Cardiac disease is one of the leading causes of death in dogs. Automatic cardiomegaly detection has great significance in helping clinicians improve the accuracy of the diagnosis process. Deep ...learning methods show promising results in improving cardiomegaly classification accuracy, while they are still not widely applied in clinical trials due to the difficulty in mapping predicted results with input radiographs. To overcome these challenges, we first collect large-scale dog heart X-ray images. We then develop a dog heart labeling tool and apply a few-shot generalization strategy to accelerate the label speed. We also develop a regressive vision transformer model with an orthogonal layer to bridge traditional clinically used VHS metric with deep learning models. Extensive experimental results demonstrate that the proposed model achieves state-of-the-art performance.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The metastatic organotropism has been one of the cancer's greatest mysteries since the 'seed and soil' hypothesis. Although the role of EGFR in cancer cells is well studied, the effects of secreted ...EGFR transported by exosomes are less understood. Here we show that EGFR in exosomes secreted from gastric cancer cells can be delivered into the liver and is integrated on the plasma membrane of liver stromal cells. The translocated EGFR is proved to effectively activate hepatocyte growth factor (HGF) by suppressing miR-26a/b expression. Moreover, the upregulated paracrine HGF, which binds the c-MET receptor on the migrated cancer cells, provides fertile 'soil' for the 'seed', facilitating the landing and proliferation of metastatic cancer cells. Thus, we propose that EGFR-containing exosomes derived from cancer cells could favour the development of a liver-like microenvironment promoting liver-specific metastasis.
Exosomes derived from cells have been found to mediate signal transduction between cells and to act as efficient carriers to deliver drugs and small RNA. Hepatocyte growth factor (HGF) is known to ...promote the growth of both cancer cells and vascular cells, and the HGF‐cMET pathway is a potential clinical target. Here, we characterized the inhibitory effect of HGF siRNA on tumor growth and angiogenesis in gastric cancer. In addition, we showed that HGF siRNA packed in exosomes can be transported into cancer cells, where it dramatically downregulates HGF expression. A cell co‐culture model was used to show that exosomes loaded with HGF siRNA suppress proliferation and migration of both cancer cells and vascular cells. Moreover, exosomes were able to transfer HGF siRNA in vivo, decreasing the growth rates of tumors and blood vessels. The results of our study demonstrate that exosomes have potential for use in targeted cancer therapy by delivering siRNA.
HGF siRNA packed in exosomes can be transported into cancer cells, and down‐regulates HGF expression, and suppress proliferation and migration of both cancer cells and vascular cells.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Malignant tumors, including colorectal cancer (CRC), usually rely on ATP generation through aerobic glycolysis for both rapid growth and chemotherapy resistance. The M2 isoform of pyruvate kinase ...(PKM2) has a key role in catalyzing glycolysis, and PKM2 expression varies even within a single tumor. In this study, we confirmed that expression of PKM2 is heterogeneous in CRC cells, namely high in oxaliplatin‐resistant cells but relatively low in sensitive cells, and found that chemoresistant cells had enhanced glycolysis and ATP production. In addition, we report a PKM2‐dependent mechanism through which chemosensitive cells may gradually transform into chemoresistant cells. The circular RNA hsa_circ_0005963 (termed ciRS‐122 in this study), which was determined to be a sponge for the PKM2‐targeting miR‐122, was positively correlated with chemoresistance. In vitro and in vivo studies showed that exosomes from oxaliplatin‐resistant cells delivered ciRS‐122 to sensitive cells, thereby promoting glycolysis and drug resistance through miR‐122 sponging and PKM2 upregulation. Moreover, si‐ciRS‐122 transported by exosomes could suppress glycolysis and reverse resistance to oxaliplatin by regulating the ciRS‐122–miR‐122–PKM2 pathway in vivo. Exosomes derived from chemoresistant CRC cells could transfer ciRS‐122 across cells and promote glycolysis to reduce drug susceptibility in chemosensitive cells. This intercellular signal delivery suggests a potential novel therapeutic target and establishes a foundation for future clinical applications in drug‐resistant CRC.
Exosomes from oxaliplatin‐resistant colorectal cancer (CRC) cells transferred ciRS‐122 to oxaliplatin‐sensitive cells, enhancing glycolysis and drug resistance by promoting PKM2 expression. Furthermore, ciRS‐122 targeting through exosome‐delivered small interfering (si)RNA in vivo enhanced the drug response, indicating a novel potential approach for the reversion of oxaliplatin resistance in CRC.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Accumulating evidence has been found that circular RNA (circRNA) plays a critical role in the initiation and development of various diseases by modulating gene expression in the cytoplasm. However, ...the role of circ_0044366 (termed circ29) in gastric cancer (GC) has yet to be elusive. We detected that exosomal circ29 was confirmed to be highly expressed in GC and can significantly impair the proliferation, migration, tube formation of HUVEC by exosomal communication. Interestingly, this effect could be blocked by the effect of miR-29a. In brief, we confirmed that circ29, as a sponge of miR-29a, plays a responsible role in the occurrence and development of GC by regulating the VEGF pathway. Therefore, it may be used as a potential target for the treatment of GC.
•circ_0044366 was highly expressed in gastric cancer.•circ_0044366 could be used as a sponge of miR-29a.•circ_0044366 can regulate the function of vascular cells through miR-29a/VEGF.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In quantitative real-time polymerase chain reaction (qRT-PCR) experiments, accurate and reliable target gene expression results are dependent on optimal amplification of house-keeping genes (HKGs). ...RNA-seq technology offers a novel approach to detect new HKGs with improved stability. Goat (Capra hircus) is an economically important livestock species and plays an indispensable role in the world animal fiber and meat industry. Unfortunately, uniform and reliable HKGs for skin research have not been identified in goat. Therefore, this study seeks to identify a set of stable HKGs for the skin tissue of C. hircus using high-throughput sequencing technology.
Based on the transcriptome dataset of 39 goat skin tissue samples, 8 genes (SRP68, NCBP3, RRAGA, EIF4H, CTBP2, PTPRA, CNBP, and EEF2) with relatively stable expression levels were identified and selected as new candidate HKGs. Commonly used HKGs including SDHA and YWHAZ from a previous study, and 2 conventional genes (ACTB and GAPDH) were also examined. Four different experimental variables: (1) different development stages, (2) hair follicle cycle stages, (3) breeds, and (4) sampling sites were used for determination and validation. Four algorithms (geNorm, NormFinder, BestKeeper, and ΔCt method) and a comprehensive algorithm (ComprFinder, developed in-house) were used to assess the stability of each HKG. It was shown that NCBP3 + SDHA + PTPRA were more stably expressed than previously used genes in all conditions analysis, and that this combination was effective at normalizing target gene expression. Moreover, a new algorithm for comprehensive analysis, ComprFinder, was developed and released.
This study presents the first list of candidate HKGs for C. hircus skin tissues based on an RNA-seq dataset. We propose that the NCBP3 + SDHA + PTPRA combination could be regarded as a triplet set of HKGs in skin molecular biology experiments in C. hircus and other closely related species. In addition, we also encourage researchers who perform candidate HKG evaluations and who require comprehensive analysis to adopt our new algorithm, ComprFinder.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Immune-based therapy is a promising type of treatment for hepatocellular carcinoma (HCC) but has only been partially successful due to the high heterogeneity in HCC tumor. The differences in the ...degree of tumor cell progression and in the activity of tumor immune microenvironment could lead to varied clinical outcome. Accurate subgrouping for recurrence risk is an approach to address the issue of such heterogeneity. It remains under investigation as whether integrating quantitative whole slide image (WSI) features with the expression profile of immune marker genes can improve the risk stratification, and whether clinical outcome prediction can assist in understanding molecular biology that drives the outcome.
We included a total of 231 patients from the Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) project. For each patient, we extracted 18 statistical metrics corresponding to a global region of interest and 135 features regarding nucleus shape from WSI. A risk score was developed using these image features with high-dimensional survival modeling. We also introduced into the model the expression profile of 66 representative marker genes relevant to currently available immunotherapies. We stratified all patients into higher and lower-risk subgroup based on the final risk score selected from multiple models generated, and further investigated underlying molecular mechanisms associated with the risk stratification.
One WSI feature and three immune marker genes were selected into the final recurrence-free survival (RFS) prediction model following the best integrated modeling framework. The resultant score showed a significantly improved prediction performance on the test dataset (mean time-dependent AUCs = 0.707) as compared to those of other types (e.g: mean time-dependent AUCs of AJCC tumor stage = 0.525) of input data integration. To assess that the risk score could provide a higher-resolution risk stratification, a lower-risk subgroup (or a higher-risk subgroup) was arbitrarily assigned according to score falling below (or above) the median score. The lower risk subgroup had significantly longer median RFS time than that of the higher-risk patients (median RFS = 903 vs. 265 days, log-rank test p-value< 0.0001). Additionally, the higher-risk subgroup, in contrast to the lower-risk patients were characterized with a significant downregulation of immune checkpoint genes, suppressive signal in tumor immune response pathways, and depletion of CD8 T cells. These observations for the higher-risk subgroup suggest that new targets for adoptive or checkpoint-based combined systemic therapies may be useful.
We developed a novel prognostic model to predict RFS for HCC patients, using one feature that can be automatically extracted from routine histopathological images, as well as the expression profiles of three immune marker genes. The methodology used in this paper demonstrates the feasibility of developing prognostic models that provide both useful risk stratification along with valuable biological insights into the underlying characteristics of the subgroups identified.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cervical cancer is a widespread malignancy among women, leading to a substantial global health impact. Despite extensive research, our understanding of the basic molecules and pathogenic processes of ...cervical squamous cell carcinoma is still insufficient. This investigation aims to uncover immune-related genes linked to CESC and delineate their functions. Leveraging data from the GEO and ImmPort databases, a total of 22 immune-related genes were identified. Multiple tools, including DAVID, the human protein atlas, STRING, GeneMANIA, and TCGA, were employed to delve into the expression and roles of these immune genes in CESC, alongside their connections to the disease's pathological features. Through RT-PCR, the study confirmed notable disparities in
8 and
10 mRNA expression between CESC and normal cervical tissue. The TCGA dataset's immune-related information reinforced the association of
8 and
10 with immune infiltration in CESC. This research sheds light on the potential of
8 and
10 as promising therapeutic targets and essential prognostic factors for individuals diagnosed with CESC.
Hypoxia is one of the important properties of solid tumor. However, oxygen supply within tumors is generally heterogeneous according to the distance from the nearest blood vessel. The discrepancy of ...metastatic potential exists between hypoxic cancer cells and relatively normoxic cancer cells. But the molecular mechanism remains poorly understood.
Differential expression of circRNAs in plasma exosomes of CRC patients and normal subjects was performed by screening. Exosomes were isolated by ultra-centrifugation and RNA expressions were determined by RT-qPCR. The migratory capacity of cells was performed by high intension imaging, wound healing assay and transwell chamber migration assay.
Circ-133 is enriched in the plasma exosomes of CRC patients and increased with the disease progression. Exosomal circ-133 derived from hypoxic cells delivered into normoxic cells and promoted cancer metastasis by acting on miR-133a/GEF-H1/RhoA axis. Meanwhile, animal experiments revealed that knockdown of circ-133 can inhibit tumor metastasis. Circ-133 is expected to be a new biomarker for monitoring tumor progression and might be a novel therapeutic target.
Hypoxia-derived exosomal circ-133 transported into normaxic cancer cells and promoted cell migration via miR-133a/GEF-H1/RhoA axis. This study reveals a potential mechanism for that the intra-tumor heterogeneity of oxygen promote cancer progression.
To investigate whether preoperative localization of sentinel lymph node (SLN) by contrast-enhanced ultrasound (CEUS) can further improve the accuracy of sentinel lymph node biopsy (SLNB).
Collect ...published literatures or conference reports by searching electronic databases. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) evaluation method is used to evaluate the quality of the screened literatures. The pooled risk ratio of cancer metastasis of SLN identified by CEUS (CE-SLN) compared with SLN not identified by CEUS (nonCE-SLN) is calculated, and the pooled diagnostic accuracy of CE-SLN for pathological status of all SLNs is also evaluated.
Through search and screening, a total of 16 studies were included, of which five and seven studies, respectively, entered the meta-analysis of metastatic risk ratio and diagnostic accuracy. The localization rate of preoperative CEUS for sentinel lymph nodes was 70 to 100%. The meta-analysis shows that the risk of metastasis of SLN identified by CEUS is significantly higher than that not identified by CEUS, 26.0% vs 4.6%, and risk ratio (RR) is 6.08 (95% CI 4.17-8.85). In early-stage breast cancer, the pathological status of CE-SLN is a good representative of all SLNs, with a pooled sensitivity of 98% (95% CI 0.94-1.00), pooled specificity of 100% (95% CI 0.99-1.00), diagnostic odds ratio (DOR) of 2153.18 (95% CI 476.53-9729.06), and area under the subject receiver operating characteristic (SROC) curve of 0.9968.
In early-stage breast cancer, preoperative localization of SLN by CEUS is expected to further improve the accuracy of sentinel lymph node biopsy (SLNB).
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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