BACKGROUND Metastatic cardiac tumors are known to occur more frequently than primary cardiac tumors,however,they often remain asymptomatic and are commonly dis-covered on autopsy.Malignant tumors with a relatively hig...BACKGROUND Metastatic cardiac tumors are known to occur more frequently than primary cardiac tumors,however,they often remain asymptomatic and are commonly dis-covered on autopsy.Malignant tumors with a relatively high frequency of cardiac metastasis include mesothelioma,melanoma,lung cancer,and breast cancer,whereas reports of esophageal cancer with cardiac metastasis are rare.CASE SUMMARY The case of a 60-year-old man who complained of dysphagia is presented.Upper gastrointestinal endoscopy showed a submucosal tumor-like elevated lesion in the esophagus causing stenosis.Contrast-enhanced computed tomography showed left atrial compression due to the esophageal tumor,multiple liver and lung metastases,and a left pleural effusion.Pathological examination of a biopsy speci-men from the esophageal tumor showed spindle-shaped cells,raising suspicion of esophageal sarcoma.The disease progressed rapidly,and systemic chemotherapy was deemed necessary,however,due to his poor general condition,adminis-tration of cytotoxic agents was considered difficult.Given his high Combined Positive Score,nivolumab was administered,however,the patient soon died from the disease.The autopsy confirmed spindle cell carcinoma(SCC)of the esophagus and cardiac metastasis with similar histological features.Cancer stem cell markers,ZEB1 and TWIST,were positive in both the primary tumor and the cardiac metastasis.CONCLUSION To the best of our knowledge,there have been no prior reports of cardiac metastasis of esophageal SCC.This case highlights our experience with a patient with esophageal SCC who progressed rapidly and died from the disease,with the autopsy examination showing cardiac metastasis.展开更多
AIM: To elucidate the localization of vasodilator stimulated phosphoprotein (VASP), a cytoskeletal organizing protein and a substrate of protein kinases A and G in mitotic gastric cancer cells. METHODS: Immunofluoresc...AIM: To elucidate the localization of vasodilator stimulated phosphoprotein (VASP), a cytoskeletal organizing protein and a substrate of protein kinases A and G in mitotic gastric cancer cells. METHODS: Immunofluorescence microscopy was used to observe the localization of a-tubulin, VASP and Ser157 phosphorylated VASP (p-VASP) in interphase of mitotic gastric cancer of the cell line SGC-7901. RESULTS: Immunofluorescence staining showed that p-VASP but not VASP was co-localized with a-tubulin on spindle poles and fibers in prophase, metaphase and anaphase of the mitotic process of the gastric cancer cell line SGC-7901. H89, an inhibitor of protein kinases A and G, had no effect on the localization of p-VASP on the spindles. CONCLUSION: VASP may play a role in assembling and stabilizing the mitotic spindle of cells, and phosphorylation of the protein is the precondition for it to exert this function.展开更多
Triple-negative breast cancer(TNBC)is characterized by fast growth,high metastasis,high invasion,and a lack of therapeutic targets.Mitosis and metastasis of TNBC cells are two important biological behaviors in TNBC ma...Triple-negative breast cancer(TNBC)is characterized by fast growth,high metastasis,high invasion,and a lack of therapeutic targets.Mitosis and metastasis of TNBC cells are two important biological behaviors in TNBC malignant progression.It is well known that the long noncoding RNA AFAP1-AS1 plays a crucial role in various tumors,but whether AFAP1-AS1 is involved in the mitosis of TNBC cells remains unknown.In this study,we investigated the functional mechanism of AFAP1-AS1 in targeting Polo-like Kinase 1(PLK1)activation and participating in mitosis of TNBC cells.We detected the expression of AFAP1-AS1 in the TNBC patient cohort and primary cells by in situ hybridization(ISH),northern blot,fluorescent in situ hybridization(FISH)and cell nucleus/cytoplasm RNA fraction isolation.High AFAP1-AS1 expression was negatively correlated with overall survival(OS),disease-free survival(DFS),metastasis-free survival(MFS)and recurrence-free survival(RFS)in TNBC patients.We explored the function of AFAP1-AS1 by transwell,apoptosis,immunofluorescence(IF)and patient-derived xenograft(PDX)models in vitro and in vivo.We found that AFAP1-AS1 promoted TNBC primary cell survival by inhibiting mitotic catastrophe and increased TNBC primary cell growth,migration and invasion.Mechanistically,AFAP1-AS1 activated phosphorylation of the mitosis-associated kinase PLK1 protein.Elevated levels of AFAP1-AS1 in TNBC primary cells increased PLK1 pathway downstream gene expression,such as CDC25C,CDK1,BUB1 and TTK.More importantly,AFAP1-AS1 increased lung metastases in a mouse metastasis model.Taken together,AFAP1-AS1 functions as an oncogene that activates the PLK1 signaling pathway.AFAP1-AS1 could be used as a potential prognostic marker and therapeutic target for TNBC.展开更多
Sleep spindles are an electroencephalogram(EEG)biomarker of non-rapid eye movement(NREM)sleep and have important implications for clinical diagnosis and prognosis.However,it is challenging to accurately detect sleep s...Sleep spindles are an electroencephalogram(EEG)biomarker of non-rapid eye movement(NREM)sleep and have important implications for clinical diagnosis and prognosis.However,it is challenging to accurately detect sleep spindles due to the complexity of the human brain and the uncertainty of neural mechanisms.To improve the reliability and objectivity of sleep spindle detection and to compensate for the limitations of manual annotation,this study proposes a new automatic detection algorithm based on Matching Pursuit(MP)and Least Squares Boosting(LSBoost),where the automatic sleep spindle detection algorithm can help reduce the visual annotation workload of sleep clinicians.Specifically,MP is a time-frequency analysis method suitable for extracting spindle wave characteristics,which can accurately locate spindle waves on a time-frequency plane.LSBoost is an ensemble learning classification method to deal with unbalanced data.Initially,theMP method is used to search for EEG segments that are possible spindle waves from the filtered raw EEG data.Then,the designed feature segments are thrown into the LSBoost classifier to further identify the real spindles from all candidates and output the final results.The proposed method is verified on the common public dataset DREAMS.The experiment results showthat the sensitivity and F1-scores based on the sample-based assessments achieve 68.2% and 55.4%,respectively.Furthermore,the Recall and F1-score based on the event assessments are 83.8% and 70.8%,respectively.These results show that the proposed algorithm is robust to the subject changes in the DREAMS dataset.In addition,it improves the quality of sleep spindle detection,which is expected to assist the manual marking of experts.展开更多
Numerous factors affect the increased temperature of a machine tool, including prolonged and high-intensity usage,tool-workpiece interaction, mechanical friction, and elevated ambient temperatures, among others. Conse...Numerous factors affect the increased temperature of a machine tool, including prolonged and high-intensity usage,tool-workpiece interaction, mechanical friction, and elevated ambient temperatures, among others. Consequently,spindle thermal displacement occurs, and machining precision suffers. To prevent the errors caused by thetemperature rise of the Spindle fromaffecting the accuracy during themachining process, typically, the factory willwarm up themachine before themanufacturing process.However, if there is noway to understand the tool spindle’sthermal deformation, the machining quality will be greatly affected. In order to solve the above problem, thisstudy aims to predict the thermal displacement of the machine tool by using intelligent algorithms. In the practicalapplication, only a few temperature sensors are used to input the information into the prediction model for realtimethermal displacement prediction. This approach has greatly improved the quality of tool processing.However,each algorithm has different performances in different environments. In this study, an ensemble model is used tointegrate Long Short-TermMemory (LSTM) with Support VectorMachine (SVM). The experimental results showthat the prediction performance of LSTM-SVM is higher than that of other machine learning algorithms.展开更多
BACKGROUND Spindle and kinetochore-associated complex subunit 3(SKA3)is a malignancyassociated gene that plays a critical role in the regulation of chromosome separation and cell division.However,the molecular mechani...BACKGROUND Spindle and kinetochore-associated complex subunit 3(SKA3)is a malignancyassociated gene that plays a critical role in the regulation of chromosome separation and cell division.However,the molecular mechanism through which SKA3 regulates tumor cell proliferation in hepatocellular carcinoma(HCC)has not been fully elucidated.AIM To investigate the molecular mechanisms underlying the role of SKA3 in HCC.METHODS SKA3 expression,clinicopathological,and survival analyses were performed using multiple public database platforms,and the results were verified by Western blot and immunohistochemistry staining using collected clinical samples.Functional enrichment analyses were performed to evaluate the biological functions and molecular mechanisms of SKA3 in HCC.Furthermore,the Tumor Immune Estimation Resource and single-sample Gene Set Enrichment Analysis(ssGSEA)algorithms were utilized to investigate the abundance of tumor-infiltrating immune cells in HCC.The response to chemotherapeutic drugs was evaluated by the R package“pRRophetic”.RESULTS We found that upregulated SKA3 expression was significantly correlated with poor prognosis in patients with HCC.Multivariable Cox regression analysis indicated that SKA3 was an independent risk factor for survival.GSEA revealed that SKA3 expression may facilitate proliferation and migratory processes by regulating the cell cycle and DNA repair.Moreover,patients with high SKA3 expression had significantly decreased ratios of CD8+T cells,natural killer cells,and dendritic cells.Drug sensitivity analysis showed that the high SKA3 group was more sensitive to sorafenib,sunitinib,paclitaxel,doxorubicin,gemcitabine,and vx-680.CONCLUSION High SKA3 expression led to poor prognosis in patients with HCC by enhancing HCC proliferation and repressing immune cell infiltration surrounding HCC.SKA3 may be used as a biomarker for poor prognosis and as a therapeutic target in HCC.展开更多
BACKGROUND Undifferentiated pleomorphic sarcomas,also known as spindle cell sarcomas,are a relatively uncommon subtype of soft tissue sarcomas in clinical practice.CASE SUMMARY We present a case report of a 69-year-ol...BACKGROUND Undifferentiated pleomorphic sarcomas,also known as spindle cell sarcomas,are a relatively uncommon subtype of soft tissue sarcomas in clinical practice.CASE SUMMARY We present a case report of a 69-year-old female patient who was diagnosed with undifferentiated spindle cell soft tissue sarcoma on her left thigh.Surgical excision was initially performed,but the patient experienced a local recurrence following multiple surgeries and radioactive particle implantations.High-intensity focused ultrasound(HIFU)was subsequently administered,resulting in complete ablation of the sarcoma without any significant complications other than bone damage at the treated site.However,approximately four months later,the patient experienced a broken lesion at the original location.After further diagnostic workup,the patient underwent additional surgery and is currently stable with a good quality of life.CONCLUSION HIFU has shown positive outcomes in achieving local control of limb spindle cell sarcoma,making it an effective non-invasive treatment option.展开更多
文摘BACKGROUND Metastatic cardiac tumors are known to occur more frequently than primary cardiac tumors,however,they often remain asymptomatic and are commonly dis-covered on autopsy.Malignant tumors with a relatively high frequency of cardiac metastasis include mesothelioma,melanoma,lung cancer,and breast cancer,whereas reports of esophageal cancer with cardiac metastasis are rare.CASE SUMMARY The case of a 60-year-old man who complained of dysphagia is presented.Upper gastrointestinal endoscopy showed a submucosal tumor-like elevated lesion in the esophagus causing stenosis.Contrast-enhanced computed tomography showed left atrial compression due to the esophageal tumor,multiple liver and lung metastases,and a left pleural effusion.Pathological examination of a biopsy speci-men from the esophageal tumor showed spindle-shaped cells,raising suspicion of esophageal sarcoma.The disease progressed rapidly,and systemic chemotherapy was deemed necessary,however,due to his poor general condition,adminis-tration of cytotoxic agents was considered difficult.Given his high Combined Positive Score,nivolumab was administered,however,the patient soon died from the disease.The autopsy confirmed spindle cell carcinoma(SCC)of the esophagus and cardiac metastasis with similar histological features.Cancer stem cell markers,ZEB1 and TWIST,were positive in both the primary tumor and the cardiac metastasis.CONCLUSION To the best of our knowledge,there have been no prior reports of cardiac metastasis of esophageal SCC.This case highlights our experience with a patient with esophageal SCC who progressed rapidly and died from the disease,with the autopsy examination showing cardiac metastasis.
基金Supported by National Natural Science Foundation of China, No. 30340036 and 30470891 Startup Grant from Jiangsu University, and Grant of Zhenjiang Key Institute of Clinical Laboratory Medicine (SH2006066)
文摘AIM: To elucidate the localization of vasodilator stimulated phosphoprotein (VASP), a cytoskeletal organizing protein and a substrate of protein kinases A and G in mitotic gastric cancer cells. METHODS: Immunofluorescence microscopy was used to observe the localization of a-tubulin, VASP and Ser157 phosphorylated VASP (p-VASP) in interphase of mitotic gastric cancer of the cell line SGC-7901. RESULTS: Immunofluorescence staining showed that p-VASP but not VASP was co-localized with a-tubulin on spindle poles and fibers in prophase, metaphase and anaphase of the mitotic process of the gastric cancer cell line SGC-7901. H89, an inhibitor of protein kinases A and G, had no effect on the localization of p-VASP on the spindles. CONCLUSION: VASP may play a role in assembling and stabilizing the mitotic spindle of cells, and phosphorylation of the protein is the precondition for it to exert this function.
基金National Natural Science Foundation of China (39925018, 90508002 , 30121001) Chinese Academy of Science (KSCX 1-R65 and RSCX2-H10)+2 种基金 National Basic Research Program of China (973 project, 2002CB713700) American Cancer Society (RPG-99-173-01) a Gcc Breast Cancer Research award and National Institutes of Health grants DK56292 and CA89019 to XY (a GCC Eminent Scholar) and NS36194 (JW).
基金supported by the Natural Science Foundation of China(Nos.82002782,82202657)the Guangdong Basic and Applied Basic Research Foundation(2022A1515012021,2020A1515110930).
文摘Triple-negative breast cancer(TNBC)is characterized by fast growth,high metastasis,high invasion,and a lack of therapeutic targets.Mitosis and metastasis of TNBC cells are two important biological behaviors in TNBC malignant progression.It is well known that the long noncoding RNA AFAP1-AS1 plays a crucial role in various tumors,but whether AFAP1-AS1 is involved in the mitosis of TNBC cells remains unknown.In this study,we investigated the functional mechanism of AFAP1-AS1 in targeting Polo-like Kinase 1(PLK1)activation and participating in mitosis of TNBC cells.We detected the expression of AFAP1-AS1 in the TNBC patient cohort and primary cells by in situ hybridization(ISH),northern blot,fluorescent in situ hybridization(FISH)and cell nucleus/cytoplasm RNA fraction isolation.High AFAP1-AS1 expression was negatively correlated with overall survival(OS),disease-free survival(DFS),metastasis-free survival(MFS)and recurrence-free survival(RFS)in TNBC patients.We explored the function of AFAP1-AS1 by transwell,apoptosis,immunofluorescence(IF)and patient-derived xenograft(PDX)models in vitro and in vivo.We found that AFAP1-AS1 promoted TNBC primary cell survival by inhibiting mitotic catastrophe and increased TNBC primary cell growth,migration and invasion.Mechanistically,AFAP1-AS1 activated phosphorylation of the mitosis-associated kinase PLK1 protein.Elevated levels of AFAP1-AS1 in TNBC primary cells increased PLK1 pathway downstream gene expression,such as CDC25C,CDK1,BUB1 and TTK.More importantly,AFAP1-AS1 increased lung metastases in a mouse metastasis model.Taken together,AFAP1-AS1 functions as an oncogene that activates the PLK1 signaling pathway.AFAP1-AS1 could be used as a potential prognostic marker and therapeutic target for TNBC.
基金funded by the Guangdong Basic and Applied Basic Research Foundation(Grant Nos.2021A1515011853 and 2020A1515110294)the National Natural Science Foundation of China(Grant Nos.61906019 and 62076103)+2 种基金STI 2030-Major Projects 2022ZD0208900Guangzhou Science and Technology Plan Project(Grant No.202102020877)the Guangzhou Science and Technology Plan Project Key Field R&D Project(202007030005).
文摘Sleep spindles are an electroencephalogram(EEG)biomarker of non-rapid eye movement(NREM)sleep and have important implications for clinical diagnosis and prognosis.However,it is challenging to accurately detect sleep spindles due to the complexity of the human brain and the uncertainty of neural mechanisms.To improve the reliability and objectivity of sleep spindle detection and to compensate for the limitations of manual annotation,this study proposes a new automatic detection algorithm based on Matching Pursuit(MP)and Least Squares Boosting(LSBoost),where the automatic sleep spindle detection algorithm can help reduce the visual annotation workload of sleep clinicians.Specifically,MP is a time-frequency analysis method suitable for extracting spindle wave characteristics,which can accurately locate spindle waves on a time-frequency plane.LSBoost is an ensemble learning classification method to deal with unbalanced data.Initially,theMP method is used to search for EEG segments that are possible spindle waves from the filtered raw EEG data.Then,the designed feature segments are thrown into the LSBoost classifier to further identify the real spindles from all candidates and output the final results.The proposed method is verified on the common public dataset DREAMS.The experiment results showthat the sensitivity and F1-scores based on the sample-based assessments achieve 68.2% and 55.4%,respectively.Furthermore,the Recall and F1-score based on the event assessments are 83.8% and 70.8%,respectively.These results show that the proposed algorithm is robust to the subject changes in the DREAMS dataset.In addition,it improves the quality of sleep spindle detection,which is expected to assist the manual marking of experts.
基金supported by the Ministry of Science and Technology,Taiwan,under Grant MOST 110-2218-E-194-010。
文摘Numerous factors affect the increased temperature of a machine tool, including prolonged and high-intensity usage,tool-workpiece interaction, mechanical friction, and elevated ambient temperatures, among others. Consequently,spindle thermal displacement occurs, and machining precision suffers. To prevent the errors caused by thetemperature rise of the Spindle fromaffecting the accuracy during themachining process, typically, the factory willwarm up themachine before themanufacturing process.However, if there is noway to understand the tool spindle’sthermal deformation, the machining quality will be greatly affected. In order to solve the above problem, thisstudy aims to predict the thermal displacement of the machine tool by using intelligent algorithms. In the practicalapplication, only a few temperature sensors are used to input the information into the prediction model for realtimethermal displacement prediction. This approach has greatly improved the quality of tool processing.However,each algorithm has different performances in different environments. In this study, an ensemble model is used tointegrate Long Short-TermMemory (LSTM) with Support VectorMachine (SVM). The experimental results showthat the prediction performance of LSTM-SVM is higher than that of other machine learning algorithms.
基金Beijing Hope Run Special Fund of Cancer Foundation of China,No.LC2020L05.
文摘BACKGROUND Spindle and kinetochore-associated complex subunit 3(SKA3)is a malignancyassociated gene that plays a critical role in the regulation of chromosome separation and cell division.However,the molecular mechanism through which SKA3 regulates tumor cell proliferation in hepatocellular carcinoma(HCC)has not been fully elucidated.AIM To investigate the molecular mechanisms underlying the role of SKA3 in HCC.METHODS SKA3 expression,clinicopathological,and survival analyses were performed using multiple public database platforms,and the results were verified by Western blot and immunohistochemistry staining using collected clinical samples.Functional enrichment analyses were performed to evaluate the biological functions and molecular mechanisms of SKA3 in HCC.Furthermore,the Tumor Immune Estimation Resource and single-sample Gene Set Enrichment Analysis(ssGSEA)algorithms were utilized to investigate the abundance of tumor-infiltrating immune cells in HCC.The response to chemotherapeutic drugs was evaluated by the R package“pRRophetic”.RESULTS We found that upregulated SKA3 expression was significantly correlated with poor prognosis in patients with HCC.Multivariable Cox regression analysis indicated that SKA3 was an independent risk factor for survival.GSEA revealed that SKA3 expression may facilitate proliferation and migratory processes by regulating the cell cycle and DNA repair.Moreover,patients with high SKA3 expression had significantly decreased ratios of CD8+T cells,natural killer cells,and dendritic cells.Drug sensitivity analysis showed that the high SKA3 group was more sensitive to sorafenib,sunitinib,paclitaxel,doxorubicin,gemcitabine,and vx-680.CONCLUSION High SKA3 expression led to poor prognosis in patients with HCC by enhancing HCC proliferation and repressing immune cell infiltration surrounding HCC.SKA3 may be used as a biomarker for poor prognosis and as a therapeutic target in HCC.
文摘BACKGROUND Undifferentiated pleomorphic sarcomas,also known as spindle cell sarcomas,are a relatively uncommon subtype of soft tissue sarcomas in clinical practice.CASE SUMMARY We present a case report of a 69-year-old female patient who was diagnosed with undifferentiated spindle cell soft tissue sarcoma on her left thigh.Surgical excision was initially performed,but the patient experienced a local recurrence following multiple surgeries and radioactive particle implantations.High-intensity focused ultrasound(HIFU)was subsequently administered,resulting in complete ablation of the sarcoma without any significant complications other than bone damage at the treated site.However,approximately four months later,the patient experienced a broken lesion at the original location.After further diagnostic workup,the patient underwent additional surgery and is currently stable with a good quality of life.CONCLUSION HIFU has shown positive outcomes in achieving local control of limb spindle cell sarcoma,making it an effective non-invasive treatment option.