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1.
Oral Oncol ; 104: 104641, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32182548

RESUMO

OBJECTIVES: Patients with prior irradiated head and neck cancer (HNC) who are ineligible for definitive retreatment have limited local palliative options. We report the largest series of the use of the Quad Shot (QS) regimen as a last-line local palliative therapy. MATERIALS AND METHODS: We identified 166 patients with prior HN radiation therapy (RT) treated with QS regimen (3.7 Gy twice daily over 2 consecutive days at 4 weeks intervals per cycle, up to 4 cycles). Palliative response defined by symptom(s) relief or radiographic tumor reduction, locoregional progression free survival (LPFS), overall survival (OS) and radiation-related toxicity were assessed. RESULTS: Median age was 66 years. Median follow-up for all patients was 6.0 months and 9.7 months for living patients. Overall palliative response rate was 66% and symptoms improved in 60% of all patients. Predictors of palliative response were > 2 year interval from prior RT and 3-4 QS cycles. Median LPFS was 5.1 months with 1-year LPFS 17.7%, and median OS was 6.4 months with 1-year OS 25.3%. On multivariate analysis, proton RT, KPS > 70, presence of palliative response and 3-4 QS cycles were associated with improved LPFS and improved OS. The overall Grade 3 toxicity rate was 10.8% (n = 18). No Grade 4-5 toxicities were observed. CONCLUSION: Palliative QS is an effective last-line local therapy with minimal toxicity in patients with previously irradiated HNC. The administration of 3-4 QS cycles predicts palliative response, improved PFS, and improved OS. KPS > 70 and proton therapy are associated with survival improvements.

2.
Cancer ; 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32097507

RESUMO

BACKGROUND: Proton therapy (PT) improves outcomes in patients with nasal cavity (NC) and paranasal sinus (PNS) cancers. Herein, the authors have reported to their knowledge the largest series to date using intensity-modulated proton therapy (IMPT) in the treatment of these patients. METHODS: Between 2013 and 2018, a total of 86 consecutive patients (68 of whom were radiation-naive and 18 of whom were reirradiated) received PT to median doses of 70 grays and 67 grays relative biological effectiveness, respectively. Approximately 53% received IMPT. RESULTS: The median follow-up was 23.4 months (range, 1.7-69.3 months) for all patients and 28.1 months (range, 2.3-69.3 months) for surviving patients. The 2-year local control (LC), distant control, disease-free survival, and overall survival rates were 83%, 84%, 74%, and 81%, respectively, for radiation-naive patients and 77%, 80%, 54%, and 66%, respectively for reirradiated patients. Among radiation-naive patients, when compared with 3-dimensional conformal proton technique, IMPT significantly improved LC (91% vs 72%; P < .01) and independently predicted LC (hazard ratio, 0.14; P = .01). Sixteen radiation-naive patients (24%) experienced acute grade 3 toxicities; 4 (6%) experienced late grade 3 toxicities (osteoradionecrosis, vision loss, soft-tissue necrosis, and soft tissue fibrosis) (grading was performed according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 5.0]). Slightly inferior LC was noted for patients undergoing reirradiation with higher complications: 11% experienced late grade 3 toxicities (facial pain and brain necrosis). Patients treated with reirradiation had more grade 1 to 2 radionecrosis than radiation-naive patients (brain: 33% vs 7% and osteoradionecrosis: 17% vs 3%). CONCLUSIONS: PT achieved remarkable LC for patients with nasal cavity and paranasal sinus cancers with lower grade 3 toxicities relative to historical reports. IMPT has the potential to improve the therapeutic ratio in these malignancies and is worthy of further investigation.

3.
World Neurosurg ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-32001397

RESUMO

OBJECTIVE: To investigate the effects of early intensive rehabilitation management on the recovery of motor function and activities of daily living in patients with moderate traumatic brain injury. METHODS: Eighty-seven patients (age range, 18-65 years) with traumatic brain injury that met the enrollment criteria were randomly divided into 2 groups. Group 1 received early and high-intensity rehabilitation management (from 7 days after injury, 7 d/wk, 4 times/d, 1 h/session) for 4 weeks; group 2 received ordinary rehabilitation (from 14 days after injury, 5 d/wk, 2 times/d, 1 h/session) for 4 weeks. The Fugl-Meyer Assessment (FMA, motor function) and Barthel Index (BI) were used to assess the daily living functional state before treatment, 3 months after injury, and 6 months after injury. The Glasgow Coma Scale (GCS) was used to assess outcomes 6 months after injury. RESULTS: Three months after rehabilitation, the FMA (motor function) score was significantly higher in the early intensive intervention group versus the control group (59.83 ± 11.87 vs. 44.56 ± 8.32, respectively; P < 0.05); no significant between-group differences were found in the GCS score or BI score (P > 0.05). Six months after rehabilitation, the FMA score and BI score were significantly higher in the early intensive intervention group versus the control group (FMA: 73.18 ± 16.55 vs. 57.86 ± 10.67, P < 0.01; BI: 87.17 ± 13.85 vs. 60.68 ± 11.98, P < 0.01, respectively). The GCS score was higher in the early intensive intervention group versus the control group (4.24 ± 0.91 vs. 3.43 ± 0.88, P < 0.05, respectively) 6 months after injury. CONCLUSIONS: Early intensive rehabilitation management might be more beneficial for neurologic function and activities of daily living in patients with moderate traumatic brain injury.

5.
Oncol Rep ; 43(1): 318-327, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31789405

RESUMO

Bromodomain proteins such as BRD4 chromatin regulator are attractive cancer therapeutic targets. ANCCA (AAA+ nuclear coregulatory cancer­associated protein, also known as ATPase family AAA domain containing 2 or ATAD2) is a novel oncology drug target and contains a bromodomain and an ATPase domain. Our research group as well as others previously identified ANCCA/ATAD2 as a putative oncogene and a poor prognosis factor in many types of cancer including triple­negative breast cancer (TNBC). In the present study, it is reported for the first time that the expression of ANCCA was highly induced by DNA­damaging chemotherapy agents such as carboplatin, doxorubicin and mitomycin C, as well as ionizing radiation. Notably, ANCCA is required for efficient dissolution of DNA damage foci and homologous recombination. Further studies revealed that ANCCA mediates the optimal expression and activation of DNA damage response and repair factors including Chk1, Chk2 and BRCA1, and that ANCCA is recruited to the promoter of BRCA1 in response to DNA damage. Moreover, ANCCA knockdown sensitizes TNBC cells to carboplatin. Collectively, these data provide the first evidence indicating that ANCCA is a novel mediator of DNA damage response and repair and that targeting ANCCA can enhance the efficacy of radiation and chemotherapies.

6.
Expert Rev Med Devices ; 17(1): 27-32, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31778610

RESUMO

Introduction: Potential complications associated with screw malposition may result in neurological deficits or vascular injuries. Spine surgery has significantly developed under the assistance of technological progress. The advantages of applying robotic technology in spine surgery include the possibility of improving screw accuracy, reducing complications, decreasing fluoroscopy use.Areas covered: We critically evaluated the current literature on the radiographic and clinical outcomes of robotic-assisted spine surgery, including accuracy, radiation exposure, operative time, and complication rates.Expert opinion: Robotic-assisted spine surgery shows promising results and has the potentials for further investigations. The robot-assisted spine surgery is appeared to be more accurate in pedicle screw placement than the free-hand technique. In general, the robot-assisted technique is associated with shorter radiation exposure time but longer operative time than free-hand technique. For higher accuracy of robotic-assisted spine surgery, technical advancement and high-quality researches are needed. Artificial intelligent technology, decompression function, and higher accuracy are the directions for the development of robotic-assisted spine surgery.

7.
J Agric Food Chem ; 68(1): 193-205, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31826610

RESUMO

Gynostemma pentaphyllum possesses neuroprotective bioactivity. However, the effect of gypenosides on hypoxia-induced neural damage remains obscure. In this study, Gyp, the active fraction extracted from G. pentaphyllum and its bioactive compounds as well as the underlying molecular mechanisms were investigated. Eighteen dammarane-type saponins were isolated from Gyp. The absolute configurations of six unreported compounds (13-18) were assessed via electron capture detection (ECD) analyses. The results of cell viability assay showed that Gyp and its bioactive compounds (13-16 and 18) effectively protected PC12 cells from hypoxia injury. Gyp pretreatment also improved mice spatial memory impairment caused by hypoxia exposure. At the molecular level, Gyp and its bioactive compounds could activate the signaling pathways of ERK, Akt, and CREB in vitro and in vivo. In summary, Gyp and its bioactive compounds could prevent hypoxia-induced injury via ERK, Akt, and CREB signaling pathways.


Assuntos
Proteína de Ligação a CREB/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Gynostemma/química , Hipóxia/tratamento farmacológico , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Proteína de Ligação a CREB/genética , Sobrevivência Celular , MAP Quinases Reguladas por Sinal Extracelular/genética , Humanos , Hipóxia/genética , Hipóxia/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Células PC12 , Extratos Vegetais/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Saponinas/administração & dosagem
8.
Dev Cell ; 52(2): 196-209.e9, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31866205

RESUMO

Saturated fatty acids (SFAs) (the "bad" fat), especially palmitate (PA), in the human diet are blamed for potential health risks such as obesity and cancer because of SFA-induced lipotoxicity. However, epidemiological results demonstrate a latent benefit of SFAs, and it remains elusive whether a certain low level of SFAs is physiologically essential for maintaining cell metabolic hemostasis. Here, we demonstrate that although high-level PA (HPA) indeed induces lipotoxic effects in liver cells, low-level PA (LPA) increases mitochondrial functions and alleviates the injuries induced by HPA or hepatoxic agent carbon tetrachloride (CCl4). LPA treatment in mice enhanced liver mitochondrial activity and reduced CCl4 hepatotoxicity with improved blood levels of aspartate aminotransferase (AST), alanine transaminase (ALT), and mitochondrial aspartate transaminase (m-AST). LPA-mediated mitochondrial homeostasis is regulated by CDK1-mediated SIRT3 phosphorylation, which in turn deacetylates and dimerizes CPT2 to enhance fatty acid oxidation. Thus, an advantageous effect is suggested by the consumption of LPA that augments mitochondrial metabolic homeostasis via CDK1-SIRT3-CPT2 cascade.

9.
Chemosphere ; 240: 124848, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31541901

RESUMO

Establishment of numerical water quality criteria (WQC) has brought increasing interest in China. However, toxicity data to develop robust WQC values (number of toxicity data ≥8) of contaminants based solely on endemic and indigenous species are insufficient. In this study, interspecies correlation estimation (ICE) models were developed using a combination of North American ICE models supplemented with China-specific species to resolve this problem. A total of 207 significant surrogate-predicted models (p < 0.05, F-test) were derived: 119, 66 and 22 models for vertebrates, invertebrates and plant surrogate species, respectively. Model cross-validation success rate (≥80%), mean square error (MSE, ≤ 0.54), R2 (≥0.78) and taxonomic distance (≤4, within the same class) were selected as guiding criteria to screen the resulted ICE models. The differences of 5th percentile hazard concentrations (HC5s) for 6 chemicals (2,4-dichlorophenol, triclosan, tetrabromobisphenol A, nitrobenzene, perfluorooctane sulfonate and octabromodiphenyl ether) calculated from ICE-based and measured toxicity-based SSDs were within 3-fold among models. Although the number of derived ICE models was not comprehensive and continues to be improved, they can already be used in the development of WQC targeting protection of aquatic life and environmental risk assessments for chemicals lacking toxicity data.


Assuntos
Poluentes Químicos da Água/química , Qualidade da Água/normas , Animais , China , Especificidade da Espécie
10.
Front Oncol ; 9: 1201, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31803610

RESUMO

Tumor cells, including cancer stem cells (CSCs) resistant to radio- and chemotherapy, must enhance metabolism to meet the extra energy demands to repair and survive such genotoxic conditions. However, such stress-induced adaptive metabolic alterations, especially in cancer cells that survive radiotherapy, remain unresolved. In this study, we found that CPT1 (Carnitine palmitoyl transferase I) and CPT2 (Carnitine palmitoyl transferase II), a pair of rate-limiting enzymes for mitochondrial fatty acid transportation, play a critical role in increasing fatty acid oxidation (FAO) required for the cellular fuel demands in radioresistant breast cancer cells (RBCs) and radiation-derived breast cancer stem cells (RD-BCSCs). Enhanced CPT1A/CPT2 expression was detected in the recurrent human breast cancers and associated with a worse prognosis in breast cancer patients. Blocking FAO via a FAO inhibitor or by CRISPR-mediated CPT1A/CPT2 gene deficiency inhibited radiation-induced ERK activation and aggressive growth and radioresistance of RBCs and RD-BCSCs. These results revealed that switching to FAO contributes to radiation-induced mitochondrial energy metabolism, and CPT1A/CPT2 is a potential metabolic target in cancer radiotherapy.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31794406

RESUMO

OBJECTIVE: Histologic grade and Ki-67 proliferation status are important clinical indictors for breast cancer prognosis and treatment. The purpose of this study is to improve prediction accuracy of these clinical indicators based on tumor radiomic analysis. METHODS: We jointly predicted Ki-67 and tumor grade with a multitask learning framework by separately utilizing radiomics from tumor MRI series. Additionally, we showed how multitask learning models (MTLs) could be extended to combined radiomics from the MRI series for a better prediction based on the assumption that features from different sources of images share common patterns while providing complementary information. Tumor radiomic analysis was performed with morphological, statistical and textural features extracted on the DWI and dynamic contrast-enhanced MRI (DCE-MRI) series of the precontrast and subtraction images, respectively. RESULTS: Joint prediction of Ki-67 status and tumor grade on MR images using the MTL achieved performance improvements over that of single-task-based predictive models. Similarly, for the prediction tasks of Ki-67 and tumor grade, the MTL for combined precontrast and apparent diffusion coefficient (ADC) images achieved AUCs of 0.811 and 0.816, which were significantly better than that of the single-task- based model with p values of 0.005 and 0.017, respectively. CONCLUSION: Mapping MRI radiomics to two related clinical indicators improves prediction performance for both Ki-67 expression level and tumor grade. SIGNIFICANCE: Joint prediction of indicators by multitask learning that combines correlations of MRI radiomics is important for optimal tumor therapy and treatment because clinical decisions are made by integrating multiple clinical indicators.

12.
Neurotherapeutics ; 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31820273

RESUMO

Depression, plus the accompanying memory impairment, is one of the leading causes of disability worldwide. Thus, there is a critical need to develop new drugs based on distinct strategies. FG-4592, an inhibitor of prolyl hydroxylase, activates the hypoxia-inducible factor-1 (HIF-1) pathway, to produce multiple effects on cell properties. Here, we examined whether FG-4592 has antidepressant effects, using a chronic unpredictable mild stress (CUMS) procedure to establish rodent depression models. We found that FG-4592 not only reversed depressive behaviors but also improved CUMS-induced memory impairment. Mechanistically, FG-4592 could play an important role in promoting hippocampal neurogenesis and synaptic plasticity. At the molecular level, FG-4592 was found to activate HIF-1 and cAMP-responsive element-binding protein/brain-derived neurotrophic factor signaling pathways in vivo, as well as promote the expression of postsynaptic density (PSD) proteins, PSD95 and Homer1. An examination of primary hippocampal neurons showed that FG-4592 promoted dendritic growth. Taken together, our results not only provide an experimental basis for the future application of FG-4592 in clinical treatment of depression but also support the argument that the HIF-1 signaling pathway is a promising target for the treatment of depression.

14.
Opt Express ; 27(21): 29962-29971, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684251

RESUMO

High performance solar-blind photodetectors have been fabricated from diamond wafers. The peak responsivity is 13.0 A/W at 222 nm with a dark current of 0.93 nA under 60 V bias. The rise and decay times of the photodetector are about 1.3 µs and 203 µs, respectively. The responsivity and response time of the device are both among the best values ever reported for diamond-based photodetectors. A solar-blind optical communication system has been constructed by employing the diamond photodetector as a signal receiver for the first time. Benefiting from the high spectral selectivity of the diamond photodetector, the communication system has excellent anti-interference ability. The results reported in this paper may pave the way for the future application of diamond-based solar-blind photodetectors in confidential communications.

15.
Artif Cells Nanomed Biotechnol ; 47(1): 4182-4193, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31722575

RESUMO

The clinical benefit of cancer immunotherapy, including tumour vaccines, is influenced by immunosuppressive factors in the tumour microenvironment. Among these factors, cancer-associated fibroblasts (CAFs) and their products, such as fibroblast activation protein-α (FAPα), greatly affect tumourigenesis, development, metastasis and treatment tolerance, which make them promising immunotherapy targets for cancer patients. Our previous study reported that a whole cell tumour vaccine (WCTV) expressing FAPα inhibited tumour growth by simultaneously attacking cancer cells and CAFs. This study aimed to improve WCTVs with xenoantigens to end immune tolerance and to further activate the adaptive immune system. In the present study, we designed a WCTV by transducing a vector encoding human FAPα (hFAPα) into murine tumour cells and evaluated its efficacy in multiple solid tumour models. Immunotherapy with this WCTV effectively delayed tumour growth and prevented recurrence. The anti-tumour responses were clearly linked to antigen-specific cytotoxic T cells, whereas CD4(+) T lymphocytes also played a role. Humoural immune responses were activated because the adoptive transfer of immunoglobulins induced abscopal anti-tumour effects, and autoantibodies against FAPα were specifically detected in the sera of immunized mice. Moreover, an increased number of apoptotic tumour cells along with a reduced number of CAFs within the tumours suggest that xenogeneic FAPα-based WCTV has the potential to drive T cell and antibody responses against cancer cells and CAFs. This finding could offer an advanced strategy to treat multiple solid tumours with individualized cancer immunotherapy techniques.

16.
Sensors (Basel) ; 19(22)2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31744095

RESUMO

This study presents a low-power multi-lead wearable electrocardiogram (ECG) signal sensor system design that can simultaneously acquire the electrocardiograms from three leads, I, II, and V1. The sensor system includes two parts, an ECG test clothing with five electrode patches and an acquisition device. Compared with the traditional 12-lead wired ECG detection instrument, which limits patient mobility and needs medical staff assistance to acquire the ECG signal, the proposed vest-type ECG acquisition system is very comfortable and easy to use by patients themselves anytime and anywhere, especially for the elderly. The proposed study incorporates three methods to reduce the power consumption of the system by optimizing the micro control unit (MCU) working mode, adjusting the radio frequency (RF) parameters, and compressing the transmitted data. In addition, Huffman lossless coding is used to compress the transmitted data in order to increase the sampling rate of the acquisition system. It makes the whole system operate continuously for a long period of time and acquire abundant ECG information, which is helpful for clinical diagnosis. Finally, a series of tests were performed on the designed wearable ECG device. The results have demonstrated that the multi-lead wearable ECG device can collect, process, and transmit ECG data through Bluetooth technology. The ECG waveforms collected by the device are clear, complete, and can be displayed in real-time on a mobile phone. The sampling rate of the proposed wearable sensor system is 250 Hz per lead, which is dependent on the lossless compression scheme. The device achieves a compression ratio of 2.31. By implementing a low power design on the device, the resulting overall operational current of the device is reduced by 37.6% to 9.87 mA under a supply voltage of 2.1 V. The proposed vest-type multi-lead ECG acquisition device can be easily employed by medical staff for clinical diagnosis and is a suitable wearable device in monitoring and nursing the off-ward patients.

17.
Oncol Rep ; 42(6): 2706-2715, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31638245

RESUMO

Cancer­associated fibroblasts (CAFs) are known to be essential in cancer initiation and development. However, the role of CAFs in promoting ovarian cancer (OC) invasion remains to be fully elucidated. To address this in the present study, 49 clinical OC specimens were used to evaluate the roles of CAFs in promoting ovarian tumor migration and invasion and disease progression. It was found that the sushi repeat­containing protein, X­linked (SRPX) and hemicentin 1 (HMCN1) genes were significantly upregulated in CAFs from high­grade serous carcinoma (HGSC) and clear cell carcinoma (CCC) samples, the two major histological types of OC with frequently poor patient survival rates. The short hairpin (sh)RNA­mediated silencing of SRPX and HMCN1 in fibroblasts significantly suppressed the Transwell invasive activities of OC cells. Further experiments showed that SRPX and HMCN1 regulated the invasiveness of OC via the Ras homology family member A (RhoA) signaling pathway in fibroblasts. Therefore, the findings of the present study suggest that targeting the CAF genes, SRPX and HMCN1, can inhibit OC migration and invasion. These data highlight the importance of CAF­OC crosstalk signaling in cancer invasion and demonstrate the potential for improved efficacy of OC treatment by targeting CAF­SRPX/HMCN1.

18.
Sci Rep ; 9(1): 14186, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578359

RESUMO

In arid areas of China, water shortage and heavy carbon emissions have been threatening agricultural sustainability and which has become a vital issue. A field experiment was conducted to explore how different mulching affects soil moisture and temperature, CO2 fluxes, forage-maize hay yield and nutritional value during 2 consecutive years: 2014 and 2015. The field experiment showed that mulching materials had distinct effects on soil moisture and temperature and CO2 fluxes. The soil temperature and CO2 fluxes were in order of common plastic film mulching (PFM) > bio-degradable mulch mulching (BMM) > no mulching (CK) > straw mulching (SM), while the soil moisture was in order of PFM > BMM > SM > CK over these two years. Compared with CK, hay yield respectively increased by 23.25%, 22.51% and 5.27% for PFM, BMM and SM, WUE increased by 35.60%, 32.34% and 10.88%, and the total nutrient yields increased by 17.75%, 21.35% and 6.95%, respectively. To sum up, in combination with ecology and environmental protection, bio-degradable mulch could replace common plastic film and bio-degradable mulch should be popular in future. As bio-degradable mulch is green non-pollution, it is conducive to the sustainable development of agricultural ecosystem.

19.
Breast Cancer Res ; 21(1): 112, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31623683

RESUMO

BACKGROUND: Heterogeneity is a common finding within tumours. We evaluated the imaging features of tumours based on the decomposition of tumoural dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data to identify their prognostic value for breast cancer survival and to explore their biological importance. METHODS: Imaging features (n = 14), such as texture, histogram distribution and morphological features, were extracted to determine their associations with recurrence-free survival (RFS) in patients in the training cohort (n = 61) from The Cancer Imaging Archive (TCIA). The prognostic value of the features was evaluated in an independent dataset of 173 patients (i.e. the reproducibility cohort) from the TCIA I-SPY 1 TRIAL dataset. Radiogenomic analysis was performed in an additional cohort, the radiogenomic cohort (n = 87), using DCE-MRI from TCGA-BRCA and corresponding gene expression data from The Cancer Genome Atlas (TCGA). The MRI tumour area was decomposed by convex analysis of mixtures (CAM), resulting in 3 components that represent plasma input, fast-flow kinetics and slow-flow kinetics. The prognostic MRI features were associated with the gene expression module in which the pathway was analysed. Furthermore, a multigene signature for each prognostic imaging feature was built, and the prognostic value for RFS and overall survival (OS) was confirmed in an additional cohort from TCGA. RESULTS: Three image features (i.e. the maximum probability from the precontrast MR series, the median value from the second postcontrast series and the overall tumour volume) were independently correlated with RFS (p values of 0.0018, 0.0036 and 0.0032, respectively). The maximum probability feature from the fast-flow kinetics subregion was also significantly associated with RFS and OS in the reproducibility cohort. Additionally, this feature had a high correlation with the gene expression module (r = 0.59), and the pathway analysis showed that Ras signalling, a breast cancer-related pathway, was significantly enriched (corrected p value = 0.0044). Gene signatures (n = 43) associated with the maximum probability feature were assessed for associations with RFS (p = 0.035) and OS (p = 0.027) in an independent dataset containing 1010 gene expression samples. Among the 43 gene signatures, Ras signalling was also significantly enriched. CONCLUSIONS: Dynamic pattern deconvolution revealed that tumour heterogeneity was associated with poor survival and cancer-related pathways in breast cancer.

20.
Radiol Oncol ; 53(3): 307-315, 2019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31553703

RESUMO

Background Endometrial adenocarcinoma (EAC) is one of the most commonly diagnosed gynaecological malignancies among female population of the developed countries. DUSP6 is a negative regulator of ERK signaling, which is a molecular switch involved in MAPK signaling during the progress of malignancies. DUSP6 was previously found to inhibit tumorigenesis and EMT-associated properties in several cancers, however, its exact role in EAC remains unclear Methods The level of DUSP6, (E-cad) and (N-cad) in EAC cancerous tissues and respective adjacent non-cancerous tissues were examined by western-blot or immunohistochemistry. The cell growth, invasion and migration abilities were measured in Ishikawa 3H12 endometrial cancer cell lines with overexpressed or knock down DUSP6. Protein levels of EMT-associated markers E-cadherin, N-cadherin and Vimentin were also determined. The impacts of DUSP6 on ERK signaling was assessed by detection of ERK and p-ERK. Results Down-regulation of DUSP6 was observed in EAC compared with the normal controls. The overexpression of DUSP6 significantly attenuated tumor cell growth, invasion, migration abilities and inhibited EMT-associated markers, while knock down of DUSP6 showed opposite trends. Overexpression of DUSP6 also down-regulated p-ERK and the knock down of DUSP6 inversely up-regulated p-ERK level. Conclusions DUSP6 inhibited cell growth, invasion and migration abilities in Ishikawa 3H12 cells as well as attenuating EMT-associated properties. This tumor suppressive effect of DUSP6 in EAC is achieved by inhibiting ERK signaling pathway.

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