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1.
Zhonghua Wai Ke Za Zhi ; 62(6): 613-618, 2024 Apr 29.
Artigo em Chinês | MEDLINE | ID: mdl-38682634

RESUMO

Subchondral bone cysts after cartilage repair are abnormal cavities that develop near the site of repaired cartilage defects and may communicate with the joint cavity.Research indicates that they may be associated with factors such as elevated external hydraulic pressure, bone bruising due to abnormal stress, internal inflammation, and inadequate blood supply.These cysts are closely linked to bone marrow edema.It has been observed that cysts following cartilage repair frequently occur after various procedures, including bone marrow stimulation, autologous or allogeneic osteochondral transplantation, and autologous chondrocyte transplantation.They represent a significant pathological change post-cartilage repair, influencing the process, quality, and outcome of the repair.Consequently, they have become an important parameter for evaluating the effectiveness of cartilage repair.This article provides a review of studies on the occurrence, development mechanisms, and pathological structures of subchondral bone cysts after cartilage repair using different techniques.It explores the clinical implications and potential of utilizing these cysts to assess the success of cartilage repair, enhancing understanding in this field.Such insights are expected to lay a foundation for the prevention and treatment of subchondral bone cysts following various cartilage repair procedures.

2.
J Dent Res ; 102(7): 795-805, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37246810

RESUMO

Immune checkpoint molecule PD-1, expressed on the cell surface, impairs antigen-driven activation of T cells and thus plays a critical role in tumorigenesis, progression, and the poor prognosis of oral squamous cell carcinoma (OSCC). In addition, increasing evidence indicates that PD-1 carried on small extracellular vesicles (sEVs) also mediates tumor immunity, although their contributions to OSCC are yet unclear. Here, we investigated the biological functions of sEV PD-1 in patients with OSCC. The cell cycle, proliferation, apoptosis, migration, and invasion of CAL27 cell lines treated with or without sEV PD-1 were examined in vitro. We performed mass spectrometry to investigate the underlying biological process, combined with an immunohistochemical study of SCC7-bearing mice models and OSCC patient samples. In vitro data demonstrated that sEV PD-1 induced senescence and subsequent epithelial-mesenchymal transition (EMT) in CAL27 cells by ligating with tumor cell surface PD-L1 and activating the p38 mitogen-activated protein kinase (MAPK) pathway. Comprehensive immunohistochemical analysis of the xenograft mice models and OSCC patient samples revealed a very close correlation between the level of circulating sEV PD-1 and lymph node metastasis. These results demonstrate that circulating sEV PD-1 triggers senescence-initiated EMT in a PD-L1-p38 MAPK-dependent manner, contributing to tumor metastasis. It also suggests that the inhibition of sEV PD-1 may be a promising therapeutic target for the treatment of OSCC.


Assuntos
Carcinoma de Células Escamosas , Vesículas Extracelulares , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Animais , Camundongos , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Antígeno B7-H1 , Receptor de Morte Celular Programada 1 , Neoplasias Bucais/metabolismo , Vesículas Extracelulares/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Transição Epitelial-Mesenquimal , Movimento Celular
4.
Benef Microbes ; 14(5): 503-524, 2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-38656098

RESUMO

Benign prostatic hyperplasia (BPH) can cause urethral compression, bladder stone formation, and renal function damage, which may endanger the life of patients. Therefore, we aimed to develop plant-based preparations for BPH treatment with no side effects. In this study, the Lactiplantibacillus plantarum 322Hp, Lactobacillus acidophilus 322Ha, and Limosilactobacillus reuteri 322Hr were used to ferment rape pollen. The fermented rape pollen was subsequently converted into fermented rape pollen powder (FRPP) through vacuum freeze-drying technology. After fermenting and drying, the bioactive substances and antioxidant capacity of FRPP were significantly higher than those of unfermented rapeseed pollen, and FRPP had a longer storage duration, which can be stored for over one year. To investigate the therapeutic effect of FRPP on BPH, a BPH rat model was established by hypodermic injection of testosterone propionate. The BPH rats were treated differently, with the model group receiving normal saline, the positive control group receiving finasteride, and the low, medium, and high dose FRPP group receiving FRPP at doses of 0.14 g/kg/d, 0.28 g/kg/d, and 0.56 g/kg/d, respectively. The results indicate that medium dose FRPP reduced the levels of hormone such as testosterone, dihydrotestosterone, and oestradiol in rats with BPH by about 32%, thus bringing the prostate tissue of BPH rats closer to normal. More importantly, medium dose FRPP treatment had a significant effect on the composition of gut microbiota in rats with BPH, increasing the levels of beneficial genera (such as Coprococcus and Jeotgalicoccus), and decreasing the levels of harmful pathogens (such as Turicibacter and Clostridiaceae_Clostridium) in the gut. This study showed that medium dose FRPP reduced the hormone level and regulated the unbalanced gut microbiota in BPH rats, thereby alleviating BPH.


Assuntos
Fermentação , Microbioma Gastrointestinal , Pólen , Pós , Hiperplasia Prostática , Masculino , Animais , Pólen/química , Microbioma Gastrointestinal/efeitos dos fármacos , Ratos , Hiperplasia Prostática/microbiologia , Ratos Sprague-Dawley , Modelos Animais de Doenças , Testosterona/metabolismo , Di-Hidrotestosterona/metabolismo , Brassica rapa/química , Brassica rapa/microbiologia , Próstata/microbiologia , Próstata/efeitos dos fármacos , Brassica napus/química , Lactobacillus plantarum/metabolismo , Propionato de Testosterona , Hormônios/metabolismo
5.
Zhonghua Wai Ke Za Zhi ; 59(9): 795-798, 2021 Sep 01.
Artigo em Chinês | MEDLINE | ID: mdl-34404179

RESUMO

The mechanism of osteoarthritis is still not completely clear,the current treatment can not effectively prevent the disease from progressing.In order to study osteoarthritis,researchers have developed various models,including in vitro models (two-dimension and three-dimension cell culture models and bioreactor culture models) and in vivo models (spontaneous,genetically modified,invasive and non-invasive models).These models are important tools for studying the mechanism of disease occurrence and development,which can simulate the whole process or a certain stage of pathological changes,as well as evaluating the effect of treatment.This paper reviews the osteoarthritis models and their characteristics in order to provide reference for osteoarthritis research.

7.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi ; 55(10): 913-920, 2020 Oct 07.
Artigo em Chinês | MEDLINE | ID: mdl-33036505

RESUMO

Objective: To investigate the efficacy, safety and advantages of gasless unilateral axillary approach (GUAA) in endoscopic thyroid surgery. Methods: A total of 334 patients who underwent the GUAA endoscopic thyroid surgery (GUAA group) or conventional open thyroid surgery (OS group) in the Department of Head and Neck Surgery of Zhejiang Cancer Hospital from January 2017 to June 2018 were retrospectively analyzed. There were 45 males and 289 females, aged from 12 to 72 years old, of whom 139 patients were assigned to GUAA group and 195 patients to OS group. Pathological results included papillary thyroid carcinoma (282 cases), nodular goiter (41 cases) and thyroid adenoma (11 cases). Surgical exploration development curve of GUAA group was drawn and was divided into two parts: the technical exploration stage and the technical stable stage. Surgical efficiency, incidences of complications, and incision satisfaction were compared between GUAA group in technical stable stage and OS group. SPSS 25.0 software was adopted for statistical analysis. Results: The mean age in GUAA group was younger than that in OS group, with a significant difference [(35.3±9.5) years vs. (48.1±10.6) years, t=11.31, P<0.01]. The cases in the endoscope group were divided into technical exploration stage for 51 cases and technical stable stage for 88 cases according to the exploration and development curve. In unilateral radical thyroidectomy and unilateral thyroid lobectomy, the mean operation time [(90.6±18.6) min and (93.5±22.0) min] and postoperative drainage volumes [(121.5±87.6) ml and (155.5±69.1) ml] of GUAA group in the stable stage were more than those of OS group [(61.6±15.6) min and (46.5±8.4) min] and [(93.2±42.3) ml and (78.9±48.7) ml]. The difference was statistically significant (t=12.28, 7.23, 3.35 and 3.05 respectively, all P<0.05), but there were no significant differences in surgical bleeding volumes between two groups [(12.7±6.8) ml vs. (13.5±7.7) ml, t=0.74, P>0.05 and (16.3±14.1) ml vs. (11.9±5.1) ml, t=1.05, P>0.05]. Compared with OS group, GUAA group had the lower incidence of anterior cervical discomfort during swallowing (2.3% vs. 29.2%, P<0.01) and the higher incision satisfaction score (1.1±0.5 vs. 2.8±0.7, t=21.12, P<0.01), however, GUAA group had the higher incidence of supraclavicular (or infraclavicular) numbness after surgery (5.7% vs. 0, P<0.01). And there was no significant difference in the incidences of temporary recurrent laryngeal nerve injury, bleeding, hematoma, infection, lymphatic leakage or chylous leakage after surgery between two groups (P>0.05). Conclusion: GUAA endoscopic thyroid surgery is a safe method with high cosmetic satisfaction.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Adolescente , Adulto , Idoso , Carcinoma Papilar/cirurgia , Criança , Endoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Adulto Jovem
8.
Eur Rev Med Pharmacol Sci ; 24(11): 6072-6079, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32572922

RESUMO

OBJECTIVE: This study aims to explore the expression pattern and clinical significance of circ_001680 in gastric carcinoma (GC) process. PATIENTS AND METHODS: Circ_001680 levels in 40 pairs of GC and paracancerous ones were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between circ_001680 and GC clinicopathological parameters was analyzed. AGS and SGC-7901 cells were used for constructing circ_001680 knockdown models by shRNA transfection. Proliferative and metastatic abilities in GC cells with circ_001680 knockdown were examined by cell counting kit-8 (CCK-8) and transwell assay, respectively. Dual-Luciferase reporter assay was conducted to clarify the interaction between circ_001680 and MAP2. Their co-regulation on GC process was detected through rescue experiments. RESULTS: Circ_001680 was highly expressed in GC tissues and cell lines. High level of circ_001680 predicted high incidences of lymphatic and distant metastasis, and poor prognosis in GC patients. Knockdown of circ_001680 suppressed proliferative and metastatic abilities in AGS and SGC-7901 cells. MAP2 was the target gene binding circ_001680, which was lowly expressed in GC. In addition, MAP2 was negatively correlated to circ_001680. Knockdown of MAP2 could abolish the suppressed proliferative and metastatic abilities in GC cells with circ_001680 knockdown. CONCLUSIONS: Circ_001680 is highly expressed in GC tissues and closely related to metastasis and prognosis in GC patients, which promotes the proliferative and metastatic abilities in GC cells by negatively interacting with MAP2.


Assuntos
Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Linhagem Celular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
Artigo em Chinês | MEDLINE | ID: mdl-31434370

RESUMO

Objective: To analyse the mental state of patients with allergic rhinitis (AR) in Chengdu. Methods: One thousand five hundred and thirty-six AR patients from Sichuan Provincial Integrated Traditional Chinese and Western Medicine Hospital, West China Hospital of Sichuan University, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Sichuan People's Hospital, Sichuan Second Hospital of Traditional Chinese Medicine were selected from July 2013 to January 2018. Eight hundred and twenty-seven patients were screened into study group by inclusion and exclusion standards. The symptom check list 90 (SCL-90) was used to group and score the mental state of these patients according to nine classification criteria: gender, BMI, age, marital status, monthly salary, disease duration, living environment, education level and working environment. Then, the scores were compared within groups. Inter-group comparison was made between the study group and the Chinese norm, and the positive factors for psychological disorders were extracted. Four symptoms in the study group, i.e. nasal itching, sneezing, clear discharge and nasal congestion, were scored on the visual analogue scale (VAS). SPSS 19.0 software was used to carry out statistical analysis. Partial correlation analysis was performed between the positive factors and the symptom scores by multiple regression statistical method. Results: The total score of SCL-90 in the study group was 2.64±0.25, which was accorded with mild to moderate mental health impairment. There were 124 (15.0%) without mental health damage, 176 (21.3%) with mild damage, 474 (57.3%) with mild to moderate damage, 41 (5.0%) with moderate to severe damage and 12 (1.4%) with severe damage. The in-group comparison showed that the top three categories of different items were the living environment, gender and working environment. The scores of somatization, obsessive-compulsive symptoms, interpersonal sensitivity, depression, anxiety, psychosis, other (sleep, diet) and total average score of urban residents were higher than that of country residents (3.29±0.61 vs 2.65±0.50, 2.81±0.77 vs 2.05±0.38, 3.10±0.19 vs 2.49±0.67, 3.40±0.84 vs 2.49±0.70, 3.04±0.64 vs 2.33±0.51, 3.02±0.55 vs 2.40±0.77, 3.40±0.41 vs 2.52±0.77, 2.91±0.11 vs 2.29±0.40, Z value was 4.88, 5.25, 4.57, 5.91, 5.09, 4.63, 5.55, -4.55, respectively, all P<0.05). Women scored higher than man for somatization, interpersonal sensitivity, depression and others (2.66±0.51 vs 2.00±0.45, 3.37±0.47 vs 2.63±0.51, 3.44±0.57 vs 2.85±0.52, 3.47±0.36 vs 2.76±0.45, Z value was -5.10, -5.51, -4.86, -5.28, respectively, all P<0.05). The scores of somatization, interpersonal sensitivity, psychosis and other (sleep, diet) were higher in the indoor group than those in the outdoor group (3.49±0.64 vs 2.78±0.46, 3.33±0.30 vs 2.56±0.68, 3.28±0.60 vs 2.67±0.31, 3.50±0.85 vs 2.85±0.37, Z value was 5.31, 5.79, 4.89, 5.00, respectively, all P<0.05). The outdoor group scored higher on obsessive-compulsive symptoms, anxiety and hostility (3.44±0.40 vs 2.83±0.35, 3.40±0.50 vs 2.57±0.93, 3.34±0.88 vs 2.69±0.56, Z value was 4.96, 6.22, 5.08, respectively, all P<0.05). The inter-group comparison found that depression, anxiety, psychosis and other (sleep, diet) could be partially correlated with VAS scores as 4 positive factors. The results of partial correlation analysis showed that depression was positively correlated with sneezing and nasal runny discharge, anxiety was positively correlated with nasal itching and nasal obstruction, psychosis was positively correlated with nasal itching and sneezing, and other (sleep, diet) was positively correlated with nasal runny discharge and nasal obstruction. Conclusion: AR patients have mild to moderate mental health impairments, which are correlated with AR symptoms.


Assuntos
Transtornos Mentais/diagnóstico , Rinite Alérgica/psicologia , China , Feminino , Humanos , Masculino , Transtornos Mentais/etiologia , Testes de Estado Mental e Demência , Rinite Alérgica/classificação , Rinite Alérgica/complicações , Rinite Alérgica/diagnóstico
11.
Transplant Proc ; 51(10): 3364-3368, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31358449

RESUMO

BACKGROUND: High hepatitis B virus (HBV) DNA level is strongly associated with hepatocellular carcinoma (HCC) development in chronic HBV infection. The aim of this study was to investigate the association between intrahepatic HBV DNA titer and post-liver transplantation (LT) prognosis for HBV-related HCC (HBV-HCC) patients. METHODS: A total of 60 patients with HBV-HCC who underwent LT were retrospectively studied. Using quantitative TaqMan fluorescent real-time polymerase chain reaction assay, HBV total DNA (tDNA) and covalently closed circular DNA (cccDNA) were both quantified in tumor tissue (TT) and adjacent non-tumor tissue (ANTT) from the explanted liver. RESULTS: The loads of tDNA and cccDNA in ANTT were associated with serum HBV DNA levels. Multivariate analysis showed that the presence of vascular invasion and cccDNA in TT were independent risk factors for tumor recurrence. The group of patients with cccDNA titers ≥31ogl0 copies/µg in TT had significantly higher cumulative recurrence rates than those with <31ogl0 copies/µg group. The cccDNA titers predicted the tumor recurrence with an area under the receiver operating characteristic curve of 0.664. CONCLUSIONS: Our findings would assist the clinical implementation of a more personalized therapy for tumor recurrence control and improve the prognosis of HBV-HCC patients.


Assuntos
Carcinoma Hepatocelular/virologia , DNA Viral/análise , Vírus da Hepatite B/genética , Neoplasias Hepáticas/virologia , Transplante de Fígado/efeitos adversos , Recidiva Local de Neoplasia/virologia , Complicações Pós-Operatórias/virologia , Adulto , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , DNA Circular/análise , Feminino , Hepatite B Crônica/complicações , Hepatite B Crônica/cirurgia , Hepatite B Crônica/virologia , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Fatores de Risco
12.
13.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi ; 53(10): 745-750, 2018 Oct 07.
Artigo em Chinês | MEDLINE | ID: mdl-30347533

RESUMO

Objective: To investigate the effects of sIL-13Rα2 on the apoptosis of goblet cell in nasal mucosa of allergic rhinitis rats. Methods: Forty healthy male Wistar rats were randomly divided into 4 groups (10 rats per group): control group (group A), AR group (group B), sIL-13Rα2 group (group C) and triamcinolone acetonide group (group D). Ovalbumin (OVA) and aluminum hydroxide were used to establish the AR rat model. After the establishment of AR rat models, 50 µl PBS, 100 µg/50 µl IL-13Rα2 and 3.5 µg/50 µl triamcinolone acetonide were respectively dropped into each nasal cavity of every rat two times a week from 4 to 10 week in group B, group C and group D. Group A was operated with saline instead of OVA. The nasal mucosa tissues were collected at 24 h after the final administration. AB-PAS staining method was used to detect the quantity and secretion of goblet cells in the nasal mucosa tissue of all groups. Immunohistochemistry method was used to detect the expression of Bax proteins.Apoptosis was detected by TUNEL method.ANOVA analysis was used to compare multiple groups, and LSD-t test was used to compare the two groups.Pearson correlation analysis was used to analyze the correlation between the Bax positive cell rate of goblet cells and the rate of apoptotic cells. The difference was statistically significant with P<0.05. Results: Compared with group A, there were more goblet cells and hypersecretion of mucus in the nasal mucosa tissue of rats in group B while fewer in group C. The goblet cells in group C and group D were significantly fewer than that in group B (0.639 00±0.831 vs 0.956 7±0.980, 0.661 90±0.657 vs 0.956 7±0.980, t value was 2.748, 2.767, respectively, all P<0.05). The immunohistochemistry results showed that the positive expression rates of Bax protein in goblet cells of group C and group D were significantly higher than that in group B (0.880 2±0.125 vs 0.568 7±0.953, 0.938 4±0.200 vs 0.568 7±0.953, t value was -2.292, -2.685, respectively, all P<0.05). The apoptosis rates of goblet cell in nasal mucosa of group C and group D were also significantly higher than that in group B (0.516 0±0.079 vs 0.274 0±0.056, 0.535 4±0.829 vs 0.274 0±0.056, t value was -17.671, -2.225, respectively, all P<0.05). The expression of Bax protein and apoptosis of goblet cells were positively correlated (r=0.859, P<0.01). Conclusion: sIL-13Rα2 can induce apoptosis of the goblet cells in nasal mucosa of allergic rhinitis rats, by inhibiting IL-13 and up regulating Bax.


Assuntos
Modelos Animais de Doenças , Células Caliciformes/efeitos dos fármacos , Subunidade alfa2 de Receptor de Interleucina-13/administração & dosagem , Interleucina-13/antagonistas & inibidores , Mucosa Nasal/imunologia , Rinite Alérgica/imunologia , Proteína X Associada a bcl-2/metabolismo , Adjuvantes Imunológicos , Hidróxido de Alumínio , Animais , Apoptose , Células Caliciformes/imunologia , Células Caliciformes/metabolismo , Imunossupressores , Masculino , Mucosa Nasal/citologia , Ovalbumina , Distribuição Aleatória , Ratos , Ratos Wistar , Triancinolona Acetonida , Regulação para Cima
15.
Zhonghua Fu Chan Ke Za Zhi ; 52(9): 612-617, 2017 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-28954450

RESUMO

Objective: To explore relations between pseudo vascular invasion (PVI) and laparoscopic operation in patients with stage Ⅰa endometrial carcinoma. Methods: Details of stage Ⅰa endometrial carcinoma patients' clinical information and pathological sections who received operation treatment between January 2008 and October 2015 were obtained from the Dalian Maternal and Child Health Hospital. There were 515 cases entrolled into this study, including 332 (64.5%) cases performed surgery by laparoscopy and 183 (35.5%) cases undergone abdominal surgery. The vascular invasion rate and the microscopic manifestations of PVI in two groups were retrospectively compared and analyzed. The follow-up period ended February 2017, the adjuvant treatment and prognosis of patients with lympho-vascular space invasion (LVSI) and PVI were analysed. Results: (1) Seventy-five of 515 cases with stage Ⅰa endometrial carcinoma, there were seven-five cases found with tumor cells in lympho-vascular space, including 52 cases of LVSI and 25 cases of PVI (2 cases of both). The incidence of cancer emboli in lympho-vascular space and LVSI in laparoscopic group and laparotomy group were respectively 15.4% (51/332) vs 13.1% (24/183) and 9.6% (32/332) vs 10.9% (20/183), there were no significant differences (all P>0.05). But the rate of PVI between the two group was significantly different [6.3% (21/332) vs 2.2% (4/183), P=0.036], laparoscopic group was higher than that in laparotomy group. (2) Of 332 cases in laparoscopic group, 21 cases was found PVI, containing 8 cases showed tumor tissue with mesenchyme or papillary structures located in large thick wall vessels of the outer lateral myometrium, 13 cases showed the tumor tissue was away from the vessel wall. Among 183 cases in laparotomy group, 3 cases with PVI which the tumor tissue was away from the vessel wall, and 1 with interstitial tissue. (3) During the follow-up period, 7 of 75 cases (both LVSI and PVI) were lost, and 66 cases were relapse-free survival, 2 cases recurred at fifth months and died respectively at 7, 20 months after the operation. This 2 cases were both PVI of laparoscopic group, and the pathological type was endometrioid adenocarcinoma grade 3, and adjuvant treatment was not accepted after the operation. The relapse-free survival with LVSI was 49 months and 46 months for cases with PVI. Conclusion: s Laparoscopic operation could increase PVI in patients with stage Ⅰa endometrial carcinoma, while does not increase LVSI. It is not yet possible to demonstrate that PVI affects the prognosis of patients.


Assuntos
Carcinoma Endometrioide/cirurgia , Neoplasias do Endométrio/cirurgia , Laparoscopia , Laparotomia , Miométrio/patologia , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Estudos Retrospectivos
16.
Ann Oncol ; 28(7): 1495-1507, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28383660

RESUMO

BACKGROUND: Deletion of the chromatin remodeler chromodomain helicase DNA-binding protein 1 (CHD1) is a common genomic alteration found in human prostate cancers (PCas). CHD1 loss represents a distinct PCa subtype characterized by SPOP mutation and higher genomic instability. However, the role of CHD1 in PCa development in vivo and its clinical utility remain unclear. PATIENTS AND METHODS: To study the role of CHD1 in PCa development and its loss in clinical management, we generated a genetically engineered mouse model with prostate-specific deletion of murine Chd1 as well as isogenic CHD1 wild-type and homozygous deleted human benign and PCa lines. We also developed patient-derived organoid cultures and screened patients with metastatic PCa for CHD1 loss. RESULTS: We demonstrate that CHD1 loss sensitizes cells to DNA damage and causes a synthetic lethal response to DNA damaging therapy in vitro, in vivo, ex vivo, in patient-derived organoid cultures and in a patient with metastatic PCa. Mechanistically, CHD1 regulates 53BP1 stability and CHD1 loss leads to decreased error-free homologous recombination (HR) repair, which is compensated by increased error-prone non-homologous end joining (NHEJ) repair for DNA double-strand break (DSB) repair. CONCLUSIONS: Our study provides the first in vivo and in patient evidence supporting the role of CHD1 in DSB repair and in response to DNA damaging therapy. We uncover mechanistic insights that CHD1 modulates the choice between HR and NHEJ DSB repair and suggest that CHD1 loss may contribute to the genomic instability seen in this subset of PCas.


Assuntos
Proteínas Cdh1/deficiência , Reagentes de Ligações Cruzadas/farmacologia , Quebras de DNA de Cadeia Dupla , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Neoplasias da Próstata/terapia , Animais , Proteínas Cdh1/genética , Linhagem Celular Tumoral , Reparo do DNA por Junção de Extremidades , Relação Dose-Resposta a Droga , Regulação para Baixo , Deleção de Genes , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Humanos , Masculino , Camundongos Knockout , Fenótipo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Estabilidade Proteica , Tolerância a Radiação , Reparo de DNA por Recombinação , Fatores de Tempo , Células Tumorais Cultivadas , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/metabolismo
17.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 52(4): 232-237, 2017 Apr 09.
Artigo em Chinês | MEDLINE | ID: mdl-28412789

RESUMO

Objective: To explore the clinical application of home-made temporomandibular joint (TMJ) prostheses. Methods: Self-developed TMJ prostheses were applied for end stage osteoarthritis, TMJ ankylosis, condylar tumors after biomechanical examination. The stability of the prostheses toward bone was evaluated during operation. Post-operative CT scans and clinical follow-ups were taken to check changes of mouth opening, position of the prostheses, bone resorption around the screws, and heterotopic bone formation around artificial condyle. Results: There were 6 patients accepted 7 prostheses smoothly without infection and other complications. Post-operative follow-ups were from 6 to 13 months with a mean of 7.6 months. Mouth opening was significantly improved from (16.2±14.4) mm before operation to (31.5±4.8) mm during follow-ups (P=0.01). All prostheses were stable without screw loose and heterotopic bone formation. Conclusions: Home-made TMJ prostheses were stable after primary clinical application, but the long-term results need to be observed.


Assuntos
Anquilose/cirurgia , Artroplastia de Substituição , Neoplasias Ósseas/cirurgia , Prótese Articular , Osteoartrite/cirurgia , Transtornos da Articulação Temporomandibular/cirurgia , Articulação Temporomandibular/cirurgia , Reabsorção Óssea/diagnóstico por imagem , Parafusos Ósseos , Feminino , Seguimentos , Humanos , Masculino , Côndilo Mandibular , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
18.
Zhonghua Zhong Liu Za Zhi ; 39(3): 216-219, 2017 Mar 23.
Artigo em Chinês | MEDLINE | ID: mdl-28316223

RESUMO

Objective: To evaluate the feasibility and efficacy of biweekly paclitaxel and platinum chemotherapy followed by surgery for esophageal squamous cell carcinoma. Methods: We retrospectively analyzed the clinicopathological data of 20 patients with esophageal squamous cell carcinoma treated in our hospital between January 2012 and March 2016. All patients received biweekly paclitaxel and platinum chemotherapy followed by surgery. Results: 20 cases received preoperative chemotherapy for 3-8 cycles with an average of 4 cycles. The main chemotherapy-related adverse events were bone marrow suppression (18/20, 90.0%), followed by vomiting and nausea (10/20, 50.0%). Five patients (25.0%) had grade 4 neutropenia and all toxicities were torlerable and manageable. After chemotherapy, all patients received surgery. The histological responses in the primary tumors were grade 1 in 13 (65.0%) patients, grade 2 in 7 (35.0%) patients, and grade 3 in 0 (0%) patient. None had disease progression. Downstaging of T-stage was observed in 5 cases (25.0%) after chemotherapy. Among them, 4 cases were with moderate histologicl responses and one case with mild histological response. The incidence of postoperative complications was 25.0%(5/20), and the complications were improved following symptomatic treatments. There was no treatment-related death. Conclusions: Biweekly paclitaxel and platinum chemotherapy followed by surgery for esophageal squamous cell carcinoma is safe and effective. Further randomized clinical trial should be conducted to assess the value of this therapeutic regimen in the preoperative chemotherapy for esophageal cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/patologia , Terapia Combinada/métodos , Esquema de Medicação , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Incidência , Masculino , Náusea/induzido quimicamente , Neutropenia/induzido quimicamente , Paclitaxel/administração & dosagem , Compostos de Platina/administração & dosagem , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Vômito/induzido quimicamente
19.
Eur Rev Med Pharmacol Sci ; 20(1): 75-81, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26813456

RESUMO

OBJECTIVE: To study the correlation factors of bone marrow suppression in breast cancer radiotherapy and find out the method to guide the target area, dose limitation for breast cancer to reduce the risk of bone marrow suppression. PATIENTS AND METHODS: 72 cases of breast cancer patients were collected through retrospective, clinical control study. For patients with Grade 0-3, bone marrow suppression in the course of radiotherapy, the dose-volume parameters (V5, V10, V20, V30, V50, D20, D40, D60, D80, D100, Min, Max, Dmean) of the chest and rib of each patient were collected and analyzed from multiple points including tumor stage, age, lesion location, surgical approach, chemotherapy regimen and the number of cycles, bone dose-volume parameters. RESULTS: The relative parameters of the rib in the middle and severe bone marrow suppression group were significantly higher than those in the mild bone marrow depression group and the p values of V5, V10, V20, V30, Dmean, D40, D60, D80, D100 were less than 0.05. The difference of V50 in the two groups was statistically significant (p <0.05). For chemotherapy regimens containing doxorubicin, epirubicin, cyclophosphamide, the differences between bone marrow suppression group and non-bone marrow suppression were statistically significant (p =0.002). CONCLUSIONS: The dose-volume parameters of the rib radiation is one of the main factors causing the suppression of bone marrow in radiotherapy, and the volume of the 50Gy irradiation is also a contribution to the bone marrow. For patients accepted chemotherapy with doxorubicin, epirubicin, cyclophosphamide before radiotherapy, bone marrow suppression is more likely to occur during radiotherapy. After radical mastectomy or the volume of thoracic rib is increased because of the small breast, the occurrence of bone marrow suppression is increased. The effects of radiation on the bone marrow suppression were small, while its effect on the ribs was more evident, especially on the ribs V20 and Dmean and the difference was statically significant.


Assuntos
Medula Óssea , Neoplasias da Mama , Radioterapia de Intensidade Modulada , Adulto , Idoso , Medula Óssea/efeitos dos fármacos , Neoplasias da Mama/radioterapia , Feminino , Humanos , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Radioterapia Conformacional/efeitos adversos , Estudos Retrospectivos , Costelas/efeitos da radiação
20.
Zhonghua Fu Chan Ke Za Zhi ; 51(12): 928-933, 2016 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-28057129

RESUMO

Objective: To explore the expression of Ras-related protein 11 (Rab11) in hypoxia, the effect of Rab11 on the invasion and migration of cervical cancer cell line SiHa and its possible mechanism. Methods: SiHa cells were divided into 4 groups, the normoxic blank group (normal culture in normoxia), the hypoxic blank group (normal culture in hypoxia), the negative control group [transfection of negative control small interfering RNA (siRNA) in hypoxia], the Rab11-siRNA group (transfection of Rab11 siRNA in hypoxia). Western blot was used to examine the expression of Rab11, integrin α5, integrin ß3, phosphorylated focal adhesion kinase (p-FAK), phosphorylated phosphatidylinositol 3 kinase (p-PI3K) protein, together with the expression of Ras correlative C3 creotoxin substrate 1 (Rac1), which was critical in regulating cell invasion. The mRNA expression of Rab11 in the 4 groups was detected by realtime-qPCR. The cell invasion was detected by matrigel assay, while the cell migration was detected by transwell assay. Immunofluorescence was used to identify intracellular location of Rac1 in SiHa cell. Results: (1) The expression of Rab11, intergrin α5, intergrin ß3, p-FAK, p-PI3K and Rac1 in the normoxic blank group were 0.56±0.04, 0.33±0.03, 0.32±0.03, 0.36±0.03, 0.35±0.03 and 0.47±0.03, respectively. In the hypoxic blank group, they were 0.73±0.03, 0.74±0.03, 0.61±0.03, 0.62±0.03, 0.60±0.03 and 0.73±0.03, respectively. In the negative control group, their expressions were 0.72±0.03, 0.73±0.03, 0.59±0.03, 0.61±0.03, 0.59±0.03 and 0.72±0.03, respectively. While in the Rab11-siRNA group, they were 0.44±0.03, 0.30±0.03, 0.29±0.03, 0.30±0.03, 0.30±0.03 and 0.34±0.04, respectively. The expressions of Rab11, α5, ß3, p-FAK, p-PI3K and Rac1 were significantly higher in the hypoxic blank group than in the normoxic blank group (P<0.05), and were significantly lower in the Rab11-siRNA group than in the hypoxic blank group and the negative control group (P<0.05). (2) The expressions of Rab11-mRNA were 1.000±0.000, 1.454±0.114, 1.442±0.101, 0.570± 0.046 in the normoxic blank group, the hypoxic blank group, the negative control group and the Rab11-siRNA group, respectively. It was significantly higher in the hypoxic blank group than in the normoxic blank group (P<0.05), and was significantly lower in the Rab11-siRNA group than in the hypoxic blank group and the negative control group (P<0.05). (3) By Matrigel, the invasion cell number in the normoxic blank group, the hypoxic blank group,the negative control group and the Rab11-siRNA group were 65±12, 106±16, 104± 17 and 50±11, respectively. The invasion capacity was significantly higher in the hypoxic blank group than in the normoxic blank group (P<0.05), and was significantly lower in the Rab11-siRNA group than in the hypoxic blank group and the negative control group (P<0.05). (4) By transwell assay, the migration cells in the normoxic blank group, the hypoxic blank group, the negative control group and the Rab11-siRNA group were 127±12, 169±15, 161±13 and 77±13, respectively. The capacity of invasion was significantly higher in the hypoxic blank group than in the normoxic blank group (P<0.05), and was significantly lower in the Rab11-siRNA group than in the hypoxic blank group and the negative control group (P<0.05). (5) The immunofluorescence showed that the red fluorescence intensity around nucleus was significantly increased in the normoxic blank group, the hypoxic blank group and the negative control group than in the Rab11-siRNA group. Conclusions: Hypoxia could promote the invasion and migration of SiHa cells. In hypoxia, the down regulation of Rab11 expression could inhibit the invasion and migration of SiHa cells. This might be due to the decreased expression of the intergrin α5, intergrin ß3, p-FAK, p-PI3K and Rac1 protein.


Assuntos
Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo/genética , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Neoplasias do Colo do Útero/patologia , Linhagem Celular Tumoral , Feminino , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Fosfatidilinositol 3-Quinases , RNA Mensageiro/metabolismo , Transfecção , Neoplasias do Colo do Útero/metabolismo
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