Efficient and selective removal of Pb(Ⅱ) from landfill leachate using L-serine-modified polyethylene/polypropylene nonwoven fabric synthesized via radiation grafting technique

In this study,to efficiently remove Pb(Ⅱ) from aqueous environments,a novel L-serine-modified polyethylene/polypropylene nonwoven fabric sorbent(NWF-serine)was fabricated through the radiation grafting of glycidyl methacrylate and subsequent L-serine modification.The effect of the absorbed dose was investigated in the range of 5–50 kGy.NWF-serine was characterized by Fourier transform infrared spectroscopy,thermogravimetric analysis,and scanning electron microscopy.Batch adsorption tests were conducted to investigate the influences of pH,adsorption time,temperature,initial concentration,and sorbent dosage on the Pb(Ⅱ) adsorption performance of NWF-serine.The results indicated that Pb(Ⅱ) adsorption onto NWF-serine was an endothermic process,following the pseudo-second-order kinetic model and Langmuir isotherm model.The saturated adsorption capacity was 198.1 mg/g.NWF-serine exhibited Pb(Ⅱ) removal rates of 99.8% for aqueous solutions with initial concentrations of 100 mg/L and 82.1% for landfill leachate containing competitive metal ions such as Cd,Cu,Ni,Mn,and Zn.Furthermore,NWF-serine maintained 86% of its Pb(Ⅱ) uptake after five use cycles.The coordination of the carboxyl and amino groups with Pb(Ⅱ) was confirmed using X-ray photoelectron spectroscopy and extended X-ray absorption fine structure analysis.

Systemic immune-inflammation index for predicting prognosis of colorectal cancer

AIM To investigate the clinical significance of preoperative systemic immune-inflammation index(SII) in patients with colorectal cancer(CRC). METHODS A retrospective analysis of 1383 cases with CRC was performed following radical surgery. SII was calculated with the formula SII =(P × N)/L, where P, N, and L refer to peripheral platelet, neutrophil, and lymphocyte counts, respectively. The clinicopathological features and follow-up data were evaluated to compare SII with other systemic inflammation-based prognostic indices such as the neutrophil-lymphocyte ratio(NLR) and platelet-lymphocyte ratio(PLR) in patients with CRC.RESULTS The optimal cut-off point for SII was defined as 340. The overall survival(OS) and disease-free survival(DFS) were better in patients with low NLR, PLR, and SII(P < 0.05). The SII was an independent predictor of OS and DFS in multivariate analysis. The area under the receiver-operating characteristics(ROC) curve for SII(0.707) was larger than those for NLR(0.602) and PLR(0.566). In contrast to NLR and PLR, SII could effectively discriminate between the TNM subgroups. CONCLUSION SII is a more powerful tool for predicting survival outcome in patients with CRC. It might assist the identification of high-risk patients among patients with the same TNM stage.

Lymph node micrometastasis and its correlation with MMP-2 expression in gastric carcinoma

AIM： To examine matrix metalloproteinase-2 （MMP-2） expression in gastric cancer tissues and to evaluate its relationship with lymph node micrometastasis. MATERIALS： The authors studied 850 lymph nodes resected from 30 patients with gastric carcinoma who underwent gastrectomy with lymphadenetomy using reverse transcription polymerase chain reaction （RT-PCR） assay in addition to H-E staining. MMP-2 expression of the tumor tissues was detected by immunohistochemical technique （EliVision^TM plus）. RESULTS： MMP-2 expression was positive in 21 （70%） cases and negative in g （30%） cases. No significant correlations were found between MMP-2 expression and other variables such as age, gender, tumor location, tumor diameter, Lauren classification and lymphatic invasion. In contrast, MMP-2 expression correlated significantly with depth of tumor infiltration （P = 0.022）, lymph node metastasis （P = 0.030） and tumor differentiation （P = 0.043）. Lymph node micrometastases were detected in 77 （12.5%） lymph nodes of 14 （46.7%） gastric carcinoma patients. MMP-2 expression was positive in 12 （85.7%） of the 14 patients with lymph node micrometastasis, and in g （56.3%） of the 16 patients without lymph node micrometastasis （P = 0.118）. CONCLUSIONS： Our results demonstrate that MMP-2 expression has significant correlation with tumor invasion, tumor differentiation and lymph node metastases. MMP-2 expression may be an important biological characteristics and significant prognostic parameter of gastric carcinoma. We also conclude that MMP-2 may participate in the development of lymph node micrometastasis of gastric carcinoma. Further investigations are needed to draw a conclusion.

Novel immunological and nutritional-based prognostic index for gastric cancer

AIM: To assess the prognostic significance of immunological and nutritional-based indices, including the prognostic nutritional index(PNI), neutrophillymphocyte ratio(NLR), and platelet-lymphocyte ratio in gastric cancer.METHODS: We retrospectively reviewed 632 gastric cancer patients who underwent gastrectomy between1998 and 2008. Areas under the receiver operating characteristic curve were calculated to compare the predictive ability of the indices, together with estimating the sensitivity, specificity and agreement rate.Univariate and multivariate analyses were performed to identify risk factors for overall survival(OS). Propensity score analysis was performed to adjust variables to control for selection bias.RESULTS: Each index could predict OS in gastric cancer patients in univariate analysis, but only PNI had independent prognostic significance in multivariate analysis before and after adjustment with propensity scoring(hazard ratio, 1.668; 95% confidence interval:1.368-2.035). In subgroup analysis, a low PNI predicted a significantly shorter OS in patients with stage Ⅱ-Ⅲ disease(P = 0.019, P < 0.001), T3-T4 tumors(P <0.001), or lymph node metastasis(P < 0.001). Canton score, a combination of PNI, NLR, and platelet, was a better indicator for OS than PNI, with the largest area under the curve for 12-, 36-, 60-mo OS and overall OS(P = 0.022, P = 0.030, P < 0.001, and P = 0.024,respectively). The maximum sensitivity, specificity, and agreement rate of Canton score for predicting prognosis were 84.6%, 34.9%, and 70.1%, respectively.CONCLUSION: PNI is an independent prognostic factor for OS in gastric cancer. Canton score can be a novel preoperative prognostic index in gastric cancer.

Efficacy of adjuvant XELOX and FOLFOX6 chemotherapy after D2 dissection for gastric cancer

AIM: To compare the efficacy of capecitabine and oxaliplatin (XELOX) with 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX6) in gastric cancer patients after D2 dissection. METHODS: Between May 2004 and June 2010, patients in our gastric cancer database who underwent D2 dissection for gastric cancer at the First Affiliated Hospital of Sun Yat-Sen University were retrospectively analyzed. A total of 896 patients were enrolled into this study according to the established inclusion and exclusion criteria. Of these patients, 214 received the XELOX regimen, 48 received FOLFOX6 therapy and 634 patients underwent surgery only without chemotherapy. Overall survival was compared among the three groups using Cox regression and propensity score matchedpair analyses. RESULTS: Patients in the XELOX and FOLFOX6 groups were younger at the time of treatment (median age 55.2 years; 51.2 years vs 58.9 years), had more undifferentiated tumors (70.1%; 70.8% vs 61.4%), and more lymph node metastases (80.8%; 83.3% vs 57.7%), respectively. Overall 5-year survival was 57.3% in the XELOX group which was higher than that (47.5%) in the surgery only group (P = 0.062) and that (34.5%) in the FOLFOX6 group (P = 0.022). Multivariate analysis showed that XELOX therapy was an independent prognostic factor (hazard ratio = 0.564, P < 0.001). After propensity score adjustment, XELOX significantly increased overall 5-year survival compared to surgery only (58.2% vs 44.2%, P = 0.025) but not compared to FOLFOX6 therapy (48.5% vs 42.7%, P = 0.685). The incidence of grade 3/4 adverse reactions was similar between the XELOX and FOLFOX6 groups, and more patients suffered from hand-foot syndrome in the XELOX group (P = 0.018). CONCLUSION: Adjuvant XELOX therapy is associated with better survival in patients after D2 dissection, but does not result in a greater survival benefit compared with FOLFOX6 therapy.

(-)-Epigallocatechin-3-gallate inhibits VEGF expression induced by IL-6 via Stat3 in gastric cancer

AIM: To demonstrate that (-)-Epigallocatechin-3-gallate (EGCG) inhibits vascular endothelial growth factor (VEGF) expression and angiogenesis induced by interleukin-6 (IL-6) via suppressing signal transducer and activator of transcription 3 (Stat3) activity in gastric cancer. METHODS: Human gastric cancer (AGS) cells were treated with IL-6 (50 ng/mL) and EGCG at different concentrations. VEGF, total Stat3 and activated Stat3 protein levels in the cell lyses were examined by Western blotting, VEGF protein level in the conditionedmedium was measured by enzyme-linked immunosorbent assay, and the level of VEGF mRNA was evaluated by reverse transcription polymerase chain reaction (RTPCR). Stat3 nuclear translocation was determined by Western blotting with nuclear extract, and Stat3-DNA binding activity was examined with Chromatin immunoprecipitation (ChIP) assay. IL-6 induced endothelial cell proliferation was measured with 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazoliumbromide assay, in vitro angiogenesis was determined with endothelial cell tube formation assay in Matrigel, and IL-6-induced angiogenesis in vitro was measured with Matrigel plug assay. RESULTS: There was a basal expression and secretion of VEGF in AGS cells. After stimulation with IL-6, VEGF expression was apparently up-regulated and a 2.4-fold increase was observed. VEGF secretion in the conditioned medium was also increased by 2.8 folds. When treated with EGCG, VEGF expression and secretion were dose-dependently decreased. IL-6 also increased VEGF mRNA expression by 3.1 folds. EGCG treatment suppressed VEGF mRNA expression in a dose-dependent manner. EGCG dose-dependently inhibited Stat3 activation induced by IL-6, but did not change the total Stat3 expression. When treated with EGCG or AG490, VEGF expressions were reduced to the level or an even lower level in the tumor cells not stimulated with IL-6. However, PD98059 and LY294002 did not change VEGF expression induced by IL-6. EGCG inhibited Stat3 nucleus translocation, and Stat3-DNA binding activity was also markedly decreased by EGCG. Furthermore, EGCG inhibited IL-6 induced vascular endothelial cell proliferation and tube formation in vitro and angiogenesis in vitro . CONCLUSION: EGCG inhibits IL-6-induced VEGF expression and angiogenesis via suppressing Stat3 activity in gastric cancer, which has provided a novel mechanistic insight into the anti-angiogenic activity of EGCG.

Clinicopathological features and trend changes of gastric carcinoma in Southern China

AIM: To investigate the clinicopathological features of gastric carcinoma in southern China and disease trends changes over the last 18 years.

Effect of lymph node micrometastases on prognosis of gastric carcinoma

AIM： To evaluate the relationship between lymph node micrometastases and prognosis of patients with gastric carcinoma and to evaluate the significance of the new assessment of nodal status in determining the pN categories in the 5th edition of the UICC TNM classification.METHODS： A total of 850 lymph nodes from 30 patients with gastric carcinoma who underwent gastrectomy with lymphadenectomy were assessed by reverse transcription polymerase chain reaction assay in addition to histologic examination. Cytokeratin-20 gene marker was used in this assay.RESULTS： Routine examination by HE staining confirmed metastasis in 233 lymph nodes from 20 patients. All these 233 lymph nodes were oltokeratin-20 positive. Moreover, lymph node micrometastases were detected in an additional 67 lymph nodes in 12 of these 20 patients. Lymph node micrometastases were also detected in t0 lymph nodes from 2 of 10 patients who had no obvious metastases identified by HE staining. Totally, lymph node micrometastases were identified by the reverse transcription polymerase chain reaction assay in 77 （12.5%） lymph nodes from 14 （46.7%） patients with gastric carcinoma. Of 27 patients who underwent curative resection, 7 （25.9%） were up-staged （from Ⅰ B stage to Ⅱ stage in 1 patient, from IB stage to ⅢA stage in 1 patient, from Ⅱ stage to ⅢA stage in 1 patient, from ⅢA stage to ⅢB stage in 1 patient, from ⅢA stage to Ⅳ stage in 1 patient, from ⅢB stage to Ⅳ stage in 2 patients）. In a median follow-up of 32 （range 8-36） too, Kaplan-Meier survival analysis showed significant improvements in median survival （22.86 ± 3.17 mo, 95% CI： 16.64-29.08 mo vs 18.00 ± 7.4 mo, 95% CI： 3.33-32.67 mo） of patients with negative lymph node micrometastases over patients with positive lymph node micrometastases （log-rank, P 〈 0.05）.CONCLUSION： Lymph node micrometastases have a significant impact on the current staging system of gastric carcinoma, and are significant risk factors for prognosis of patients with gastric carcinoma.

Vagina vasorum dissection during D2 lymphadenectomy for gastric carcinoma

AIM: To explore the relationship between metastasis and vagina vasorum in the progress of gastric carcinoma and to find some facts and references for gastric surgeons. METHODS: One hundred and seven specimens of left or right gastric arteries (55 left and 52 right) were gathered from 59 patients undergoing radical gastrectomy for gastric carcinoma. All the frozen specimens were cut into 3 μm-thick sections and stained with hematoxylin-eosin (HE) and immunohistochemical method separately. Cytokeratin (CK) and mesothelial cells (MC) were stained with immunohistochemical method. Cancer cells inside vagina vasorum were detected and the structure of artery wall was observed under microscope. RESULTS: Metastatic cancer cells or tubercles were found inside vagina vasorum in some stage Ⅲ or Ⅳ specimens, but not in stageⅠor Ⅱ specimens. Tumor cells in vagina vasorum were CK positive in 26 specimens of 14 tumors. Among them, stage Ⅲ was found in 4 specimens of 2 tumors, and stage Ⅳ in 22 specimens of 12 tumors. None of these specimens was positive for MC. The positive rate of CK increased with TNM staging. Compared with the lower part, tumors in the upper and middle parts of stomach were more likely to metastasize into vagina vasorum. CONCLUSION: Vagina vasorum dissection should be performed during D2 lymphadenectomy for TNM stage Ⅲ or Ⅳ gastric carcinoma.

Rare case of an abdominal mass: Reactive nodular fibrous pseudotumor of the stomach encroaching on multiple abdominal organs

Reactive nodular fibrous pseudotumor(RNFP), which presents abdominal clinical manifestations and malignant radiographic results, usually requires radical resection as the treatment. However, RNFP has been recently described as an extremely rare benign postinflammatory lesion of a reactive nature, which typically arises from the sub-serosal layer of the digestive tract or within the surrounding mesentery in association with local injury or inflammation. In addition, a postoperative diagnosis is necessary to differentiate it from the other reactive processes of the abdomen. Furthermore, RNFP shows a good prognosis without signs of recurrence or metastasis. A 16-year-old girl presented with a 3-mo history of epigastric discomfort, and auxiliary examinations suggested a malignant tumor originating from the stomach; postoperative pathology confirmed RNFP, and after a 2-year follow-up period, the patient did not display any signs of recurrence. This case highlights the importance of preoperative pathology for surgeons who may encounter similar cases.

Detection of hMSH2 and hMLH1 mutations in Chinese hereditary non-polyposis colorectal cancer kindreds

AIM： To establish and validate the mutation testing for identification and characterization of hereditary non-polyposis colorectal cancer （HNPCC） in suspected Chinese patients. METHODS： Five independent Chinese kindreds with HNPCC fulfilling the classical Amsterdam criteria were collected. Genomic DNA was extracted after informed consent was obtained. The coding region of hMSH2 and hMLH1 genes was detected by polymerase chain reaction （PCR） and denaturing high-performance liquid chromatography （DHPLC）. Mutations identified in the proband by DHPLC were directly sequenced using a 377 DNA sequencer, analyzed with a basic local alignment tool （BLAST）, and tested in the corresponding family members by direct DNA sequencing. RESULTS： Mutations were identified in two Chinese HNPCC kindreds. One was the missense mutation of hMSH2 c.1808A→G resulting in Asp 603 Gly identified in the proband of the fifth HNPCC （HNPCCS） kindred. In the HNP5 kindred, three family members were found to have this mutation and two of them had colorectal cancer. The other mutation of hMLH1 c.1882A→G was identified in the HNP2 kindred＇s proband, which might be the nonsense mutation analyzed by BLAST. CONCLUSION： Pedigree investigation and mutation testing of hMSH2 and hMLH1 are the practical methods to identify high-risk HNPCC patients in China.

Effect of somatostatin in advanced gastric cancer after D2 radical gastrectomy

AIM:To study the effect of somatostatin in patients with advanced gastric cancer who received D2 lymphadenectomy and vagina vasorum dissection.METHODS:Using a prospective,single-blind,placebocontrolled design,patients with advanced gastric cancer were randomized into a study group(n=61)and a control group(n=59).Patients in the study group were given somatostatin for 5-7 d starting 6 h after the operation,and patients in the control group were given normal saline.Preoperative and nonoperative complications in the perioperative period,as well as differenttypes of postoperative drainage in the two groups were compared.RESULTS:There was no significant difference between the study group and the control group for preoperative clinicopathological indicators.We found no significant difference between the two groups for the overall incidence of complications,but a lower percentage of peritoneal effusion was observed in the treatment group(1.6%vs 10.2%,P<0.05).There were no significant differences between the two groups in the incidence of postoperative pancreatic dysfunction and chylous fistula.However,there were significant differences in the amylase concentration in drainage fluid,volume and duration of drainage,volume and duration of chylous fistula and peritoneal drainage,and volume and duration of gastric tube drainage.The study group did not show any increase in mean hospitalization cost and the cost reduced when the postoperative complications occurred.CONCLUSION:Postoperative somatostatin reduces volume and duration of surgical drainage and related complications.Somatostatin may improve safety of gastric cancer surgery,reducing postoperative complications and promoting recovery.

Pathological diagnosis is maybe non-essential for special gastric cancer: Case reports and review

Histopathological results are critical for the diagnosis and surgical decision regarding gastric cancer. How-ever, opposite opinions from radiology and pathology can sometimes affect clinical decisions. The two cases reported in this article were both highly suspected as gastric cancer by clinical manifestations and radiologic findings, although both showed negative results in the first biopsy examination. One was confirmed as gastric cancer by the time of the 6 th biopsy, while the other was still negative even after 8 biopsies. With a definite pathologic result and the agreement of the patient for the latter case, both of them finally received surgery. Postoperative pathological examination revealed find-ings that were the same as Borrmann type Ⅳ gastric cancer. We believed that duplicate biopsies under ra-diologic guidance were necessary for highly suspected gastric cancer cases in the absence of a definite pathol-ogy result, and patients should be under close follow-up. We propose that, if gastric cancer is highly sus-pected when typical radiology changes of widely diffuse gastric parietal lesions suffice to exclude lymphoma and other similar situations, and even in absence of a posi-tive biopsy result, a diagnostic laparotomy under lapa-roscopy and even radical gastrectomy may be reason-ably performed by an experienced gastric cancer center with the agreement of the patient after being decided by a multidisciplinary discussion team.

Risk factors for adverse outcome in low rectal cancer

AIM: To demonstrate the oncologic outcomes of low rectal cancer and to clarify the risk factors for survival, focusing particularly on the type of surgery performed. METHODS: Data from patients with low rectal carcinomas who underwent surgery, either sphincter-preserving surgery (SPS) or abdominoperineal resection (APR), at The First Aff iliated Hospital of Sun Yat-sen University in China from August 1994 to December 2005 were retrospectively analyzed. RESULTS: Of 331 patients with low rectal cancer, 159 (48.0%) were treated with SPS. A higher incidence of positive resection margins and a higher 5-year cumulative local recurrence rate (14.7% vs 6.8%, P = 0.041) were observed in patients after APR compared to SPS.The five-year overall survival (OS) was 54.6% after APR and 66.8% after SPS (P = 0.018), and the 5-year disease-free survival (DFS) was 52.9% after APR and 65.5% after SPS (P = 0.013). In multivariate analysis, poor OS and DFS were signif icantly related to positive resection margins, pT3-4, and pTNM Ⅲ-Ⅳ but not to the type of surgery. CONCLUSION: Despite a higher rate of positive resection margins after APR, the type of surgery was not identif ied as an independent risk factor for survival.

Branched fibrous amidoxime adsorbent with ultrafast adsorption rate and high amidoxime utilization for uranium extraction from seawater

Direct collection of uranium from low uranium systems via adsorption remains challenging.Fibrous sorbent materials with amidoxime(AO)groups are promising adsorbents for uranium extraction from seawater.However,low AO adsorption group utilization remains an issue.We herein fabricated a branched structure containing AO groups on polypropylene/polyethylene spun-laced nonwoven(PP/PE SNW)fibers using grafting polymerization induced by radiation(RIGP)to improve AO utilization.The chemical structures,thermal properties,and surface morphologies of the raw and treated PP/PE SNW fibers were studied.The results show that an adsorptive functional layer with a branching structure was successfully anchored to the fiber surface.The adsorption properties were investigated using batch adsorption experiments in simulated seawater with an initial uranium concentration of 500μg·L^(−1)(pH 4,25℃).The maximum adsorption capacity of the adsorbent material was 137.3 mg·g^(−1)within 24 h;moreover,the uranyl removal reached 96%within 240 min.The adsorbent had an AO utilization rate of 1/3.5 and was stable over a pH range of 4–10,with good selectivity and reusability,demonstrating its potential for seawater uranium extraction.

Vascularizing lymph node dissection for advanced gastric cancer: A single-institution experience

AIM: To compare the short- and long-term outcomes of vascularizing lymph node dissection (VLND) and non-vascularizing lymph node dissection (NVLND) from a single institution.METHODS: Data of 315 patients with advanced gastric cancer who underwent standard D2 lymphadenectomy with curative intent was collected between January 1994 and December 2006. One hundred and fifty-two patients received VLND while 163 patients received NVLND. Short- and long-term clinical outcomes were compared between the two groups.RESULTS: The median followed-up time was 82 mo. The rate of postoperative complications in the VLND group was 13.2%, while that in the NVLND group was 11.7% (P = 0.686). The overall 5-year survival rate was 64% in the VLND group and 59% in the NVLND group (P = 0.047). When subgroup analyses were performed according to Bormann type, type of differentiation and lymph node status, survival benefit was demonstrated in patients with Bormann type III or IV (59% vs 50%, P = 0.032), undifferentiated type (63% vs 49%, P = 0.021) or presence of lymph node metastasis (53% vs 38%, P = 0.010) in the VLND group.CONCLUSION: D2 VLND in advanced gastric cancer treatment allows survival benefit with acceptable morbidity and mortality. VLND for patients with potentially curable advanced gastric cancer is feasible and safe when performed by a well-trained surgical team.

RAD51 potentiates synergistic effects of chemotherapy with PCI-24781 and cis-diamminedichloroplatinum on gastric cancer

AIM:To explore the efficacy of PCI-24781,a broadspectrum,hydroxamic acid-derived histone deacetylase inhibitor,in the treatment of gastric cancer(GC).METHODS:With or without treatment of PCI-24781and/or cis-diamminedichloroplatinum(CDDP),GC cell lines were subjected to functional analysis,including cell growth,apoptosis and clonogenic assays.Chromatin immunoprecipitation and luciferase reporter assays were used to determine the interacting molecules and the activity of the enzyme.An in vivo study was carried out in GC xenograft mice.Cell culture-based assays were represented as mean±SD.ANOVA tests were used to assess differences across groups.All pairwise comparisons between tumor weights among treatment groups were made using the Tukey-Kramer method for multiple comparison adjustment to control experimental-wise typeⅠ error rates.Significance was set at P<0.05.RESULTS:PCI-24781 significantly reduced the growth of the GC cells,enhanced cell apoptosis and suppressed clonogenicity,and these effects synergized with the effects of CDDP.PCI-24781 modulated the cell cycle and significantly reduced the expression of RAD51,which is related to homologous recombination.Depletion of RAD51 augmented the biological functions of PCI-24781,CDDP and the combination treatment,whereas overexpressing RAD51 had the opposite effects.Increased binding of the transcription suppressor E2F4 on the RAD51 promoter appeared to play a major role in these processes.Furthermore,significant suppression of tumor growth and weight in vivo was obtained following PCI-24781 treatment,which synergized with the anticancer effect of CDDP.CONCLUSION:These data suggest that RAD51 potentiates the synergistic effects of chemotherapy with PCI-24781 and CDDP on GC.

The effect of FasL gene transfer to islet cells on pancreatic islet allografts

OBJECTIVE: To investigate the effect of FasL gene transfer to islet cells on pancreatic islet allografts. METHODS: A recombinant and replication-deficient type-5 adenovirus encoding murine FasL (AdV- FasL) was constructed by the method of calcium phosphate precipitation. Pancreatic islets were infected with the recombinant adenovirus AdV-FasL, and transplanted into diabetic recipients. FasL expression was detected by RT-PCR and immunohistochemistry. The survival of allografts and the apoptosis of gene transferred islet allografts were analyzed. RESULTS: All animals receiving islet allograft alone returned to a diabetic state by several days (mean survival time 6.3±0.6 days). Compared with the control group, no delayed rejection and prolonged survival of allografts were observed in the group of FasL gene transfer. The rejection was accelerated and the allograft survival was shortened to 3.4±0.2 days (P<0.05). Pancreatic islets infected with AdV- FasL demonstrated positive staining of FasL at 24 h, with an increased intensity at 48 h, but not in AdV-5 infected or uninfected islets. TUNEL labeling of pancreatic islet allografts at 24, 48 h revealed apoptosis that was not in AdV-5 infected allografts. CONCLUSIONS: Though co-transplantation of FasL-expressing testicular cells can induce privilege of islet allografts and prolong allograft survival, direct expression of FasL on islet allografts infected with AdV-FasL may accelerate islets rejection by islet apoptosis and granulocyte infiltration.

Anti-EGFR therapy in metastatic colorectal cancer:mechanisms and potential regimens of drug resistance

Cetuximab and panitumumab,as the highly effective antibodies targeting epidermal growth factor receptor(EGFR),have clinical activity in the patients with metastatic colorectal cancer(mCRC).These agents have good curative efficacy,but drug resistance also exists at the same time.The effects of KRAS,NRAS,and BRAF mutations and HER2 amplification on the treatment of refractory mCRC have been elucidated and the corresponding countermeasures have been put forward.However,the changes in EGFR and its ligands,the mutations or amplifications of PIK3CA,PTEN,TP53,MET,HER3,IRS2,FGFR1,and MAP2K1,the overexpression of insulin growth factor-1,the low expression of Bcl-2-interacting mediator of cell death,mismatch repair-deficient,and epigenetic instability may also lead to drug resistance in mCRC.Although the emergence of drug resistance has genetic or epigenetic heterogeneity,most of these molecular changes relating to it are focused on the key signaling pathways,such as the RAS/RAF/mitogen-activated protein kinase or phosphatidylinositol 3-kinase/Akt/mammalian target of the rapamycin pathway.Accordingly,numerous efforts to target these signaling pathways and develop the novel therapeutic regimens have been carried out.Herein,we have reviewed the underlying mechanisms of the resistance to anti-EGFR therapy and the possible implications in clinical practice.