MITF regulates the subcellular location of HIF1α through SUMOylation to promote the invasion and metastasis of daughter cells derived from polyploid giant cancer cells.

High concentrations of cobalt chloride (CoCl2) can induce the formation of polyploid giant cancer cells (PGCCs) in various tumors, which can produce daughter cells with strong proliferative, migratory and invasive abilities via asymmetric division. To study the role of hypoxia­inducible factor (HIF) 1α in the formation of PGCCs, colon cancer cell lines Hct116 and LoVo were used as experimental subjects. Western blotting, nuclear and cytoplasmic protein extraction and immunocytochemical experiments were used to compare the changes in the expression and subcellular localization of HIF1α, microphthalmia­associated transcription factor (MITF), protein inhibitor of activated STAT protein 4 (PIAS4) and von Hippel­Lindau disease tumor suppressor (VHL) after treatment with CoCl2. The SUMOylation of HIFα was verified by co­immunoprecipitation assay. After inhibiting HIF1α SUMOylation, the changes in proliferation, migration and invasion abilities of Hct116 and LoVo were compared by plate colony formation, wound healing and Transwell migration and invasion. In addition, lysine sites that led to SUMOylation of HIF1α were identified through site mutation experiments. The results showed that CoCl2 can induce the formation of PGCCs with the expression level of HIF1α higher in treated cells than in control cells. HIF1α was primarily located in the cytoplasm of control cell. Following CoCl2 treatment, the subcellular localization of HIF1α was primarily in the nuclei of PGCCs with daughter cells (PDCs). After treatment with SUMOylation inhibitors, the nuclear HIF1α expression in PDCs decreased. Furthermore, their proliferation, migration and invasion abilities also decreased. After inhibiting the expression of MITF, the expression of HIF1α decreased. MITF can regulate HIF1α SUMOylation. Expression and subcellular localization of VHL and HIF1α did not change following PIAS4 knockdown. SUMOylation of HIF1α occurs at the amino acid sites K391 and K477 in PDCs. After mutation of the two sites, nuclear expression of HIF1α in PDCs was reduced, along with a significant reduction in the proliferation, migration and invasion abilities. In conclusion, the post­translation modification regulated the subcellular location of HIF1α and the nuclear expression of HIF1α promoted the proliferation, migration and invasion abilities of PDCs. MITF could regulate the transcription and protein levels of HIF1α and participate in the regulation of HIF1α SUMOylation.

Amide proton transfer weighted combined with diffusion kurtosis imaging for predicting lymph node metastasis in cervical cancer.

OBJECTIVE: To investigate the value of amide proton transfer weighted (APTw) combined with diffusion kurtosis imaging (DKI) in quantitative prediction of lymph node metastasis (LNM) in cervical carcinoma (CC). METHODS: Data of 19 LNM(+) and 50 LNM(-) patients with CC were retrospectively analyzed. 3.0 T MRI scan was performed before the operation, including APTw and DKI. After post-processing, quantitative magnetization transfer ratio asymmetric at 3.5 ppm [MTRasym (3.5 ppm)], mean kurtosis (MK), and mean diffusivity (MD) maps were obtained. The MTRasym(3.5 ppm), MK, and MD values were respectively measured by two observers, and intra-class correlation coefficients (ICC) were used to test the consistency of the results. The independent samples t-test or Mann-Whitney U test was used to compare the differences in the values of each parameter. The ROC curve was used to analyze the predictive performance of parameters with significant differences and their combination parameter. RESULTS: The two observers had good agreement in the measurement of each data (ICC > 0.75). The MTRasym(3.5 ppm) and MK values of the LNM(+) group(3.260 ± 0.538% and 0.531 ± 0.202) were higher than those of the LNM(-) group(2.698 ± 0.597% and 0.401 ± 0.148) (P < 0.05), while there was no significant difference in MD values between the two groups(P > 0.05). The area under the curves (AUCs) of MTRasym(3.5 ppm), MK value, and MTRasym(3.5 ppm) + MK value were 0.763, 0.716, and 0.813, respectively, when predicting LNM status of CC. CONCLUSION: APTw and DKI can quantitatively predict LNM status of CC, which is of importance in clinical diagnosis and treatment.

Multimodal MRI for Estimating Her-2 Gene Expression in Endometrial Cancer.

PURPOSE: To assess the value of multimodal MRI, including amide proton transfer-weighted imaging (APT), diffusion kurtosis imaging (DKI), and T2 mapping sequences for estimating human epidermal growth factor receptor-2 (Her-2) expression in patients with endometrial cancer (EC). METHODS: A total of 54 patients with EC who underwent multimodal pelvic MRI followed by biopsy were retrospectively selected and divided into the Her-2 positive (n = 24) and Her-2 negative (n = 30) groups. Her-2 expression was confirmed by immunohistochemistry (IHC). Two observers measured APT, mean kurtosis (MK), mean diffusivity (MD), and T2 values for EC lesions. RESULTS: The Her-2 (+) group showed higher APT values and lower MD and T2 values than the Her-2 (-) group (all p < 0.05); there was no significant difference in MK values (p > 0.05). The area under the receiver operating characteristic curve (AUC) of APT, MD, T2, APT + T2, APT + MD, T2 + MD, and APT + MD + T2 models to identify the two groups of cases were 0.824, 0.695, 0.721, 0.824, 0.858, 0.782, and 0.860, respectively, and the diagnostic efficacy after combined APT + MD + T2 value was significantly higher than those of MD and T2 values individually (p = 0.018, 0.028); the diagnostic efficacy of the combination of APT + T2 values was significantly higher than that of T2 values separately (p = 0.028). Weak negative correlations were observed between APT and T2 values (r = -0.365, p = 0.007), moderate negative correlations between APT and MD values (r = -0.560, p < 0.001), and weak positive correlations between MD and T2 values (r = 0.336, p = 0.013). The APT values were independent predictors for assessing Her-2 expression in EC patients. CONCLUSION: The APT, DKI, and T2 mapping sequences can be used to preoperatively assess the Her-2 expression in EC, which can contribute to more precise treatment for clinical preoperative.

Diffusion kurtosis imaging with multiple quantitative parameters for predicting microsatellite instability status of endometrial carcinoma.

PURPOSE: To explore the value of Diffusion kurtosis imaging (DKI) with multiple quantitative parameters in predicting microsatellite instability (MSI) status in endometrial carcinoma (EC). METHODS: Data of 38 patients with EC were retrospectively analyzed, including 12 MSI and 26 microsatellite stability (MSS). All patients underwent preoperative 1.5T MR examination. The quantitative values of the DKI sequence in the tumor parenchyma of the two groups, including mean kurtosis (MK), axial kurtosis (Ka), radial kurtosis (Kr), fractional anisotropy (FA), fractional anisotropy of kurtosis (FAk), mean diffusivity (MD), axial diffusivity (Da), and radial diffusivity (Dr) were measured by two observers, respectively. RESULTS: The MK, Ka, Kr, FA, FAk, MD, Da, and Dr values of the MSI group were 1.074 ± 0.162, 1.253 ± 0.229, 0.886 ± 0.205, 0.207 ± 0.041, 0.397 ± 0.129, 0.890 ± 0.158 µm2/ms, 1.083 ± 0.218 µm2/ms, and 0.793 ± 0.133 µm2/ms, and 0.956 (0.889,1.002), 1.048 ± 0.211, 0.831 ± 0.099, 0.188 ± 0.061, 0.334 (0.241,0.410), 1.043 ± 0.217 µm2/ms, 1.235 ± 0.229 µm2/ms, and 0.946 ± 0.215 µm2/ms in the MSS group. The MK and Ka values of the MSI group were higher than those of the MSS group (P<0.05), while the MD and Dr values were lower than those of the MSS group (P<0.05). The AUC of MK, Ka, MD, and Dr values in predicting MSI status of EC was 0.763, 0.729, 0.731, 0.748, respectively. The sensitivity was 58.3%, 50.0%, 65.4%, 61.5%, and the specificity was 96.2%, 92.3%, 75.0%, 83.3%, respectively. CONCLUSION: DKI can provide multiple quantitative parameters for predicting the MSI status of EC, and assist gynecologist to optimize the treatment plan for the patients.

Improved differentiation between stage I-II endometrial carcinoma and endometrial polyp with combination of APTw and IVIM MR imaging.

PURPOSE: To assess the value of amide proton transfer weighted (APTw) combined with intra-voxel incoherent motion (IVIM) imaging in differential diagnosis of stage I-II endometrial carcinoma (EC) and endometrial polyp (EP). METHODS: A total of 53 female patients (37 cases with EC and 16 cases with EP) confirmed by surgical resection or biopsy from June 2019 to Jan. 2022 were retrospectively reviewed. All patients underwent 3.0 T magnetic resonance imaging (MRI) examination including diffusion weighted imaging (DWI), APTw and IVIM scans. The pure diffusion coefficient (D), pseudo-diffusion coefficient (D⁎), perfusion fraction (f), apparent diffusion coefficient (ADC) and APT values were independently measured by two observers. Intra-class correlation coefficients (ICC) were used to test the consistency of measurements by the two observers. Mann-Whitney U test was performed to analyze the difference of each parameter between EC and EP groups. Receiver operator characteristic (ROC) analysis was performed, and the Delong test was used for ROC curve comparison. Pearson's correlation analysis was used to assess the correlation between APTw and IVIM parameters. RESULTS: There was no significant difference in clinical manifestations between the two groups (P > 0.05). APT and D⁎ values of the EC group were significantly higher than those of the EP group [APT: 2.64 ± 0.50% vs. 2.05 ± 0.58%; and D⁎: (54.06 ± 36.06) × 10-3 mm2/s vs. (30.54 ± 16.67) × 10-3 mm2/s]. D, f and ADC values of EC group were significantly lower than those of EP group [D: 0.62(0.53,0.76) × 10-3 mm2/s vs. (1.45 ± 0.48) × 10-3 mm2/s; f: 22.18 ± 8.08% vs. 30.80 ± 8.92%; and ADC: (0.88 ± 0.16) × 10-3 mm2/s vs. (1.57 ± 0.43) × 10-3 mm2/s]. The area under ROC curves were observed as: AUC (IVIM+APT) > AUC (D) > AUC (ADC) > AUC (APT) > AUC (f) > AUC (D⁎). Delong test suggested statistical significance between AUC by APT and D, D and D⁎, D and f, D⁎ and ADC, APT and com(IVIM+APT), D⁎ and com(IVIM+APT), as well as f and com(IVIM+APT). No significant correlation between the APT and IVIM parameters was observed in either EC or EP group. CONCLUSION: Both APT and IVIM parameters showed statistical differences between EC and EP. With combination of APT and IVIM parameters, the diagnostic accuracy between EC and EP can be significantly improved.

APTw combined with mDixon-Quant imaging to distinguish the differentiation degree of cervical squamous carcinoma.

Background: To investigate the value of amide proton transfer weighted (APTw) imaging combined with modified Dixon fat quantification (mDixon-Quant) imaging in determining the degree of differentiation of cervical squamous carcinoma (CSC) against histopathologic. Methods: Magnetic resonance imaging (MRI) data were collected from 52 CSC patients. According to histopathologic results, patients were divided into the poorly differentiated group (37 cases) and the well/moderately differentiated group (15 cases). The APTw value by APTw imaging and the fat fraction (FF) and transverse relaxation rate R 2 * values by mDixon-Quant were independently measured by two radiologists. Intra-class correlation coefficients (ICCs) were used to test the consistency of APTw, FF, and R 2 * values measured by the two observers. The Mann-Whitney U test was used to analyze the difference in each parameter between the two groups. Logistic regression analysis was used to assess the association between the degree of differentiation on histopathology and imaging parameters by APTw and mDixon Quant. The ROC curve was used to evaluate the diagnostic efficacy of various parameters and their combination in distinguishing the degree of CSC differentiation on histopathology. The DeLong test was used to access the differences among the area under the ROC curves (AUCs). The Pearson correlation coefficient was used to evaluate the correlation between APTw and mDixon-Quant imaging parameters. Results: The APTw means were 2.95 ± 0.78% and 2.05 (1.85, 2.65)% in the poorly and well/moderately differentiated groups, respectively. The R 2 * values were 26.62 (21.99, 33.31)/s and 22.93 ± 6.09/s in the poorly and well/moderately differentiated groups, respectively (P < 0.05). The AUCs of APTw, R 2 * , and their combination were 0.762, 0.686, and 0.843, respectively. The Delong test suggested statistical significance between R 2 * and the combination of APTw and R 2 * . R 2 * values showed a significant correlation with APTw values in the poorly differentiated group. Conclusions: APTw combined with mDixon-Quant can be used to efficiently distinguish the differention degrees of CSC diagnosed on histopathology.

The roles of connexins and gap junctions in the progression of cancer.

Gap junctions (GJs), which are composed of connexins (Cxs), provide channels for direct information exchange between cells. Cx expression has a strong spatial specificity; however, its influence on cell behavior and information exchange between cells cannot be ignored. A variety of factors in organisms can modulate Cxs and subsequently trigger a series of responses that have important effects on cellular behavior. The expression and function of Cxs and the number and function of GJs are in dynamic change. Cxs have been characterized as tumor suppressors in the past, but recent studies have highlighted the critical roles of Cxs and GJs in cancer pathogenesis. The complex mechanism underlying Cx and GJ involvement in cancer development is a major obstacle to the evolution of therapy targeting Cxs. In this paper, we review the post-translational modifications of Cxs, the interactions of Cxs with several chaperone proteins, and the effects of Cxs and GJs on cancer. Video Abstract.

The combined application of amide proton transfer imaging and diffusion kurtosis imaging for differentiating stage Ia endometrial carcinoma and endometrial polyps.

OBJECTIVE: This study aims to explore the diagnostic performance of amide proton transfer (APT) imaging combined with diffusion kurtosis imaging (DKI) in differentiating stage Ia endometrial carcinoma (EC) and endometrial polyps (EP). METHODS: All patients were scanned with APT and DKI sequences with 3.0 T MRI before surgery. The MRI data of 32 patients with histopathologically confirmed stage Ia EC and 17 patients with EP were retrospectively analyzed. Amide proton transfer, mean kurtosis (MK) and mean diffusivity (MD) values were measured. ROC curves were employed to evaluate the efficiency of differentiating and diagnosing stage Ia EC and EP, followed by the Delong test to compare the differences between the areas under the curve (AUCs) of each parameter. Additionally, the Pearson correlation analysis was performed to assess the correlation between APT values and MK and MD. RESULTS: The measured APT, MK, and MD values of the patients with stage Ia EC were 2.609 ± 0.504%,0.641 ± 0.113 and 0.904(0.816, 1.108) µm2/ms, while those of patients with EP were1.909 ± 0.418%, 0.495 ± 0.069, and 1.650 (1.458, 1.815) µm2/ms. The AUCs of APT, MK, MD, MK + MD, and APT + MK + MD in differentiating stage Ia EC and EP were.850, 0.879, 0.893, 0.930 and 0.976, respectively. The AUCs of APT + MK + MD were significantly higher than the AUCs of APT or MK (P < 0.05). The APT value was weakly and positively correlated with the MK value (r = 0.299, P = 0.037), while the APT value was moderately and negatively correlated with the MD value (r = -0.520, P < 0.001). CONCLUSION: Both APT and DKI effectively differentiated stage Ia EC and EP; however, when combined, APT and DKI improved the ability to differentiate these diseases, boosting the value of using a combination of these modalities in clinical applications.

Effects of high temperature and acidic solutions on the pore characteristics and mechanical properties of sandstone.

Sandstone is a common construction material widely distributed in mountain tunnels. Its stability determines the safety and service life of tunnel projects. The surrounding rock of the tunnel is subject to frequent fire incidents and long-term erosion by acidic groundwater throughout its entire life cycle. This study investigated the pore characteristics and mechanical properties of sandstone under different high temperatures and acidic solutions. The T2 spectrum distribution, pore size distribution, porosity, compressive strength, and elastic modulus of sandstone were observed through uniaxial compression tests and nuclear magnetic resonance (NMR) tests. The results showed that high temperature and acidic solutions significantly affected the T2 spectrum distribution, pore size distribution, porosity, compressive strength, and elastic modulus of sandstones, and their effects on the pore structure and mechanical properties of sandstone differed in each stage. The effect of high temperature on the pore structure and mechanical properties of sandstone was stronger than that of the acidic solutions. In addition, the mechanism of damage formation is characterized by the porosity variation of sandstone. The pore structure of sandstone showed a close linear relationship with mechanical properties, indicating that changes in microstructure inevitably affected the macroscopic mechanical properties of sandstone. These findings can guide the construction and repair of rock failure induced by fire and acidic groundwater, providing a reference for associated tunnel projects.

Amide Proton Transfer-Weighted Imaging Combined With Intravoxel Incoherent Motion for Evaluating Microsatellite Instability in Endometrial Cancer.

BACKGROUND: Microsatellite instability (MSI), caused by mismatch repair (MMR) protein defects that lead to uncorrectable mismatch bases, results in the accumulation of gene mutations and ultimately to tumors. Preoperative prediction of MSI can provide a basis for personalized and precise treatment of endometrial cancer (EC) patients. PURPOSE: To investigate amide proton transfer weighting (APTw) imaging combined with intravoxel incoherent motion (IVIM) in the assessment of MSI in EC. STUDY TYPE: Retrospective. POPULATION: A total of 71 patients with EC (12 classified as the MSI group and 22 as the microsatellite stabilization [MSS] group after entering and leaving the group standard). FIELD STRENGTH/SEQUENCE: A 3.0 T/IVIM, diffusion-weighted imaging (DWI) and APTw. ASSESSMENT: Amide proton transfer (APT) value, apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo diffusion coefficient (D*), and perfusion fraction (f) were calculated and compared between MSI and MSS groups. STATISTICAL TESTS: The Kendall's W test; Mann-Whitney U-test; Chi-square test or Fisher's exact test; logistic regression analysis; Area under the receiver operating characteristic (ROC) curve (AUC); The Delong test; Pearson or Spearman correlation coefficients. The significance threshold was set at P < 0.05. RESULTS: APT and D* values of the MSI group were significantly higher than those of the MSS group. While ADC, D, and f values in the MSI group were significantly lower than those in the MSS group. The multivariate analysis revealed that only APT and D* values were independent predictors to evaluate the MSI status. And the ROC curves indicated that the combination of APT and D* values could distinguish the MSI status of EC with the highest diagnostic efficacy (AUC = 0.973), even without significant difference to those by APT (AUC = 0.894) or D* (AUC = 0.920) value separately (P = 0.149 and 0.078, respectively). CONCLUSION: Combination of APTw and IVIM imaging may serve as an effective noninvasive method for clinical assessment of MSI in EC. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Multi-parametric MRI-based radiomics for preoperative prediction of multiple biological characteristics in endometrial cancer.

Purpose: To develop and validate multi-parametric MRI (MP-MRI)-based radiomics models for the prediction of biological characteristics in endometrial cancer (EC). Methods: A total of 292 patients with EC were divided into LVSI (n = 208), DMI (n = 292), MSI (n = 95), and Her-2 (n = 198) subsets. Total 2316 radiomics features were extracted from MP-MRI (T2WI, DWI, and ADC) images, and clinical factors (age, FIGO stage, differentiation degree, pathological type, menopausal state, and irregular vaginal bleeding) were included. Intra-class correlation coefficient (ICC), spearman's rank correlation test, univariate logistic regression, and least absolute shrinkage and selection operator (LASSO) were used to select radiomics features; univariate and multivariate logistic regression were used to identify clinical independent risk factors. Five classifiers were applied (logistic regression, random forest, decision tree, K-nearest neighbor, and Bayes) to construct radiomics models for predicting biological characteristics. The clinical model was built based on the clinical independent risk factors. The combined model incorporating the radiomics score (radscore) and the clinical independent risk factors was constructed. The model was evaluated by ROC curve, calibration curve (H-L test), and decision curve analysis (DCA). Results: In the training cohort, the RF radiomics model performed best among the five classifiers for the three subsets (MSI, LVSI, and DMI) according to AUC values (AUCMSI: 0.844; AUCLVSI: 0.952; AUCDMI: 0.840) except for Her-2 subset (Decision tree: AUC=0.714), and the combined model had higher AUC than the clinical model in each subset (MSI: AUCcombined =0.907, AUCclinical =0.755; LVSI: AUCcombined =0.959, AUCclinical =0.835; DMI: AUCcombined = 0.883, AUCclinical =0.796; Her-2: AUCcombined =0.812, AUCclinical =0.717; all P<0.05). Nevertheless, in the validation cohort, significant differences between the two models (combined vs. clinical model) were found only in the DMI and LVSI subsets (DMI: AUCcombined =0.803, AUCclinical =0.698; LVSI: AUCcombined =0.926, AUCclinical =0.796; all P<0.05). Conclusion: The radiomics analysis based on MP-MRI and clinical independent risk factors can potentially predict multiple biological features of EC, including DMI, LVSI, MSI, and Her-2, and provide valuable guidance for clinical decision-making.

Roles of follistatin-like protein 3 in human non-tumor pathophysiologies and cancers.

Follistatin-like protein 3 (FSTL3) is a type of FSTLs. By interacting with a disintegrin and metalloproteinase 12 (ADAM12), transforming growth factor-ß ligands (activin, myostatin and growth differentiation factor (GDF) 11), FSTL3 can either activate or inhibit these molecules in human non-tumor pathophysiologies and cancers. The FSTL3 gene was initially discovered in patients with in B-cell chronic lymphocytic leukemia, and subsequent studies have shown that the FSTL3 protein is associated with reproductive development, insulin resistance, and hematopoiesis. FSTL3 reportedly contributes to the development and progression of many cancers by promoting tumor metastasis, facilitating angiogenesis, and inducing stem cell differentiation. This review summarizes the current pathophysiological roles of FSTL3, which may be a putative prognostic biomarker for various diseases and serve as a potential therapeutic target.

Platycodin D sensitizes KRAS-mutant colorectal cancer cells to cetuximab by inhibiting the PI3K/Akt signaling pathway.

Cetuximab is a monoclonal antibody against epidermal growth factor receptor that blocks downstream signaling pathways of receptor tyrosine kinases, including Ras/Raf/MAPK and PI3K/Akt, thereby inhibiting tumor cell proliferation and inducing cancer cell apoptosis. Owing to KRAS mutations, the effectiveness of cetuximab is usually limited by intrinsic drug resistance. Continuous activation of the PI3K/Akt signaling pathway is another reason for cetuximab resistance. Platycodin-D, a bioactive compound isolated from the Chinese herb Platycodon grandiflorum, regulates Akt in different trends based on tissue types. To investigate whether platycodin-D can sensitize KRAS-mutant colorectal cancer cells to cetuximab by inhibiting the PI3K/Akt signaling pathway, HCT116 and LoVo cells were treated with cetuximab and platycodin-D. LY294002 and SC79 were used to regulate Akt to further evaluate whether platycodin-D sensitizes cells to cetuximab by inhibiting Akt. Our results confirmed that platycodin-D increased the cytotoxic effects of cetuximab, including inhibition of growth, migration, and invasion, via downregulation of PI3K and Akt phosphorylation in HCT116 and LoVo cells both in vitro and in vivo. Given these data, platycodin-D may sensitize KRAS-mutant colorectal cancer cells to cetuximab via inhibition of the PI3K/Akt signaling pathway.

Polyploid giant cancer cells and cancer progression.

Polyploid giant cancer cells (PGCCs) are an important feature of cellular atypia, the detailed mechanisms of their formation and function remain unclear. PGCCs were previously thought to be derived from repeated mitosis/cytokinesis failure, with no intrinsic ability to proliferate and divide. However, recently, PGCCs have been confirmed to have cancer stem cell (CSC)-like characteristics, and generate progeny cells through asymmetric division, which express epithelial-mesenchymal transition-related markers to promote invasion and migration. The formation of PGCCs can be attributed to multiple stimulating factors, including hypoxia, chemotherapeutic reagents, and radiation, can induce the formation of PGCCs, by regulating the cell cycle and cell fusion-related protein expression. The properties of CSCs suggest that PGCCs can be induced to differentiate into non-tumor cells, and produce erythrocytes composed of embryonic hemoglobin, which have a high affinity for oxygen, and thereby allow PGCCs survival from the severe hypoxia. The number of PGCCs is associated with metastasis, chemoradiotherapy resistance, and recurrence of malignant tumors. Targeting relevant proteins or signaling pathways related with the formation and transdifferentiation of adipose tissue and cartilage in PGCCs may provide new strategies for solid tumor therapy.

Roles of tumor-associated neutrophils in tumor metastasis and its clinical applications.

Metastasis, a primary cause of death in patients with malignancies, is promoted by intrinsic changes in both tumor and non-malignant cells in the tumor microenvironment (TME). As major components of the TME, tumor-associated neutrophils (TANs) promote tumor progression and metastasis through communication with multiple growth factors, chemokines, inflammatory factors, and other immune cells, which together establish an immunosuppressive TME. In this review, we describe the potential mechanisms by which TANs participate in tumor metastasis based on recent experimental evidence. We have focused on drugs in chemotherapeutic regimens that target TANs, thereby providing a promising future for cancer immunotherapy.

Amide proton transfer weighted imaging combined with dynamic contrast-enhanced MRI in predicting lymphovascular space invasion and deep stromal invasion of IB1-IIA1 cervical cancer.

Objectives: To investigate the value of amide proton transfer weighted (APTw) imaging combined with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting intermediate-risk factors of deep stromal invasion (DSI) and lymphovascular vascular space invasion (LVSI) in cervical cancer. Methods: Seventy patients with cervical cancer who underwent MRI before operation from July 2019 to February 2022 were retrospectively included in this study. Clinical information including age, histologic subtype etc. were recorded for patients. ATPw imaging parameter APTmean and DCE-MRI parameters Ktrans, Kep and Ve were measured and analyzed. The independent-sample t-test, Mann-Whitney U test, or Chi-square test was used to compare the differences of parameters between DSI/LVSI positive and negative groups. Logistic analysis was used to develop a combined predictive model. The receiver operating characteristic curve was for predictive performance. ANOVA and Kruskal-Wallis test were used to compare the differences of consecutive parameters among multiple groups. Results: Ktrans and SCC-Ag were independent factors in predicting DSI; Ktrans+SCC-Ag had the highest AUC 0.819 with sensitivity and specificity of 71.74% and 91.67%, respectively. APTmean and Ktrans were independent factors in predicting LVSI; APTmean+Ktrans had the highest AUC 0.874 with sensitivity and specificity of 92.86% and 75.00%, respectively. Ktrans and Ve could discriminate coexistence of DSI and LVSI from presence of single one, APTmean could discriminate the presence of DSI or LVSI from no risk factor presence. Conclusion: The combination of APTw and DCE-MRI is valuable in predicting intermediate-risk factors of DSI and LVSI in cervical cancer.

Integrated regulation of chondrogenic differentiation in mesenchymal stem cells and differentiation of cancer cells.

Chondrogenesis is the formation of chondrocytes and cartilage tissues and starts with mesenchymal stem cell (MSC) recruitment and migration, condensation of progenitors, chondrocyte differentiation, and maturation. The chondrogenic differentiation of MSCs depends on co-regulation of many exogenous and endogenous factors including specific microenvironmental signals, non-coding RNAs, physical factors existed in culture condition, etc. Cancer stem cells (CSCs) exhibit self-renewal capacity, pluripotency and cellular plasticity, which have the potential to differentiate into post-mitotic and benign cells. Accumulating evidence has shown that CSCs can be induced to differentiate into various benign cells including adipocytes, fibrocytes, osteoblast, and so on. Retinoic acid has been widely used in the treatment of acute promyelocytic leukemia. Previous study confirmed that polyploid giant cancer cells, a type of cancer stem-like cells, could differentiate into adipocytes, osteocytes, and chondrocytes. In this review, we will summarize signaling pathways and cytokines in chondrogenic differentiation of MSCs. Understanding the molecular mechanism of chondrogenic differentiation of CSCs and cancer cells may provide new strategies for cancer treatment.

Hepatic fat quantification of magnetic resonance imaging whole-liver segmentation for assessing the severity of nonalcoholic fatty liver disease: comparison with a region of interest sampling method.

BACKGROUND: Accurate and early assessment of the hepatic fat content is crucial for patients with nonalcoholic fatty liver disease (NAFLD). For years, magnetic resonance imaging (MRI) has been considered the optimal noninvasive method for the assessment of fat accumulation. To avoid time-consuming manual placement of multiple regions of interest (ROI), the use of whole-liver segmentation has been proposed to measure liver fat, mainly for heterogeneous fat deposition. However, it remains uncertain whether the hepatic mean fat fraction (FF) obtained by whole-liver segmentation with the inclusion of intrahepatic vasculature is consistent with the traditional ROI sampling method. In this study, we assessed the accuracy of hepatic mean FF obtained by whole-liver segmentation in patients of NAFLD with different severities using the ROI sampling method as a reference standard. METHODS: Hepatic FFs were measured by whole-liver segmentation and the ROI sampling method (reference standard) using MRI scanning with the iterative decomposition of water and fat with echo an asymmetry at least-square estimation-iron quantification (IDEAL-IQ) sequence. SPSS version 25.0 software was used to analyze the correlation and consistency of data between the two methods. RESULTS: There was a strong correlation in hepatic FF between whole-liver segmentation and the ROI sampling method in healthy, mild, and moderate steatosis patients (r = 0.943, 0.990, and 0.961, respectively). Bland-Altman analysis showed a small bias of +0.50±0.27 and +0.05±0.30, which indicated a small overestimation when using whole-liver segmentation in healthy subjects and mild NAFLD patients. The 95% limits of agreement ranged from +1.02 to -0.03, and from +0.65 to -0.55, respectively. However, a small bias of -0.96±0.77 was also evident, which indicated a small underestimation when using whole-liver segmentation in moderate NAFLD patients. The 95% limits of agreement ranged from +0.56 to -2.48. CONCLUSIONS: Due to inclusion of the intrahepatic vasculature, whole-liver segmentation has some effects on hepatic FF assessment in patients with different NAFLD severities; yet, it does not significantly affect the assessment of whole-liver FF in MRI FF maps.

Cell Fusion-Related Proteins and Signaling Pathways, and Their Roles in the Development and Progression of Cancer.

Cell fusion is involved in many physiological and pathological processes, including gamete binding, and cancer development. The basic processes of cell fusion include membrane fusion, cytoplasmic mixing, and nuclear fusion. Cell fusion is regulated by different proteins and signaling pathways. Syncytin-1, syncytin-2, glial cell missing 1, galectin-1 and other proteins (annexins, myomaker, myomerger etc.) involved in cell fusion via the cyclic adenosine-dependent protein kinase A, mitogen-activated protein kinase, wingless/integrase-1, and c-Jun N-terminal kinase signaling pathways. In the progression of malignant tumors, cell fusion is essential during the organ-specific metastasis, epithelial-mesenchymal transformation, the formation of cancer stem cells (CSCs), cancer angiogenesis and cancer immunity. In addition, diploid cells can be induced to form polyploid giant cancer cells (PGCCs) via cell fusion under many kinds of stimuli, including cobalt chloride, chemotherapy, radiotherapy, and traditional Chinese medicine. PGCCs have CSC-like properties, and the daughter cells derived from PGCCs have a mesenchymal phenotype and exhibit strong migration, invasion, and proliferation abilities. Therefore, exploring the molecular mechanisms of cell fusion can enable us better understand the development of malignant tumors. In this review, the basic process of cell fusion and its significance in cancer is discussed.

Potential value of the PixelShine deep learning algorithm for increasing quality of 70 kVp+ASiR-V reconstruction pelvic arterial phase CT images.

OBJECTIVE: To investigate the effect of a deep learning-based denoising algorithm, PixelShine (PS), on the quality of 70 kVp pelvic arterial phase CT images. MATERIALS AND METHODS: A retrospective analysis was performed on arterial phase pelvic CT images from 33 patients (body-mass index ≤ 20 kg/m2) obtained with a GE Revolution CT (70 kVp tube voltage; adaptive statistical iterative reconstruction-Veo-filtered back projection, 50% blending) and designated group A. Group B images were then obtained by applying PS to group A image datasets. Subjective image quality was evaluated by two radiologists with a 5-point scoring system; the scores of the groups were compared. Image signal was assessed using CT values of the urinary bladder. CT and standard deviation (SD) values of the gluteus maximus were measured, and SD values of the gluteus maximus were used to represent image noise. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the bladder were calculated. Image noise, SNR, and CNR of two groups were compared using paired t-tests. RESULTS: The subjective visual image quality scores of groups A and B, respectively, were 3.11 ± 0.30 vs. 3.82 ± 0.57; image noise was 15.79 ± 2.05 Hounsfield units (HU) vs. 11.06 ± 2.22 HU; SNRs of bladder were 0.50 ± 0.23 vs. 0.79 ± 0.39; and CNRs of bladder were 3.72 ± 0.85 vs. 5.14 ± 1.27. Group B showed better subjective image quality, lower image noise, and improved SNR and CNR, compared to group A; these differences were statistically significant (P < 0.05). The noise of group B was approximately 30% lower than that of group A; the SNR and CNR values of group B were improved by approximately 58% and 38%, respectively. CONCLUSION: Using 70 kVp +ASiR-V, PS can improve the image quality of pelvic arterial phase CT images, significantly reduce the image noise, and improve the SNR and CNR.