Increasing attention has been focused on the antitumor activity of artemisinin derivatives in recent years, for artemisinin had been reported to have cytotoxic effects against HL-60, P388 and MCF-7 tumor cells. We report here the synthesis and evaluation for antitumor activity of a series of artemisinin-ether derivatives bearing tetrahydropyrrole, morpholine, piperidine, substituted piperidines and azoles with various linkers. Sixteen 10-O-substituted dihydroartemisinin derivatives were designed and synthesized, all of which have never been reported in literatures and whose antiproliferative effects on human breast cancer MCF-7, MCF-7/Adr and HL-60 cells were determined by MTT assay or direct cell counting. Each of these artemisinin derivatives possessed better effects than dihydroartemisinin evidently against HL-60 and MCF-7 cells growth, while less potent than doxorubicin. All target compounds exhibited significantly improved potency compared to DHA and doxorubicin on the doxorubicin-resistant MCF-7/Adr cells, so did they in their sensitive counterparts MCF-7 cells. Among them, compounds GF02, GH04 and ZH04 showed strong activity against these three cell lines growth. Further research is undergoing.
Antineoplastic Agents ; chemical synthesis ; chemistry ; Artemisinins ; chemical synthesis ; chemistry ; Breast Neoplasms ; pathology ; Cell Proliferation ; Doxorubicin ; Drug Design ; HL-60 Cells ; drug effects ; Humans ; MCF-7 Cells ; drug effects

In this study,the common critical medical cases were organically combined with SimMan simulation system,which enabled students to deeply understand the diagnosis,treatment of disease and clinical operation as consulting real patients.Also,it could improve their clinical thinking ability,clinical skills and operational level.

Hepatocellular carcinoma (HCC) is the most common pathological type of liver cancer with high mortality.The cognitive limitations of pathogenesis and development of HCC is an important reason for its poor prognosis.Long noncoding RNA (lncRNA) is an important part of gene regulation and has expression specificity in different tissues and different disease types.In recent years,studies on the role of lncRNA in development of cancer are gradually deepening,which provide novel methods and ideas for early diagnosis,disease control and prognosis assessment of HCC.This article reviewed the research progresses of lncRNA in HCC.

OBJECTIVETo research (CAG)n polymorphism of androgen receptor gene in idiopathic azoospermic and oligospermic Chinese men, and to explore its correlation with the development of dyszoospermia.

METHODSFifty-two men with oligospermia and 31 with azoospermia were enrolled, the number of CAG sequence repeats determined by PCR and denaturing polyacrylamide gel electrophoresis (PAGE), and (CAG)n polymorphism analyzed.

RESULTSThe CAG repeats in the men with oligospermia and those with azoospermia were 22.19 and 22.13 respectively.

CONCLUSIONThe polymorphism of the repeat length of the (CAG) n satellite in androgen receptor gene may affect spermatogenesis and have a less important role in male infertility.

Adult ; Electrophoresis, Polyacrylamide Gel ; Exons ; Humans ; Infertility, Male ; genetics ; Male ; Oligospermia ; genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Receptors, Androgen ; genetics ; Trinucleotide Repeats ; genetics

OBJECTIVETo investigate the structural and functional changes of internal anal sphincter (IAS) in children with functional constipation (FC), and to evaluate the association between the thickness of IAS and the severity of clinical symptoms.

METHODSA total of 35 children with FC(constipation group,17 with incontinence) between June 2008 and December 2008 at the Shengjing Hospital of China Medical University were evaluated using anal manometry and endosonography. These patients were compared to 23 hospitalized children who were excluded for digestive and endocrinal diseases(control group). A validated symptom score(SS) was used to assess the severity of symptoms. The sum of SS ranged between 0 and 65.

RESULTSAnorectal manometry showed reflex relaxation of IAS in response to distension of rectal balloon in all patients. Rectal perceptional threshold in FC group was significantly higher than that in the controls[(42.4 ± 19.5) ml vs.(29.1 ± 15.6) ml, P<0.05]. The lowest volume for inducing reflex relaxation of IAS was significantly higher than that in the controls [(55.6 ± 31.6) ml vs.(30.5 ±13.8) ml, P<0.05]. The thickening of IAS was noted in all the patients[(3.8 ± 1.7) mm vs.(2.5 ± 1.0) mm, P<0.05]. However, there was no significant difference between FC and control in median resting anal sphincter pressure[(170.8 ± 62.3) mm Hg vs. (161.3 ± 51.1) mm Hg, P>0.05]. The median symptom score was 9.3 ± 4.3 in the FC group. The thickness of IAS correlated significantly with total symptom severity score(r=0.407, P<0.05). There was no correlation between thickness of IAS and age, sex, or duration of disease(P>0.05).

CONCLUSIONSStructural and functional changes of internal anal sphincter exist in children with functional constipation. The thickness of internal anal sphincter correlates significantly with symptom severity.

Anal Canal ; diagnostic imaging ; physiopathology ; Child ; Child, Preschool ; Constipation ; diagnostic imaging ; physiopathology ; Endosonography ; Female ; Humans ; Male

ObjectiveTo evaluate the neurobiological characteristics of human histio-amniotic mesenchymal (hAMCs) and effect of hAMCs transplantation into the brain to treat Parkinson's disease(PD) modle mice.MethodsThe expressions of mesenchymal stem cells, neural stem cells, dopaminergic neurons and markers related to neurogenesis such as Vimentin, STRO-1, nestin, CD133, β-tubulin, TH, DAT, Ngn2 and mash-1 in hAMCs were evaluated through immunocytochemical stain; and the mRNA transcriptions of neural stem cell markers, Vimentin and nestin in hAMCs were detected by RT-PCR. The PD model was induced by MPTP(i.p.) in C57BL/6 mice transplanted with hAMCs into the right striatum. The therapeutical effect of hAMCs on PD mice was evaluated by spontaneous movement, rotating bar test and the immunohistochemistry of anti-human chondrosome and TH antibodies in striatum.ResultshAMCs induced by nerve cells culture medium, expressed mesenchymal stem cells, neural stem cells, dopaminergic neurons and other specific markers related to neurogenesis mentioned above. The frequency of spontaneous movement in PD mice was significantly increased(P<0-05), and the time of rotating bar was obviously prolonged(P<0-05) after transplantation with hAMCs.ConclusionhAMCs possess the characteristics of nerve cells after cultured in vitro and can significantly recover the damage of motor function induced by MPTP after transplantation into striatum in PD model mice.

Human thioredoxin reductase (TrxR) system is associated with cancer cell growth and anti-apoptosis process. Effects of 1,2-[bis(1,2-benzisoselenazolone-3(2H)-ketone)]ethane (BBSKE), a novel TrxR inhibitor, were investigated on human leukemia cell lines HL-60 and K562. BBSKE treatment induced cell growth inhibition and apoptosis in both cell lines. Apoptosis induced by BBSKE is through Bcl-2/Bax and caspase-3 pathways. Ehrlich's ascites carcinoma-bearing mice were used to investigate the anti-tumor effect of BBSKE in vivo. Tumor-bearing mice treated with BBSKE showed an increase of life span with a comparable effect to cyclophosphamide (CTX). These results suggest a potential usage of BBSKE as a therapeutic agent against non-solid tumors.
Apoptosis ; drug effects ; Bridged Bicyclo Compounds, Heterocyclic ; pharmacology ; Cell Proliferation ; drug effects ; Enzyme Inhibitors ; pharmacology ; HL-60 Cells ; Humans ; K562 Cells ; Organoselenium Compounds ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; physiology ; Thioredoxin-Disulfide Reductase ; antagonists & inhibitors ; bcl-2-Associated X Protein ; physiology

OBJECTIVEThe aim of this study was to evaluate the correlation of protein expressions of CXC chemokine receptor 4 (CXCR4), vascular endothelial growth factor-C (VEGF-C) and cytokeratin 19 (CK-19) with lymph node metastasis (LNM) in patients with hepatocellular carcinoma (HCC), and their survival.

METHODSThe expressions of CXCR4, VEGF-C and CK-19 in HCC patients with (n = 123) or without (n = 145) LNM were determined using tissue microarray and immunohistochemical staining. The relationship between clinicopathological features and CXCR4, VEGF-C and CK-19 were analyzed. Evaluation of immunostaining was performed semiquantitatively by visual assessment.

RESULTSThe UICC T stage, and expressions of nuclear CXCR4, VEGF-C and CK-19 were independent risk factors for LNM. Nuclear CXCR4, VEGF-C and CK-19 expression were predictive factors for LNM in HCC patients. In patients with LNM, the median survival time was 15.1 months for patients with high nuclear CXCR4 expression and 24.5 months for those with low nuclear CXCR4 expression. The median survival time was 15.1 months for patients with high tumor VEGF-C expression and 31.1 months for those with low tumor VEGF-C expression. The median survival time was 12.0 months for patients with positive CK-19 expression and 19.2 months for patients with negative CK-19 expression. Patients with high nuclear CXCR4, VEGF-C or CK-19 expression had significantly poorer prognosis than those with low expression (all P < 0.05). PVT, UICC T stage and expressions of nuclear CXCR4, VEGF-C, and CK-19 were independent prognostic factors.

CONCLUSIONIncreased protein expressions of nuclear CXCR4, VEGF-C, and CK-19 are independent risk factors for developing lymph node metastasis, and they are significantly correlated with LNM and poor outcome in HCC patients.

Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Nucleus ; metabolism ; Female ; Follow-Up Studies ; Humans ; Keratin-19 ; metabolism ; Liver Neoplasms ; metabolism ; pathology ; Lymphatic Metastasis ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Proportional Hazards Models ; Receptors, CXCR4 ; metabolism ; Risk Factors ; Survival Rate ; Vascular Endothelial Growth Factor C ; metabolism

OBJECTIVETo investigate the change of early serum TNF-alpha and IL-6 levels in acute cerebral infarction and its significances.

METHODSSerum TNF-alpha and IL-6 levels in 30 health subjects and 35 patients with acute cerebral infarction (ACI) within 6 hours of onset were measured by enzyme linked immunosorbent assay (ELISA); neurological deficits scores (NDS) in all cases were determined, and Spearman test was used for correlation.

RESULTSThe serum levels of TNF-alpha and IL-6 in ACI group were markedly higher than those in health subjects and there was a positive correlation of TNF-alpha and IL-6 levels with 6 h NDS (rs=0.89 and 0.93, P<0.001) and with NDS progression (rs=0.90 and 0.91, P<0.001). Early serum TNF-alpha and IL-6 levels in progressive cerebral infarction (PCI) group were evidently higher than those in stable cerebral infarction (SCI)[(49.56+/-12.12) pg/L compared with (24.30+/-7.4) ng/L and (39.76+/-7.88) ng/L compared with (20.78+/-6.28) ng/L, respectively, P<0.01)].

CONCLUSIONThe early serum levels of TNF-alpha and IL-6 in ACI markedly increase and are closely correlated with disease severity; which may be of value in PCI risk evaluation.

Acute Disease ; Adult ; Aged ; Biomarkers ; blood ; Cerebral Infarction ; blood ; Early Diagnosis ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Interleukin-6 ; blood ; Male ; Middle Aged ; Time Factors ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo investigate the FDG uptake characteristics, the factors affecting 18F-FDG uptake and the extra CT diagnostic value of 18F-FDG PET/CT scan in the malignant tumor with false negative 18F-FDG PET image.

METHODSThe data of PET/CT image in 17 patients with various kinds of cancers were reviewed and analyzed by visual observation and semi-quantity analysis ( SUV). The results were compared with the CT and histopathological diagnosis, respectively.

RESULTSOf 6 well-differentiated HCC patients confirmed by histopathological diagnosis, one had two lesions in the right lobe of the liver. One of these two lesions showed low FDG uptake on 18F-FDG PET scan and low density on CT scan. The other one was not shown on either 18F-FDG PET or plain CT scan. But on enhanced CT scan, these two lesions were found to be inhomogeneous with high density at arterial phase. The false negative 18F-FDG PET images of one gastric signet ring cell carcinoma in the gastric fundus with right adnexa metastasis, 3 renal cell carcinoma, one greater omentum and peritoneal metastatic adenocarcinoma and one well-differentiated prostate cancer were caused by normal physical uptake in the digestive tract or FDG retention in the urinary system due to normal excretion. The size of three metastases was smaller than or equal to 1 cm in diameter, however, two primary lesions of these metastases showed high FDG uptake and only one was negative on either 18F-FDG PET or CT scan. In this series, 68.8% of the primary tumors and 66.7% of metastases were found to show abnormal density on CT scan, and 31. 2% of the primary tumors and 33. 3% of metastases were not detectable on either PET or CT images.

CONCLUSIONFalse negative 18F-FDG PET in malignant tumor may be correlated with the pathologic type, differentiation degree and the lesion size. Combining CT information with PET or paying attention to the scan methods during 8 F-FDG PET examination may reduce the rate of false negative 18F-FDG PET diagnosis in various kinds of malignant tumors.

Adenocarcinoma ; diagnostic imaging ; secondary ; Adult ; Aged ; Carcinoma, Hepatocellular ; diagnostic imaging ; pathology ; Carcinoma, Renal Cell ; diagnostic imaging ; pathology ; Carcinoma, Signet Ring Cell ; diagnostic imaging ; pathology ; False Negative Reactions ; Female ; Fluorodeoxyglucose F18 ; Humans ; Kidney Neoplasms ; diagnostic imaging ; pathology ; Liver Neoplasms ; diagnostic imaging ; pathology ; Male ; Middle Aged ; Omentum ; diagnostic imaging ; Peritoneal Neoplasms ; diagnostic imaging ; secondary ; Positron-Emission Tomography ; methods ; Radiographic Image Enhancement ; Stomach Neoplasms ; diagnostic imaging ; pathology ; Tomography, X-Ray Computed