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1.
Zhonghua Nei Ke Za Zhi ; 63(1): 81-88, 2024 Jan 01.
Artigo em Zh | MEDLINE | ID: mdl-38186122

RESUMO

Objective: To verify the predictive value of the Second Revision of the International Staging System (R2-ISS) in newly diagnosed patients with multiple myeloma (MM) who underwent first-line autologous hematopoietic stem cell transplantation (ASCT) in a new drug era in China. Methods: This multicenter retrospective cohort study enrolled patients with newly diagnosed MM from three centers in China (Beijing Chao-Yang Hospital, Capital Medical University; the First Affiliated Hospital, Sun Yat-Sen University, and the Second Affiliated Hospital of Naval Medical University) from June 2008 to June 2018. A total of 401 newly diagnosed patients with MM who were candidates for ASCT were enrolled in this cohort, all received proteasome inhibitor and/or immunomodulator-based induction chemotherapy followed by ASCT. Baseline and follow-up data were collected. The patients were regrouped using R2-ISS. Progression-free survival (PFS) and overall survival (OS) were analyzed. The Kaplan-Meier method was used to analyze the survival curve and two survival curves were compared using the log-rank test. Cox regression analysis were performed to analyze the relationship between risk factors and survival. Results: The median age of the patients was 53 years (range 25-69 years) and 59.5% (240 cases) were men. Newly diagnosed patients with renal impairment accounted for 11.5% (46 cases). According to Revised-International Staging System (R-ISS), 74 patients (18.5 %) were diagnosed with stage Ⅰ, 259 patients (64.6%) with stage Ⅱ, and 68 patients (17.0%) with stage Ⅲ. According to the R2-ISS, the distribution of patients in each group was as follows: 50 patients (12.5%) in stage Ⅰ, 95 patients (23.7%) in stage Ⅱ, 206 patients (51.4%) in stage Ⅲ, and 50 patients (12.5%) in stage Ⅳ. The median follow-up time was 35.9 months (range, 6-119 months). According to the R2-ISS stage, the median PFS in each group was: 75.3 months for stage Ⅰ; 62.0 months for stage Ⅱ, 39.2 months for stage Ⅲ, and 30.3 months for stage Ⅳ; and the median OS was not reached, 86.6 months, 71.6 months, and 38.5 months, respectively. There were statistically significant differences in PFS and OS between different groups (both P<0.001). Multivariate Cox regression analysis showed that stages Ⅲ and Ⅳ of the R2-ISS were independent prognostic factors for PFS (HR=2.37, 95%CI 1.30-4.30; HR=4.50, 95%CI 2.35-9.01) and OS (HR=4.20, 95%CI 1.50-11.80; HR=9.53, 95%CI 3.21-28.29). Conclusions: The R2-ISS has significant predictive value for PFS and OS for transplant-eligible patients with MM in the new drug era. However, the universality of the R2-ISS still needs to be further verified in different populations.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Prognóstico , Estudos Retrospectivos , Transplante Autólogo
2.
Zhonghua Nei Ke Za Zhi ; 61(2): 164-171, 2022 Feb 01.
Artigo em Zh | MEDLINE | ID: mdl-35090251

RESUMO

Objective: To evaluate the prognostic value of CD56 expression in newly diagnosed MM (NDMM). Methods: A total of 332 NDMM patients were enrolled in Beijing Chaoyang Hospital, Capital Medical University from January 1, 2011 to January 1, 2021, with a median age of 60 years and a male to female ratio of 1.2∶1. CD56 expression on myeloma cells was detected by flow cytometry before induction therapy. Overall survival (OS) and progression-free survival (PFS) data were collected. In order to reduce the confounding factors, the propensity score matching technique was used to match CD56 positive versus negative patients at a ratio of 1∶1. Results: Among 332 patients, CD56 positivity rate was 65.1% (216/332). Patients with CD56 expression had significantly longer median OS (58.4 vs. 43.1 months, P=0.024) and PFS (28.7 vs. 24.1 months, P=0.013) than those with negative CD56. Univariate Cox proportional hazards regression analyses showed that CD56 expression was positively correlated with OS (HR=0.644, 95%CI 0.438-0.947, P=0.025) and a favorable prognostic factor for PFS (HR=0.646, 95%CI 0.457-0.913,P=0.013). The favorable effect of CD56 expression on PFS was confirmed in multivariate analysis (HR=0.705, 95%CI 0.497-0.998, P=0.049), but OS was not affected (P>0.05).In the propensity score matching analysis, 194 patients with 97 in each group were identified. CD56 positivity consistently predicted longer PFS (34.2 vs.25.1 months, P=0.047), but not OS (63.4 vs.43.1 months, P=0.056). Conclusion: These results demonstrate that CD56 expression is a favorable prognostic factor for PFS of newly diagnosed MM patients.


Assuntos
Mieloma Múltiplo , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos
3.
Ann Oncol ; 32(2): 218-228, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33188874

RESUMO

BACKGROUND: Primary analysis of the phase III trial BG01-1323L demonstrated that utidelone plus capecitabine significantly improved progression-free survival (PFS) and overall response rate (ORR) versus capecitabine alone in heavily-pretreated patients with metastatic breast cancer (MBC). Here, we report the final overall survival (OS) analysis and updates of other endpoints. PATIENTS AND METHODS: In total, 405 patients were randomised 2:1 to receive utidelone (30 mg/m2 IV daily, days 1-5, over 90 min) plus capecitabine (1000 mg/m2 orally b.i.d., days 1-14) or capecitabine alone (1250 mg/m2 orally b.i.d., days 1-14) every 21 days. The secondary endpoint, OS, was estimated using the Kaplan-Meier product-limit approach at a two-sided alpha level of 0.05 after the prespecified 310 death events had been reached. Exploratory analyses of the primary endpoint, PFS, and the secondary endpoint, ORR, were also done. Safety was analysed in patients who had at least one dose of study drug. RESULTS: At the final OS analysis, the median duration of follow-up was 19.6 months in the utidelone plus capecitabine group and 15.4 months in the capecitabine alone group. In the intention-to-treat population, 313 deaths had occurred at data cut-off, 203 of 270 patients in the combination group and 110 of 135 in the monotherapy group. Median OS in the combination group was 19.8 months compared with 16.0 months in the monotherapy group [hazard ratio (HR) = 0.75, 95% confidence intervals (CI) 0.59-0.94, P = 0.0142]. The updated analysis of PFS and ORR showed that the combination therapy remained superior to monotherapy. Safety results were similar to those previously reported with respect to incidence, severity and specificity. No late-emerging toxicities or new safety concerns occurred. CONCLUSIONS: For heavily-pretreated, anthracycline- and taxane-resistant MBC patients, utidelone plus capecitabine significantly improved OS versus capecitabine alone. These results support the use of utidelone plus capecitabine as a novel therapeutic regimen for patients with MBC.


Assuntos
Antraciclinas , Neoplasias da Mama , Antraciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Capecitabina/uso terapêutico , Intervalo Livre de Doença , Fluoruracila/uso terapêutico , Humanos , Taxoides/uso terapêutico , Resultado do Tratamento
4.
Zhonghua Yi Xue Za Zhi ; 101(38): 3164-3167, 2021 Oct 19.
Artigo em Zh | MEDLINE | ID: mdl-34674429

RESUMO

Objective: To investigate whether the abundance or diversity of intestinal flora in breast cancer (BC) patients effects on the degree of tumor infiltration lymphocytes in breast cancer tissues. Methods: Between March 2017 and October 2017, a total of 80 biopsy-confirmed female patients with BC were enrolled in the present study at the Breast Center of the Fourth Hospital of Hebei Medical University (Shijiazhuang, China), age distribution ranged from 37 to 74 years, which were divided into three groups based on the infiltration of tumor-infiltrating lymphocytes, as follows: high infiltration of TILs (TIL-H) 25 cases, medium infiltration of TILs (TIL-M) 34 cases and low infiltration of TILs (TIL-L) 21 cases. DNA of the intestinal flora was determined by Illumina sequencing and taxonomy of 16S ribosomal RNA genes. Compare the differences in the abundance or diversity of intestinal flora between these three groups. The relationship between tumor-infiltrating lymphocytes and clinical characteristics was analyzed by χ2 tested, and the relationship with intestinal flora was analyzed by ß diversity. Results: There were 3, 174, 2, 996, and 2, 877 different OUTs in the TIL-H, TIL-M, and TIL-L groups. The ß-diversity distribution was statistically significant (weighted UniFrac, P<0.01; unweighted UniFrac, P<0.01) when comparing the three groups (TIL-H vs. TIL-M vs. TIL-L), the differences between TIL-L and TIL-H groups were greatest. Conclusions: The infiltration level of tumor-infiltrating lymphocytes in breast cancer patients was closely related to the diversity of intestinal flora.


Assuntos
Neoplasias da Mama , Microbioma Gastrointestinal , Adulto , Idoso , China , Feminino , Humanos , Linfócitos do Interstício Tumoral , Pessoa de Meia-Idade
5.
Zhonghua Wai Ke Za Zhi ; 58(2): 105-109, 2020 Feb 01.
Artigo em Zh | MEDLINE | ID: mdl-32074808

RESUMO

Objective: To summarize the status of immediate breast reconstruction (IBR) after mastectomy in Beijing City, Tianjin City and Hebei Province. Methods: A retrospective analysis was made on the data of 382 cases with breast cancer who were treated and followed up successfully with immediate breast reconstruction after mastectomy from January 2012 to December 2016 in Beijing City, Tianjin City and Hebei Province. Clinic data of the followed-up 382 cases (all female, age (38.5±4.2) years (range: 24 to 70 years)), including general information, tumor information, sugery methods, and treatments after surgery were collected. The survival status, metastasis,complications and prognosis were followed up. Cosmetic effcet was evalated by Harris method, and life quality by Functional Assessment of Cancer Therapy-Breast scale (FACT-B). χ(2) test was used to compare the difference between year 2012 and year 2013 to 2016. Bonferroni method was used to correct the inspection level, which was 0.05/10=0.005. The trend of IBR rate (ratio of IBR to modified radical mastectomy) from 2013 to 2016 was analyzed by trend χ(2) test. Results: There was 46 cases in stage 0, 152 cases in stage Ⅰ, 165 cases in stage Ⅱ, 19 cases in stage Ⅲ. Twenty-five cases was treated by neoadjuvant chemotherapy, 231 by chemotherapy and 35 by radiotherapy. The proportion of implant reconstruction was 48.7% (186/382), more than expanded of 21.5% (82/382), with latissimus dorsi of 12.0% (46/382), TRAM of 8.9% (34/382), DIEP of 2.1% (8/382), and latissimus plus implant of 6.8% (26/382). According to the Harris standard, the excellent and good rate of the cosmetic effect of the reconstructed breast was 93.7%. The score of FACT-B was 108.20±16.9 (range: 67 to 144) 1 year postoperatively. Compared with 2012, the IBR rate was significant increased, till 2015, the IBR rate was 153/10 000 cases (χ(2)=47.028, P=0.000). Conclusions: There is a significant increase on IBR rate in Beijing City, Tianjin City and Hebei province by year. Most of cases received IBR is stage Ⅰ to Ⅱ. Implant reconstruction is the main reconstructive method. Postoperative cosmetic effects and quality of life are both meet patients' demon.


Assuntos
Neoplasias da Mama , Mamoplastia , Mastectomia , Adulto , Pequim , Neoplasias da Mama/cirurgia , Feminino , Humanos , Qualidade de Vida , Estudos Retrospectivos
6.
J Biol Regul Homeost Agents ; 33(3): 773-785, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31165609

RESUMO

This study aimed to investigate the role of long-chain non-coding RNA CTBP1-AS in breast cancer progression and cell invasion as well as migration. Clinical data of breast cancer patients (N = 155) in our hospital was collected for further analysis. qRT-PCR was used to detect LncRNA CTBP1-AS expression levels in human normal breast epithelial cell (MCF-10A) and breast cancer cells (MCF-7, BT- 549, MDA-MB-231 and MDA-MB-435). LncRNA CTBP1-AS knock-down and overexpressed lentivirus vectors were constructed to transfect breast cancer cells. Colony formation assay was employed to detect cell proliferative abilities. Flow cytometry was performed to detect cell apoptosis ratio. Wound healing scratch assay was used to detect cell migration, and Transwell matrigel assay was used to detect cell invasion. Bioinformatics analysis was performed to predict the downstream targets of LncRNA CTBP1-AS, which were further validated by dual-luciferase reporter gene system. The results showed that LncRNA CTBP1-AS was aberrantly overexpressed in breast cancer tissues and breast cancer cells compared to the control group. Moreover, the expression levels of LncRNA CTBP1-AS were positively related with tumor size, histological grade and the expression levels of Ki-67 and Her2. Further analysis showed that LncRNA CTBP1-AS expression levels negatively correlated with patient survival time and clinical prognosis. Of note, overexpressed LncRNA CTBP1-AS promoted breast cancer cell proliferation and invasion as well as migration, and decreased cell apoptosis ratio. Bioinformatics analysis and dual-luciferase reporter gene system results validated that microRNA-940 was the downstream target of LncRNA CTBP1-AS. Interestingly, overexpressed microRNA-940 abrogated the effects of LncRNA CTBP1-AS on cell proliferation, apoptosis, and invasion. In conclusion, overexpressed LncRNA CTBP1- AS promoted breast cancer cell proliferation, invasion as well as migration, inhibited cell apoptosis and accelerated breast cancer development by sponging microRNA-940.


Assuntos
Neoplasias da Mama/patologia , RNA Longo não Codificante/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Invasividade Neoplásica
7.
Neoplasma ; 66(1): 54-62, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30509089

RESUMO

Let-7 was one of the earliest discovered miRNAs and while it reportedly acts as a tumor suppressor in various solid tumors, its function in breast cancer has not been fully studied. Therefore, we examined let-7a and MAGE-A1 expression in breast tissues by qRT-PCR and found that let-7a expression significantly correlates with larger tumor size, higher histological grade (p<0.05) and is significantly lower in patients with Her-2-positive cancers and Ki-67 >14% (p=0.028 and p=0.023). MAGE-A1 expression incidence is 50.8% (33/65) and it inversely correlates with let-7a expression (p=0.008). let-7a inhibition of breast cancer cell proliferation, migration and invasion was also observed in in vitro cell culture experiments, and dual-luciferase reporter assays showed that melanoma-associated antigen A1 (MAGE-A1) was its target gene; the target comprised bases 451-457 of the 3'UTR region of the MAGE-A1 mRNA. RT-qPCR and Western blot analyses showed that let-7a inhibited MAGE-A1 expression at both the nucleic acid and protein levels. In our final co-transfection experiment, we targeted MAGE-A1 in a breast cancer cell line and observed that let-7a inhibited cell proliferation, migration and invasion. These combined results confirm that let-7a functions as a tumor suppressor by targeting MAGE-A1 in breast cancer and it therefore provides a novel target in breast cancer clinical treatment.


Assuntos
Neoplasias da Mama/patologia , Proliferação de Células , Antígenos Específicos de Melanoma/genética , MicroRNAs/genética , Linhagem Celular Tumoral , Movimento Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos
8.
Artigo em Zh | MEDLINE | ID: mdl-31594134

RESUMO

Objective: To establish a CT image radiomics-based prediction model for the differential diagnosis of silicosis and tuberculosis nodules. Methods: A total of 53 patients with silicosis and 89 patients with tuberculosis who underwent routine CT scans in Suzhou Fifth People's Hospital from January to August, 2018 were enrolled in this study. AK/ITK software was used to segment the images to obtain 139 silicosis lesions and 119 tuberculosis lesions. For each lesion image, 396 features were extracted, and feature dimension reduction was applied to select the most characteristic feature subset. Support vector machine (SVM) , feedforward back propagation neural network (FNN-BP) , and random forest (RF) were implemented using R software (Rstudio V1.1.463) , and the algorithm that achieved the largest area under of the receiver operating characteristic (ROC) curve (AUC) was selected as the final prediction model. Results: RF was the best prediction model for the differential diagnosis of silicosis and tuberculosis nodules, with an accuracy of 83.1%, a sensitivity of 0.76, a specificity of 0.9, and an AUC of 0.917 (95% confidence interval: 0.8431-0.9758) . RF had a significantly larger AUC than SVM and FNN-BP (P<0.05) . Conclusion: CT image-based RF prediction model can be used to differentially diagnose silicosis and tuberculosis nodules.


Assuntos
Silicose/diagnóstico por imagem , Tuberculose/diagnóstico por imagem , Diagnóstico Diferencial , Humanos , Interpretação de Imagem Assistida por Computador , Modelos Teóricos , Redes Neurais de Computação , Curva ROC , Máquina de Vetores de Suporte , Tomografia Computadorizada por Raios X
9.
Zhonghua Zhong Liu Za Zhi ; 40(9): 672-675, 2018 Sep 23.
Artigo em Zh | MEDLINE | ID: mdl-30293391

RESUMO

Objective: To analyze the feature of breast complex cystic masses and to classify it at ultrasonography (US), which applied to the Breast Imaging Reporting and Data System (BI-RADS) categories 4a to 4c with pathological results as the golden standards. Methods: The ultrasonographic data and clinical features of 78 patients with complex cystic masses confirmed by pathology in Cancer Hospital from July 2014 to June 2017 were retrospectively reviewed. The complex cystic breast masses were divided into four classes on the basis of their US features: type 1 [thick wall and (or) thick septa (> 0.5 mm)], type 2 (one or more intra-cystic masses), type 3 (mixed cystic and solid components with cystic components more than 50%) and type 4 (mixed cystic and solid components with solid components more than 50%). Positive values (PPVs) were calculated for each type. Multiple linear regression analysis was used to analyze the ultrasonographic features of the masses (lesion size, margins, blood flow resistance index, calcification, and axillary lymph nodes, etc.) with malignant correlation. Results: There were 81 lesions in 78 patients. Among the 81 masses based on US appearance, 14 (17.3%) were classified as type Ⅰ, 18 (22.2%) as type Ⅱ, 18 (22.2%) as type Ⅲ, and 31 (38.3%) as type Ⅳ. The positive predictive values of the malignant lesions of type Ⅰ, type Ⅱ, Ⅲ and Ⅳ were 7.1%, 16.7%, 61.1% and 48.3%, respectively (P=0.040). In all the 81 masses, 14 were BI-RADS categories 4a, 18 were BI-RADS categories 4b and 49 were BI-RADS categories 4c. Masses with maximum diameter equal to or larger than 2.0 cm, unclear margins, RI≥0.7 and presence of abnormal axillary nodes assessment had a high probability of malignancy (P=0.030, 0.038, <0.001 and 0.025, respectively). Conclusion: Ultrasound typing is helpful for differentiating benign and malignant breast complex cysts and classifying BI-AIDS 4a to 4c, thus providing clearer treatment for clinical practice.


Assuntos
Cisto Mamário/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Ultrassonografia Mamária , Axila , Cisto Mamário/classificação , Cisto Mamário/patologia , Neoplasias da Mama/classificação , Diagnóstico Diferencial , Feminino , Humanos , Modelos Lineares , Linfonodos/diagnóstico por imagem , Estudos Retrospectivos
10.
Zhonghua Yi Xue Za Zhi ; 98(16): 1236-1241, 2018 Apr 24.
Artigo em Zh | MEDLINE | ID: mdl-29747311

RESUMO

Objective: To compare the bioequiavailability of paclitaxel for injection (albumin bound) (PAB) and reference listed drug abraxane in the patients with metastatic breast cancer, and to investigate the safety and efficacy in the extension treatments of PAB. Methods: This study was random, two cycles, self-crossover control study in the bioequiavailability stage. PAB was the investigational drug T and Abraxane was the reference drug R. Patients were randomly assigned to two cycles therapy of either R→T or T→R(260 mg/m(2)/21d). Non-PD patients entered in the extension treatments of the investigational drug PAB(260 mg/m(2)/21d) until the disease progression or the intolerance toxicity. Results: From Mar 1, 2016 to May 24, 2016, we enrolled 40 patients. The blood concentration-time curve and the parameters of pharmacokinetics indicated the two drugs were the bioequivalent drug products in the initial two cycles crossover-therapy.The incidence of adverse drug reactions were 89.7% vs 97.4% in investigational drug vs reference drug and grade 3/4 toxicities were 20.5% vs 21.1%(P=1.000). Patients received a median of 7 treatment cycles(range 1-23) and a median of 260mg/m(2) actual drug dose (range 220-260 mg/m(2)). Seven patients (17.5%) had dose reductions because of toxicities (260 mg/m(2) reduce to 220 mg/m(2)). Twenty-two patients (55%) discontinued treatment prematurely because of toxicity.Overall response rates (ORR) were 40% (95% CI, 24.8%-55.2%). For patients who received PAB as first-line vs non-first-line therapy, the ORR were 43.8% vs 25%. For patients who taxane-naïve vs taxane-pretreated, the ORR were 45.5% vs 37.9%. Median PFS was 49 weeks(95% CI, 30weeks-NA). Conclusion: The paclitaxel for injection (albumin bound) (PAB) and reference listed drug abraxane are the bioequivalent drug products.The toxicity and efficacy of the PAB are similar with abraxane.The more therapy chances for Chinese patients will come by the research and development of domestic drugs.


Assuntos
Neoplasias da Mama , Paclitaxel Ligado a Albumina , Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Paclitaxel , Resultado do Tratamento
11.
Zhonghua Yi Xue Za Zhi ; 98(16): 1231-1235, 2018 Apr 24.
Artigo em Zh | MEDLINE | ID: mdl-29747310

RESUMO

Objective: To explore the efficacy and safety of polyethylene glycal recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patiens with breast cancer. Methods: There were two parts in the present phase Ⅳ clinical study. One was a randomized, controlled clinical study. Patients in this study received PEG-rhG-CSF or rhG-CSF in the first cycle and followed with both PEG-rhG-CSF in the rest of 3 cycles. The other one was a single arm study. Patients who developed Ⅲ/Ⅳ grade neutropenia in the screening cycle received PEG-rhG-CSF in the rest of 3 cycles chemotherapy. Results: In the first cycle of randomized, controlled study, the incidence of Ⅳ grade neutropenia are 31.48% and 35.58% respectively in PEG-rhG-CSF and rhG-CSF group, with no statistically significant differences (P=0.527 6). The duration of Ⅳ grade neutropenia respectively are 2.22±1.58 and 3.00±1.59 days, with a statistically significant difference (P=0.016 6). In the single arm study, the incidence of Ⅳ grade neutropenia was 57.76% in screening cycle. And the incidence decreased to 16.35%, 10%, and 8.57% in the followed 3 cycle after the use of PEG-rhG-CSF. The incidence of adverse effects was 5.06%, and the major adverse effect was bone pain which with an incidence of 2.8%. Conclusion: The fixed 6mg dose of PEG-rhG-CSF can effectively prevent neutropenia in patients with breast cancer in multicycle chemotherapy and it has a low incidence of adverse events and mild adverse reaction.


Assuntos
Neutropenia/induzido quimicamente , Neoplasias da Mama , Fator Estimulador de Colônias de Granulócitos , Humanos , Neoplasias Pulmonares , Polietileno , Proteínas Recombinantes
12.
Proteins ; 85(3): 417-423, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27802573

RESUMO

Our information-driven docking approach HADDOCK is a consistent top predictor and scorer since the start of its participation in the CAPRI community-wide experiment. This sustained performance is due, in part, to its ability to integrate experimental data and/or bioinformatics information into the modelling process, and also to the overall robustness of the scoring function used to assess and rank the predictions. In the CASP-CAPRI Round 1 scoring experiment we successfully selected acceptable/medium quality models for 18/14 of the 25 targets - a top-ranking performance among all scorers. Considering that for only 20 targets acceptable models were generated by the community, our effective success rate reaches as high as 90% (18/20). This was achieved using the standard HADDOCK scoring function, which, thirteen years after its original publication, still consists of a simple linear combination of intermolecular van der Waals and Coulomb electrostatics energies and an empirically derived desolvation energy term. Despite its simplicity, this scoring function makes sense from a physico-chemical perspective, encoding key aspects of biomolecular recognition. In addition to its success in the scoring experiment, the HADDOCK server takes the first place in the server prediction category, with 16 successful predictions. Much like our scoring protocol, because of the limited time per target, the predictions relied mainly on either an ab initio center-of-mass and symmetry restrained protocol, or on a template-based approach whenever applicable. These results underline the success of our simple but sensible prediction and scoring scheme. Proteins 2017; 85:417-423. © 2016 Wiley Periodicals, Inc.


Assuntos
Algoritmos , Biologia Computacional/métodos , Simulação de Acoplamento Molecular/estatística & dados numéricos , Proteínas/química , Benchmarking , Sítios de Ligação , Cristalografia por Raios X , Bases de Dados de Proteínas , Simulação de Acoplamento Molecular/métodos , Ligação Proteica , Conformação Proteica , Mapeamento de Interação de Proteínas , Projetos de Pesquisa , Software , Eletricidade Estática , Homologia Estrutural de Proteína , Termodinâmica
13.
Zhonghua Yi Xue Za Zhi ; 97(24): 1857-1861, 2017 Jun 27.
Artigo em Zh | MEDLINE | ID: mdl-28648008

RESUMO

Objective: Circulating tumor cells (CTC) have become an important part of liquid biopsy, which have underwent a process from simple counting to molecular typing and genotyping. To this end, we used Cellcollector to verify the effectiveness and safety of CTC detection in patients with breast tumor, and to conduct the following analysis. Methods: One hundred and ninety patients who received treatment in six leading Chinese cancer centers were involved from April to August in 2016. Among which, 127 patients were diagnosed as metastatic breast cancer, and the other 63 patients as benign breast tumors. Results: In metastatic breast cancer group, 74.8%(95/127) were CTC positive. While in benign tumor group, they were all CTC negative patients. The area under the Receiver Operating Characteristic curve were 0.832(95%CI: 0.784-0.879). The sensitivity of Cellcollector was 74.8%, specificity was 100% (Youden index 0.748). A total of 117 patients in MBC groups received a second detection of Cellcollector after 3-4 weeks, among which 44.4% (52/117) were CTC positive patients. The incidence of adverse events and severe adverse events in MBC was 66.9%(85/127) and 39.8% (53/127). Furthermore, we used Cellcollector to perform the HER2 testing and gene sequencing. Conclusions:In vivo isolation of CTCs overcomes blood volume limitations compared to other approaches. The further application of molecular typing and gene typing might help to implement CTC-based "liquid biopsies" into clinical decision making.


Assuntos
Neoplasias da Mama/diagnóstico , Células Neoplásicas Circulantes , Biomarcadores Tumorais , Contagem de Células , China , Humanos , Metástase Neoplásica , Receptor ErbB-2
14.
Zhonghua Bing Li Xue Za Zhi ; 46(8): 525-529, 2017 Aug 08.
Artigo em Zh | MEDLINE | ID: mdl-28810291

RESUMO

Objective: To investigate the significance of extranodal extension of axillary lymph nodes (ALN-ENE) metastases in post-operative primary invasive breast carcinoma of non-specific type. Methods: Six hundred and thirty-eight invasive breast cancer cases confirmed by postoperative pathological examination were collected from January 2006 to December 2008. The relationship of lymph node metastases and ALN-ENE with other lymph node parameters and patient outcome was analyzed. Results: Among 638 cases, 263 (41.2%) showed axillary lymph node metastases. ALN-ENE was present in 91 cases (36.4%). The rate of ALN-ENE increased with pT stage and tumor size. Five-year recurrence-free survival rate (RFS) and 5-year overall survival rate (OS) was 86.6% and 91.2% respectively for ALN-ENE positive group, and both were lower than ALN-ENE negative group (P<0.01). One hundred and forty-nine patients with 1 to 3 positive lymph nodes had a 5-year RFS of 91.9%, and 5-year OS of 92.3%, less than ALN-ENE negative group (P<0.01). Univariate analysis showed ALN-ENE positively correlated with lymph node metastasis. Multivariate analysis suggested that ENE was associated with increased recurrence risk and shortened recurrence-free and overall survival, especially in patients with 1 to 3 positive lymph nodes; and it was an independent prognostic factor (P<0.01). Conclusions: The number of lymph nodes metastases is an important predictor of survival in breast cancer patients. ALN-ENE is an independent risk indicator for recurrence and overall survival. For patients with 1 to 3 metastatic axillary lymph nodes, ALN-ENE could alter the patient's clinical pathologic staging, and therefore it is an independent prognostic factor.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Metástase Linfática , Análise de Variância , Axila , Feminino , Humanos , Invasividade Neoplásica , Recidiva Local de Neoplasia , Prognóstico , Taxa de Sobrevida
15.
Neoplasma ; 63(1): 44-56, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26639233

RESUMO

Epithelial-mesenchymal transition (EMT) is a crucial step in tumor metastasis. Triple negative (TN) breast cancer, a high metastasis phenotype, has been verified to be associated with EMT. Melanoma associated antigen-A (MAGE-A) is exclusively expressed in cancers with high aggressiveness as well as unfavorable prognosis and likely to be associated with EMT of triple negative breast cancer (TNBC). The aim of the study is to analyze the expression profile of MAGE-A in breast cancer and the correlation between MAGE-A and EMT of TNBC. Immunohistochemistry (IHC) was performed to assess the prevalence of MAGE-A, vimentin, E-cadherin and ß-catenin in breast cancer tissues and correlate them with clinical pathological parameters. The association between MAGE-A and EMT markers was also evaluated. Scratch assay and transwell invasion assay were carried out to evaluate the impact of MAGE-A down-regulation on migration and invasion of the breast cancer cells. Real-time PCR was also conducted to evaluate alterations in EMT markers with decrease in MAGE-A. The results showed that MAGE-A was absent in normal tissue but expressed in tumor samples with the incidence of 49.17% (P=0.008). MAGE-A staining was higher in TNBC (76.47%, 13/17), followed by HER-2(+) (53.85%, 7/13) and Luminal set (43.33%, 39/90), and it was significantly correlated with ER (-), PR (-), HER-2 (-), lymph nodes involvement and higher histological grade (P<0.05). E-cadherin-positivity was frequent in Luminal set (94.44%, 85/90) and linked to ER (+), negative lymph nodes and lower histological grade (P<0.05). Vimentin expression was often observed in TNBC (70.56%, 12/17) and ER (-), PR (-), lymph nodes (+) groups (P<0.05). Expression of ß-catenin was prevalent in Luminal set (93.33%, 84/90) and correlated with ER (+), PR (+) and lower histological grade (P<0.05). MAGE-A was inversely associated with E-cadherin (P=0.011) and ß-catenin (P=0.048) but expressed in the same trend with vimentin (P=0.000). Migration and invasion of MDA-MB-231 were inhibited when MAGE-A decreased. Increase in epithelial markers and decline in mesenchymal indicators were also seen with MAGE-A reduction. Snail, Slug, ZEB1 and ZEB2 were also down-regulated. In conclusion, MAGE-A may be responsible for high aggressiveness and EMT of TNBC and can be a new choice for targeted therapy.


Assuntos
Transição Epitelial-Mesenquimal/fisiologia , Neoplasias de Mama Triplo Negativas/genética , Antígenos de Neoplasias , Antígeno CD146/genética , Antígeno CD146/metabolismo , Caderinas/metabolismo , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico , Neoplasias de Mama Triplo Negativas/patologia , Vimentina , beta Catenina/metabolismo
16.
Genet Mol Res ; 14(1): 170-9, 2015 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-25729948

RESUMO

The objective of the current study was to assess the utility of 64-row helical computed tomography angiography (CTA) in the evaluation of extremity vascular traumas. The extremities from 17 clinical cases of suspected traumatic vascular damage were evaluated using 64-row helical CTA. To evaluate extremity vascular traumas using CTA, volume rendering, multiple planar reconstruction, and curved planar reconstruction technology were applied to accurately and rapidly indicate the type and extent of blood vessel damage, as well as any relationship with injuries to adjacent bones, joints, soft tissue swelling, or hematomas. The types of extremity vascular traumas evaluated included damaged arteries, artery spasms or block, blood vessels shifted because of pressure, pseudo aneurysms, arteriovenous fistula, and vein occlusion. The results of the study indicated that 64-row helical CTA could be highly efficient and accurate in the evaluation of extremity vascular traumas, and could aid in making clinical assessments.


Assuntos
Angiografia/métodos , Extremidades/diagnóstico por imagem , Tomografia Computadorizada Espiral/métodos , Lesões do Sistema Vascular/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fêmur/irrigação sanguínea , Humanos , Artéria Ilíaca/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Ruptura , Adulto Jovem
19.
Minerva Med ; 105(1): 51-6, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24351978

RESUMO

AIM: Aim of the study was to observe the impact of bone marrow damage induced by local irradiation on leukopenia. METHODS: For the human study, five cancer patients received local radiation therapy. Bone marrow aspiration was conducted to measure nucleated cell count and 99mTc-Sc sulfur colloid ECT imaging was carried out to examine bone marrow function. For the animal study, fifty New Zealand white rabbits were divided into 3 groups: non-irradiated control group (N.=10), abdomen irradiation group (irradiation area did not cover bone marrow) (N.=20), chest irradiation group (irradiation area covered bone marrow) (N.=20). Nucleated cell counts were taken after confirming onset of leukopenia. RESULTS: Bone marrow of five patients proliferated normally. ECT imaging showed no abnormality in the pattern of red bone marrow distribution. Hematopoietic function was mildly active. CONCLUSION: Suppressed myeloproliferative function does not fully account for irradiation-induced leukopenia.


Assuntos
Células da Medula Óssea/efeitos da radiação , Medula Óssea/efeitos da radiação , Leucócitos/efeitos da radiação , Leucopenia/etiologia , Animais , Medula Óssea/diagnóstico por imagem , Células da Medula Óssea/diagnóstico por imagem , Proliferação de Células/efeitos da radiação , Neoplasias Esofágicas/radioterapia , Feminino , Doença de Hodgkin/radioterapia , Humanos , Neoplasias Pulmonares/radioterapia , Masculino , Neoplasias Nasofaríngeas/radioterapia , Coelhos , Cintilografia , Coloide de Enxofre Marcado com Tecnécio Tc 99m
20.
Zhonghua Xue Ye Xue Za Zhi ; 45(4): 351-356, 2024 Apr 14.
Artigo em Zh | MEDLINE | ID: mdl-38951062

RESUMO

Objective: The effect and safety of etoposide combined with G-CSF were compared with those of cyclophosphamide combined with G-CSF in autologous peripheral blood mobilization in patients with multiple myeloma (MM) . Methods: Patients with MM who received autologous peripheral blood stem cell mobilization and collection in the Department of Hematology, Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 1, 2020 to July 31, 2023 were included. A total of 134 patients were screened by propensity score matching technology according to a 1∶1 ratio. A total of 67 cases were each treated with ETO combined with G-CSF mobilization scheme (ETO group) and CTX combined with G-CSF mobilization scheme (CTX group). Their clinical data were retrospectively analyzed. Results: ①Collection results: the ETO and CTX groups [2 (1-3) d vs 2 (1-5) d; P<0.001] and CD34(+) cells [7.62×10(6) (2.26×10(6)-37.20×10(6)) /kg vs 2.73×10(6) (0.53×10(6)-9.85×10(6)) /kg; P<0.001] were collected. The success rate of collection was 100.0% (67/67) versus 76.1% (51/67) (P<0.001). Excellent rate of collection was 82.1% (55/67) versus 20.9% (14/67; P<0.001). Two patients in the ETO group switched protocols after 1 day of collection, and 11 patients in the CTX group switched protocols after 1-2 days of collection. ②Adverse reactions: granular deficiency with fever (21.5%[14/65] vs. 10.7%[6/56]; P=0.110), requiring platelet transfusion [10.7% (7/65) vs 1.8% (1/56) ; P=0.047]. ③Until the end of follow-up, 63 cases in the ETO group and 54 cases in the CTX group have undergone autologous transplantation. The median number of CD34(+) cells infused in the two groups was 4.62×10(6) (2.14×10(6)-19.89×10(6)) /kg versus 2.62×10(6) (1.12×10(6)-5.31×10(6)) /kg (P<0.001), neutrophil implantation time was 11 (9-14) d versus 11 (10-14) d (P=0.049), and platelet implantation time was 11 (0-19) d vs. 12 (0-34) d (P=0.035). One case in the CTX group experienced delayed platelet implantation. Conclusion: The mobilization scheme of etoposide combined with G-CSF requires relatively platelet transfusion, but the collection days are shortened. The collection success rate, excellent rate, and the number of CD34(+) cells obtained are high, and the neutrophil and platelet engraftment is accelerated after transplantation.


Assuntos
Ciclofosfamida , Etoposídeo , Fator Estimulador de Colônias de Granulócitos , Mobilização de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Transplante Autólogo , Humanos , Mieloma Múltiplo/terapia , Etoposídeo/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Ciclofosfamida/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Estudos Retrospectivos , Células-Tronco de Sangue Periférico , Transplante de Células-Tronco de Sangue Periférico/métodos , Feminino , Masculino , Pessoa de Meia-Idade
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