Cell fusion between tumor cells and macrophages promotes the metastasis of OSCC patient through the activation of the chemokine signaling pathway.

BACKGROUND: Tumor metastasis is responsible for the high mortality rate of patients with oral squamous cell carcinoma (OSCC). Although many hypotheses have been proposed to elucidate the mechanism of tumor metastasis, the origin of the metastatic tumor cells remains unclear. In this study, we explored the role of cell fusion in the formation of OSCC metastatic tumor cells. METHODS: Murine OSCC tumor cells and macrophages were fused in vitro, and the cell proliferation, migration, and phagocytosis abilities of hybrid cells and parental cells were compared. Subsequently, we compared the transcriptome differences between hybrid and parental cells. RESULTS: Murine OSCC tumor cells and macrophages were successfully fused in vitro. The cytological and molecular experimental results revealed that OSCC tumor cells obtained a migration-related phenotype after fusion with macrophages, and the migration ability of hybrid cells was related to the activation of the "chemokine signal pathway". CONCLUSION: After fusion with macrophages, the chemokine signaling pathway in OSCC tumor cells was activated, leading to metastasis.

The feasibility of discriminating BRONJ lesion bone with Raman spectroscopy.

Background: With the frequent use of Bisphosphonates (BPs), the morbidity of BP-related osteonecrosis of the jaw (BRONJ) is also increasing. However, the prevention and treatment of BRONJ is faced with enormous challenges. This study aimed to illuminate the influence of BP administration in the rat mandible and explore the feasibility of discriminating BRONJ lesion bone with Raman spectroscopy. Materials and methods: First, we explored the time- and mode-dependent effects of BP administration on the rat mandible with Raman spectroscopy. Second, the BRONJ rat model was constructed, and the lesion and healthy bone components were analyzed using Raman spectroscopy. Results: When only BPs were administered, no rats showed BRONJ symptoms, and no difference could be found in the Raman spectra. However, when combined with local surgery, six (6/8) rats showed BRONJ symptoms. The Raman spectra also showed a significant difference between the lesion and healthy bone. Conclusion: In the progression of BRONJ, BPs and local stimulation play an essential role. Both BPs administration and local stimulation need to be controlled to prevent BRONJ. Moreover, BRONJ lesion bone in rats could be discriminated with Raman spectroscopy. This novel method would become a complement in the treatment of BRONJ in the future.

Zn0.4Mg0.6Fe2O4 nanoenzyme: a novel chemo-sensitizer for the chemotherapy treatment of oral squamous cell carcinoma.

Hypoxic and acidic environments are the two main components of the microenvironment contributing to the poor efficacy of chemotherapy drugs in the treatment of oral squamous cell carcinoma (OSCC). In this study, we synthesized a series of Zn1-x Mg x Fe2O4 nanomaterials with enzyme-like properties, including catalase (CAT)-like, peroxidase (POD)-like, and glutathione (GSH)-like activity in an acidic environment. Among them, Zn0.4Mg0.6Fe2O4 performed the best and effectively increased the efficacy of doxorubicin (DOX) chemotherapy for the treatment of OSCC with reduced cardiotoxicity. Therefore, Zn0.4Mg0.6Fe2O4 could serve as a novel chemosensitizer in the treatment of OSCC.

Accurately Locating Metastatic Foci in Lymph Nodes With Lugol's Iodine-Enhanced Micro-CT Imaging.

BACKGROUND: Accurate evaluation of lymph node (LN) status is the key factor to determine the treatment and evaluate prognosis for patients with cancer. However, traditional pathological examination resulted in a 30% false-negative rate of detection of metastases in LNs. This study aimed to utilize Lugol's iodine (I2-IK)-enhanced micro-CT imaging to reveal the 3-dimensional structure of regional LNs and decrease the false-negative rate in pathological examination. METHODS: To explore the feasibility of I2-IK-enhanced micro-CT imaging in locating metastatic lesion in LNs, nonmetastatic and metastatic LNs from mice were used to mimic the imaging process. Then, the LNs from oral squamous cell carcinoma (OSCC) patients were applied to verify the value of I2-IK-enhanced micro-CT imaging in revealing LN structure and locating metastatic lesions in LNs. The glycogen content in nonmetastatic and metastatic LNs was further detected by the use of a glycogen assay kit and periodic acid-Schiff (PAS) staining to explain the imaging differences between them. RESULTS: In nude mice, 0.5% I2-IK staining for 4 h was the best parameter for normal LN. The metastatic foci in metastatic LNs were also clearly outlined in this condition. For nonmetastatic LNs from patients with OSCC, 1% I2-IK staining for 12 h was the best parameter. However, due to the increased volume of metastatic LNs, the image effect of 3% I2-IK staining for 12 h was superior to 1% I2-IK staining [tumor background ratio (TBR), 3% vs. 1%, 1.89 ± 0.10 vs. 1.27 ± 0.07, p < 0.001]. Compared with subsequent pathological sections, we found the CT intensity of metastatic foci in LNs and muscle tissues was significantly higher than in nonmetastatic regions. Meanwhile, the glycogen content of metastatic foci in LNs detected was also significantly higher than in nonmetastatic region. CONCLUSIONS: I2-IK-enhanced micro-CT imaging could identify the spatial location of metastatic foci in LNs. This will be an effective method to assist in decreasing the LN false-negative rate for cancer pathology.

Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveals distinct cancer-associated fibroblasts in head and neck squamous cell carcinoma.

BACKGROUND: The heterogeneity of cancer-associated fibroblasts (CAFs) in head and neck squamous cell carcinoma (HNSCC) has been widely acknowledged, but has not yet been elucidated. The potential roles and clinical relevance of CAFs subclusters in HNSCC progression remain obscure. METHODS: In this study, we combined single-cell and bulk tissue transcriptome profiles of HNSCC with clinical data from The Cancer Genome Atlas (TCGA). The Seurat package was used to perform single-cell RNA-seq analysis to distinguish distinct CAFs subtypes. Prognostic relevance of several CAFs markers was assessed and functional analysis was also performed. RESULTS: We identified eight CAFs subclusters; of these, seven showed enhanced expression levels in HNSCC tumor tissues compared to normal tissue, and three (clusters 0, 3, and 4) were associated with poorer overall survival. Further functional analysis revealed that cluster 0 was characterized by myofibroblasts with high alpha smooth muscle actin (aSMA) expression and enrichment in smooth muscle contraction. The cluster 3 exhibited expression of extracellular matrix (ECM)-related genes and was enriched in epithelial-mesenchymal transition (EMT)-related gene sets. Cluster 4 expressed high levels of the major histocompatibility complex (MHC) class II family, which was characterized as antigen-presenting CAFs. CONCLUSIONS: We determined CAFs heterogeneity in HNSCC. 8 CAFs subclusters were recognized and 3 of which were prognosis related. The 3 CAFs subclusters showed distinct phenotypes enriched in myofibroblast function, ECM remodeling and antigen-presenting function respectively.

Sentinel lymph node biopsy in oral cavity cancer using indocyanine green: A systematic review and meta-analysis.

This meta-analysis was conducted to evaluate the value of indocyanine green (ICG) in guiding sentinel lymph node biopsy (SLNB) for patients with oral cavity cancer. An electronic database search (PubMed, MEDLINE, Cochrane Library, Embase, and Web of Science) was performed from their inception to June 2020 to retrieve clinical studies of ICG applied to SLNB for oral cavity cancer. Data were extracted from 14 relevant articles (226 patients), and 9 studies (134 patients) were finally included in the meta-analysis according to the inclusion and exclusion criteria. The pooled sentinel lymph node (SLN) sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 88.0% (95% confidence interval [CI], 74.0-96.0), 64.0% (95% CI, 61.0-66.0), 2.45 (95% CI, 1.31-4.60), 0.40 (95% CI, 0.17-0.90), and 7.30 (95% CI, 1.74-30.68), respectively. The area under the summary receiver operating characteristic curve was 0.8805. In conclusion, ICG applied to SLNB can effectively predict the status of regional lymph nodes in oral cavity cancer.

A thermally activated delayed fluorescence photosensitizer for photodynamic therapy of oral squamous cell carcinoma under low laser intensity.

In this report, a new thermally activated delayed fluorescence (TADF) molecule [2-(4-triphenylvinyl-phenyl)-anthraquinone (TPE-AQ)] was synthesized. This nanomaterial has satisfactory photostability. Through In vitro analysis, it was found that these TADF nanoparticles (NPs) targeted lysosomes in oral cancer cells. ROS were released under irradiation with a 450-nm laser, and the growth of xenograft tumors in mouse models was inhibited in vivo. More interestingly, radiation exposure caused little damage to normal tissues due to the low irradiation intensity (mA) used in the photodynamic therapy (PDT) treatment of oral cancer. Therefore, these TADF NPs provide new possibilities for the development of new PDT drugs for biomedical applications. In future work, possible functional modifications of TADF NPs for increased potency in clinical applications will be addressed.

The Diagnostic Accuracy of Liquid Exosomal miRNAs for Cancer Detection: a Meta-Analysis.

BACKGROUND: Early diagnosis of cancer is related to a good prognosis. Noninvasive methods of body fluid diagnosis are receiving more and more attention. Many studies have shown that exosomal miRNAs in body fluids may be potential biomarkers. Therefore, we conducted a meta-analysis to assess the overall diagnostic value of liquid exosomal miRNAs for cancer. METHODS: Relevant research was retrieved from multiple electronic databases. The research quality was evaluated based on the QUADAS-2 scale in Review Manager 5.3. Diagnostic value was evaluated by data analysis using Stata 16.0, and Meta-DiSc 1.4. RESULTS: The meta-analysis included 23 articles and 79 research units. The pooled sensitivity was 0.74, specificity was 0.78, the diagnostic likelihood ratio positive was 3.55, the diagnostic likelihood ratio negative was 0.29, diagnostic OR was 14.26, and area under the curve was 0.8621. These results provide evidence for liquid exosomal miRNAs as potential biomarkers. CONCLUSIONS: Liquid exosomal miRNAs are potential biomarkers for cancer diagnosis. In particular, diagnosis based on multiple miRNAs is more valuable than a single miRNA.

Comparative study on the diagnostic value of intravenous/peritumoral injection of indocyanine green for metastatic lymph node location in patients with head and neck squamous cell carcinoma (HNSCC).

BACKGROUND: Accurate assessment of regional lymph node (LN) status is essential for the treatment of head and neck squamous cell carcinoma (HNSCC) patients. In this study, we aimed to compare the difference between intravenous injection of indocyanine green (ICG) and peritumoral injection of ICG in the location of metastatic LNs. METHODS: Twenty-nine patients were enrolled in this study with 13 patients receiving intravenous injection of ICG and 16 patients receiving peritumoral injection of ICG. During the surgery, the fluorescence-positive LNs in vivo were sent to undergo frozen section after fluorescence intensity was recorded. After the cervical LN dissection, all LNs were sorted by region, and the fluorescence intensity was recorded before the LNs were sent for paraffin section. RESULTS: During the surgery, both intravenous or peritumoral injections with near-infrared (NIR) fluorescence imaging of ICG had their respective pros and cons in vivo, with the sensitivity and specificity being 62.5%/75% and 98.1%/89.1% respectively. After the surgery, both methods could reduce the pathological workload by preselecting the LNs at-risk in the premise of accurate assessing the cervical LN stage. However, intravenous ICG administration was more valuable in determining all types of LN status according to the fluorescence intensity [area under the curve (AUC): 0.91 vs. 0.78, P<0.001]. CONCLUSIONS: With the assistance of NIR fluorescence imaging using ICG, both administration methods could reduce the postoperative complication and the pathological workload, whereas the intravenous mode of ICG administration is superior in application value.

Thymoquinone loaded calcium alginate and polyvinyl alcohol carrier inhibits the 7,12-dimethylbenz[a]anthracene-induced hamster oral cancer via the down-regulation of PI3K/AKT/mTOR signaling pathways.

Oral cancer is a multifactorial cancer that affects millions of peoples worldwide. The current exploration aimed to evaluate the mechanisms that thymoquinone nanoencapsulated carrier and its effects on 7,12-Dimethylbenz[a]anthracene (DMBA) stimulated hamster buccal pouch cancer in Syrian hamster model. Nanocarrier was characterized by SEM, TEM, FTIR analysis. The incidence of tumor, and biochemicals makers was studied through standard methods. The mRNA expression level of inflammatory markers NF-κBp50, NF-κBp65, and PI3K/AKT/mTOR markers in the buccal tissues of control and experimental animals were investigated through RT-PCR analysis. In thymoquinone (TQ) loaded calcium alginate and polyvinyl alcohol carrier (TQ/Ca-alg-PVA) no squamous cell carcinogenesis developed and others moderate dysplasia revealed differentiated form of hyperplasia and keratosis. In biochemical analyses with DMBA + TQ/Ca-alg-PVA (20 mg/kg bw) orally administered hamsters showed restored the antioxidants, detoxification, xenobiotic metabolising enzymes in DMBA induced plasma and oral tissues of hamsters. Further, mRNA expression level of NF-κBp50/p65 and PI3K/AKT/mTOR were upregulated in the DMBA alone painted hamster. In contrast, these expressions were down regulated in orally TQ/Ca-alg-PVA treated experimental animals. This ability more eligible to deregulate the inflammatory and PI3K/AKT/mTOR signaling pathway that proved it suppresses anti-invasion/metastasis activity during hamster buccal pouch carcinogenesis. From this study, we recommended that TQ/Ca-alg-PVA has documented as effective chemopreventive agents, in further many molecular machineries need to study.

Sentinel lymph node biopsy in oral cavity cancer using indocyanine green: A systematic review and meta-analysis

This meta-analysis was conducted to evaluate the value of indocyanine green (ICG) in guiding sentinel lymph node biopsy (SLNB) for patients with oral cavity cancer. An electronic database search (PubMed, MEDLINE, Cochrane Library, Embase, and Web of Science) was performed from their inception to June 2020 to retrieve clinical studies of ICG applied to SLNB for oral cavity cancer. Data were extracted from 14 relevant articles (226 patients), and 9 studies (134 patients) were finally included in the meta-analysis according to the inclusion and exclusion criteria. The pooled sentinel lymph node (SLN) sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 88.0% (95% confidence interval [CI], 74.0-96.0), 64.0% (95% CI, 61.0-66.0), 2.45 (95% CI, 1.31-4.60), 0.40 (95% CI, 0.17-0.90), and 7.30 (95% CI, 1.74-30.68), respectively. The area under the summary receiver operating characteristic curve was 0.8805. In conclusion, ICG applied to SLNB can effectively predict the status of regional lymph nodes in oral cavity cancer.

Lugol's Iodine-Enhanced Micro-CT: A Potential 3-D Imaging Method for Detecting Tongue Squamous Cell Carcinoma Specimens in Surgery.

BACKGROUND: A positive surgical margin (PSM) following oral cancer resection results in local recurrence and poor prognosis. Mono-block tumor specimens, especially from the tumor base, are difficult to evaluate. This inaccurate sampling ultimately leads to a false pathological diagnosis. Lugol's iodine (I2-IK)-enhanced micro-CT is an emerging method to image tumor specimens. This study explores the feasibility of I2-IK-enhanced micro-CT to evaluate the surgical margin for tongue squamous cell carcinoma (TSCC) specimens and to further seek optimal staining parameters. METHODS: Rabbit tongue tissues and human TSCC samples were imaged via I2-IK-enhanced micro-CT. The optimal I2-IK concentration and staining time were determined before clinical application using tissue shrinkage, micro-CT image quality, and effect on pathological diagnosis as assessment criteria. Next, 6 TSCC specimens were used to verify the process feasibility of surgical margin imaging with the optimal parameters. Finally, the possible reason by which I2-IK could enhance micro-CT imaging was validated in vitro. RESULTS: I2-IK staining influenced specimen shrinkage, micro-CT image quality, and pathological image quality in a concentration- and time-dependent manner. After comprehensively considering these indicators, 3% I2-IK staining for 48 and 12 h were found to be optimal for rabbit tongue tissues and TSCC samples, respectively. This method could provide a detailed 3-D structure of TSCC samples compared with H&E sections. Moreover, tumor and normal tissues could be differentiated by their glycogen content, which has high affinity with I2-IK. CONCLUSIONS: I2-IK-enhanced micro-CT could, thus, indicate the tumor margin and assist pathological sampling in patients with TSCC postoperation.

Functional blockade of cancer-associated fibroblasts with ultrafine gold nanomaterials causes an unprecedented bystander antitumoral effect.

Cancer-associated fibroblasts (CAFs) play a critical role in the onset and progression of malignancies, such as oral squamous cell carcinoma (OSCC), making CAFs a promising druggable target. In this study, gold nanoparticles (GNPs) exhibited unprecedented size dependent anti-CAF potential, wherein the smallest GNPs outperformed their larger counterparts. Specifically, a subset of proteins and cytokines that is responsible for the invasive outgrowth of OSCC cells was found to decrease post exposure of OSCC patient-derived CAFs to GNPs. Moreover, the administration of GNPs (3 nm in diameter) could effectively abrogate the growth of OSCC tumors in vivo, offering a novel means to manage OSCC in the clinic. Besides targeting cancer cells, our results collectively verify the feasibility of blocking dominant cells in the microenvironment to eradicate tumors, shedding light on the future design of nanomedicines.

Real-time surveillance of surgical margins via ICG-based near-infrared fluorescence imaging in patients with OSCC.

BACKGROUND: Local recurrence is the main cause of death among patients with oral squamous cell carcinoma (OSCC). This study assessed near-infrared fluorescence (NIF) imaging and spectroscopy to monitor surgical margins intraoperatively for OSCC. METHODS: Cytological and animal experiments were first performed to confirm the feasibility of monitoring surgical margins with NIF imaging and spectroscopy. Then, 20 patients with OSCC were included in the clinical trials. At 6-8 h after 0.75 mg/kg indocyanine green (ICG) injection, all patients underwent surgery with NIF imaging. During the surgery, both NIF images and quantified fluorescence intensity were acquired to monitor the surgical margins. RESULTS: In cytological and animal experiments, the results showed it was feasible to monitor surgical margins with NIF imaging and spectroscopy. Fluorescence was detected in primary tumors in all patients. The fluorescence intensities of the tumor, peritumoral, and normal tissues were 398.863 ± 151.47, 278.52 ± 84.89, and 274.5 ± 100.93 arbitrary units (AUs), respectively (P < 0.05). The SBR of tumor to peritumoral tissue and normal tissues was computed to be 1.45 ± 0.36 and 1.56 ± 0.41, respectively. After primary tumor excision, the wounds showed abnormal fluorescence in four patients (4/20), and residual cancer cells were confirmed by pathological examination in two patients (2/20). CONCLUSION: These findings confirmed the complementary value of NIF imaging during radical tumor resection of OSCC. Before tumor resection, we could utilize the fluorescence margin produced by ICG NIF imaging to determine the surgical margin. Moreover, after tumor blocks were removed, the status of surgical margin could also be evaluated rapidly by ICG NIF imaging of tumor bed and in vitro specimens.

Glutathione-sensitive and folate-targeted nanoparticles loaded with paclitaxel to enhance oral squamous cell carcinoma therapy.

In this study, a drug delivery system based on glutathione (GSH)-sensitive and folic acid (FA)-targeted nanoparticles loaded with paclitaxel (FA-PEG-S-S-PCL@PTX, FA-NPs) was developed. First, we proved that the FA receptor was significantly expressed in 95 oral squamous cell carcinoma (OSCC) specimens (57.9%). This provided feasibility to release FA-targeted nanoparticles in tumour sites for patients with OSCC. Next, FA-NPs were synthesized and characterized. In vitro, we found enhancement in FA-mediated endocytosis in the HSC3 cells with FA overexpression. Therefore, paclitaxel (PTX) from FA-NPs could be precisely released due to the disulfide bonds that were cleaved by a redox reaction. In vivo, FA-NPs could be accumulated in mice bearing HSC3 cells, where they exhibited effective antitumor effects when compared to the treatments with free PTX and PEG-S-S-PCL@PTX. In summary, this novel drug system has an opportunity to improve OSCC treatment.

The feasibility of locating the affected bone of BRONJ with indocyanine green.

The morbidity of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is also increasing with the use of bisphosphonates (BPs). Removing affected bone accurately is the most effective treatment. This study aimed to explore the feasibility of Indocyanine green (ICG)-based Near-Infrared fluorescence (NIF) imaging to remove BRONJ affected bone. Firstly, the rat model of BRONJ was constructed. And 5 mg/kg ICG were injected via tail vein, after 12 hr, the affected and healthy bone were dissected for ICG-based NIF imaging and quantification detection of fluorescence intensity. Finally, all the bone samples were sent for further pathological examination. All the affected bone tissues in rat BRONJ model were fluorescence developed with ICG. And the fluorescence developed regions were further confirmed as affected bone tissues with pathological examination. The fluorescence intensity in affected bone tissues, adjacent, and opposite bone tissues was 1.93*107 ± 2.08*106, 1.19*106 ± 2.33*105, and 1.24*106 ± 1.57*105, respectively (p < .05). Conclusions It was feasible that the extent of affected bone in rat model with BRONJ could be estimated intraoperative via ICG-based NIF imaging. This novel approach would become an auxiliary method in the treatment of patients with BRONJ in the future.

Milk-exosome based pH/light sensitive drug system to enhance anticancer activity against oral squamous cell carcinoma.

A multimodal drug delivery system targeting the tumor microenvironment is an inspiring method for treating cancer tissues, including oral squamous cell carcinomas (OSCC). Such approaches require an efficient and safe drug carrier. Bovine milk derived exosomes are ideal because the source is adequate and have advantages of both synthetic and cell-mediated nano carriers. In the present study, we developed a pH/light sensitive drug system based on milk-exosomes for OSCC therapy. It was called exosome-doxorubicin-anthracene endoperoxide derivative (Exo@Dox-EPT1, NPs). Milk-exosomes were conjugated to doxorubicin (Dox) by a pH-cleavable bond, which can rapture under an acidic microenvironment. Besides, endoperoxides and chlorin e6 (Ce6) were also loaded and the endoperoxides undergo thermal cycloreversion and release singlet oxygen to kill cancer cells. We have also investigated the body distribution, antitumor effects, and biocompatibility of the nanoparticles. The new milk-exosome-based drug delivery system showed controlled drug-release, biocompatibility and, proved to be effective in treating OSCC.

A near infrared light-triggered human serum albumin drug delivery system with coordination bonding of indocyanine green and cisplatin for targeting photochemistry therapy against oral squamous cell cancer.

To ensure site-specific drug delivery/release in tumor cells and cancer-associated fibroblasts (CAFs) and reduce the systemic toxicity of chemotherapy, a novel drug delivery system called human serum albumin-indocyanine green-cisplatin nanoparticles (HSA-ICG-DDP NPs) was developed in our study. We characterized this system in vitro and in vivo and showed synergistic effects with photodynamic therapy (PDT), photothermal therapy (PTT) and chemotherapy; thereby it can significantly improve therapeutic efficacy compared with cancer monotherapy. High expression of secreted protein acidic and rich in cysteine (SPARC) in oral squamous cell cancer (OSCC) and CAFs was also confirmed in our study. Our study also found that the cellular uptake of HSA-ICG-DDP NPs in tumor cells and CAFs can be enhanced by SPARC-mediated endocytosis. Cisplatin (DDP) release from the NPs in the tumor site can be precisely triggered by the cleavage of the coordination bond of ICG-DDP via a near infrared (NIR)-induced photothermal effect of ICG. Treatment with HSA-ICG-DDP NPs induced generation of reactive oxygen species (ROS) and cytotoxicity in SPARC-highly expressed tumor and CAFs. On in vivo treatment, HSA-ICG-DDP NPs were accumulated within the tumor tissue, where they exhibited stronger antitumor effects, compared to treatment with ICG, HSA-ICG and DDP. Therefore, this novel NIR-triggered drug release system displays potential for the improvement of OSCC treatment through its synergistic effects of PTT/PDT and chemotherapy.

Serum miR-20a and miR-486 are potential biomarkers for discriminating colorectal neoplasia: A pilot study.

AIM: Recent advances in circulating microRNAs (miRNAs) as noninvasive biomarkers have provided promising prospect in detecting colorectal cancer (CRC). However, the capability of miRNAs for detecting colorectal neoplasia (CRN, including precancerous lesions and curable stage CRCs) remains unclear. This study aimed to identify the potential of serum miRNAs (miR-20a, miR-486, miR-92a, and miR-135b) selected from the literature for discriminating CRN patients. MATERIALS AND METHODS: The serum samples from 46 CRN patients and 33 healthy controls were analyzed with quantitative reverse transcription-polymerase chain reaction. RESULTS: Serum miR-20a and miR-486 were significantly downregulated in CRN patients compared to that of in healthy controls (fold change = 0.697 and 0.696, P = 0.01 and 0.05, respectively). The serum level of miR-92a was not significantly different between two groups, while miR-135b level in serum was too low to be accurately quantified. In addition, serum miR-486 level was much more downregulated in tubulovillous adenoma and high-grade intraepithelial neoplasia patients than that of in healthy controls. For miR-20a and miR-486, the area under the receiver operating characteristic curve for discriminating CRN patients were 0.676 and 0.629, respectively, while their combined value was 0.698. No significant correlation was observed between miR-20a and miR-486 serum levels with age, gender, location, or lesion size. CONCLUSION: The results suggested that serum miR-20a and miR-486 could be potential noninvasive biomarkers for identifying CRN patients.

Nitroxide radical-modified CuS nanoparticles for CT/MRI imaging-guided NIR-II laser responsive photothermal cancer therapy.

Herein, we reported nitroxide radical-modified CuS nanoparticles (CuS-NO˙ NPs), and they exhibited a typical absorption peak at 1182 nm. Due to such a long wavelength absorbance, CuS-NO˙ NPs exhibited excellent therapeutic outcome and low damage to normal tissues. Besides, we simultaneously achieved CuS-NO˙ NPs for MRI and CT dual-modal imaging, which successfully provided a new strategy for imaging-guided tumor treatment, thus increasing potential clinical applications for cancer treatment.