RESUMO
Objective: To quantitatively analyze the reticulin fiber intensity density (RFD) in patients with myelodysplastic syndrome (MDS) by using the computer-aided grid point method, and preliminarily explore its correlation with the prognosis of MDS patients. Methods: Bone marrow (BM) slices from 32 primary MDS patients treated in Tongren Hospital Shanghai Jiao Tong University School of Medicine from February 2017 to December 2019 were observed. Images were taken by the optical microscope imaging system after the Gomori staining. The computer grid marking software was developed according to the principle of the mesh micrometer to assess RFD, meanwhile, the artificial semi-quantitative were used to assess the fibrosis of bone marrow. The co-relation between the above two methods was evaluated, and the relationship between RFD and prognosis of MDS patients were further investigated with Cox regression analysis. Results: Of the patients, there were 17 males and 15 females with a median age of 69 years (32-91 years). The RFD quantitatively analyzed by the computer-based method was positively correlated with the myelofibrosis grade by the artificial semi-quantitative analysis (r=0.497, P=0.004). The RFD in patients diagnosed with MDS complicated with excess blasts (MDS-EB) was significantly higher than that in the non-MDS-EB group((9.55%±0.75%) vs (1.71%±0.23%), P<0.001). Cox regression model analysis showed that the RFD of MDS patients had better prognostic value when compared with the artificial semi-quantitative analysis, which was also a poor prognostic factor (RR=1.337, 95%CI: 1.085-1.648, P=0.006). The overall survival (OS) of patients with RFD>5.54% was significantly shorter than that with RFD≤5.54% (P=0.001). The OS of MDS-EB patients with RFD>9.81% was significantly shorter than that in patients with RFD≤9.81% (P=0.003). Conclusion: Abnormal proliferative fibrosis of bone marrow is a potential high-risk factor for poor prognosis of MDS patients.
Assuntos
Síndromes Mielodisplásicas , Mielofibrose Primária , Idoso , China , Feminino , Humanos , Masculino , Prognóstico , Estudos RetrospectivosRESUMO
Biliary tract cancers(BTC),including gallbladder cancer and cholangiocarcinoma,has the characteristics of low early diagnosis rate,complex anatomy,insensitivity to radiotherapy and chemotherapy, and poor prognosis.In recent years,immunotherapy as a new method,has made great progress in the treatment of advanced malignant tumors.Immunotherapy is gradually applied in the treatment of BTC,such as inhibitory agents targeting the immune checkpoint receptor pathway,adoptive immunotherapy and tumor vaccines.
Assuntos
Neoplasias dos Ductos Biliares , Neoplasias do Sistema Biliar , Colangiocarcinoma , Imunoterapia , Neoplasias dos Ductos Biliares/terapia , Neoplasias do Sistema Biliar/terapia , Colangiocarcinoma/terapia , HumanosRESUMO
Objective: To investigate the expression pattern of tropomyosin 2(TPM2) in aorta of patients with aortic dissection and explore its clinical implication. Methods: Thirteen cases with acute type A aortic dissection(TAAD) diagnosed by transabdominal aortic angiography from 2015 in Tongji Hospital were included. During the operation, the aortic wall tissues of these patients were collected. Ten patients with heart transplantation were selected as control group, and normal aortic wall tissues were taken. The hematoxylin-eosin (HE) and Verhoeff's Van Gieson (EVG) staining were performed to observe the morphological changes of aorta. The mRNA expression level of TPM2 was measured by real-time fluorescent quantitative-PCR, and the protein levels of TPM2 were detected by Western blot and immunohistochemical staining. Image The J software was used to collect the optical density values of each point on the image, obtain the integrated optical density(IOD) value, and calculate the average density(%, IOD/area of the target distribution area). Results: HE and EVG staining revealed medial degeneration and broken elastic fiber in aorta of TAAD patients. The mRNA expression levels of TPM2 were significantly upregulated in aorta of TAAD patients as compared to the control group (P<0.05), so as the TPM2 protein expression levels ((9.73±1.20)% vs. (0.11±0.04)%, P<0.05). And TPM2 was mainly expressed in cytoplasm. Conclusion: The increased expression of TPM2 in TAAD patients hints that TPM2 might be involved in the pathogenesis of aortic dissection.
Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Dissecção Aórtica/genética , Aorta , Aneurisma da Aorta Torácica/genética , Expressão Gênica , Humanos , RNA Mensageiro , Tropomiosina/metabolismoRESUMO
Objective: To investigate the association between plasma selenium exposure and the risk of impaired glucose regulation (IGR). Methods: A case-control study was conducted to select IGR patients who were admitted to the outpatient clinic of the Department of Endocrinology to perform oral glucose tolerance test(OGTT) at the Tongji Hospital affiliated to the Tongji Medical College from September 2004 to 2016 as a case group. Participants with normal glucose tolerance recruited from an unselected group of population undergoing routine health examinations in the same hospital were selected as a control group. The control group was matched according to the age (±5 years old) and sex of the case group. The inclusion criteria for subjects recruited were as follows: age ≥30 years, body mass index (BMI) <40â¯kg/m(2), no history of a diagnosis of IGR or type 2 diabetes, and no history of receiving pharmacological treatment for hyperlipidemia or hypertension. Patients with any clinically systemic disease such as neurological or endocrine disease, acute illness, chronic inflammatory disease or infectious disease were excluded from the study. A total of 1 957 subjects, 897 in the case group and 1 060 in the control group, were included. Questionnaires were used to collect information of all subjects, and peripheral venous blood was collected after fasting and OGTT, respectively. Plasma selenium, fasting blood glucose, blood lipid (total cholesterol, triglycerides, high density lipoprotein cholesterol, and low density lipoprotein cholesterol) and 2 h OGTT plasma glucose concentration were detected, respectively. The subjects were divided into low, medium and high concentration groups according to the tertiles of plasma selenium concentration in the control group. The multivariate unconditional logistic regression analysis was performed to analyze the association between plasma selenium exposure and IGR. Results: The age (mean±SD) of the case and control group was (53.71±11.38) and (53.95±12.17) years old. The plasma selenium concentration [M (P(25), P(75))] in the case group was 92.81(77.07, 107.05) µg/L, which was significantly higher than the control group [88.73 (77.13, 100.88) µg/L] (P<0.05). The results of multivariate unconditional logistic regression analysis showed that after adjusting for age, sex, BMI, family history of diabetes and hypertension, the risk of IGR was higher in the high-concentration group and the low-concentration group compared with the middle-concentration group, the values of OR (95%CI) were 1.22 (95%CI: 0.94-1.59) and 1.81 (95%CI: 1.42-2.30), respectively. Conclusion: The study suggested a U-shaped association between plasma selenium and IGR.
Assuntos
Diabetes Mellitus Tipo 2 , Intolerância à Glucose , Selênio , Adulto , Idoso , Glicemia/metabolismo , Índice de Massa Corporal , Estudos de Casos e Controles , Pré-Escolar , China/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Glucose , Humanos , Pessoa de Meia-Idade , Selênio/sangueRESUMO
Objectives: To study the clinical characteristics of pancreatic tuberculosis, and therefore to improve the diagnosis and treatment of this disease. Methods: The clinical data of 10 patients with pancreatic tuberculosis form 1990 to 2017 were reviewed, including clinical characteristics, laboratory tests and imaging features. Results: The ten patients aged 28 to 71 (median 56) years. All of them presented varying degrees of abdominal pain and weight loss (3 to 8 kg). Hypo-echoic pancreatic masses were shown by abdominal ultra-sound in 7 cases, and cystic-solid masses with thick wall was shown by abdominal CT scan in 4 cases, but dilatation of the pancreatic duct was found in none of the 10 cases. Hemoglobin levels lower than 12 g/L were found in 6 cases, and ESR more than 20 mm/1 h was present in 7 cases. Four cases received PPD test, but only one was positive. CA19-9 was found to be higher than normal (27 IU/ml) in 3 cases (39.2 IU/ml, 125.7 IU/ml, 88.9 IU/ml respectively). Three cases received T-spot.TB tests, and all the results were positive. Seven cases received laparotomy, and the other 3 received endoscopic ultrasound-guided biopsy. Caseous necrosis and Langerhans cells were found in all the 10 cases. Nine patients were treated by 6 to 12 months' anti-tuberculosis therapies, and at 1-5 years' follow-up, 8 were cured and 1 improved. Conclusions: The manifestations of pancreatic tuberculosis were easy to be confused with other diseases, and therefore a comprehensive understanding of history and careful examinations were important for a correct diagnosis. Once the diagnosis was made, prompt standard anti-tuberculosis therapy could lead to a favorable outcome.
Assuntos
Abdome/diagnóstico por imagem , Pancreatopatias/diagnóstico , Tomografia Computadorizada por Raios X , Tuberculose/diagnóstico , Adulto , Idoso , Antituberculosos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Pancreatopatias/tratamento farmacológico , Pancreatopatias/microbiologia , Tuberculose/tratamento farmacológico , Tuberculose/microbiologiaRESUMO
Objective: To explore the relationship between liver controlled attenuation parameters (CAP) and body fat mass and its distribution. Methods: From May to December 2018, 978 adult patients visited at the fatty liver center of the Third People's Hospital of Changzhou were treated. The patient's liver controlled attenuation parameters were measured by transient elastography and the body fat mass and its distribution were measured by bioelectrical impedance technology. Pearson's correlation coefficient was adopted to describe the correlation between liver CAP value and body mass index (BMI), body fat mass index (BFMI), trunk fat mass index (TFMI), limbs fat mass index (LFMI) and visceral fat area (VFA). Receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to evaluate BMI, BFMI, TFMI, LFMI and VFA to differentiate the cut-off points and efficacy of CAP for diagnosing grading of fatty liver changes in S0-1 and S2-3. Results: In 653 cases of male, S0 ~ S3 accounted for 4.90%, 3.37%, 22.36% and 69.37%, respectively, and in 325 cases of females, S0 ~ S3 accounted for 7.38%, 6.46%, 13.23% and 72.92%, respectively. Female patients had more visceral, trunk and limbs fat than male (P < 0.01). Body mass, body fat mass, body fat percentage, BMI, BFMI, TFMI, LFMI, and VFA were increased in male and female patients with increasing liver fat grade (P < 0.01). CAP values ââof male and female patients were positively correlated with BMI, BFMI, TFMI, LFMI and VFA. Percentage of body fat mass increased with increasing liver fat grade (male: F = 13.42, P < 0.001; female: F = 3.22, P = 0.023); while limb fat mass percentage did not increase with liver fat grade (Male: F = 1.13, P = 0.34; female: F = 1.05, P = 0.37). Hepatic steatosis grading (S0 ~ 1 or S2 ~ 3) diagnosed with CAP were distinguished through BMI, BFMI, TFMI, LFMI and VFA. AUC was 0.80 ~ 0.82 in males (P < 0.01), and 0.75 ~ 0.78 in females (P < 0.01). Conclusion: The liver CAP value is positively correlated with the body's limbs, trunk and visceral fat, and has a strong correlation with trunk and visceral fat. BMI, BFMI, TFMI, LFMI and VFA up to some extent can identify the CAP diagnosis of grading of fatty liver changes in S0-1 and S2-3.
Assuntos
Adiposidade , Técnicas de Imagem por Elasticidade , Fígado Gorduroso/diagnóstico por imagem , Tecido Adiposo , Adulto , Biópsia , Índice de Massa Corporal , Feminino , Humanos , Fígado/diagnóstico por imagem , Masculino , Análise Multivariada , Curva ROCRESUMO
Objective: To report the epidemiological and clinical characteristics of liver hemangioma in health adults from a large sample of Health Examination Database. Methods: A retrospective study was performed to analyze the epidemiological and clinical Characteristics of liver hemangioma from people who underwent examination in China-Japan friendship hospital from 2014 to 2016. The analysis was also included the relationship between gender or age and the incidence and tumor size. Results: A total of 83 964 healthy adults (age≥18) were included in the study. The overall incidence of liver hemangioma was 2.95%. There was no significant difference of liver hemangiomas incidence between male which was 3.03%, and which was 2.88% in female. Liver hemangiomas incidence had shown obviously increased with patients' age, as the evidence indicating that the prevalence of liver hemangioma in <30 age group was only 1.87%, and the prevalence of liver hemangioma in 41-50 age group raised to 3.72%. While the size of liver hemangioma in different genders was also increasing with age, the tumor size of liver hemangioma in <30 age group was the smallest. Under 50 years old, the size of female patients' liver hemangioma was larger than that of male patients in each age group. The size of female patients' liver hemangioma had obviously decreased over 60 years old. Conclusion: The progress of liver hemangioma was highly influenced by age and gender.
Assuntos
Hemangioma , Neoplasias Hepáticas , Adulto , China , Feminino , Hemangioma/epidemiologia , Humanos , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Objective: To study the correlation between the level of serum Chitinase-3-like protein 1 (CHI3L1) and the significant liver fibrosis and liver cirrhosis in patients with chronic liver disease, and to evaluate its diagnostic value. Methods: 165 patients with chronic liver disease were selected, liver histopathological examination was performed to detect serum CHI3L1 concentration. Four indexes of hepatic fibrosis (type III procollagen, collagen IV, laminin, hyaluronic acid), aspartate aminotransferase/platelet ratio index (APRI) and FIB-4 (fibrosis- 4) scores were based on the pathological findings of liver biopsy and compared the advantages and disadvantages of serum CHI3L1 with other methods for the diagnosis of hepatic fibrosis and liver cirrhosis. A multivariate regression analysis model was created, and receiver operating characteristic curve was analyzed. Results: The level of serum CHI3L1 increased with increase of fibrosis stage and was highest in liver cirrhosis stage. In the period of S0 to 1, the levels of S2 to 3 and S4 were 62.82 (41.40 ~ 87.20), 70.94 (48.47 to 122.60) and 141.06 (78.18 ~ 197.40), and there were statistically significant differences between the groups (P < 0.001). The area under the curve for the diagnosis of significant liver fibrosis was 0.68 (0.60 to 0.77), and 0.74 (0.65 to 0.83) for cirrhosis in CHI3L1. Multivariate regression analysis showed that CHI3L1 was an independent predictor of significant fibrosis and cirrhosis. The combined diagnostic model based on CHI3L1, collagen IV and FIB-4 scores further improved the diagnostic value. The area under the curve for the diagnosis of significant fibrosis and cirrhosis was 0.79 (0.72 to 0.86) and 0.80 (0.73 to 0.87), respectively. Conclusion: CHI3L1 has a good diagnostic value in patients with chronic liver disease with significant fibrosis and liver cirrhosis. The diagnostic model in combination with other markers like Collagen IV and FIB-4 scores could further improve the diagnostic value and is worthy of further study.
Assuntos
Cirrose Hepática , Aspartato Aminotransferases , Biomarcadores , Biópsia , Plaquetas , Proteína 1 Semelhante à Quitinase-3 , Doença Crônica , Colágeno Tipo III , Colágeno Tipo IV , Humanos , Ácido Hialurônico , Laminina , Contagem de Plaquetas , Curva ROC , Soro , Índice de Gravidade de DoençaRESUMO
On 13 June 2013, a fever and diarrhoea outbreak occurred in a boarding school in Sichuan Province. We conducted a field investigation and compared food exposure of 81 case students and 104 control students (years 7 and 8) in order to identify the source of infection. There were 401 cases identified (399 students and two cooks). The attack rates were 23-46% in nursery, primary, and secondary schools, but 0% in the high school. Eighty-five percent of case students, consumed cowpea salad compared to 60% of control students at lunch on 12 June (odds ratio 3·1, 95% confidence interval 1·3-7·8). The cowpeas were stored at room temperature for 3 h in a bucket previously used to store raw ingredients. The bucket was cleaned using water without a disinfectant. There were two buckets of cowpea, one for the high-school students and another for the other students. This Salmonella outbreak was likely caused by the cowpea salad due to cross-contamination via a storage bucket.
Assuntos
Surtos de Doenças , Fabaceae/microbiologia , Microbiologia de Alimentos , Almoço , Intoxicação Alimentar por Salmonella/epidemiologia , Salmonella typhimurium/fisiologia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Intoxicação Alimentar por Salmonella/microbiologia , Instituições Acadêmicas , EstudantesRESUMO
Objective: To investigate the clinical effectiveness of super pulsed carbon dioxide fractional laser debridement surgery on the treatment of chronic wounds. Methods: From December 2018 to May 2019, 37 patients with chronic wounds who met the inclusion criteria were admitted to the Affiliated Hospital of Southwest Medical University for a prospective randomized controlled study. Using the random number table, the patients were divided into surgical debridement group (19 patients, 4 males and 15 females, aged (58±16) years, 25 wounds) and laser debridement group (18 patients, 9 males and 9 females, aged (58±10) years, 23 wounds). In patients of surgical debridement group, oedematous and aging granulation tissue was scraped from the wound by scalpel handle or curet, and the residual necrotic tissue was removed by sharp surgical instruments. In patients of laser debridement group, oedematous and aging granulation tissue and necrotic tissue was removed by super pulsed carbon dioxide fractional laser therapeutic machine, laser gasification debridement was performed repeatedly till fresh normal tissue layer observed. In patients of the two groups, according to the wound in the first 3 d after the first debridement, debridement dressing was performed twice at least as before, then wound debridement dressing was performed once every 1 to 4 days as before according to the wound conditions. The wound healing rates on 7, 14, 21, and 28 d after the first debridement were calculated. The positive rates of bacterial culture of wounds before and after the first debridement were calculated. The color and texture of the wound granulation tissue before the first debridement and on 7, 14, and 28 d after the first debridement were observed and scored. The pain scores before every debridement, during every debridement, and after every debridement dressing change were evaluated by visual analogue scale. The times of debridement dressing change were recorded. Data were statistically analyzed with two independent sample t test, analysis of variance for repeated measurement, Fisher's exact probability test, Mann-Whitney U test, and Bonferroni correction. Results: (1) On 7, 14, 21, and 28 d after the first debridement, the wound healing rates of patients in laser debridement group (29.5% (24.1%, 36.0%), 47.1% (42.7%, 62.4%), 71.4% (62.2%, 76.8%), and 88.6% (79.2%, 96.3%) were significantly higher than those of surgical debridement group (1.6% (1.0%, 12.8%), 12.7% (2.0%, 16.6%), 24.5% (8.9%, 45.5%), 43.9% (23.2%, 70.8%), Z=3.477, 3.553, 2.721, 2.193, P<0.05 or P<0.01). (2) Before the first debridement, the positive rates of bacterial culture of wounds in patients of laser debridement group and surgical debridement group were 92% (23/25) and 91% (21/23), respectively, which were similar (P>0.05). After the first debridement, the positive rate of bacterial culture of wounds of patients in surgical debridement group was 64% (16/25), which was significantly higher than 13% (3/23) of laser debridement group (P<0.01). (3) On 7, 14, and 28 d after the first debridement, the scores of color and texture of wound granulation tissue of patients in laser debridement group were significantly higher than those of surgical debridement group (Z=3.420, 5.682, 6.142, 4.461, 5.337, 4.458, P<0.01). (4) The pain scores during every debridement and after every debridement dressing change in patients of laser debridement group were significantly lower than those of surgical debridement group (t=2.847, 5.046, P<0.05 or P<0.01). (5) The time of debridement dressing change in laser debridement group was 8.0 (7.0, 10.0) times, which was significantly less than 10.0 (9.5, 12.5) times in surgical debridement group (Z=2.261, P<0.05). Conclusions: Compared with traditional surgical debridement method, super pulsed carbon dioxide fractional laser debridement surgery is more effective in treating patients with chronic wounds. Laser debridement makes the wound healing more efficiently with reduced pain and better infection control; significantly reduces the number of dressing changes, and is especially suitable for the wound treatment in outpatients.
Assuntos
Desbridamento , Adulto , Idoso , Dióxido de Carbono , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , CicatrizaçãoRESUMO
The existence of a cubic fluorite-type SnO(2) and a hexagonal TiO(2) (which may be related to the fluorite structure) have been demonstrated by an in situ x-ray diffraction study in which a diamond-anvil pressure cell was used after the samples had been heated by a continuous yttrium-aluminum-garnet laser. At room temperature, the lattice parameter for SnO(2) (fluorite) is a = 4.925 +/- 0.005 angstroms and those for TiO(2) (fluorite-related) are a = 9.22 +/- 0.01 angstroms and c = 5.685 +/- 0.006 angstroms at about 250 kilobars. The volume change associated with the transition from rutile to fluorite (or related structure) is about -8 percent for SnO(2) and -10.5 percent for TiO(2) at transition. Upon release of pressure, both the fluorite-type SnO(2) and the TiO(2) reverted to the alpha-PbO(2) structure at room temperature. The hypothesis that the earth's lower mantle is composed of oxide phases might be feasible if it were possible for SiO(2) to possess the fluorite structure or its related forms at high pressure, as shown for SnO(2) and TiO(2) in this study. The oxide hypothesis proposed here differs from that postulated by Birch in that the primary coordination of silicon is 6 for Birch's hypothesis and 8 for the hypothesis presented here.
RESUMO
Pyrope garnet (Mg(3)Al(2)Si(3)O(12)) has been found to transform to an ilmenite-type phase at a loading pressure between 240 and 250 kilobars and at about 1000 degrees to 1400 degrees C in a diamond-anvil press coupled with laser heating. The lattice parameters for the ilmenite-type phase of (Mg(.75) Al(.25))(Si(.75) Al(.25))O(3) are a(0) = 4.755 +/- 0.002 and c(0) = 13.360 +/- 0.005 angstroms. The zero-pressure volume change associated with the garnet-ilmenite transition is calculated to be -7.1 percent. This result verifies the prediction that pyrope garnet would transform to the ilmenite structure at high pressure first suggested in 1962 by Clark et al. and Ringwood.
RESUMO
An x-ray diffractiotn study of thulium at room temperature and high pressure by means of a diamond-anvil press has shown that thulium transforms from a hexagonal close-packed structure to the samarium type, as other rareearth elements (gadolinium, terbium, dysprosium, and holmium) do. Unlike the other rare-earth elements, thulium (hexagonal close-packed) has an axial ratio (c/a) that is independent of pressure within experimental error and the transition is reversible. The transition occurs with increasing pressure in the range of 60 to 116 kilobars. The lattice paralieters of the samarium-type phase of thulium at about 116 kilobars are a = 3.327 +/- 0.005 angstroms and c = 23.48 +/- 0.04 angstroms, and the volume change at the transition is estimated to be - 0.5 percent of the volume of the hexagonal close-packed phase at the transition.
RESUMO
OBJECTIVE: Osteosarcoma (OS) is a commonly diagnosed bone malignancy in children and adolescents. Nuclear division cycle 80 (NDC80) is a crucial regulator of the cell division cycle that has recently been identified as a novel oncoprotein in various solid tumors; however, its role in OS remains poorly understood. The aim of this study was to investigate correlations between NDC80 expression in OS patients and clinicopathological features and prognosis. PATIENTS AND METHODS: We began this study by determining NDC80 expression in sarcoma patients using the Oncomine Platform. Then, we measured NDC80 mRNA expression by RT-PCR in 26-paired fresh OS and adjacent normal samples. Finally, we analyzed NDC80 expression by immunohistochemistry in a retrospective cohort of 154 OS patients. RESULTS: NDC80 mRNA was abnormally overexpressed not only in OS, but also in other sarcomas including liposarcoma, myxofibrosarcoma, and leiomyosarcoma. In the retrospective analysis, NDC80 expression was significantly correlated with TNM stage (p=0.023) and distant metastasis (p=0.008). OS patients with high NDC80 expression had a significantly worse OS-specific (p=0.002) and disease-free survival (p=0.001) compared with those with low NDC80 expression. Furthermore, univariate and multivariate analyses suggested that NDC80 expression together with TNM stage, distant metastasis and preoperative chemotherapy response are significant independent prognostic factors affecting OS-specific and disease-free survival (p<0.05). CONCLUSIONS: Our study highlighted a novel insight into the clinical significance of NDC80 expression in OS patients and suggested its potential as a clinically actionable biomarker for prognostic prediction and therapy decisions.
Assuntos
Neoplasias Ósseas/genética , Proteínas Nucleares/genética , Osteossarcoma/genética , Biomarcadores Tumorais , Proteínas do Citoesqueleto , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: Topoisomerase IIß binding protein 1 (TopBP1) is involved in DNA damage and replication checkpoint and has been shown to be related to tumorigenesis in many cancer types. This study aimed to evaluate the biological role and clinicopathological significance of TopBP1 in OS. PATIENTS AND METHODS: TopBP1 expression in sarcoma patients was determined through the Oncomine database, and the prognostic role of TopBP1 expression was assessed in a retrospective cohort study. CCK-8 assay and colony formation assay were employed to evaluate the effect of TopBP1 on proliferation and chemoresistance in OS cells. Cell apoptosis and cell cycle assay were used to assess the effect of TopBP1 on apoptosis and cycle of OS cells. RESULTS: We observed that TopBP1 expression was elevated not only in OS, but also in other sarcoma types including myxofibrosarcoma, liposarcoma, and leiomyosarcoma. Knockdown of TopBP1 using small interfering (si) RNA blocked cell proliferation and colony formation ability, and caused cell apoptosis as well as G1-phase arrest in OS cells. Moreover, TopBP1 knockdown decreased the chemoresistance of OS cells to both doxorubicin and cisplatin. Lastly, the retrospective cohort study showed that high TopBP1 expression was not only associated with high local recurrence and low necrosis rate, but also correlated with poor overall survival and disease-free survival of OS patients. CONCLUSIONS: Our findings indicate that TopBP1 contributes to the cell survival and chemoresistance to doxorubicin and cisplatin of OS, suggesting TopBP1 may serve as a novel target for inhibition of progression and chemotherapeutic resistance in OS patients.
Assuntos
Neoplasias Ósseas/patologia , Proteínas de Transporte/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas Nucleares/metabolismo , Osteossarcoma/patologia , Adulto , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/mortalidade , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/genética , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Estimativa de Kaplan-Meier , Masculino , Recidiva Local de Neoplasia , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/genética , Osteossarcoma/tratamento farmacológico , Osteossarcoma/mortalidade , Prognóstico , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Estudos RetrospectivosRESUMO
The origin of cancers is associated with etiology as well as therapeutics. Several studies reveal that malignancies in children can originate in utero. However, a diagnostic approach to distinguish between cancers initiated pre- or postnatally is absent. Here we identified a transcriptional factor FEV (fifth Ewing variant) that was expressed in fetal hematopoietic cells and became silent after birth. We characterized that FEV was essential for the self-renewal of hematopoietic stem cells (HSCs). We next found that FEV was expressed in most infant leukemia samples, but seldom in adult samples, in accord with the known prenatal origins of the former. We further determined the majority of pediatric acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML) were FEV positive. Moreover, FEV knockdown markedly impaired the leukemia-propagating ability of leukemic stem cells. We therefore identified FEV is unique to fetal HSCs and stably expressed in leukemic cells of prenatal origin. It may also provide a tractable therapeutic target.