Genomic instability is one of the most pervasive characteristics of cancer cells,and DNA damage response (DDR) pathway plays a crucial role in genomic stability.The DDR pathway is a complex signaling network,which involves cell DNA repair,apoptosis and cell cycle regulation.Deficiencies in these repair pathways can result in several different genetic disorders,including cancer.Targeted therapy based on inhibiting the DDR pathway in cancers offers a novel therapy strategy for patients with tumors lacking specific DDR functions.Many small-mole-cule compounds targeting DDR pathway are typically developed for solid cancer therapy.The poly (ADP-ribose) polymerase (PARP) inhibitor is a kind of DDR inhibitors which exploits the principle of synthetic lethality to selectively kill cancer cells.This review highlights the molecular mechanisms of PARP inhibitor action,the progress of PARP inhibitors in cancer therapy,drug resistance and the challenge of PARP inhibitor in the future.

Objective To explore the relationship between apolipoprotein E gene polymorphism and cerebral infarction in Taishun county.Methods Determination of 112 cases of Taishun Siqian cerebral infarction patients and healthy persons 88 cases of ApoE gene polymorphism,and the cerebral infarction patients were admitted to the hospital for different period of time after the NIHSS score.Results The cerebral infarction group and the control group were ApoE -/3 genotype most were 70.5%(79 /112)and 63.6%(56 /88),both had significant difference(P >0.05);The cerebral infarction group and the control group in terms of ApoE -up to 3,respectively 82.1%(92 /112)and 75.6%(66.5 /88),both had no significant difference (P >0.05).The cerebral infarction group epsilon 4 to 9.8%(11 /112),and was significantly higher than that of the control group 4.0%(3.5 /88);E2 was 6.2% (7 /112), which was significantly lower than that of the control group [19.3% (17 /88)],the differences were significant (χ2 =6.189,7.970,all P <0.05).Carrying ApoE -4 of the cerebral infarction patient each time period at the time of admission,admission 7d and 14d NIHSS scores were not carrying epsilon 4 patients increased significantly (t =7.853,6.185,5.165,allP <0.05);and at each time point carrying epsilon 2 gene in patients with and without carry-ing epsilon 2 patients NIHSS scores had no significant difference (P >0.05 ).Conclusion Cerebral infarction patients ApoE gene polymorphism and disease progression and prognosis are closely related,ApoE -4 Taishun Siqian cerebral infarction patients predisposing factors.At the same time,the detection of apoE genotype and NIHSS score is helpful to the prognosis of the patients.

Up to date, eight types of human herpes viruses have been identified, all of which are ubiquitous, and usually establish latent infection in the host after primary infection. Since most of the herpes viruses are maintained in an asymptomatic form, they are often neglected. However, under some circumstances, these herpes viruses can cause fatal or severe diseases. Furthermore, the association of herpes viruses with hematopoietic malignancies is attracting researchers' attention. With the extensive development of hematopoietic stem cell and organ transplantation, reports regarding transplantation failure and complication caused by infection of human herpes virus has been increasing. Cytokine storm was firstly suggested as the mechanism of graft-versus-host diseases. In recent years, which has also been applied in the pathogenesis research of inflammation, and is supposed to play an important role in severe virus infection. In this paper, through discussing the possible role of latent infection of human herpes virus in the failure or complication of bone marrow or hematopoietic stem cell transplantation, and in refractory leukemia, the function and significance of latent infection of human herpes virus and the cytokine storm it caused were investigated.
Cytokines ; immunology ; Hematopoietic System ; immunology ; virology ; Herpesviridae Infections ; Humans ; Virus Latency

AIMTo develop an HPLC method for the determination of crocetin in rat plasma and study the pharmacokinetics in rats.

METHODSHypersil C18 column (5 microns, 4.6 mm x 200 mm) was used at column temperature 30 degrees C. The mobile phase consisted of methanol-water-acetic acid (75:24.5:0.5) at the flow rate of 1.0 mL.min-1. The UV detection wave length was 423 nm.

RESULTSThe calibration curve was linear (gamma = 0.9996) in the range from 0.49 microgram.mL-1 to 7.87 micrograms.mL-1 for crocetin. The mean recovery was 105.2%. The lowest detectable concentration of crocetin was 0.14 microgram.mL-1 (S/N = 3). The RSDs of within-day and between-day were all less than 5%. The plasma crocetin was steady. The HPLC method of determination of crocetin in the plasma was established. After single dose of 50 mg.kg-1 ig in 10 rats, the main pharmacokinetic parameters were estimated as follows: T1/2 alpha (30 +/- 6) min, Tmax(65 +/- 16) min, Cmax(5.0 +/- 1.0) microgram.mL-1, AUC0-T(845 +/- 109) microgram.min.mL-1, Vd(5.0 +/- 0.8) L.kg-1. Crocetin was shown to be absorbed into the blood through the gastrointestinal tract.

CONCLUSIONThis method is quick, precise and reliable. Crocetin was shown to be quickly absorbed in rats.

Animals ; Antineoplastic Agents, Phytogenic ; blood ; isolation & purification ; pharmacokinetics ; Carotenoids ; blood ; isolation & purification ; pharmacokinetics ; Chromatography, High Pressure Liquid ; methods ; Crocus ; chemistry ; Female ; Male ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley

In our screening for photosensitizers from natural resources, four alkaloids were isolated from Glycosmis pentaphylla by various chromatography techniques. Their structures were identified as glycoborinine (1), glybomine B (2), carbalexin A (3) and N-p-coumaroyltyramine (4) by spectral analysis. Their photoactivated antimicrobial activities were evaluated by thin-layer chromatography (TLC) agar overlay assay against Staphylococcus aureus and Bacillus subtilis. It was found that compounds 1 and 4 showed photo-activated antimicrobial activities. Meantime, photo-activated DNA binding activities of these compounds were also assessed by using a specially prepared 1.8 kb DNA fragment and restriction enzymes. Under UVA irradiation, compound 1 showed moderate inhibition on Nde I, Xba I, Nco I and Bcl I which have either 5'-TpA or 5'-ApT and trace or no inhibition on other restriction enzymes. It showed a similar inhibition pattern with the reference 8-methoxypsoralen. However, compounds 2-4 showed no inhibition against any of the restriction enzymes.

As pioneer of tumor stem cell research, leukemia stem cell research has not only important theoretical significance, but also clinical application potential. The survival and development of stem cells are directly impacted by their microenvironment. The research on leukemia stem cells and their microenvironment are now becoming a hot topic. The author presumes that stem cells are a population with heterogenecity and hierarchy; any single cell from the population is difficult to form a clone; the interaction between the leukemia stem cell and its microenvironment can be described by the concept of leukemia stem cell niche. In this article, the leukemia cell population with heterogenecity and hierarchy as well as leukemia stem cell niche were summarized and discussed.
Cell Line, Tumor ; Humans ; Leukemia ; genetics ; pathology ; Neoplastic Stem Cells ; metabolism ; pathology ; Stem Cell Niche ; cytology ; Stromal Cells ; cytology ; immunology

Objective To investigate the causes,diagnosis and treatment of small intestine bleeding.Methods Sixty-eight cases of small intestine bleeding from January 2000 to June 2010 were retrospectively analyzed.Among all cases,4 underwent routine hemostatic treatment under colonoscopy,40treated with open surgery and 24 patients with laparoscopic therapy.Among them,57 cases underwent part resection for some small intestine,completely laparoscopic resection of diverticula was performed in 7patients.Results Neoplasms was the leading cause of small intestine bleeding,accounting for 48.5％ (33/68)in these patients,followed by small intestine diverticulum accounted for 29.4％ ( 20/68 ),intestinal infective diseases accounted for 14.7％ ( 10/68 ) and vascular disease accounted for 7.4％ ( 5/68 ).Conclusion The clinical manifestations of small intestinal bleeding showed no specific signs.Neoplasm,intestine diverticulum and intestinal infective diseases are the most common causes of small intestinal bleeding.Small intestinal bleeding can be diagnosed in intraoperative colonoscopy.Surgery is the most effective treatment for small intestinal bleeding.

OBJECTIVETo investigate the influence of drug properties on the encapsulation effiency (EE) and drug release of transfersomes for a proper transfersome preparation.

METHODTo prepare the transfersomes of colchicines (CLC), vincristine sulfate (VCR) and mitoxantrone hydrochloride (DHAD) with the same materials and methods, and then measure their EE. To find out the relationship between drug properties like solubility, molecular weight and charges, and EE. To performe the drug release experiments of various types of transfersomes in vitro, and compare their differences.

RESULTVCR and DHAD are lipophilic or hydrophilic, owing positive charges and large molecular weight, as a result, their EE are high, while CLC is amphipathic, neutral, and of small molecular weight, its EE is very low. As DHAD can insert into the membrane of transfersome, the drug release of DHAD-T in vitro is much slower than that of VCR-T.

CONCLUSIONTo prepare transfersomes with high EE, drugs that are lipophilic or hydrophilic, high molecular weight and opposite charges to the membrane should be chosen. Interaction between drugs and membrane will influnce the rate of drug release.

Antineoplastic Agents ; administration & dosage ; chemistry ; Antineoplastic Agents, Phytogenic ; administration & dosage ; chemistry ; Colchicine ; administration & dosage ; chemistry ; Deoxycholic Acid ; Drug Carriers ; Gout Suppressants ; administration & dosage ; chemistry ; Mitoxantrone ; administration & dosage ; chemistry ; Particle Size ; Phosphatidylcholines ; Solubility ; Technology, Pharmaceutical ; methods ; Vincristine ; administration & dosage ; chemistry

Relapse, which puzzled several generations of hematologists, is the bottle-neck of radical treatment for leukemias. The progress of Human Microbiome Project at the beginning of 21st century suggested that human body was a super-organism constituted by the core of human cells and symbiotic microorganisms. The elucidation and characterization of endogenous retrovirus and prion protein suggested the possible effects of co-evolutional microorganisms on human health. Recently, the elucidation of the roles of tunneling nanotubes in intercellular communication and transportation suggested a novel way for cellular communication and transport of oncogenic materials. The role and significance of in vivo cell fusion have been studied in more detail. On the other hand, donor cell leukemia was reported. All of these approaches provide novel insights for studying the mechanism of leukemia relapse. Based on previous work, the authors suggest the hypothesis: there are two possible mechanisms for the relapse of leukemias: the minimal residual disease (MRD) and intercellular transportation of oncogenic materials.
Cell Fusion ; Humans ; Leukemia ; pathology ; Neoplasm, Residual ; pathology ; Recurrence

on,size and the extent structures of atrial septal defect on line.