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2.
Eur Rev Med Pharmacol Sci ; 27(5): 1985-1988, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36930496

RESUMO

BACKGROUND: An increasing number of atypical endometrial hyperplasia (AEH) or endometrial cancer (EC) patients with fertility requirements choose conservative management, such as oral high-dose progesterone. Most of them use assisted reproductive technology (ART) to become pregnant after experiencing remission. However, the outcome of pregnancy is not ideal, probably because of long-term drug application in large doses or invasive uterine cavity treatment. CASE REPORT: We presented a case of AEH who underwent direct pregnancy with good results without any treatment for her pathological endometrium. We described her endometrial histological results pre-and post-pregnancy in detail, hitherto absent from reports on this topic. CONCLUSIONS: Patients with a strong desire to bear children at the time of an AEH diagnosis could consider taking 1-2 years to try a pregnancy before treating their AEH.


Assuntos
Hiperplasia Endometrial , Neoplasias do Endométrio , Preservação da Fertilidade , Humanos , Gravidez , Feminino , Hiperplasia Endometrial/diagnóstico , Hiperplasia Endometrial/patologia , Prognóstico , Neoplasias do Endométrio/terapia , Neoplasias do Endométrio/tratamento farmacológico , Endométrio/patologia , Estudos Retrospectivos
4.
Zhonghua Yi Xue Za Zhi ; 102(32): 2489-2494, 2022 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-36008318

RESUMO

Objective: To evaluate the incidence of thromboembolism in a cohort of patients with lung cancer who received immune checkpoint inhibitors (ICIs), and explore relevant clinical risk factors. Methods: We retrospectively collected and analyzed the clinical data of patients with confirmed primary lung cancer and treated with ICIs between March 2018 and June 2021 at three hospitals in China (Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Fudan University Shanghai Cancer Center and Zhongshan Hospital of Fudan University). The cumulative incidence and risk factors of thromboembolism in these patients were analyzed using a competitive risk model. Results: A total of 804 patients were enrolled, there were 623 males and 181 females, with a median age of 59 years (ranged 28-86 years). Of these, 62 patients encountered 65 thromboembolic events, including 51 venous thromboembolism events (VTE) and 14 arterial thromboembolism events. The cumulative incidence of thromboembolism events at 3, 6, 12 and 24 months were 4.3%, 6.1%, 10.1% and 16.8%, respectively. And the cumulative incidence of venous thromboembolism events at 3, 6, 12 and 24 months were 3.4%, 4.7%, 9.0% and 13.3%, respectively. Multivariate analysis showed that history of thromboembolism (HR=6.345, 95%CI: 2.917-13.802,P<0.001),liver metastasis (HR=2.249, 95%CI: 1.123-4.502,P=0.022) and peripherally inserted central venous catheter (HR=3.674, 95%CI: 1.751-7.712, P<0.001) were independent risk factors for venous thromboembolism during ICIs therapy in patients with lung cancer. Conclusions: Patients with lung cancer under ICIs therapy are at high risk of thromboembolism. And history of thromboembolism, liver metastasis and peripherally inserted central venous catheter are risk factors of venous thromboembolism.


Assuntos
Neoplasias Hepáticas , Neoplasias Pulmonares , Tromboembolia Venosa , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Imunoterapia , Incidência , Neoplasias Pulmonares/complicações , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Tromboembolia Venosa/epidemiologia
7.
Zhonghua Yi Xue Za Zhi ; 100(31): 2457-2461, 2020 Aug 18.
Artigo em Chinês | MEDLINE | ID: mdl-32819063

RESUMO

Objective: To analyze the clinical efficacy and safety of cyberknife in the treatment of patients with primary large hepatocellular carcinoma over 70 years old. Methods: A total of 82 patients (58 males and 24 females) with large hepatocellular carcinoma aged over 70 years (70 to 85 years, (75±4) years) with a median tumor diameter of 6.7 cm (5.0~10.0 cm) were retrospectively collected. All patients were diagnosed by pathology or radiography in the Cancer Radiotherapy Center of the Fifth Medical Center of the PLA General Hospital from March 2014 to December 2018, and treated with cyberknife stereotactic radiotherapy. Progression free survival rate (PFS), local control rate (LC), overall survival rate (OS) and adverse reactions were observed at 1, 2 and 3 years. Kaplan-Meier was used for survival analysis, and Cox regression model was used to analyze survival-related factors. Results: All 82 patients successfully completed radiation therapy with a median survival time of 20 months, a median PFS of 10 months, an objective response rate of 64.63% (53/82), and a disease control rate of 85.37% (70/82). After treatment, the PFS at 1, 2, and 3 years were 39.0% (32/82), 22.1% (18/82), and 17.1% (14/82), respectively; the LC at 1, 2, and 3 years were 95.1% (78/82), 92.3% (76/82), and 92.3% (76/82), respectively; and the OS at 1, 2, and 3 years were 68.3% (56/82), 48.8% (40/82) and 31.7% (26/82), respectively. Nine patients suffered from radiation-induced liver disease (RILD), and there were no deaths due to RILD. Cox regression analysis showed that alpha-fetoprotein (AFP) was an independent risk factor for OS (HR=2.304, 95%CI 1.118-4.747;P<0.05). Conclusion: Cyberknife treatment for patients with primary large hepatocellular cancer over 70 years old has higher LC and OS, better curative effect, and less treatment-related adverse reactions.


Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Radiocirurgia , Idoso , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
8.
Zhonghua Bing Li Xue Za Zhi ; 49(5): 454-457, 2020 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-32392929

RESUMO

Objective: To study the clinical and pathologic factors of papillary thyroid microcarcinoma (PTMC) and its significance as a histopathologic subtype of papillary thyroid carcinoma (PTC). Methods: A retrospective study of 719 patients with non-high-risk PTMC who underwent surgery for the first time in the Peking University People's Hospital from January 2007 to June 2019 was conducted, the relationship between clinicopathologic factors and lymph node metastasis, and the expression of four tumor markers CK19, HMBE1, Galectin-3 and CD56 by immunohistochemistry were evaluated. Some comparisons were made with PTC. Results: The peak patients' age was 40-49 years for both non-high-risk PTMC and PTC; the lymph node metastasis rate was higher in the 30-39 years age group than the 50-59 years age group (P<0.05); the lymph nodes metastasis rate was significantly higher for multiple lesions than for single lesion (P<0.05). Lymph node metastasis rate of PTMC with capsular invasion was significantly higher than those without (P<0.05). There was no significant correlation between lymph node metastasis of PTMC and patients' gender, tumor location, tumor size, and lymphocytic thyroiditis. The expression rates of CK19, HMBE1 and Galectin-3 both in PTMC and PTC were 100%, and the expression rates of CD56 were 25.6% (85/332) and 20.0% (70/350) respectively. Conclusion: As the main pathologic subtype of PTC, a variety of clinicopathologic factors of PTMC are related to lymph node metastasis, and it is highly recommended to pay close attention to PTMC. The expression of tumor marker CD56 alone cannot be used as a basis to exclude PTMC and PTC.


Assuntos
Neoplasias da Glândula Tireoide , Adulto , Doença de Hashimoto , Humanos , Linfonodos , Metástase Linfática , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
10.
Animal ; 14(7): 1382-1391, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32051055

RESUMO

Cadmium (Cd) is a toxic heavy metal that poses a threat to the health of humans and animals. It can cause serious damage to the small intestine, which is the main absorption site of Cd and the primary target organ after oral administration. Our previous study found that zinc chelate of hydroxy analogue of methionine (Zn-HMTB), a new type of feed additive, decreased Cd accumulation in the liver and kidneys. The aim of this study was to investigate the effect of Zn-HMTB on Cd absorption and Cd-induced toxicity in the small intestine of piglets. Twenty-four piglets (Landrace × Large White, 13.22 ± 0.58 kg BW) were randomly divided into four dietary treatment groups: basal diet, and diets containing 30 mg/kg Cd from CdCl2 and 0, 100 or 200 mg/kg Zn from Zn-HMTB. The experiment lasted 27 days. The feed intake and final BW of each piglet were recorded at the end of the experiment. Gastrointestinal (GI) tract tissue and samples of liver, kidney, spleen, heart, lung and longissimus muscle tissue and faeces were collected. The concentrations of Cd and metal trace elements in the GI tract and organs were analysed, as was the relative messenger RNA (mRNA) expression of inflammatory cytokines and metal element transporters in the small intestine, and epithelial apoptosis in the small intestine. The results showed that, compared with Cd-treated piglets, piglets in the Zn-HMTB and Cd cotreatment groups had less Cd deposition in the stomach, ileum, caecum, colon, liver, kidneys, spleen, lungs, heart and muscles (P < 0.05), and lower Cd concentrations in faeces (P < 0.05), suggesting that Zn-HMTB increased Cd absorption and the excretion of Cd in other forms (possibly urine). Zinc chelate of hydroxy analogue of methionine increased Zn deposition in the jejunum and the relative mRNA expression of divalent metal transporters 1 and zinc transporter 5 in the duodenum (P < 0.05), indicating that Zn-HMTB may promote the absorption and transportation of Cd and Zn together by upregulating metal element transporters. Competition between Zn and Cd may be responsible for accelerating Cd excretion. Furthermore, Zn-HMTB reduced Cd-induced apoptosis of enterocytes and inflammatory stimuli in the small intestine, suggesting that Zn-HMTB reduced Cd-induced toxicity to the small intestine. These results suggest that Zn-HMTB can be helpful in decreasing Cd accumulation in the GI tract and organs of piglets and relieving Cd-induced toxicity to the small intestine but cannot reduce the absorption of Cd.


Assuntos
Cádmio , Quelantes , Metionina , Zinco , Animais , Cádmio/toxicidade , Quelantes/farmacologia , Humanos , Intestino Delgado , Intestinos , Suínos , Zinco/farmacologia
12.
Eur Rev Med Pharmacol Sci ; 23(9): 3867-3875, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31115014

RESUMO

OBJECTIVE: This study aimed at exploring the role and mechanism of Krüppel-like factor 5 (KLF5) in the migration, invasion, epithelial-mesenchymal transition (EMT) induction and proliferation in laryngeal cancer human epithelial type 2 (Hep-2) cells, and to provide a new sight for the treatment of laryngeal carcinoma. MATERIALS AND METHODS: Hep-2 cells were randomly divided into three groups: control group (Control), KLF5 siRNA group (siKLF5) and control-siRNA group (NC). The effects of KLF5 inhibition on cell proliferation and apoptosis were assessed by 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometer, respectively. Wound healing assay and transwell invasion experiments were used to determine cell migration and invasion. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot were used to compare the levels of KLF5, EMT-related genes E-cadherin, N-cadherin, Vimentin and Zinc finger transcription factors (Snail, Slug) expressions. The levels of nuclear transcription factor-κB (NF-κB-p65) and IκBα were also detected by Western blot. RESULTS: Compared with the Control group, the proliferation rate of Hep-2 cells in the siKLF5 group was significantly decreased while the apoptosis rate was increased (p<0.05). Meanwhile, the migration and invasion ability of Hep-2 cells were markedly decreased (p<0.05). E-cadherin protein expression was up-regulated while Vimentin, N-cadherin, Snail, and Slug protein expression levels were downregulated in siKLF5 group (p<0.05). Silencing KLF5 could inhibit the expression of NF-κB phosphorylation at p65 and the IκBα degradation (p<0.05). CONCLUSIONS: These results revealed that silencing KLF5 expression reduced the proliferation, migration and invasion and EMT abilities by inhibiting the NF-κB pathway in Hep-2 cells. Our results suggest that KLF5 may be a potential therapeutic target in laryngeal carcinoma.


Assuntos
Transição Epitelial-Mesenquimal , Fatores de Transcrição Kruppel-Like/metabolismo , NF-kappa B/metabolismo , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Fatores de Transcrição Kruppel-Like/antagonistas & inibidores , Fatores de Transcrição Kruppel-Like/genética , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , Inibidor de NF-kappaB alfa/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Fatores de Transcrição da Família Snail/metabolismo , Fator de Transcrição RelA/metabolismo , Vimentina/metabolismo
13.
Zhonghua Bing Li Xue Za Zhi ; 48(2): 92-97, 2019 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-30695858

RESUMO

Objective: To investigate the expression of immunomarkers CK7, CK20, CK17, CDX2, MUC1 and MUC2 in primary adenocarcinoma of the ampulla of Vater, to explore the role of these markers in the histopathologic subclassification of ampullary carcinoma; and to provide biologic basis for precision treatment of patients with different types of ampullary carcinoma. Methods: Forty-two cases of primary ampullary carcinoma were collected at Peking University People's Hospital, from 2012 to 2018 year. There were 22 males and 20 females. Aged range 42 to 88 years old, with mean aged (62±11) years. Among the patients, 6 was high differentiation, 19 median differentiation, and 17 low differentiation. Immunohistochemical studies on the expression of CK7, CK20, CK17, CDX2, MUC1 and MUC2 were performed in 42 cases of primary ampullary carcinoma. The relationship between different ampullary carcinoma subtypes and clinicopathologic survival data was analyzed using SPSS 16.0 statistical software. Results: Three histopathologic subtypes were observed. Among 42 cases, 8(19.0%)were classified as intestinal subtype, which showed a positive expression rate of 8/8 for both CK20 and CDX2, and 5/8 for MUC2. Both CK7 and CK17 were weakly expressed in one case (1/8). No expression was observed for MUC1 in this subtype. Twenty-two (52.4%,22/42) cases were classified as pancreaticobiliary subtype, which showed a positive expression rate of 100.0%(22/22) for both CK7 and MUC1, and 90.9% (20/22) for CK17. No expression was observed for CK20, CDX2 and MUC2.The remaining 12 (28.6%) cases were classified as mixed subtype, which showed variable expression patterns. The expression frequencies of these 6 immunomarkers in different subtypes of ampullary carcinoma did not correlate with various clinicopathologic factors such as patient gender and age, tumor size, histologic differentiation, pancreatic and bile duct invasion, or the depth of duodenal invasion. However, stage Ⅲ+Ⅳ diseases were more commonly seen in pancreaticobiliary type (63.6%,14/22) than intestinal type (2/8) and mixed type (3/9; χ(2)=6.508, P=0.039). Follow-up data showed a trend of better survival rate for patients with intestinal subtype than those with mixed and pancreaticobiliary subtypes. Conclusions: Ampullary carcinoma can be subclassified into three different subtypes using a panel of six immunomarkers, especially for the identification of subtypes of poorly differentiated carcinoma. CK7, CK17 and MUC1 are major markers of pancreaticobiliary subtype, whereas CK20, CDX2 and MUC2 are useful markers for intestinal subtype. The mixed subtype variably expresses these markers. The prognosis of patients with intestinal subtype appears better than that of pancreaticobiliary and mixed subtypes. Accurate subtyping of ampullary carcinoma is clinically important to patient management and prognosis assessment.


Assuntos
Adenocarcinoma/química , Ampola Hepatopancreática/química , Biomarcadores Tumorais/análise , Neoplasias do Ducto Colédoco/química , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ampola Hepatopancreática/patologia , Fator de Transcrição CDX2/análise , Neoplasias do Ducto Colédoco/patologia , Feminino , Humanos , Imuno-Histoquímica , Queratina-17/análise , Queratina-20/análise , Queratina-7/análise , Masculino , Pessoa de Meia-Idade , Mucina-1/análise , Mucina-2/análise
15.
Zhonghua Zhong Liu Za Zhi ; 40(10): 787-792, 2018 Oct 23.
Artigo em Chinês | MEDLINE | ID: mdl-30392345

RESUMO

Objective: To investigate the clinical effectiveness of postoperative nutritional support in patients undergoing hepatectomy for hepatocellular carcinoma (HCC). Methods: A total of 379 HCC patients who received partial hepatectomy from January 2010 to December 2013 in Department of Hepatobiliary Surgery of Cancer Hospital, Chinese Academy of Medical Sciences were selected. Based on the nutritional method, all of the enrolled patients were divided into two group: 142 patients who received early enteral nutrition (EEN) combined with parenteral nutrition (PN) were identified as EEN+ PN group; 237 patients who received total parenteral nutrition (TPN) were identified as TPN group. These two groups were even divided into two subgroups, centrally located HCC (cl-HCC) and non-centrally located HCC (ncl-HCC). The clinical effectiveness of different groups was assessed and compared. Results: The age, gender, body mass index (BMI), the maximum diameter of the tumor, the amount of operative bleeding and postoperative infective rate did not show statistically significant differences between EEN+ PN group and TPN group (P>0.05). On the seventh postoperative day (7(th) POD), aspartate transaminase (AST) of EEN+ PN group and TPN group were (41.6±2.0) IU/L and (50.4±3.2) IU/L respectively, and the difference was statistically significant (P<0.05). Alkaline phosphatase (ALP) of these two groups were (80.8±2.4) IU/L and (90.2±2.3) IU/L, respectively, and the difference was statistically significant (P<0.05). Total bilirubin (TBIL) of these two groups were (15.8±0.7) µmol/L and (19.1±0.7) µmol/L, respectively, and the difference was statistically significant (P<0.05). On the 7(th) POD, AST in cl-HCC subgroups of EEN+ PN group and TPN group were (39.6±2.6) IU/L and (61.0±7.0) IU/L, respectively, and the difference was statistically significant (P<0.05). TBIL in cl-HCC subgroups of these two groups were (14.4±0.9) µmol/L and (20.7±1.3) µmol/L, respectively, and the difference was statistically significant (P<0.05). On the 7(th) POD, ALP in ncl-HCC subgroups of these two groups were (79.3±3.0) IU/L and (89.9±3.1) IU/L, respectively, and the difference was statistically significant (P<0.05). The total length of stay (t-LOS) of these two groups were (15.8±0.4) days and (17.1±0.4) days, respectively, and the difference was statistically significant (P<0.05). Postoperative LOS (postop-LOS) of these two groups were (8.6±0.2) days and (10.1±0.3) days, respectively, and the difference was statistically significant (P<0.05). Total length of stay (t-LOS) in ncl-HCC subgroups of these two groups were (15.1±0.5) days and (16.6±0.3) days, respectively, and the difference was statistically significant (P<0.05). Postoperative LOS (postop-LOS) in ncl-HCC subgroups of these two groups were (8.4±0.2) days and (9.5±0.2) days, respectively, and the difference was statistically significant (P<0.05). Postoperative LOS (postop-LOS) in cl-HCC subgroups of these two groups were (8.7±0.2) days and (11.0±0.8) days, respectively, and the difference was statistically significant (P<0.05). Postoperative hospitalization expenses of these two groups were (20 855.0±549.8) yuan and (23 373.0±715.5) yuan, respectively, and the difference was statistically significant (P<0.05). Postoperative hospitalization expenses in cl-HCC subgroups of these two groups were (21 012.0±748.5) yuan and (24 697.0±1 409.0) yuan, respectively, and the difference was statistically significant (P<0.05). Conclusion: EEN+ PN can improve the liver function, shorten the postoperative hospitalization time and reduce the postoperative hospitalization expenses of HCC patients in need of nutritional support.


Assuntos
Carcinoma Hepatocelular/cirurgia , Nutrição Enteral , Hepatectomia , Neoplasias Hepáticas/cirurgia , Nutrição Parenteral , Cuidados Pós-Operatórios , Nutrição Enteral/economia , Humanos , Tempo de Internação/economia , Apoio Nutricional , Nutrição Parenteral/economia , Cuidados Pós-Operatórios/economia , Cuidados Pós-Operatórios/métodos , Período Pós-Operatório , Resultado do Tratamento
16.
Eur Rev Med Pharmacol Sci ; 22(9): 2801-2808, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29771432

RESUMO

OBJECTIVE: To explore whether microRNA-377 could participate in the development of Alzheimer's disease (AD) by regulating CDH13. MATERIALS AND METHODS: In this research, AD model was constructed by the SH-SY5Y cells. The expression levels of microRNA-377 and CDH13 in the AD model were detected by quantitative Real-time polymerase chain reaction (qRT-PCR). The cell viability and apoptosis after knockdown of microRNA-377 and CDH13 were measured by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. The regulatory mechanism of microRNA-377 on CDH13 was confirmed by dual-luciferase reporter gene assay, qRT-PCR and Western blot. RESULTS: Downregulated microRNA-377 and upregulated CDH13 were observed after successful construction of the AD model. Cell viability in the AD model group was significantly reduced compared with that of the control group. Moreover, downregulated microRNA-377 could further inhibit the cell viability, which was reversed by CDH13 knockdown. Cell apoptosis in the AD model group was enhanced after microRNA-377 knockdown, which was rescued by decreasing the expression level of CDH13. MicroRNA-377 was confirmed to regulate the expression level of CDH13 by dual-luciferase reporter gene assay, qRT-PCR and Western blot. CONCLUSIONS: MicroRNA-377 could regulate the expression level of CDH13 by promoting cell proliferation and inhibiting cell apoptosis, thus participating in the occurrence of the Alzheimer's disease.


Assuntos
Doença de Alzheimer/metabolismo , Caderinas/biossíntese , MicroRNAs/fisiologia , Doença de Alzheimer/genética , Apoptose/fisiologia , Caderinas/genética , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Sobrevivência Celular/fisiologia , Expressão Gênica , Humanos
17.
Curr Oncol ; 24(6): e518-e523, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29270061

RESUMO

BACKGROUND: In this paper, we report on the process of strategic planning in the Radiation Medicine Program (rmp) at the Princess Margaret Cancer Centre. The rmp conducted a strategic planning exercise to ensure that program priorities reflect the current health care environment, enable nimble responses to the increasing burden of cancer, and guide program operations until 2020. METHODS: Data collection was guided by a project charter that outlined the project goal and the roles and responsibilities of all participants. The process was managed by a multidisciplinary steering committee under the guidance of an external consultant and consisted of reviewing strategic planning documents from close collaborators and institutional partners, conducting interviews with key stakeholders, deploying a program-wide survey, facilitating an anonymous and confidential e-mail feedback box, and collecting information from group deliberations. RESULTS: The process of strategic planning took place from December 2014 to December 2015. Mission and vision statements were developed, and core values were defined. A final document, Strategic Roadmap to 2020, was established to guide programmatic pursuits during the ensuing 5 years, and an implementation plan was developed to guide the first year of operations. CONCLUSIONS: The strategic planning process provided an opportunity to mobilize staff talents and identify environmental opportunities, and helped to enable more effective use of resources in a rapidly changing health care environment. The process was valuable in allowing staff to consider and discuss the future, and in identifying strategic issues of the greatest importance to the program. Academic programs with similar mandates might find our report useful in guiding similar processes in their own organizations.

18.
Zhonghua Gan Zang Bing Za Zhi ; 25(6): 440-445, 2017 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-28763862

RESUMO

Objective: To establish a screening system for anti-metastatic small-molecule compounds based on perinucleolar compartment (PNC) prevalence in liver cancer cells and to investigate its validity. Methods: Polypyrimidine tract-binding protein (PTB) monoclonal antibody was used to measure the PNC prevalence in HepG2, HepG2M, and Huh7 cells, and wound healing assay and transwell assay were used to analyze the migration and invasion abilities of hepatoma cells. HepG2M cells were used as the model for the screening of anti-metastatic small-molecule compounds, and after the treatment with the compounds A1, A4, and E696, qPCR was used to measure the expression of metastasis-related miRNAs (miR-141 and miR-200c). A one-way analysis of variance was used for comparison of data between multiple groups. Results: PTB immunofluorescence assay showed that HepG2M cells had the highest PNC prevalence, followed by Huh7 and HepG2 cells, and PNC prevalence was positively correlated with the metastasis and invasion abilities of hepatoma cells. The PNC prevalence of HepG2M cells was reduced to 22.88% ±4.61% by A1, 14.22% ± 3.05% by A4, and 26.12% ± 4.94% by E696. Wound healing assay showed that the 48-hour scratch ratio increased from 17.70% ± 3.34% to 64.50% ± 2.65%, 83.40% ± 5.10%, and 57.20% ± 3.06% (F = 171.1, P < 0.01), respectively. Transwell assay showed that the number of invasive cells was reduced from 264.33 ± 30.50 to 104.33 ± 13.50, 58.00 ± 11.00, and 111.33 ± 19.50 (F = 59.87, P < 0.01), respectively. The anti-metastatic effect of these three compounds was positively correlated with their ability to destroy PNC. A4 upregulated the expression of miR-141 and miR-200c in a dose-dependent manner, and after HepG2M cells were treated with A4 at a concentration of 5 µM, 10 µM, or 20 µM, the level of miR-141 was increased to 3.61 ± 0.78, 8.12 ± 1.15, and 18.24 ± 2.44 folds (F = 88.01, P < 0.01), respectively, and that of miR-200c was increased to 2.82 ± 0.43, 4.82 ± 0.89, and 10.74 ± 1.22 folds (F = 87.94, P < 0.01), respectively. Conclusion: The screening system for anti-metastatic small-molecule compounds based on PNC prevalence can provide an effective technical platform for research and development of anti-metastatic drugs for liver cancer.


Assuntos
Núcleo Celular , Detecção Precoce de Câncer , Neoplasias Hepáticas/patologia , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias/diagnóstico , Adulto , Biomarcadores , Movimento Celular , Humanos , MicroRNAs , Proteína de Ligação a Regiões Ricas em Polipirimidinas , Prevalência
19.
Hum Exp Toxicol ; 36(8): 802-812, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27596071

RESUMO

Nano nickel oxide (NiO), widely used in industry, has recently been discovered to have pulmonary toxicity. However, no subchronic exposure studies about nano NiO-induced pulmonary fibrosis have been reported. The objective of this study was to investigate pulmonary fibrosis induced by nano NiO and its potential mechanism in rats. Male Wistar rats ( n = 40, 200-240 g) were randomized into control group, nano NiO groups (0.015, 0.06, and 0.24 mg/kg), and micro NiO group (0.024 mg/kg). All rats were killed to collect lung tissue after intratracheal instillation of NiO particles twice a week for 6 weeks. To identify pulmonary fibrosis, Masson trichrome staining, hydroxyproline content, and collagen protein expression were performed. The results showed widespread lung fibrotic injury in histological examination and increased content of hydroxyproline, collagen types I and III in rat lung tissue exposed to nano NiO. To explore the potential pulmonary fibrosis mechanism, transforming growth factor beta 1 (TGF- ß1) content was measured by enzyme-linked immunosorbent assay, and the messenger RNA expression of key indicators was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The TGF- ß1 content was increased in nano NiO exposure groups, as well as the upregulated gene expression of TGF- ß1, Smad2, Smad4, matrix metalloproteinase, and tissue inhibitor of metalloproteinase. The findings indicated that nano NiO could induce pulmonary fibrosis, which may be related to TGF- ß1 activation.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Níquel/toxicidade , Fibrose Pulmonar/induzido quimicamente , Fator de Crescimento Transformador beta1/metabolismo , Animais , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Fator de Crescimento Transformador beta1/genética
20.
Clin Oncol (R Coll Radiol) ; 28(12): e184-e191, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27542573

RESUMO

AIMS: Breast radiotherapy treatment is commonly managed by a multidisciplinary team to ensure optimal delivery of care. We sought a new model of care whereby a clinical specialist radiation therapist (CSRT) delineates the cavity target for whole breast radiotherapy treatment planning and the radiation oncologist validates the contour during final plan review. This study evaluated the radiation oncologist's acceptance of these contours and identified characteristics of cavities suitable for CSRT-directed contouring. MATERIALS AND METHODS: Following specialised breast oncology education and training by the radiation oncologist, the CSRT prospectively delineated cavities in 30 tangential breast radiotherapy cases and consulted the radiation oncologist in 'complex' cases but directed 'non-complex' cases for treatment planning. Changes to CSRT contours were evaluated using the conformity index. Breast density, time since surgery and cavity location, size and visualisation score [CVS: range 1 (no visible cavity) to 5 (homogenous cavity)] were captured. RESULTS: Of the 30 CSRT delineated cavities contours, the CSRT directed 20 (66.7%) cases for planning without radiation oncology review; 19 were accepted (without changes) by the radiation oncologist upon final plan review and one was changed by the radiation oncologist (conformity index = 0.93) for boost treatment and did not affect the tangential treatment plan. Ten (33.3%) cases, all CVS ≤ 3, were reviewed with the radiation oncologist before planning (conformity index = 0.88 ± 0.12). CVS was inversely correlated with breast density and cavity size (P < 0.01). CONCLUSIONS: The CSRT delineated cavities appropriate for clinical radiotherapy treatment planning in women with well-visualised cavities, whereas 'complex' cases with dense breast parenchyma, CVS ≤ 3, and/or cases needing boost radiotherapy treatment required review with the radiation oncologist before planning.


Assuntos
Neoplasias da Mama/radioterapia , Pessoal de Saúde , Radioterapia (Especialidade) , Planejamento da Radioterapia Assistida por Computador/métodos , Feminino , Humanos , Recursos Humanos
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