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OBJECTIVES: This study sought to provide contemporary data from a multi-institution with respect to DNA-repair genes (DRGs) status and its impact on effects of platinum-based chemotherapy in treatment-emergent neuroendocrine prostate cancer (t-NEPC), for which little data exist. PATIENTS AND METHODS: All patients were retrospectively collected with eligible biopsied tissues for targeted next generation sequencing (NGS). The main outcomes were radiologic progression-free survival and overall survival according to Response Evaluation Criteria in Solid Tumors, version 1.1. RESULTS: Among the 43 NEPC patients, 13/43 (30%) harbored homozygous deletions, deleterious mutations, or both in DRGs. Eleven patients (11/13, 85%) with DRGs aberrations had effective response, including 7 patients with BRCA1/2 defects and 2 with mismatch repair-deficient caused by MSH2 alterations. While significantly fewer responders (30%) were detected in patients without DRGs aberrations (odds ratio = 12.83, p = 0.003). Compared with patients without genomic DRGs aberrations, the hazard ratio (HR) for radiologic progression in those with DRGs defects was 0.42 (95% confidence interval [CI]: 0.19-0.93), and the HR for death was 0.65 (95% CI: 0.24-1.72). The most common adverse event of Grade 3 or 4 was anemia, as noted in 7 patients (16%). CONCLUSION: The DRGs status is therapeutically meaningful in t-NEPC. Given the potential responses to platinum-based chemotherapy, our findings support the clinical use of NGS in t-NEPC patients to identify DRGs aberrations.
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Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/genética , Reparo do DNA/genética , Compostos de Platina/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Idoso , Antineoplásicos , Proteína BRCA1/genética , Proteína BRCA2/genética , Carboplatina/uso terapêutico , Carcinoma Neuroendócrino/patologia , Cisplatino/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that a pair of the data panels showing the results of Transwell invasion assays (specifically, the 'C42 / shCON' and the PC3 / CON panels) featured in Fig. 3F on p. 927 contained overlapping sections, such that data that were intended to show the results from differently performed experiments appeared to have been derived from the same original source. The authors were able to reexamine their original data files, and realized that this figure had been inadverently assembled incorrectly. The revised version of Fig. 3, containing the correct representative image of the PC3shCON group, is shown on the next page. The authors also noted that the statistics in Fig. 3G remained correct, and did not require correction on account of the error made in assembling this figure. Similarly, note that the correction made to this figure does not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and all the authors agree with its publication. They also apologize to the readership for any inconvenience caused. [Oncology Reports 45: 921932, 2021; DOI: 10.3892/or.2021.7920].
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BACKGROUND: Based on the literature and data on its clinical trials, the incidence of venous thromboembolism (VTE) in patients undergoing neurosurgery has been 3.0%~26%. We used advanced machine learning techniques and statistical methods to provide a clinical prediction model for VTE after neurosurgery. METHODS: All patients (n = 5867) who underwent neurosurgery from the development and retrospective internal validation cohorts were obtained from May 2017 to April 2022 at the Department of Neurosurgery at the Sanbo Brain Hospital. The clinical and biomarker variables were divided into pre-, intra-, and postoperative. A univariate logistic regression (LR) was applied to explore the 67 candidate predictors with VTE. We used a multivariable logistic regression (MLR) to select all significant MLR variables of MLR to build the clinical risk prediction model. We used a random forest to calculate the importance of significant variables of MLR. In addition, we conducted prospective internal (n = 490) and external validation (n = 2301) for the model. RESULTS: Eight variables were selected for inclusion in the final clinical prediction model: D-dimer before surgery, activated partial thromboplastin time before neurosurgery, age, craniopharyngioma, duration of operation, disturbance of consciousness on the second day after surgery and high dose of mannitol, and highest D-dimer within 72 h after surgery. The area under the curve (AUC) values for the development, retrospective internal validation, and prospective internal validation cohorts were 0.78, 0.77, and 0.79, respectively. The external validation set had the highest AUC value of 0.85. CONCLUSIONS: This validated clinical prediction model, including eight clinical factors and biomarkers, predicted the risk of VTE following neurosurgery. Looking forward to further research exploring the standardization of clinical decision-making for primary VTE prevention based on this model.
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Bladder cancer is the most common malignant tumor of the urinary system, and in China it is first among urogenital system tumors. More therapeutic targets are still urgently required to combat this disease. Lamin B2 (LMNB2) is a type of nuclear lamina filament protein, which is involved in multiple cellular processes, and known as an oncogene affecting the progression of multiple types of cancers. Although the multiple effects of LMNB2 on cancer progression have been elucidated, its possible role in bladder cancer remains unclear. In the present study, it was determined that LMNB2 expression was upregulated in human bladder cancer tissues, and its expression was correlated with the prognosis and the clinical features, including tumor stage (P=0.001) and recurrence (P=0.006) of patients with bladder cancer. In addition, it was further revealed that LMNB2 depletion inhibited bladder cancer cell proliferation, stimulated cell cycle arrest and apoptosis in vitro, and suppressed tumor growth of bladder cancer cells in mice. Furthermore, the present data revealed that LMNB2 promoted the proliferation of bladder cancer cells via transcriptional activation of CDCA3 expression. Therefore, the role of LMNB2 in bladder cancer progression was demonstrated, and may serve as a promising therapeutic target for bladder cancer treatment.
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Lamina Tipo B , Neoplasias da Bexiga Urinária , Animais , Apoptose/fisiologia , Ciclo Celular/fisiologia , Proteínas de Ciclo Celular/biossíntese , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Lamina Tipo B/biossíntese , Lamina Tipo B/genética , Lamina Tipo B/metabolismo , Camundongos , Regulação para Cima , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologiaRESUMO
The aim of this study was to investigate the biological function and molecular mechanism of ARPC1A (actin related protein 2/3 complex subunit 1A) in prostate cancer progression. RT-qPCR and IHC results showed that the level of ARPC1A in prostate cancer tissues was significantly higher than that in adjacent tissues. The results of TCGA (the cancer genome atlas) database analysis showed that high expression of ARPC1A indicates poor prognosis in prostate cancer patients. In vitro functional experiments confirmed that downregulation of ARPC1A expression resulted in decreased cell viability and invasive ability of prostate cancer cells, as ARPC1A knockdown promoted ferroptosis. The transcriptional regulation mechanism of STAT3 (signal transduction and activators of transcription 3) on ARPC1A was elucidated by Co-IP, ChIP and luciferase reporter assays. In vivo experiments also supported the in vitro results. We propose that reduced ARPC1A expression inhibits prostate cancer cell viability and invasion in a ferroptotic manner. The ARPC1A level may serve as an independent predictor of prognosis in prostate cancer patients.
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Complexo 2-3 de Proteínas Relacionadas à Actina/metabolismo , Ferroptose , Neoplasias da Próstata , Fator de Transcrição STAT3 , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Próstata/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de SinaisRESUMO
In order to investigate the hypolipidaemic and antioxidant effects of various dark teas produced from different post-fermentation using the same raw material, a hyperlipidaemia zebrafish model combined with binding bile salts assay and antioxidant assays were performed in this study. Results showed that the hypolipidaemic effect of dark tea extracts increased significantly (p < 0.05) while the antioxidant ability decreased sharply compared with raw material. Particularly, Liupao tea (50%) and Pu-erh tea (48%) showed promising hypolipidaemic potential; however, the antioxidant capacity of Pu-erh tea decreased (31-49%) most dramatically. Besides, the levels of total polyphenols and catechins decreased sharply, but theabrownin, gallic acid, and caffeine increased significantly after post-fermentation. Moreover, the potential mechanisms of regulating hyperlipidaemia by dark tea extracts were discussed. These results suggest that microbial fermentation significantly affects the bioactivity of dark teas, and provide theoretical basis for processing and improving of dark tea products for hyperlipidaemia therapy.
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Antioxidantes , Chá , Animais , Antioxidantes/análise , China , Fermentação , Extratos Vegetais , Peixe-ZebraRESUMO
Traditional alternating-current-driven electroluminescent (AC-EL) devices adopting a sandwich structure are commonly used in solid-state lighting and displays, while the emerging coplanar-electrode alternating-current-driven light-emitting variants manifest excellent application prospects in intelligent, multifunctional, and full-color displays, and sensing purposes. In this work, an asymmetrically enhanced coplanar-electrode AC-EL device with a universal and straightforward architecture is designed based on the impedance adjustment strategy. This newly devised asymmetric structure extends the functionalities of the coplanar-electrode AC-EL devices by overcoming the bottlenecks of complicated patterning procedures and high driving voltages of symmetric configuration. The developed device design enables a new type of information encryption and ultrahighly stretchable patterned displays. Notably, the novel encryption appliances demonstrate feasible encryption/decryption features, multiple encryptions, and practical applicability; the biaxially stretchable display devices achieve the highest tensile performance in the field of stretchable electroluminescent pattern displays, and outperform the ultrahighly stretchable sandwich devices in terms of simple patterning process, higher brightness, wider color gamut, and long-term stability. The proposed configuration opens up new avenues for AC-EL devices toward a plethora of smart applications in wearable electronics with intelligent displays, dynamic interaction of human-machine interface, and soft robotics.
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Cell division cycle-associated 5 (CDCA5) can regulate cell cycle-related proteins to promote the proliferation of cancer cells. The purpose of the present study was to investigate the expression level of CDCA5 in prostate cancer (PCa) and its effect on PCa progression. The signalling pathway by which CDCA5 functions through was also attempted to elucidate. Clinical specimens of PCa patients were collected from the Second Hospital of Tianjin Medical University. The expression level of CDCA5 in cancer tissues and paracancerous tissues from PCa patients was detected by RT-qPCR analysis and IHC. The relationship between the expression level of CDCA5 and the survival rate of PCa patients was analysed using TCGA database. Two stable cell lines (C4-2 and PC-3) with CDCA5 knockdown were established, and the effects of CDCA5 on PCa cell proliferation were detected by MTT and colony formation assays. Flow cytometry was performed to detect the effect of CDCA5 on the PCa cell division cycle, and western blot analysis was used to determine changes in ERK phosphorylation levels after CDCA5 knockdown. The effect of CDCA5 expression on prostate tumour growth was assessed using a mouse xenograft model. The results revealed that the mRNA and protein expression levels of CDCA5 were significantly higher in PCa tissues than in paracancerous tissues. High CDCA5 expression was associated with the prognosis of patients with PCa. CDCA5 expression knockdown significantly reduced the number of PCa cells in mitoses and inhibited their proliferation in vitro and in vivo. When CDCA5 was knocked down, the phosphorylation level of ERK was also reduced. Collectively, CDCA5 was upregulated and affected the prognosis of patients with PCa. Decreased CDCA5 expression inhibited PCa cell proliferation by inhibiting the ERK signalling pathway. Thus, CDCA5 may be a potential therapeutic target for PCa.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Ciclo Celular/metabolismo , Sistema de Sinalização das MAP Quinases , Neoplasias da Próstata/patologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Idoso , Animais , Ciclo Celular , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Prognóstico , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/mortalidadeRESUMO
Current power supply networks across the world are mostly based on three-phase electrical systems as an efficient and economical way for generation, transmission and distribution of electricity. Now, many electrically driven devices are relying on direct current or single-phase alternating current power supply that complicates utilization of three-phase power supply by requiring additional elements and costly switching mechanisms in the circuits. For example, light-emitting devices, which are now widely used for displays, solid-state lighting etc. typically operate with direct current power sources, although single-phase alternating current driven light-emitting devices have also gained significant attention in the recent years. Yet, light-emitting devices directly driven by a three-phase electric power has never been reported before. Benefiting from our precious work on coplanar electrodes structured light-emitting devices, in this article we demonstrate proof of a concept that light-emitting components can be driven by three-phase electric power without utilizing intricate back-end circuits and can compose state detection sensors and pixel units in a single device inspiring from three primary colors. Here we report a three-phase electric power driven electroluminescent devices fabricated featuring of flexibility and multi-functions. The design consists of three coplanar electrodes with dielectric layer(s) and light emission layer(s) coated on a top of input electrodes. It does not require transparent electrodes for electrical input and the light emission occurs when the top light-emitting layers are connected through a polar bridge. We demonstrate some applications of our three-phase electric power driven electroluminescent devices to realize pixel units, interactive rewritable displays and optical-output sensors. Furthermore, we also demonstrate the applicability of three-phase electrical power source to drive organic light-emitting devices with red, green and blue-emitting pixels and have shown high luminance (up to 6601 cd/m2) and current efficiency (up to 16.2 cd/A) from fabricated three-phase organic light-emitting devices. This novel geometry and driving method for electroluminescent devices is scalable and can be utilized even in a wider range of other types of light-emitting devices and special units.
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INTRODUCTION: Tumors of the pineal region are rare, and metastatic carcinoma occurring in the pineal region is extremely rare. No previous reports have described pineal region metastasis with intraventricular seeding. PATIENT CONCERNS: We report a case of a 51-year-old woman presented with a 1-week history of severe headache, nausea, and vomiting. Imaging examination revealed 2 lesions in the pineal region and the right lateral ventricle. DIAGNOSIS: Pinealocytoma or germinoma was considered as the preoperative diagnosis. The postoperative pathological diagnosis was small cell neuroendocrine carcinoma. After bronchoscopic biopsy, small cell lung cancer was confirmed. INTERVENTIONS: A right frontal craniotomy and a translateral ventricle approach were performed to remove 2 lesions completely. And regular radiotherapy and chemotherapy were initiated after surgery. OUTCOMES: The patient was discharged from the hospital 2 weeks after operation and went to another cancer hospital for bronchoscopic biopsy, radiotherapy, and chemotherapy. Finally, the patient died 2 years after surgical treatment. CONCLUSION: Metastatic tumors of the pineal region are very rare. For patients with pineal lesions, a diagnosis of a metastatic tumor should be considered. Retrograde cerebrospinal fluid circulation might be the reason for a secondary metastasis.
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Neoplasias Pulmonares/patologia , Pinealoma/secundário , Carcinoma de Pequenas Células do Pulmão/patologia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Pinealoma/cirurgiaRESUMO
PURPOSE: KIF20A is essential in the process of spindle assembly and cytokinesis regulation. The role of KIF20A during tumorigenesis and tumor development has been well studied in several cancers. But the association between the KIF20A clinical role and prostate cancer (PCa) has not been reported yet. In this study, we investigated its potential prognostic effect and its role in progression of prostate cancer. METHODS: Real-time quantitative polymerase chain reaction and Western blots were used to investigate the KIF20A transcription and translation levels in 7 pairs of fresh PCa tissue and adjacent normal prostate tissue. Immunohistochemistry (IHC) was used to investigate the KIF20A protein level in 114 PCa tissue samples. Bioinformatics analysis was performed to analyze the effect of KIF20A in oncologic prognosis in PCa patients. MTT assay, transwell assay, and colony formation assay in vitro and tumor formation assay in vivo were performed to evaluate the biological behavior of KIF20A in prostate cancer. RESULTS: KIF20A was significantly elevated in tumor tissue compared with normal prostate tissue at both the mRNA and the protein level. High expression of KIF20A at the protein level was correlated with adverse clinicopathological features. Bioinformatics analysis showed that the high KIF20A expression group has a poor biochemical recurrence- (BCR-) free survival. Knocking down KIF20A suppressed the proliferation, migration, and invasion of the prostate cancer cell both in vitro and in vivo. CONCLUSIONS: Our data demonstrated that the high expression of KIF20A was associated with poor clinical outcome and targeting KIF20A could reduce proliferation, migration, and invasion of the prostate cancer cell, indicating that KIF20A might be a potential prognostic and therapeutic target for PCa patients.