Animals ; Cells, Cultured ; Male ; Phenols ; toxicity ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Sertoli Cells ; drug effects ; metabolism ; Steroidogenic Factor 1 ; genetics ; metabolism

Lenalidomide is an immunomodulatory, antiangiogenic drug that is a structural analog of thalidomide. Studies showed that lenalidomide may work through various mechanisms in hematologic malignancies. These mechanisms involved direct cytotoxicity as well as through indirect effects on tumor immunity etc. It is approved by the Food and Drug Administration for treatment of multiple myeloma and myelodysplastic syndromes, and proved to have a good efficacy. Recent studies demonstrate that oral lenalidomide alone produces durable responses with manageable adverse events in patients with non-Hodgkin's lymphoma, relapsed/refractory Hodgkin's lymphoma, chronic lymphocytic leukemia and older patients with acute myeloid leukemia etc, warranting further investigation of treatment for these patients. This review focuses the related studies and the latest progression about lenalidomide in hematological malignancies in order to provide some references and help to the use of lenalidomide for the treatment of hematological malignancies.
Angiogenesis Inhibitors ; therapeutic use ; Hematologic Neoplasms ; drug therapy ; Humans ; Multiple Myeloma ; drug therapy ; Myelodysplastic Syndromes ; drug therapy ; Thalidomide ; analogs & derivatives ; therapeutic use

ObjectiveTo investigate the gene expressions of TAZ and Wnt/β-catenin on the postosteogenic cells of mesenchymal stem cells(MSC)in multiple myeloma(MM)patients and to explore the potential therapeutic target of multiple myeloma bone disease (MBD).MethodsBone marrow mononuclear cells MNC from MM and controls were isolated,cultured,expanded and then induced to osteogenic differentiation.Realtime quantitative RT-PCR was employed to detect the osteogenic markers (TAZ,Wnt/β-catenin,OPN,OC,ALP and Cbf α1); and alizarin red staining for mineral deposition.The mRNA expressions of TAZ and Wnt/β-catenin in the two groups were analysed.ResultsAlizarin red staining was positive and the red calcium nodules were appeared on the post-osteogenic cells of MSC.The mRNA expressions of OC,ALP and Cbf α1 were 2.0958±0.5665,2.6670±0.3847,0.8463±0.3473,respectively,on the post-osteogenic cells of MSC in the experimental groups,which were significantly higher than those of pre-osteogenic cells(1.3487±0.9291,1.1452±0.6054,0.4439±0.2945) (t =2.171,6.709,2.795; all P ＜ 0.05).The mRNA expressions of OPN,OC,ALP and Cbf α1 were 2.1096±0.8267,2.8991±0.3531,4.3045±0.2844,1.3273±0.4075,respectively,on the post-osteogenic cells of MSC in the controls,which were significantly higher than those of pre-osteogenic cells (1.2200±0.9091,0.8780±0.3927,1.9161±0.2684,0.6736±0.2513) (t =2.289,12.103,25.134,4.411; all P ＜ 0.05).The mRNA expressions of OPN,OC,ALP,Cbf α1 were 1.2710±0.5636,2.0958±0.5665,2.6670± 0.3847,0.8463+0.3473,respectively,on the post-osteogenic cells of MSC in the experimental groups,which were significantly lower than those of control groups(2.1096 ±0.8267,2.8991 ±0.3531,4.3045±0.2844,1.3273±0.4075) (t =-2.650,-3.805,-10.822,-2.841; all P ＜ 0.05).The mRNA expression of TAZ and β-catenin were 2.2315±1.0723 and 0.5801±0.2159 on the post-osteogenic cells of MSC in MM patients,which were significantly lower than those of control groups (4.4140±0.8325,0.9516±0.2920) (t =±5.085,-3.235;both P ＜ 0.05).ConclusionThe gene expressions of OPN,OC,ALP and Cbf α1,the osteogenesis related genes,are increased in post-osteogenic cells of MSC,which showed the MSC have been successfully induced to osteoblasts.Comparing with control groups,the osteogenic potential of MSC in MM patients is lower.Based on the above research,TAZ and Wnt/β-catenin may present a novel target for the future therapy of MBD.

OBJECTIVE: To determine the normal range of the 33 elements (Li, Be, B, Mg, Al, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, As, Se, Rb, Sr, Zr, Mo, Ag, Cd, Sb, Cs, Ba Au, Hg, Tl, Pb, Th and U) in human whole blood of general population in Hunan province. METHODS: Blood samples were analyzed by inductively coupled plasma-mass spectrometry (ICP-MS) to determine the normal range. The influences of district, gender and age to the element content in blood samples were also observed. RESULTS: The normal range of 33 elements in blood samples from general population in Hunan province were obtained. Gender was shown to statistically influence the concentrations of B, Mg, Ca, Ti, Mn, Fe, Co, Cu, Zn, As, Se, Rb, Sr, Ag, Cd, Cs, Hg and Pb (P < 0.05), while age was shown to influence the concentrations of Co, Ni, Cs and Hg in women (P < 0.05) as well as Cu, Se and Hg in men (P < 0.05). CONCLUSION Although there are variables in different districts, the normal ranges of trace element in blood of the four cities in Hunan province are established.
Age Factors ; Asian People/ethnology* ; China ; Female ; Humans ; Male ; Mass Spectrometry/methods* ; Reference Standards ; Reference Values ; Residence Characteristics ; Sex Factors ; Trace Elements/blood*

Melittin exhibits high antibacterial potency against drug-resistant bacteria. However, the clinical utility of melittin is limited by its serious hemolytic activity. Thus, the need for developing novel melittin analogues with high antimicrobial activity and low hemolytic activity has grown. We designed, synthesized, and evaluated 20 novel melittin analogues with varying hydrophobic, polar or positively charged amino acids. The results showed that 8 compounds had antimicrobial activity (MIC: 1-4 μg·mL^-1) against gram-positive pathogens equal to or better than that of melittin, and 16 compounds had low hemolytic activity (HC₅₀ ≥ 11.9 μg·mL^-1). Compounds 13 (MIC: 2-4 μg·mL^-1) and 15 (MIC: 1-2 μg·mL^-1) showed equal or better antimicrobial activity against both susceptible and resistant strains of Staphylococcus aureus and Enterococcus faecium compared to melittin (MIC: 4 μg·mL^-1). Compound 13 (HC₅₀: 24.0 ± 4.3 μg·mL^-1) displayed noticeably decreased hemolytic activity compared to melittin (HC₅₀: 5.3 ± 0.4 μg·mL^-1). This work established a base for further study on the structure-activity relationships and structure-toxicity relationships of melittin.

OBJECTIVETo study the value of ultrasound elastography in the evaluation of ethanol-induced lesions of liver.

METHODSAlcohol with a dose of 2 ml was injected into a fresh porcine liver under ultrasound guidance to create stiff necrosis. Then freehand elastography of the lesion from the identical scan plane was obtained with Siemens SONOLINE Antares system using VF10-5 probe at about every 30 seconds till 6 minutes later. The original high-quality radio-frequency data were acquired through an ultrasound research interface provided by the ultrasound system. Corresponding elastograms were then produced offline using cross-corre-lation technique and compared with gross specimen.

RESULTSA hyperechoic area with acoustic shadow below appeared immediately after alcohol injection. The hyperechoic area diffused and its boundary was illegible following injection. On the contrary, the ethanol-induced lesion in elastography appeared as a low strain hard region surrounded by high-strain soft hepatic tissues with clear but irregular boundaries. Sequential elastograms with the lesion boundaries sketched showed that the lesion area grew in the first 3 minutes after ethanol injection and then reached a plateau, which corresponded to the gross specimen.

CONCLUSIONUltrasound elastography can be used to detect and evaluate the diffusion of ethanol-induced hepatic lesion.

Animals ; Disease Models, Animal ; Elasticity Imaging Techniques ; methods ; Ethanol ; adverse effects ; Humans ; Liver ; diagnostic imaging ; pathology ; Liver Diseases ; diagnosis ; diagnostic imaging ; pathology ; Swine

OBJECTIVETo study the value of ultrasound elastography in evaluation of ethanol-induced lesions of liver.

METHODSAlcohol with a dose of 2 ml was injected into a fresh porcine liver under ultrasound guidance to create stiff necrosis. Then freehand elastography of the lesion from the identical scan plane was obtained with SONOLINE Antares system using VF10-5 probe at about every 30 seconds till 6 minutes later. The original high quality radiofrequency data were acquired through an ultrasound research interface which was provided by the ultrasound system. Then, corresponding elastograms were produced offline using cross-correlation technique and compared with gross pathology findings.

RESULTSGray-scale sonogram showed a hyperechoic area with acoustic shadow below appeared immediately after alcohol injection. The hyperechoic area tended to be diffuse and its boundary to be illegible with time. On the contrary, the ethanol-induced lesion in elastogram appeared as a low strain hard region surrounded by high strain soft hepatic tissues, with clear but irregular boundaries. Sequential elastograms with the sketched lesion boundaries showed that the lesion area increased in the first 3 minutes after ethanol injection, and then reached a plateau which corresponding to gross specimen.

CONCLUSIONUltrasound elastography is capable of detecting and evaluating the diffusion of ethanol-induced hepatic lesion, and more sensitive and accurate than routine sonography.

Animals ; Elasticity ; Elasticity Imaging Techniques ; instrumentation ; methods ; Ethanol ; pharmacology ; Liver ; diagnostic imaging ; drug effects ; pathology ; Swine ; Ultrasonics

To provide the profiles of metabolism of mitomycin C (MMC) by human liver microsomes in vitro, MMC was incubated with human liver microsomes, then the supernatant component was isolated and detected by HPLC. Types of metabolic enzymes were estimated by the effect of NADPH or dicumarol (DIC) on metabolism of MMC. Standard, reaction, background control (microsomes was inactivated), negative control (no NADPH), and inhibitor group (adding DIC) were assigned, the results were analyzed by Graphpad Prism 4. 0 software. Reaction group compared with background control and negative control groups, 3 NADPH-dependent absorption peaks were additionally isolated by HPLC after MMC were incubated with human liver microsomes. Their retention times were 10. 0, 14. 0, 14. 8 min ( named as Ml, M2, M3) , respectively. Their formation was kept as Sigmoidal dose-response and their Km were 0. 52 (95% CI, 0. 40 - 0.67) mmol x L(-1), 0. 81 (95% CI, 0. 59 - 1. 10) mmol x L(-1), 0. 54 (95% CI, 0. 41 -0. 71) mmol x L(-1) , respectively. The data indicated that the three absorption peaks isolated by HPLC were metabolites of MMC. DIC can inhibit formation of M2, it' s dose-effect fitted to Sigmoidal curve and it' s IC50 was 59. 68 (95% CI, 40. 66 - 87. 61) micromol x L(-1) , which indicated DT-diaphorase could take part in the formation of M2. MMC can be metabolized by human liver microsomes in vitro, and at least three metabolites of MMC could be isolated by HPLC in the experiment, further study showed DT-diaphorase participated in the formation of M2.
Antibiotics, Antineoplastic ; metabolism ; Chromatography, High Pressure Liquid ; methods ; Dicumarol ; pharmacology ; Dose-Response Relationship, Drug ; Enzyme Inhibitors ; pharmacology ; Humans ; Microsomes, Liver ; drug effects ; enzymology ; metabolism ; Mitomycin ; metabolism

The myelodysplastic syndromes (MDS) include a diverse groups of clonal and potentially malignant bone marrow disorders. Evidences exist that microenvironment cells from MDS marrow show functional abnormalities, which may be relevant to the incidence of such a disease. Mesenchymal stem cells (MSCs) are a very important component of hematopoietic microenvironment. This study was supposed to investigate the biological characteristics and functions of MSC derived from patients with MDS in low-risk. MSCs from bone marrow samples of 11 low-risk MDS patients were isolated, cultured and expanded. Morphology, immunophenotype and osteoblasts differentiation were analyzed. Their capacity of proliferation and hematopoietic supporting in vitro were measured. A real-time quantitative reverse transcriptase polymerase chain reaction method (RQ RT-PCR) was used for detecting the expression levels of relative cytokines and chemokines in MSC. MSCs from healthy donors were used as controls. The results showed that the culture-expanded cells from MDS patients displayed a typical fibroblast-like morphology. Cells were positive for SH2 (CD105), SH3 (CD73), Thy-1 (CD90), while negative for CD34 and CD45. After induction, these cells could differentiate into osteoblasts. The proliferative ability of MSCs in MDS patients were not different from those of MSC isolated from normal bone marrow (p > 0.05), however, their capacity of hematopoietic supporting in vitro were significantly weaker (p < 0.05). RQ RT-PCR detection indicated that the SDF-1 gene expression level in MSCs of low-risk MDS patients was significantly higher than that in MSC derived from healthy donors (p < 0.01). It is concluded that the abnormal function of MSC influences the regulation of hemotopoiesis in the bone marrow microenvironment of MDS patients. It is worthy to further investigate the new clue in etiological mechanism and therapeutic strategies for MDS.
Bone Marrow Cells ; pathology ; Chemokine CXCL12 ; genetics ; metabolism ; Hematopoiesis ; Humans ; Mesenchymal Stromal Cells ; pathology ; physiology ; Myelodysplastic Syndromes ; pathology ; physiopathology ; Risk Factors

OBJECTIVETo report the diagnosis, differential diagnosis and treatment of a rare case of primary bone marrow CD8+ cytotoxic T-cell lymphoma coexpressed CD20.

METHODSThe clinical characteristics, therapeutic course and the outcome of this patient were reviewed. Meanwhile, a series of examinations including morphology, flow cytometry, immunohistochemistry and molecular biology of bone marrow and skin samples were also performed.

RESULTSBone marrow biopsy showed an extensive involvement by abnormal T lymphocytes. Flow cytometry and immunohistochemistry showed weakly positive CD20, CD8(+), CD2(+), CD3(+), CD5(+), TIA(+), PAX-5(-), CD4(-), CD56(-), CD57(-), CD30(-), ALK-1(-), P53(-), TdT(-), Ki-67≈5%. A final diagnosis of primary bone marrow CD8+ cytotoxic T-cell lymphoma coexpressed CD20 was made. The patient initially presented a relatively indolent course was, but he was expired in the end 3 years later due to extensive involvements of skin and other organs though timely therapy was administrated.

CONCLUSIONPrimary bone marrow CD8 cytotoxic T-cell lymphoma coexpressed CD20 was encountered rarely in clinical practice, which might be a challenging in terms of diagnosis and differential diagnosis. Further investigation of pathogenesis and therapeutic strategies of this rare disease was warranted.

Antigens, CD20 ; metabolism ; CD8-Positive T-Lymphocytes ; metabolism ; pathology ; Humans ; Lymphoma, T-Cell ; diagnosis ; pathology ; Male ; Middle Aged ; T-Lymphocytes, Cytotoxic ; metabolism ; pathology