Immunomodulatory drug lenalidomide is a synthetic compound derived by modifying the chemical structure of thalidomide to improve its potency and reduce its side effects. Lenalidomide is a 4-amino-glutamyl analogue of thalidomide that has emerged as a drug with activity against various hematological and solid malignancies. It is approved by FDA in USA for clinical use in myelodysplastic syndromes with deletion of chromosome 5q and multiple myeloma. Studies have shown that lenalidomide exert anti-tumor activity probably by various mechanisms in hematologic malignancies, such as immunomodulation, anti-angiogenesis and effects on signal transduction. In this article, the progresses of study on these problems are reviewed.
Hematologic Neoplasms ; immunology ; Humans ; Immunologic Factors ; Thalidomide ; analogs & derivatives ; pharmacology

Objective To investigate the effect of exogenous hydrogen sulfide on myocardial NF-κB signaling pathway in rats with hemorrhagic shock (HS).Methods Forty adult male rats,weighing 250-300 g,were randomly divided into 4 groups (n =10 each):sham operation group (Sham group),sham operation + NaHS group (Sham + NaHS group),HS group and HS + NaHS group.HS was induced by withdrawing blood from the femoral artery.After HS,NaHS 28 μmol/kg was injected intraperitoneally at 10 min before resuscitation in groups HS + NaHS and Sham + NaHS.MAP was monitored and recorded at 0,1.5,2,3,4 and 6 h after blood-letting.The rats were then sacrificed and hearts were removed for determination of phosphorylated IKKβ (pIKKβ),IκBα (pIκBα),NF-κB p65 (pNF-κB p65) and high-mobility group box 1 (HMGB1) and for examination of myocardial ultrastructure with light and electron microscope.Results Compared with Sham and Sham + NaSH groups,MAP was significantly decreased and the expression of pIKKβ,pIκBα,pNF-κB p65 and HMGB1 was up-regulated in HS and HS + NaHS groups (P ＜ 0.05).Compared with HS group,MAP was significantly increased and the expression of pIKKβ,pIκBα,pNF-κB p65 and HMGB1 was down-regulated in HS + NaHS group (P ＜ 0.05).The pathologic changes were attenuated in HS + NaHS group compared with group HS.Conclusion Exogenous hydrogen sulfide can attenuate myocardial injury induced by HS through inhibition of NF-κB signaling pathway and reduction of inflammatory response.

Female ; Humans ; Leukemia, Promyelocytic, Acute ; Pregnancy ; Tretinoin

Adult ; Aged ; Amifostine ; therapeutic use ; Benzene ; poisoning ; Female ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; chemically induced ; drug therapy

OBJECTIVETo investigate the effects of host-derived p38 mitogen-activated protein kinase subunit 38 (p38MAPK) and the hepatitis B virus X antigen (HbxAg) on cell proliferation and apoptosis in human hepatocellular carcinoma (HCC), and to study the mechanism underlying hepatocarcinogenesis.

METHODSLiver tissues were biopsied from healthy individuals and patients with chronic hepatitis B (CHB), liver cirrhosis, paratumor cirrhosis, and HCC. Immunohistochemical staining was used to detect expressions of HBxAg, p38MAPK, cell cycle G2/M phase-related factors (cdc25B, p34cdc2, cyclin B1), and cell proliferation factor ki-67.The terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling method (known as TUNEL) was used to detect apoptosis.

RESULTSThe highest rates of HBxAg were detected in CHB (65.0%) and HCC (44.4%) liver samples, and the antigen was mainly expressed in nuclei. Increasingly higher rates of p38MAPK, cdc25B, cyclin B1, and p34cdc2 expression were detected with increases in disease severity: normal liver (40.0%, 20.0%, 20.0%, and 30.0%, respectively), chronic hepatitis B (60.0%, 65.0%, 40.0%, and 50.0%, respectively), liver cirrhosis (65.0%, 75.0%, 70.0%, and 55.0%, respectively), paratumor cirrhosis (66.7%, 75.0%, 75.0%, and 63.9%, respectively), and HCC (77.8%, 80.6%, 80.6%, and 72.2%, respectively). In addition, the intracellular location of p38MAPK expression was different under different disease conditions, showing nuclear expression in CHB and liver cirrhosis samples and cytoplasmic expression in paratumor cirrhosis and HCC samples (x2 = 1.11, P more than 0.05). The proliferation index (PI) and the apoptosis index (AI) were both increased along with disease severity (normal more than CHB more than paratumor cirrhosis more than HCC) (PI: 0.0000+/-0.000, 0.0502+/-0.011, 0.0411+/-0.009, 0.0762+/-0.017; AI: 0.0351+/-0.024, 0.0607+/-0.022, 0.0562+/-0.013, 0.0716+/-0.011), with the notable exception for liver cirrhosis (PI: 0.1810+/-0.036 and AI: 0.1200+/-0.018). PI in poorly-differentiated HCC (0.2285+/-0.062) was significantly higher than in well-differentiated HCC (0.1216+/-0.032, t = 2.082, P = 0.044). AI in well-differentiated HCC (0.152+/-0.026) was significantly higher than in poorly-differentiated HCC (0.081+/-0.022, t = 2.129, P = 0.041).

CONCLUSIONSIn the process of hepatocarcinogenesis, HBxAg may cause a series of abnormal changes in cell cycle, proliferation and apoptosis by affecting the expression of p38MAPK.

Apoptosis ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Cycle ; Cell Division ; Cell Proliferation ; Hepatitis B, Chronic ; pathology ; Humans ; Liver Cirrhosis ; pathology ; Liver Neoplasms ; metabolism ; pathology ; Trans-Activators ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVETo investigate the roles of p38 MAPK in apoptosis of the normal liver cell, the paratumor cirrhosis hepatocellular cell and the hepatocellular carcinoma cell.

METHODSThree cell lines were adopted (the normal liver cell line HL-7702, the paratumor cirrhosis hepatocellular cell line QSG-7701 and the hepatocellular carcinoma cell line QGY-7703) and treated with Diamminedichloroplatin (DDP, cisplatin) and p38MAPK inhibitor SB203580. The apoptosis and cell cycles were detected by flow cytometry and electromicroscopy. The expressions of p38MAPK, CDC25B, p34cdc2 and cyclinB1 were detected by immunocytochemical staining , confocal microscopy and western blot.

RESULTSThe apoptotic rates in all three cell lines pretreated with DDP increased obviously and the rates in normal liver cells and HCC cells increased continuously even after SB203580 treatment, whereas in paratumor cirrhosis cells the rate decreased and the cell cycle stopped at S phase.

CONCLUSIONCisplatin induces apoptosis in the paratumor cirrhosis hepatocellular cell line QSG-7701 via activation of p38MAPK pathway and it differs in the normal liver cells from the hepatocellular carcinoma cells.

Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Line, Tumor ; Cisplatin ; pharmacology ; Humans ; Imidazoles ; pharmacology ; Liver Neoplasms ; metabolism ; pathology ; Pyridines ; pharmacology ; p38 Mitogen-Activated Protein Kinases ; metabolism

Biomarkers, Tumor ; metabolism ; Carcinoma, Hepatocellular ; genetics ; metabolism ; CpG Islands ; Cyclin-Dependent Kinase Inhibitor p57 ; genetics ; metabolism ; DNA Methylation ; Gene Expression Regulation, Neoplastic ; Humans ; In Situ Hybridization ; Liver ; metabolism ; Liver Neoplasms ; genetics ; metabolism ; Polymerase Chain Reaction ; methods ; Promoter Regions, Genetic ; RNA, Messenger ; genetics ; metabolism

Objeetive To investigate the efficacy and safety of long -term intravenous itraconazole for the treatment of invasive fungal infection ( IFI) in patients with hematological malignancies.Methods Sixty -nine patients with above mentioned conditions and diagnosed as IFI was administered at a dose of 200 mg every 12 hours for 2 days and followed by 200 mg every 24 hours at least 14 days.Responses were determined on the basis of clinical and microbiological criteria.Results The total response rates related to itraconazole among the IFI patients were 87.0%(60/69).Adverse effects rates were 18.8%, and 70% adverse effects happened winthin the first 14 days after intravenous itraconazole adminis-tered.Conclusion Long -term intravenous intraconazole antifungal treatment is effective and safe for hematologic malignancies with IFIs.

Objective:To discuss the characteristics of ultrasound diagnosis of optic disc capillary hemangioma.Methods:The study analyzed retrospectively 7 cases of optic disc capillary hemangioma diagnosed in the Beijing Tongren Hospital from 2015 to 2018. The size, morphology, internal echo, and secondary changes of the lesion were analyzed during ultrasound examination.Color Doppler flow imaging was used to check the blood flow in the lesion.Results:Pre-optic disc occupying lesions could be detected in the ultrasound images of the 7 cases. Lesion size: average base diameters (5.39±1.90)mm×(4.79±1.28)mm, average height (3.61±1.37)mm. Lesion morphology: 5 cases were round, and 2 cases were irregular. Echo within the lesion: 3 cases had medium echo inside the lesion, and 4 cases had high echo inside the lesion. Internal echo characteristics: 5 cases had uniform echo, and 2 cases had uneven echo. Secondary changes: 6 cases had secondary retinal detachment and vitreous opacity, and 1 cases was accompanied by retinal hemangioma in other parts. In all cases, blood flow signals could be detected inside the space-occupying lesions, which were in the form of branches, stripes or spots, and the blood flow spectrum showed a parallel spectrum of arteries and veins.Conclusions:Ultrasound examination of optic disc capillary hemangioma has certain characteristics, which can provide a valuable follow-up basis for clinical diagnosis.