Objective: To evaluate the efficiency and safety of ibandronate at the initial loading dose in the treatment of metastatic bone pain (MBP) induced by non-small cell lung cancer (NSCLC). Methods: Thirty cases of NSCLC patients who were admitted to our hospital from May 2006 to July 2007 were retrospectively analyzed. They received loading dose of ibandronate for MBP treatment. Ibandronate was given to the patients intravenously at initial loading dose of 6 mg for more than 15 min on 3 consecutive days. Then ibandronate was administered repeatedly at 6 mg every 3 to 4 months. The response time, pain score, QOL score, daily morphine consumption dose were recorded. The serum markers such as calcium, creatinine, alkaline phosphatase (AKP) were monitored. Results: Twenty nine cases were eligible to evaluate the efficiency and safety. Among them, the MBP of 25 cases (86.2%) were relieved. Their average response time was 2.9 ± 0.8 days. The pain score was significantly decreased after treatment and the life qualities of patients were markedly improved (P <0.001). The morphine consumption dose was reduced by about 20 to 40 mg in 4 cases after treatment. The serum calcium level increased in 7 patients before treatment and declined to the normal level after treatment. The adverse reaction was relieved after treatment and no renal toxicity was observed. Conclusion: Administration of ibandronate at initial loading dose had quick on-set and mild side effects. It could significantly relieve metastasis bone pain and improve QOL, reduce the morphine consumption dose and avoid morphine-induced adverse reaction, and effectively decrease serum calcium level. Administration of ibandronate at initial loading dose is a new promising option for treatment of the MBP in NSCLC.

AIMTo determine the molecular weight and first-order structure of somatostatin.

METHODSThe molecular weight of somatostatin was determined by electrospray ionization mass spectrometry. Somatostatin was deoxidized by 2-mercaptoethanol. A series of typical fragment ions of deoxidized product were obtained by insource collision-induced dissociation (CID).

RESULTSThe m/z of quasi-molecular ion [M + H]+ of somatostatin was 1,637.8 and [M + Na]+ was 1,659.5. The m/z of double-charge ion [M + 2H]2+ was 819.5 and [M + H + Na]2+ was 830.3. It showed that the molecular weight of somatostatin was 1,636.7. The y and b series of fragment ions of deoxidized product were obtained by adjusting the fragmentor voltage. It was determined that the first-order structure of deoxidized product of somatostatin was A-G-C-K-N-F-F-W-K-T-F-T-S-C.

CONCLUSIONThe molecular weight and first-order structure of somatostatin were confirmed.

Amino Acid Sequence ; Molecular Structure ; Molecular Weight ; Somatostatin ; analysis ; chemistry ; Spectrometry, Mass, Electrospray Ionization ; methods

OBJECTIVETo investigate the effects of Shexiang Baoxin Pill (SBP) on function of endothelial progenitor cells (EPCs) and its nitric oxide (NO) secretion.

METHODSTotal mononuclear cells were isolated from human peripheral blood by ficoll density gradient centrifugation and inoculated on the human fibro-ligandin encrusting plate. After 7 days of in vitro culture, adherent cells were collected and incubated with SBP for 24 h. The proliferation, migration, adhesive activity, vasculogenesis capacity and NO secretion of EPCs were assayed using MTT, Transwell chamber, adhesion determination, in vitro vasculogenesis kit and nitrate reductase method, respectively.

RESULTSEPCs incubated with SBP showed the capacities higher than those of control in proliferation, migration, adhesion, in vitro vasculogenesis, and with a higher NO concentration in the culture supernatant.

CONCLUSIONSBP can improve the function of EPCs, which might be a novel mechanism of its effects in improving vascular endothelial function and promoting angiogenesis.

Cell Differentiation ; physiology ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; Endothelial Cells ; cytology ; metabolism ; physiology ; Humans ; Leukocytes, Mononuclear ; cytology ; Nitric Oxide ; biosynthesis ; Stem Cells ; cytology ; metabolism ; physiology

OBJECTIVETo evaluate computed tomography (CT) and magnetic resonance imaging (MRI) findings in patients with autoimmune pancreatitis (AIP).

METHODSThe imaging findings of pancreas and extra-pancreas in 24 patients with AIP were retrospectively reviewed. Among them, CT scan was performed in 18 patients, MRI in 11, and bGth CT and MRI in 10.

RESULTSThe pancreas showed diffuse enlargement (25%, 6/24), focal enlargement (37. 5%, 9/24), combined enlargement (25%, 6/24) ,and no enlargement (12. 5%, 9/24). Unenhanced CT showed hypoattenuation in AIP area (n = 2) . After intravenous injection of contrast medium, 17 patients showed abnormal contrast enhancement in the affected pancreatic parenchyma, including hypoattenuation during the arterial phase (50%, 9/18) and hyper attenuation during the delayed phase (94. 4%, 17/18). Precontrast MRI showed abnormal signal intense (n =9), including hypointense on T1-weight images (T1 WI) (n = 7), hyperintense (n = 7) and hypointense (n = 2) on T2-weight images (TIWI). Enhanced MRI demonstrated abnormal contrast enhancement within lesions (n = 11), including hypoattenuation during the arterial phase (81. 8%, 9/11) and good enhancement during the delayed phase (100%, 11111). A capsule-like rim was seen around pancreas (37. 5%, 9/24), among which CT detected in 6 out of 18 patients and MRI found in 7 out of 11 patients.The main pancreatic duct lumen within lesions has no visualization (100%, 24/24) and upstream dilation of the main pancreatic duct (n = 8) , ranging from 2. 2 to 4. 5 mm(mean 3. 1 0. 47 mm) in diameter. Narrowing of the common bile duct was shown in 14 patients. Miscellaneous findings were: infiltration of extrapancreatic vein (n = 9) and artery (n = 1); mild fluid collection around pancreas (n = 2); pseudocysts (n = 3). Fourteen patients also presented one or more of the following extrapancreatic imaging findings: narrowing of the intra-hepatic bile duct or hilar duct (n = 5); thickening of gallbladder wall (n = 5); fibrosis in mesenteric (n = 2), in retroperitoneal (n = 2) and in ligamentum teres hepatis (n = 1); renal involvement (n = 3); peri-pancreatic or para-aortic lymphadenopathy (n = 10); and ulcerative colitis (n = 3).

CONCLUSIONAIP display some characteristic CT and MRI imaging features: sausage-like change of the pancreas; capsule-like rims around lesions; delayed contrast enhancement in the affected pancreatic parenchyma; segment or diffuse pancreatic duct stenosis but mild upstream dilation and extrapancreatic organs involvement. CT and MRI findings combining with serological tests and pancreas biopsy can assist physicians to make accurate and timely diagnosis.

Adult ; Aged ; Autoimmune Diseases ; diagnosis ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Pancreas ; diagnostic imaging ; pathology ; Pancreatitis ; diagnosis ; Retrospective Studies ; Tomography, X-Ray Computed

This paper reports the surface morphology and I-V curves of porous silicon (PS) samples and related devices. The observed fabrics on the PS surface were found to affect the electrical property of PS devices. When the devices were operated under different external bias (10 V or 3 V) for 10 min, their observed obvious differences in electrical properties may be due to the different control mechanisms in the Al/PS interface and PS matrix morphology.
Electrochemistry ; instrumentation ; methods ; Electrodes ; Electromagnetic Fields ; Gold ; chemistry ; Materials Testing ; Molecular Conformation ; Porosity ; Silicon ; chemistry ; Surface Properties

OBJECTIVETo study the effects of a small interfering RNA targeting CXCR-4 (shRNA-CXCR4) on angiogenesis of human breast cancer cells.

METHODSThe expression of CXCR4 mRNA and protein in 3 breast cancer cell lines with CXCR-4 silencing mediated by shRNA-CXCR4 was detected by RT-PCR and Western blotting, respectively. The morphological changes of human umbilical vein endothelial cells (HUVECs) were observed in co-culture with human breast cancer cells after CXCR4 gene silencing.

RESULTSCXCR4 mRNA and protein expressions decreased significantly in MCF-7, MDA-MB-231 and MDA-MB-435s breast cancer cells after the gene silencing (P<0.05). Gene silencing with shRNA-CXCR4 in human breast cancer cells significantly inhibited the ability of HUVECs to form tubular structures in the co-culture (P<0.05).

CONCLUSIONGene silencing by shRNA-CXCR4 can obviously lower the angiogenesis-inducing ability of human breast cancer cells.

Breast Neoplasms ; blood supply ; genetics ; Cell Line, Tumor ; Coculture Techniques ; Endothelial Cells ; cytology ; Female ; Humans ; Neovascularization, Pathologic ; genetics ; RNA Interference ; RNA, Messenger ; genetics ; metabolism ; RNA, Small Interfering ; genetics ; Receptors, CXCR4 ; genetics ; metabolism ; Umbilical Veins ; cytology

AIMTo investigate antimalarial mechanism of Qinghaosu ( QHS) and its derivatives.

METHODSThe electronic structure of QHS and its derivatives were completely optimized and calculated at B3LYP/6-31G * level, while the route was at HF/STO-3G level.

RESULTSThe peroxide bridge is the active center of QHS and induced by ferrous iron to produce cyclic product.

CONCLUSIONHeme can link with QHS derivatives.

Antimalarials ; chemistry ; isolation & purification ; Artemisia ; chemistry ; Artemisinins ; chemistry ; isolation & purification ; Electron Transport ; Free Radicals ; chemistry ; Heme ; chemistry ; Models, Chemical ; Peroxides ; chemistry ; Plants, Medicinal ; chemistry ; Quantum Theory

OBJECTIVETo investigate the effect of adenosine A2A receptor knockout (A(2A)RKO) on relationship between continuous activation of phospho-c-Jun N-terminal kinase (P-JNK) and expression of nerve cell apoptosis in hippocampus CA1 domain of newborn mice after hypoxia/ischemia brain damage(HIBD) and its potential mechanism.

METHODSA(2A)RKO mice and adenosine A2A receptor wildtype (A(2A)RWT) littermates (n = 80) were divided into Sham operation group (S) and model group (M), 1, 3 and 7 day after HIBD, totally 8 groups. HIBD was developed with 7 day-old neonatal mice according classical Rice-Vannucci method. It was tested the effect of A(2A)RKO on short-term neurofunctional outcomes consisted of three developmental reflexes (righting, geotaxis and cliff aversion), the changes of brain pathology with hematoxylin-eosin (HE) staining and Nissl staining, the expressions of nerve cell apoptosis with terminal deoxynucleotidyl transferase mediated dUTP-biotin nick-end labeling(TUNEL) staining and P-JNK were observed by immunohistochemistry.

RESULTSThe neurological behavior injuries and brain histopathological damages and nerve apoptosis cells were aggravated in A(2A)RKO newborn mice after HIBD. The positive expressions of P-JNK were significantly higher in the ischemic hippocampus CA1 domain after HIBD than ones in group S respectively (P < 0.01), reaching to peak at 1 day and then began gradually decreasing. P-JNK expression in model knockout(MKO) at 1, 3 and 7 day increased greatly compared to those in the previous time point of corresponding model wildtype (MWT) (P < 0.01, P < 0.05, P > 0.05); there was a positive correlation between the expressions of P-JNK and nerve cell apoptosis after HIBD in newborn mice(r = 0.837, P < 0.01).

CONCLUSIONEarly continuous activation of P-JNK might be involved in the aggravated nerve apoptosis cells and brain damage induced by A(2A) RKO newborn mice after HIBD.

Animals ; Animals, Newborn ; Apoptosis ; Hypoxia-Ischemia, Brain ; metabolism ; pathology ; JNK Mitogen-Activated Protein Kinases ; metabolism ; Mice ; Mice, Knockout ; Neurons ; drug effects ; metabolism ; pathology ; Receptor, Adenosine A2A ; genetics

OBJECTIVETo investigate the impact of erlotinib as a second or third line treatment on the symptoms and quality of life (QOL) in patients with advanced non-small cell lung cancer (NSCLC).

METHODSFifty patients with stage III b and IV NSCLC, treated previously with at least one regimen of platinum-based chemotherapy, received 150 mg of erlotinib orally, once a day till disease progression. QOL was assessed by European Organization for Research and Treatment of Cancer QLQ-C30 and the lung cancer module (QLQ-LC13). The primary end points for QOL analysis were time to deterioration of three common lung cancer symptoms: cough, dyspnea and pain.

RESULTSAmong 47 evaluable cases, there were partial remission (PR) in 18 cases, stable disease (SD) in 21 cases, and progressive disease (PD) in 8 cases. After two cycles of treatment, the mean scores of global QOL and all 5 functioning scales except the cognitive function increased significantly (P < 0.05). Mean scores of major general symptoms, hypodynamia and anorexia, and disease-related symptoms alleviated significantly. Both response rates of five functioning and global QOL were more than 44% after erlotinib treatment. Response rates of major general symptoms and disease-related symptoms varied from 14% to 76%. Patients with complete or partial response likely had improvement in the QOL response (P < 0.05), and the time to major symptom deterioration in those were significantly longer (P < 0.001) than that in patients with stable or even progressive disease.

CONCLUSIONErlotinib is effective to improve not only survival, but also tumor-related symptoms and quality of life in patients with advanced NSCLC previously treated with cisplatin-contained regimens. The improvement in the quality of life is positively correlated with objective tumor response.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Disease Progression ; Erlotinib Hydrochloride ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Quality of Life ; Quinazolines ; therapeutic use ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; therapeutic use ; Remission Induction ; Salvage Therapy ; Treatment Failure

BACKGROUNDHyaluronidase (Hyase) is an enzyme which hydrolyses hyaluronan (HA), a large nonsulfated glycosaminoglycan. Several genes have been identified to code for hyaluronidases in humans. Its role has only recently been underlined in the invasion of prostate cancer, colonic cancer, and breast cancer. Moreover, the findings were in agreement with some experimental results which showed that HA-derived oligosaccharides had angiogenesis-promoting activity. All these findings prompted us to investigate factors that had been characterized as putative invasive factors in different human breast cancer-derived cell lines.

METHODSWe selected two series of human breast cancer-derived cell lines whose expression of estrogen receptors (ER) was previously published. Hyaluronidase secretion in culture medium and expression of matrix metallo-proteinase (MMP)-9, cathepsin-D (cath-D) and vascular endothelial growth factor (VEGF) by cells were determined. We also investigated cell invasiveness in the Matrigel invasion assay, and studied the capability of cancer cells to promote in vitro formation of tubules by endothelial cells.

RESULTSER(-) cells secreted significantly more hyaluronidase (P < 0.001) and expressed significantly more VEGF (P < 0.01), MMP-9 (P < 0.05) and cath-D (P < 0.0001) than ER(+) cells. Invasion through Matrigel by ER(-) Hyase(+) cells was significantly higher than that by ER(+) Hyase(-) cells (P < 0.05). In both cases, invasion was decreased by heparin (P < 0.05). When ECV-304 endothelial cells were co-cultivated in millicell chambers with cancer cells, ECV-304 cells were induced to form tubules. Tubule formation was demonstrated to be more prominent with ER(-) Hyase(+) cells than with ER(+) Hyase(-) cells (P < 0.05).

CONCLUSIONInvasive features of ER(-) breast cancer cells can be characterized in vitro by an invasive Matrigel assay, as the induction of tubule formation by ECV-304 endothelial cells, higher secretion of hyaluronidase, and higher expression of proteinases MMP-9, cath-D, and the angiogenesis promoting factor VEGF.

Breast Neoplasms ; metabolism ; Cathepsin D ; metabolism ; Cell Line, Tumor ; Humans ; Hyaluronoglucosaminidase ; metabolism ; Immunohistochemistry ; Matrix Metalloproteinase 9 ; metabolism ; Neoplasm Invasiveness ; genetics ; Receptors, Estrogen ; genetics ; Vascular Endothelial Growth Factor A ; metabolism