Zn2+-interference and H2S-mediated gas therapy based on ZnS-tannic acid nanoparticles synergistic enhancement of cell apoptosis for specific treatment of prostate cancer.

Zn2+ and H2S are essential to maintain normal prostate function, and sometimes can evolve into weapons to attack and destroy prostate cancer (PCa) cells. Nevertheless, how to achieve the targeted and effective release of Zn2+ and H2S, and reverse the concentration distribution within PCa tumor cells still highly challenging. Herein, combined with these pathological characteristics of prostate, we proposed a tumor microenvironment (TME) responsive Zn2+-interference and H2S-mediated gas synergistic therapy strategy based on a nanoplatform of tannic acid (TA) modified zinc sulfide nanoparticles (ZnS@TA) for the specific treatment of PCa. Once the constructed pH-responsive ZnS@TA internalized by cancer cells, it would instantaneously decomposed in acidic TME, and explosively release excess Zn2+ and H2S exceeding the cell self-regulation threshold. Meanwhile, the in situ produced Zn2+ and H2S synergistic enhancement of cell apoptosis, which is evidenced to increase levels of Bax and Bax/Bcl-2 ratio, release of Cytochrome c in cancer cells, contributing to inhibit the growth of tumor. Moreover, the TA in cooperation with Zn2+ specifically limits the migration and invasion of PCa cells. Both in vitro and in vivo results demonstrate that the Zn2+-interference in combination with H2S-mediated gas therapy achieves an excellent anti-tumor performance. Overall, this nanotheranostic synergistic therapy provides a promising direction for exploring new strategies for cancer treatment based on specific tumor pathological characteristics, and provides a new vision for promoting practical cancer therapy.

Curcumin Inhibits Proliferation of Renal Cell Carcinoma in vitro and in vivo by Regulating miR-148/ADAMTS18 through Suppressing Autophagy / 中国结合医学杂志

OBJECTIVE@#To explore the effect of curcumin on the proliferation of renal cell carcinoma and analyze its regulation mechanism.@*METHODS@#In RCC cell lines of A498 and 786-O, the effects of curcumin (2.5, 5, 10 µ mo/L) on the proliferation were analyzed by Annexin V+PI staining. Besides, A498 was inoculated into nude mice to establish tumorigenic models, and the model mice were treated with different concentrations of curcumin (100, 200, and 400 mg/kg), once daily for 30 days. Then the tumor diameter was measured, the tumor cells were observed by hematoxylin-eosin staining, and the protein expressions of miR-148 and ADAMTS18 were detected by immunohistochemistry. In vitro, after transfection of miR-148 mimics, miR-148 inhibitor or si-ADAMTS18 in cell lines, the expression of ADAMTS18 was examined by Western blotting and the cell survival rate was analyzed using MTT. Subsequently, Western blot analysis was again used to examine the autophagy phenomenon by measuring the relative expression level of LC3-II/LC3-I; autophagy-associated genes, including those of Beclin-1 and ATG5, were also examined when miR-148 was silenced in both cell lines with curcumin treatment.@*RESULTS@#Curcumin could inhibit the proliferation of RCC in cell lines and nude mice. The expression of miR-148 and ADAMTS18 was upregulated after curcumin treatment both in vitro and in vivo (P<0.05). The cell survival rate was dramatically declined upon miR-148 or ADAMTS18 upregulated. However, si-ADAMTS18 treatment or miR-148 inhibitor reversed these results, that is, both of them promoted the cell survival rate.@*CONCLUSION@#Curcumin can inhibit the proliferation of renal cell carcinoma by regulating the miR-148/ ADAMTS18 axis through the suppression of autophagy in vitro and in vivo. There may exist a positive feedback loop between miR-148 and ADAMTS18 gene in RCC.

Curcumin Inhibits Viability of Clear Cell Renal Cell Carcinoma by Down-Regulating ADAMTS18 Gene Methylation though NF-κ B and AKT Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of curcumin on viability of clear cell renal cell carcinoma (ccRCC) and analyze its possible mechanism.@*METHODS@#In cell lines of A498 and 786-O, the effects of curcumin (1.25, 2.5, 5 and 10 μ mol/L) on the viability of ccRCC were analyzed at 24, 48 and 72 h by MTT assay. The protein expression levels of ADAMTS18 gene, p65, phosphorylation p65 (pp65), AKT, phosphorylation AKT (pAKT) and matrix metallopeptidase 2 (MMP-2) before and after curcumin (10 μ mol/L) treatment were examined by Western blotting. Real-time PCR and methylation specific PCR (MSP) were applied to analyze the expression and methylation level of ADAMTS18 gene before and after curcumin treatment (10 μ mol/L).@*RESULTS@#Curcumin significantly inhibited the viability of A498 and 786-O cell lines in a dose- and time-dependent manner (P<0.01). Up-regulation of ADAMTS18 gene expression with down-regulation of ADAMTS18 gene methylation was reflected after curcumin treatment, accompanied by down-regulation of nuclear factor κ B (NF-κ kB) related protein (p65 and pp65), AKT related protein (AKT and pAKT), and NF-κ B/AKT common related protein MMP-2. With ADAMTS18 gene overexpressed, the expression levels of p65, AKT and MMP2 were downregulated, of which were conversely up-regulated in silenced ADAMTS18 (sh-ADAMTS18). The expression of pp65, pAKT and MMP2 in sh-ADAMTS18 was down-regulated after being treated with PDTC (NF-κ B inhibitor) and LY294002 (AKT inhibitor).@*CONCLUSIONS@#Curcumin could inhibit the viability of ccRCC by down-regulating ADAMTS18 gene methylation though NF-κ B and AKT signaling pathway.

Suprapubic cystostomy versus nonsuprapubic cystostomy during monopolar transurethral resection of prostate: a propensity score-matched analysis / 亚洲男科学杂志(英文版)

We aim to reassess the safety of the monopolar transurethral resection of the prostate (M-TURP) without suprapubic cystostomy at our institution over the past decade. This retrospective study was conducted in patients who underwent M-TURP at Peking University First Hospital between 2003 and 2013. A total of 1680 patients who had undergone M-TURP were identified, including 539 patients in the noncystostomy group and 1141 patients in the cystostomy group. After propensity score matching, the number of patients in each group was 456. Smaller reductions in hemoglobin and hematocrit (10.9 g vs 17.6 g and 3.6% vs 4.7%, respectively) were found in the noncystostomy group. In addition, patients undergoing surgery without cystostomy had their catheters removed earlier (4.6 days vs 5.2 days), required shorter postoperative stays in the hospital (5.1 days vs 6.0 days), and were at lower risk of operative complications (5.7% vs 9.2%), especially bleeding requiring blood transfusion (2.9% vs 6.1%). Similar findings were observed in cohorts of prostates of 30-80 ml and prostates >80 ml. Furthermore, among patients with a resection weight >42.5 g or surgical time >90 min, or even propensity-matched patients based on surgical time, those with cystostomy seemed to be at a higher risk of operative complications. These results suggest that M-TURP without suprapubic cystostomy is a safe and effective method, even among patients with larger prostates, heavier estimated resection weights, and longer surgical times.

Comparison of safety and effectiveness between retroperitoneal laparoscopic tumor aspiration and laparoscopic partial nephrectomy in the treatment of renal angiomyolipoma / 北京大学学报(医学版)

OBJECTIVE@#To compare the safety and treatment effectiveness of retroperitoneal laparoscopic tumor aspiration and laparoscopic partial nephrectomy (LPN) in the treatment of renal angiomyolipoma (RAML).@*METHODS@#We retrospectively reviewed the clinical data of patients with pathologically confirmed RAML who received operation between August 2010 and August 2016 in the Department of Urology, Peking University First Hospital. Among them, a series of 121 patients were included in this trial according to the inclusion criteria, of which 74 cases could be collected and followed-up effectively. Based on the detailed surgical route, the 74 patients were divided into groups A and B: group A, which underwent retroperitoneal laparoscopic tumor aspiration, included 43 cases; group B, which received retroperitoneal LPN, included 31 cases. Patient demographics, intraoperative variables and postoperative outcomes were reported and compared between the groups.@*RESULTS@#No statistical difference was detected in both groups before the treatment. Intraoperatively, the mean estimated blood loss was 48.7 mL in group A and 102.9 mL in group B, and the mean operative time was 70.1 min (21.2 min of warm ischemia time included) in group A and 103.6 min (28.5 min of warm ischemia time included) in group B, which were both statistically different. In group A, no complications occurred and yet 2 complications of transfusion and 1 complication of urine leakage were discovered in group B, although all finally recovered only with conservative treatment. A statistical difference was observed in the complication rates. Post-operatively, the mean serum creatinine level was 1.13 mg/dL in group A, and the level was 1.08 mg/dL in group B, in which no evident difference was detected. In a mean 52.6-months' follow-up, a recurrence of 3 cases in group A (7.0%) and a recurrence of 2 cases in group B (6.5%) were reported. No evident difference was also detected between the groups in the tumor recurrence rates.@*CONCLUSION@#Due to the improvements in the intraoperative blood loss and operative time, retroperitoneal laparoscopic tumor aspiration may be provided with more potential advantages in the safety, also with equal efficacy of lower tumor recurrence rates when compared with the traditional retroperitoneal LPN in the treatment of RAML.

[Effect of Valerian Ligusticum Pill on angiogenesis after injury of cerebral ischemia reperfusion in rats].

This study was designed to detect the impact of Valerian Ligusticum Pill（VLP） on cerebral ischemia reperfusion injury in rats, and explore the mechanism of angiogenesis. Sixty SD male rats were randomly divided into five groups, including sham operation group, model group, VLP-low（30 mg·kg-1） group, VLP-high(50 mg·kg-1) group and nimodipine (10 mg·kg-1) group. The ischemia reperfusion injury model was induced by occlusion of middle cerebral artery with suture embolus, reperfusion after 30 minutes' ischemia. When the rats were awake, the first neurological function scores was determined with modified neurological severity score（m NSS）. The rats were given VLP(30 mg·kg-1, 50 mg·kg-1) and nimodipine（10 mg·kg-1） through intragastric administration at 2 m L, once a day for a total of 7 days, while an equal amount of distilled water was used in the sham operation group and model control group. After 7 days, the rats were given second neurological function scores, and improvement of neurological function = [the first score] - [the second score]. The rats were sacrificed to investigate the infarction volume percentage with 2,3,5-triphenyl tetrazolium chloride method; do the qualitative and half quantitative analyses for protein vascular endothelial growth factor receptor 2（VEGFR2） in the tissue of cortex infarction around by Western blot; detect the new blood vessels of cortex infarction around by ki67/lectin immunofluorescence double staining method. Results suggest that VLP could significantly improve the neurological function, reduce the percentage of infarct volume, increase the expression of VEGFR2 and number of new blood vessels in the cortex infarction around compared with model group. In conclusion, VLP may relive the acute cerebral ischemia reperfusion injury in rats by inducing angiogenesis.

Performance verification and field applicability evaluation of biochemical modules in field POCT system(type A) / 军事医学

Objective To evaluate the performance of emergency test and the applicability under complex field conditions of biochemical modules of field point-of-care test ( POCT ) system ( type A ) .Methods The precision and anti-interference ability of albumin ( ALB ) , total bilirubin ( TBIL ) , alanine transaminase ( ALT ) , aspartate transaminase (AST),blood area nitrogen(BUN),creatinine(CREA),uric acid(UA),lactate dohydrogenase(LDH),creatine kinase ( CK) ,and glucose( GLU) detected by field POCT system( A) were analyzed according to standards formulated by National Committee for Clinical Laboratory Standards(NCCLS).Field POCT system(A) and Coulter Beckman AU2700 automatic biochemical analyzer were used to detect the serum of 22 clinical cases respectively.After simulating the field environment by adjusting the temperature and humidity, we compared the results of mixed serum under different environment conditions. Results The coefficients of variation in total precision of ALB,TBIL,ALT,AST,BUN,CREA,UA,LDH,CK,and GLU detected by field POCT system(A) were 3.34%,6.54%,6.01%,4.80%,3.95%,5.59%,3.33%,6.19%,7.40%,and 4.56%(LevelⅠ);and 3.08%,4.47%,4.02%,4.31%,3.76%,4.22%,2.93%,5.25%,6.39%,and 4.35%(LevelⅡ) respectively.When triglycerides( TG) level was at 21 mmol/L, the interference rate was below 10%.When bilirubin level was at 120 μmol/L, the interference rate of ALT,AST and CREA was -33.33%,-22.99%,20.00%(LevelⅠ), and -22.13%,-14.55%,and 8.70%(LevelⅡ),respectively.When its level was at 240 μmol/L, the interference rate of UA was -16.67%and -24.69%, respectively at two levels;if hemoglobin( Hb) was at 170 mg/dl, the interference rate of TBIL and LDH was 20.00%,and 99.26%(LevelⅠ),and 15.38%,and 40.79%(LevelⅡ),respectively;if it was at 340 mg/dl, the interference rate of ALT and AST was 9.84% and 13.79%(LevelⅠ), and 12.30%,and 12.27%(LevelⅡ),respectively;if it was at 510 mg/dl, the interference rate of CREA,UA and Ck in LevelⅠwas 26.67%, 16.67%,and 11.74%.The R2 of linear regression between field POCT system( A) and AU2700 automatic biochemical analyzer were 0.961,0.995,0.989,0.995,0.990,0.989,0.989,0.963,0.978,and 0.993, respectively.The POCT system could not work at 35℃ or higher temperature, and there was no difference in the results of detection between temperatures of 10-30℃or RH of 70%-90% and normal temperature and humidity(20℃,RH 50%) (P>0.05). However, the result of ALT and CK at high temperature and humidity was significantly higher than at normal temperature and humidity(P<0.001,and P=0.011, respectively).Conclusion The biochemical module of field POCT system(A) has a good correlation with the common large biochemical analyzer, and its precision meets the requirement of laboratory detection, but jaundice and hemolytsis can interfere in several tests to varying degrees.The POCT system can basically ensure accurate detection under field conditions of temperature and humidity, but should not work under extreme environments.

Effect of Valerian Ligusticum Pill on angiogenesis after injury of cerebral ischemia reperfusion in rats / 药学学报

This study was designed to detect the impact of Valerian Ligusticum Pill (VLP) on cerebral ischemia reperfusion injury in rats, and explore the mechanism of angiogenesis. Sixty SD male rats were randomly divided into five groups, including sham operation group, model group, VLP-low (30mg·kg-1) group, VLP-high (50mg·kg-1) group and nimodipine (10mg·kg-1) group. The ischemia reperfusion injury model was induced by occlusion of middle cerebral artery with suture embolus, reperfusion after 30 minutes' ischemia. When the rats were awake, the first neurological function scores was determined with modified neurological severity score (mNSS). The rats were given VLP (30mg·kg-1, 50mg·kg-1) and nimodipine (10mg·kg-1) through intragastric administration at 2 mL, once a day for a total of 7 days, while an equal amount of distilled water was used in the sham operation group and model control group. After 7 days, the rats were given second neurological function scores, and improvement of neurological function=[the first score]-[the second score]. The rats were sacrificed to investigate the infarction volume percentage with 2,3,5-triphenyl tetrazolium chloride method; do the qualitative and half quantitative analyses for protein vascular endothelial growth factor receptor 2 (VEGFR2) in the tissue of cortex infarction around by Western blot; detect the new blood vessels of cortex infarction around by ki67/lectin immunofluorescence double staining method. Results suggest that VLP could significantly improve the neurological function, reduce the percentage of infarct volume, increase the expression of VEGFR2 and number of new blood vessels in the cortex infarction around compared with model group. In conclusion, VLP may relive the acute cerebral ischemia reperfusion injury in rats by inducing angiogenesis.

Meta-Analysis of Circulating Endothelial Cells and Circulating Endothelial Progenitor Cells as Prognostic Factors in Lung Cancer.

BACKGROUND: The aim of this study was to analyze the prognostic implications of pretreatment circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CEPCs) for the survival of patients with lung cancer. MATERIALS AND METHODS: Relevant literature was identified using Medline and EMBASE. Patient clinical characteristics, overall survival (OS) and progression-free survival (PFS) together with CEC and CEPC positive rates before treatment were extracted. STATA 12.0 was used for our analysis and assessment of publication bias. RESULTS: A total of 13 articles (8 for CEC and 5 for CEPC, n=595 and n=244) were pooled for the global meta-analysis. The odds ratio (OR) for OS predicted by pretreatment CECs was 1.641 [0.967, 2.786], while the OR for PFS was 1.168 [0.649, 2.100]. The OR for OS predicted by pretreatment CEPCs was 12.673 [5.274, 30.450], while the OR for PFS was 4.930 [0.931, 26.096]. Subgroup analyses were conducted according to clinical staging. Odds ratio (OR) showed the high level of pretreatment CECs only correlated with the OS of patients with advanced lung cancer (stage III-IV). CONCLUSIONS: High counts of CECs seem to be associated only with worse 1-year OS in patients with lung cancer, while high level of pretreatment CEPCs correlate with both worse PFS and OS.

Investigation of vital signs on admission time and traumatic classification of the inpatients injured in Lushan earthquake / 重庆医学

Objective To understand the vital signs on admission time and traumatic classification of the inpatients injured in Lushan Earthquake ,and provide a basis evidence for handling major disasters and treating masses of injured patients .Methods The information of patients injured in Lushan Earthquake who were admitted in Chengdu Military General Hospital was collected by“No .1 Military Medical Project” hospital information system and self-edited “Questionnaire for Hospitalized Patients Injured in 4 .20 Lushan Earthquake” .The data of the vital signs on admission time and traumatic classification of these patients were analyzed by SPSS 16 .0 .Results A total of 65 civilian patients were admitted in this hospital .Among these patients ,there were 30 men (46 .15% )and 35 women(53 .85% );with mean age of(45 .74 ± 20 .96)years old .On admission time ,the abnormal rates of tempera-ture ,pulse ,respiratory rate ,systolic pressure ,diastolic pressure of these patients were 18 .46% ,6 .15% ,21 .54% ,12 .31% and 23 .08% ,respectively .48(73 .85% )patients had closed injury .Traumatic condition:8(12 .31% )patients in mild degree ,17(26 .15% ) patients in moderate degree ,32 patients(49 .23% )patients in severe degree and 8(12 .31% )patients in critical degree .The top 4 traumatic parts were as follows :33(50 .77% )patients got waist(abdomen)division and pelvis(perineum);31(47 .69% )patients got lower limb injuries;18(27 .69% )patients got chest and back injuries and 10(15 .38% )patients got facial injuries .There were 39 skin and soft tissue injuries ,counting for 60 .00% ,and 38 fractures ,counting for 58 .46% .Conclusion The epidemiological characteris-tics of earthquake injuries are founded by analyzing the vital signs on admission time and traumatic classification of the inpatients in-jured in Lushan earthquake ,which suggests attention of the relevant scholars and departments .

The upregulation of dihydropyrimidine dehydrogenase in liver is involved in acquired resistance to 5-fluorouracil.

BACKGROUND: Acquired resistance to 5-fluorouracil (5-FU) is one of the important reasons for failure in 5-FU-based chemotherapy. The upregulation of dihydropyrimidine dehydrogenase (DPD) in tumours was reported as an important factor for acquired 5-FU resistance. The aim of this study is to examine whether intra-hepatic DPD was involved in acquired 5-FU resistance. METHODS: HT-29 human colorectal xenograft tumours were established in nude mice. After long-term exposure to 5-FU, some of the tumour became "resistant" and the others remained "sensitive" to 5-FU. DPD expression levels in the livers and tumours of "resistant", "sensitive" or untreated mice were examined, and pharmacokinetics of 5-FU in rats' plasma were investigated. Gimeracil, a DPD inhibitor, was checked whether it could reverse the reduced bioavailability of 5-FU. RESULTS: DPD expression was upregulated obviously in tumours of "resistant" mice as reported previously. Importantly, DPD expression was also upregulated significantly in livers of "resistant" mice, compared with those of "sensitive" or untreated mice. Furthermore, the upregulation of DPD expression in livers led to accelerated metabolism of 5-FU. Gimeracil was found to reverse the reduced serum 5-FU concentration. The cultured tumour cells from 5-FU treated mice showed relative sensitivity to higher concentration of 5-FU, even the "resistant" tumour cells. CONCLUSION: Our study suggested that the upregulation of DPD in liver may be involved in acquired resistance to 5-FU, and DPD inhibitors or increasing 5-FU dosage may have potential application in overcoming 5-FU acquired resistance.

Some experience of field medical station equipment and materials management / 中国医疗器械杂志

The field medical station in military hospital plays an important role in the military logistic system. To better accomplish the duty of medical support mission, the problems of medical equipment and material store house management in the field medical station are discussed. Some targeted suggestions are introduced from daily management and the use of equipment respectively. It can be used as reference for other military hospitals to accomplish different medical support tasks.

Contra-lateral needling in the treatment of hemiplegia due to acute ischemic stroke.

Contra-lateral Needling, a traditional acupuncture technique, means contra-lateral acupuncture by inserting needles into acupoints on the relative healthy side of the body opposite to the injured side to treat diseases such as apoplexy with high efficacy. However, there are not many well-designed and controlled clinical evidences found in the literature. Therefore the present study was designed to assess its therapeutic responses in the treatment of hemiplegia due to acute ischemic stroke. A clinical study was conducted with randomly selected 106 patients who have acute ischemic stroke confirmed by MRI. The subjects were assigned into 3 groups: 45 in the contra-lateral needling group received acupuncture on the unaffected limbs; 45 in the conventional acupuncture group received acupuncture on the hemiplegic limbs; and 16 in the non-acupuncture group received the similar medical and nursing care as subjects in other two groups but no acupuncture treatment. Acupuncture was given daily for 45 minutes for 30 days. The clinical therapeutic responses rate, Neurological Deficits Score (NDS), Modified Barthel Index (MBI) and Fugl-Meger Assertion (FMA) were used to evaluate the effectiveness of 30 days treatment. The therapeutic response rate of the contra-lateral needling group was 46.67%, while 31.11% in the conventional acupuncture group, and 18.75% in the non-acupuncture group. The NDS of Contra-lateral needling group decreased more significantly than that of the conventional acupuncture group (p < 0.01). The study also found that the MBI and FMA of Contra-lateral needling group increased more significantly than those of the conventional acupuncture group (p < 0.01, respectively). Contra-lateral needling might be more effective than the conventional acupuncture in the treatment of hemiplegia due to acute ischemic stroke in terms of increasing the recovery of neurological functions, promoting ADL (activities for daily living) rehabilitation and the limbs motor function.

Different combination schedules of gemcitabine with endostar affect antitumor efficacy.

PURPOSE: Antiangiogenic drugs inhibit tumor growth by decreasing blood supply and causing transient "normalization" of the tumor vasculature, thereby improving the delivery of systemic chemotherapy. A higher dose of antiangiogenic drugs may lead to a more marked decrease in intratumoral blood flow but may concomitantly cause a decrease in delivery of chemotherapeutic agents. The purpose of this study was to define an optimal schedule for the combination of gemcitabine with a recombinant endostatin, endostar. METHODS: We evaluated the antitumor effects with different schedules of gemcitabine combined with or without endostar. The changes of vascular endothelial growth factor (VEGF) levels in tumor extracts and sera after gemcitabine treatment were examined. Endostar was also assessed for its abilities to inhibit the increase in VEGF levels. Apoptotic cells and microvessel density within tumor tissue were also examined. RESULTS: Endostar administered simultaneously with or following gemcitabine improved the inhibition of tumor growth, compared with gemcitabine alone. VEGF levels decreased immediately after gemcitabine treatment, but increased in the following several days. Endostar administered simultaneously with or following gemcitabine could inhibit the increase in VEGF levels, thereby cause a decreased vessel density and an increased apoptosis in tumor tissue. CONCLUSIONS: Our finding suggested that endostar given simultaneously with or following gemcitabine might be optimal to enhance the antitumor effect.

Comparative proteomic analysis of irinotecan-sensitive colorectal carcinoma cell line and its chemoresistant counterpart.

In this study, we used two-dimensional gel electrophoresis and MALDI-Q-TOF-MS/MS analysis to examine the global protein expression of a pair of colorectal carcinoma cell lines, SW620 and irinotecan-resistant SW620. Of the 30 spots identified as differentially expressed proteins (±over twofold, P<0.05) between the two cell lines, 26 spots (corresponding to 26 unique proteins) were positively identified by MALDI-Q-TOF-MS/MS analysis. These proteins could be grouped into main classes including metabolism (15.38%), cell SSproliferation/differentiation (11.53%), molecular chaperone (11.53%), mRNA splicing (11.53%), and so on. The proteins, which might be involved in the development of tumor drug resistance, such as α-enolase, cofilin, and thioredoxin-dependent peroxide 1, have been validated by western blot analysis and have been discussed. The proteins identified in this study may be useful in showing the mechanisms underlying irinotecan resistance.

Prognostic influence of metformin as first-line chemotherapy for advanced nonsmall cell lung cancer in patients with type 2 diabetes.

BACKGROUND: It has been reported that antidiabetic drugs affect the risk of cancer and the prognosis of patients with diabetes, but few studies have demonstrated the influence of different antidiabetic agents on outcomes after anticancer therapy among patients with cancer. The objective of this study was to evaluate the influence of the antidiabetic drugs metformin and insulin on the prognosis of patients with advanced nonsmall cell lung cancer (NSCLC) plus type 2 diabetes who received first-line chemotherapy. METHODS: Data on patients with NSCLC who had diabetes from 5 hospitals in China during January 2004 to March 2009 were reviewed retrospectively. Ninety-nine patients were included in the final analysis. The influence of metformin and insulin on chemotherapy response rates and survival in these patients was evaluated. RESULTS: Chemotherapy with metformin (Group A) produced superior results compared with insulin (Group B) and compared with drugs other than metformin and insulin (Group C) in terms of both progression-free survival (PFS) (8.4 months vs 4.7 months vs 6.4 months, respectively; P = .002) and overall survival (OS) (20.0 months vs 13.1 months vs 13.0 months, respectively; P = .007). Although no significant differences in the response rate (RR) were observed between these 3 groups, when groups B and C (ie, the nonmetformin group) were combined, there was a tendency for better disease control in Group A than that in nonmetformin group. No significant difference in survival was observed between chemotherapy with insulin (Group B) versus other drugs (Group C). CONCLUSIONS: The current data suggested that metformin may improve chemotherapy outcomes and survival for patients who have NSCLC with diabetes.

Interleukin-15 enhances T-cell responses by stimulation with dendritic cells.

INTRODUCTION: Cytokines play important roles in regulating immune responses. Interleukin-2 (IL-2) has usually been used as an adjuvant to enhance antitumour immune responses. However, its crucial role in activation-induced cell death, inhibition of homeostatic proliferation of CD8+ memory T cells and its notable biological side effects impair its prospect of application. IL-15 has several similar functions to IL-2 and shows potential advantages over IL-2, and is being investigated to enhance antitumour dendritic cell (DC) vaccine strategies in our ongoing studies. OBJECTIVE: In this preliminary study, we evaluated the ability of IL-15, compared with IL-2, to act as an adjuvant to enhance T-cell responses activated by DCs in vitro. MATERIALS AND METHODS: Bone marrow-derived DCs (BMDCs) were pulsed with tumour antigens and used to stimulate lymphocyte responses in the presence of IL-15 or IL-2. The activated T lymphocytes were examined by flow cytometric analysis, and interferon-γ (IFN-γ) enzyme-linked immunospot and cytotoxicity assays. RESULTS: IL-15 was observed to activate lymphocytes with comparable phenotype characteristics of activated/memory CD8+ lymphocytes, compared with IL-2. Both in primary and secondary stimulation with DCs, when using IL-15 as an adjuvant, activated lymphocytes showed higher proportions of IFN-γ-secreting subsets. In secondary stimulation with BMDCs in the presence of IL-15, the activated lymphocytes showed a stronger cytotoxicity to antigen-specific tumour target cells. CONCLUSIONS: Our study suggested that IL-15 might be a prospective adjuvant for a DC vaccine strategy against cancers. The further observation that IL-15 acts as an adjuvant for an antitumour DC vaccine strategy is worth investigating.

Interaction of green tea polyphenol epigallocatechin-3-gallate with sunitinib: potential risk of diminished sunitinib bioavailability.

Sunitinib, a novel oral multi-targeted tyrosine kinase inhibitor for patients with metastatic renal cell carcinoma (mRCC) and advanced gastrointestinal stromal tumor, has a good prospect for clinical application and is being investigated for the potential therapy of other tumors. We observed the phenomenon that drinking tea interfered with symptom control in an mRCC patient treated with sunitinib and speculated that green tea or its components might interact with sunitinib. This study was performed to investigate whether epigallocatechin-3-gallate (EGCG), the major constituent of green tea, interacted with sunitinib. The interaction between EGCG and sunitinib was examined in vitro and in vivo. (1)H nuclear magnetic resonance ((1)H-NMR) spectroscopy and mass spectrometry (MS) were used to analyze the interaction between these two molecules and whether a new compound was formed. Solutions of sunitinib and EGCG were intragastrically administered to rats to investigate whether the plasma concentrations of sunitinib were affected by EGCG. In this study, we noticed that a precipitate was formed when the solutions of sunitinib and EGCG were mixed under both neutral and acidic conditions. (1)H-NMR spectra indicated an interaction between EGCG and sunitinib, but no new compound was observed by MS. Sticky semisolid contents were found in the stomachs of sunitinib and EGCG co-administrated mice. The AUC(0-∞) and C (max) of plasma sunitinib were markedly reduced by co-administration of EGCG to rats. Our study firstly showed that EGCG interacted with sunitinib and reduced the bioavailability of sunitinib. This finding has significant practical implications for tea-drinking habit during sunitinib administration.

A Decomposition Principle for Complexity Reduction of Artificial Neural Networks.

A decomposition principle is developed for systematic determination of the dimensionality and the connections of Hopfield-type associative memory networks. Given a set of high dimensional prototype vectors of given memory objects, we develop decomposition algorithms to extract a set of lower dimensional key features of the pattern vectors. Every key feature can be used to build an associative memory with the lowest complexity, and more than one key feature can be simultaneously used to build networks with higher recognition accuracy. In the latter case, we further propose a "decomposed neural network" based on a new encoding scheme to reduce the network complexity. In contrast to the original Hopfield network, the decomposed networks not only increase the network's storage capacity, but also reduce the network's connection complexity from quadratic to linear growth with the network dimension. Both theoretical analysis and simulation results demonstrate that the proposed principle is powerful. Copyright 1996 Elsevier Science Ltd

Purification of recombinant human IE—2 by McAb affinity chromatography / 中国免疫学杂志

For purifying recombinant human IL—2 (rhIL—2),the columns of immunoabsorptionwere prepared with 4 anti—IL—2 McAb (9B12,9F5,9B2 and 8H7) purified by caprylic acid.Although 4 McAbs differ as regards their antigen—antibody binding characteristics,all they canserve as effective immnoabsorbents,provided optimum condition was adopted.The recoveryrate of 9B12,9F5,8H7 and 9B2 columns were 49.2%,37.5%,31.5% and 18.8% respec-tively.The purity of rhIL—2 obtained was more than 95% and biological activity remainedhigher.