavity for local treatment on the basis of the control group. The blood loss, operation time and postoperative hospital stay were compared between two groups. Hematocrit, hemoglobin, D-dimer and fibrinogen levels were analyzed before and after operation, and the incidence of thrombotic complications was observed. RESULTS: The total blood loss, dominant blood loss, hidden blood loss and postoperative drainage volume of the observation group were significantly lower than those of the control group (P<0.05), and the postoperative hospital stay was significantly shorter than that of the control group (P<0.05). The postoperative hemoglobin and hematocrit of two groups were significantly lower than those before operation (P<0.05), while the postoperative hemoglobin and hematocrit of the observation group were significantly higher than those of the control group (P<0.05). The incidence of thrombotic complications in the observation group was 10.42%, which was not significantly different from that in the control group (11.54%)(P>0.05). CONCLUSION: Tranexamic acid combined with systemic and local application has important clinical significance in reducing perioperative blood lossand blood cell loss in patients with intertrochanteric fracture, and has good safety.


Assuntos
Antifibrinolíticos , Fraturas do Quadril , Ácido Tranexâmico , Antifibrinolíticos/uso terapêutico , Perda Sanguínea Cirúrgica , Fêmur , Fraturas do Quadril/tratamento farmacológico , Fraturas do Quadril/cirurgia , Humanos , Hemorragia Pós-Operatória , Resultado do Tratamento
8.
J Orthop Surg Res ; 16(1): 83, 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33494774

RESUMO

BACKGROUND: Whether resurface the patella or not in total knee arthroplasty (TKA) was controversial. In 2013, we conducted a meta-analysis of randomized controlled trials (RTCs). After that, plenty of studies have been carried out, but there still existed a great deal of controversy. In order to update our previous study, we conducted this update meta-analysis to evaluate the efficacy of patellar resurfacing in TKA. METHODS: Databases were searched for RCTs comparing the outcomes of patellar resurfacing and nonresurfacing in TKA. Outcomes of knee relevant indicators were analysed. To see the short- and long-term effects, we calculated the data in total and divided the patients who were followed up for ≤ 3 years and ≥ 5 years into two subgroups as well. RESULTS: Thirty-two trials assessing 6887 knees were eligible. There was a significant difference in terms of reoperation (in total and ≥ 5 years), Knee Society Score (KSS), function score (in total and ≥ 5 years) and noise. While no significant difference was found in the following items: reoperation (≤ 3 years), anterior knee pain (AKP), function score (≤ 3 years), range of motion (ROM), Oxford score, the Knee Injury and Osteoarthritis Outcome Score (KOOS), visual analogue score (VAS), Feller score, patellar tilt and the patients' satisfaction. CONCLUSIONS: We found that patellar resurfacing could reduce the occurrence of reoperation and noise after surgery, as well as increase the KSS and function score, while it might not influence the outcomes such as AKP, ROM, Oxford score, KOOS, VAS, Feller score, patellar tilt and the patients' satisfaction. The results are different from our previous finding in the meta-analysis. In conclusion, we prefer patellar resurfacing in TKA.


Assuntos
Artroplastia do Joelho/métodos , Patela/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Feminino , Seguimentos , Humanos , Masculino , Reoperação/estatística & dados numéricos , Fatores de Tempo , Resultado do Tratamento
9.
Nat Commun ; 12(1): 3913, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34162888

RESUMO

Human FOXP3+ regulatory T (Treg) cells are central to immune tolerance. However, their heterogeneity and differentiation remain incompletely understood. Here we use single-cell RNA and T cell receptor sequencing to resolve Treg cells from healthy individuals and patients with or without acute graft-versus-host disease (aGVHD) who undergo stem cell transplantation. These analyses, combined with functional assays, separate Treg cells into naïve, activated, and effector stages, and resolve the HLA-DRhi, LIMS1hi, highly suppressive FOXP3hi, and highly proliferative MKI67hi effector subsets. Trajectory analysis assembles Treg subsets into two differentiation paths (I/II) with distinctive phenotypic and functional programs, ending with the FOXP3hi and MKI67hi subsets, respectively. Transcription factors FOXP3 and SUB1 contribute to some Path I and Path II phenotypes, respectively. These FOXP3hi and MKI67hi subsets and two differentiation pathways are conserved in transplanted patients, despite having functional and migratory impairments under aGVHD. These findings expand the understanding of Treg cell heterogeneity and differentiation and provide a single-cell atlas for the dissection of Treg complexity in health and disease.


Assuntos
Diferenciação Celular/genética , Fatores de Transcrição Forkhead/imunologia , Transdução de Sinais/genética , Análise de Célula Única/métodos , Linfócitos T Reguladores/imunologia , Transcriptoma/genética , Western Blotting , Ensaio de Imunoadsorção Enzimática , Fatores de Transcrição Forkhead/metabolismo , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/metabolismo , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , RNA-Seq/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/metabolismo
10.
J Hematol Oncol ; 14(1): 149, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34530888

RESUMO

CD19 chimeric antigen receptor (CAR)-T cells have been used to treat patients with refractory chronic lymphocytic leukemia (CLL). However, approximately 50% of patients do not respond to this therapy. To improve the clinical outcome of these patients, it is necessary to develop strategies with other optimal targets to enable secondary or combinational CAR-T cell therapy. By screening a panel of surface antigens, we found that CD32b (FcγRIIb) was homogeneously expressed at high site density on tumor cells from CLL patients. We then developed a second-generation CAR construct targeting CD32b, and T cells transduced with the CD32 CAR efficiently eliminated the CD32b+ Raji leukemic cell line in vitro and in a mouse xenograft model. Furthermore, CD32b CAR-T cells showed cytotoxicity against primary human CLL cells that were cultured in vitro or transplanted into immunodeficient mice. The efficacy of CD32b CAR T cells correlated with the CD32b density on CLL cells. CD32b is not significantly expressed by non-B hematopoietic cells. Our study thus identifies CD32b as a potential target of CAR-T cell therapy for CLL, although further modification of the CAR construct with a safety mechanism may be required to minimize off-target toxicity.


Assuntos
Imunoterapia Adotiva , Leucemia Linfocítica Crônica de Células B/terapia , Receptores de IgG/genética , Animais , Linhagem Celular Tumoral , Expressão Gênica , Humanos , Imunoterapia Adotiva/métodos , Leucemia Linfocítica Crônica de Células B/genética , Camundongos
11.
Biochem Biophys Res Commun ; 400(1): 151-6, 2010 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-20709020

RESUMO

Angiogenesis is critical to a wide range of physiological and pathological processes. Scutellarin, a major flavonoid of a Chinese herbal medicine Erigeron breviscapus (Vant.) Hand. Mazz. has been shown to offer beneficial effects on cardiovascular and cerebrovascular functions. However, scutellarin's effects on angiogenesis and underlying mechanisms are not fully elucidated. Here, we studied angiogenic effects of scutellarin on human umbilical vein endothelial cells (HUVECs) in vitro. Scutellarin was found by MTT assay to induce proliferation of HUVECs. In scutellarin-treated HUVECs, a dramatic increase in migration was measured by wound healing assay; Transwell chamber assay found significantly more invading cells in scutellarin-treated groups. Scutellarin also promoted capillary-like tube formation in HUVECs on Matrigel, and significantly upregulated platelet endothelial cell adhesion molecule-1 at both mRNA and protein levels. Scutellarin's angiogenic mechanism was investigated in vitro by measuring expression of angiogenic factors associated with cell migration and invasion. Scutellarin strongly induced MMP-2 activation and mRNA expression in cultured HUVECs in a concentration-dependent manner. Taken together, these results suggest that scutellarin promotes angiogenesis and may form a basis for angiogenic therapy.


Assuntos
Indutores da Angiogênese/farmacologia , Apigenina/farmacologia , Endotélio Vascular/efeitos dos fármacos , Glucuronatos/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Endotélio Vascular/citologia , Endotélio Vascular/fisiologia , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/biossíntese , Inibidor Tecidual de Metaloproteinase-3/metabolismo , Veias Umbilicais/citologia , Veias Umbilicais/efeitos dos fármacos
12.
Transl Cancer Res ; 9(8): 5020-5025, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35117865

RESUMO

Ureteral metastasis from breast cancer (BC) is very rare, and only a few cases have been reported. We report the first patient with ureteral involvement from human epidermal receptor 2 (HER2) enriched metastatic BC. A 51-year-old woman with HER2-enriched metastatic BC with liver metastasis was diagnosed at her first visit, achieving complete tumor regression by chemotherapy, anti-HER2 treatment, modified mastectomy and radiotherapy. After 1 year, she complained light left flank pain for 1 month, with an elevated cancer antigen 15-3 (CA15-3) level in blood. Computed tomography showed a left proximal ureteral lesion causing ureterectasis and hydronephrosis. A ureteroscope-guided biopsy of the ureteral lesion revealed poorly differentiated carcinoma from metastatic BC. Diagnosing ureter metastasis from BC were established by histopathology and immunohistochemistry. The flank pain and ureteral lesion were absolutely relieved after chemotherapy and anti-HER2 treatment, and CA15-3 level decreased to normal. Regular follow-up examinations every 3 months are performed at our outpatient clinic. With a 20 months follow-up, there has been no further progression up to now. Ureteral metastasis of BC shows nonspecific symptoms, and it is important to recognize this unusual manifestation so that timely appropriate treatment can be initiated in order to better prognosis. Chemotherapy plus anti-HER2 treatment are most effective for hepatic and ureteral metastasis from BC.

13.
J Invest Surg ; 33(8): 709-714, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31070071

RESUMO

Purpose: The removal of the giant breast fibroadenoma (GFA) with esthetic repair of the severe deformed breast is a surgical challenge. Materials and Methods: This was a retrospective study of data of 10 patients with GFAs who treated with a modified round block technique at the Department of Breast Surgery, Hangzhou First People's Hospital (Hangzhou, Zhejiang province, China) from March 2014 to June 2017. Preoperatively, according to the degree of excess skin and asymmetry, a four-point approach was designed. The area between the inner and outer circles was de-epidermized. The tumors were entirely stripped off along the capsule through an incision on a part of the outer circle. To avoid the nipple-areola complex widening, purse-string suture technique was used. Results: Patients' age ranged from 12 to 32 years (mean age, 23 years), and the largest tumor weighed 2 kg, with a diameter of 16.5 cm. After a mean follow-up of 25 months (range, 9-32 months), no local recurrences were found. Cosmetic results were satisfactory with breast symmetry and minimal scarring. Complications were minimal and widening of the periareolar scar was slight as well. Conclusion: The modified round block technique is recommended to resect GFA in order to improve the cosmetic results with minimal scar.


Assuntos
Neoplasias da Mama/cirurgia , Mama/patologia , Cicatriz/diagnóstico , Fibroadenoma/cirurgia , Mastectomia Segmentar/métodos , Adolescente , Adulto , Mama/diagnóstico por imagem , Mama/cirurgia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Criança , China , Cicatriz/etiologia , Cicatriz/prevenção & controle , Estética , Feminino , Fibroadenoma/diagnóstico , Fibroadenoma/patologia , Humanos , Imageamento por Ressonância Magnética , Mastectomia Segmentar/efeitos adversos , Mamilos/cirurgia , Satisfação do Paciente , Estudos Retrospectivos , Índice de Gravidade de Doença , Técnicas de Sutura , Resultado do Tratamento , Ultrassonografia Mamária , Adulto Jovem
14.
Transl Cancer Res ; 8(1): 180-190, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35116747

RESUMO

BACKGROUND: MicroRNAs (miRNAs) play an essential role in the initiation, progression and metastasis of breast cancer. It has been confirmed that miR-30b is involved in various cancers. However, the specific involvement of miR-30b on breast cancer metastasis remains unknown. In the current study, we aimed to investigate the role of miR-30b in the progression and metastasis of breast cancer in vitro. METHODS: We up-regulated the expression of miR-30b in breast cancer cell lines SKBR3 and MDA-MB-231 by transfecting pCMV-miR-30b vector. CCK8, colony formation, Transwell, and flow cytometry assays were used to examine cell proliferation, migration, invasion and apoptosis, respectively. A dual-luciferase reporter assay was performed to identify the relationship between miR-30b and the target gene. Western blot assay was used to detect related proteins. RESULTS: Our data showed that the overexpression of miR-30b significantly inhibited proliferation, migration and invasion abilities in SKBR3 and MDA-MB-231 cells. Meanwhile, overexpression of miR-30b induced cell apoptosis for both SKBR3 and MDA-MB-231 cells by regulating the expression of apoptosis-related proteins (Bcl-2, Bax, active Caspase-3, and Caspase-9). Moreover, miR-30b inhibited the activation of the PI3K/Akt signaling pathway by decreasing the phosphorylation levels of Akt and mTOR. Furthermore, we determined that miR-30b could down-regulate the expression of Derlin-1 in a post-transcriptional manner by employing the dual-luciferase reporter and western blot assays. Further analysis demonstrated that depletion of Derlin-1 inhibited Akt phosphorylation, and Derlin-1 could restore the effect of miR-30b on Akt. In addition, the CCK8 assay showed that Derlin-1 could partly reverse the inhibition of cell proliferation of SKBR3 and MDA-MB-231 cells mediated by miR-30b. CONCLUSIONS: Our data demonstrated that miR-30b suppresses the progression and metastasis of breast cancer via inhibition of the PI3K/Akt signaling pathway by targeting Derlin-1 in vitro. This suggests that miR-30b might be a novel potent target for breast cancer therapy.

16.
Oncol Lett ; 16(1): 1212-1218, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30061943

RESUMO

The aim of the present study was to improve the conventional wire-guided localization biopsy (WGLB) of breast microcalcifications to overcome disadvantages associated with the procedure, including inaccurate localization and large specimen volume. The novel approach described in the present study was termed double wire-guided localization and rotary cutting biopsy (DWGLB). Prior to surgery, the precise localization of the lesions was assessed using two wires under the assistance of mammography X-ray and ultrasound, followed by complete excision of the lesions using a novel rotary cutting tool. The cylindrical specimen was placed on a scaled specimen holder for pathological examination. DWGLB was performed in 108 patients with the classification of as Breast Imaging Reporting and Data System score 4A. Percutaneous localization of the lesions guided by a mammography X-ray and ultrasound were successful in all 108 lesions (100%) with one puncture attempt. The lesions were precisely excised in all of 108 patients, and included 13 malignant lesions (DCIS of breast in 7 cases, DCIS with focal invasive carcinoma in 3 cases and invasive ductal carcinoma in 3 cases). The average distance of the BARD Dualok to the lesion was 4.1 mm; the average weight of specimens was 8.5 g. Compared with WGLB, DWGLB offers several advantages, including more accurate localization of lesions, a more standardized biopsy method and a smaller specimen volume. DWGLB can also provide the precise position of lesions in the specimen for further pathological examination.

17.
Anticancer Res ; 31(1): 39-45, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21273578

RESUMO

BACKGROUND: 5-Aminolevulinic acid (ALA) has been used as a photodynamic sensitizer for cancer treatment using photodynamic therapy. However, the light has markedly limited penetration depth. It was found that ALA also responds to low energy ultrasound, which has the capability to penetrate deep into tissues. Therefore, sonodynamic therapy (SDT) is a promising method for noninvasive treatment of tumors embedded deep in the tissue. It is desirable to kill the cancer cells via apoptosis rather than necrosis, and therefore, it is necessary to gain a better understanding of the mechanisms of treating cancer using SDT. MATERIALS AND METHODS: The apoptosis of SAS cells induced by pulsed 1.05MHz ultrasound in combination with ALA was investigated in vitro. RESULTS: The cells exposed to SDT with 10 µg/ml ALA displayed significantly higher apoptosis than cells treated by ultrasound alone. There was notably increased reactive oxygen species (ROS) production in the cells treated by SDT with ALA than by ultrasound alone, resulting in higher lipid peroxidation (LPO) level and more cells losing their mitochondrial membrane potential (MMP). CONCLUSION: ALA-mediated SDT produced strong apoptotic effects on SAS cells, which were mainly related to the excessive intracellular ROS production followed by LPO increase and MMP decrease.


Assuntos
Ácido Aminolevulínico/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/patologia , Fármacos Fotossensibilizantes/farmacologia , Neoplasias da Língua/patologia , Terapia por Ultrassom , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Terapia Combinada , Citometria de Fluxo , Humanos , Peroxidação de Lipídeos , Metaloproteinases da Matriz/metabolismo , Potencial da Membrana Mitocondrial , Espécies Reativas de Oxigênio/metabolismo , Neoplasias da Língua/tratamento farmacológico , Neoplasias da Língua/metabolismo , Células Tumorais Cultivadas
18.
Oncol Rep ; 24(5): 1153-60, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20878105

RESUMO

To examine the effect of scutellarin on adhesion and migration of oral squamous cell carcinoma (OSCC), the HSC-4 and SAS human OSCC cells were treated with various concentrations of scutellarin. Scutellarin cytotoxicity was evaluated by MTT assays; migration of tongue cancer cells was assessed by wound healing and Transwell chemotaxis; αvß6 integrin and E-cadherin expression was assessed by immunofluorescence and reverse transcription polymerase chain reaction. Scutellarin at 75 nM significantly inhibited tongue cancer cell proliferation and at 15 nM, significantly reduced HSC-4 and SAS cell motility by 46.3% and 44%, respectively. Scutellarin inhibited SAS cell adhesion to fibronectin in a dose-dependent manner. However, it had no significant effect on HSC-4 cell adhesion to fibronectin; at the same concentration, HSC-4 cells adhered more strongly to fibronectin than SAS cells. Following treatment with scutellarin, E-cadherin and desmoplakin protein levels were increased, whereas E-cadherin mRNA expression was unchanged; protein levels of αvß6 integrin were decreased-consistent with the change in αvß6 integrin mRNA. After a 3 nM scutellarin treatment, levels of desmoplakin in HSC-4 and SAS cells increased by 79.9% and 74.5%, respectively. Scutellarin (3 nM) increased expression of E-cadherin in HSC-4 and SAS cells by 37.9% and 52%, respectively, and decreased the expression of αvß6 integrin by 45.4% and 47.2%, respectively. This study shows that scutellarin inhibits tumor cell proliferation and migration and regulates cell adhesion in OSCC cells; this may be closely related to up-regulation of E-cadherin and down-regulation of αvß6 integrin.


Assuntos
Antígenos de Neoplasias/biossíntese , Apigenina/farmacologia , Caderinas/biossíntese , Carcinoma de Células Escamosas/patologia , Movimento Celular/efeitos dos fármacos , Glucuronatos/farmacologia , Integrinas/biossíntese , Neoplasias da Língua/patologia , Antígenos de Neoplasias/genética , Caderinas/genética , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Adesão Celular/efeitos dos fármacos , Adesão Celular/fisiologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Sobrevivência Celular/fisiologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Integrinas/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Neoplasias da Língua/tratamento farmacológico , Neoplasias da Língua/genética , Neoplasias da Língua/metabolismo
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