Augmentation of abnormal cells in the brain causes brain tumor(BT),and early screening and treatmentwill reduce its harshness in patients.BT’s clinical level screening is usually performed with Magnetic Resonance Ima...Augmentation of abnormal cells in the brain causes brain tumor(BT),and early screening and treatmentwill reduce its harshness in patients.BT’s clinical level screening is usually performed with Magnetic Resonance Imaging(MRI)due to its multi-modality nature.The overall aims of the study is to introduce,test and verify an advanced image processing technique with algorithms to automatically extract tumour sections from brain MRI scans,facilitating improved accuracy.The research intends to devise a reliable framework for detecting the BT region in the twodimensional(2D)MRI slice,and identifying its class with improved accuracy.The methodology for the devised framework comprises the phases of:(i)Collection and resizing of images,(ii)Implementation and Segmentation of Convolutional Neural Network(CNN),(iii)Deep feature extraction,(iv)Handcrafted feature extraction,(v)Moth-Flame-Algorithm(MFA)supported feature reduction,and(vi)Performance evaluation.This study utilized clinical-grade brain MRI of BRATS and TCIA datasets for the investigation.This framework segments detected the glioma(low/high grade)and glioblastoma class BT.This work helped to get a segmentation accuracy of over 98%with VGG-UNet and a classification accuracy of over 98%with the VGG16 scheme.This study has confirmed that the implemented framework is very efficient in detecting the BT in MRI slices with/without the skull section.展开更多
BACKGROUND Duodenal neuroendocrine tumours(DNETs)are rare neoplasms.However,the incidence of DNETs has been increasing in recent years,especially as an incidental finding during endoscopic studies.Regrettably,there is...BACKGROUND Duodenal neuroendocrine tumours(DNETs)are rare neoplasms.However,the incidence of DNETs has been increasing in recent years,especially as an incidental finding during endoscopic studies.Regrettably,there is no consensus regarding the ideal treatment of DNETs.Even there are few studies on the clinical features and survival analysis of DNETs.AIM To analyze the clinical characteristics and prognostic factors of patients with duodenal neuroendocrine tumours.METHODS The clinical data of DNETs diagnosed in the First Affiliated Hospital of Air Force Military Medical University from June 2011 to July 2022 were collected.Neuroen-docrine tumours located in the ampulla area of the duodenum were divided into the ampullary region group;neuroendocrine tumours in any part of the duo-denum outside the ampullary area were divided into the nonampullary region group.Using a retrospective study,the clinical characteristics of the two groups and risk factors affecting the survival of DNET patients were analysed.RESULTS Twenty-nine DNET patients were screened.The male to female ratio was 1:1.9,and females comprised the majority.The ampullary region group accounted for 24.1%(7/29),while the nonampullary region group accounted for 75.9%(22/29).When diagnosed,the clinical symptoms of the ampullary region group were mainly abdominal pain(85.7%),while those of the nonampullary region groups were mainly abdominal distension(59.1%).There were differences in the composition of staging of tumours between the two groups(Fisher's exact probability method,P=0.001),with nonampullary stage II tumours(68.2%)being the main stage(P<0.05).After the diagnosis of DNETs,the survival rate of the ampullary region group was 14.3%(1/7),which was lower than that of 72.7%(16/22)in the nonampullary region group(Fisher's exact probability method,P=0.011).The survival time of the ampullary region group was shorter than that of the nonampullary region group(P<0.000).The median survival time of the ampullary region group was 10.0 months and that of the nonampullary region group was 451.0 months.Multivariate analysis showed that tumours in the ampulla region and no surgical treatment after diagnosis were independent risk factors for the survival of DNET patients(HR=0.029,95%CI 0.004-0.199,P<0.000;HR=12.609,95%CI:2.889-55.037,P=0.001).Further analysis of nonampullary DNET patients showed that the survival time of patients with a tumour diameter<2 cm was longer than that of patients with a tumour diameter≥2 cm(t=7.243,P=0.048).As of follow-up,6 patients who died of nonampullary DNETs had a tumour diameter that was≥2 cm,and 3 patients in stage IV had liver metastasis.Patients with a tumour diameter<2 cm underwent surgical treatment,and all survived after surgery.CONCLUSION Surgical treatment is a protective factor for prolonging the survival of DNET patients.Compared to DNETs in the ampullary region,patients in the nonampullary region group had a longer survival period.The liver is the organ most susceptible to distant metastasis of nonampullary DNETs.展开更多
Detecting brain tumours is complex due to the natural variation in their location, shape, and intensity in images. While having accurate detection and segmentation of brain tumours would be beneficial, current methods...Detecting brain tumours is complex due to the natural variation in their location, shape, and intensity in images. While having accurate detection and segmentation of brain tumours would be beneficial, current methods still need to solve this problem despite the numerous available approaches. Precise analysis of Magnetic Resonance Imaging (MRI) is crucial for detecting, segmenting, and classifying brain tumours in medical diagnostics. Magnetic Resonance Imaging is a vital component in medical diagnosis, and it requires precise, efficient, careful, efficient, and reliable image analysis techniques. The authors developed a Deep Learning (DL) fusion model to classify brain tumours reliably. Deep Learning models require large amounts of training data to achieve good results, so the researchers utilised data augmentation techniques to increase the dataset size for training models. VGG16, ResNet50, and convolutional deep belief networks networks extracted deep features from MRI images. Softmax was used as the classifier, and the training set was supplemented with intentionally created MRI images of brain tumours in addition to the genuine ones. The features of two DL models were combined in the proposed model to generate a fusion model, which significantly increased classification accuracy. An openly accessible dataset from the internet was used to test the model's performance, and the experimental results showed that the proposed fusion model achieved a classification accuracy of 98.98%. Finally, the results were compared with existing methods, and the proposed model outperformed them significantly.展开更多
In this letter,we explore into the potential role of the recent study by Zeng et al.Rectal neuroendocrine tumours(rNETs)are rare,originate from peptidergic neurons and neuroendocrine cells,and express corresponding ma...In this letter,we explore into the potential role of the recent study by Zeng et al.Rectal neuroendocrine tumours(rNETs)are rare,originate from peptidergic neurons and neuroendocrine cells,and express corresponding markers.Although most rNETs patients have a favourable prognosis,the median survival period significantly decreases when high-risk factors,such as larger tumours,poorer differentiation,and lymph node metastasis exist,are present.Clinical prediction models play a vital role in guiding diagnosis and prognosis in health care,but their complex calculation formulae limit clinical use.Moreover,the prognostic models that have been developed for rNETs to date still have several limitations,such as insufficient sample sizes and the lack of external validation.A high-quality prognostic model for rNETs would guide treatment and follow-up,enabling the precise formulation of individual patient treatment and follow-up plans.The future development of models for rNETs should involve closer collab-oration with statistical experts,which would allow the construction of clinical prediction models to be standardized and robust,accurate,and highly general-izable prediction models to be created,ultimately achieving the goal of precision medicine.展开更多
BACKGROUND Colorectal cancer is the third most prevalent malignancy globally and ranks second in cancer-related mortality,with the liver being the primary organ of metastasis.Preoperative chemotherapy is widely recomm...BACKGROUND Colorectal cancer is the third most prevalent malignancy globally and ranks second in cancer-related mortality,with the liver being the primary organ of metastasis.Preoperative chemotherapy is widely recommended for initially or potentially resectable colorectal liver metastases(CRLMs).Tumour pathological response serves as the most important and intuitive indicator for assessing the efficacy of chemotherapy.However,the postoperative pathological results reveal that a considerable number of patients exhibit a poor response to preoperative chemotherapy.Body mass index(BMI)is one of the factors affecting the tumori-genesis and progression of colorectal cancer as well as prognosis after various antitumour therapies.Several studies have indicated that overweight and obese patients with metastatic colorectal cancer experience worse prognoses than those with normal weight,particularly when receiving first-line chemotherapy regimens in combination with bevacizumab.AIM To explore the predictive value of BMI regarding the pathologic response following preoperative chemotherapy for CRLMs.METHODS A retrospective analysis was performed in 126 consecutive patients with CRLM who underwent hepatectomy following preoperative chemotherapy at four different hospitals from October 2019 to July 2023.Univariate and multivariate logistic regression models were applied to analyse potential predictors of tumour pathological response.The Kaplan-Meier method with log rank test was used to compare progression-free survival(PFS)between patients with high and low BMI.BMI<24.0 kg/m^(2) was defined as low BMI,and tumour regression grade 1-2 was defined as complete tumour response.RESULTS Low BMI was observed in 74(58.7%)patients and complete tumour response was found in 27(21.4%)patients.The rate of complete tumour response was significantly higher in patients with low BMI(29.7%vs 9.6%,P=0.007).Multivariate analysis revealed that low BMI[odds ratio(OR)=4.56,95%confidence interval(CI):1.42-14.63,P=0.011],targeted therapy with bevacizumab(OR=3.02,95%CI:1.10-8.33,P=0.033),preoperative carcinoembryonic antigen level<10 ng/mL(OR=3.84,95%CI:1.19-12.44,P=0.025)and severe sinusoidal dilatation(OR=0.17,95%CI:0.03-0.90,P=0.037)were independent predictive factors for complete tumour response.The low BMI group exhibited a significantly longer median PFS than the high BMI group(10.7 mo vs 4.7 mo,P=0.011).CONCLUSION In CRLM patients receiving preoperative chemotherapy,a low BMI may be associated with better tumour response and longer PFS.展开更多
BACKGROUND We described a case of a patient with a meningioma in the posterior fossa presenting atypically with an isolated unilateral vocal cord palsy causing severe respiratory distress.This is of interest as the pa...BACKGROUND We described a case of a patient with a meningioma in the posterior fossa presenting atypically with an isolated unilateral vocal cord palsy causing severe respiratory distress.This is of interest as the patient had no other symptomatology,especially given the size of the mass,which would typically cause a pressure effect leading to neurological and auditory symptoms.CASE SUMMARY This case report described a 48-year-old male who was married with two children and employed as a car guard.He had a medical history of asthma for the past 10 years controlled with an as-needed beta 2 agonist metered dose inhaler.He initially presented to our facility with severe respiratory distress.He reported a 1-wk history of shortness of breath and wheezing that was not relieved by his bronchodilator.He had no constitutional symptoms or impairment of hearing.On clinical examination,the patient’s chest was“silent.”Our initial assessment was status asthmaticus with type 2 respiratory failure,based on the history of asthma,a“silent chest,”and the arterial blood gas results.CONCLUSION A posterior fossa meningioma of such a large size and with extensive infiltration rarely presents with an isolated unilateral vocal cord palsy.The patient’s chief presenting feature was severe respiratory distress,which combined with his background medical history of asthma,was misleading.Clinicians should thus consider meningioma as a differential diagnosis for a unilateral vocal cord palsy even without audiology involvement.展开更多
Aim: To reveal the exonic and 3’UTR sequences of KRAS, TP53, APC, BRAF, PIK3CA genes in sporadic colorectal tumors and to investigate the clinical relevance of 3’UTR variations in miRNA profiles. Methods: In the stu...Aim: To reveal the exonic and 3’UTR sequences of KRAS, TP53, APC, BRAF, PIK3CA genes in sporadic colorectal tumors and to investigate the clinical relevance of 3’UTR variations in miRNA profiles. Methods: In the study, the exonic and 3’UTR sequences of five genes in 12 sporadic colorectal tumors were extracted by next generation sequencing. In tumors with variation in the 3’UTR region, the changes caused by the variation in the miRNA binding profile were detected. The expression profile of these miRNAs in colorectal and other solid tumors compared to normal tissue was determined. Pathway analysis was performed to determine which signaling pathways miRNAs affect. Results: Case-10 in our study was wild type KRAS and received cetuximab treatment and developed drug resistance. In this case, it was concluded that the expression of KRAS increased and tumorigenesis progressed due to miRNAs that do not bind to this region due to variations in the 3’UTR region. Among these miRNAs, hsa-miR-124-3p was found to have decreased expression in colorectal tumors and to be associated with the ECM-receptor interaction pathway. Conclusion: Variations in the 3’UTR regions of genes critical in the process of carsinogenesis are associated with drug resistance and the process of tumorigenesis.展开更多
Objective:To evaluate the efficacy of neoadjuvant chemotherapy before and after neoadjuvant chemotherapy for intermediate and advanced breast cancer using 3.0T MR and ultrasound in combination with tumour markers(CEA,...Objective:To evaluate the efficacy of neoadjuvant chemotherapy before and after neoadjuvant chemotherapy for intermediate and advanced breast cancer using 3.0T MR and ultrasound in combination with tumour markers(CEA,CA-153,CA125),and to provide therapeutic references for the clinicians,so as to better satisfy the needs of treatment for intermediate and advanced breast cancer patients.Methods:The team collected 30 patients who were diagnosed with intermediate and advanced breast cancer by biopsy and received neoadjuvant chemotherapy,and divided them into sensitive and insensitive groups according to the MP grading of postoperative pathological results.The team retrospectively analysed the changes in the values of serum CEA,CA-153,and CA 125 before and after the neoadjuvant chemotherapy,the changes in the average ADC of the lesions before and after the observation by MRI,and the changes in the volume and size of lesions before and after the observation by ultrasonography to assess the effects of neoadjuvant chemotherapy individually,and the results of neoadjuvant chemotherapy were evaluated individually.The effect of neoadjuvant chemotherapy was assessed independently.Each of the above was evaluated independently,and the accuracy of each item was calculated by comparing the evaluation results with the pathological examination results,and the accuracy of the single item was compared with the accuracy of the three combined tests to determine whether the combined evaluation was more consistent.Results:All three examination and testing methods can achieve high accuracy,and the combined evaluation of the three is more accurate than the evaluation of the single way,and the difference is statistically significant(P<0.05).Conclusion:In neoadjuvant chemotherapy for breast cancer patients,the combined assessment of MR,CDFI and tumour markers can more comprehensively and accurately assess the effect of ADC,and more accurately guide the clinical treatment and determine the prognosis.展开更多
Objective:This study aimed to investigate the effectiveness and value of MRI and CT in the diagnosis of retroperitoneal tumours.Methods:60 patients with retroperitoneal tumours admitted to our hospital between July 20...Objective:This study aimed to investigate the effectiveness and value of MRI and CT in the diagnosis of retroperitoneal tumours.Methods:60 patients with retroperitoneal tumours admitted to our hospital between July 2022 and March 2023 were selected as the study subjects.All of them received MRI and CT examinations.The detection of the two examination methods was compared and analyzed using the pathological findings as the standard.Results:The detection rate of MRI(58/60,96.67%)was significantly higher than that of CT(50/60,83.33%),and the difference was significant(P=0.015<0.05).Conclusion:Both MRI and CT have important application values in the diagnosis of retroperitoneal tumours.MRI has advantages in observing soft tissue structures,nerve tissues,etc.,and can provide more detailed anatomical structure information,which can help differentiate the retroperitoneal tumours and locate them accurately.CT,on the other hand,has unique advantages in observing the skeletal structure and the density of certain tumours,etc.It can quickly obtain comprehensive imaging information,which helps to determine the extent and invasion of the tumour.展开更多
The surgical removal of renal cancer,along with the thrombectomy of the inferior vena cava tumour thrombus,represents a remarkable milestone in urological surgery.This procedure is not only technically demanding but a...The surgical removal of renal cancer,along with the thrombectomy of the inferior vena cava tumour thrombus,represents a remarkable milestone in urological surgery.This procedure is not only technically demanding but also requires a high level of surgical expertise.Managing renal cancer combined with a vena cava tumour thrombus poses significant challenges,especially when dealing with combined grade Ⅱ-Ⅳ inferior vena cava tumour thrombus.The complexity of these cases is further exacerbated by the delicate anatomical structures involved and the need to preserve critical vessels while effectively removing the tumour.The Upper Urethral Tumour Treatment Centre of Weifang People's Hospital successfully treated a challenging case of left renal tumour combined with grade II inferior vena cava tumour thrombus.The surgical team,led by experienced urological surgeons,meticulously planned and executed the procedure,ensuring minimal trauma to the patient and complete removal of the tumour.This achievement not only demonstrates the hospital's commitment to providing state-of-the-art surgical care but also highlights the importance of continued research and training in urological oncology.The successful outcome of this case is a testament to the expertise and dedication of the medical team and offers hope to patients facing similar complex surgical challenges.展开更多
We report on an unusual case presenting with a cardiac pseudo-tumour on echocardiogram, which corresponded to a large soft tissue mural thickening around the mid-right coronary artery. There were similar but not as th...We report on an unusual case presenting with a cardiac pseudo-tumour on echocardiogram, which corresponded to a large soft tissue mural thickening around the mid-right coronary artery. There were similar but not as thick mural lesions around other parts of the coronary arteries. The so-called “pigs-in-a-blanket” sign on computed tomography (CT) scan was pathognomonic of IgG4 coronary arteritis. The IgG4 level was grossly elevated at more than 10 times the upper limit of normal. Positron emission tomography (PET)-CT scans with 18F-fluoro-deoxy-glucose (FDG) and 68Ga-Fibroblast Activation Protein Inhibitor (FAPI) were performed to assess the extent of organ involvement of the IgG4-related disease. The patient was treated with 8 injections of rituximab with good serological response. However, the coronary arteritis findings on CT scan remained unchanged.展开更多
Tumour rupture of gastrointestinal stromal tumours(GISTs)has been considered to be a remarkable risk factor because of its unfavourable impact on the oncological outcome.Although tumour rupture has not yet been includ...Tumour rupture of gastrointestinal stromal tumours(GISTs)has been considered to be a remarkable risk factor because of its unfavourable impact on the oncological outcome.Although tumour rupture has not yet been included in the current tumor-node-metastasis classification of GISTs as a prognostic factor,it may change the natural history of a low-risk GIST to a high-risk GIST.Originally,tumour rupture was defined as the spillage or fracture of a tumour into a body cavity,but recently,new definitions have been proposed.These definitions distinguished from the prognostic point of view between the major defects of tumour integrity,which are considered tumour rupture,and the minor defects of tumour integrity,which are not considered tumour rupture.Moreover,it has been demonstrated that the risk of disease recurrence in R1 patients is largely modulated by the presence of tumour rupture.Therefore,after excluding tumour rupture,R1 may not be an unfavourable prognostic factor for GISTs.Additionally,after the standard adjuvant treatment of imatinib for GIST with rupture,a high recurrence rate persists.This review highlights the prognostic value of tumour rupture in GISTs and emphasizes the need to carefully take into account and minimize the risk of tumour rupture when choosing surgical strategies for GISTs.展开更多
Pancreatic cancer is a high mortality malignancy with almost equal mortality and morbidity rates.Both normal and tumour tissues of the pancreas were previously considered sterile.In recent years,with the development o...Pancreatic cancer is a high mortality malignancy with almost equal mortality and morbidity rates.Both normal and tumour tissues of the pancreas were previously considered sterile.In recent years,with the development of technologies for highthroughput sequencing,a variety of studies have revealed that pancreatic cancer tissues contain small amounts of bacteria and fungi.The intratumour microbiome is being revealed as an influential contributor to carcinogenesis.The intratumour microbiome has been identified as a crucial factor for pancreatic cancer progression,diagnosis,and treatment,chemotherapy resistance,and immune response.A better understanding of the biology of the intratumour microbiome of pancreatic cancer contributes to the establishment of better early cancer screening and treatment strategies.This review focuses on the possible origins of the intratumour microbiome in pancreatic cancer,the intratumour localization,the interaction with the tumour microenvironment,and strategies for improving the outcome of pancreatic cancer treatment.Thus,this review offers new perspectives for improving the prognosis of pancreatic cancer.展开更多
BACKGROUND Ultrasound is a vital tool for the diagnosis and management of colorectal cancer(CRC).Contrast-enhanced ultrasound(CEUS)is a non-invasive,safe,and cost-effective method for evaluating tumour blood vessels,t...BACKGROUND Ultrasound is a vital tool for the diagnosis and management of colorectal cancer(CRC).Contrast-enhanced ultrasound(CEUS)is a non-invasive,safe,and cost-effective method for evaluating tumour blood vessels,that play a crucial role in tumour growth and progression.AIM To explore CEUS’s role in the quantitative evaluation of CRC blood vessels and their correlation with angiogenesis markers and prognosis.METHODS This study prospectively enrolled 100 patients with CRC confirmed by histo-pathology.All patients received preoperative CEUS examinations.Quantitative parameters,such as peak intensity(PI),time to peak(TTP),and area under the curve(AUC),were derived from time-intensity curve(TIC)analysis.Tumour tissue samples were obtained during surgery and examined immunohistochem-ically to assess the expression of angiogenesis markers,including vascular endo-thelial growth factor(VEGF)and microvessel density(MVD).The correlation between CEUS parameters,angiogenesis markers,and clinicopathological features was evaluated using appropriate statistical tests.RESULTS Quantitative CEUS parameters(PI,TTP,and AUC)showed significant correlations with VEGF expression(P<0.001)and MVD(P<0.001),indicating a strong link between tumour blood vessels and angiogenesis.Increased PI,reduced TTP,and expanded AUC values were significantly related to higher tumour stage(P<0.001),lymph node metastasis(P<0.001),and distant metastasis(P<0.001).Furthermore,these parameters were recognized as independent predictors of overall survival and disease-free survival in multivariate analysis(P<0.001).CONCLUSION CEUS has a high potential in guiding treatment planning and predicting patient outcomes.However,more com-prehensive,multicentre studies are required to validate the clinical utility of CEUS in CRC management.展开更多
The advent of single-cell RNA sequencing(scRNA-seq)has provided insight into the tumour immune microenvironment(TIME).This review focuses on the application of scRNA-seq in investigation of the TIME.Over time,scRNA-se...The advent of single-cell RNA sequencing(scRNA-seq)has provided insight into the tumour immune microenvironment(TIME).This review focuses on the application of scRNA-seq in investigation of the TIME.Over time,scRNA-seq methods have evolved,and components of the TIME have been deciphered with high resolution.In this review,we first introduced the principle of scRNA-seq and compared different sequencing approaches.Novel cell types in the TIME,a continuous transitional state,and mutual intercommunication among TIME components present potential targets for prognosis prediction and treatment in cancer.Thus,we concluded novel cell clusters of cancerassociated fibroblasts(CAFs),T cells,tumour-associated macrophages(TAMs)and dendritic cells(DCs)discovered after the application of scRNA-seq in TIME.We also proposed the development of TAMs and exhausted T cells,as well as the possible targets to interrupt the process.In addition,the therapeutic interventions based on cellular interactions in TIME were also summarized.For decades,quantification of the TIME components has been adopted in clinical practice to predict patient survival and response to therapy and is expected to play an important role in the precise treatment of cancer.Summarizing the current findings,we believe that advances in technology and wide application of single-cell analysis can lead to the discovery of novel perspectives on cancer therapy,which can subsequently be implemented in the clinic.Finally,we propose some future directions in the field of TIME studies that can be aided by scRNA-seq technology.展开更多
Rectal neuroendocrine tumours represent a rare colorectal tumour with a 10 fold increased prevalence due to incidental detection in the era of colorectal screening.Patient outcomes with early diagnosis are excellent.H...Rectal neuroendocrine tumours represent a rare colorectal tumour with a 10 fold increased prevalence due to incidental detection in the era of colorectal screening.Patient outcomes with early diagnosis are excellent.However endoscopic recognition of this lesion is variable and misdiagnosis can result in suboptimal endoscopic resection with subsequent uncertainty in relation to optimal long-term management.Endoscopic techniques have shown particular utility in managing this under-recognized neuroendocrine tumour.展开更多
The role of B cells in anti-tumour immunity is still debated and,accordingly,immunotherapies have focused on targeting T and natural killer cells to inhibit tumour growth1,2.Here,using high-throughput flow cytometry a...The role of B cells in anti-tumour immunity is still debated and,accordingly,immunotherapies have focused on targeting T and natural killer cells to inhibit tumour growth1,2.Here,using high-throughput flow cytometry as well as bulk and single-cell RNA-sequencing and B-cell-receptor-sequencing analysis of B cells temporally during B16F10 melanoma growth,we identified a subset of B cells that expands specifically in the draining lymph node over time in tumour-bearing mice.The expanding B cell subset expresses the cell surface molecule T cell immunoglobulin and mucin domain 1(TIM-1,encoded by Havcr1)and a unique transcriptional signature,including multiple co-inhibitory molecules such as PD-1,TIM-3,TIGIT and LAG-3.Although conditional deletion of these co-inhibitory molecules on B cells had little or no effect on tumour burden,selective deletion of Havcr1 in B cells both substantially inhibited tumour growth and enhanced effector T cell responses.Loss of TIM-1 enhanced the type 1 interferon response in B cells,which augmented B cell activation and increased antigen presentation and co-stimulation,resulting in increased expansion of tumour-specific effector T cells.Our results demonstrate that manipulation of TIM-1-expressing B cells enables engagement of the second arm of adaptive immunity to promote anti-tumour immunity and inhibit tumour growth.展开更多
Netrin-1 is upregulated in cancers as a protumoural mechanism1.Here we describe netrin-1 upregulation in a majority of human endometrial carcinomas(ECs)and demonstrate that netrin-1 blockade,using an anti-netrin-1 ant...Netrin-1 is upregulated in cancers as a protumoural mechanism1.Here we describe netrin-1 upregulation in a majority of human endometrial carcinomas(ECs)and demonstrate that netrin-1 blockade,using an anti-netrin-1 antibody(NP137),is effective in reduction of tumour progression in an EC mouse model.We next examined the efficacy of NP137,as a first-in-class single agent,in a Phase I trial comprising 14 patients with advanced EC.As best response we observed 8 stable disease(8 out of 14,57.1%)and 1 objective response as RECIST v.1.1(partial response,1 out of 14(7.1%),51.16%reduction in target lesions at 6 weeks and up to 54.65%reduction during the following 6 months).To evaluate the NP137 mechanism of action,mouse tumour gene profiling was performed,and we observed,in addition to cell death induction,that NP137 inhibited epithelial-to mesenchymal transition(EMT).By performing bulk RNA sequencing(RNA-seq),spatial transcriptomics and single-cell RNA seq on paired pre-and on-treatment biopsies from patients with EC from the NP137 trial,we noted a net reduction in tumour EMT.This was associated with changes in immune infiltrate and increased interactions between cancer cells and the tumour microenvironment.Given the importance of EMT in resistance to current standards of care2,we show in the EC mouse model that a combination of NP137 with carboplatin-paclitaxel outperformed carboplatin-paclitaxel alone.Our results identify netrin-1 blockade as a clinical strategy triggering both tumour debulking and EMT inhibition,thus potentially alleviating resistance to standard treatments.展开更多
Recurrence is the key factor affecting the prognosis of osteosarcoma.Currently,there is a lack of clinically useful tools to predict osteosarcoma recurrence.The application of pathological images for artificial intell...Recurrence is the key factor affecting the prognosis of osteosarcoma.Currently,there is a lack of clinically useful tools to predict osteosarcoma recurrence.The application of pathological images for artificial intelligence‐assisted accurate prediction of tumour out-comes is increasing.Thus,the present study constructed a quantitative histological image classifier with tumour nuclear features to predict osteosarcoma outcomes using haema-toxylin and eosin(H&E)‐stained whole‐slide images(WSIs)from 150 osteosarcoma patients.We first segmented eight distinct tissues in osteosarcoma H&E‐stained WSIs,with an average accuracy of 90.63%on the testing set.The tumour areas were auto-matically and accurately acquired,facilitating the tumour cell nuclear feature extraction process.Based on six selected tumour nuclear features,we developed an osteosarcoma histological image classifier(OSHIC)to predict the recurrence and survival of osteo-sarcoma following standard treatment.The quantitative OSHIC derived from tumour nuclear features independently predicted the recurrence and survival of osteosarcoma patients,thereby contributing to precision oncology.Moreover,we developed a fully automated workflow to extract quantitative image features,evaluate the diagnostic values of feature sets and build classifiers to predict osteosarcoma outcomes.Thus,the present study provides a novel tool for predicting osteosarcoma outcomes,which has a broad application prospect in clinical practice.展开更多
Objective:This study aimed to evaluate the safety and efficacy outcomes of percutaneous radiofrequency ablation(RFA)for localised renal cell carcinoma(RCC)in a tertiary hospital patient who remained unfit for surgical...Objective:This study aimed to evaluate the safety and efficacy outcomes of percutaneous radiofrequency ablation(RFA)for localised renal cell carcinoma(RCC)in a tertiary hospital patient who remained unfit for surgical intervention.Methods:We retrospectively analysed survival outcomes for patients with biopsy proven RCC treated by RFA at Royal Perth Hospital between September 2009 and May 2018.Complication data were gathered for all patients that underwent renal RFA along with 2-and 5-year recurrence-free survival(RFS)rate and compared the outcomes with data from previous studies.Results:A total of 69 patients(73 procedures)were eligible for the study,and those patients had biopsy-proven RCC with a minimum of 2-year follow-up.The complication rate was 8.2%(6/73)and local recurrence rate 9.6%(7/73).Two-year RFS is 95.7% and 5-year RFS is 78.8% on a median 3.82-year follow-up(interquartile range 1.90-5.75 years).Conclusion:RFA performed at our centre was found to be safe and effective with low complication rates and durable RFS in line with expectations from existing research.Our study demonstrated that RFA is an alternative modality of treatment for small renal tumours in patients unfit for surgical approach.展开更多
文摘Augmentation of abnormal cells in the brain causes brain tumor(BT),and early screening and treatmentwill reduce its harshness in patients.BT’s clinical level screening is usually performed with Magnetic Resonance Imaging(MRI)due to its multi-modality nature.The overall aims of the study is to introduce,test and verify an advanced image processing technique with algorithms to automatically extract tumour sections from brain MRI scans,facilitating improved accuracy.The research intends to devise a reliable framework for detecting the BT region in the twodimensional(2D)MRI slice,and identifying its class with improved accuracy.The methodology for the devised framework comprises the phases of:(i)Collection and resizing of images,(ii)Implementation and Segmentation of Convolutional Neural Network(CNN),(iii)Deep feature extraction,(iv)Handcrafted feature extraction,(v)Moth-Flame-Algorithm(MFA)supported feature reduction,and(vi)Performance evaluation.This study utilized clinical-grade brain MRI of BRATS and TCIA datasets for the investigation.This framework segments detected the glioma(low/high grade)and glioblastoma class BT.This work helped to get a segmentation accuracy of over 98%with VGG-UNet and a classification accuracy of over 98%with the VGG16 scheme.This study has confirmed that the implemented framework is very efficient in detecting the BT in MRI slices with/without the skull section.
基金The study protocol was approved by the Clinical Research Ethics Committee of Honghui Hospital,Xi’an Jiaotong University(No.202401004).
文摘BACKGROUND Duodenal neuroendocrine tumours(DNETs)are rare neoplasms.However,the incidence of DNETs has been increasing in recent years,especially as an incidental finding during endoscopic studies.Regrettably,there is no consensus regarding the ideal treatment of DNETs.Even there are few studies on the clinical features and survival analysis of DNETs.AIM To analyze the clinical characteristics and prognostic factors of patients with duodenal neuroendocrine tumours.METHODS The clinical data of DNETs diagnosed in the First Affiliated Hospital of Air Force Military Medical University from June 2011 to July 2022 were collected.Neuroen-docrine tumours located in the ampulla area of the duodenum were divided into the ampullary region group;neuroendocrine tumours in any part of the duo-denum outside the ampullary area were divided into the nonampullary region group.Using a retrospective study,the clinical characteristics of the two groups and risk factors affecting the survival of DNET patients were analysed.RESULTS Twenty-nine DNET patients were screened.The male to female ratio was 1:1.9,and females comprised the majority.The ampullary region group accounted for 24.1%(7/29),while the nonampullary region group accounted for 75.9%(22/29).When diagnosed,the clinical symptoms of the ampullary region group were mainly abdominal pain(85.7%),while those of the nonampullary region groups were mainly abdominal distension(59.1%).There were differences in the composition of staging of tumours between the two groups(Fisher's exact probability method,P=0.001),with nonampullary stage II tumours(68.2%)being the main stage(P<0.05).After the diagnosis of DNETs,the survival rate of the ampullary region group was 14.3%(1/7),which was lower than that of 72.7%(16/22)in the nonampullary region group(Fisher's exact probability method,P=0.011).The survival time of the ampullary region group was shorter than that of the nonampullary region group(P<0.000).The median survival time of the ampullary region group was 10.0 months and that of the nonampullary region group was 451.0 months.Multivariate analysis showed that tumours in the ampulla region and no surgical treatment after diagnosis were independent risk factors for the survival of DNET patients(HR=0.029,95%CI 0.004-0.199,P<0.000;HR=12.609,95%CI:2.889-55.037,P=0.001).Further analysis of nonampullary DNET patients showed that the survival time of patients with a tumour diameter<2 cm was longer than that of patients with a tumour diameter≥2 cm(t=7.243,P=0.048).As of follow-up,6 patients who died of nonampullary DNETs had a tumour diameter that was≥2 cm,and 3 patients in stage IV had liver metastasis.Patients with a tumour diameter<2 cm underwent surgical treatment,and all survived after surgery.CONCLUSION Surgical treatment is a protective factor for prolonging the survival of DNET patients.Compared to DNETs in the ampullary region,patients in the nonampullary region group had a longer survival period.The liver is the organ most susceptible to distant metastasis of nonampullary DNETs.
基金Ministry of Education,Youth and Sports of the Chezk Republic,Grant/Award Numbers:SP2023/039,SP2023/042the European Union under the REFRESH,Grant/Award Number:CZ.10.03.01/00/22_003/0000048。
文摘Detecting brain tumours is complex due to the natural variation in their location, shape, and intensity in images. While having accurate detection and segmentation of brain tumours would be beneficial, current methods still need to solve this problem despite the numerous available approaches. Precise analysis of Magnetic Resonance Imaging (MRI) is crucial for detecting, segmenting, and classifying brain tumours in medical diagnostics. Magnetic Resonance Imaging is a vital component in medical diagnosis, and it requires precise, efficient, careful, efficient, and reliable image analysis techniques. The authors developed a Deep Learning (DL) fusion model to classify brain tumours reliably. Deep Learning models require large amounts of training data to achieve good results, so the researchers utilised data augmentation techniques to increase the dataset size for training models. VGG16, ResNet50, and convolutional deep belief networks networks extracted deep features from MRI images. Softmax was used as the classifier, and the training set was supplemented with intentionally created MRI images of brain tumours in addition to the genuine ones. The features of two DL models were combined in the proposed model to generate a fusion model, which significantly increased classification accuracy. An openly accessible dataset from the internet was used to test the model's performance, and the experimental results showed that the proposed fusion model achieved a classification accuracy of 98.98%. Finally, the results were compared with existing methods, and the proposed model outperformed them significantly.
基金Supported by the National Natural Science Foundation of China,No.82100599 and No.81960112the Jiangxi Provincial Department of Science and Technology,No.20242BAB26122+1 种基金the Science and Technology Plan of Jiangxi Provincial Administration of Traditional Chinese Medicine,No.2023Z021the Project of Jiangxi Provincial Academic and Technical Leaders Training Program for Major Disciplines,No.20243BCE51001.
文摘In this letter,we explore into the potential role of the recent study by Zeng et al.Rectal neuroendocrine tumours(rNETs)are rare,originate from peptidergic neurons and neuroendocrine cells,and express corresponding markers.Although most rNETs patients have a favourable prognosis,the median survival period significantly decreases when high-risk factors,such as larger tumours,poorer differentiation,and lymph node metastasis exist,are present.Clinical prediction models play a vital role in guiding diagnosis and prognosis in health care,but their complex calculation formulae limit clinical use.Moreover,the prognostic models that have been developed for rNETs to date still have several limitations,such as insufficient sample sizes and the lack of external validation.A high-quality prognostic model for rNETs would guide treatment and follow-up,enabling the precise formulation of individual patient treatment and follow-up plans.The future development of models for rNETs should involve closer collab-oration with statistical experts,which would allow the construction of clinical prediction models to be standardized and robust,accurate,and highly general-izable prediction models to be created,ultimately achieving the goal of precision medicine.
基金National Natural Science Foundation of China,No.82170618.
文摘BACKGROUND Colorectal cancer is the third most prevalent malignancy globally and ranks second in cancer-related mortality,with the liver being the primary organ of metastasis.Preoperative chemotherapy is widely recommended for initially or potentially resectable colorectal liver metastases(CRLMs).Tumour pathological response serves as the most important and intuitive indicator for assessing the efficacy of chemotherapy.However,the postoperative pathological results reveal that a considerable number of patients exhibit a poor response to preoperative chemotherapy.Body mass index(BMI)is one of the factors affecting the tumori-genesis and progression of colorectal cancer as well as prognosis after various antitumour therapies.Several studies have indicated that overweight and obese patients with metastatic colorectal cancer experience worse prognoses than those with normal weight,particularly when receiving first-line chemotherapy regimens in combination with bevacizumab.AIM To explore the predictive value of BMI regarding the pathologic response following preoperative chemotherapy for CRLMs.METHODS A retrospective analysis was performed in 126 consecutive patients with CRLM who underwent hepatectomy following preoperative chemotherapy at four different hospitals from October 2019 to July 2023.Univariate and multivariate logistic regression models were applied to analyse potential predictors of tumour pathological response.The Kaplan-Meier method with log rank test was used to compare progression-free survival(PFS)between patients with high and low BMI.BMI<24.0 kg/m^(2) was defined as low BMI,and tumour regression grade 1-2 was defined as complete tumour response.RESULTS Low BMI was observed in 74(58.7%)patients and complete tumour response was found in 27(21.4%)patients.The rate of complete tumour response was significantly higher in patients with low BMI(29.7%vs 9.6%,P=0.007).Multivariate analysis revealed that low BMI[odds ratio(OR)=4.56,95%confidence interval(CI):1.42-14.63,P=0.011],targeted therapy with bevacizumab(OR=3.02,95%CI:1.10-8.33,P=0.033),preoperative carcinoembryonic antigen level<10 ng/mL(OR=3.84,95%CI:1.19-12.44,P=0.025)and severe sinusoidal dilatation(OR=0.17,95%CI:0.03-0.90,P=0.037)were independent predictive factors for complete tumour response.The low BMI group exhibited a significantly longer median PFS than the high BMI group(10.7 mo vs 4.7 mo,P=0.011).CONCLUSION In CRLM patients receiving preoperative chemotherapy,a low BMI may be associated with better tumour response and longer PFS.
文摘BACKGROUND We described a case of a patient with a meningioma in the posterior fossa presenting atypically with an isolated unilateral vocal cord palsy causing severe respiratory distress.This is of interest as the patient had no other symptomatology,especially given the size of the mass,which would typically cause a pressure effect leading to neurological and auditory symptoms.CASE SUMMARY This case report described a 48-year-old male who was married with two children and employed as a car guard.He had a medical history of asthma for the past 10 years controlled with an as-needed beta 2 agonist metered dose inhaler.He initially presented to our facility with severe respiratory distress.He reported a 1-wk history of shortness of breath and wheezing that was not relieved by his bronchodilator.He had no constitutional symptoms or impairment of hearing.On clinical examination,the patient’s chest was“silent.”Our initial assessment was status asthmaticus with type 2 respiratory failure,based on the history of asthma,a“silent chest,”and the arterial blood gas results.CONCLUSION A posterior fossa meningioma of such a large size and with extensive infiltration rarely presents with an isolated unilateral vocal cord palsy.The patient’s chief presenting feature was severe respiratory distress,which combined with his background medical history of asthma,was misleading.Clinicians should thus consider meningioma as a differential diagnosis for a unilateral vocal cord palsy even without audiology involvement.
文摘Aim: To reveal the exonic and 3’UTR sequences of KRAS, TP53, APC, BRAF, PIK3CA genes in sporadic colorectal tumors and to investigate the clinical relevance of 3’UTR variations in miRNA profiles. Methods: In the study, the exonic and 3’UTR sequences of five genes in 12 sporadic colorectal tumors were extracted by next generation sequencing. In tumors with variation in the 3’UTR region, the changes caused by the variation in the miRNA binding profile were detected. The expression profile of these miRNAs in colorectal and other solid tumors compared to normal tissue was determined. Pathway analysis was performed to determine which signaling pathways miRNAs affect. Results: Case-10 in our study was wild type KRAS and received cetuximab treatment and developed drug resistance. In this case, it was concluded that the expression of KRAS increased and tumorigenesis progressed due to miRNAs that do not bind to this region due to variations in the 3’UTR region. Among these miRNAs, hsa-miR-124-3p was found to have decreased expression in colorectal tumors and to be associated with the ECM-receptor interaction pathway. Conclusion: Variations in the 3’UTR regions of genes critical in the process of carsinogenesis are associated with drug resistance and the process of tumorigenesis.
基金Weifang Science and Technology Development Programme Project(Medicine)(2021YX144)Weifang Municipal Health Commission Chinese Medicine Research Project(WFZYY2024-1-014).
文摘Objective:To evaluate the efficacy of neoadjuvant chemotherapy before and after neoadjuvant chemotherapy for intermediate and advanced breast cancer using 3.0T MR and ultrasound in combination with tumour markers(CEA,CA-153,CA125),and to provide therapeutic references for the clinicians,so as to better satisfy the needs of treatment for intermediate and advanced breast cancer patients.Methods:The team collected 30 patients who were diagnosed with intermediate and advanced breast cancer by biopsy and received neoadjuvant chemotherapy,and divided them into sensitive and insensitive groups according to the MP grading of postoperative pathological results.The team retrospectively analysed the changes in the values of serum CEA,CA-153,and CA 125 before and after the neoadjuvant chemotherapy,the changes in the average ADC of the lesions before and after the observation by MRI,and the changes in the volume and size of lesions before and after the observation by ultrasonography to assess the effects of neoadjuvant chemotherapy individually,and the results of neoadjuvant chemotherapy were evaluated individually.The effect of neoadjuvant chemotherapy was assessed independently.Each of the above was evaluated independently,and the accuracy of each item was calculated by comparing the evaluation results with the pathological examination results,and the accuracy of the single item was compared with the accuracy of the three combined tests to determine whether the combined evaluation was more consistent.Results:All three examination and testing methods can achieve high accuracy,and the combined evaluation of the three is more accurate than the evaluation of the single way,and the difference is statistically significant(P<0.05).Conclusion:In neoadjuvant chemotherapy for breast cancer patients,the combined assessment of MR,CDFI and tumour markers can more comprehensively and accurately assess the effect of ADC,and more accurately guide the clinical treatment and determine the prognosis.
文摘Objective:This study aimed to investigate the effectiveness and value of MRI and CT in the diagnosis of retroperitoneal tumours.Methods:60 patients with retroperitoneal tumours admitted to our hospital between July 2022 and March 2023 were selected as the study subjects.All of them received MRI and CT examinations.The detection of the two examination methods was compared and analyzed using the pathological findings as the standard.Results:The detection rate of MRI(58/60,96.67%)was significantly higher than that of CT(50/60,83.33%),and the difference was significant(P=0.015<0.05).Conclusion:Both MRI and CT have important application values in the diagnosis of retroperitoneal tumours.MRI has advantages in observing soft tissue structures,nerve tissues,etc.,and can provide more detailed anatomical structure information,which can help differentiate the retroperitoneal tumours and locate them accurately.CT,on the other hand,has unique advantages in observing the skeletal structure and the density of certain tumours,etc.It can quickly obtain comprehensive imaging information,which helps to determine the extent and invasion of the tumour.
文摘The surgical removal of renal cancer,along with the thrombectomy of the inferior vena cava tumour thrombus,represents a remarkable milestone in urological surgery.This procedure is not only technically demanding but also requires a high level of surgical expertise.Managing renal cancer combined with a vena cava tumour thrombus poses significant challenges,especially when dealing with combined grade Ⅱ-Ⅳ inferior vena cava tumour thrombus.The complexity of these cases is further exacerbated by the delicate anatomical structures involved and the need to preserve critical vessels while effectively removing the tumour.The Upper Urethral Tumour Treatment Centre of Weifang People's Hospital successfully treated a challenging case of left renal tumour combined with grade II inferior vena cava tumour thrombus.The surgical team,led by experienced urological surgeons,meticulously planned and executed the procedure,ensuring minimal trauma to the patient and complete removal of the tumour.This achievement not only demonstrates the hospital's commitment to providing state-of-the-art surgical care but also highlights the importance of continued research and training in urological oncology.The successful outcome of this case is a testament to the expertise and dedication of the medical team and offers hope to patients facing similar complex surgical challenges.
文摘We report on an unusual case presenting with a cardiac pseudo-tumour on echocardiogram, which corresponded to a large soft tissue mural thickening around the mid-right coronary artery. There were similar but not as thick mural lesions around other parts of the coronary arteries. The so-called “pigs-in-a-blanket” sign on computed tomography (CT) scan was pathognomonic of IgG4 coronary arteritis. The IgG4 level was grossly elevated at more than 10 times the upper limit of normal. Positron emission tomography (PET)-CT scans with 18F-fluoro-deoxy-glucose (FDG) and 68Ga-Fibroblast Activation Protein Inhibitor (FAPI) were performed to assess the extent of organ involvement of the IgG4-related disease. The patient was treated with 8 injections of rituximab with good serological response. However, the coronary arteritis findings on CT scan remained unchanged.
文摘Tumour rupture of gastrointestinal stromal tumours(GISTs)has been considered to be a remarkable risk factor because of its unfavourable impact on the oncological outcome.Although tumour rupture has not yet been included in the current tumor-node-metastasis classification of GISTs as a prognostic factor,it may change the natural history of a low-risk GIST to a high-risk GIST.Originally,tumour rupture was defined as the spillage or fracture of a tumour into a body cavity,but recently,new definitions have been proposed.These definitions distinguished from the prognostic point of view between the major defects of tumour integrity,which are considered tumour rupture,and the minor defects of tumour integrity,which are not considered tumour rupture.Moreover,it has been demonstrated that the risk of disease recurrence in R1 patients is largely modulated by the presence of tumour rupture.Therefore,after excluding tumour rupture,R1 may not be an unfavourable prognostic factor for GISTs.Additionally,after the standard adjuvant treatment of imatinib for GIST with rupture,a high recurrence rate persists.This review highlights the prognostic value of tumour rupture in GISTs and emphasizes the need to carefully take into account and minimize the risk of tumour rupture when choosing surgical strategies for GISTs.
文摘Pancreatic cancer is a high mortality malignancy with almost equal mortality and morbidity rates.Both normal and tumour tissues of the pancreas were previously considered sterile.In recent years,with the development of technologies for highthroughput sequencing,a variety of studies have revealed that pancreatic cancer tissues contain small amounts of bacteria and fungi.The intratumour microbiome is being revealed as an influential contributor to carcinogenesis.The intratumour microbiome has been identified as a crucial factor for pancreatic cancer progression,diagnosis,and treatment,chemotherapy resistance,and immune response.A better understanding of the biology of the intratumour microbiome of pancreatic cancer contributes to the establishment of better early cancer screening and treatment strategies.This review focuses on the possible origins of the intratumour microbiome in pancreatic cancer,the intratumour localization,the interaction with the tumour microenvironment,and strategies for improving the outcome of pancreatic cancer treatment.Thus,this review offers new perspectives for improving the prognosis of pancreatic cancer.
文摘BACKGROUND Ultrasound is a vital tool for the diagnosis and management of colorectal cancer(CRC).Contrast-enhanced ultrasound(CEUS)is a non-invasive,safe,and cost-effective method for evaluating tumour blood vessels,that play a crucial role in tumour growth and progression.AIM To explore CEUS’s role in the quantitative evaluation of CRC blood vessels and their correlation with angiogenesis markers and prognosis.METHODS This study prospectively enrolled 100 patients with CRC confirmed by histo-pathology.All patients received preoperative CEUS examinations.Quantitative parameters,such as peak intensity(PI),time to peak(TTP),and area under the curve(AUC),were derived from time-intensity curve(TIC)analysis.Tumour tissue samples were obtained during surgery and examined immunohistochem-ically to assess the expression of angiogenesis markers,including vascular endo-thelial growth factor(VEGF)and microvessel density(MVD).The correlation between CEUS parameters,angiogenesis markers,and clinicopathological features was evaluated using appropriate statistical tests.RESULTS Quantitative CEUS parameters(PI,TTP,and AUC)showed significant correlations with VEGF expression(P<0.001)and MVD(P<0.001),indicating a strong link between tumour blood vessels and angiogenesis.Increased PI,reduced TTP,and expanded AUC values were significantly related to higher tumour stage(P<0.001),lymph node metastasis(P<0.001),and distant metastasis(P<0.001).Furthermore,these parameters were recognized as independent predictors of overall survival and disease-free survival in multivariate analysis(P<0.001).CONCLUSION CEUS has a high potential in guiding treatment planning and predicting patient outcomes.However,more com-prehensive,multicentre studies are required to validate the clinical utility of CEUS in CRC management.
基金supported by the National Key Research Development Program of China(2021YFA1301203)the National Natural Science Foundation of China(82103031,82103918,81973408)+6 种基金the Clinical Research Incubation Project,West China Hospital,Sichuan University(22HXFH019)the China Postdoctoral Science Foundation(2019 M653416)the International Cooperation Project of Chengdu Municipal Science and Technology Bureau(2020-GH02-00017-HZ)the“1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University”(ZYJC18035,ZYJC18025,ZYYC20003,ZYJC18003)the GIST Research Institute(GRI)IIBR grants funded by the GISTthe National Research Foundation of Korea funded by the Korean government(MSIP)(2019R1C1C1005403,2019R1A4A1028802 and2021M3H9A2097520)the Post-Doctor Research Project,West China Hospital,Sichuan University(2021HXBH054)。
文摘The advent of single-cell RNA sequencing(scRNA-seq)has provided insight into the tumour immune microenvironment(TIME).This review focuses on the application of scRNA-seq in investigation of the TIME.Over time,scRNA-seq methods have evolved,and components of the TIME have been deciphered with high resolution.In this review,we first introduced the principle of scRNA-seq and compared different sequencing approaches.Novel cell types in the TIME,a continuous transitional state,and mutual intercommunication among TIME components present potential targets for prognosis prediction and treatment in cancer.Thus,we concluded novel cell clusters of cancerassociated fibroblasts(CAFs),T cells,tumour-associated macrophages(TAMs)and dendritic cells(DCs)discovered after the application of scRNA-seq in TIME.We also proposed the development of TAMs and exhausted T cells,as well as the possible targets to interrupt the process.In addition,the therapeutic interventions based on cellular interactions in TIME were also summarized.For decades,quantification of the TIME components has been adopted in clinical practice to predict patient survival and response to therapy and is expected to play an important role in the precise treatment of cancer.Summarizing the current findings,we believe that advances in technology and wide application of single-cell analysis can lead to the discovery of novel perspectives on cancer therapy,which can subsequently be implemented in the clinic.Finally,we propose some future directions in the field of TIME studies that can be aided by scRNA-seq technology.
文摘Rectal neuroendocrine tumours represent a rare colorectal tumour with a 10 fold increased prevalence due to incidental detection in the era of colorectal screening.Patient outcomes with early diagnosis are excellent.However endoscopic recognition of this lesion is variable and misdiagnosis can result in suboptimal endoscopic resection with subsequent uncertainty in relation to optimal long-term management.Endoscopic techniques have shown particular utility in managing this under-recognized neuroendocrine tumour.
文摘The role of B cells in anti-tumour immunity is still debated and,accordingly,immunotherapies have focused on targeting T and natural killer cells to inhibit tumour growth1,2.Here,using high-throughput flow cytometry as well as bulk and single-cell RNA-sequencing and B-cell-receptor-sequencing analysis of B cells temporally during B16F10 melanoma growth,we identified a subset of B cells that expands specifically in the draining lymph node over time in tumour-bearing mice.The expanding B cell subset expresses the cell surface molecule T cell immunoglobulin and mucin domain 1(TIM-1,encoded by Havcr1)and a unique transcriptional signature,including multiple co-inhibitory molecules such as PD-1,TIM-3,TIGIT and LAG-3.Although conditional deletion of these co-inhibitory molecules on B cells had little or no effect on tumour burden,selective deletion of Havcr1 in B cells both substantially inhibited tumour growth and enhanced effector T cell responses.Loss of TIM-1 enhanced the type 1 interferon response in B cells,which augmented B cell activation and increased antigen presentation and co-stimulation,resulting in increased expansion of tumour-specific effector T cells.Our results demonstrate that manipulation of TIM-1-expressing B cells enables engagement of the second arm of adaptive immunity to promote anti-tumour immunity and inhibit tumour growth.
文摘Netrin-1 is upregulated in cancers as a protumoural mechanism1.Here we describe netrin-1 upregulation in a majority of human endometrial carcinomas(ECs)and demonstrate that netrin-1 blockade,using an anti-netrin-1 antibody(NP137),is effective in reduction of tumour progression in an EC mouse model.We next examined the efficacy of NP137,as a first-in-class single agent,in a Phase I trial comprising 14 patients with advanced EC.As best response we observed 8 stable disease(8 out of 14,57.1%)and 1 objective response as RECIST v.1.1(partial response,1 out of 14(7.1%),51.16%reduction in target lesions at 6 weeks and up to 54.65%reduction during the following 6 months).To evaluate the NP137 mechanism of action,mouse tumour gene profiling was performed,and we observed,in addition to cell death induction,that NP137 inhibited epithelial-to mesenchymal transition(EMT).By performing bulk RNA sequencing(RNA-seq),spatial transcriptomics and single-cell RNA seq on paired pre-and on-treatment biopsies from patients with EC from the NP137 trial,we noted a net reduction in tumour EMT.This was associated with changes in immune infiltrate and increased interactions between cancer cells and the tumour microenvironment.Given the importance of EMT in resistance to current standards of care2,we show in the EC mouse model that a combination of NP137 with carboplatin-paclitaxel outperformed carboplatin-paclitaxel alone.Our results identify netrin-1 blockade as a clinical strategy triggering both tumour debulking and EMT inhibition,thus potentially alleviating resistance to standard treatments.
基金supported by the China Postdoctoral Science Foundation(2021M692792)National Natural Science Foun-dation of China(82103499,81872173,82072959,U1809205,61771249,91959207,81871352)+2 种基金Natural Science Foundation of Jiangsu Province of China(BK20181411)Natural Science Foundation of Zhejiang Province(LD21H160002)Med-ical and Health Science and Technology Plan of Department of Health of Zhejiang Province(WKJ‐ZJ‐1821).
文摘Recurrence is the key factor affecting the prognosis of osteosarcoma.Currently,there is a lack of clinically useful tools to predict osteosarcoma recurrence.The application of pathological images for artificial intelligence‐assisted accurate prediction of tumour out-comes is increasing.Thus,the present study constructed a quantitative histological image classifier with tumour nuclear features to predict osteosarcoma outcomes using haema-toxylin and eosin(H&E)‐stained whole‐slide images(WSIs)from 150 osteosarcoma patients.We first segmented eight distinct tissues in osteosarcoma H&E‐stained WSIs,with an average accuracy of 90.63%on the testing set.The tumour areas were auto-matically and accurately acquired,facilitating the tumour cell nuclear feature extraction process.Based on six selected tumour nuclear features,we developed an osteosarcoma histological image classifier(OSHIC)to predict the recurrence and survival of osteo-sarcoma following standard treatment.The quantitative OSHIC derived from tumour nuclear features independently predicted the recurrence and survival of osteosarcoma patients,thereby contributing to precision oncology.Moreover,we developed a fully automated workflow to extract quantitative image features,evaluate the diagnostic values of feature sets and build classifiers to predict osteosarcoma outcomes.Thus,the present study provides a novel tool for predicting osteosarcoma outcomes,which has a broad application prospect in clinical practice.
文摘Objective:This study aimed to evaluate the safety and efficacy outcomes of percutaneous radiofrequency ablation(RFA)for localised renal cell carcinoma(RCC)in a tertiary hospital patient who remained unfit for surgical intervention.Methods:We retrospectively analysed survival outcomes for patients with biopsy proven RCC treated by RFA at Royal Perth Hospital between September 2009 and May 2018.Complication data were gathered for all patients that underwent renal RFA along with 2-and 5-year recurrence-free survival(RFS)rate and compared the outcomes with data from previous studies.Results:A total of 69 patients(73 procedures)were eligible for the study,and those patients had biopsy-proven RCC with a minimum of 2-year follow-up.The complication rate was 8.2%(6/73)and local recurrence rate 9.6%(7/73).Two-year RFS is 95.7% and 5-year RFS is 78.8% on a median 3.82-year follow-up(interquartile range 1.90-5.75 years).Conclusion:RFA performed at our centre was found to be safe and effective with low complication rates and durable RFS in line with expectations from existing research.Our study demonstrated that RFA is an alternative modality of treatment for small renal tumours in patients unfit for surgical approach.