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Background: Concurrent chemoradiotherapy is the preferred treatment for stage IVB cervical cancer; however, some patients experience a poor prognosis. The prognostic significance of body composition indicators, including visceral obesity, has been extensively investigated in patients with cancer. This study aimed to assess the impact of body composition indicators, specifically pretreatment fat content, on the survival outcomes of patients with stage IVB cervical cancer. Methods: We retrospectively analyzed clinical information from patients diagnosed with stage IVB cervical cancer between 2010 and 2018. We measured visceral obesity (visceral-to-subcutaneous adipose tissue area ratio [VSR]) and skeletal muscle index (SMI) on pretreatment computed tomography (CT) images. We evaluated the impact of these body composition parameters on the prognosis of patients with cervical cancer. Results: Overall, 116 patients were included, 81 of whom had complete clinical and imaging information. Based on the cut-off values from X-tile analysis, we categorized patients into high and low VSR and SMI groups. The overall survival (OS) rate of patients with a high VSR was significantly higher than that of patients with a low VSR (P = 0.022). Multivariate Cox regression analysis showed that a low VSR was an independent risk factor for the prognosis of patients with stage IVB cervical cancer. Conclusion: Visceral obesity before radiotherapy and chemotherapy has a protective effect on the prognosis of patients with stage IVB cervical cancer, while low muscle index and VSR are associated with poor prognosis.
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OBJECTIVES: This study aimed to evaluate the clinical value of the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) for assessing disease activity in patients with SLE. METHODS: Clinical data were collected from patients with SLE who were admitted at the Second Affiliated Hospital of Soochow University from January 2009 to December 2022. The glucocorticoid dose grading was used as the gold standard for disease activity assessment in SLE. The SLE-DAS value was calculated, and the SLE disease activity status was graded based on the SLE-DAS value. Another scoring criterion, the SLE Disease Activity Index 2000 (SLEDAI 2000), served as a control. Spearman correlation analysis was used to calculate the correlation between the scoring criteria and other variables. RESULTS: The analysis included 396 patients with SLE. A strong correlation was found between SLE-DAS and SLEDAI 2000 (ρ=0.709, 95% CI 0.648 to 0.766, p<0.001), with median SLE-DAS and SLEDAI 2000 scores of 15.32 (7.90 to 24.45) and 13 (8 to 19), respectively. Compared with the SLEDAI 2000 value, the SLE-DAS value correlated better with glucocorticoid dose grading (ρ=0.434 vs 0.518), gammaglobulin use (ρ=0.170 vs 0.318) and immunosuppressant use (ρ=0.122 vs 0.221). A moderate correlation based on disease activity grading was found between SLE-DAS and glucocorticoid dose grading (ρ=0.441), whereas a mild correlation was observed between SLEDAI 2000 and glucocorticoid dose grading (ρ=0.325). Additionally, SLE-DAS revealed a positive correlation with severe thrombocytopenia, cardiac involvement and pulmonary involvement but not SLEDAI 2000. CONCLUSION: Compared with SLEDAI 2000, SLE-DAS may provide a more accurate disease activity assessment in patients with SLE, especially those with severe thrombocytopenia and cardiopulmonary involvement.
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Glucocorticoides , Lupus Eritematoso Sistémico , Índice de Severidad de la Enfermedad , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/fisiopatología , Femenino , Masculino , Estudios Retrospectivos , Adulto , Persona de Mediana Edad , Glucocorticoides/uso terapéutico , Adulto JovenRESUMEN
OBJECTIVES: To explore the performance of laboratory items alone in systemic lupus erythematosus (SLE) classification. METHODS: Our cohort consisted of 352 and 385 (control) patients with and without SLE. This study evaluated the performance of the American College of Rheumatology (ACR)-1997, Systemic Lupus International Collaborating Clinics (SLICC)-2012, European League Against Rheumatism (EULAR)/ACR-2019, and Systemic Lupus Erythematosus Risk Probability Index (SLERPI) using laboratory items alone, including blood and urine test results. RESULTS: The median ratio of laboratory items/total items was 66.7%, 75.0%, 60.4%, and 77.4% in ACR-1997, SLICC-2012, EULAR/ACR-2019, and SLERPI, respectively. After including laboratory items alone, the sensitivity of ACR-1997, SLICC-2012, EULAR/ACR-2019, and SLERPI was 31.3% (95% confidence interval [CI]: 26.4%-36.4%), 79.8% (95% CI: 75.3%-83.9%), 75.9% (95% CI: 71.0%-80.2%), and 85.2% (95% CI: 81.1%-88.8%), respectively. We referenced the SLERPI and removed the additional restrictions, i.e., SLICC-2012 criteria only needs to fulfill at least four items (mSLICC-2012) and EULAR/ACR-2019 criteria needs to have ≥ 10 points (mEULAR/ACR-2019) to qualify for SLE classification. The mSLICC-2012 and mEULAR/ACR-2019 criteria, including laboratory items alone, newly identified 13 and 25 patients, respectively. Based on laboratory items alone, the combination of mSLICC-2012, mEULAR/ACR-2019, and SLERPI identified 348 patients with an improved sensitivity of 90.6% (95% CI: 87.1%-93.5%). Patients, who were classified according to the mEULAR/ACR-2019 criteria, all met the other criteria. CONCLUSION: Incorporating laboratory items alone was clinically feasible to help identify SLE. SLERPI and SLICC-2012, using laboratory items alone, were more worthwhile to promote in the clinic compared with EULAR/ACR-2019. Key Points ⢠Laboratory items play a crucial role in the SLE classification criteria, and incorporating laboratory items alone was clinically feasible to help in the identification of SLE. ⢠The SLERPI and SLICC-2012, using laboratory items alone, were more worthwhile to promote in the clinic compared with EULAR/ACR-2019, and the combination of the two could further improve the sensitivity. ⢠The relative simplicity of evaluating laboratory indices may help nonrheumatologists and inexperienced rheumatologists to identify SLE more quickly, thereby reducing the risk of delayed diagnosis in patients.
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Lupus Eritematoso Sistémico , Enfermedades Reumáticas , Reumatología , Humanos , Estados Unidos , Reumatología/métodos , Lupus Eritematoso Sistémico/diagnóstico , Reumatólogos , ProbabilidadRESUMEN
OBJECTIVES: To explore the relationship of tumour-associated antigens (TAAs) with the clinical manifestations and serological markers of SLE. METHODS: This was a retrospective study. Clinical data of SLE patients were extracted from the electronic medical records, including serum levels of TAAs such as alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen (CA) 19-9, CA125, CA15-3 and cytokeratin 19-fragments (CYFRA21-1). TAA positivity was defined as serum level exceeding the upper limit of the corresponding reference range. RESULTS: A total of 149 SLE patients (SLE group) and 149 age- and sex-matched healthy subjects (control group) were enrolled. Compared with healthy controls, the SLE group had higher positivity rates for CA19-9 and CYFRA21-1, and elevated serum levels of CA125, CA15-3 and CYFRA21-1. SLE patients with TAA positivity were older, had a higher prevalence of serous effusion, pericardial effusion, albuminuria and thrombocytopenia, and lower positivity rate for anti-dsDNA than patients without TAA positivity. The levels of serum creatinine (SCR), blood urea nitrogen, glutamic oxalate transaminase and 24-h urinary protein were also higher in SLE patients with TAA positivity, but platelet count and serum albumin levels were lower. On logistic regression, thrombocytopenia and SCR levels were identified as independent risk factors for TAA positivity. CA125 positivity rate and serum levels of CA125 were associated with SLE disease activity. CONCLUSION: The positivity rates and serum levels of some TAAs were elevated in SLE, and thrombocytopenia and SCR levels were independent risk factors for TAA positivity.
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Lupus Eritematoso Sistémico , Neoplasias , Trombocitopenia , Humanos , Biomarcadores de Tumor , Antígeno Ca-125/metabolismo , Estudios Retrospectivos , Antígeno CA-19-9 , Mucina-1RESUMEN
The objective of this study was to investigate the relationship between serum tumor markers and serous effusion in systemic lupus erythematosus (SLE) patients, thereby contributing preliminary data on the utility of these tumor markers in diagnosing serous effusion. In this retrospective analysis, clinical data of SLE patients were extracted from electronic medical records. This included the levels of serum tumor markers, including pro-gastrin-releasing peptide, neuron-specific enolase (NSE), cytokeratin-19 fragments (CYFRA 21-1), various carbohydrate antigens (CA 153, CA 125, CA 19-9), along with carcinoembryonic antigen, and alpha-fetoprotein. Positivity of tumor markers was established based on serum levels surpassing the upper threshold of the respective reference ranges. This study included 149 eligible patients with SLE, of whom 38 (25.50%) had serous effusion, and the prevalence of pleural, pericardial, and peritoneal effusions was 11.41%, 14.77%, and 6.71%, respectively. The analysis revealed that patients with serous effusion had higher scores on the SLE Disease Activity Index 2000 (SLEDAI 2000) than those without serous effusion. Notably, this disparity remained significant when the serositis score was excluded from the SLEDAI 2000 calculation. The positivity rate and serum levels of CA 125 were higher in patients with serous effusion and pleural effusion. Patients with pericardial effusion demonstrated an elevated CYFRA 21-1 positivity rate and serum CA 125 and CYFRA 21-1 levels compared to patients without pericardial effusion. CA 125 and NSE were higher both in terms of positivity rate and serum levels for patients with peritoneal effusion. Through receiver operating characteristic curve analysis, a moderate relationship was discerned between the conjoined levels of CYFRA 21-1 and CA 125 and the occurrence of pericardial effusion. Additionally, CA 125, NSE, and their combination revealed the moderate diagnostic ability of peritoneal effusion. In summary, this study observed elevated serum levels of various tumor markers in SLE patients exhibiting serous effusion, which is likely attributable to lupus-induced inflammation. These findings suggest that serum tumor markers can be valuable in diagnosing pericardial and peritoneal effusions.
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Intensive cancer treatment with drug combination is widely exploited in the clinic but suffers from inconsistent pharmacokinetics among different therapeutic agents. To overcome it, the emerging nanomedicine offers an unparalleled opportunity for encapsulating multiple drugs in a nano-carrier. Herein, a two-step super-assembled strategy was performed to unify the pharmacokinetics of a peptide and a small molecular compound. In this proof-of-concept study, the bioinformatics analysis firstly revealed the potential synergies towards hepatoma therapy for the associative inhibition of exportin 1 (XPO1) and ataxia telangiectasia mutated-Rad3-related (ATR), and then a super-assembled nano-pill (gold nano drug carrier loaded AZD6738 and 97-110 amino acids of apoptin (AP) (AA@G)) was constructed through camouflaging AZD6738 (ATR small-molecule inhibitor)-binding human serum albumin onto the AP-Au supramolecular nanoparticle. As expected, both in vitro and in vivo experiment results verified that the AA@G possessed extraordinary biocompatibility and enhanced therapeutic effect through inducing cell cycle arrest, promoting DNA damage and inhibiting DNA repair of hepatoma cell. This work not only provides a co-delivery strategy for intensive liver cancer treatment with the clinical translational potential, but develops a common approach to unify the pharmacokinetics of peptide and small-molecular compounds, thereby extending the scope of drugs for developing the advanced combination therapy.
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The fiber structures of tumor microenvironment (TME) are well-known in regulating tumor cell behaviors, and the plastic remolding of TME has recently been suggested to enhance tumor metastasis as well. However, the interrelationship between the fiber microarchitecture and matrix plasticity is inextricable by existing in vitro models. The individual roles of fiber microarchitecture and matrix plasticity in tuning tumor cell behaviors remain elusive. This study develops an interpenetrating collagen-alginate hydrogel platform with independently tunable matrix plasticity and fiber microarchitecture through an interpenetrating strategy of alginate networks and collagen I networks. With this hydrogel platform, it is demonstrated that tumor cells in high plasticity hydrogels are more extensive and aggressive than in low plasticity hydrogels and fiber structures only have influence in high plasticity hydrogels. The study further elucidates the underlying mechanisms through analyzing the distribution of forces within the matrix and tracking the focal adhesions (FAs) and finds that highly plastic hydrogels can activate the FAs formation, whereas the maturation and stability of FAs are dominated by fiber dispersion. This study not only establishes new ideas on how cells interact with TME cues but also would help to further finely tailor engineered hydrogel platforms for studying tumor behaviors in vitro.
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Alginatos , Hidrogeles , Hidrogeles/química , Alginatos/química , Colágeno/química , Colágeno Tipo I/química , Movimiento Celular , Matriz ExtracelularRESUMEN
Mechanotherapy is proposed as a new option for cancer treatment. Increasing evidence suggests that characteristic differences are present in the nuclear mechanics and mechanotransduction of cancer cells compared with those of normal cells. Recent advances in understanding nuclear mechanics and mechanotransduction provide not only further insights into the process of malignant transformation but also useful references for developing new therapeutic approaches. Herein, we present an overview of the alterations of nuclear mechanics and mechanotransduction in cancer cells and highlight their implications in cancer mechanotherapy.
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Mecanotransducción Celular , Neoplasias , Humanos , Núcleo CelularRESUMEN
Background: Individual survival prediction is of vital importance to optimize the individualized treatment of metastatic cervical cancer (mCC) patients. The goal of this study was to identify the potential risk factors for the survival of mCC patients and construct a nomogram for their prognosis. Methods: Medical records of patients with newly diagnosed mCC at the First Affiliated Hospital of Xi'an Jiaotong University were reviewed retrospectively. Risk factors were identified using Cox proportional hazards analysis and Kaplan-Meier curves. Random forest was used to identify factors associated with therapy strategy. Nomogram and dynamic nomogram were established using 'rms' and "DynNom" R package. Results: A total of 98 patients with mCC were finally identified. In Cox analyses, multiple metastases and concurrent chemoradiotherapy (CCRT) were identified as independent predictors for overall survival (OS). We further explored the prognostic value of metastatic number and sites and therapy strategies for mCC patients by Kaplan-Meier curves. A dynamic nomogram including metastases number and sites (multiple metastases, liver and lymph node (LN) above diaphragm metastases) and chemoradiotherapy strategies (CCRT, postradiotherapy chemotherapy, and radiotherapy to metastatic sites) was constructed for predicting the prognosis of mCC patients. For newly diagnosed patients, we strongly recommended the combination of chemotherapy and definitive pelvic radiotherapy and, if possible, radiation to metastatic site, but CCRT should be implemented with caution. We constructed a dynamic nomogram indicating that patients with younger age, shorter symptom duration, and better laboratory test results are suitable for CCRT. Conclusion: Survival analyses showed that the metastatic number and sites and therapy strategies are associated with the prognosis of mCC patients. The CCRT and prognostic nomograms may help clinicians to make better clinical decisions and effectively predict the prognosis for newly diagnosed mCC patients.
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Aim: To evaluate the diagnostic performance of the American College of Rheumatology (ACR)-1997, the Systemic Lupus International Collaborating Clinics (SLICC)-2012, and the European League against Rheumatism (EULAR)/ACR-2019 classification criteria in adult patients with systemic lupus erythematosus (SLE). Methods: PubMed, Embase, Web of Science and Cochrane Library databases were searched for literature comparing the three classification criteria of ACR-1997, SLICC-2012 and EULAR/ACR-2019, which took clinical diagnosis as reference. Meta-analysis was used to evaluate and compare the sensitivity, specificity and diagnostic odds ratio of ACR-1997, SLICC-2012 and EULAR/ACR-2019. To assess the early diagnosis capability of the classification criteria, subgroups of patients with disease duration < 3 years and < 1 year were selected for comparison of sensitivity and specificity based on the inclusion of the original study. The sensitivity and specificity of each item in three sets of classification criteria were evaluated. In addition, the clinical and immunological characteristics of patients who did not meet the three classification criteria were compared. Results: Nine original studies were included in the analysis, including 6404 SLE patients and 3996 controls. Results showed that the diagnostic odds ratios (95% confidence interval) of the SLICC-2012 [136.35 (114.94, 161.75)] and EULAR/ACR-2019 [187.47 (158.00, 222.42)] were higher than those of the ACR-1997 [67.53 (58.75, 77.63)]. Compared with ACR-1997[(0.86 (0.82, 0.89)], SLICC-2012[(0.96 (0.93, 0.97)] and EULAR/ACR-2019[(0.95 (0.92, 0.97)] had higher sensitivity. The specificity of the three classification criteria was similar: ACR-1997, SLICC-2012, and EULAR/ACR-2019 were 0.93 (0.89, 0.95), 0.86 (0.79, 0.91), and 0.91 (0.85, 0.95), respectively. The sensitivity of SLICC-2012 and EULAR/ACR-2019 were higher than that of ACR-1997 in early-course subgroups. Patients who did not meet ACR-1997 had more hypocomplementemia, patients who did not meet SLICC-2012 had more cutaneous lupus and photosensitivity, and patients who did not meet EULAR/ACR-2019 had more cutaneous lupus and leucopenia. Conclusions: SLICC-2012 and EULAR/ACR-2019 have better diagnostic ability than the ACR-1997, and the sensitivity of the former two criteria is also higher than that of the latter; Moreover, the SLICC-2012 and EULAR/ACR-2019 for patients in the early stages of disease performed equally excellent.
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Lupus Eritematoso Cutáneo , Lupus Eritematoso Sistémico , Enfermedades Reumáticas , Reumatología , Adulto , Humanos , Estados Unidos , Reumatología/métodos , Lupus Eritematoso Sistémico/diagnóstico , Sensibilidad y EspecificidadRESUMEN
Parkinson's disease (PD) is a common neurodegenerative disease that affects the motor system and progressively worsens with age. Current treatment options for PD mainly target symptoms, due to our limited understanding of the etiology and pathophysiology of PD. A variety of preclinical models have been developed to study different aspects of the disease. The models have been used to elucidate the pathogenesis and for testing new treatments. These models include cell models, non-mammalian models, rodent models, and non-human primate models. Over the past few decades, Caenorhabditis elegans (C. elegans) has been widely adopted as a model system due to its small size, transparent body, short generation time and life cycle, fully sequenced genome, the tractability of genetic manipulation and suitability for large scale screening for disease modifiers. Here, we review studies using C. elegans as a model for PD and highlight the strengths and limitations of the C. elegans model. Various C. elegans PD models, including neurotoxin-induced models and genetic models, are described in detail. Moreover, met.
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Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Animales , Caenorhabditis elegans/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , Modelos Animales de Enfermedad , Neurotoxinas , RoedoresRESUMEN
Radiotherapy has led to important clinical advances; existing cancer radiotherapy resistance is one remaining major challenge. Recently, biophysical cues in the tumor microenvironment (TME) have been regarded as the new hallmarks of cancer, playing pivotal roles in various cancer behaviors and treatment responses, including radiotherapy resistance. With recent advances in micro/nanotechnologies and functional biomaterials, radiotherapy exerts great influence on biophysical cues in TME, which, in turn, significantly affect the response to radiotherapy. Besides, various strategies have emerged that target biophysical cues in TME, to potentially enhance radiotherapy efficacy. Therefore, this paper reviews the four biophysical cues (i.e., extracellular matrix (ECM) microarchitecture, ECM stiffness, interstitial fluid pressure, and solid stress) that may play important roles in radiotherapy resistance, their possible mechanisms for inducing it, and their change after radiotherapy. The emerging therapeutic strategies targeting the biophysical microenvironment, to explore the mechanism of radiotherapy resistance and develop effective strategies to revert it for improved treatment efficacy are further summarized.
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Neoplasias , Oncología por Radiación , Humanos , Microambiente Tumoral , Neoplasias/radioterapia , Matriz Extracelular/patología , BiofisicaAsunto(s)
Enfermedades Cutáneas Vasculares , Vasculitis Leucocitoclástica Cutánea , Humanos , Vasculitis Leucocitoclástica Cutánea/inducido químicamente , Vasculitis Leucocitoclástica Cutánea/diagnóstico , Vasculitis Leucocitoclástica Cutánea/tratamiento farmacológico , Glucocorticoides/efectos adversos , Piperidinas/efectos adversosRESUMEN
The E3 ubiquitin ligase adaptor Speckle-type POZ protein (SPOP) plays an important tumour suppressor role in prostate cancers (PCa), with mutation rate up to 15%. However, how SPOP mutations regulate prostate tumorigenesis remains elusive. Here, we report the identification of cell division cycle associated 5 (CDCA5) as a SPOP substrate. We found that SPOP interacts with CDCA5 and promotes its polyubiquitin degradation in a degron-dependent manner. This effect was greatly impaired by introducing PCa associated SPOP mutations. Importantly, we found that CDCA5 was essential for PCa cells to survive and proliferate. CDCA5 depletion in PCa cells led to cessation of proliferation, G2M arrest, severe sister chromatid aggregation disturbance, and apoptosis. we also found that CDCA5 knockdown decreased the protein expression of p-GSK3ß, increased the activity of caspase-3, caspase-9, and the Bax/Bcl-2 ratio. Besides, we confirmed that CDCA5 interrupted cancer cell behavior via the AKT pathway. In contrast, silencing SPOP or overexpressing CDCA5 increased cell proliferation. Consistently, depleting SPOP along with CDCA5, or overexpressing CDCA5 along with SPOP also caused the growth of cells repressed. Consistent with the functional role of CDCA5, the mRNA and protein levels of CDCA5 were significantly increased in PCa, compared to normal tissues, and its high expression was associated with more severe lymph node metastasis, higher Gleason score, and poorer prognosis. Together, our data showed that SPOP plays a crucial role in inhibiting tumorigenesis and partly achieved this by promoting the degradation of oncoprotein CDCA5.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Biomarcadores de Tumor/metabolismo , Proteínas de Ciclo Celular/metabolismo , Regulación Neoplásica de la Expresión Génica , Proteínas Nucleares/metabolismo , Neoplasias de la Próstata/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Represoras/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Apoptosis , Biomarcadores de Tumor/genética , Ciclo Celular , Proteínas de Ciclo Celular/genética , Proliferación Celular , Humanos , Masculino , Proteínas Nucleares/genética , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Proteolisis , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Represoras/genética , Células Tumorales Cultivadas , UbiquitinaciónRESUMEN
Prostate cancer is one of the most common causes of cancer incidence and death in men, with the mortality caused primarily by the late-stage and metastatic forms of the disease. The mechanisms and molecular markers for prostate cancer metastasis are not fully understood. Speckle type Poz Protein (SPOP) is an E3 ubiquitin ligase adaptor that is often mutated in prostate cancer. In this study, we sequenced the SPOP gene in 198 prostate cancer patients and found 16 mutations in the cohort. Multivariate analysis revealed that SPOP mutations correlated with the clinical stage of the disease and strongly with metastasis. We identified ITCH as a candidate protein for SPOP-mediated degradation via mass spectrometry. We demonstrated the interaction between SPOP and ITCH, and found that the SPOP F133L mutation disrupted the SPOP-ITCH interaction, leading to a subsequent increase in the ITCH protein level. Further, we found that the SPOP knockdown led to higher levels of Epithelial- mesenchymal transition (EMT) proteins and increased cell invasion. Together, our results highlight the functional significance of the SPOP-ITCH pathway in prostate cancer metastasis.
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Previous studies have shown that both long intergenic non-coding RNA 00963 (Linc00963) and tripartite motif containing 24 (TRIM24) are activators of the PI3K/AKT pathway, and both are involved in the carcinogenesis and progression of prostate cancer. However, the regulatory mechanisms between Linc00963 and TRIM24 are still unclear. In this study, we aimed to elucidate the underlying relationship between Linc00963 and TRIM24 in castration-resistant prostate cancer (CRPC). We found that TRIM24, an established oncogene in CRPC, was positively correlated with Linc00963 in prostate cancer tissues. In addition, TRIM24 was positively regulated by Lin00963 in CRPC cells. Mechanistically, TRIM24 was the direct target of microRNA-655 (miR-655) in CRPC cells, and Linc00963 could competitively bind miR-655 and upregulate TRIM24 expression. Using gain- and loss-of- function assays and rescue assays, we identified that miR-655 inhibits TRIM24 expression and cell proliferation and colony forming ability in CRPC, and that Linc00963 promotes TRIM24 expression, cell proliferation, and colony forming ability of CRPC cells by directly suppressing miR-655 expression. We further identified that Linc00963 could promote tumor growth of CRPC cells by inhibiting miR-655 and upregulating TRIM24 axis in vivo. Taken together, our study reveals a new mechanism for the Linc00963/miR-655/TRIM24 competing endogenous RNA (ceRNA) network in accelerating cell proliferation in CRPC in vitro and in vivo, and suggests that Linc00963 could be considered a novel therapeutic target for CRPC.
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OBJECTIVE: The outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) has caused more than 26 million cases of Corona virus disease (COVID-19) in the world so far. To control the spread of the disease, screening large numbers of suspected cases for appropriate quarantine and treatment are a priority. Pathogenic laboratory testing is typically the gold standard, but it bears the burden of significant false negativity, adding to the urgent need of alternative diagnostic methods to combat the disease. Based on COVID-19 radiographic changes in CT images, this study hypothesized that artificial intelligence methods might be able to extract specific graphical features of COVID-19 and provide a clinical diagnosis ahead of the pathogenic test, thus saving critical time for disease control. METHODS: We collected 1065 CT images of pathogen-confirmed COVID-19 cases along with those previously diagnosed with typical viral pneumonia. We modified the inception transfer-learning model to establish the algorithm, followed by internal and external validation. RESULTS: The internal validation achieved a total accuracy of 89.5% with a specificity of 0.88 and sensitivity of 0.87. The external testing dataset showed a total accuracy of 79.3% with a specificity of 0.83 and sensitivity of 0.67. In addition, in 54 COVID-19 images, the first two nucleic acid test results were negative, and 46 were predicted as COVID-19 positive by the algorithm, with an accuracy of 85.2%. CONCLUSION: These results demonstrate the proof-of-principle for using artificial intelligence to extract radiological features for timely and accurate COVID-19 diagnosis. KEY POINTS: ⢠The study evaluated the diagnostic performance of a deep learning algorithm using CT images to screen for COVID-19 during the influenza season. ⢠As a screening method, our model achieved a relatively high sensitivity on internal and external CT image datasets. ⢠The model was used to distinguish between COVID-19 and other typical viral pneumonia, both of which have quite similar radiologic characteristics.