Predictive Value of a Radiomics Nomogram Model Based on Contrast-Enhanced Computed Tomography for KIT Exon 9 Gene Mutation in Gastrointestinal Stromal Tumors.

OBJECTIVES: To establish and validate a radiomics nomogram model for preoperative prediction of KIT exon 9 mutation status in patients with gastrointestinal stromal tumors (GISTs). MATERIALS AND METHODS: Eighty-seven patients with pathologically confirmed GISTs were retrospectively enrolled in this study. Imaging and clinicopathological data were collected and randomly assigned to the training set (n = 60) and test set (n = 27) at a ratio of 7:3. Based on contrast-enhanced CT (CE-CT) arterial and venous phase images, the region of interest (ROI) of the tumors were manually drawn layer by layer, and the radiomics features were extracted. The intra-class correlation coefficient (ICC) was used to test the consistency between observers. Least absolute shrinkage and selection operator regression (LASSO) were used to further screen the features. The nomogram of integrated radiomics score (Rad-Score) and clinical risk factors (extra-gastric location and distant metastasis) was drawn on the basis of multivariate logistic regression. The area under the receiver operating characteristic (AUC) curve and decision curve analysis were used to evaluate the predictive efficiency of the nomogram, and the clinical benefits that the decision curve evaluation model may bring to patients. RESULTS: The selected radiomics features (arterial phase and venous phase features) were significantly correlated with the KIT exon 9 mutation status of GISTs. The AUC, sensitivity, specificity, and accuracy in the radiomics model were 0.863, 85.7%, 80.4%, and 85.0% for the training group (95% confidence interval [CI]: 0.750-0.938), and 0.883, 88.9%, 83.3%, and 81.5% for the test group (95% CI: 0.701-0.974), respectively. The AUC, sensitivity, specificity, and accuracy in the nomogram model were 0.902 (95% confidence interval [CI]: 0.798-0.964), 85.7%, 86.9%, and 91.7% for the training group, and 0.907 (95% CI: 0.732-0.984), 77.8%, 94.4%, and 88.9% for the test group, respectively. The decision curve showed the clinical application value of the radiomic nomogram. CONCLUSION: The radiomics nomogram model based on CE-CT can effectively predict the KIT exon 9 mutation status of GISTs and may be used for selective gene analysis in the future, which is of great significance for the accurate treatment of GISTs.

Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001).

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.

PI3K δ inhibitor PI-3065 induces apoptosis in hepatocellular carcinoma cells by targeting survivin.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, and its clinical treatment remains challenging. The development of new treatment regimens is important for effective HCC treatment. Phosphoinositide 3-kinase (PI3K) is a lipid kinase that plays an important role in cell growth and metabolism and is overexpressed in nearly 50% of patients with HCC. Studies have shown that PI-3065, a small-molecule inhibitor of phosphatidylinositol 3-kinase delta, significantly inhibits solid breast cancer. However, its antitumor effects against HCC and the underlying mechanisms remain unclear. In the present study, we found that PI-3065 dose- and time-dependently reduced HCC cell viability and induced apoptosis while posing no obvious apoptotic toxicity in normal liver cells. Further mechanistic analysis showed that PI-3065 induced apoptosis mainly by inhibiting survivin protein expression, decreasing mitochondrial membrane potential, and promoting cytochrome C release. Simultaneously, PI-3065 markedly suppressed the colony formation, migration, and epithelial-mesenchymal transition abilities of HCC cells. Furthermore, transplantation of nude mice with HCC tumors showed that PI-3065 inhibits HCC tumor growth in vivo by targeting survivin. In summary, PI-3065 specifically inhibited survivin expression and exerted anti-HCC activity in vivo and in vitro, suggesting that it may serve as an effective antitumor drug for HCC treatment, which warrants further study.

p53 m6A modulation sensitizes hepatocellular carcinoma to apatinib through apoptosis.

Hepatocellular carcinoma (HCC) is insidious and prone to metastasis and recurrence. Currently, no effective treatment is available for HCC. Furthermore, HCC does not respond to various radio- and chemotherapies, and the molecular mechanism of treatment resistance is unclear. Here, we found that p53 n6-methyladenosine (m6A) played a decisive role in regulating HCC sensitivity to chemotherapy via the p53 activator RG7112 and the vascular endothelial growth factor receptor inhibitor apatinib. Our results reveal that p53 activation plays a crucial role in chemotherapy-induced apoptosis and reducing cell viability. Moreover, decreasing m6A methyltransferase (e.g., methyltransferase-like 3, METTL3) expression through chemotherapeutic drug combinations reduced p53 mRNA m6A modification. p53 mRNA m6A modification blockage induced by S-adenosyl homocysteine or siRNA-mediated METTL3 inhibition enhanced HCC sensitivity to chemotherapy. Importantly, we observed that downregulation of METTL3 and upregulation of p53 expression by oral administration of chemotherapy drugs triggered apoptosis and xenograft tumor growth inhibition in nude mice. Based on these findings, we hypothesize that a METTL3-m6A-p53 axis could be a potential target in HCC therapy.

Resina Draconis extract exerts anti-HCC effects through METTL3-m6A-Survivin axis.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Herbal medicines have become an important treasure reservoir for anti-HCC drugs because of their high efficiency and low toxicity. Herein, we investigated whether a 75% ethanol extract from Resina Draconis (ERD) exhibited comprehensive anti-HCC effects both in vivo and in vitro. We revealed that ERD effectively inhibited proliferation and triggered apoptosis of HCC cells in a dose- and time-dependent maner, posing no apparent apoptotic toxicity to normal liver cells. Moreover, ERD significantly inhibited the migration, invasion and metastasis of HCC cells. Importantly, ERD treatment effectively inhibited the growth of xenograft HCC in nude mice with low toxicity and low side effects. Molecular mechanism analysis showed that ERD strongly reduced the expression of anti-apoptotic protein Survivin, ultimately leading to the cleavage activation of apoptosis executive proteins such as Caspase 3 and Poly (ADP-ribose) polymerase (PARP). Survivin gene silencing apparently sensitized the apoptotic effect induced by ERD. Further experiments revealed that ERD inhibited N6-methyladenosine (m6 A) modification in Survivin mRNA by downregulating Methyltransferase-like 3 (METTL3) expression and reducing the binding rate of METTL3 and Survivin mRNA. Together, our findings suggest that ERD can be severed as a novel anti-HCC natural product by targeting METTL3-m6 A-Survivin axis.

Autophagy is involved in Ficus carica fruit extract-induced anti-tumor effects on pancreatic cancer.

Pancreatic cancer (PaCa), a common and highly lethal malignant cancer, is often insensitive to radio- and/or chemotherapy. Therefore, effective treatment regiments are still lacking. Herein, we found that an extract of Ficus carica fruit (EFCF) exerted anti-tumor effects on PaCa cells. EFCF induced cell viability inhibition and apoptotic cell death in two PaCa cell lines in a dose- and time dependent manner. EFCF effectively suppressed the migration, metastasis, invasion, and colony formation of PaCa cells. Mechanistically, EFCF stimulated an increase in intracellular ROS to promote cell death and senescence. EFCF treatment also triggered autophagy, and autophagy inhibition enhanced EFCF-induced cell death. We found that EFCF decreased mitochondrial membrane potential and promoted lipid peroxidation. Moreover, intragastric administration of EFCF effectively suppressed xenograft PaCa growth inhibition by activating cell death. EFCF had no apparent toxicity to normal pancreatic epithelial cells. Together, these findings suggest that EFCF may be a potential treatment for PaCa.

The potential roles of p53 signaling reactivation in pancreatic cancer therapy.

Globally, pancreatic cancer (PC) is a common and highly malignant gastrointestinal tumor that is characterized by an insidious onset and ready metastasis and recurrence. Over recent decades, the incidence of PC has been increasing on an annual basis; however, the pathogenesis of this condition remains enigmatic. PC is not sensitive to radio- or chemotherapy, and except for early surgical resection, there is no curative treatment regime; consequently, the prognosis for patients with PC is extremely poor. Transcription factor p53 is known to play key roles in many important biological processes in vertebrates, including normal cell growth, differentiation, cell cycle progression, senescence, apoptosis, metabolism, and DNA damage repair. However, there is a significant paucity of basic and clinical studies to describe how p53 gene mutations or protein dysfunction facilitate the occurrence, progression, invasion, and resistance to therapy, of malignancies, including PC. Herein, we describe the involvement of p53 signaling reactivation in PC treatment as well as its underlying molecular mechanisms, thereby providing useful insights for targeting p53-related signal pathways in PC therapy.

PAQR4 promotes the development of hepatocellular carcinoma by activating PI3K/AKT pathway.

Progestin and adipoQ receptor 4 (PAQR4) is a novel tumorigenic factor that promotes cell proliferation and metastasis in lung and breast cancer, but its role in hepatocellular carcinoma (HCC) is unknown. The aim of our study was to explore its role and underlying mechanism in the development of HCC. Analysis of GEPIA database indicated that PAQR4 was highly expressed in HCC samples, and the mRNA level of PAQR4 was negatively correlated with the overall survival of HCC patients. Knockdown of PAQR4 in Hep3B cells suppressed cell proliferation by hindering G1/S transition of cell cycle as shown by the flow cytometry analysis. PAQR4 knockdown also expedited the cell apoptosis. Knockdown of PAQR4 repressed the migratory and invasive potential of Hep3B cells. PAQR4 knockdown sensitized Hep3B cells to apatinib-based chemotherapy. PAQR4 knockdown blocked the activation of PI3K/AKT pathway, as reflected by the reduced phosphorylation of AKT and p85. Conversely, overexpression of PAQR4 exerted opposite effects in Huh-7 cells. PI3K inhibitor LY294002 could eliminate the effects of PAQR4 on cell proliferation, apoptosis, chemoresistance, and invasion. In tumor xenograft model, knockdown of PAQR4 suppressed tumor growth in vivo, while PAQR4 overexpression promoted tumor growth. Collectively, our data suggest that PAQR4 has a tumorigenic effect on HCC progression by activating PI3K/AKT pathway.

Applying arterial enhancement fraction (AEF) texture features to predict the tumor response in hepatocellular carcinoma (HCC) treated with Transarterial chemoembolization (TACE).

BACKGROUND: To evaluate the application of Arterial Enhancement Fraction (AEF) texture features in predicting the tumor response in Hepatocellular Carcinoma (HCC) treated with Transarterial Chemoembolization (TACE) by means of texture analysis. METHODS: HCC patients treated with TACE in Shengjing Hospital of China Medical University from June 2018 to December 2019 were retrospectively enrolled in this study. Pre-TACE Contrast Enhanced Computed Tomography (CECT) and imaging follow-up within 6 months were both acquired. The tumor responses were categorized according to the modified RECIST (mRECIST) criteria. Based on the CECT images, Region of Interest (ROI) of HCC lesion was drawn, the AEF calculation and texture analysis upon AEF values in the ROI were performed using CT-Kinetics (C.K., GE Healthcare, China). A total of 32 AEF texture features were extracted and compared between different tumor response groups. Multi-variate logistic regression was performed using certain AEF features to build the differential models to predict the tumor response. The Receiver Operator Characteristic (ROC) analysis was implemented to assess the discriminative performance of these models. RESULTS: Forty-five patients were finally enrolled in the study. Eight AEF texture features showed significant distinction between Improved and Un-improved patients (p < 0.05). In multi-variate logistic regression, 9 AEF texture features were applied into modeling to predict "Improved" outcome, and 4 AEF texture features were applied into modeling to predict "Un-worsened" outcome. The Area Under Curve (AUC), diagnostic accuracy, sensitivity, and specificity of the two models were 0.941, 0.911, 1.000, 0.826, and 0.824, 0.711, 0.581, 1.000, respectively. CONCLUSIONS: Certain AEF heterogeneous features of HCC could possibly be utilized to predict the tumor response to TACE treatment.

The HSP90 inhibitor, XL888, enhanced cell apoptosis via downregulating STAT3 after insufficient radiofrequency ablation in hepatocellular carcinoma.

AIMS: Radiofrequency ablation (RFA) is the first-line option for early-stage hepatocellular carcinoma (HCC). However, the residual tumor attributed to insufficient RFA (iRFA) led to tumor recurrence and metastasis. Novel combination strategies are urgently needed to enhance efficiency of RFA. MAIN METHODS: For in vitro iRFA models, HCC cells were placed in a water bath at 46 °C for 10 min and then returned to the original incubator. For in vivo models, HCC cells were implanted subcutaneously into nude mice. The nude mice were then randomly assigned into 4 groups: control group, XL888 group, iRFA group, combination of XL888 and iRFA group. CCK8 was performed to detect cell viability; Hoechst 33258 was used to explore nuclear morphology; The expression levels of proteins were demonstrated by western blotting; Co-localization of HSP90 and STAT3 was elucidated by immunofluorescence confocal microscopy; Immunohistochemistry was used to explore expression levels of proteins at tissue level. KEY FINDINGS: XL888 promoted apoptosis of HCC cells induced by heat via inhibiting expression levels of Mcl-1 and cleaved-caspase 3 in vivo and in vitro. XL888 attenuated the complex formation of HSP90 and STAT3, leading to decreased expression levels of STAT3 and p-STAT3. In human HCC tissues, IHC scores of HSP90 were positively correlated with those of STAT3. Overexpression of STAT3 rescued cell apoptosis induced by co-treatment of XL888 and heat. SIGNIFICANCE: We implied that XL888 promoted apoptosis of HCC cells induced by heat via disrupting the binding of HSP90 and STAT3, providing theoretical basis for a novel combination strategy for HCC.

Targeting Bcl-2 for cancer therapy.

Apoptosis deficiency is one of the most important features observed in neoplastic diseases. The Bcl-2 family is composed of a subset of proteins that act as decisive apoptosis regulators. Research and clinical studies have both demonstrated that the hyperactivation of Bcl-2-related anti-apoptotic effects correlates with cancer occurrence, progression and prognosis, also having a role in facilitating the radio- and chemoresistance of various malignancies. Therefore, targeting Bcl-2 inactivation has provided some compelling therapeutic advantages by enhancing apoptotic sensitivity or reversing drug resistance. Therefore, this pharmacological route turned into one of the most promising routes for cancer treatment. This review discusses some of the well-defined and emerging roles of Bcl-2 as well as its potential clinical value in cancer therapeutics.

A preliminary single-center investigation of percutaneous biliary stenting in malignant hilar biliary obstruction: what impacts the clinical success and the long-term outcomes?

PURPOSE: The purpose of this study is to investigate the influencing factors that may impact the clinical success, jaundice-free time, and overall survival in patients of malignant hilar biliary obstruction (MHBO) treated with a self-expanding metallic stent (SEMS). MATERIALS AND METHODS: Patients diagnosed with MHBO and treated with SEMS through percutaneous access from 1 Jul. 2013 to 1 Jul. 2018 were enrolled in this monocentric study. Demographic information, disease baseline measurements, and interventional strategies were collected and examined. Bilirubin was measured 1-3 days before and 3-7 days after stenting using the unit of "µmol/L." The bilirubin reduction ratio was compared between different study groups, which were separated by specific characteristics. Univariate and multivariate analyses were performed to evaluate each characteristic's impact on jaundice-free time (JF) and overall survival time (OS). Statistical analyses were conducted using SPSS 14.0, p < 0.05 indicated significance. RESULTS: Eighty patients were enrolled. Direct bilirubin (DB) and indirect bilirubin (IB) both significantly decreased after stenting (U = 1575.0, p < 0.001; U = 1541.0, p < 0.001). The DB reduction ratio of the "nearby lymph metastases" group was significantly higher (U = 566.0, p = 0.037). The IB reduction ratio in the "single stent" group was significantly higher (U = 554.0, p = 0.018). Sixty-six cases reached jaundice recurrence, the median JF was 6 months, and the 95% confidence interval was 4.411 ~ 7.589 months. Fifty-eight cases ended in death, the median OS was 7 months, and the 95% confidence interval was 5.759 ~ 8.241 months. "Nearby lymph metastases" and "distant metastases" independently impacted OS (OR = 2.344, p = 0.013; OR = 3.239, p = 0.042). "IB reduction ratio" independently impacted both JF and OS (OR = 0.422, p = 0.021; OR = 0.315, p = 0.001). CONCLUSION: The goal of treatment in patients with MHBO is to recover liver function. However, the overall survival is greatly impacted by the presence of metastases. Managing to obtain adequate liver function recovery may improve the long-term outcomes in affected patients.

Radiomics Analysis of PET and CT Components of 18F-FDG PET/CT Imaging for Prediction of Progression-Free Survival in Advanced High-Grade Serous Ovarian Cancer.

OBJECTIVE: To investigate radiomics features extracted from PET and CT components of 18F-FDG PET/CT images integrating clinical factors and metabolic parameters of PET to predict progression-free survival (PFS) in advanced high-grade serous ovarian cancer (HGSOC). METHODS: A total of 261 patients were finally enrolled in this study and randomly divided into training (n=182) and validation cohorts (n=79). The data of clinical features and metabolic parameters of PET were reviewed from hospital information system(HIS). All volumes of interest (VOIs) of PET/CT images were semi-automatically segmented with a threshold of 42% of maximal standard uptake value (SUVmax) in PET images. A total of 1700 (850×2) radiomics features were separately extracted from PET and CT components of PET/CT images. Then two radiomics signatures (RSs) were constructed by the least absolute shrinkage and selection operator (LASSO) method. The RSs of PET (PET_RS) and CT components(CT_RS) were separately divided into low and high RS groups according to the optimum cutoff value. The potential associations between RSs with PFS were assessed in training and validation cohorts based on the Log-rank test. Clinical features and metabolic parameters of PET images (PET_MP) with P-value <0.05 in univariate and multivariate Cox regression were combined with PET_RS and CT_RS to develop prediction nomograms (Clinical, Clinical+ PET_MP, Clinical+ PET_RS, Clinical+ CT_RS, Clinical+ PET_MP + PET_RS, Clinical+ PET_MP + CT_RS) by using multivariate Cox regression. The concordance index (C-index), calibration curve, and net reclassification improvement (NRI) was applied to evaluate the predictive performance of nomograms in training and validation cohorts. RESULTS: In univariate Cox regression analysis, six clinical features were significantly associated with PFS. Ten PET radiomics features were selected by LASSO to construct PET_RS, and 1 CT radiomics features to construct CT_RS. PET_RS and CT_RS was significantly associated with PFS both in training (P <0.00 for both RSs) and validation cohorts (P=0.01 for both RSs). Because there was no PET_MP significantly associated with PFS in training cohorts. Only three models were constructed by 4 clinical features with P-value <0.05 in multivariate Cox regression and RSs (Clinical, Clinical+ PET_RS, Clinical+ CT_RS). Clinical+ PET_RS model showed higher prognostic performance than other models in training cohort (C-index=0.70, 95% CI 0.68-0.72) and validation cohort (C-index=0.70, 95% CI 0.66-0.74). Calibration curves of each model for prediction of 1-, 3-year PFS indicated Clinical +PET_RS model showed excellent agreements between estimated and the observed 1-, 3-outcomes. Compared to the basic clinical model, Clinical+ PET_MS model resulted in greater improvement in predictive performance in the validation cohort. CONCLUSION: PET_RS can improve diagnostic accuracy and provide complementary prognostic information compared with the use of clinical factors alone or combined with CT_RS. The newly developed radiomics nomogram is an effective tool to predict PFS for patients with advanced HGSOC.

m6A RNA Methylation Regulators Act as Potential Prognostic Biomarkers in Lung Adenocarcinoma.

N6-methyladenosine [m(6)A/m6A] methylation is one of the most common RNA modifications in eukaryotic cell mRNA and plays an important regulatory role in mRNA metabolism, splicing, translocation, stability, and translation. Previous studies have demonstrated that the m6A modification is highly associated with tumor cell proliferation, migration, and invasion. In the present study, five m6A regulatory factors have been revealed, namely heterogeneous nuclear ribonucleoprotein A2/B1(HNRNPA2B1), heterogeneous nuclear ribonucleoprotein C (HNRNPC), Vir like m6A methyltransferase associated protein (KIAA1429/VIRMA), RNA binding motif protein 15 (RBM15) and methyltransferase like 3 (METTL3), which are closely related to the overall survival (OS) of patients with lung adenocarcinoma (LUAD). These five m6A regulatory factors exhibited potential prognostic value for the 1, 3, and 5-years survival outcomes of LUAD patients. Our findings revealed that several signaling pathways, such as cell cycle, DNA replication, RNA degradation, RNA polymerase, nucleotide excision repair and basal transcription factors, are activated in the high-risk group of LUAD patients.

Risk Factors for Local Bone Destruction Progression in Palliative Percutaneous Vertebroplasty for Vertebral Metastases and the Significance of Bone Cement Filling Rates.

BACKGROUND: For palliative percutaneous vertebroplasty (PVP) for vertebral metastases, local bone destruction progression (LBDP) commonly occurs in the previously treated vertebrae. There were no studies regarding LBDP and its risk factors in previous reports, and there was no uniform evaluation method for the distribution of bone cement in the vertebrae. OBJECTIVES: We aimed to investigate the risk factors for LBDP after PVP for palliative treatments in patients with vertebral metastases. We also proposed that filling rates could be used as a simple evaluation method to detect vertebral metastases and explored its clinical significance. STUDY DESIGN: This was a retrospective study. SETTING: A university hospital. METHODS: A total of 48 patients and 54 vertebrae that had received PVP as a palliative treatment for vertebral metastases were recruited between October 2012 to October 2019 from the Shengjing Hospital of the China Medical University. We collected and evaluated the data including age, gender, cement filled completely or not, cement dose used, the cement distribution score, time of LBDP, and so on, and the filing rate we proposed was also included. RESULTS: This retrospective study divided 48 patients and 54 vertebrae into group A for those with an LBDP of less than 6 months (n = 41), and group B for those with an LBDP of 6 or more months (n = 13). The complete filling of bone cement and bone cement dose in group B was much higher than that in group A (2.85 ± 0.97 vs. 4.12 ± 1.77; P = 0.027), and the time of recurrent pain in group B was significantly higher compared with that in group A (8.46 ± 2.73 vs. 3.39 ± 1.63; P < 0.0001). There was a statistical difference in the Saliou score and filling rate between the 2 groups (11.77 ± 3.17 vs. 9.34 ± 3.28, P = 0.023; 0.752 ± 0.227 vs. 0.489 ± 0.161, P < 0.0001). Univariate logistic analysis showed that complete filling of cement, the cement dose, Saliou score, and filling rate were statistically significant predictors of LBDP occurring in less than 6 months. Multivariate logistic analysis showed that the filling rate was an independent predictor of patients with vertebral metastases developing LBDP in less than 6 months (odds ratio, < 0.001; 95% confidence interval, < 0.001-0.006; P = 0.0007). The cutoff value for the filling rate calculated from the receiver operating characteristic (ROC) curve analysis was 0.646, which could identify patients who had LBDP in less than 6 months of PVP with a sensitivity of 85.4% and specificity of 84.6%. The 6-month LBDP in the 0.646 or less ROC curve group was higher than that in the greater than 0.646 ROC curve group (97.22% vs. 55.56%, P < 0.0001). LIMITATIONS: The retrospective nature and small sample size were significant. Variation in the time and state of bone cement injected during all PVP procedures was a bias. There was no pathological diagnosis of all vertebral metastases. CONCLUSIONS: The cement dose, complete filling of cement, Saliou score, and filling rate were factors negatively related to LBDP occurring in less than 6 months. Patients with lower filling rates are maybe more likely to have early LBDP compared with those with higher filling rates.

Foeniculum vulgare seed extract induces apoptosis in lung cancer cells partly through the down-regulation of Bcl-2.

The factors behind the pathogenesis of lung cancer are not clear, and treatment failure is generally caused by drug resistance, recurrence, and metastasis. Development of new therapeutic agents to overcome drug-resistance remains a challenge clinically. Various extracts of Foeniculum vulgare have shown promising anticancer activity; however, effects on lung cancer and the underlying molecular mechanisms of action are not clear. In the present study, we found that the ethanol extract of Foeniculum vulgare seeds (EEFS) significantly reduced lung cancer cell growth in vitro and in vivo. EEFS decreased the viability of and triggered apoptosis in the lung cancer cell lines NCI-H446 and NCI-H661. EEFS induced apoptosis mainly through inhibition of Bcl-2 protein expression, reduction of mitochondrial membrane potential, and release of Cytochrome C. Moreover, EEFS significantly inhibited colony formation and cell migration in lung cancer cells. EEFS also effectively inhibited the growth of xenograft tumors derived from NCI-446 cells by reducing Bcl-2 protein expression and inducing apoptosis. Taken together, these findings suggest that EEFS exerts anti-lung cancer activity by targeting the Bcl-2 protein and may have potential as a therapeutic drug for lung cancer.

Foeniculum vulgare seed extract exerts anti-cancer effects on hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. The prognosis of HCC is very poor due to the absence of symptoms and a lack of effective treatments. Studies have shown that various Foeniculum vulgare (fennel) extracts exhibit anti-cancer effects on malignant tumors such as skin cancer and prostate cancer. However, the anti-tumor activity of Foeniculum vulgare and its underlying molecular mechanisms towards HCC are unknown. Here, we provide fundamental evidence to show that the 75% ethanol extract of Foeniculum vulgare seeds (FVE) reduced cell viability, induced apoptosis, and effectively inhibited cell migration in HCC cells in vitro. HCC xenograft studies in nude mice showed that FVE significantly inhibited HCC growth in vivo. Mechanistic analyses showed that FVE reduced survivin protein levels and triggered mitochondrial toxicity, subsequently inducing caspase-3 activation and apoptosis. Survivin inhibition effectively sensitized HCC cells to FVE-induced apoptosis. Moreover, FVE did not induce a decrease in survivin or apoptotic toxicity in normal liver cells. Collectively, in vivo and in vitro results suggest that FVE exerts inhibitory effects in HCC by targeting the oncoprotein survivin, suggesting FVE may be a potential anti-cancer agent that may benefit patients with HCC.

Therapeutic potential of p53 reactivation in cervical cancer.

Cervical cancer (CC) is one of most common malignancies affecting women worldwide. To date, surgical resection is the only effective radical remedy for CC at its early stages, while the prognosis of metastatic or recurrent CC is very poor. Dysfunction of the tumor suppressor p53 due to aberrant expression, post-translational modification, mutations, SNPs, and LOH as well as sequestration by viral antigens and MDM2/HDM2-mediated degradation is closely associated with the therapeutic insensitivity and relapse of many malignancies, including CC. Accumulating studies have demonstrated that restoration of p53 activity can induce cell cycle arrest and apoptosis, eliminate radio- and chemotherapy resistance, and inhibit tumor growth in CC cells. Therefore, activation of wild-type p53 as well as restoration of p53 function seems appealing as a therapeutic strategy. In this review, we focus on the potential roles of p53 reactivation in CC treatment and their underlying molecular mechanisms towards the development of novel therapies.

Potential diagnostic and therapeutic roles of exosomes in pancreatic cancer.

Pancreatic cancer (PaCa) is considered an aggressive but still asymptomatic malignancy. Due to the lack of effective diagnostic markers, PaCa is often diagnosed during late metastatic stages. Besides surgical resection, no other treatment appears to be effective during earlier stages of the disease. Exosomes are related to a class of nanovesicles coated by a bilayer lipid membrane and enriched in protein, nucleic acid, and lipid contents. They are widely present in human body fluids, including blood, saliva, and pancreatic duct fluid, with functions in signal transduction and material transport. A large number of studies have suggested for a crucial role for exosomes in PaCa, which may be utilized to improve its future diagnosis and treatment, but the underlying molecular mechanisms as well as their potential clinical applications are largely unknown. By collecting and analyzing the most up-to-date literature, here we summarize the current progress of the clinical applications related to exosomes in PaCa. Therefore, we presently provide some rationale for the potential value of exosomes in PaCa, thereby promoting putative applications in targeted PaCa treatment.