[Clinical research in cell therapy of liver diseases: progress and challenges].

The high incidence of chronic liver disease is a serious threat to public health, and the current comprehensive internal medicine treatment is ineffective. Liver transplantation is limited by the shortage of liver source and post-transplant rejection, and thus unmet the clinical needs. More importantly, cell therapy shows great promise for the treatment of chronic liver disease. Over recent years, domestic and foreign scholars have carried out a variety of cell therapy preclinical and clinical trials for critical liver disease, and achieved certain results, providing new methods for the treatment of chronic liver diseases. This review discusses the cell therapy research status and application progress, various existing problems and challenges, and key issues of mesenchymal stem cells in the treatment of chronic liver diseases.

[An in vitro model study of computer-guided endodontic microsurgery].

Objective: To assess and compare the accuracies and operating time of endodontic microsurgery performed by operators with different levels of experience in endodontics using computer-guided techniques including dynamic and static navigations in a surgical simulation model. Methods: Six pairs of three dimensional (3D)-printed models of upper and lower jaws were set up on dental manikins. A total of 120 teeth (10 teeth each jaw) were included in the models. Microsurgeries of osteotomy and root-resection were performed on the models by two operators with different experience, namely novices and experts, under of free hand (FH)(n=20), dynamic navigation (DN)(n=20), and static navigation (SN)(n=20) conditions, respectively. The duration of each operation was recorded. Cone-beam CT was taken for 3D-printed models before and after the operation. The path of preoperative surgery planning was simulated. The linear deviations at the entry and the end point and the angular deviation of the access path between the simulated and the actual operation were compared by the software. Results: Significant difference of the entry deviation was observed between the novices and the experts in the FH group [(1.44±0.49) and (1.02±0.58) mm] (q=4.67, P=0.020). There were no significant differences between the novices and the experts in the end point and angular deviations (P>0.05). For the novices, the entry deviations in both DN and SN groups [(0.76±0.32) and (0.66±0.20) mm] were significantly lower than those in FH group (q=7.58, P<0.001; q=8.66, P<0.001). The angular deviations in the abovementioned two groups (5.0°±3.5°, 3.9°±2.1°) were significantly lower than that in FH group (10.9°±6.1°) (q=7.38, P<0.001; q=8.70, P<0.001). For the experts, significant differences were found only in the angular deviations among DN, SN and FH groups (3.6°±1.9°, 3.2°±1.7° and 8.2°±3.9°) (q=5.74, P=0.001; q=6.29, P<0.001). The operation durations were significantly shortened for both the novices [(4.80±2.15), (1.09±0.48) min] (q=14.60, P<0.001; q=20.10, P<0.001) and the experts [(3.40±1.96),(1.02±0.34) min] (q=5.86, P<0.001; q=9.37, P<0.001) by using DN and SN techniques. Regarding the differences between tooth types, in FH group, the operating time on the anterior teeth was significantly shorter than that on the posterior teeth (q=8.14, P<0.001; q=5.20, P=0.007), while in DN and SN groups, there were no significant differences in the operating time between two tooth types (P>0.05). No significant differences were discovered in the accuracies on the anterior and posterior teeth among three techniques or between two kinds of operators (P>0.05). Conclusions: Dynamic and static navigation techniques could assist the clinicians, especially the novices, to improve the accuracies and shorten the operating time of osteotomy and root resection microsurgeries.

[The progress and challenges in immunotherapy for the difficulty- to- treat liver diseases].

As a digestive organ, the liver has the functions of metabolism, synthesis, and detoxification. It is also an immune organ and plays an important role in maintaining anti-infection, autoimmune stability, and anti-tumor. In particular, the liver has unique immunological advantages. Its immune cells can maintain the liver's immune homeostasis and participate in immunoregulation. A variety of immunotherapy is used in clinical trials for the treatment of difficult and critical liver diseases. This review mainly summarizes the recent clinical trials of immunotherapy in chronic hepatitis B, cirrhosis, hepatocellular carcinoma, and autoimmune liver disease.

[Effects of programmed death receptor-1 antibody in patients with hepatitis B-associated liver cancer].

Objective: To investigate the effect of programmed death receptor (PD)-1 antibody therapy in patients with hepatitis B-associated liver cancer. Methods: Data of 29 chronically infected HBV patients with liver cancer who received PD-1 antibody combined with tyrosine kinase inhibitor in the Department of Infectious Diseases of the Fifth Medical Center of PLA General Hospital from March 2020 to January 2021 were selected. At the same time, all of the above-mentioned hepatitis B virus (HBV) patients were treated with nucleos(t)ide analogues. Patients clinical diagnostic data, laboratory test results, tumor response and the incidence of adverse reactions were collected retrospectively to understand the overall safety, therapeutic anti-tumor effect, HBV changes condition and the correlation between HBV changes and anti-tumor PD-1 antibody efficacy, high viral load treatment condition, and HBV reactivation safety issues. Statistical analysis was performed by non-parametric rank sum test. Results: Therapeutic anti-tumor effect and safety profile were good in patients. The complete remission rate was reached 27.6%. Adverse reactions were mostly mild, and the incidence of serious adverse reactions was low. After 12 weeks of follow-up, HBV DNA and hepatitis B surface antigen (HBsAg) was quantitatively decreased (P < 0.05). HBV DNA and HBsAg were decreased more significantly in patients with progressive disease (PD), stable disease (SD) and partial response (PR) (P < 0.05). Five patients with HBV DNA ≥ 10(4) IU/ml had responded well to the tumor treatment without serious adverse reactions. One patient had a slight increase in HBV DNA and alanine aminotransferase, while there was no HBV reactivation and correlated liver damage. Conclusion: Patients with HBV-associated liver cancer who received combined therapy have good anti-tumor efficacy and safety profile. PD-1 treatment has a certain effect on HBV. Compared with non-responders, patients with tumor response have better antiviral treatment efficacy. The safety of treatment in patients with high viral load is manageable, and there are no safety issues related to HBV reactivation.

The role of CD8 T cells in controlling HIV beyond the antigen-specific face.

OBJECTIVES: Understanding the determinants of HIV immune control is important for seeking viable HIV prevention, treatment and curative strategies. The antigen-specific roles of CD8 T cells in controlling primary HIV infection have been well documented, but their abilities to control the latent HIV reservoir is less well studied. METHODS: The scientific literature on this issue was searched on PubMed. RESULTS: Recent reports have demonstrated that CD8 T cells are also involved in the control of viral replication in HIV-infected individuals receiving antiretroviral therapy (ART). However, based on accumulating evidence, the antiviral role of CD8 T cells in ART patients may not be achieved via an antigen-specific manner as HIV-specific CD8 T cells can sense, but not effectively eliminate, cells harbouring intact provirus without first being activated. Our recent study indicated that virtual memory CD8 T cells, a semi-differentiated component of CD8 T cells, may be involved in the mechanism restraining the HIV DNA reservoir in ART patients. CONCLUSIONS: In this review, we summarize recent findings on the role of CD8 T cells in controlling HIV, highlighting differences between conventional antigen-specific and innate-like CD8 T cells. A better understanding of the roles of CD8 T cells during HIV infection should benefit the informed design of immune-based treatment strategies.

[Key gene leading to poor prognosis of triple-negative breast cancer based on bioinformatics analysis].

Objective: To find the possible targets for the study and treatment of triple-negative breast cancer (TNBC), and to analyze and predict the key genes affecting the prognosis of TNBC by bioinformatics. Methods: Raw data on transcriptome sequencing of clinical specimens from patients with TNBC were searched by searching GEO Datasets in the National Center for Biotechnology Information (NCBI) database. The differential gene was then submitted to the Enrichr website for pathway enrichment. Survival analysis was used to finally identify the most significant differences in the prognosis of patients with TNBC. Results: Only ADAM9 gene showed a significant correlation with the poor prognosis of patients with TNBC (P<0.05), and ADAM9 only showed specificity associated with prognosis in patients with TNBC, and was not with other breast cancer types. Conclusion: ADAM9 gene has been proved to be related to the poor prognosis in patients with TNBC. Therefore, ADAM9 gene can be regarded as a possible key gene leading to lymph node metastasis and poor prognosis in patients with TNBC.

[Efficacy and peripheral immunity analysis of allogeneic natural killer cells therapy in patients with hepatocellular carcinoma].

OBJECTIVE: To evaluate the safety and efficacy of allogeneic natural killer (NK) cells in the treatment of primary hepatocellular carcinoma (HCC), and to elucidate the mechanism of NK cells therapy. METHODS: Twenty-one patients with primary HCC treated with allogeneic NK cells at the Fifth Medical Center of the PLA General Hospital were followed up for 1 year. Peripheral blood mononuclear cells (PBMCs) were isolated from patient-related donors and cultured in vitro for 15 days and infused to the patients in two consecutive days. Clinical data and laboratory data were collected and analyzed, including survival, clinical features, imaging changes, hematology, immunology, and biochemical indicators to evaluate the safety and efficacy of allogeneic NK cell therapy. The changes of peripheral blood lymphocyte subsets after treatment were also analyzed to explore the possible anti-tumor mechanisms. RESULTS: (1) Of the 21 patients with primary HCC, 11 patients were treated once, 5 patients were treated twice, and 5 patients were treated 3 times. After allogeneic NK cells infusion, 10 patients had fever, 1 patient had slight hepatalgia and 1 patient had slight headache, no other adverse events occurred including acute and chronic graft-versus-host disease (GVHD). They resolved spontaneously within 8 hours without other treatment. (2) The total disease control rate was 76.2% during one-year follow-up. Among them, the patients with Barcelona clinic liver cancer (BCLC) stage A had a disease control rate of 100%, stable disease (SD) in 10 cases; BCLC stage B patients had a disease control rate of 60%, partial response (PR) in 1 case, and SD 2 in cases; BCLC stage C patients had a disease control rate of 50%, complete response (CR) in 1 case, and 2 cases of PR. (3) The frequencies of NK cells and CD8+ T cells in peripheral blood were significantly lower than that before at 24 hours after treatment, and the frequencies of CD4+ T cells and CD4/CD8 were significantly higher than the baseline. CONCLUSION: Allogeneic NK cells have good safety and efficacy in the treatment of primary HCC. The anti-tumor effect of the allogeneic NK cells may play an important role in the activation of the patient's natural immune system and delay disease progression, suggesting that allogeneic NK cells combined with sorafenib may be a very effective treatment for advanced HCC, and further large-sample multicenter randomized controlled clinical trials are needed to validate this result.

[Progress and prospects of clinical cell therapy for liver cirrhosis and liver cancer].

The treatment options for liver cancer and liver cirrhosis are limited. Cell therapy (immune cells, stem cells) can significantly improve the therapeutic effect by actively regulating body's immunity. In addition, when choosing different methods of cell therapy, clinicians should also fully consider the adverse reactions associated with cell therapy. This article reviews the progress of cells therapy in clinical trials of liver cancer and liver cirrhosis, including therapeutic mechanism, advantages, disadvantages and limitations.

Upregulated miR-29c suppresses silica-induced lung fibrosis through the Wnt/ß-catenin pathway in mice.

Silicosis is an irreversible lung disease resulting from long-term inhalation of occupational dust containing silicon dioxide. However, the pathogenesis of silicosis has not been clearly understood yet. Accumulating evidence suggests that miR-29 may have a significant anti-fibrotic capacity, meanwhile it may relate to Wnt/ß-catenin pathway. The purpose of this study was to discuss the role of miR-29 in the progression of silicosis. A lentiviral vector was constructed, named Lv-miR-29c, which was overexpressing miR-29c. In vivo, intratracheal treatment with Lv-miR-29c significantly increased expression of miR-29c, and reduced expression of ß-catenin, matrix metalloproteinase (MMP)-2, and MMP-9 in the lung and levels of transforming growth factor-beta 1 (TGF-ß1) and interleukin-6 (IL-6) in bronchoalveolar lavage fluid, and notably attenuated pulmonary fibrosis as evidenced by hydroxyproline content in silica-administered mice. These results indicated that miR-29c inhibited the development of silica-induced lung fibrosis. Thus, miR-29c may be a candidate target for silicosis treatment via its regulation of the Wnt/ß-catenin pathway.

[Effects of workplace health promotion in a wind power equipment manufacturing factory].

Objective: To explore the effects of workplace health promotion in a wind power equipment manufacturing factory. Methods: Based on investigation of occupational hazard factors, personal protective equipment (PPE) application, occupational health management and healthy life style, health promotion strategy and intervention were implemented in this factory. The sample size was 56 for monitoring of occupational hazard factors before and after intervention, 283 and 259 for questionnaire before and after intervention. Results: After intervention, the qualified rate of workplace occupational hazard factors increased from 67.9% to 82.1%. The abnormal rate of occupational health surveillance among workers decreased from 24.7% to 11.6%. The rates of correct use of PPE increased from 39.6% to 80.7%. The rates of awareness of occupational health increased from 10.2% to 71.8%. The rates of awareness of chronic disease increased from 10.2% to 77.2%. Two-week consultation rate decreased from 6.4% to 4.2%. Smoking rate decreased from 12.4% to 10.4%. Conclusion: Workplace health promotion is effective measures for reducing occupational hazard factors exposure and improving workers' health.

Neuropeptide Y mediates glucocorticoid-induced osteoporosis and marrow adiposity in mice.

UNLABELLED: Increased neuropeptide Y (NPY) expression occurred in the glucocorticoid-induced osteoporotic skeleton. NPY knockout mice exhibited a minor response to the glucocorticoid-mediated exacerbation of bone accretion and fatty marrow pathogenesis. NPY deletion restored SITR1 signaling and enhanced PPARγ ubiquitination of bone tissue, an alternative strategy for ameliorating glucocorticoid-induced skeletal deterioration. INTRODUCTION: Glucocorticoid excess is observed to worsen the pathogenesis of osteoporosis and fatty marrow. This study was undertaken to investigate the contribution of neuropeptide Y (NPY) to glucocorticoid-induced bone loss and marrow adiposity. METHODS: NPY knockout and wild-type mice were administered methylprednisolone for four consecutive weeks. Bone mineral density, microarchitecture, and calcein-labeled mineral acquisition were quantified by µCT, dual energy X-ray absorptiometry, and histomorphometry. Expression of osteogenic and adipogenic markers and acetylation states of PPARγ were detected by RT-quantitative PCR, immunoprecipitation, and immunoblotting. RESULTS: High NPY levels were associated with glucocorticoid-induced trabecular bone deterioration and marrow fat accumulation. Mice lacking NPY had high bone mass concomitant with spacious trabecular and cortical bone microstructure. NPY deletion shielded skeletal tissues from the glucocorticoid-induced impediment of bone mass, trabecular morphometric characteristics, mineral accretion activity, and fatty marrow development. Ex vivo, NPY deficiency sustained osteogenic differentiation capacity and curtailed the glucocorticoid-mediated escalation of adipocyte formation reactions of primary bone-marrow mesenchymal cells. NPY deletion appeared to modulate Y1 and Y2 receptors, sirtuin 1, ERK, and p38 signaling pathways, an effect that facilitated hypoacetylation and ubiquitination of adipogenic transcription factor PPARγ in the skeletal tissues exposed to glucocorticoid stress. CONCLUSIONS: NPY mediates the glucocorticoid-induced disturbance of mineral accretion and marrow adipogenesis through post-translational modification of PPARγ. This study brings a new molecular insight into the disintegration of adipogenic and osteogenic activities within glucocorticoid-mediated osteoporotic skeletons. Control of NPY is an alternative strategy to ameliorate glucocorticoid-induced bone destruction and fatty marrow.

[Safety and efficacy of human umbilical cord derived-mesenchymal stem cell transplantation for treating patients with HBV-related decompensated cirrhosis].

OBJECTIVE: To retrospectively investigate the efficacy of human umbilical cord-derived mesenchymal stem cells (UC-MSC) as clinical treatment for HBV-related decompensated liver cirrhosis (HBV-DLC)•D. METHODS: Sixty patients with HBV-DLC were given standard medical treatment combined with a 3-month regimen of UC-MSC at a dose of 0.5-1.0×10(6) cells/kg/month. Another group of patients with HBV-DLC (n=120; control group) that was matched (2:1) to the case group by age, sex, diagnosis, and follow-up period was given the standard medical treatment only. We reviewed all patients' data of biochemical tests, imaging examinations, Child-Pugh scores, and adverse reactions. Comparisons of continuous data between the two groups were made by independent-sample t-test, and comparisons of categorical data were made by chi-square test. RESULTS: Compared with the control group, the group that received the combination UC-MSC treatment showed a significant rise in cholinesterase, globulin and alkaline phosphatase, and reduced Child-Pugh scores during the follow-up period. However, there was no significant difference between the groups of patients for levels of alanine transaminase, total bilirubin, albumin, total cholesterol, or prothrombin activity. CONCLUSIONS: Addition of the UC-MSC treatment to the standard therapy could help to improve liver function in patients with HBV-DLC.

PD-1/PD-L1 costimulatory pathway-induced mouse islet transplantation immune tolerance.

BACKGROUND: Programmed death-1/PD-1 ligand-1 (PD-1/PD-L1) costimulatory signals may play an important role in T-cell-induced immune response. The aim of this study is to investigate the role of the PD-1/PD-L1 costimulatory pathway on immunotolerance induction in mouse pancreatic islet transplantation. METHODS: Full-length mouse PD-L1 cDNA was subcloned into pShuttle-GFP-CMV(-) shuttle plasmid. The product was cut by certain restriction endonuclease and ligated with pAdxsi vector. The adenovirus bone plasmid was transformed into DH5α-competent bacteria. After linearization, the recombined adenovirus DNA was transfected into 293 cells for package and amplification. Streptozotocin was injected intraperitoneally into C57BL/6 (H-2(b)) mouse to induce diabetic model recipient. Recipients were randomly divided into 3 groups. Group A was the control. Group B and group C were injected with Ad-EGFP and Ad-PD-L1 through the tail vein, respectively, 1 day before islet transplantation. The 300 to 400 islets of DBA/2 (H-2(d)) were transplanted into the renal subcapsular space of the diabetic model recipient. We monitored and analyzed the blood glucose levels and the survival time of grafts after transplantation. RESULTS: Recombinant adenovirus Ad-PD-L1 had high efficiency expression of PD-L1 in recipient mouse. The blood glucose concentration of mice in the Ad-PD-L1 gene treatment group was obviously lower than that of the control and Ad-EGFP treatment groups and was stable and kept within the normal range at post-transplant 21 days. The survival time of grafts in the Ad-PD-L1 group (27.6 ± 3.5 days) was significantly longer than in the control (7.8 ± 0.33 days) and Ad-EGFP groups (7.6 ± 0.59 days), P < .01. Mixed lymphocyte response showed a specific decrease reaction of recipient lymphocyte vs donor lymphocyte. Flow cytometry detection showed that unsplit cells occupied 90% of recipient mouse lymphocytes, but unsplit cells among normal C57BL/6 mouse lymphocytes without Ad-PD-L1 gene treatment were 51 in the control group. The differences between them were significant (P < .01). CONCLUSION: Recombinant adenovirus Ad-PD-L1 has been successfully constructed. In mouse pancreatic islet transplantation, it can suppress the activation of recipient T lymphocyte through the PD-1/PD-L1 costimulatory pathway, and significantly prolong the survival time of grafts.

MicroRNA-19b targets Mfn1 to inhibit Mfn1-induced apoptosis in osteosarcoma cells.

Accumulative evidence has confirmed that, miR-17-92, a typical polycistronic mRNA cluster, was up-regulated in various solid tumors, and play an important role in the occurrence and development progress of tumors. In our study, we detected the six members of miR-17-92 cluster in osteosarcoma cell line, finding that the expression of miR-17 and miR-19b was up-regulated significantly. Further studies have found that Mfn1 was one of the target genes of miR-19b and the transcription and expression level of Mfn1 were down-regulated by miR-19b. MTS, flow cytometry, TUNEL-DAPI, Annexin V-FITC and transwell assay demonstrated that Mfn1 significantly blocked the cell cycle, promoted apoptosis and inhibited proliferation and invasion of osteosarcoma cells. Whereas, miR-19b targets 3'UTR sequences of Mfn1 genes inhibit the expression of Mfn1, thus inhibited Mfn1 triggered anti-cancer effect. Taken together, miR-19b functions by targeting Mfn1 reduce the protein expression level, thus provides a novel target to understand the molecular biology and genetics mechanisms of occurrence and development of osteosarcoma, contributing to the diagnosis and therapy of osteosarcoma.

Research progress in the radioprotective effect of superoxide dismutase.

Irradiation from diverse sources is ubiquitous and closely associated with human activity. Radiation therapy (RT), an important component of the multiple radiation origins, contributes significantly to oncotherapy by killing tumor cells. On the other hand, RT can also cause some undesired normal tissue injuries that afflict numerous cancer patients. Although many promising radioprotective agents are emerging, few of them have entered the market successfully due to various limitations. At present, the most accepted hypothesis for the radiation-caused injury involves reactive oxygen species (ROS) generation. Superoxide dismutase (SOD), the unique enzyme responsible for the dismutation of superoxide radicals, is expected to occupy an indispensable position in the treatment of ROS-mediated tissue injuries originating from exposure to radiation. This review focuses on the mechanism of radioprotection by SOD at the tissue or organ level, cellular level, and molecular level, respectively, in order to provide references for further investigation of radiation injury and development of new radioprotectors.

Increased Th17 cells contribute to disease progression in patients with HBV-associated liver cirrhosis.

T helper (Th) 17 cells have been demonstrated to participate in the pathogenesis of HBV-associated liver damage. However, little is known regarding the immunopathogenic role of liver fibrosis in patients with HBV-associated liver cirrhosis. The aims of this study were to evaluate whether Th17 cells are related to disease progression in patients and to explore the possible mechanisms. The frequencies of circulating Th17 cells were analysed in 78 patients with hepatitis B and cirrhosis (Child A: 34; Child B: 22; Child C 22) and matched controls. Liver samples were collected from 13 patients with HBV-associated cirrhosis, 23 patients with chronic hepatitis B and 12 healthy controls for immunohistochemical analysis. IL-17 receptor expression was studied on liver biopsies and in human hepatic stellate cells as well as their response to recombinant IL-17 by flow cytometry. Patients with hepatitis B-associated cirrhosis with more severe disease displayed significant increases in peripheral numbers of Th17 cells as well as in IL-17 plasma levels. The increased intrahepatic IL-17(+) cells correlated positively with fibrotic staging scores and clinical progression from CHB to cirrhosis. Moreover, many IL-17(+) cells were located in fibrotic areas in the liver of patients with cirrhosis. In vitro, IL-17 together with IL-17-activated monocytes, could promote the activation of stellate cells, which, in turn, aggravated liver fibrosis and the inflammatory response. In summary, increased peripheral and intrahepatic Th17 cells are enriched in patients with hepatitis B and cirrhosis and contribute further to the severity of disease progression through induction of stellate cell activation.

Immunomodulatory properties and therapeutic application of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are multi-potent progenitor cells that are isolated from the bone marrow and several adult organs and tissues. These cells possess remarkable immunosuppressive properties and can inhibit the proliferation and function of the major immune cell populations, including T cells, B cells and natural killer (NK) cells; modulate the activities of dendritic cells (DCs); and induce regulatory T cells both in vivo and in vitro. These unique properties make MSCs ideal candidates for clinical application as immunosuppressants. The immunomodulatory effect of MSCs is mediated by a non-specific anti-proliferative action of these cells, which is dependent on cell-cell contact or secreted soluble factors such as indoleamine 2,3-dioxygenase (IDO), prostaglandin E(2) (PGE(2) ), nitric oxide (NO), histocompatibility leucocyte antigen-G (HLA-G), transforming growth factor (TGF)-ß, interferon (IFN)-γ and interleukin (IL)-1ß. Considerable progress has been obtained in preclinical studies on MSCs, including those on their ability to activate allogeneic cells. This review examines the current understanding of the immunomodulatory properties of MSCs and its therapeutic implication for immune-mediated diseases and transplant rejection.

Effect of heparin-superoxide dismutase on γ-radiation induced DNA damage in vitro and in vivo.

The effects of heparin-superoxide dismutase (SOD) conjugate (heparin-SOD) on γ-radiation induced DNA damage in vivo and in vitro were evaluated. Plasmid pcDNA3.0 solution was mixed with heparin-SOD, SOD, and a mixture of heparin and SOD (heparin + SOD), respectively, and irradiated with (60)Co at a dosage of 120 Gy. DNA injury was analyzed using agarose gel electrophoresis. The results showed that the degree of injury of pcDNA3.0 mixed with heparin-SOD, SOD, or heparin + SOD was less than that of untreated pcDNA3.0, and among them the degree of injury of pcDNA3.0 mixed with heparin-SOD was the least. It also showed that the protective effect increased with an increase of heparin-SOD concentration. The effects of SOD and heparin-SOD on the DNA damage and tumor inhibition rate of (60)Co γ-radiation exposure on tumor-bearing mice were also studied. Agarose gel electrophoresis showed that, when different SOD samples were administered before irradiation, the thymus DNA injuries of heparin-SOD, SOD, or heparin + SOD groups were more serious than that of the control group, and the DNA injuries of heparin-SOD or heparin + SOD groups were the most serious, which contradicted the above in vitro experiments. However, when heparin-SOD was administered post irradiation, it showed a repairing effect on the injured DNA.

Expression of KL-6 mucin, a human MUC1 mucin, in intrahepatic cholangiocarcinoma and its potential involvement in tumor cell adhesion and invasion.

AIMS: Aberrant expressions of KL-6 mucin were proved to be associated with worse tumor behaviors of many carcinomas. This study was to evaluate the expression KL-6 mucin, a human MUC1 mucin, in intrahepatic cholangiocarcinoma (CC) and its significance in tumor progression. MAIN METHODS: KL-6 mucin expressions in 21 patients with CC, 12 with combined hepatocellular and cholangiocarcinoma (cHCC-CC), and 78 with hepatocellular carcinoma (HCC) were detected by immunohistochemical staining. The effects of two glycosylation inhibitors (tunicamycin and benzyl-alpha-N-acetylgalactosamine (BAG)) on CC cell proliferations were assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assays. KL-6 mucin expressions were detected by immunocytochemical staining and western blotting after tunicamycin or BAG treatment. Cell adhesive and invasive properties were evaluated by adhesion tests and transwell chamber assays after tunicamycin or BAG treatment. KEY FINDINGS: Positive KL-6 mucin staining was observed in all CC tissues and CC areas of cHCC-CC tissues. Immunocytochemical staining and western blotting showed that KL-6 mucin expressions were significantly reduced after both inhibitors treatment. Cell adhesive properties were significantly decreased after both inhibitors treatment, while cell invasive abilities were significantly decreased after BAG but not tunicamycin treatment. SIGNIFICANCE: This study indicated that KL-6 mucin might be a specific tumor target for CC. Therapeutic strategies that target glycosylation of KL-6 mucin may be useful to control aggressive behaviors of CC.