Background and purpose:Radiotherapy is the main method to manage head and neck tumors.About half of the patients with malignant tumor in head and neck could obtain long term survival through radiotherapy or other therapy combined with radiotherapy.However,it is necessary to clinically detect whether carotid stenosis is a major sequela of head and neck irradiation,especially in long term survivors such as patients with nasopharyngeal carcinoma.We analyzed this injury and the degree of carotid stenosis,and its related factors to provide information to reduce and delay the incidence of this injury.Methods:We analyzed the degree of arterial stenosis of the nasopharyngeal carcinoma patients who received radiotherapy and had survived more than three years in Cancer Hospital Fudan University,compared with newly diagnosed as nasopharyngeal carcinoma before radiotherapy.The degree of carotid artery injury was observed and the clinical factors which affect its occurrence and development.All patients were low differentiated squamous cell carcinoma confirmed by pathology.All patients were examined with color doppler ultrasound to detect the carotid artery.The main end points were the diameter of carotid artery,the peak systolic and end diastolic velocities.Results:Arterial stenosis was more common in the reserch group than the control group(80% vs 20%,P＜0.001).The common and internal carotid arteries were most commonly involved(70% vs 20%,P＜0.001;6313% vs 10%,P＜0.001),followed by the external carotid artery(30% vs 3.3%,P=0.015).Significant stenosis was only found in the research group,common carotid arteries 36.7%,internal carotid arteries 23.3%,external carotid arteries10%.Conclusion:This study showed that radiation could cause significant carotid stenosis in nasopharyngeal carcinoma patients who had received radiotherapy more than 3 years previously.Carotid stenosis developed more frequently in the common carotid artery and intemal carotid artery on the side that had received radiotherapy.

Background and purpose:Bone metastases leads to the destruction of bones by changing the level of bone turnover markers.The purpose of this study was to assess the clinical application value of bone turnover markers in bone metastases for non-small cell lung cancer,which included the diagnosis and spread behavior of bone metastases.Methods:AKP,β-CTx,OST and BALP were measured in 76 NSCLC with bone metastases patients and 44 normal people.Results:The level ofAKP,β-CTx and BALP in patients with bone metastasis was significantly higher than in the subjects without bone metastases.There were significant correlations among the bone turnover markers.The levels of BALP and OST were significantly positively correlated with the extent of bone metastasis.Patients with high-levels of CTx and low-levels of BALP had a higher risk of pathologic fracture.Conclusion:In patients with bone metastases from NSCLC,bone turnover markers can help make diagnoses and evaluate severity of disease.It potentially has a wide range of uses in clinical practice.

Background and purpose:Oxaliplatin is a new cytotoxic platinum compound widely used in antineoplastic treatments.Peripheral neuropathy characterized by allodynia remains the most common way to limit the usage of oxaliplatin.Oxaliplatin-associated neuropathic pain is often resistant to standard analgesics.The effects of antidepressant agents such as desipramine and fluoxetine on chemotherapy-induced neuropathic pain were investigated so as to provide experimental evidence for clinical treatment.Methods:A single injection of oxaliplatin(30 mg/kg)intraperitoneal was injected into a test subject,a mouse that had chronic neuropathic pain.Using the von Frey filament as a touch stimulator,the mechanical withdrawal threshold(MWT)was measured when observing allodynia.The MWT was measured before and 1 h after the administration of desipramin and fluoxetine.Results:Desipramine and fluoxetine both have the potential to increase the MWT in mice with oxaliplatin-induced neuropathic pain.Pretreatment with antagonists such as an opioid receptor like naloxone could deepen their effects.Furthermore,when desipramine is combined with an opioid analgesic as buprenorphine,it causes an augmentation in the MWT.Conclusion:Antidepressants desipramine and fluoxetine antagonize oxaliplatin-induced neuropathic pain by inhibiting allodynia.Furthermore,the tricyclic antidepressing agent desipramine could enhance the effects of buprenorphine in subjects with oxaliplatin-induced pain,suggesting a synergistic effect for opioid analgesic.

Background and purpose:It was reported that erythropoietin may directly or indirectly induce the tumor cells to proliferate and result in diseases progression when recombinant human erythropoictin is used clinically in cancer-related anemia.Recently,the expression of erythropoietin-receptor(Epo-R)was detected in breast cancer.This study was done to detect the expression of Epo-R,estrogen receptor(ER),progesterone receptor(PR)and human epidermal growth factor receptor 2(Her-2)in breast cancer,and to investigate the relationships between these indexes and the clinical significance.Methods:Sixty breast cancer patients were analyzed,the expression of Epo-R and microvascular density(MVD)were detected by immunohistochernistry,in order to clarify the relationships between the expression level of Epo-R,MVD and ER,PR,Her-2.Results:The rate of Epo-R expression was 78.3%,the mean number of positive tumor cells was 39±24,while the tissue MVD was 25±9.The expression level of Epo-R was positively correlated with the MVD.Also,the level of MVD was higher in the group of Epo-R positive than the negative,which has significant difference(t=3.4252,P＜0.001).The expression level of ER,PR has no definite relationships with Epo-R,MVD.The expression level of Her-2 was both closely associated with Epo-R,MVD.The expression level of Epo-R has an obvious relationship with clinical stage,lymph node status and the size(P＜0.001).The value of MVD was positively correlated with lymph node status,while not with clinical stage and the size.Conclusion:The expression level of Epo-R was markedly higher in breast cancer,and has a positive correlation with the tissue MVD.The expression level of Epo-R and MVD were significantly associated with Her-2,but not with ER and PR.It may contribute to clarifying the clinicopathological characteristics and prognosis of breast cancer by detecting both the expression level of Epo-R and MVD.

Background and purpose:The expression of dickkopf homolog 3 gene(DKK3)is always reduced or absent in tumors,instead part of the tumor vascular endothelial expressed DKK3.vWF is a macromolecular glycoprote synthesized and released by vascular endothelial cells and megakaryocytes.However,vWF was also expressed by tumor.The relationship between these 2 factors and the occurrence of cancer is still unclear.The purpose of this study was to observe the expression of DKK3 and vWF proteins in colorectal carcinoma and determine their clinical significance through finding their association with MVD and correlation with each other.Methods:Immunohistochemistry staining was used to detect the expression of DKK3,vWF proteins and MVD in the colorectal carcinoma tissue microarrays that contained 94 colorectal carcinoma specimens.Results:The expression of DKK3 in colorectal carcinoma was lower than or nonexistent compared to that in normal tissues(P＜0.05).The expression of vWF in colorectal carcinoma was higher than that in normal tissues(P＜0.05).Expression of DKK3 and vWF in colorectal carcinoma were not correlated to the age or gender of the patients,invasive depth,or tumor locus of the colorectal carcinoma (P＞0.05).Correlations with the expression of DKK3 and vWF in colorectal carcinoma were only found with differentiation and iynphnode metastasis (P＜0.05).However,the expression of DKK3 and vWF in colorectal carcinoma was not correlated to MVD(P＞0.05).The expression of DKK3 was not correlated to the expression of vWF in coiorectal carcinoma(r=0.1310,P=0.2090).Conclusion:A lowered expression of DKK3 and higher expression of vWF may be associated with the carcinogenesis,various biological behaviors and metastasis of colorecml carcinoma.These 2 factors can be used as important biological markers for colorectal cancer.

Background and purpose:Proteasome inhibitors constitute a novel class of antitumor agents that has a complex mechanism of action.Previous studies have confirmed that proteasome inhibitor MG-132 can significantly inhibit Hep-2 cell growth and induce cell apoptosis in a manner that is dependent on dosage and time.But it also induced p-STAT3 protein expression.The aim of this study was to explore whether the STAT3 gene can,by transfecting short hair pin RNA(shRNA),enhance the anti-tumor effect of MG-132 on human laryngeal carcinoma cells.Methods:Hep-2 cells were plated into 96-well and 6-well plates and incubated overnight.Then,they were treated with MG-132 alone and combined with pshSTAT3.Their cell growth was detected by MTT assay,and apoptosis was examined with flow cytometry.The protein expression of p-STAT3 was detected by Western blotting.Results:MTT assay showed that a combined group inhibited the proliferation of Hep-2 cells compared to the MG-132 group and pshSTAT3 group(P＜0.01).Flow cytometry showed that apoptosis of the combined group was significantly higher than the MG-132 group and pshSTAT3 group (P＜0.01).Western blotting showed that the p-STAT3 protein expression up-regulation was observed in the MG-132 group,whereas down-regulation was expressed in the combined group and pshSTAT3 group.Conclusion:The shRNA targeting STAT3 gene can prevent the up-regulation of p-STAT3 protein following a MG-132 treatment thereby significantly enhancing the anti-tunlor effect of the protease inhibitor,MG-132,on human laryngeal carcinoma cells.

Background and purpose:A pressing obstacle in clinical chemotherapy is drug resistance in breast cancer.A nano-delivery system,which has many advantages as a drug carrier,such as carrying anticancer drugs,can be used effectively to overcome drug resistance in tumors.This paper examined a new nano-delivery system,called calcium phosphate and glycerophosphocholine-mPEG(CAP/GPC-MPEG)composite nanoparticle and its influence on the cellular drug uptake of BCRP-over expressing mitoxantrone(MIT)-resistant breast cancer cell MCF-7/MIT.This paper will also examine its effect on overcoming drug resistance in the MCF-7/MIT cells.Methods:After the calcium phosphate and GPC-mPEG composite nanoparticles were designed and prepared,the entrapment efficiency and in vitro drug release of mitoxantrone-loaded nanoparticles were investigated.Quantitative comparisons were made between cellular uptake of drug-loaded nanoparticles and free drugs.Finally,a confocal laser scanning microscopy Was used to compare the subcellular distribution of drug-loaded nanoparticles and the free drugs.Results:Calcium phosphate and GPC-mPEG composite nanoparticles were nanoporous spherical particles with diameters between 50-100 mn.The MIT-loaded nanoparticles have an entrapment efficiency of(89.45±0.05)%.Although the drug-loaded nanoparticles showed an initial burst of drug release,it was followed by a more sustained release.The concentration of mitoxantrone was 1.89 times treated with MIT-loaded nanoparticles for 1 h compared to that treated with free mitoxantrone for 1 h in MCF-7/MIT cells.and which was 2.33 times in MCF-7 cells.Fluorescent red mitoxantrone appeared in the cytoplasm and nucleus of the MCF-7 and MCF-7,MIT cells treated with MlT-loaded nanoparticles whereas it is almost undetected in both cells treated with free mitoxantrone.Conclusion:Calcium phosphate and GPC-mPEG composite nanoparticles Can promote the cellular uptake and entering of mitoxantrone to the nucleus in MCF-7 and its corresponding BCRP-over expressing MIT-resistant MCF-7/MIT breast cancer cell lines.This nanoparticle is a potential nano-carrier for overcoming drug resistance in tumors.

Background and purpose:Previous studies have shown that Bubl was a critical component of the spindle checkpoint.Paclitaxel sensitivity was considered to be dependent on the functionality of this spindle checkpoint.This study investigated the effects of pEGFP-Bubl-shRNA plasmid stably transfected into the cell cycle and its sensitivity in human ovarian cancer cell line A2780.Methods:After the pEGFP-Bubl-shRNA plasmid and empty plasmids were constructed.they were transfected into A2780 cells by the Lipofectamine 2000~(TM).The nontransfected cells were the control.RT-PCR and Western blotting were used to determine the target gene and protein expression.The rate of proliferation inhibition was tested by an MTT assay,apoptosis and cell cycles were determined by flow cytometry,and the mitotic index was determined bv Hoechst33342 dye.Results:RT-PCR and Western blotting showed that pEGFP-Bubl-shRNA/A2780 group displayed a low expression of Bubl compared to the A2780 and pEGFP-Cl/A2780 group(P＜0.05).The sensitivity of the pEGFP-Bubl-shRNA/A2780 group was significantly lower than the non-transfccted and pEGFP-Cl/A2780 cells(P＜0.05).Flow cytometry revealed that the rates of G2/M phase and apoptosis were significantly lower in the pEGFP-Bubl-shRNA/A2780 group than those in the control group (P＜0.05).Conclusion:Bubl plays an important role in the paclitaxel treatment.A down-regulation of Bubl could reduce the drug sensitivity and rate of G_2/M cells in human ovarian cancer cell line A2780.

CXCR4 has long been considered as the unique receptor of CXCL12,and CXCL12/CXCR4 axis plays a prominent role in tumorigenesis.However,a novel receptor for CXCL12,named CXCR7,has been recently identified and also plays an important role in tumorigenesis.This review summarized current studies regarding the functions of CXCR4 and CXCR7 in cancer and the recent therapeutic approaches that target these receptors or their ligands.

Background and purpose:Five-year survival rate of post-operation patients with non-small cell lung cancer(NSCLC)is less than 40%.Treatments after recurrence are difficult.Our study aimed to evaluate the efficacy of pemetrexed on postoperative recurrence of NSCLC.Methods:From Jan.2006 to Sep.2008,40 NSCLC with postoperative recurrence were observed.All patients had received pemetrexed(ALIMTA)500 mg/m2 or carboplatin eonbined.Results:Among the 40 patients,partial response in 10 patients(25.00%),stable disease in 19 patients(47.50%),progressive disease in 11 patients(27.50%).The total response rate was 25.00%and clinical benefit control rate was 72.50%.Pemetrexed had significantly better disease control rate in female than in male (9 1.30% vs 47.06%,P=0.034),in adenocarcinoma patients than in non-adenocarcinoma's(87.10% vs 22.22%,P=0.001).Median overall survival time(MST)was 10.70 months.Progression-free survival time(PFS)was 5.18 months.Adenocarcinoma patients had longer PFS than non-adenocarcinoma patients.Conclusion:Pemetrexed demonstrates significant antitumor activity and good tolerance in these patients.