Progress and reflection on the therapeutic strategy of targeting the pancreatic cancer microenvironment / 中国肿瘤临床

Pancreatic cancer(PC)is a highly malignant disease.Significant fibrosis and tumor heterogeneity are important characteris-tics of PC that have been attributed to the poor chemotherapeutic response and poor prognosis of patients with PC.Therefore,it is im-perative to develop more effective treatment strategies to improve the survival rate of PC patients.In order to improve the response rates and accuracy of treatment for PC,domestic and foreign scholars have directed their efforts in elucidating the mechanisms of tu-mor microenvironment that mediate PC development to identify more effective treatment strategies targeting this microenvironment. This paper reviews the latest advances and therapeutic strategies for targeting the tumor microenvironment,under the concept of pre-cise treatment,and also provides a new idea for further improving the survival rates of patients with PC.

Mechanism of the synergistic analgesic effect between choline and acetaminophen / 药学学报

This study was designed to investigate the synergistic analgesic effect between choline (Cho) and acetaminophen (Ace). Mice were treated with 0.6% acetic acid solution by intraperitoneal injection to build acetate writhing model. The KM mice were randomly divided into four groups:control group (n=10), Cho group (n=50), Ace group (n=50), combination group (Cho+Ace group, n=40), then the writhing times were counted respectively. OriginPro8.5 was used to calculate ED 50. The isobolographic analysis was used to test the interaction of Cho and Ace. To explore the mechanism, forty KM mice were randomly divided into control group, Cho group, Ace group and Cho + Ace group. Blood was collected for detection of TNF-α, IL-6, PGE2 and NF-κB content using ELISA kits. The result ED 50 was calculated as followings. ED50 of Cho and Ace was 19.47 mg·kg-1 and 20.56 mg·kg-1. The concentrations were 2.94 mg·kg-1 for Cho and 3.15 mg·kg-1 for Ace in the combination test. The levels of TNF-α, IL-6, PGE2 and NF-κB in Cho group and Ace group were lower than those in the control group (Pα, IL-6, PGE2, NF-κB in Cho + Ace group were reduced further (P< 0.05). The results revealed that Cho and Ace have synergistic analgesic effects, which may associate with inhibition of the NF-κB signaling pathway.

Selection and therapeutic effect evaluation of chemotherapy regimens for pancreatic cancer / 临床肝胆病杂志

Pancreatic cancer is a highly malignant tumor and its treatment is still a challenge.Recent studies have shown that medication plays an important role in preoperative and postoperative adjuvant therapy for locally advanced pancreatic cancer and is also a major thera-peutic method for advanced pancreatic cancer.It can improve the survival time and quality of life in patients with pancreatic cancer.Tradi-tional chemotherapy regimens based on gemcitabine and fluorouracil have limited effects in the treatment of advanced pancreatic cancer,and studies on molecular targeted therapies have achieved some progress in recent years.With reference to related guidelines or consensus on the diagnosis and treatment of pancreatic cancer and important clinical trials of the treatment of pancreatic cancer,this article elaborates on the selection and therapeutic effect evaluation of chemotherapy regimens for pancreatic cancer.We believe that with the research and develop-ment of new drugs and the application of new techniques,the treatment of pancreatic cancer will achieve new breakthroughs in future.

The fusion protein of cytoplasmic transduction peptide (CTP)-HBcAg18-27-Tapasin enhances specific immune response to hepatitis B virus and inhibits viral replication in transgenic mice / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the effect of protein transduction domain-hepatitis B virus core antigen (CTP-HBcAg18-27)-Tapasin fusion protein-induced specific cytotoxic T lymphocyte (CTL) response on hepatitis B virus (HBV) replication in HBV transgenic mice.</p><p><b>METHODS</b>Twenty HBV-transgenic mice were randomly divided into two groups for a 3-week course of once weekly subcutaneous immunizations with either CTP-HBcAg18-27-Tapasin fusion protein or CTP-HBcAg18-27. Mice administered isotonic saline served as blank controls. Expressions of cytokines in splenocytes were analyzed by flow cytometry. Serum levels of hepatitis B surface antigen (HBsAg) and HBV DNA were determined by microparticle enzyme immunoassay and real-time fluorescent PCR assay, respectively. Expression of HBsAg in hepatic tissues was detected by immunohistochemistry.</p><p><b>RESULTS</b>Immunization with 100 mug of CTP-HBcAg18-27-Tapasin fusion protein led to a significant increase in proportions of CTLs in spleen (2.70%+/-0.20% vs. 50 mug of CTP-HBcAg18-27-Tapasin: 1.66%+/-0.53%, 50 mug of CTP-HBcAg18-27: 1.26%+/-0.56%, and blank controls: 0.75%+/-0.71%; F = 741.45, P = 0.000) and up-regulation of inflammatory cells in hepatic tissue. In addition, both immunizations of CTP-HBcAg18-27-Tapasin led to significant decreases in serum HBsAg and HBV DNA levels compared to those in the CTP-HBcAg18-27 group.</p><p><b>CONCLUSION</b>HBV-related modification of the expression of the molecular chaperone Tapasin may affect its interaction with intracellular antigen peptides, thereby leading to increases the number of specific CTLs in the spleen, decreases in serum HBsAg and HBV DNA levels, and down-regulation of HBsAg expression in hepatic tissue. These results obtained in HBV-transgenic mice suggest that the CTP-HBcAg18-27-Tapasin fusion protein has anti-HBV activity.</p>

Application of intraoperative magnetic resonance imaging and multimodal navigation in surgical resection of glioblastoma / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of intraoperative magnetic resonance imaging (iMRI) and multimodal navigation in surgical resection of glioblastoma.</p><p><b>METHODS</b>Between February 2009 and July 2010, 76 glioblastoma patients underwent surgical resection guided by iMRI and multimodal navigation. The cohort consisted of 43 male and 33 female patients, with a mean age of 49 years (range: 14-79 years). Rates of gross total resection (GTR) and extent of resection (EoR) were calculated at first and final iMRI scans.Pearson χ(2) test was used to compare the rates of GTR.</p><p><b>RESULTS</b>iMRI and multimodal navigation were successfully implemented in all cases. Rates of GTR were misestimated by neurosurgeons in 24 cases (31.6%), which were confirmed by first iMRI. Total tumor resection were achieved in 20 cases (26.3%) as a result of iMRI scan, increasing the rates of gross total resection from 52.6% to 78.9% (χ(2) = 11.692, P = 0.001). Extent of resection in 28 patients who underwent further tumor resection were increased from 81.5% to 98.1%, leading to the overall extent of resection improved from 92.3% to 98.4%. At 3-month follow-up, 3 cases (3.9%) developed permanent neurologic deficits. The mean clinical follow-up was 15.6 months (range 3.0-45.0 months). The 2-year overall survival rate was 19.7%. The median progression-free survival of gross total resection group was 12 months (95% CI: 10.1-13.9 months), compared with 9 months (95%CI: 7.9-10.1 months) of the subtotal resection group (χ(2) = 4.756, P = 0.029). The overall survival of gross total resection group was 16 months (95% CI: 13.7-18.3 months), compared with 12 months (95% CI: 9.7-14.3 months) of the subtotal resection group (χ(2) = 7.885, P = 0.005).</p><p><b>CONCLUSION</b>Combined with multimodal navigation, iMRI helps maximize surgical resection of glioblastoma, preserving neurological function while increasing progression-free survival and overall survival.</p>

Protective effects of estrogen on mitochondria in human umbilical vascular endothelial cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the protective effects of estrogen on the mitochondria in human umbilical vascular endothelial cells (HUVECs).</p><p><b>METHODS</b>HUVECs were exposed to H2O2 at 250 micromol/L for 4 h with or without pretreatment with 17-estradiol (E2) and ICI182780. Complex IV activity of the cells was measured with chromometry, and 2, 7-dichlorofluorescein diacetate (DCFH-DA) was used to determine intracellular reactive oxygen species (ROS). Intracellular adenosine triphosphate (ATP) level was quantified with a luciferin- and luciferase-based assay.</p><p><b>RESULTS</b>Compared to the blank control group, H2O2 caused a decrease in complex IV activity, intracellular ATP level, and the cell viability, but elevated intracellular ROS. E2 pretreatment of cells significantly attenuated these effects of H2O2 exposure. ICI182780 administered prior to E2 pretreatment antagonized the protective effects of E2 against H2O2 exposure.</p><p><b>CONCLUSION</b>E2 offers mitochondrial protective effects on HUVECs, which is mediated by the estrogen receptors.</p>

A new synthetic tripeptide inhibits L-arginine transport in macrophages / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of a new synthetic tripeptide [Arg(NO(3))- Lys(OCH(3))- Arg(NO(3))] on L-arginine/NO pathway in the macrophage cell strain RAW246.7.</p><p><b>METHODS</b>The cultured macrophages exposed to lipopolysaccharide (LPS, 1 microg/L) treatment were randomly divided into 3 groups (n=6) and treated with distilled water, 1x10(-4) mol/L tripeptide and 1x10(-4) mol/L L-arginine, NG-monomethyl-L-arginine (L-NMMA) for 24 h, respectively. The macrophages were incubated for 24 h with LPS (1 microg/L) and in the presence of different concentrations of L-arginine (0 to 2 mmol/L), or in normal culture medium (containing 0.5 mmol/L L-arginine) for 24 h with LPS (1 microg/L) and in the presence of tripeptide of 0 to 10x10(-4) mol/L. The changes of [(3)H]-L-arginine transport and NO production from the macrophages were measured.</p><p><b>RESULT</b>NO release from macrophages incubated in the LPS-containing culture medium was 50 folds, and [(3)H]-L-arginine uptake 2.7 folds that in cells in normal culture medium. Tripeptide (1x10(-4) mol/L) inhibited [(3)H]-L-arginine transport and NO production by 67% and 71% respectively. The effect of tripeptide was stronger than L-NMMA (P<0.05). Extracellular L-arginine caused a concentration-dependent increase in nitrite production, which reached the maximum at concentrations above 0.5 mmol/L Km for nitrite production of 0.162+/-0.015 mmol/L and Vmax of 91.2+/-2.3 micromol/(24h.10(6) cells). L-arginine transport and NO production were inhibited by tripeptide, but their dose-dependent pattern of changes was different with EC50 of 0.21x10(-4) mol/L and 1.27x10(-4) mol/L, respectively.</p><p><b>CONCLUSIONS</b>Activation of macrophages with LPS induces nitrite accumulation in the culture medium, which is dependent on the presence of extracellular L-arginine. The tripeptide induces dysfunction of L-arginine/NO pathway in macrophages, potently inhibits L-arginine transport and competitively combine the active sites of nitric oxide synthase.</p>