A series of novel sorafenib analogues were designed and synthesized. The cytotoxic activities of these compounds were tested in four tumor cell lines. Some of the compounds showed potent antiproliferative activity against the tested cell lines with IC50 = 4-20 micromol x L(-1). Some compounds demonstrated competitive antiproliferative activities to sorafenib against tested cancer cell lines. Among them, compound 7c demonstrated significant inhibitory activities on ACHN, HCT116 and MDA-MB-231 cell lines with IC50 values of 9.01, 4.97, 6.61 micromol x L(-1), respectively.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Inhibitory Concentration 50 ; Molecular Structure ; Niacinamide ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Phenylurea Compounds ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

Objective To analyze the CT imaging features of Castleman disease and enhance our knowledge of Castleman disease.Methods Twenty two patients with lymph node biopsy-proved or surgeryproved Castleman disease were retrospectively reviewed in this study.Of the 22 patients,18 had localized lesion and 4 patients had multicentric lesions.Correlation was made between CT and pathologic findings.Results Eighteen patients with localized Castleman disease had the hyaline-vascular type and showed well-circumscribed masses with soft-tissue density [mean CT value,(45 ± 16) HU],punctate or bifurcate calcification and linear low-density areas on non-enhanced CT images.All localized masses showed significant enhancementwith an increase of(56 ± 22)HU on arterial phase and showed residual enhancement and some low-density areas on delayed phase.Enhancing patterns were variable,including homogeneous enhancement,gradual enhancement from the edge to the center of mass and heterogeneous enhancement.Four patients with localized lesion demonstrated enhancing vessels around masses.Four patients with muhicentric CD belonged to the plasma cell type and had multiple enlarged lymph nodes.Plasma cell type masses with homogeneous density also showed enhancement after injection of contrast media but appeared to reveal a less increase of (32 ± 10) HU than the hyaline vascular type.Conclusions The localized Castleman disease showed certain characteristics on CT imaging includingcalcification and contrast enhancing patterns,which could help in the differential diagnosis of this disease.The muhicentric Castleman disease did not reveal any useful imaging features.

Objective To investigate the relationship between the white matter fiber connectivity of the anterior commissure (AC) and schizophrenia, and to explore the role of AC connectivity in cognitive functions in first-episode schizophrenia. Methods Twenty-four patients with first-episode schizophrenia and 29 healthy controls underwent diffu-sion tensor imaging (DTI) to measure fractional anisotropy (FA). Fiber tracking was then used to reconstruct the white matter fiber connectivity of AC to examine the white matter integrity. We also analyzed the relationship between AC integ-rity and cognitive function. Results Compared to healthy controls, patients with first-episode schizophrenia had a signifi-cant reduction in mean FA of AC tracts [(0.48±0.07) vs. (0.54±0.05),P=0.002],longer completion time in trail making test(TMT)[TMT_A: (55.19 ± 19.15) vs. (36.61 ± 11.72), P<0.001;TMT_B: (88.84 ± 38.92) vs. (53.75 ± 23.41), P<0.001] and worse performance in logical memory test [immediate logical memory score:(6.12±3.85) vs. (11.69±3.68), P<0.001;delay logical memory score:(3.33±3.16) vs. (9.83±4.15), P<0.001]. In addition, there was negatively correlation of mean FA of AC tracts with TMT_A completion time (r=-0.458, P=0.037) or TMT_B completion time (r=-0.541, P=0.011) in patients with schizophrenia, but not in controls. Conclusion This study supports the disconnection hypothesis of schizo-phrenia. The deficit of AC microstructure integrity may be partly responsible for impaired executive functions in schizo-phrenia, suggesting that the integrity of white matter fiber is an important endophenotype of schizophrenia.

Objective To study the value of DSA for hepatic vascular anatomy,and to evaluate the efficacy of portal vein occlusion in rabbits with hepatic VX2 tumor.Methods Twenty New Zealand white rabbits were randomly divided into two groups with 10 in each group,including test group A and positive control group B of ham operation.For the test group A,portal branch ligation(PBL)was performed for the left external branch after 3 weeks of the tumor implantation to the left external lobe.Two weeks later,the DSA of hepatic artery and portal vein were performed in all of the rabbits.Results The total displaying effectiveness of the branches of hepatic artery by DSA was better than that by vascular perfusion.There was hypovascular blood supply to hepatic artery implantation of the tumor in the test group A,comparing with that of the group B.Conclusion DSA can clearly display spacial details of the hepatic vascular anatomy in rabbits,and play an important role in post-procedual evaluation of the portal vein occlusion in rabbits.

OBJECTIVETo compare thoracoscopic esophagectomy with traditional esophagectomy in radical mediastinal lymphadenectomy for esophageal cancer, and to explore the feasibility and safety of thoracoscopic mediastinal lymphadenectomy for esophagectomy.

METHODSClinical data associated with perioperation and mediastinal lymph nodes clearance of 304 patients undergoing radical operation of esophageal cancer via left neck-right chest-upper abdomen in our department from June 2009 to June 2011 were analyzed retrospectively. Among 304 cases, 199 received traditional open radical resection and 105 thoracoscopic esophagectomy. The intrathoracic mediastinal lymph node metastasis rate, extent of metastasis, time of operation, blood loss and complications between two groups were compared.

RESULTSAll the 304 cases completed their operations successfully. A total of 3724 mediastinal lymph nodes were removed, mean 12.3±7.0 per case, including 1065 in thoracoscopic group, mean 10.1±5.5 per case, and 2659 in open group, mean 13.3±7.5 per case, whose difference was significant. But further analysis according to the postoperative pathologic staging showed no significant difference of above lymph nodes removed between two groups. Mediastinal lymph node metastasis was found in 126 patients with a rate of 41.4%, which was 35.6% and 44.7% in thoracoscopic and open groups respectively without significant difference(P>0.05). The left laryngeal recurrent nerve lymph node metastasis rate in open group and thoracoscopic group was 16.1% and 6.7% respectively, and the difference was significant(P<0.05). Differences of lymph node metastasis rate in other regions were not significant between the two groups. There were 365 positive lymph nodes, and the lymph node metastasis degree was 9.8%. which was 8.2% and 10.5% in thoracoscopic group and open group respectively(P<0.05), besides metastasis degree of open group was much higher in right laryngeal recurrent nerve and subcarinal lymph node region. The overall complication rate was 36.8%, which was 28.6% in thoracoscopic group and 41.2% in open group respectively with significant difference(P<0.05). There were no significant differences in operative time and blood loss between the two groups(both P>0.05).

CONCLUSIONRadical mediastinal lymphadenectomy with thoracoscopic esophagectomy is technically safe and feasible for early to moderate stage esophageal cancer with similar lymph nodes removed and lower complication morbidity. In the early period of carrying out thoracoscopic radical mediastinal lymphadenectomy, laryngeal recurrent nerve and subcarinal lymph node region should be identified to prevent incidental injury.

Blood Loss, Surgical ; Esophageal Neoplasms ; pathology ; surgery ; Esophagectomy ; methods ; Humans ; Lymph Node Excision ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; pathology ; Mediastinum ; pathology ; Operative Time ; Retrospective Studies

The purpose of this study is to investigate the activity and mechanism of a new anti-tumor agent T03. MTT and colony formation assay were performed to determine anti-proliferation activity of T03 in vitro. Antitumor activity was observed by Renca xenograft model in vivo. The effect of T03 on cell cycle and apoptosis were measured by FCM analysis. Western blotting was performed to investigate the expression level of proteins in HepG2 cell lines treated with T03. T03 had anti-tumor activity by inhibiting tumor cell growth and colony formation in vitro, especially on hepatocellular carcinoma cells (HCC). At the concentration of 10 micromol x L(-1), T03 induced cell apoptosis and cell cycle arrest in HCC. Moreover, it proved that T03 reduced the tumor weight with the rate of 42.30% without any obviously side effect in Renca xenograft model. At the concentration of 2.0 micromol x L(-1), T03 was able to reduce the level of p-c-Raf (Ser259), and thus blocked Raf/MEK/ERK and AKT signaling in HepG2 cell lines. The result suggested that T03 has the potential to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo, particularly active against HCC, indicating T03 and its analogues may serve as a new anti-cancer drug against hepatocellular carcinoma.
Animals ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; pathology ; Cell Cycle Checkpoints ; drug effects ; Cell Proliferation ; drug effects ; Hep G2 Cells ; drug effects ; Humans ; Liver Neoplasms ; pathology ; Signal Transduction ; drug effects ; Xenograft Model Antitumor Assays

OBJECTIVETo investigate the characteristics of lymphatic metastasis in different types of adenocarcinoma of the esophagogastric junction (AEG) and provide guidance for surgical approach adoption.

METHODSClinical data of 228 patients with AEG undergoing surgery were analyzed retrospectively. According to Siewert classification, there were 9 cases of type I (3.9%) who all underwent left thoracoabdominal approach procedures. A total of 121 patients belonged to type II (53.1%), of whom 12 underwent left transthoracic approach, 48 left thoracoabdominal approach, and 61 transabdominal approach. Ninety-eight patients belonged to type III (43%), of whom 22 underwent left thoracoabdominal approach procedures and 76 transabdominal. The pattern of lymph node metastasis was analyzed and the association between surgical approach and oncological clearance was examined.

RESULTSThe resection margin was positive in 20(8.8%) patients, including 10 with type II (8.3%) and 10 with type III (10.2%), and the difference was not statistically significant (P>0.05). The rate of positive resection margin was 12.4%(17/137) in the transabdominal group and 16.7%(2/12) in the left transthoracic group, both significantly higher than the left thoracoabdominal group (1.1%, 1/88) (both P<0.05). Lymph node metastasis was found in 159(69.7%) patients. The metastasis was found in 4 of 9 patients with type I cancer and two were thoracic metastasis, no metastasis was found in the upper mediastinum. For type II cancer, the rate of lymph node metastasis was 66.9%(81/121), including thoracic metastasis ( n=32, 26.4%) and abdominal metastasis (n=81, 66.9%). For type III cancer, the rate of lymph node metastasis was 66.9%(81/121), including thoracic metastasis (n=15, 15.3%) and abdominal metastasis (n=69, 70.4%).

CONCLUSIONSFor type I AEG, left thoracoabdominal approach should be used because the pattern of lymph node metastasis is similar to that of the distal esophageal carcinoma. For type II , left thoracoabdominal approach should be used to ensure adequate resection of the tumor and clearance of lymph node in the lower esophagus and upper mediastinum because of high rate of intrathoracic lymph node metastasis. For type III cancer, transabdominal incision offers better benefit with less impact on respiratory function. However, thoracic incision should be used to ensure adequate clearance for tumors of larger size and significant external invasion.

Adenocarcinoma ; pathology ; surgery ; Adult ; Aged ; Aged, 80 and over ; Esophagectomy ; methods ; Esophagogastric Junction ; pathology ; surgery ; Female ; Humans ; Lymph Node Excision ; methods ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; pathology ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

Objective To investigate the relationship between multi-slice spiral CT perfusion imaging and tumor angiogenesis and cell cycle protein D1 (cyclinD1) expression in patients with peripheral lung cancer. Methods Seventy-three patients with peripheral lung cancer underwent 16-slice spiral CTperfusion imaging. The CT perfusion imaging were analyzed for time density curve (TDC), perfusion parametric maps and the respective perfusion parameters (BF, BV, PS, PH, and PHpm/PHa). Correlation between the respective perfusion parameters and immunohistochemical findings of MVD measurement and cyclinD1 expression were evaluated. Statistical method used one factor analysis of variance (One-wayANOVA) and Pearson correlation analysis. Results The shape of TDC of three groups of peripheral lung cancers (adenocarcinoma, squamous cell carcinoma, and other type of cancer) was similar. They showed a steeper slope, was obvious increase of nodular HU value [ peak height of TDC is respectively (44. 87±6. 83), (34. 91 ± 8.05), (40. 66±5. 87) HU ], changed little after reaching peak height, became flat at peak, had a platform. Forty-four patients were cyclinD1 positive expression, the peripheral lung cancers with cyclinD1 positive expression showed significantly higher MVD value than that of the peripheral lung cancers with cyclinD1 negative expression [ respectively (33.88± 14. 81), (23. 17±11.66) band/high magnification, P < 0. 01]. The cancers with cyclinD1 positive expression showed significantly higher PH,PHpm/PHa, BF,BV, PS value than those of the cancers with cyelinD1 negative expression[respectively P <0. 05]. MVD was positively correlated with PH, PHpm/PHa, BF, BV, and PS of the three groups ofcancers with cyclinD1 positive expression. Among, the correlation coefficient (r value) of BV, PS, BF was0. 409, 0. 517,0. 503 respectively(all P < 0. 01). MVD was significantly correlated with them. The r valueof PH, PHpm/PHa is 0. 319,0. 324 respectively(all P < 0. 05). MVD was less correlated with them. MVDwas not correlated with PH, PHpm/PHa, BF, BV, and PS of the three groups of cancers with cyclinD1 negative expression. Conclusions Multi-slice spiral CT perfusion imaging moderately correlated with tumorangiogenesis and reflected MVD measurement and cyclinD1 expression. It provided not only a noninvasive method of quantitative assessment for blood flow patterns of peripheral lung cancer but also an applicable diagnostic method for peripheral lung cancer.

Coronary Artery Bypass ; adverse effects ; Female ; Humans ; Male ; Mammary Arteries ; injuries

OBJECTIVETo study the survival time of recombination rival in environment and inactivation ability of different disinfectant and ultraviolet radiation against virus.

METHODSNC membranes absorbed the recombinant adenovirus (rADV) or herpes simplex virus (rHSV) with green fluorescence protein (GFP) were laid, or immersed in various concentration of different disinfectants such as ethanol, sodium hypochlorite, lysol and geramine and then taked out them every 15 min, or exposed under ultraviolet radiation, then the NC membranes were adsorbed 1 h in cell, 37 degrees C 5% CO2 48 h. The results were observed under the fluorescence microscope.

RESULTS(1) the average survival time of rHSV under environment is less than 60 min, rADV is almost up to 2 h. (2) The infection ability of rHSV and rADV was inactived 15 min by both ethanol (100%, 70% and 50%) and sodium hypochlorite (5%, 2.5% and 1.25%). (3) Two virus can be killed by 0.1% bromogeramine. (4) Both 5% and 2.5% lysol, but rADV can not lost the infection on Vero Cell until 75 min by 1.25% Lysol. (5) The rHSV was inactivated under ultraviolet radiation, but rADV was not.

CONCLUSIONThe survival time of is different from both envelope rival and the no-envelope viral under nature environment and the inactivate ability of disinfectant also is different between two model virus; Disinfectant should be choose according to virus type.

Adenoviridae ; drug effects ; radiation effects ; Disinfectants ; toxicity ; Disinfection ; methods ; Risk ; Simplexvirus ; drug effects ; radiation effects ; Sodium Hypochlorite ; toxicity ; Sterilization ; methods ; Ultraviolet Rays ; Virus Diseases ; Virus Inactivation ; Virus Physiological Phenomena ; drug effects ; radiation effects ; Viruses ; drug effects ; radiation effects