Primary lung cancer is one of the most common malignant tumors in China. Approximately 60% of lung cancer patients have distant metastasis at the initial diagnosis, so it is necessary to find new ...tumor markers for early diagnosis and individualized treatment. Tumor markers contribute to the early diagnosis of lung cancer and play important roles in early detection and treatment, as well as in precision medicine, efficacy monitoring, and prognosis prediction. The pathological diagnosis of lung cancer in small biopsy specimens determines whether there are tumor cells in the biopsy and tumor type. Because biopsy is traumatic and the compliance of patients with multiple biopsies is poor, liquid biopsy has become a hot research direction. Liquid biopsies are advantageous because they are nontraumatic, easy to obtain, reflect the overall state of the tumor, and allow for real-time monitoring. At present, liquid biopsies mainly include circulating tumor cells, circulating tumor DNA, exosomes, microRNA, circulating RNA, tumor platelets, and tumor endothelial cells. This review introduces the research progress and clinical application prospect of liquid biopsy technology for lung cancer.
MicroRNA‐24‐3p (miR‐24‐3p) has been implicated as a key promoter of chemotherapy resistance in numerous cancers. Meanwhile, cancer‐associated fibroblasts (CAFs) can secret exosomes to transfer ...miRNAs, which mediate tumour development. However, little is known regarding the molecular mechanism of CAF‐derived exosomal miR‐24‐3p in colon cancer (CC). Hence, this study intended to characterize the functional relevance of CAF‐derived exosomal miR‐24‐3p in CC cell resistance to methotrexate (MTX). We identified differentially expressed HEPH, CDX2 and miR‐24‐3p in CC through bioinformatics analyses, and validated their expression in CC tissues and cells. The relationship among HEPH, CDX2 and miR‐24‐3p was verified using ChIP and dual‐luciferase reporter gene assays. Exosomes were isolated from miR‐24‐3p inhibitor–treated CAFs (CAFs‐exo/miR‐24‐3p inhibitor), which were used in combination with gain‐of‐function and loss‐of‐function experiments and MTX treatment. CCK‐8, flow cytometry and colony formation assays were conducted to determine cell viability, apoptosis and colony formation, respectively. Based on the findings, CC tissues and cells presented with high expression of miR‐24‐3p and low expression of HEPH and CDX2. CDX2 was a target gene of miR‐24‐3p and could up‐regulate HEPH. Under MTX treatment, overexpressed CDX2 or HEPH and down‐regulated miR‐24‐3p reduced cell viability and colony formation and elevated cell apoptosis. Furthermore, miR‐24‐3p was transferred into CC cells via CAF‐derived exosomes. CAF‐derived exosomal miR‐24‐3p inhibitor diminished cell viability and colony formation and increased cell apoptosis in vitro and inhibited tumour growth in vivo under MTX treatment. Altogether, CAF‐derived exosomal miR‐24‐3p accelerated resistance of CC cells to MTX by down‐regulating CDX2/HEPH axis.
Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide and the fastest growing malignancy in the United States. With a 5-year survival rate below 12%, effective ...therapies for HCC are needed. Current treatments for HCC include microwave and radiofrequency ablation, high intensity focused ultrasound, liver transplant, surgical resection, and localized embolizations. However, each of these approaches has some limitation, making it imperative to develop improved methods for sensitizing tumors prior to therapy. We hypothesized that the use of ultrasound-triggered microbubble destruction (UTMD), which sensitizes tumors to radiotherapy by inducing vascular endothelial cell apoptosis, will selectively sensitize malignant tissue to radiotherapy and improve outcomes. To test this, 18 nude rats were inoculated in the right liver lobe with Hu7.5 HCC cells and after tumor formation, received 5 Gy radiotherapy, UTMD, or UTMD prior to radiotherapy. Compared to radiotherapy alone, there was a 170% reduction in tumor growth 7 days post treatment and a 3.2X improvement in median survival time when radiotherapy was combined with UTMD. These results indicate that UTMD is an effective adjunct when combined with radiotherapy to treat HCC.
•Microbubble cavitation results in a reduction in HCC tumor vascularity.•UTMD before radiation therapy improves tumor control in an orthotopic model of HCC.•UTMD showed no effects on overall liver function tests compared to control groups.•Vascular disruption does not increase tumor hypoxia within the treatment window.
Hepatocellular cancer (HCC) has been reported to belong to one of the highly vascularized solid tumours accompanied with angiogenesis of human umbilical vein endothelial cells (HUVECs). KDM5A, an ...attractive drug target, plays a critical role in diverse physiological processes. Thus, this study aims to investigate its role in angiogenesis and underlying mechanisms in HCC. ChIP‐qPCR was utilized to validate enrichment of H3K4me3 and KDM5A on the promotor region of miR‐433, while dual luciferase assay was carried out to confirm the targeting relationship between miR‐433 and FXYD3. Scratch assay, transwell assay, Edu assay, pseudo‐tube formation assay and mice with xenografted tumours were conducted to investigate the physiological function of KDM5A‐miR‐433‐FXYD3‐PI3K‐AKT axis in the progression of HCC after loss‐ and gain‐function assays. KDM5A p‐p85 and p‐AKT were highly expressed but miR‐433 was down‐regulated in HCC tissues and cell lines. Depletion of KDM5A led to reduced migrative, invasive and proliferative capacities in HCC cells, including growth and a lowered HUVEC angiogenic capacity in vitro. Furthermore, KDM5A suppressed the expression of miR‐433 by demethylating H3K4me3 on its promoterregion. miR‐433 negatively targeted FXYD3. Depleting miR‐433 or re‐expressing FXYD3 restores the reduced migrative, invasive and proliferative capacities, and lowers the HUVEC angiogenic capacity caused by silencing KDM5A. Therefore, KDM5A silencing significantly suppresses HCC tumorigenesis in vivo, accompanied with down‐regulated miR‐433 and up‐regulated FXYD3‐PI3K‐AKT axis in tumour tissues. Lastly, KDM5A activates the FXYD3‐PI3K‐AKT axis to enhance angiogenesis in HCC by suppressing miR‐433.
Osteosarcoma, one of the common malignant tumors in the skeletal system, originates in mesenchymal tissue, and the most susceptible area of occurrence is the metaphysis with its abundant blood ...supply. Tumors are characterized by highly malignant spindle stromal cells that can produce bone-like tissue. Most of the osteosarcoma are primary, and a few are secondary. Osteosarcoma occurs primarily in children and adolescents undergoing vigorous bone growth and development. Most cases involve rapid tumor development and early blood metastasis. In recent years, research has grown in the areas of molecular biology, imaging medicine, biological materials, applied anatomy, surgical techniques, biomechanics, and comprehensive treatment of tumors. With developments in molecular biology and tissue bioengineering, treatment methods have also made great progress, especially in comprehensive limb salvage treatment, which significantly enhances the quality of life after surgery and improves the 5-year survival rate of patients with malignant tumors. This article provides a review of limb salvage, immunotherapy, gene therapy, and targeted therapy from traditional amputation to neoadjuvant chemotherapy, providing a reference for current clinical treatments for osteosarcoma.
Much of the volume of solid tumors typically exists in a chronically hypoxic microenvironment that has been shown to result in both chemotherapy and radiation therapy resistance. The purpose of this ...study was to use localized microbubble delivery to overcome hypoxia prior to therapy.
In this study, surfactant-shelled oxygen microbubbles were fabricated and injected intravenously to locally elevate tumor oxygen levels when triggered by noninvasive ultrasound in mice with human breast cancer tumors. Changes in oxygen and sensitivity to radiation therapy were then measured.
In this work, we show that oxygen-filled microbubbles successfully and consistently increase breast tumor oxygenation levels in a murine model by 20 mmHg, significantly more than control injections of saline solution or untriggered oxygen microbubbles (P < .001). Using photoacoustic imaging, we also show that oxygen delivery is independent of hemoglobin transport, enabling oxygen delivery to avascular regions of the tumor. Finally, we show that overcoming hypoxia by this method immediately prior to radiation therapy nearly triples radiosensitivity. This improvement in radiosensitivity results in roughly 30 days of improved tumor control, providing statistically significant improvements in tumor growth and animal survival (P < .03).
Our findings demonstrate the potential advantages of ultrasound-triggered oxygen delivery to solid tumors and warrant future efforts into clinical translation of the microbubble platform.
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide due to its high degree of malignancy, high incidence, and low survival rate. However, the underlying ...mechanisms of hepatocarcinogenesis remain unclear. Long non coding RNA (lncRNA) has been shown as a novel type of RNA. lncRNA by acting as ceRNA can participate in various biological processes of HCC cells, such as tumor cell proliferation, migration, invasion, apoptosis and drug resistance by regulating downstream target gene expression and cancer-related signaling pathways. Meanwhile, lncRNA can predict the efficacy of treatment strategies for HCC and serve as a potential target for the diagnosis and treatment of HCC. Therefore, lncRNA serving as ceRNA may become a vital candidate biomarker for clinical diagnosis and treatment. In this review, the epidemiology of HCC, including morbidity, mortality, regional distribution, risk factors, and current treatment advances, was briefly discussed, and some biological functions of lncRNA in HCC were summarized with emphasis on the molecular mechanism and clinical application of lncRNA-mediated ceRNA regulatory network in HCC. This paper can contribute to the better understanding of the mechanism of the influence of lncRNA-mediated ceRNA networks (ceRNETs) on HCC and provide directions and strategies for future studies.
Objectives
Current diagnosis of nonalcoholic fatty liver disease (NAFLD) relies on biopsy or MR‐based fat quantification. This prospective study explored the use of ultrasound with artificial ...intelligence for the detection of NAFLD.
Methods
One hundred and twenty subjects with clinical suspicion of NAFLD and 10 healthy volunteers consented to participate in this institutional review board‐approved study. Subjects were categorized as NAFLD and non‐NAFLD according to MR proton density fat fraction (PDFF) findings. Ultrasound images from 10 different locations in the right and left hepatic lobes were collected following a standard protocol. MRI‐based liver fat quantification was used as the reference standard with >6.4% indicative of NAFLD. A supervised machine learning model was developed for assessment of NAFLD. To validate model performance, a balanced testing dataset of 24 subjects was used. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy with 95% confidence interval were calculated.
Results
A total of 1119 images from 106 participants was used for model development. The internal evaluation achieved an average precision of 0.941, recall of 88.2%, and precision of 89.0%. In the testing set AutoML achieved a sensitivity of 72.2% (63.1%–80.1%), specificity of 94.6% (88.7%–98.0%), positive predictive value (PPV) of 93.1% (86.0%–96.7%), negative predictive value of 77.3% (71.6%–82.1%), and accuracy of 83.4% (77.9%–88.0%). The average agreement for an individual subject was 92%.
Conclusions
An ultrasound‐based machine learning model for identification of NAFLD showed high specificity and PPV in this prospective trial. This approach may in the future be used as an inexpensive and noninvasive screening tool for identifying NAFLD in high‐risk patients.
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