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1.
BMC Cancer ; 24(1): 936, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090564

RESUMO

PURPOSE: To evaluate the dosimetric characteristics of ZAP-X stereotactic radiosurgery (SRS) for single brain metastasis by comparing with two mature SRS platforms. METHODS: Thirteen patients with single brain metastasis treated with CyberKnife (CK) G4 were selected retrospectively. The prescription dose for the planning target volume (PTV) was 18-24 Gy for 1-3 fractions. The PTV volume ranged from 0.44 to 11.52 cc.Treatment plans of thirteen patients were replanned using the ZAP-X plan system and the Gamma Knife (GK) ICON plan system with the same prescription dose and organs at risk (OARs) constraints. The prescription dose of PTV was normalized to 70% for both ZAP-X and CK, while it was 50% for GK. The dosimetric parameters of three groups included the plan characteristics (CI, GI, GSI, beams, MUs, treatment time), PTV (D2, D95, D98, Dmin, Dmean, Coverage), brain tissue (volume of 100%-10% prescription dose irradiation V100%-V10%, Dmean) and other OARs (Dmax, Dmean),all of these were compared and evaluated. All data were read and analyzed with MIM Maestro. One-way ANOVA or a multisample Friedman rank sum test was performed, where p < 0.05 indicated significant differences. RESULTS: The CI of GK was significantly lower than that of ZAP-X and CK. Regarding the mean value, ZAP-X had a lower GI and higher GSI, but there was no significant difference among the three groups. The MUs of ZAP-X were significantly lower than those of CK, and the mean value of the treatment time of ZAP-X was significantly shorter than that of CK. For PTV, the D95, D98, and target coverage of CK were higher, while the mean of Dmin of GK was significantly lower than that of CK and ZAP-X. For brain tissue, ZAP-X showed a smaller volume from V100% to V20%; the statistical results of V60% and V50% showed a difference between ZAP-X and GK, while the V40% and V30% showed a significant difference between ZAP-X and the other two groups; V10% and Dmean indicated that GK was better. Excluding the Dmax of the brainstem, right optic nerve and optic chiasm, the mean value of all other OARs was less than 1 Gy. For the brainstem, GK and ZAP-X had better protection, especially at the maximum dose. CONCLUSION: For the SRS treating single brain metastasis, all three treatment devices, ZAP-X system, CyberKnife G4 system, and GammaKnife system, could meet clinical treatment requirements. The newly platform ZAP-X could provide a high-quality plan equivalent to or even better than CyberKnife and Gamma Knife, with ZAP-X presenting a certain dose advantage, especially with a more conformal dose distribution and better protection for brain tissue. As the ZAP-X systems get continuous improvements and upgrades, they may become a new SRS platform for the treatment of brain metastasis.


Assuntos
Neoplasias Encefálicas , Radiocirurgia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Humanos , Radiocirurgia/métodos , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Masculino , Planejamento da Radioterapia Assistida por Computador/métodos , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Radiometria , Idoso , Adulto , Órgãos em Risco/efeitos da radiação
2.
World J Surg Oncol ; 22(1): 248, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39267055

RESUMO

BACKGROUND: The novel anti-HER2 antibody drug conjugates (ADCs) can effectively improve the long-term survival of patients with HER2-low expression breast cancer. However, pathological responses to neoadjuvant therapy (NAT) within HER2-low expression breast cancer, the relationship between pathological response and prognosis and the transformation of HER2 status are all now poorly understood. METHODS: The patients with HER2-0 and HER2-low expression breast cancer receiving NAT at Harbin Medical University Cancer Hospital between Jan. 2014 and Nov. 2018 were retrospectively explored. HER2 low expression refers to the IHC 1 + or 2 + and FISH negative. The Kappa test was utilized for analyzing the consistency rate of HER2 expression. To evaluate disease-free survival (DFS) and overall survival (OS), this research employed both the Kaplan-Meier analysis and the Cox regression. RESULTS: In this study, 178 patients with HER2-0 and 344 patients with HER2-low expression breast cancer were included. In comparison with the HER2-0 group, it is shown that patients in the HER2-low group have more possibility to be younger compared to those 50 years old (P < 0.014), have more premenopausal patients (P < 0.001), a higher proportion of hormone receptor (HR) positive patients (P < 0.001), and less proportion of stage III V patients (P < 0.034). When NAT was finished, the pCR rate became 23.6% in the HER2-0 group while 22.1% in the HER2-low group, and there was also a higher pCR rate in HR- patients in comparison with that in HR + patients (P < 0.01). Considering HER2 expression inconsistency, the overall HER2 inconsistency rate was 30.4% (Kappa = 0.431, P < 0.01). Among patients initially diagnosed as HER2-0, 34% (N = 61) were re-diagnosed as HER2-low after NAT. After stratification by HR expression status, HR+/HER2-0 patients transformed to HER2-low after NAT in 37%, and 32% of HR- patients changed from HER2-0 to HER2-low. In this survival analysis, there were both better DFS rates (P = 0.009) and OS rates (P = 0.026) in the HR-/HER2-low patients in comparison with the HR-/HER2-0 patients, while the HER2-0 and HER2-low patients in the HR + group had no significant survival difference. Additionally, for non-pCR patients, there was better DFS (P = 0.029) and OS (P = 0.038) in the HER2-low group in comparison with that of the HER2-0 group, while no significant survival difference exists between pCR patients. CONCLUSION: After HR stratification, there are unique clinical characteristics and prognostic outcomes in HER2-low expression breast cancer, which indicates the potential to become a specific molecular subtype of breast cancer. The significant instability of HER2-low expression status between primary tumor and residual invasive disease suggests that multiple detections of HER2 status should be emphasized in NAT strategies.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Terapia Neoadjuvante , Receptor ErbB-2 , Humanos , Feminino , Receptor ErbB-2/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/metabolismo , Neoplasias da Mama/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Retrospectivos , Prognóstico , Taxa de Sobrevida , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Seguimentos , Terapia Neoadjuvante/métodos , Adulto , Idoso
3.
J Appl Clin Med Phys ; : e14471, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39102876

RESUMO

PURPOSE: To investigate the dose rate dependence of MapCHECK3 and its influence on measurement accuracy, as well as the effect of dose rate correction. MATERIALS AND METHODS: The average and instantaneous dose rate dependence of MapCHECK2 and MapCHECK3 were studied. The accuracy of measurements was investigated where the dose rate differed significantly between dose calibration of the MapCHECK and the measurement. Measurements investigated include: the central axis dose for different fields at different depths, off-axis doses outside the field, and off-axis doses along the wedge direction. Measurements using an ion chamber were taken as the reference. Exponential functions were fit to account for average and instantaneous dose rate dependence for MapCHECK3 and used for dose rate correction. The effect of the dose rate correction was studied by comparing the differences between the measurements for MapCHECK (with and without the correction) and the reference. RESULTS: The maximum dose rate dependence of MapCHECK3 is greater than 2.5%. If the dose calibration factor derived from a 10 × 10 cm2 open field at 10 cm depth was used for measurements, the average differences in central diode dose were 0.8% ± 1.0% and 1.0% ± 0.8% for the studied field sizes and measurement depths, respectively. The introduction of wedge would not only induce -1.8% ± 1.3% difference in central diode dose, but also overestimate the effective wedge angle. After the instantaneous dose rate correction, above differences can be changed to 1.9% ± 8.1%, 0.2% ± 0.1%, and 0.0% ± 0.9%. The pass rate can be improved from 98.4% to 98.8%, 98.3%-100.0%, and 96.3%-100.0%, respectively. CONCLUSION: Compared with MapCHECK2 (SunPoint1 diodes), the more pronounced dose rate dependence of MapCHECK3 (SunPoint2 diodes) should be carefully considered. To ensure highly accurate measurement, it is suggested to perform the dose calibration at the same condition where measurement will be performed. Otherwise, the dose rate correction should be applied.

4.
Mol Cancer ; 21(1): 176, 2022 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-36071523

RESUMO

Immunotherapy, especially immune checkpoint inhibitors (ICIs), has revolutionized the treatment of many types of cancer, particularly advanced-stage cancers. Nevertheless, although a subset of patients experiences dramatic and long-term disease regression in response to ICIs, most patients do not benefit from these treatments. Some may even experience cancer progression. Immune escape by tumor cells may be a key reason for this low response rate. N6-methyladenosine (m6A) is the most common type of RNA methylation and has been recognized as a critical regulator of tumors and the immune system. Therefore, m6A modification and related regulators are promising targets for improving the efficacy of tumor immunotherapy. However, the association between m6A modification and tumor immune escape (TIE) has not been comprehensively summarized. Therefore, this review summarizes the existing knowledge regarding m6A modifications involved in TIE and their potential mechanisms of action. Moreover, we provide an overview of currently available agents targeting m6A regulators that have been tested for their elevated effects on TIE. This review establishes the association between m6A modifications and TIE and provides new insights and strategies for maximizing the efficacy of immunotherapy by specifically targeting m6A modifications involved in TIE.


Assuntos
Neoplasias , Evasão Tumoral , Adenosina/análogos & derivados , Humanos , Imunoterapia , Neoplasias/genética , Neoplasias/terapia , RNA , Evasão Tumoral/genética
5.
Zhongguo Yi Liao Qi Xie Za Zhi ; 46(1): 108-113, 2022 Jan 30.
Artigo em Zh | MEDLINE | ID: mdl-35150120

RESUMO

To study an automatic plan(AP) method for radiotherapy after breast-conserving surgery based on TiGRT system and and compare with manual plan (MP). The dosimetry parameters of 10 patients and the evaluation of scoring table were analyzed, it was found that the targets dose of AP were better than that of MP, but there was no statistical difference except for CI, The V5, V20 and V30 of affected lungs and whole lungs in AP were lower than all that in MP, the Dmean of hearts was slightly higher than that of MP, but the difference was not statistically significant, the MU of AP was increase by 16.1% compared with MP, the score of AP evaluation was increase by 6.1% compared with MP. So the AP could be programmed and automated while ensuring the quality of the plan, and can be used to design the plans for radiotherapy after breast-conserving surgery.


Assuntos
Neoplasias da Mama , Radioterapia de Intensidade Modulada , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia Segmentar , Órgãos em Risco , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador
6.
Mol Cancer ; 20(1): 36, 2021 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608029

RESUMO

Early detection is crucial to improve breast cancer (BC) patients' outcomes and survival. Mammogram and ultrasound adopting the Breast Imaging Reporting and Data System (BI-RADS) categorization are widely used for BC early detection, while suffering high false-positive rate leading to unnecessary biopsy, especially in BI-RADS category-4 patients. Plasma cell-free DNA (cfDNA) carrying on DNA methylation information has emerged as a non-invasive approach for cancer detection. Here we present a prospective multi-center study with whole-genome bisulfite sequencing data to address the clinical utility of cfDNA methylation markers from 203 female patients with breast lesions suspected for malignancy. The cfDNA is enriched with hypo-methylated genomic regions. A practical computational framework was devised to excavate optimal cfDNA-rich DNA methylation markers, which significantly improved the early diagnosis of BI-RADS category-4 patients (AUC from 0.78-0.79 to 0.93-0.94). As a proof-of-concept study, we performed the first blood-based whole-genome DNA methylation study for detecting early-stage breast cancer from benign tumors at single-base resolution, which suggests that combining the liquid biopsy with the traditional diagnostic imaging can improve the current clinical practice, by reducing the false-positive rate and avoiding unnecessary harms.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/genética , Ácidos Nucleicos Livres/genética , Metilação de DNA , Sequenciamento Completo do Genoma/métodos , Biomarcadores Tumorais/genética , Detecção Precoce de Câncer , Epigênese Genética , Feminino , Humanos , Biópsia Líquida , Mamografia , Estudo de Prova de Conceito , Estudos Prospectivos , Ultrassonografia Mamária
7.
J Nanobiotechnology ; 19(1): 344, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34706736

RESUMO

BACKGROUND: The use of magnetic nanozymes (NZs) with the ability to synchronize gas therapy through photodynamic and chemotherapy in the treatment of breast cancer has received much attention. RESULTS: Hence, in this study, we designed a bovine lactoferrin-coated iron sulfide NZs containing doxorubicin (abbreviated as: FeS-Dox@bLf NZs) by wet-chemical synthesis method. Then, the physicochemical characteristics of synthesized NZs were explored by several methods. Also, the level of Fe2+, H2S and Dox releases from FeS-Dox@Lf NZs. Also, the cytotoxic effects of FeS-Dox@Lf NZs were investigated by cellular assays. After intravenous injections of NZs and laser irradiation, significant effects of FeS-Dox@Lf NZs on mice weight and tumor status were observed. Afterwards, not only the distribution of Dox in the body was examined by fluorescent, but also the time of Fe clearance and the amount of Dox and Fe retention in vital tissues were determined. The findings confirm that FeS-Dox@Lf NZs, in addition to targeted drug distribution in tumor tissue, resulted in superior therapeutic performance compared to free Dox due to reduced Dox side effects in vital tissues, and increased level of free radicals in 4T1 cells. CONCLUSION: Overall, FeS-Dox@Lf NZs with the ability to synchronize chemotherapy and gas therapy raised hopes for more effective treatment of breast cancer.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/farmacologia , Compostos Ferrosos/farmacologia , Terapia a Laser/métodos , Lasers , Animais , Antineoplásicos/uso terapêutico , Apoptose , Neoplasias da Mama/radioterapia , Linhagem Celular Tumoral , Doxorrubicina/uso terapêutico , Portadores de Fármacos/uso terapêutico , Tratamento Farmacológico/métodos , Feminino , Compostos Ferrosos/química , Compostos Ferrosos/uso terapêutico , Lactoferrina/farmacologia , Lactoferrina/uso terapêutico , Camundongos
8.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 38(1): 161-168, 2021 Feb 25.
Artigo em Zh | MEDLINE | ID: mdl-33899441

RESUMO

Image-guided radiation therapy using magnetic resonance imaging (MRI) is a new technology that has been widely studied and developed in recent years. The technology combines the advantages of MRI imaging, and can offer online real-time tracking of tumor and adjacent organs at risk, as well as real-time optimization of radiotherapy plan. In order to provide a comprehensive understanding of this technology, and to grasp the international development and trends in this field, this paper reviews and summarizes related researches, so as to make the researchers and clinical personnel in this field to understand recent status of this technology, and carry out corresponding researches. This paper summarizes the advantages of MRI and the research progress of MRI linear accelerator (MR-Linac), online guidance, adaptive optimization, and dosimetry-related research. Possible development direction of these technologies in the future is also discussed. It is expected that this review can provide a certain reference value for clinician and related researchers to understand the research progress in the field.


Assuntos
Radioterapia Guiada por Imagem , Imageamento por Ressonância Magnética , Aceleradores de Partículas , Radiometria , Planejamento da Radioterapia Assistida por Computador
9.
J Cell Physiol ; 235(11): 7923-7932, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-31957871

RESUMO

Increasing evidence indicates that long noncoding RNAs (lncRNAs) play pivotal roles during tumorigenesis in multiple types of cancers. However, little is known about the exact role of plasmacytoma variant translocation 1 (PVT1) in human pan-cancer. Here, we report the oncogenic role and function of PVT1 in human pan-cancer, including breast cancer. The expression of PVT1 in human tumor tissues and nontumor tissues, the upstream regulation of PVT1 and the relationship between its expression and prognosis and chemoresistance were examined by using The Cancer Genome Atlas data. PVT1 expression is higher in human cancer tissues compared with adjacent noncancerous tissues, and patients with high levels of PVT1 expression usually have tumors with a higher TNM stage. High PVT1 expression is also associated with worse disease outcomes in patients with cancer. Hypomethylation and transcription factor binding in the PVT1 promoter locus activates its transcriptional expression. Guilt by association analysis revealed that PVT1 may be involved in processes associated with tumorigenesis. Moreover, PVT1 may trigger chemoresistance in human cancer. These results indicated that PVT1 may act as an oncogenic driver and maybe a potential therapeutic target in human cancer.


Assuntos
Neoplasias da Mama/genética , Carcinogênese/genética , Metilação de DNA/genética , RNA Longo não Codificante/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico , Regiões Promotoras Genéticas/genética
10.
J Cell Physiol ; 235(2): 1795-1807, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31332783

RESUMO

The function of Fer-1 like family member 4 (FER1L4) in human pan-cancer is unknown. Expression of FER1L4 in tumor tissues and nontumor tissues, upstream regulation of FER1L4, and the relationship between its expression with prognosis and chemoresistance were examined by The Cancer Genome Atlas and Gene Expression Omnibus databases. Next, these results were validated in breast tumor and paired nontumor tissues in our cohort. FER1L4 expression is higher in tumor tissues compared with the adjacent nontumor tissues. High FER1L4 expression is associated with worse disease outcomes. Hypomethylation and H3K4me3 accumulation in FER1L4 promoter locus activate its transcriptional expression. Moreover, FER1L4 may trigger chemoresistance in human cancer. Gene Ontology enrichment analysis revealed that FER1L4 may be involved in processes associated with tumorigenesis. These results indicated that FER1L4 may act as an oncogenic driver and it may be a potential therapy target in human cancer.


Assuntos
Carcinogênese/genética , Neoplasias/genética , Oncogenes/genética , RNA Longo não Codificante/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos
11.
J Cell Physiol ; 235(4): 3425-3437, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31556117

RESUMO

Glutathione peroxidase 4 (GPX4) has been confirmed to inhibit ferroptosis in cancer cells, however, whether GPX4 serves as an oncogene is not clear. In this study, the expression of GPX4 and its influence to survival of patients with cancer were analyzed via public databases. Furthermore, the epigenetic regulation of GPX4 and the relation between GPX4 and chemoresistance of different anticancer drugs was also detected. Most importantly, cytological assays were performed to investigate the function of GPX4 in cancer cells. The results showed that GPX4 was higher expressed in cancer tissues than normal and was negatively associated with prognosis of patients. Furthermore, at upstream of GPX4 there was low DNA methylation sites and enhanced level of H3K4me3 and H3K27ac, indicating that high level of GPX4 in cancer may resulted from epigenetic regulation. Moreover, GPX4 was positively related to chemoresistance of anticancer drugs L-685458, lapatinib, palbociclib, and topotecan. In addition, GPX4 may potentially be involved in translation of protein, mitochondrial respiratory chain complex I assembly, electron transport oxidative phosphorylation, nonalcoholic fatty liver disease, and metabolic pathways. Finally, we detected that GPX4 inhibited ferroptosis in cancer cells, the inhibition of GPX4 via RSL3 could enhance the anticancer effect of cisplatin in vitro and in vivo. In conclusion, GPX4 acts as an oncogene and inhibits ferroptosis in cancer cells, the anticancer effect of cisplatin can be enhanced by GPX4 inhibition.


Assuntos
Metilação de DNA/efeitos dos fármacos , Ferroptose/genética , Neoplasias/tratamento farmacológico , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Células A549 , Animais , Carbamatos/farmacologia , Movimento Celular/efeitos dos fármacos , Cisplatino/farmacologia , Dipeptídeos/farmacologia , Epigênese Genética/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Xenoenxertos , Histonas/genética , Humanos , Lapatinib/farmacologia , Camundongos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Neoplasias/genética , Neoplasias/patologia , Piperazinas/farmacologia , Piridinas/farmacologia , Topotecan/farmacologia
12.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 37(1): 136-141, 2020 Feb 25.
Artigo em Zh | MEDLINE | ID: mdl-32096387

RESUMO

The segmentation of organs at risk is an important part of radiotherapy. The current method of manual segmentation depends on the knowledge and experience of physicians, which is very time-consuming and difficult to ensure the accuracy, consistency and repeatability. Therefore, a deep convolutional neural network (DCNN) is proposed for the automatic and accurate segmentation of head and neck organs at risk. The data of 496 patients with nasopharyngeal carcinoma were reviewed. Among them, 376 cases were randomly selected for training set, 60 cases for validation set and 60 cases for test set. Using the three-dimensional (3D) U-NET DCNN, combined with two loss functions of Dice Loss and Generalized Dice Loss, the automatic segmentation neural network model for the head and neck organs at risk was trained. The evaluation parameters are Dice similarity coefficient and Jaccard distance. The average Dice Similarity coefficient of the 19 organs at risk was 0.91, and the Jaccard distance was 0.15. The results demonstrate that 3D U-NET DCNN combined with Dice Loss function can be better applied to automatic segmentation of head and neck organs at risk.


Assuntos
Processamento de Imagem Assistida por Computador , Carcinoma Nasofaríngeo/patologia , Redes Neurais de Computação , Órgãos em Risco , Cabeça , Humanos , Pescoço , Tomografia Computadorizada por Raios X
13.
Zhongguo Yi Liao Qi Xie Za Zhi ; 44(6): 508-512, 2020 Dec 08.
Artigo em Zh | MEDLINE | ID: mdl-33314859

RESUMO

Flash radiotherapy is a kind of radiotherapy method using ultra-high dose rate radiation. Compared with the traditional dose rate radiotherapy, it has unique radiobiological advantages. In this paper, the principle of flash radiotherapy, the process and results of biological experiments are summarized. At the same time, the advantages and challenges of flash radiotherapy are analyzed, and the future clinical application is prospected.


Assuntos
Dosagem Radioterapêutica , Radioterapia/métodos , Tecnologia
14.
Med Res Rev ; 39(5): 1953-1999, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30820989

RESUMO

Autophagy is central to the maintenance of intracellular homeostasis across species. Accordingly, autophagy disorders are linked to a variety of diseases from the embryonic stage until death, and the role of autophagy as a therapeutic target has been widely recognized. However, autophagy-associated therapy for human diseases is still in its infancy and is supported by limited evidence. In this review, we summarize the landscape of autophagy-associated diseases and current autophagy modulators. Furthermore, we investigate the existing autophagy-associated clinical trials, analyze the obstacles that limit their progress, offer tactics that may allow barriers to be overcome along the way and then discuss the therapeutic potential of autophagy modulators in clinical applications.


Assuntos
Autofagia , Debilidade Muscular , Humanos
15.
J Cell Physiol ; 234(10): 17420-17432, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30793303

RESUMO

The function of DLEU1 in human cancer is largely unknown. The Cancer Genome Atlas data were applied to identify the landscape of differential genes between tumor tissues and normal tissues, which was further validated by our cohort data and pan-cancer data including 33 cancer types with 11,060 patients. Next, DLEU1 was selected to validate the novel finding and result showed that it promoted tumorigenesis in vitro and in vivo. Mechanistically, DLEU1 promotes SRP4 expression via increasing H3K27ac enrichment to SRP4 locus epigenetically. Moreover, epigenetic modification leads to upregulation of DLEU1 expression via decreased DNA methylation and increased H3K27ac and H3K4me3 histone modification in its locus. Finally, high expression of DLEU1 correlates with worse prognosis not only in specific cancer type patients but also in patients in the pan-cancer cohort. In summary, the work broadens the function landscape of known long noncoding RNAs in human cancer and provides novel insights into their roles in tumorigenesis.


Assuntos
Carcinogênese/metabolismo , Transformação Celular Neoplásica/genética , Regulação Neoplásica da Expressão Gênica/genética , Proteínas Supressoras de Tumor/metabolismo , Carcinogênese/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Epigênese Genética/genética , Humanos , RNA Longo não Codificante/genética , Regulação para Cima
16.
Mol Cancer ; 18(1): 89, 2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-30999914

RESUMO

BACKGROUND: The biology function of antisense intronic long noncoding RNA (Ai-lncRNA) is still unknown. Meanwhile, cancer patients with paclitaxel resistance have limited therapeutic options in the clinic. However, the potential involvement of Ai-lncRNA in paclitaxel sensitivity remains unclear in human cancer. METHODS: Whole transcriptome sequencing of 33 breast specimens was performed to identify Ai-lncRNA EGOT. Next, the role of EGOT in regulation of paclitaxel sensitivity was investigated. Moreover, the mechanism of EGOT enhancing autophagy sensitizes paclitaxel cytotoxicity via upregulation of ITPR1 expression by RNA-RNA and RNA-protein interactions was investigated in detail. Furthermore, upstream transcriptional regulation of EGOT expression was also investigated by co-immunoprecipitation and chromatin immunoprecipitation. Finally, clinical breast specimens in our cohort, TCGA and ICGC were applied to validate the role of EGOT in enhancing of paclitaxel sensitivity. RESULTS: EGOT enhances autophagosome accumulation via the up-regulation of ITPR1 expression, thereby sensitizing cells to paclitaxel toxicity. Mechanistically, on one hand, EGOT upregulates ITPR1 levels via formation of a pre-ITPR1/EGOT dsRNA that induces pre-ITPR1 accumulation to increase ITPR1 protein expression in cis. On the other hand, EGOT recruits hnRNPH1 to enhance the alternative splicing of pre-ITPR1 in trans via two binding motifs in EGOT segment 2 (324-645 nucleotides) in exon 1. Moreover, EGOT is transcriptionally regulated by stress conditions. Finally, EGOT expression enhances paclitaxel sensitivity via assessment of cancer specimens. CONCLUSIONS: These findings broaden comprehensive understanding of the biology function of Ai-lncRNAs. Proper regulation of EGOT may be a novel synergistic strategy for enhancing paclitaxel sensitivity in cancer therapy.


Assuntos
Autofagia/genética , Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica , Receptores de Inositol 1,4,5-Trifosfato/genética , RNA Longo não Codificante/genética , Adulto , Idoso , Animais , Antineoplásicos Fitogênicos/farmacologia , Autofagossomos/metabolismo , Autofagia/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Ribonucleoproteínas Nucleares Heterogêneas Grupo F-H/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo F-H/metabolismo , Humanos , Receptores de Inositol 1,4,5-Trifosfato/antagonistas & inibidores , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Paclitaxel/farmacologia , Ligação Proteica , RNA de Cadeia Dupla/genética , RNA de Cadeia Dupla/metabolismo , RNA Longo não Codificante/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Análise de Sobrevida , Transcriptoma , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Soft Matter ; 15(47): 9727-9732, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31742297

RESUMO

A facile method that combines alkali-assisted oxidation and -SH chelation with a click chemistry reaction was employed to create an F-POSS polymer surface (fluorinated octavinyl polyhedral oligomeric silsesquioxane polymer)-based Cu mesh (F-POSS-OM). The as-prepared F-POSS-OM surface displayed a cohering hierarchical nano-F-POSS polymer granule/micro-Cu(OH)2 wire structure, which provided a re-entrant geometry needed for liquid-repellency and low liquid sliding angles (<15°). Moreover, the easy-prepared structure endows the F-POSS-OM with remarkable durability for mechanical and chemical damages, including wear abrasion, tape-peeling, 100 cm-height hammer impact, severe hand twisting, strong acid/base/salt solutions, and high temperatures. Importantly, F-POSS-OM still retained excellent self-cleaning performance even after being subjected to these damages.

18.
Cell Physiol Biochem ; 45(2): 692-705, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29414807

RESUMO

BACKGROUND/AIMS: Tropomyosin-2 (TPM2) plays important roles in functions of the cytoskeleton, such as cytokinesis, vesicle transport, cell proliferation, migration and apoptosis,and these functions imply that TPM2 also plays a role in cancer development. Indeed, it has been shown that TPM2 plays a critical role in some cancers. However, the role of TPM2 in breast cancer is still poorly characterized. Thus, we explored the role of TPM2 in breast cancer. METHODS: We analysed TPM2 expression and its correlation with the clinicopathological features in breast cancer. Then, we examined the influence of hypoxia on TPM2 expression and methylation status using bisulfite sequencing PCR. Furthermore, we performed TPM2-mediated migration and invasion assays in the context of hypoxia and examined changes in matrix metalloproteinase-2 (MMP2) expression. Finally, we detected the influence of TPM2 on survival and chemotherapy drug sensitivity. RESULTS: We found that TPM2 expression is down-regulated in breast cancer cells compared to that in normal breast cells. The data from TCGA supported these results. Promoter methylation of TPM2, which could be induced by hypoxia, was responsible for its low expression. Hypoxia might regulate cell invasiveness partly by TPM2 down-regulation-mediated changes of MMP2 expression. Importantly, low TPM2 expression was correlated with lymph node metastasis (P=0.031), tumour node metastasis stage (P=0.01), histological grade (P=0.037), and shorter overall survival (P=0.028). Univariate and multivariate analyses indicated that TPM2 was an independent predictor in breast cancer patients. Paclitaxel chemotherapy did not benefit patients with low TPM2 expression (P<0.0001). TPM2 knockdown significantly reduced cell sensitivity to paclitaxel. CONCLUSION: TPM2 is a potential novel tumour suppressor gene in breast cancer. TPM2 is associated with poor survival and chemoresistance to paclitaxel in breast cancer, and TPM2 may represent a promising therapeutic gene target for breast cancer patients with chemoresistance.


Assuntos
Neoplasias da Mama/patologia , Hipóxia Celular , Tropomiosina/metabolismo , Antineoplásicos Fitogênicos/uso terapêutico , Antineoplásicos Fitogênicos/toxicidade , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Linhagem Celular Tumoral , DNA/isolamento & purificação , DNA/metabolismo , Metilação de DNA , Regulação para Baixo/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Metástase Linfática , Células MCF-7 , Metaloproteinase 2 da Matriz/metabolismo , Pessoa de Meia-Idade , Paclitaxel/uso terapêutico , Paclitaxel/toxicidade , Prognóstico , Regiões Promotoras Genéticas , Interferência de RNA , Tropomiosina/antagonistas & inibidores , Tropomiosina/genética
19.
Phys Chem Chem Phys ; 20(6): 4074-4082, 2018 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-29354819

RESUMO

A polyhedral oligomeric silsesquioxane (POSS)-based hybrid triblock copolymer - methyl methacrylate-b-perfluoroalkylethyl methacrylate-b-methacrylisobutyl polyhedral oligomeric silsesquioxane (PMMA-b-PFMA-b-PMAPOSS) was synthesized via an atom transfer radical polymerization (ATRP) method. The self-assembly behavior of triblock copolymers in selective solvents of tetrahydrofuran (THF) and trichlorotrifluoroethane (F113) was studied using dissipative particle dynamics (DPD) simulation. The effects of the block sequence and volume ratio of F113/THF were discussed. The aggregate morphology and size were also characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The simulation results showed that the spherical micelle with core-shell-corona or core-mixed shell structure could be formed and the micelle size increased with the F113 content, which was in qualitative agreement with the experimental results. The DPD simulation revealed the dynamic process of the formation of aggregates at the mesoscopic scale, which can be considered as an adjunct to experiments and provides other valuable information for the experiments.

20.
Zhongguo Yi Liao Qi Xie Za Zhi ; 42(6): 455-459, 2018 Nov 30.
Artigo em Zh | MEDLINE | ID: mdl-30560631

RESUMO

MRI simulator(MRI-Sim) images have unique clinical advantages with higher resolution of soft tissue and clearer visualization of tissue boundaries. Thus, the precise positioning of the tumor target area can be achieved and it is widely used in the field of radiotherapy. This article focuses on the acceptance test project and image quality assurance work of MRI-Sim equipment. The obtained ACR phantom images were used to analyze various image quality assurance indicators, and the results all reached the set standards, thereby ensuring that the obtained images meet the requirements of clinical applications.


Assuntos
Imageamento por Ressonância Magnética , Garantia da Qualidade dos Cuidados de Saúde , Imagens de Fantasmas
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