Local focal adhesion kinase (FAK) is a non-receptor intracellular tyrosine kinase that plays an important role in tumor initiation, development, metastasis and invasion, and is considered to be an important target for the development of antineoplastic drugs. It has both kinase-dependent and non-kinase-dependent scaffolding functions. However, traditional small molecular inhibitors can only inhibit its kinase-dependent activity, so it is difficult to target the kinase-independent scaffolding function. Therefore, there is an urgent need for novel strategies to enhance FAK targeting to lay the foundation for determining the druggability and discovery of FAK inhibitors. Proteolysis targeting chimera (PROTAC) is a new drug development strategy that can recruit E3 ligase to specifically ubiquitinylate target proteins for degradation through the proteasome system. The unique mechanism of action of the PROTAC system could be used to target and degrade the FAK protein, thus eliminating the scaffolding function of FAK. In this review, FAK protein, the signaling pathway, and small molecule inhibitors are briefly described, and the latest research progress in targeting the degradation of FAK using PROTAC technology is summarized.

OBJECTIVETo evaluate the role of 1H spetral selected point-resolved spectroscopy (SS-PRESS) sequence in distinguishing benign from malignant breast lesions by the malignancy marker of choline peak and to investigate the factors influencing the diagnosis.

METHODSA total of 131 patients (aged 24-83 years, average 44.8 years) were enrolled in this study. The examinations were performed on a 1. 5T scanner with four-channel phased array breast coil. Single-voxel proton magnetic resonance spectroscopy (1H MRS) was acquired by SS-PRESS sequence in these patients referred to surgical or biopsy consultation.

RESULTSAmong these patients, 74 were proved to have breast carcinomas and 57 have benign lesions by histopathological examinations. Thirty-one elevated choline peaks were observed in these 74 confirmed malignant lesions, and 5 detectable choline peaks were demonstrated in the 57 benign lesions. The sensitivity and specificity of 1H SS-PRESS MRS were 41.9% and 91.2%, respectively. The main factors influencing the diagnosis were signal-to-noise ratio and pathological type.

CONCLUSIONS1H SS-PRESS MRS can provide a noninvasive, biochemical measurement of metabolism and improve the specificity of breast magnetic resonance imaging. Choline peak in vivo is a specific but not sensitive marker of malignancy. Technique factors and histopathological characterization of lesions influence the detection rate.

Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; diagnosis ; pathology ; Carcinoma, Ductal, Breast ; diagnosis ; pathology ; Choline ; Female ; Fibroadenoma ; diagnosis ; pathology ; Fibrocystic Breast Disease ; diagnosis ; pathology ; Humans ; Image Enhancement ; Lymphatic Metastasis ; Magnetic Resonance Imaging ; methods ; Magnetic Resonance Spectroscopy ; methods ; Middle Aged ; Sensitivity and Specificity

OBJECTIVEIdiopathic thrombocytopenic purpura (ITP) is a hemorrhagic disease in children with blood platelets redundant destruction caused by chaotic immunological mechanism. However, some patients with ITP with negative platelet-associated antibody and ineffective adrenal cortical hormone therapy probably have special pathogenesis. It is indicated that the human cytomegalovirus (HCMV) can incubate in haemopoietic stem cell/ancestral cell to inhibit its generation and differentiation. Therefore, the study was designed to investigate HCMV-late mRNA expression in megakaryoblast for the purpose of examining the pathogenesis of ITP and to examine the effectiveness of ganciclovir on ITP.

METHODSColony forming unit-megakaryocyte (CFU-MK) of 46 ITP patients with HCMV infection were incubated. Reverse transcription-polymerase chain reaction (RT-PCR) was subsequently used for HCMV-late mRNA detection. Ganciclovir therapy was given to both positive group and negative group for comparison of therapeutic effectiveness.

RESULTSNineteen out of 46 CFU-MK culture cell specimens with positive HCMV-DNA by PCR or positive CMV-IgM by enzyme linked immunosorbent assay (ELISA) from serum of peripheral blood showed positive for HCMV-late mRNA. While, the remaining 27 were negative. Sixteen positive responders to ganciclovir therapy were observed amongst those with positive HCMV-DNA. Whereas, only 4 positive responders to ganciclovir therapy were noticed amongst those with negative HCMV-DNA. The curative effectiveness in positive group was significantly higher than that in negative group (P < 0.01).

CONCLUSIONHCMV can directly infect CFU-MK, which might be one of the mechanisms responsible for ITP. Ganciclovir is an effective therapy resulting in an increase in thrombocyte in ITP patients whose HCMV-late mRNA was positive in their CFU-MK.

Adolescent ; Antibodies, Viral ; immunology ; Antiviral Agents ; therapeutic use ; Blood Platelets ; drug effects ; immunology ; Cells, Cultured ; Child ; Child, Preschool ; Cytomegalovirus ; drug effects ; genetics ; pathogenicity ; Cytomegalovirus Infections ; drug therapy ; genetics ; immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Ganciclovir ; therapeutic use ; Humans ; Immunoglobulin M ; immunology ; Infant ; Male ; Megakaryocyte Progenitor Cells ; drug effects ; metabolism ; Purpura, Thrombocytopenic, Idiopathic ; complications ; drug therapy ; immunology ; RNA, Messenger ; RNA, Viral ; drug effects ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

The object was to study the effect of ouabain on Jurkat cells and its possible mechanism. The effect of ouabain of low concentration on Jurkat cells was confirmed by MTT, while c-myc gene transcription was measured by RT-PCR, and the phosphorylation of MAPK (ERK1/2) as well as the expression of c-myc gene was tested by Western blot respectively. The results showed that ouabain at low concentration could induce the proliferation of Jurkat in a time-and dose-dependent manner. At the same time, the phosphorylation of MAPK (ERK1/2) and the expression of c-myc gene was enhanced. In conclusion, ouabain stimulates the intracellular MAPK signal pathway by acting on the Na, K-ATPase, and thus induce the proliferation of Jurkat cells, in which the regulation of c-myc gene expression may be involved.
Blotting, Western ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Humans ; Jurkat Cells ; MAP Kinase Kinase 1 ; metabolism ; MAP Kinase Signaling System ; physiology ; Ouabain ; pharmacology ; Phosphorylation ; drug effects ; Proto-Oncogene Proteins c-myc ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Time Factors

Adolescent ; Child ; Female ; Humans ; Leukemia, Myeloid, Acute ; diagnosis ; drug therapy ; pathology ; Male ; Prognosis

OBJECTIVETo review the experience for the management of hepatocellular carcinoma with tumor thrombus in inferior vena cava.

METHODSFrom July 2003 to May 2005, hepatectomy combined with thrombectomy were performed on 7 cases of hepatocellular carcinoma with tumor thrombus in inferior vena cava. In order to remove the tumor thrombus in inferior vena cava, total hepatic vascular exclusion were adopted on all cases to control the blood flow of IVC. According to the position of extension of tumor thrombus, 5 different procedures were adopted in the cases to control the suprahepatic IVC and extract the tumor thrombus out of IVC and atrium. Procedure 1: Median sternotomy, extracorporeal bypass, cardiac arrest, incision on right atrium and IVC were performed on 1 case for thrombectomy. Procedure 2: Median sternotomy, extracorporeal bypass without cardiac arrest, incision on IVC and (or without) incision on right atrium were performed on 2 cases for thrombectomy. Procedure 3: Abdominal approach to control intrapericardial IVC through an incision on diaphragm was performed on 1 case for thrombectomy. Procedure 4: Abdominal approach to control suprahepatic IVC above diaphragm through a small incision made on vena cava foramen for thrombectomy was performed on 1 case. Procedure 5: Abdominal approaches to control suprahepatic IVC below diaphragm for thrombectomy were performed on 2 cases.

RESULTSAll operations were successfully performed. The postoperative complications included pleural effusion in 1 case, subphrenic fluid collection in 1 case and wound infection in 1 case. The average survival time of 7 cases was 9.8 month. The longest survival time was 26 months.

CONCLUSIONHepatectomy and thrombectomy can be safely performed on the case of HCC combined with tumor thrombus in IVC. Surgical treatment can relieve the patient from the risk of sudden death caused by heart failure and pulmonary.

Adult ; Aged ; Carcinoma, Hepatocellular ; pathology ; surgery ; Embolectomy ; methods ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms ; pathology ; surgery ; Male ; Middle Aged ; Neoplastic Cells, Circulating ; Vena Cava, Inferior ; pathology

Objective To determine the proportions and correlates of recent HIV infections among newly reported HIV/AIDS cases from 2005 through 2009 in Dehong prefecture, Yunnan province. Methods All available serum samples of newly reported HIV/AIDS cases during 2005-2009 period in Dehong prefecture, were tested using the BED HIV incidence capture enzyme immunoassay (BED-CEIA). Results A total of 9367 HIV/AIDS cases were newly reported in 2005through 2009, of whom 7252 (77.4%) were tested with BED-CEIA. Among the tested, 954 (13.2%)were positive for BED-CEIA and were regarded as recent HIV infections. The proportion of recent HIV infection among newly reported HIV/AIDS cases was 11.21% in 2005, 11.87% in 2006, 17.55%in 2007, 13.22% in 2008, and 12.22% in 2009. Multiple logistic regression analysis indicated that the proportion of recent HIV infections among newly reported HIV/AIDS cases in 2009 was significantly higher among females, those aged 11-19 years, and internal residents outside of Dehong prefecture,but significantly lower among immigrants who were mostly from Myanmar, than local residents.Conclusion From 2005 to 2009, the proportion of recent HIV infections among newly reported HIV/AIDS cases in Dehong prefecture in Yunnan province was fluctuating slightly. Future research is needed to examine its long-term and secular trend. Such proportion was significantly different by different sociodemographic characteristics.

OBJECTIVETo analyze the relationship between T cell subsets and clinical data.

METHODSmononuclear cells were collected from 103 patients with acute leukemia (AL) and 28 healthy volunteers, and percentage changes of CD3CD4, CD3CD8 and CD4 CD25 Foxp3 cell subsets were assayed by flow cytometory. Relationship between the T subsets and clinical features of the patients was analyzed.

RESULTSRatio of CD3 T cells decreased more significantly in patients with >50% blast cells than that in patients with <50% blast cells, while the ratio of Treg between the 2 groups was not significantly different. Treg increased more statistically significantly in the patients with CD34 leukemia cell than that with CD34 leukemia cells. In constrast to the relationship between prognosis and immune cells in the patients from 3 groups (low, intermediate and high-risk group) it was found that Treg cells increased more significantly in high-risk group than that in low-risk group. By continuously monitoring immune cells in 18 patients, it was found that Treg cells gradually increased during the first 3 courses of chemotherapy, then began to decreased in the 4th course, finally approached gradually to the normal value in the 6th course, and this change correlated with the clinical remission after chemotherapy. Treg cell number in the patients with AL was significantly higher than that in healthy controls, and Treg cell number during the onset and recurrence was significantly higher than that in the period of complete remission (continuous remission for over 6 months). Compared with the changes of immune cell number between different types of disease, it was found that Treg cells were increased more significantly in acute myeloid leukemia (AML) than that in acute lymphoblastic leukemia (ALL). Proportion of Treg cells, Treg/CD4 decreased more significantly after the 1st course of chemotherapy in the group with complete remission (CR) than that in the group without CR. The complete remission rate and recurrence rate were 68.9% and 20% respectively in the group with >10% Treg cells, while the complete remission rate and recurrence rate were 85.7% and 7.69% respectively in the group with.<10% Treg cells. In comparison of the 6 recurrent patients with 32 patients with sustained CR, it was found that the ratio of Treg cells and Treg/CD4 was increased more significantly in the patients with relapse than that with CR and in control group.

CONCLUSIONDynamic change of Treg cells in the peripheral blood was closely related with clinical feature, recurrence and prognosis in the patients with acute leukemia.

Asian Continental Ancestry Group/genetics* ; Charcot-Marie-Tooth Disease/genetics* ; China ; Genetic Profile ; Humans ; Pedigree