Objective To study the mechanisms of Curcumin-induced apoptosis on human gastric cancer cell line SGC-7901.Methods SC,C-7901 cells were treated with various concentrations of Curcumin and the growth inhibition rates of it were accessed by MTT method.Apoptosis of gastric cancer cells were in- spected by flow cytometry.The expression of Fas and survivin in gastric cancer cells were evaluated by west- ern blot.Results Curcumin could effectively inhibit the growth of gastric cancer cells in dose-dependent and time-dependent manners,the sub-peak appeared and the apoptotic rate was increased.The expressions of Fas was higher in Western blot,meanwhile,the expressions of survivin was decreased.Conclusion Curcumin could significantly inhibit the growth and induce apoptosis of gastric cancer cells(SGC-7901),Curcumin could probably through up-regulating Fas and down-regulating surviving to induce apoptosis.

Objective To evaluate the efficacy and adverse effects of gefitinib in the treatment of fe- male patients with advanced adenocarcinoma of lung who had failed to previous chemotherapy.Methods These patients received 250mg of gefitinib orally,once daily until disease progression or development of intol- erable toxic reaction.They were evaluated one month after treatment and every other month thereafter.Results Among the 27 evaluable patients,there were 1 CR(3.7%),11 PR(40.8%),10 SD(37.0%)and 5 PD(18.5%). The overall response rate was 44.5%(95% CI 29%～68%);and 22 patients(81.5%)gained profit(CR+PR+ SD)from the clinical therapy(95% CI 62%～94%);the mean TTP was 7.2 months.Symptomatic improvement rate was 80.0%.The main adverse effects were mild rash and diarrhea.Conclusion gefitinib has significant efficacy in the treatment of female patients with advanced tung cancer who had failed to previous chemother- apy.Adverse effects are mild.gefitinib is a suitable therapy for these patients.

OBJECTIVETo determine whether cysteinyl leukotriene receptor agonist LTD(4) and cysteinyl leukotriene receptor 1 (CysLT(1)) antagonist pranlukast affect the differentiation of human neuroblastoma SK-N-SH cells.

METHODSSK-N-SH cell morphological changes induced by LTD(4), pranlukast and LTD(4) + pranlukast were observed with retinoid acid (RA) as the positive control. The expressions of CysLT(1) and CysLT(2) receptors were detected by immunoblotting analysis, and the expression of microtubule-associated protein-2 (MAP-2), a neuron marker, was detected by fluorescent immunostaining.

RESULTThe immunoblotting results showed that SK-N-SH cells expressed CysLT(1) receptor moderately, and CysLT(2) receptor highly. The morphological results showed that RA, pranlukast and LTD(4) + pranlukast induced the compaction of the cell bodies and the outgrowth of neurites, while LTD(4) had no significant effect. The immunostaining results showed that MAP-2 was distributed in the cell bodies in control or pranlukast-treated cells; it was distributed in cell bodies and neuritis in RA-treated cells. Pranlukast increased the numbers of MAP-2-positive cells.

CONCLUSIONThe CysLT(1)receptor antagonist pranlukast modulates the differentiation of SK-N-SH cells.

Cell Differentiation ; drug effects ; Cell Line, Tumor ; Chromones ; pharmacology ; Humans ; Immunoblotting ; Immunohistochemistry ; Leukotriene Antagonists ; pharmacology ; Leukotriene D4 ; pharmacology ; Membrane Proteins ; metabolism ; Microtubule-Associated Proteins ; metabolism ; Neuroblastoma ; metabolism ; pathology ; Receptors, Leukotriene ; metabolism

Objective To explore the effects of Cigu Xiaozhi Pills on lipotoxicity and oxidative stress in rats with non-alcoholic steatohepatitis (NASH); To discuss relevant mechanism of action. Methods SD rats were divided into six groups randomly:normal control group,model group,positive medicine group,Cigu Xiaozhi Pills high-,medium-, and low-dose groups. NASH model was established by feeding rats with high fat diet for 12 weeks. At the same time, the model rats were given medicine intervention. At the end of 12 weeks, all the experimental animals were killed and the liver and serum were taken. Serum samples were taken for detection of ALT, AST, TG, TC, T-SOD, LDL-C, MDA, GSH-Px and FFA. Liver tissues were taken for detection of T-SOD, MDA, GSH-Px and FFA. The liver histopathological changes were observed under microscope with HE staining. The ultrastructure of liver cells was observed by transmission electron microscope. The fatty degeneration of liver cells was observed by oil red O staining. Results Liver histopathological examination showed that the liver tissue of model group showed moderate to severe steatosis and inflammatory cell infiltration. Compared with normal control group, rat liver wet weight, liver index, ALT, AST, TG, TC, LDL-C, MDA and FFA in serum, and FFA and MDA in liver homogenate in model group significantly increased (P<0.05, P<0.01), while T-SOD and GSH-Px activity in serum and liver homogenate significantly decreased (P<0.05, P<0.01). Compared with model group, Cigu Xiaozhi Pills high-dose group could significantly decrease the elevation of serum ALT, AST, TG, TC, LDL-C, MDA and FFA (P<0.05, P<0.01), but increase T-SOD and GSH-Px activity in serum and liver tissue (P<0.01). The pathological section showed that:compared with model group, the hepatic lobule vacuolar degeneration and fatty degeneration were significantly reduced in Cigu Xiaozhi Pills high-, medium- and low-dose groups, and the inflammatory cell infiltration was improved. Conclusion Cigu Xiaozhi Pills can obviously improve liver function and blood lipid of NASH rat model induced by high-fat diet, enhance antioxidant capacity, reduce lipid peroxidation and achieve the purpose of prevention and treatment of NASH.

AIM:To investigate the expression of IFN-γ,IL-4 and IL-17A in asthmatic mice vaccinated with bacillus Calmette-Guérin(BCG)and hepatitis B(HepB)in the neonatal period.METHODS: BALB/c mice were ran-domly divided into BGG+HepB+ovalbumin(OVA)group(B/H/O group),B/O group,H/O group,B/H group,OVA group,BCG group,HepB group and normal saline(NS)group(n=6).The mice in B/H/O group and B/H group at 0, 7 and 14 d received subcutaneous injection of 1×105CFU BCG for 3 times,while at 0 and 28 d received intramuscular in-jection of 1.5 μg HepB on the hindlimb twice.The mice in other groups were individually vaccinated with BCG or HepB. OVA sensitization and aerosol inhalation were performed to establish the asthma model.The lung tissues were collected for HE staining.Bronchoalveolar lavage fluid(BALF)and peripheral blood(PB)were collected,and the number of eosino-phils(EOS)in BALF was counted.The serum levels of IFN-γand IL-4,and the level of IL-17A in lung tissue homoge-nate were measured by ELISA.RESULTS: The pathological changes of the lung in OVA group, B/O group, B/H/O group and H/O group were observed.There were extensive inflammatory cell infiltration around the bronchus,and epithe-lial cell hypertrophy.Those in B/H/O group and H/O group were worse than those in OVA group, while those in B/O group was better than those in OVA group.Total BALF cell counts in B/H/O group,B/O group and H/O group were de-creased(P<0.05)as compared with OVA group.The BALF EOS count in B/H/O group was higher than that in B/H group,that in B/O group was higher than that in BCG group,and that in H/O group was higher than that in HepB groups (P<0.05).Compared with H/O group, OVA group and NS group, the serum IFN-γ/IL-4 ratio in HepB group was in-creased(P<0.05),and compared with B/H/O group,B/O group,OVA group and NS group,that in B/H group was al-so increased(P<0.05).Compared with OVA group, the level of IL-17A in the lung tissues of B/H/O group and B/O group was decreased(P <0.05), and compared with B/O group, that in B/H/O group was further decreased(P <0.05).CONCLUSION:Combined vaccination of BCG and HepB reduces the inflammotory responses in the lung tissues of asthmatic mice.The mechanism may be related with the decrease in the release of IL-4, the increase in IFN-γ/IL-4, and the inhibition of IL-17A expression.

The effects of human insulin 70/30 and insulin lispro 75/25 were compared in improving postprandial blood glucose excursions in 106 patients with type 1 or 2 diabetes in a one-month,open-labelled,self- controlled trial .The results showed that treatment of diabetic patients with insulin lispro 75/25 significantly improved 2 h postprandial blood glucose excursion compared to pre-study with human insulin 70/30 (baseline) without any significant adverse events or sustained hypoglycemic episodes.These physiological benefits were associated with a patient preference for insulin lispro 75/25.

OBJECTIVETo evaluate the feasibility of HLA haploidentical peripheral blood hematopoietic stem cell transplantation (PBSCT) for patients with β thalassemia major.

METHODSSixteen patients with β thalassemia major received HLA haploidentical PBSCT from parents. Two conditioning regimens were used. Regimen A was adopted before December 2007, which consisted of fludarabine (total 150 mg/m²), busulfex (total 520 mg/m²), cyclophosphamide (CTX, total 100 mg/kg), antithymocyte globulin (ATG, total 10 mg/kg) and total body irradiation of 3 Gy. Regimen B was adopted after December 2007, which consisted of fludarabine (total 240 mg/m²), busulfex (total 520 mg/m²), CTX (total 100 mg/kg), and ATG (total 10 mg/kg). Combination of cyclosporin (CsA), methotrexate (MTX) and mycophenolate mofetil (MMF) were used for prophylaxis of graft-versus-host disease (GVHD).

RESULTSOf 16 patients, 14 (87.5%) had sustained engraftment. The median days of neutrophil exceeding 0.5 × 10⁹/L and platelet exceeding 20 × 10⁹/L were 13 days (range 10 - 17 days) and 15 days (range 14 - 20 days) after PBSCT, respectively. Complete chimerism was achieved in all the 14 patients at one month after PBSCT. One patient lost his graft with autologous reconstitution 52 days after transplantation. Four patients had grade II-IV acute GVHD and one patient had chronic extensive GVHD. In the 49-month median follow-up duration, 13 of 16 patients were alive in disease-free situation.

CONCLUSIONHLA haploidentical PBSCT, which could provide stable and sustained engraftment for thalassemia major patients with no HLA identical donor, is a promising treatment strategy.

Child ; Child, Preschool ; Female ; HLA Antigens ; genetics ; Haploidy ; Humans ; Male ; Peripheral Blood Stem Cell Transplantation ; Tissue Donors ; beta-Thalassemia ; therapy

OBJECTIVETo analyze the factors affecting pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients.

METHODSA retrospective cohort study was carried out to analyze the clinical data of 141 breast cancer patients treated with neoadjuvant chemotherapy. The factors affecting pCR and the changes of tumor receptor status before and after treatment were analyzed.

RESULTSAmong all the 141 patients, 21 patients (14.9%) achieved pCR. The rate of pCR achieved by regimens of anthracycline combined with taxane was higher (16.8%, 19/113) than that by anthracycline-containing regimens (7.1%, 1/14). The dose intensity of anthracycline had a significant correlation with pCR rate (P < 0.05). The pCR rate in the relative dose intensity of taxane ≥ 0.85 arm was higher than that of < 0.85 arm (P = 0.02). Eighty patients (56.7%) had completed more than 4 cycles of chemotherapy and the median time to achieve pCR was 6 (3 to 10) cycles. The pCR rate had a significant difference between patients < 6 and ≥ 6 cycles (7.1% vs. 22.5%,P = 0.01). Multivariate analysis showed that tumor size measured by palpation ≤ 5 cm and ≥ 6 chemotherapy cycles were significantly related with pCR rate (P < 0.05). In all the 21 pCR patients, the pre-treatment ER(-), PR(-), HER-2(-) statuses were in 14, 14 and 17 patients, respectively. The status of ER, PR, HER-2 of most patients (74.2%, 69.7% and 87.7%, respectively) was not changed after treatment. Among the patients with changes in receptor status, ER changed from negative to positive was in the majority (37.1%, 13/35 vs. 12.9%, 4/31, P < 0.05), and the percentage of changes in PR and HER-2 status had no significant differences.

CONCLUSIONSThe regimens of anthracycline combined with taxane can achieve a higher pCR rate. The lymph node and receptor status before therapy have no significant correlation with pCR. Patients who have primary tumor size ≤ 5 cm, ≥ 6 chemotherapy cycles and enough dose intensity are easier to achieve pCR. The receptor status before and after therapy should be determined, and according to any positive results, physicians can chose HER-2 targeted therapy and/or endocrine therapy after surgery to benefit the patients.

Adult ; Aged ; Aged, 80 and over ; Anthracyclines ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Bridged-Ring Compounds ; administration & dosage ; Chemotherapy, Adjuvant ; Dose-Response Relationship, Drug ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoadjuvant Therapy ; methods ; Proportional Hazards Models ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Remission Induction ; Retrospective Studies ; Taxoids ; administration & dosage ; Tumor Burden

OBJECTIVETo evaluate the relation of dose intensity and efficacy, toxicity in advanced breast cancer treated with paclitaxel as a single agent.

METHODSSeventy-one patients with advanced breast cancer received paclitaxel as a single agent with different dose intensities. According to the phase I or phase II trial, the standard dose intensity of paclitaxel was defined as 58.3 mg.(m(2))(-1).week(-1). The dose of paclitaxel was 175 mg/m(2) given every three weeks, ranging 33.3 - 70.3 mg.(m(2))(-1).week(-1) [median delivered dose intensity 58.82 mg.(m(2))(-1).week(-1)]. Efficacy and toxicity was evaluated.

RESULTSThe overall response rate in this group of advanced breast cancer was 40.8%. Responses were seen in lungs, soft tissue, bone and liver, with the response rates of 52.0%, 38.0%, 12.5%, 7.7%, respectively. When the relative dose intensity (RDI) was > 1.0, 0.9 - 1.0, < 0.9, the response rates were 44.2%, 47.6%, 0, respectively. The difference between the group (RDI >/= 0.9% - 1.0%) in 7 patients and the group (RDI < 0.9) was significant (P < 0.05). Toxicity was well tolerated, with the efficacy decreased as soon as the RDI had been reduced without embarrassing the toxicity.

CONCLUSIONPaclitaxel as a single agent therapy with standard dose intensity is effective and well tolerated by patients with advanced breast cancer.

Adult ; Aged ; Antineoplastic Agents, Phytogenic ; administration & dosage ; adverse effects ; Bone Neoplasms ; drug therapy ; secondary ; Breast Neoplasms ; drug therapy ; pathology ; Dose-Response Relationship, Drug ; Female ; Humans ; Leukopenia ; chemically induced ; Liver Neoplasms ; drug therapy ; secondary ; Middle Aged ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; adverse effects ; Remission Induction

This study investigated the effect of advanced glycation end products (AGEs) on differentiation of naïve CD4(+) T cells and the role of the receptor of AGEs (RAGE) and peroxisome proliferator-activated receptors (PPARs) activity in the process in order to gain insight into the mechanism of immunological disorders in diabetes. AGEs were prepared by the reaction of bovine serum albumin (BSA) with glucose. Human naïve CD4(+) T cells, enriched from blood of healthy adult volunteers with negative selection assay, were cultured in vitro and treated with various agents including AGEs, BSA, high glucose, PGJ2 and PD68235 for indicated time. In short hairpin (sh) RNA knock-down experiment, naïve CD4(+) T cells were transduced with media containing shRNA-lentivirus generated from lentiviral packaging cell line, Lent-X(TM) 293 T cells. Surface and intracellular cytokine stainings were used for examination of CD4(+) T cell phenotypes, and real-time PCR and Western blotting for detection of transcription factor mRNA and protein expression, respectively. The suppressive function of regulatory T (Treg) cells was determined by a [(3)H]-thymidine incorporation assay. The results showed that AGEs induced higher pro-inflammatory Th1/Th17 cells differentiated from naïve CD4(+) T cells than the controls, whereas did not affect anti-inflammatory Treg cells. However, AGEs eliminated suppressive function of Treg cells. In addition, AGEs increased RAGE mRNA expression in naïve CD4(+) T cells, and RAGE knock-down by shRNA eliminated the effect of AGEs on the differentiation of CD4(+) T cells and the reduction of suppressive function of Treg cells. Furthermore, AGEs inhibited the mRNA expression of PPARγ, not PPARα PPARγ agonist, PGJ2, inhibited the effect of AGEs on naïve CD4(+) T cell differentiation and reversed the AGE-reduced suppressive function of Treg cells; on the other hand, PPARγ antagonist, PD68235, attenuated the blocking effect of RAGE shRNA on the role of AGEs. It was concluded that AGEs may promote CD4(+) T cells development toward pro-inflammatory state, which is associated with increased RAGE mRNA expression and reduced PPARγ activity.
Adult ; Animals ; Blotting, Western ; CD4-Positive T-Lymphocytes ; drug effects ; metabolism ; Cattle ; Cell Differentiation ; drug effects ; Cells, Cultured ; Glucose ; pharmacology ; Glycation End Products, Advanced ; pharmacology ; HEK293 Cells ; Humans ; Interferon-gamma ; metabolism ; Interleukin-17 ; metabolism ; PPAR gamma ; agonists ; genetics ; metabolism ; Prostaglandin D2 ; analogs & derivatives ; pharmacology ; RNA Interference ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Serum Albumin, Bovine ; pharmacology ; T-Lymphocytes, Regulatory ; drug effects ; metabolism ; Th1 Cells ; drug effects ; metabolism ; Th17 Cells ; drug effects ; metabolism