The therapeutic effect and MR molecular imaging of FA-PEG-FePt/DDP nanoliposomes in AMF on ovarian cancer.

Purpose: This study aimed to construct targeting drug-loading nanocomposites (FA-FePt/DDP nanoliposomes) to explore their potential in ovarian cancer therapy and molecular magnetic resonance imaging (MMRI). Methods: FA-FePt-NPs were prepared by coupling folate (FA) with polyethylene-glycol (PEG)-coated ferroplatinum nanoparticles and characterized. Then cisplatin (DDP) was encapsulated in FA-FePt-NPs to synthesize FA-PEG-FePt/DDP nanoliposomes by thin film-ultrasonic method and high-speed stirring, of which MMRI potential, magnetothermal effect, and the other involved performance were analyzed. The therapeutic effect of FA-FePt/DDP nanoliposomes combined with magnetic fluid hyperthermia (MFH) on ovarian cancer in vitro and in vivo was evaluated. The expression levels of Bax and epithelial-mesenchymal transition related proteins were detected. The biosafety was also preliminarily observed. Results: The average diameter of FA-FePt-NPs was about 30 nm, FA-FePt/DDP nanoliposomes were about 70 nm in hydrated particle size, with drug slow-release and good cell-specific targeted uptake. In an alternating magnetic field (AMF), FA-FePt/DDP nanoliposomes could rapidly reach the ideal tumor hyperthermia temperature (42~44 °C). MRI scan showed that FA-FePt-NPs and FA-FePt/DDP nanoliposomes both could suppress the T2 signal, indicating a good potential for MMRI. The in vitro and in vivo experiments showed that FA-FePt/DDP-NPs in AMF could effectively inhibit the growth of ovarian cancer by inhibiting cancer cell proliferation, invasion, and migration, and inducing cancer cell apoptosis, much better than that of the other individual therapies; molecularly, E-cadherin and Bax proteins in ovarian cancer cells and tissues were significantly increased, while N-cadherin, Vimentin, and Bcl-2 proteins were inhibited, effectively inhibiting the malignant progression of ovarian cancer. In addition, no significant pathological injury and dysfunction was observed in major visceras. Conclusion: We successfully synthesized FA-FePt/DDP nanoliposomes and confirmed their good thermochemotherapeutic effect in AMF and MMRI potential on ovarian cancer, with no obvious side effects, providing a favorable strategy of integrated targeting therapy and diagnosis for ovarian cancer.

Defective modulation of LINE-1 retrotransposition by cancer-associated SAMHD1 mutants.

Long interspersed nuclear elements (LINE-1) is now considered as the only active autonomous mobile DNA in humans, LINE-1 retrotransposition activities are associated with and fluctuate during cancer initiation and progression; however, the mechanism underlying the increased LINE-1 activity in cancer is poorly understood. SAMHD1 has been reported to be a potent inhibitor of LINE-1 retrotransposition, and SAMHD1 mutations are frequently associated with cancer development. To gain insights on whether cancer-related SAMHD1 mutants affect LINE-1 activity, we explored the biochemical and cellular properties of some human mutants known correlate with the development of cancer. Most of the tested SAMHD1 cancer-related mutations were defective in LINE-1 inhibition. Interestingly we also found that SAMHD1 mutant K288T was defective for dNTPase activity but showed potent activity against LINE-1 retrotransposition. These findings suggest that LINE-1 inhibition does not depend solely on the dNTPase activity of SAMHD1. In contrast, SAMHD1's ability to inhibit ORF2p-mediated LINE-1 RNP reverse transcription was correlated with SAMHD1-mediated LINE-1 inhibition. Together, our data could also facilitate the deeper understanding for the inhibition of endogenous LINE-1 elements by SAMHD1.

The research advances of exosomes in esophageal cancer.

Esophageal carcinoma (EC) is one of the most common human digestive tract tumors, with high morbidity and mortality. It is necessary to elucidate the mechanism of cancer progression and seek early EC diagnostic markers for prompt detection and intervention. Exosomes are membrane nanovesicles secreted from many nucleated cells, 30-100 nm in diameter, containing various proteins, lipids and nucleic acids. They exist in peripheral blood, urine, ascites and other body fluids, widely engaged with intercellular material exchange and signal communication. Exosomes secreted from EC cells or tissues conduct important functions in tumor growth and progression. The detection and analysis of tumor-derived or tumor-associated exosomes has potential for EC early diagnosis and prognosis assessment. In the present paper, the exosomes' biological behaviors, isolation, detection and functions in EC progression - using as potential biomarkers for EC diagnosis or prognosis - are reviewed.

A scientometric analysis on hepatocellular carcinoma magnetic resonance imaging research from 2008 to 2017.

BACKGROUND: With the development of new magnetic resonance imaging (MRI) techniques, an increasing number of articles have been published regarding hepatocellular carcinoma magnetic resonance imaging (HCCMRI) in the past decade. However, few studies have statistically analyzed these published articles. In this study, we aim to systematically evaluate the scientific outcomes of HCCMRI research and explore the research hotspots from 2008 to 2017. METHODS: The included articles regarding HCCMRI research from 2008 to 2017 were downloaded from the Web of Science Core Collection and verified by two experienced radiologists. Excel 2016 was used to analyze the literature data, including the publication years and journals. CiteSpace V was used to perform co-occurrence analyses for authors, countries/regions and institutions and to generate the related collaboration network maps. Reference co-citation analysis (RCA) and burst keyword detection were also performed using CiteSpace V to explore the research hotspots in the past decade. RESULTS: A total of 835 HCCMRI articles published from 2008 to 2017 were identified. Journal of Magnetic Resonance Imaging published the most articles (79 publications, 9.46%). Extensive cooperating relationship were observed among countries/regions and among authors. South Korea had the most publications (199 publications, 21.82%), followed by the United States of America (USA) (190 publications, 20.83%), Japan (162 publications, 17.76%), and the People's Republic of China (148 publications, 16.23%). Among the top 10 co-cited authors, Bruix J (398 citations) was ranked first, followed by Llovet JM (235 citations), Kim YK (170 citations) and Forner A (152 citations). According to the RCA, ten major clusters were explored over the last decade; "LI-RADS data system" and "microvascular invasion" (MVI) were the two most recent clusters. Forty-seven burst keywords with the highest citation strength were detected over time. Of these keywords, "microvascular invasion" had the highest strength in the last 3 years. The LI-RADS has been constantly updated with the latest edition released in July 2018. However, the LI-RADS still has limitations in identifying certain categories of lesions by conceptual and non-quantitative probabilistic methods. Plenty of questions still need to be further answered such as the difference of diagnostic efficiency of each major/ancillary imaging features. Preoperative prediction of MVI of HCC is very important to therapeutic decision-making. Some parameters of Gd-EOB-DTPA-enhanced MRI were found to be useful in prediction of MVI, however, with a high specificity but a very low sensitivity. Comprehensive predictive model incorporating both imaging and clinical variables may be the more preferable in prediction of MVI of HCC. CONCLUSIONS: HCCMRI-related publications displayed a gradually increasing trend from 2008 to 2017. The USA has a central position in collaboration with other countries/regions, while South Korea contributed the most in the number of publications. Of the ten major clusters identified in the RCA, the two most recent clusters were "LI-RADS data system" and "microvascular invasion", indicative of the current HCCMRI research hotspots.

The Possible Mechanisms of HSV-TK/Hyperthermia Combined with 131I-antiAFPMcAb-GCV Nanospheres to Treat Hepatoma.

Our previous findings showed a good therapeutic effect of the combination of suicide gene HSV-TK, nuclide 131I, and magnetic fluid hyperthermia (MFH) on hepatoma by using magnetic nanoparticles as linkers, far better than any monotherapy involved, with no adverse effects. This combination therapy might be an eligible strategy to treat hepatic cancer. However, it is not clear how the combination regimen took the therapeutic effects. In the current study, to explore the possible mechanisms of radionuclide-gene therapy combined with MFH to treat hepatoma at tissue, cellular, and molecular levels and to provide theoretical and experimental data for its clinical application, we examined the apoptosis induction of the combination therapy and investigated the expression of the proteins related to apoptosis such as survivin, livin, bcl-2, p53, and nucleus protein Ki67 involved in cell proliferation, detected VEGF, and MVD involved in angiogenesis of tumor tissues and analyzed the pathologic changes after treatment. The results showed that the combination therapy significantly induced the hepatoma cell apoptosis. The expression of survivin, VEGF, bcl-2, p53, livin, Ki67, and VEGF proteins and microvascular density (MVD) were all decreased after treatment. The therapeutic mechanisms may be involved in the downregulation of Ki67 expression leading to tumor cell proliferation repression and inhibition of survivin, bcl-2, p53, and livin protein expression inducing tumor cell apoptosis, negatively regulating VEGF protein expression, and reducing vascular endothelial cells, which results in tumor angiogenesis inhibition and microvascular density decrease and tumor cell necrosis. These findings offer another basic data support and theoretical foundation for the clinical application of the combination therapy.

Cumulative dose of radiation therapy of hepatocellular carcinoma patients and its deterministic relation to radiation-induced liver disease.

This study aimed to investigate the relationship between dose and radiation-induced liver disease (RILD) in patients with hepatocellular carcinoma (HCC) receiving 3-dimensional conformal radiotherapy (3DCRT). Twenty-three patients with HCC who received conventional fractionated 3DCRT, including 7 who were diagnosed with classic RILD, were enrolled in this retrospective investigation. Cone-beam computed tomography (CBCT) scans were acquired at the time of treatment for each patient. The beams from each patient's treatment plan were applied to each pretreatment CBCT (the modified CBCT or mCBCT) to construct the delivered dose distribution of the day considering inter-treatment anatomy changes. The daily doses were summed together with the help of deformable image registration (DIR) to obtain the adjusted cumulative dose (Dadjusted). The dose changes to the normal liver between the original planned dose (Dplan) and Dadjusted were evaluated by V20, V30, V40, and the mean dose to normal liver (MDTNL). Univariate analysis was performed to identify the significant dose changes. Among the 23 patients, the liver V20, V30, V40, and MDTNL showed significant differences between Dplan and Dadjusted, with average values of these parameters increased by 4.1%, 4.7%, 4.5%, and 3.9 Gy, respectively (p < 0.05). The adjusted liver dose in 21 patients (91%) was higher than the planned value. For patients without and with RILD,the MDTNL was increased on average by 3.5 Gy and 4.7 Gy, and normal tissue complication probability (NTCP) increased on average by 2.8% and 7.5%, respectively. Our study found that the adjusted cumulative dose based on calculations using pretreatment mCBCT differs significantly from planned dose; the use of the dosimetric results of the initial plan was found to be less predictive of RILD as compared with Dadjusted. Determination of a reconstructed Dadjusted using the mCBCT scans are more accurate in predicting RILD and has the potential to reduce the risk of RILD.

The Recent Advances on Liver Cancer Stem Cells: Biomarkers, Separation, and Therapy.

As the third major reason of mortality related to cancer in the world, liver cancer is also the fifth most frequent cancer. Unluckily, a majority of patients succumb and relapse though many progresses have been made in detection and therapy of liver cancer. It has been put forward that in liver cancer, cancer stem cells (CSCs) hold main responsibility for the formation, invasion, metastasis, and recurrence of tumor. Strategies that are intended to target liver CSCs are playing a more and more significant role in supervising the development of liver cancer treatment and assessing new therapeutic methods. Herein, a brief review about molecule markers, signal pathways, separation, and treatment on liver cancer stem cells (LCSCs) is provided in this paper.

Tributyltin chloride-induced immunotoxicity and thymocyte apoptosis are related to abnormal Fas expression.

Tributyltin chloride (TBTC), a characteristic organotin compound, is widely used as an agricultural pesticide, as a stabiliser for polyvinyl-chloride plastics and in antifouling paints for ship hulls. Organotin compounds are known to produce toxicity in the immune system, but the mechanism underlying this immunotoxicity remains unclear. In this study, we evaluated the immunotoxic effect of TBTC on the acquired immune response, and we investigated the involvement of thymocyte apoptosis and Fas expression in the observed immunotoxicity of TBTC. Mice were randomly assigned to four groups (10 mice per group) and treated with TBTC at doses of 0, 0.5, 4 and 20 mg/kg by oral gavage for 28 days. Following TBTC administration, animals were sacrificed, and morphologic changes in the thymus and spleen were assessed. Atrophy in both the thymus and spleen was observed in all groups treated with TBTC, and the relative organ weight in the highest TBTC group (20 mg/kg) was significantly lower than that observed in the control group. We also conducted assays to assess the cellular and humoral functional responses such as plaque-forming cell assay (PFC), lymphocyte proliferation test and delayed-type hypersensitivity (DTH) response to SRBC. Our results indicate that at doses of 4 mg/kg and 20 mg/kg, TBTC could significantly suppress both the humoral and cellular immune responses when compared to the control group (p<0.05). In addition, immunohistochemical staining and flow cytometry analysis were carried out to measure the expression of Fas and thymocyte apoptosis, respectively. We observed a dose-dependent increase in thymocyte apoptosis and that Fas expression in the TBTC-treated groups (4 mg/kg and 20 mg/kg) was significantly enhanced when compared to the control group. Correlation analysis demonstrated a positive linear correlation between apoptosis and Fas expression, indicating that TBTC-induced thymocyte apoptosis may be mediated by Fas expression. Taken together, our data clearly demonstrate that TBTC-induced immunotoxicity is associated with thymocyte apoptosis and that this process is mediated by the Fas pathway.