Delphian lymph node metastasis is a novel indicator of tumor aggressiveness and poor prognosis in papillary thyroid cancer.

BACKGROUND AND OBJECTIVES: Although the significance of Delphian lymph nodes (DLNs) in patients with papillary thyroid carcinoma (PTC) has been reported, all studies have been based on a small sample size and lack a direct statement concerning prognosis. METHODS: A total of 904 consecutive patients were enrolled in the current study, and all patients were divided into two groups (DLN-positive and DLN-negative) according to the presence of DLN metastasis. RESULTS: DLN was detected in 687 patients (76.0%), and 123 (17.9%) had DLN metastasis. Compared to those in the DLN-negative group, the proportion of other central lymph node (CLN) metastases, mean number of metastatic CLNs, and mean metastatic CLN ratio were higher in the DLN-positive group (86.2 vs. 50.2%, 6.70 ± 5.19 vs. 1.60 ± 2.37, and 0.54 ± 0.25 vs. 0.18 ± 0.26, respectively; p < .001). The same phenomena were observed in the metastatic lateral lymph nodes (LLNs) between the DLN-positive and DLN-negative groups (52.0 vs. 15.4%, 7.28 ± 6.08 vs. 3.38 ± 3.73, and 0.23 ± 0.15 vs. 0.13 ± 0.12, respectively; p < .001). Patients in the DLN-positive group had shorter LLN metastasis-free survival and distant metastasis-free survival than patients in the DLN-negative group (93.5% vs. 98.6% and 95.9% vs. 98.8%, respectively, p < .05). CONCLUSIONS: DLN metastasis in PTC is associated with tumor aggressiveness and a poor prognosis.

Evaluation of MiR-1908-3p as a novel serum biomarker for breast cancer and analysis its oncogenic function and target genes.

BACKGROUND: Breast cancer is one of the most common tumors for women globally. Various miRNAs have been reported to play a crucial role in breast cancer, however the clinical significance of miR-1908-3p in breast cancer remains unclear. The present study aimed to explore the role of miR-1908-3p in breast cancer. METHODS: The expression of miR-1908-3p was detected in 50 pairs of breast cancer tissues and adjacent normal tissues, 60 breast cancer patient serum and 60 healthy volunteer serum. The functional roles of miR-1908-3p in breast cancer cells such as proliferation, migration and invasion were evaluated using CCK8, SRB, wound healing and transwell chambers. In addition, bioinformatics tools were used to identify potential targets of miR-1908-3p. RESULTS: The results showed that the expression of miR-1908-3p were increased in breast cancer tissues and serum compared with normal breast tissues and serum of healthy volunteers respectively. Furthermore, the young breast cancer patients and HER2-positive patients had a higher level of tissues' miR-1908-3p than elder breast cancer patients and HER2-negative patients, respectively. The young breast cancer patients had a higher level of serum miR-1908-3p than elder breast cancer patients, ROC analysis suggested that miR-1908-3p had the potential as a promising serum diagnostic biomarker of breast cancer. Up-regulation of miR-1908-3p promoted the cells proliferation, migration and invasion while knockdown of miR-1908-3p inhibited these processes in breast cancer cell MCF-7 and MDA-MB-231. The potential target genes of miR-1908-3p in breast cancer included ID4, LTBP4, GPM6B, RGMA, EFCAB1, ALX4, OSR1 and PPARA. Higher expression of these eight genes correlated with a better prognosis for breast cancer patients. CONCLUSIONS: These results suggest that miR-1908-3p may exert its oncogenic functions via suppression of these eight genes in breast cancer.

Metabolite profiling of human blood by surface-enhanced Raman spectroscopy for surgery assessment and tumor screening in breast cancer.

Mammography, a standard screening method for breast cancer, is effective for reducing the rate of death; however, it suffers from frequent false positive alarm and radiation risk. Besides, surgery treatment has a vital impact on the clinical outcomes of breast cancer, offering enormous benefits for breast cancer care and management. In this work, we analyzed the peripheral blood sample from breast cancer patients with pre- and post-surgery and healthy volunteers using label-free surface-enhanced Raman spectroscopy technology based on silver nanoparticles. Results showed that distinct patterns of blood belonging to specific subjects could be profiled, and corresponding accuracies of 95% and 100% were achieved by multivariate diagnostic algorithm for pre-surgery vs. post-surgery and pre-surgery vs. normal groups, respectively, providing a unique blood analysis method for surgery evaluation as well as tumor screening in breast cancer. Graphical abstract.

In vivo imaging of immediate early gene expression reveals layer-specific memory traces in the mammalian brain.

The dynamic processes of formatting long-term memory traces in the cortex are poorly understood. The investigation of these processes requires measurements of task-evoked neuronal activities from large numbers of neurons over many days. Here, we present a two-photon imaging-based system to track event-related neuronal activity in thousands of neurons through the quantitative measurement of EGFP proteins expressed under the control of the EGR1 gene promoter. A recognition algorithm was developed to detect GFP-positive neurons in multiple cortical volumes and thereby to allow the reproducible tracking of 4,000 neurons in each volume for 2 mo. The analysis revealed a context-specific response in sparse layer II neurons. The context-evoked response gradually increased during several days of training and was maintained 1 mo later. The formed traces were specifically activated by the training context and were linearly correlated with the behavioral response. Neuronal assemblies that responded to specific contexts were largely separated, indicating the sparse coding of memory-related traces in the layer II cortical circuit.

The clinicopathologic differences of central lymph node metastasis in predicting lateral lymph node metastasis and prognosis in papillary thyroid cancer associated with or without Hashimoto's thyroiditis.

This study aims to evaluate the difference of central lymph node metastases (LNM) in papillary thyroid carcinoma (PTC) associated with or without Hashimoto's thyroiditis (HT) in predicting lateral node metastasis. A retrospective case control study was performed. Patients (1276) with PTC who underwent a total or near-total thyroidectomy with at least one lymph node dissection in our institution were retrospectively reviewed. All patients were divided into two groups (HT-group and non-HT group) according to the pathological diagnosis. In HT-group, the incidence of both central and lateral LNM was lower compared with non-HT group. The average of central metastatic lymph node radio (LNR) was also lower than that in Non-HT group. The multivariate analysis showed that the number of metastatic central LNs (HT ≥ 4, Non-HT ≥ 2) and the central LNR (HT ≥ 0.4, Non-HT ≥ 0.6) were independently associated with lateral LNM. Patients with HT need larger primary tumor size, more positive central LN and higher LNR to predict the presence of lateral LNM. HT may protect against central and lateral LNM in PTC. The number of positive central LNs and central LNR in PTC could be used to determine the presence of lateral LNM and inform postoperative follow-up.

Ultrasound guided double injection of blood into cisterna magna: a rabbit model for treatment of cerebral vasospasm.

BACKGROUND: Double injection of blood into cisterna magna using a rabbit model results in cerebral vasospasm. An unacceptably high mortality rate tends to limit the application of model. Ultrasound guided puncture can provide real-time imaging guidance for operation. The aim of this paper is to establish a safe and effective rabbit model of cerebral vasospasm after subarachnoid hemorrhage with the assistance of ultrasound medical imaging. METHODS: A total of 160 New Zealand white rabbits were randomly divided into four groups of 40 each: (1) manual control group, (2) manual model group, (3) ultrasound guided control group, and (4) ultrasound guided model group. The subarachnoid hemorrhage was intentionally caused by double injection of blood into their cisterna magna. Then, basilar artery diameters were measured using magnetic resonance angiography before modeling and 5 days after modeling. RESULTS: The depth of needle entering into cisterna magna was determined during the process of ultrasound guided puncture. The mortality rates in manual control group and model group were 15 and 23 %, respectively. No rabbits were sacrificed in those two ultrasound guided groups. We found that the mortality rate in ultrasound guided groups decreased significantly compared to manual groups. Compared with diameters before modeling, the basilar artery diameters after modeling were significantly lower in manual and ultrasound guided model groups. The vasospasm aggravated and the proportion of severe vasospasms was greater in ultrasound guided model group than that of manual group. In manual model group, no vasospasm was found in 8 % of rabbits. CONCLUSIONS: The ultrasound guided double injection of blood into cisterna magna is a safe and effective rabbit model for treatment of cerebral vasospasm.

Clinical Evaluation of Coronary In-Stent Restenosis Using Dual-Source Computed Tomography.

OBJECTIVE: To explore the feasibility of dual-source computed tomography (DSCT) in the evaluation of coronary in-stent restenosis (ISR) by comparing the results of DSCT and selective coronary angiography (CAG). METHODS: In-stent restenosis examination results from DSCT were compared with those obtained using CAG. RESULTS: Among 173 stents studied, 156 yielded good quality images when evaluated with DSCT. CAG identified 38 ISR cases, while DSCT found 40. Among the 112 stents in the study with an inner diameter ≥3.0 mm, CAG identified 29 as having ISR, while DSCT reported the same finding in 30; among the 44 stents with inner diameter <3.0 mm, CAG identified ISR in 9, while DSCT found ISR in 10. CONCLUSIONS: Stent inner diameter is a key factor influencing the imaging of the stent lumen. DSCT demonstrated a higher negative predictive value in ISR assessment, suggesting that it could replace CAG for assessing the patency of stents with a larger inner diameter (≥3 mm).

Differentiation between primary central nervous system lymphomas and gliomas according to pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging.

Purpose: It is difficult to differentiate between primary central nervous system lymphoma and primary glioblastoma due to their similar MRI findings. This study aimed to assess whether pharmacokinetic parameters derived from dynamic contrast-enhanced MRI could provide valuable insights for differentiation. Methods: Seventeen cases of primary central nervous system lymphoma and twenty-one cases of glioblastoma as confirmed by pathology, were retrospectively analyzed. Pharmacokinetic parameters, including Ktrans, Kep, Ve, and the initial area under the Gd concentration curve, were measured from the enhancing tumor parenchyma, peritumoral parenchyma, and contralateral normal parenchyma. Statistical comparisons were made using Mann-Whitney U tests for Ve and Matrix Metallopeptidase-2, while independent samples t-tests were used to compare pharmacokinetic parameters in the mentioned regions and pathological indicators of enhancing tumor parenchyma, such as vascular endothelial growth factor and microvessel density. The pharmacokinetic parameters with statistical differences were evaluated using receiver-operating characteristics analysis. Except for the Wilcoxon rank sum test for Ve, the pharmacokinetic parameters were compared within the enhancing tumor parenchyma, peritumoral parenchyma, and contralateral normal parenchyma of the primary central nervous system lymphomas and glioblastomas using variance analysis and the least-significant difference method. Results: Statistical differences were observed in Ktrans and Kep within the enhancing tumor parenchyma and in Kep within the peritumoral parenchyma between these two tumor types. Differences were also found in Matrix Metallopeptidase-2, vascular endothelial growth factor, and microvessel density within the enhancing tumor parenchyma of these tumors. When compared with the contralateral normal parenchyma, pharmacokinetic parameters within the peritumoral parenchyma and enhancing tumor parenchyma exhibited variations in glioblastoma and primary central nervous system lymphoma, respectively. Moreover, the receiver-operating characteristics analysis showed that the diagnostic efficiency of Kep in the peritumoral parenchyma was notably higher. Conclusion: Pharmacokinetic parameters derived from dynamic contrast-enhanced MRI can differentiate primary central nervous system lymphoma and glioblastoma, especially Kep in the peritumoral parenchyma.

Homogentisic acid metabolism inhibits papillary thyroid carcinoma proliferation through ROS and p21-induced cell cycle arrest.

Thyroid cancer is one of the most common primary endocrine malignancies worldwide, and papillary thyroid carcinoma (PTC) is the predominant histological type observed therein. Although PTC has been studied extensively, our understanding of the altered metabolism and metabolic profile of PTC tumors is limited. We identified that the content of metabolite homogentisic acid (HGA) in PTC tissues was lower than that in adjacent non-cancerous tissues. We evaluated the potential of HGA as a novel molecular marker in the diagnosis of PTC tumors, as well as its ability to indicate the degree of malignancy. Studies have further shown that HGA contributes to reactive oxygen species (ROS) associated oxidative stress, leading to toxicity and inhibition of proliferation. In addition, HGA caused an increase in p21 expression levels in PTC cells and induced G1 arrest. Moreover, we found that the low HGA content in PTC tumors was due to the low expression levels of tyrosine aminotransferase (TAT) and p-hydroxyphenylpyruvate hydroxylase (HPD), which catalyze the conversion of tyrosine to HGA. The low expression levels of TAT and HPD are strongly associated with a higher probability of PTC tumor invasion and metastasis. Our study demonstrates that HGA could be used to diagnose PTC and provides mechanisms linking altered HGA levels to the biological behavior of PTC tumors.

68Ga-FAPI Versus 18F-FDG PET/CT in Evaluating Newly Diagnosed Breast Cancer Patients: A Head-to-Head Comparative Study.

PURPOSE: This study aimed to compare the performance of 68Ga-FAPI and 18F-FDG PET/CT in the evaluation of patients with newly diagnosed breast cancer. METHODS: Thirty-four women with newly diagnosed breast cancer who underwent both 68Ga-FAPI and 18F-FDG PET/CT within 1 week were prospectively included in the study. The imaging characteristics of primary lesions, diagnostic efficiency of lymph node metastasis (LNM), and accuracy of N stage evaluation between 2 PET/CTs were compared. RESULTS: 68Ga-FAPI showed higher SUVmax (11.06 ± 5.48 vs 8.33 ± 6.07, P = 0.02) and tumor-to-background ratio (15.32 ± 10.33 vs 8.25 ± 5.51, P < 0.001) than 18F-FDG in primary tumors. 68Ga-FAPI SUVmax was positively correlated with the pathological grade of the primary lesions and the final stage of the patients (P < 0.001). The specificity and accuracy of 68Ga-FAPI was higher than that of 18F-FDG in the diagnosis of LNMs on patient-based and lesion-based analysis (P < 0.001). The accuracy for the evaluation of N stage and N0 axillar status was 91.2% (31/34) and 85.7% (12/14) for 68Ga-FAPI, and 73.5% (25/34) and 42.9% (6/14) for 18F-FDG, respectively. CONCLUSIONS: The 68Ga-FAPI SUVmax was positively correlated with the pathological grade of the primary lesions and the final stage of the patients. 68Ga-FAPI PET/CT has higher accuracy than 18F-FDG in the evaluation of N stage, especially N0 axillar status, which is helpful to improve the treatment strategy for breast cancer patients.

Construction of a risk model based on N6 -methyladenosinerelated lncRNAs for predicting the prognosis of breast cancer.

N6-methyladenosine modification and lncRNAs are closely related to the prognosis and immunotherapy response of breast cancer patients. LncRNAs related to m6 A-associated genes were predicted based on coexpression analysis of the TCGA database. We established a novel 7-m6 A-associated lncRNA signature for predicting patient prognosis and validated it. The model was significantly correlated with survival time and survival status and was an independent predictor of overall survival (OS). Except for the M1 disease group, the model had good predictive value for OS in different subgroups. We constructed a prognostic model based on 7 m6 A-associated lncRNAs in breast cancer. This model could serve as an independent prognostic factor with tremendous predictive ability for breast cancer patients.

68Ga-Labeled Fibroblast Activation Protein Inhibitor PET/CT for the Early and Late Prediction of Pathologic Response to Neoadjuvant Chemotherapy in Breast Cancer Patients: A Prospective Study.

68Ga-labeled fibroblast activation protein inhibitor (68Ga-FAPI) PET/CT has demonstrated promising clinical results, with a higher SUVmax and tumor-to-background ratio (TBR) in breast cancer (BC) patients than 18F-FDG PET/CT. Here, we aimed to evaluate the suitability of 68Ga-FAPI PET/CT for the early and late prediction of the pathologic response to neoadjuvant chemotherapy (NAC) in BC. Methods: Twenty-two consecutive patients with newly diagnosed BC and an indication for NAC were prospectively included. All patients underwent standard chemotherapy and 68Ga-FAPI PET/CT at baseline, after 2 cycles of NAC (PET2), and 1 wk before surgery (PET3). SUVmax was measured in the primary tumor region and positive regional lymph nodes. The expression of fibroblast activation protein in the primary lesion was analyzed by immunohistochemistry. Results: Seven patients (31.8%) achieved a pathologic complete response (pCR), and 15 (68.2%) had residual tumors. Thirteen patients (59.1%) showed concentric withdrawal of the primary tumor, and 9 (40.9%) showed diffuse withdrawal. Between PET2 and PET3, the ΔSUVmax of the primary tumor (R 2 = 0.822; P = 0.001) and metastatic lymph nodes (R 2 = 0.645; P = 0.002) were significantly correlated. The absolute values of SUVmax and TBR at PET2 and PET3 were lower in patients with pCR than in those without pCR (P < 0.05). Moreover, a larger ΔSUVmax at any time point was strongly associated with pCR (P < 0.05). Similar downward trends in SUVmax, TBR, and ΔSUVmax were observed in the pattern of primary tumor reduction. For predicting pCR, the optimal cutoff values for ΔSUVmax after 2 chemotherapy cycles, ΔSUVmax before surgery, TBR after 2 chemotherapy cycles, and TBR before surgery of the primary tumor were 3.4 (area under the curve [AUC], 0.890), 1.1 (AUC, 0.978), -63.8% (AUC, 0.879), -90.8% (AUC, 0.978), 7.6 (AUC, 0.848), and 1.4 (AUC, 0.971), respectively. Immunohistochemistry showed that the SUVmax and TBR of 68Ga-FAPI PET/CT were positively correlated with fibroblast activation protein expression (P < 0.001 for both). Conclusion: Assessment of early changes in 68Ga-FAPI uptake during NAC by 68Ga-FAPI PET/CT can predict pCR and primary tumor concentric withdrawal in BC patients. 68Ga-FAPI PET/CT has great potential for the early and late prediction of the pathologic response to NAC in BC.

Targeting c-Jun inhibits fatty acid oxidation to overcome tamoxifen resistance in estrogen receptor-positive breast cancer.

Tamoxifen-based endocrine therapy remains a major adjuvant therapy for estrogen receptor (ER)-positive breast cancer (BC). However, many patients develop tamoxifen resistance, which results in recurrence and poor prognosis. Herein, we show that fatty acid oxidation (FAO) was activated in tamoxifen-resistant (TamR) ER-positive BC cells by performing bioinformatic and functional studies. We also reveal that CPT1A, the rate-limiting enzyme of FAO, was significantly overexpressed and that its enzymatic activity was enhanced in TamR cells. Mechanistically, the transcription factor c-Jun was activated by JNK kinase-mediated phosphorylation. Activated c-Jun bound to the TRE motif in the CPT1A promoter to drive CPT1A transcription and recruited CBP/P300 to chromatin, catalysing histone H3K27 acetylation to increase chromatin accessibility, which ensured more effective transcription of CPT1A and an increase in the FAO rate, eliminating the cytotoxic effects of tamoxifen in ER-positive BC cells. Pharmacologically, inhibiting CPT1A enzymatic activity with the CPT1 inhibitor etomoxir or blocking c-Jun phosphorylation with a JNK inhibitor restored the tamoxifen sensitivity of TamR cells. Clinically, high levels of phosphorylated c-Jun and CPT1A were observed in ER-positive BC tissues in patients with recurrence after tamoxifen therapy and were associated with poor survival. These results indicate that the assessment and targeting of the JNK/c-Jun-CPT1A-FAO axis will provide promising insights for clinical management, increased tamoxifen responses and improved outcomes for ER-positive BC patients.

Magnetic resonance analysis of deep cerebral venous vasospasm after subarachnoid hemorrhage in rabbits.

Objective: Arterial spasm is proved to be an inducer of cerebral ischemia and cerebral infarction, while when a venous spasm occurs, cerebral edema is seen to be caused by a disturbance in cerebral blood flow. However, it is unclear and unproven whether venous spasm occurs after subarachnoid hemorrhage (SAH). To provide the theoretical basis for treating cerebral vasospasm after SAH, magnetic resonance imaging (MRI) was employed to observe the changes in the diameter of deep cerebral veins in rabbits after SAH. Methods: Fourteen New Zealand rabbits were randomly divided into the SAH group (n = 10) and the normal saline group (NS group, n = 4). Specifically, the SAH models were established by the ultrasound-guided double injections of blood into cisterna magna. Moreover, the MRI was performed to observe the changes in the diameter of deep cerebral veins (internal cerebral vein, basilar vein, and great cerebral vein) and basilar artery before modeling (0 d) and 1, 3, 5, 7, 9, and 11 d after modeling. Results: In the SAH group, the diameter of the basilar artery showed no evident change on the 1st d. However, it became narrower obviously on the 3rd d and 5th d, and the stenosis degree was more than 30%. The diameter gradually relieved from 7th to 9th d, and finally returned to normal on the 11th d. Moreover, the diameter of the internal cerebral vein significantly narrowed on the 1st d, the stenosis degree of which was 19%; the stenosis then relieved slightly on the 3rd d (13%), reached the peak (34%) on the 5th d, and gradually relieved from 7th d to 11th d. Moreover, the stenosis degree of the basilar vein was 18% on the 1st d, 24% on the 3rd d, and reached the peak (34%) on the 5th d. Conclusion: After SAH in rabbits, the cerebral vasospasm was seen to occur in the basilar artery, and likewise, spasmodic changes took place in the deep cerebral vein. Furthermore, the time regularity of spasmodic changes between the cerebral vein and basilar artery was of significant difference, indicating that the venous vasospasm resulted in active contraction.

Rolling circle amplification (RCA) -based biosensor system for the fluorescent detection of miR-129-2-3p miRNA.

Herein, a versatile fluorescent bioanalysis platform for sensitive and specific screening of target miRNA (miR-129-2-3p) was innovatively designed by applying target-induced rolling circle amplification (RCA) for efficient signal amplification. Specifically, miR-129-2-3p was used as a ligation template to facilitate its ligation with padlock probes, followed by an RCA reaction in the presence of phi29 DNA polymerase. The dsDNA fragments and products were stained by SYBR Green I and then detected by fluorescence spectrophotometry. As a result, miR-129-2-3p concentrations as low as 50 nM could be detected. Furthermore, the expression of miR-129-2-3p in breast cancer patients was about twice that in healthy people. Therefore, the results indicated that the RCA-based biosensor system could be a valuable platform for miRNA detection in clinical diagnosis and biomedical study.

Application of competing risk model in the prognostic prediction study of patients with follicular thyroid carcinoma.

BACKGROUND: Follicular thyroid carcinoma (FTC) is an indolent carcinoma. The cumulative incidence of death from patients with FTC and the nomogram built based on the competing risks model have not been described. METHODS: The data from patients diagnosed with primary FTC were identified and extracted from the surveillance, epidemiology, and end results (SEER) program (1988-2015). The cumulative incidence function was utilized to calculate the likelihood of death resulting from thyroid cancer and other causes, respectively. Gray's test was used to examine the difference in the cumulative incidence of death between the groups. A tenfold cross-validation was applied to assess the discrimination and calibration of the model. RESULTS: A total of 9210 patients diagnosed with primary FTC were included. The median follow-up time was 92 months (1-347 months). The 5-year, 10-year, and 20-year probabilities of death from FTC were 2.84%, 5.23%, and 8.61%, respectively. The age at diagnosis, sex, tumor size, pathological subtypes, tumor extension, lymph node involvement, as well as surgical and radiotherapy methods used, were related to the cumulative incidence of death. Multivariate analysis identified several risk factors for patient survival. The model behaved well in terms of performance. A nomogram based on the model allowed the prediction of the probability of death among patients with FTC. CONCLUSIONS: The prognosis of FTC is excellent. The likelihood of death caused by thyroid cancer increases with age. Male sex, tumors larger than 4 cm, invasion, extrathyroidal extension, lymph node involvement, and distant metastases increase the risk of dying of thyroid carcinoma. The nomogram constructed on the basis of the model is potentially useful for both clinicians and patients.

Parameters of MR perfusion-weighted imaging predict the response and prognosis to high-dose methotrexate-based chemotherapy in immunocompetent patients with primary central nervous system lymphoma.

To investigate the effectiveness of dynamic susceptibility contrast-perfusion weighted imaging (DSCPWI) in predicting the progression-free survival (PFS) and chemotherapeutic responsiveness of primary central nervous system lymphoma (PCNSL) before high-dose methotrexate-based chemotherapy. DSCPWI was used to analyze 35 patients who had pathology-confirmed PCNSL. Relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), relative mean transit time (rMTT) and relative time to peak (rTTP) were measured on parameter maps. The 5th, 50th and 95th percentile values of every parameter were recorded for enhanced tumors and compared with the parameters of the normally contralateral hemisphere. The ratio of each PWI parameter (rrCBV, rrCBF, rrMTT, rrTTP) was obtained. The influence of parameters on responsiveness and PFS was investigated by univariate Kaplan-Meier analysis and logistic regression and Cox regression for multivariate analysis with a stepwise method. Differences in PWI parameters between the higher and lower vascular endothelial growth factor (VEGF) groups were assessed by the Mann-Whitney U test. Eighteen patients achieved a complete response (CRi) after four initial cycles of chemotherapy. Patients with lower age (p = 0.011), higher VEGF (p < 0.001), higher Karnofsky Performance Status (KPS) (p < 0.001), higher rrCBV95% (p < 0.001), higher rrCBV50% (p = 0.016), higher rrCBF95% (p < 0.001), higher rrCBF50% (p = 0.002) showed better PFS; there was difference on age(p = 0.044), KPS (p < 0.001), VEGF (p < 0.001), rrCBV95% (p = 0.018), rrCBF95% (p = 0.018), rrCBF50% (p = 0.007) between CRi and nonCRi. Multivariate analysis demonstrated that rrCBF95% (p = 0.037, 95% confidence interval: 1.065-7.206) was significantly associated with PFS. rCBV and rCBF may be used to assess the responsiveness and prognosis of PCNSL, and rCBF95% may be a better predictor.

Optical biosensor based on SERS with signal calibration function for quantitative detection of carcinoembryonic antigen.

Monitoring the levels of cancer biomarkers is essential for cancer diagnosis and evaluation. In this study, a novel sandwich type sensing platform based on surface-enhanced Raman scattering (SERS) technology was developed for the detection of carcinoembryonic antigen (CEA), with a limit of detection (LOD) of 0.258 ng/mL. In order to achieve sensitive detection of CEA in complex samples, gold nanoparticle monolayer modified with CEA antibodies and with aptamer-functionalized probes was fabricated to target CEA. Two gold layers were integrated into the SERS platform, which greatly enhanced the signal of the probe by generating tremendous "hot spots". Meanwhile, the intensity ratio of Raman probes and the second-order peak of the silicon wafer was used to achieve dynamic calibration of the Raman probe signal. Excitingly, this sensing platform was capable of distinguishing cancer patients from healthy individuals via CEA concentrations in blood samples with the accuracy of 100%. This sandwich structure SERS sensing platform presented promising potential to be an alternative tool for clinical biomarker detection in the field of cancer diagnosis.

SENP3 promotes tumor progression and is a novel prognostic biomarker in triple-negative breast cancer.

Background: The clinical outcome of triple-negative breast cancer (TNBC) is poor. Finding more targets for the treatment of TNBC is an urgent need. SENPs are SUMO-specific proteins that play an important role in SUMO modification. Among several tumor types, SENPs have been identified as relevant biomarkers for progression and prognosis. The role of SENPs in TNBC is not yet clear. Methods: The expression and prognosis of SENPs in TNBC were analyzed by TCGA and GEO data. SENP3 coexpression regulatory networks were determined by weighted gene coexpression network analysis (WGCNA). Least absolute shrinkage and selection operator (LASSO) and Cox univariate analyses were used to develop a risk signature based on genes associated with SENP3. A time-dependent receiver operating characteristic (ROC) analysis was employed to evaluate a risk signature's predictive accuracy and sensitivity. Moreover, a nomogram was constructed to facilitate clinical application. Results: The prognostic and expression effects of SENP family genes were validated using the TCGA and GEO databases. SENP3 was found to be the only gene in the SENP family that was highly expressed and associated with an unfavorable prognosis in TNBC patients. Cell functional experiments showed that knockdown of SENP3 leads to growth, invasion, and migration inhibition of TNBC cells in vitro. By using WGCNA, 273 SENP3-related genes were identified. Finally, 11 SENP3-related genes were obtained from Cox univariate analysis and LASSO regression. Based on this, a prognostic risk prediction model was established. The risk signature of SENP3-related genes was verified as an independent prognostic marker for TNBC patients. Conclusion: Among SENP family genes, we found that SENP3 was overexpressed in TNBC and associated with a worse prognosis. SENP3 knockdown can inhibit tumor proliferation, invasion, and migration. In TNBC patients, a risk signature based on the expression of 11 SENP3-related genes may improve prognosis prediction. The established risk markers may be promising prognostic biomarkers that can guide the individualized treatment of TNBC patients.