In the present study, a new compound named 17-(6-cinnamamido-hexylamino-)-17-demethoxygeldanamycin (CDG) was obtained by introducing the cinnamic acid (CA) group into the 17-site of geldanamycin (GDM). The anti-cancer effects of CDG in vitro and in vivo were evaluated. MTT assay was used to examine the inhibitory effect of CDG on the proliferation of MCF-7, HepG2, H460 and SW1990 cells. Immunofluorescent staining flow cytometry combined with Annexin V-FITC/PI staining were used to detect apoptotic cells. Transwell assay was used to analyze the effect of CDG on cell invasion and migration ability. Western blotting was used to detect the expression levels of RAF-1, EGFR, AKT, CDK4 and HER-2 of MCF-7, HepG2 and H460 cells. The toxicities of CDG and GDM were evaluated in mice. Using the subcutaneously transplanted MCF-7 xenograft in nude mice, inhibitory effect was evaluated in vivo. The results showed that CDG inhibited the proliferation of cancer cells (IC50: 13.6-67.4 microg.mL-1). After exposure to CDG for 48 h, most cells presented typical morphologic changes of apoptosis such as chromatin condensation or shrunken nucleus. The rates of apoptosis of MCF-7, HepG2, H460 and SW1990 cells incubated with 10 microg.mL-1 CDG were 23.16%, 27.55%, 22.21%, 20.47%, respectively. A dose-dependent reduction of migration of four cell lines was found after exposure to CDG. The decreased levels of RAF-1, EGFR, AKT, CDK4 and HER-2 showed that CDG possessed HSP90 inhibitory effect. The result of animal toxicity test on the mice suggested that CDG had lower toxicity than GDM. Meanwhile, CDG inhibited the growth of MCF-7 xenografts of athymic mice.
Animals ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Apoptosis ; drug effects ; Benzoquinones ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cyclin-Dependent Kinase 4 ; metabolism ; Female ; HSP90 Heat-Shock Proteins ; antagonists & inhibitors ; Humans ; Lactams, Macrocyclic ; chemical synthesis ; chemistry ; pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Invasiveness ; Neoplasm Transplantation ; Proto-Oncogene Proteins A-raf ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Random Allocation ; Receptor, Epidermal Growth Factor ; metabolism ; Receptor, ErbB-2 ; metabolism ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays

0.05).At different time points after ischemia-reperfusion,the expression of cytochrome C and activation of caspase-3 were lower in the transgen mice than that in the wild type rats.Conclusions Under standard condition,overexpression of bcl-xl could significantly reduce the infarct area and improve neurological function in transgene mice than those in the wild type rats.The effect of overexpression of bcl-xl might be realized through inhibiting the apoptosis of neuron,and the mechanism might be that the overexpression of bcl-xl inhibit the release of cytochrome C and the activation of caspase-3.

The endophytic microorganisms found widely in many kinds of plants mediate various effects to theirs hosts. In this study, seven different dominant endophytes (SDE01 to 07) isolated from a Hy-peraccumulator-Solanum nigrum L. were resistant to Cd2+, and the strain SDE06 survived even in the medium containing 80 mg/L of Cd2+. Bacteria strain SDE06 was identified as Bacillus sp.. The removal of Cd2+ of SDE06 in different conditions were studied. Under the optimal conditions, the incubating time was 36 h, the solution pH 6.0, the temperature was 37?C and the Cd2+ concentration of medium was 20 mg/L, the highest removal rate was up to 80.2% at this condition.

From an aqueous extract of Lonicera japonica flower buds, sixteen compounds were isolated by a combination of various chromatographic techniques including column chromatography over macroporous resin, MCI gel, silica gel, and sephadex LH-20 and reversed-phase HPLC. Their structures were elucidated by spectroscopic data analysis as 6'-O-acetylvogeloside (1), 6'-O-acetylsecoxyloganin (2), dichlorogelignate (3), guanosinyl-(3' --> 5')-adenosine monophosphate(GpA,4) , 5'-O-methyladenosine (5), 2'-O-methyladenosine (6), adenosine (7), syringin (8), methyl 4-O-β-D-glucopyranosyl caffeate (9), (-)-dihydrophaseic acid 4'-O-β-D-glucopyranoside (10), ketologanin (11), 7α-morroniside (12), 7β-morroniside (13), kingiside (14), cryptochlorogenic acid methyl ester (15), and 6-hydroxymethyl-3-pyridinol (16). All the compounds were obtained from this plant for the first time, compounds 1 and 2 are new compounds, 3 and 5 are new natural products, and 4 is the first example of dinucleoside monophosphate isolated from a plant extract.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Flowers ; chemistry ; Lonicera ; chemistry ; Mass Spectrometry ; Molecular Structure

AIMTo investigate the inhibitory activity of salvianolic acid A (SAA) on nucleoside transport in cancer cells and its antitumor effect.

METHODS[3H] thymidine and [3H] uridine transport assays were used to determine the inhibitory activity on nucleoside transport in Ehrlich carcinoma cells. The cytotoxicity to cultured cancer cells was examined with clonogenic assay. The antitumor effect in vivo was evaluated with transplantable tumor model in mice.

RESULTSSAA was shown to inhibit thymidine and uridine transport in Ehrlich carcinoma cells with IC50 values of 18.1 and 17.1 micromol x L(-1), respectively. By clonogenic assay, the IC50 of SAA for KB cells was 44.7 micromol x L(-1). SAA markedly potentiated the cytotoxicity of 5-FU and mitomycin C in KB cells as well as the cytotoxicity of MTX in human hepatoma BEL-7402 cells. For in vivo experiment, sarcoma 180 cells were transplanted sc in mice and tested drugs were administered ip. When administered separately, SAA at 200 mg x kg(-1) and 5-FU at 10 mg x kg(-1) inhibited tumor growth by 41% and 27%, respectively. Combination of the two drugs inhibited tumor growth by 63% (CDI = 0.86).

CONCLUSIONSAA is active in blocking nucleoside transport in cancer cells and potentiates the cytotoxicity of chemotherapeutic drugs. As an agent showing moderate antitumor effect in vivo, SAA might be useful in combination cancer therapy.

Animals ; Antineoplastic Agents ; pharmacology ; Antineoplastic Agents, Phytogenic ; isolation & purification ; pharmacology ; Biological Transport ; Caffeic Acids ; isolation & purification ; pharmacology ; Drug Synergism ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Female ; Fluorouracil ; pharmacology ; Humans ; KB Cells ; Lactates ; isolation & purification ; pharmacology ; Male ; Methotrexate ; pharmacology ; Mice ; Mitomycin ; pharmacology ; Neoplasm Transplantation ; Plants, Medicinal ; chemistry ; Salvia miltiorrhiza ; chemistry ; Sarcoma 180 ; metabolism ; pathology ; Tumor Cells, Cultured

OBJECTIVETo analyze characteristic CT enhancement patterns of noncalcified pulmonary tuberculomas and their pathological basis.

METHODFifty-six patients with noncalcified pulmonary tuberculomas underwent surgical resection of the tuberculomas. Enhanced CT images of these tuberculomas were reviewed and analyzed in relation to the histological findings.

RESULTSOf the 56 patients, 45 showed no enhancement in the tuberculomas, which were histologically characterized by central caseous necrosis and a poorly vascularized peripheral fibrotic zone. Eleven patients showed ring-like or eggshell enhancement, and the central low density region was histologically confirmed to be caused by caseous or liquefied necrosis, while the ring enhancement resulted pathologically from moderately or well vascularized peripheral fibrotic or granulomatous tissues.

CONCLUSIONSPulmonary tuberculomas consists mainly of caseous necrotic tissues characterized by no enhancement and ring or eggshell enhancement on dynamic contrast-enhanced CT.

Adult ; Calcinosis ; Contrast Media ; Female ; Humans ; Male ; Middle Aged ; Tomography, X-Ray Computed ; Tuberculoma ; diagnostic imaging ; metabolism ; Tuberculosis, Pulmonary ; diagnostic imaging ; metabolism ; Young Adult

OBJECTIVETo explore the inhibitory effects of endoplasmic reticulum-retained intrabody on the secretion of type IV collagenase and the invasion of human pulmonary giant cell carcinoma PG cells in vitro.

METHODSTwo expression plasmids were constructed, pcDNA3.1-CP.scFv and pcDNA3.1-ER.scFv encoding cytoplasm-retained and endoplasmic reticulum-retained single chain antibodies against the type IV collagenase, respectively. The intracellular antibody genes were transfected into the human pulmonary giant cell carcinoma PG cells. Western blot was performed to detect the expression of pcDNA3.1-CP.scFv and pcDNA3.1-ER.scFv. Gelatin zymography was performed to detect seretion of type IV collagenase in PG cells and Matrigel assay was employed for determination of the cell invasiveness.

RESULTSBoth of cytoplasm-retained and endoplasmic reticulum-retained introbodies, CP.scFv and ER.scFv, were expressed in PG cells. ER.scFv, significantly inhibited the secretion of type IV collegenase. As shown, matrix metalloproteinase 9 and matrix metalloproteinase 2 were inhibited by 85.7% and by 51.2%, respectively. However, CP.scFv did not show such inhibitory effect. The ER.scFv encoding gene-transfected PG cells were much less invasive than parental or vector control cells, the inhibition rate was 76.3% (P < 0.05), whereas CP.scFv encoding gene-transfected PG cells showed no reduction in invasiveness.

CONCLUSIONThose findings demonstrate that endoplasmic reticulum (ER)-retained intracellular antibody technology may selectively abrogate the activity of type IV collagenase in the protein trafficking and secretory pathway and effectively inhibit tumor cell invasion in vitro. Anti-type IV collagenase intrabody may be further used in cancer gene therapy.

Carcinoma, Giant Cell ; metabolism ; pathology ; Cell Line, Tumor ; Cytoplasm ; immunology ; Endoplasmic Reticulum ; immunology ; Genetic Vectors ; Humans ; Immunoglobulin Variable Region ; metabolism ; physiology ; Lung Neoplasms ; metabolism ; pathology ; Matrix Metalloproteinase 2 ; immunology ; metabolism ; Matrix Metalloproteinase 9 ; immunology ; metabolism ; Neoplasm Invasiveness ; Plasmids ; Transfection

BACKGROUNDChronic obstructive pulmonary disease (COPD) is thought to be an inflammatory immune response disease. In most cases, the disease is caused by cigarette smoke, but it has been demonstrated that only 10% to 20% of smokers will definitely suffer from COPD. Dendritic cells (DCs) are considered to be the promoter of immune responses. However, the underlying mechanisms involved are still unrevealed. In this study, we aimed to investigate the quantitative differentiation of pulmonary DC in smokers with or without COPD to explore the possible role of DCs in smokers suffering COPD.

METHODSPeripheral lung specimens from non-smokers without airflow obstruction (control group, n = 7), smokers without airflow obstruction (smoker group, n = 7) and patients with COPD (COPD group, n = 7) were investigated to detect the quantity of S-100 and CD1a positive cells by immunohistochemical or immunofluorescent assay.

RESULTSIn smokers with COPD, the number of S-100(+) DCs was higher than in the controls and smokers without COPD (P < 0.01 and P < 0.05) and there was a higher number of S-100(+) DCs in smokers with COPD than in smokers without COPD, but without a significant difference (P > 0.05). An inverse correlation was found between the number of DCs and forced expiratory volume in the first second (FEV(1))% pred (r = -0.75, P < 0.05), which was also found between the number of DCs and FEV(1)/forced vital capacity (FVC) (r = -0.72, P < 0.05). The mean number of CD1a(+) DCs, increased from non-smokers to non-COPD smokers to COPD patients, with significant differences between each group (P < 0.01).

CONCLUSIONSThe quantity of DCs significantly increased in smokers with COPD compared with non-smokers or smokers without COPD. The results suggest that DCs may play an important role in the pathogenesis of smoking-induced COPD, and the upregulation of DCs may be a potential maker to identify the smokers who have more liability to suffer from COPD.

Aged ; Antigens, CD1 ; metabolism ; Cell Differentiation ; physiology ; Dendritic Cells ; cytology ; Female ; Fluorescent Antibody Technique ; Humans ; Immunohistochemistry ; In Vitro Techniques ; Lung ; metabolism ; pathology ; Male ; Microscopy, Confocal ; Middle Aged ; Pulmonary Disease, Chronic Obstructive ; metabolism ; pathology ; S100 Proteins ; metabolism ; Smoking ; adverse effects

To investigate the effect of lidamycin (LDM) on human gastric carcinoma BGC823 cells and xenograft growth in nude mice, MTT (methyl thiazolyl tetrazolium) assay was used to determine the inhibition of BGC823 cell proliferation by LDM. Induction of apoptosis was studied by flow cytometry and TUNEL assay. The expression of VEGF was detected by Western blotting analysis. Athymic nude mice were used to determine in vivo antitumor activity. Proliferation inhibition and apoptosis induction were studied in lidamycin-treated cells. The expression of VEGF in BGC823 cells decreased in a dose-dependent manner. LDM at 0.02 mg x kg(-1) and 0.04 mg x kg(-1) suppressed the growth of BGC823 xenografts in nude mice by 57% and 72%, respectively. LDM potently induces apoptosis in human gastric carcinoma BGC823 cells and inhibits xenograft growth.
Aminoglycosides ; pharmacology ; Animals ; Antibiotics, Antineoplastic ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Enediynes ; pharmacology ; Female ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Random Allocation ; Stomach Neoplasms ; metabolism ; pathology ; Vascular Endothelial Growth Factor A ; metabolism ; Xenograft Model Antitumor Assays

OBJECTIVETo summarize the experience of diagnosis and surgical treatment for pulmonary and pleural aspergillosis.

METHODSThe clinical data of cases with pulmonary and pleural aspergillosis were analyzed retrospectively between September 1972 and June 2003. There were 53 cases with pulmonary aspergillosis and 3 cases with pleural aspergillosis. Aspergillus was found preoperatively in 8 patients by sputum culture (5 cases) or needle biopsy of the lung (2 cases) or fibro-bronchoscopic biopsy (1 case). All patients were treated with surgical procedures following X-ray film or CT scan.

RESULTSOf 53 cases with pulmonary aspergillosis, 42 lobectomies, 3 segment-Pneumonectomies, and 8 wedge resections were performed. Of three cases with pleural aspergillosis following eliminating their diseased foci in residual pleural space, two underwent thoracoplasty, one underwent postoperative closed chest drainage for one and an half month with fluconazole injected into residual pleural space repeatedly for 1 month (200 mg/100 ml, 1 time per 2 or 3 days). No operative death and major postoperative complications occurred. None of the patients had recurrent symptoms at follow-up.

CONCLUSIONWe recommend aggressive surgical resection for pulmonary and pleural aspergillosis, and the surgical result is excellent.

Adult ; Aged ; Aspergillosis ; diagnosis ; surgery ; Female ; Humans ; Lung Diseases, Fungal ; diagnosis ; surgery ; Male ; Middle Aged ; Pleurisy ; diagnosis ; surgery ; Pneumonectomy ; methods ; Retrospective Studies ; Thoracoplasty ; Treatment Outcome