Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: ...Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: Human stom- ach neoplasms model was established in nude mice. The nude mice were divided into control group, moderate-dose of rhGH group, low-dose rhGH group, 5-FU group, moderate-dose rhGH/5-FU group, and low-dose rhGH/5-FU group. The results of each group were observed after ten days. Results: After therapy, the body mass of rhGH groups was significantly increased compared with control group (P<0.05), the body mass of rhGH/5-FU groups was significantly increased compared with 5-FU group (P<0.05), but it was no significant difference between rhGH/5-FU groups and control group (P>0.05). The average tumor mass and volume of rhGH groups were not significantly increased compared with control group (P>0.05), but they were significantly reduced in 5-FU group and rhGH/5-FU groups (P<0.05). They were no significant difference between rhGH/5- FU groups and 5-FU group (P>0.05). After treatment, the percentages of S, G0/G1 and G2/M phases and proliferation index (PI) were not significantly changed in rhGH groups compared with control group (P>0.05), and the same with rhGH/5-FU groups compared with 5-FU group (P>0.05). The difference caused by dose of rhGH was not significant. Conclusion: rhGH enhances body mass, does not stimulate tumor growth, and has no adverse effects on tumor bearing nude mice. Combined with flurouracil, rhGH does not influence the efficacy of chemotherapy, and has no effect on tumor cell cycle kinetics.展开更多
Here,we discuss an important problem in medicine as development of efctive strategies for brain drug delivery.This problem is related to the blood-brain barrier(BBB),which is a“customs”controlling the entrance of di...Here,we discuss an important problem in medicine as development of efctive strategies for brain drug delivery.This problem is related to the blood-brain barrier(BBB),which is a“customs”controlling the entrance of different molecules from blood into the brain protecting the normal function of central nervous system(CNS).We show three interfaces of anatomical side of BBB and two functional types of BBB一physical and transporter barriers.Although this protective mechanism is essential for health of CNS,it also creates a hindrance to the entry of drugs into the brain.The BBB was discovered over 100 years ago but till now,there is no efective methods for brain drug delivery.There ane more than 70 approaches for overcoming BBB incuding physical,chenical and biological techniques but all of these tools have limitation to be widely used in clinical practice due to invasi venes,challenge in performing,very costly or lim-itation of drug concentration.Photodynamic therapy(PDT)is usual clinical method of surgical navigation for the resection of brain tumor and anti-cancer therapy.Nowadays,the application of PDT is considered as a potential promising tool for brain drug delivery via opening of BBB.Here,we show the first sucoessful experimental results in this field discussing the adventures and disadv antages of PDT-related BBB disruption as well as altematives to overcome these limitations and possi ble mechanisms with new pathways for brain clearance via gly mphatic and lymphatic systems.展开更多
Objective:Several studies have been conducted on the effects and toxicity of adding oxaliplatin to fluorouracilbased or capecitabine-based chemoradiotherapy(CRT)regimens as significantly increasing the toxic response ...Objective:Several studies have been conducted on the effects and toxicity of adding oxaliplatin to fluorouracilbased or capecitabine-based chemoradiotherapy(CRT)regimens as significantly increasing the toxic response without benefit to survival.In this study,we further explored the role of these two postoperative CRT regimens in patients with pathological stage N2 rectal cancer.Methods:This study was a subgroup analysis of a randomized clinical trial.A total of 180 patients with pathological stage N2 rectal cancer were eligible,85 received capecitabine with radiotherapy(RT),and 95 received capecitabine and oxaliplatin with RT.Patients in both groups received adjuvant chemotherapy[capecitabine and oxaliplatin(XELOX);or fluorouracil,leucovorin,and oxaliplatin(FOLFOX)]after CRT.Results:At a median follow-up of 59.2[interquartile range(IQR),34.0−96.8]months,the three-year diseasefree survival(DFS)was 53.3%and 64.9%in the control group and the experimental group,respectively[hazard ratio(HR),0.63;95%confidence interval(95%CI),0.41−0.98;P=0.04].There was no significant difference between the groups in overall survival(OS)(HR,0.62;95%CI,0.37−1.05;P=0.07),the incidence of locoregional recurrence(HR,0.62;95%CI,0.24−1.64;P=0.33),the incidence of distant metastasis(HR,0.67;95%CI,0.42−1.06;P=0.09)and grade 3−4 acute toxicities(P=0.78).For patients with survival longer than 3 years,the conditional overall survival(COS)was significantly better in the experimental group(HR,0.39;95%CI,0.16−0.96;P=0.03).Conclusions:Our results indicated that adding oxaliplatin to capecitabine-based postoperative CRT is safe and effective in patients with pathological stage N2 rectal cancer.展开更多
AIMS Using a new approach of regional adjuvant chemotherapy to prevent cancer cells hepatic metasta- sis after radical surgery of large bowel cancer. METHODS A model of liver with metastasis of hu- man colonic cancer ...AIMS Using a new approach of regional adjuvant chemotherapy to prevent cancer cells hepatic metasta- sis after radical surgery of large bowel cancer. METHODS A model of liver with metastasis of hu- man colonic cancer (HCC) cells in nude mice was used to observe the effect in prevention of metastasis of HCC cells inoculated via spleen applied with early postoper- ative intraperitoneal (IP) chemotherapy using large dose of 5-FU. RESULTS The incidence of metastasis to liver was decreased by 40%,the mean number of metastatic liv- er nodules in each animal was reduced by 50.89% and the mean survival times of each animal was prolonged by 48.21% by using 5-FU 40 mg/NS 40 ml/kg IP for two consecutive days as compared with the controls. CONCLUSIONS IP is a new and more effective re- gional adjuvant chemotheraputic approach in the pre- vention of liver metastasis HCC cells after radical surgery of large bowel cancer.展开更多
INTRODUCTIONIn China,primary liver cancer (PLC) ranks secondin cancer mortality since the 1990s.In the field ofPLC treatment,surgical resection remains the best,which includes large PLC resection,small PLCresection,re...INTRODUCTIONIn China,primary liver cancer (PLC) ranks secondin cancer mortality since the 1990s.In the field ofPLC treatment,surgical resection remains the best,which includes large PLC resection,small PLCresection,re-resection of subclinical recurrence,aswell as cytoreduction and sequential resection forunresectable PLC.However,recurrence展开更多
AIM To investigate the interference ofmethionine.free parenteral nutrition plus 5-Fu(-MetTPN+5-Fu)in gastric cancer cell kineticsand the side effects of the regimen.METHODS Fifteen patients with advancedgastric canc...AIM To investigate the interference ofmethionine.free parenteral nutrition plus 5-Fu(-MetTPN+5-Fu)in gastric cancer cell kineticsand the side effects of the regimen.METHODS Fifteen patients with advancedgastric cancer were randomly divided into twogroups,7 patients were given preoperatively aseven-day course of standard parenteralnutrition in combination with a five-day courseof chemotherapy(sTPN+5-Fu),while the other8 patients were given methionine-deprivedparenteral nutrition and 5-Fu(-MetTPN+5-Fu).Cell cycles of gastric cancer and normal mucosawere studied by flow cytometry(FCM).Bloodsamples were taken to measure the serumprotein,methionine(Met)and cysteine(Cys)levels,and liver and kidney functions.RESULTS As compared with the resultsobtained before the treatment,the percentage ofG<sub>0</sub>/G<sub>1</sub> tumor cells increased and that of S phasedecreased in the-MetTPN+5-Fu group,while thecontrary was observed in the sTPN+5-Fu group.Except that the ALT,AST and AKP levels wereslightly increased in a few cases receiving-MetTPN+5-Fu,all the other biochemicalparameters were within normal limits.Serum Cys level decreased slightly after the treatmentin both groups.Serum Met level of patientsreceiving sTPN+5-Fu was somewhat higher aftertreatment than that before treatment;however,no significant change occurred in the -MetTPN+5-Fu group,nor operative complications in bothgroups.CONCLUSION -MetTPN+5-Fu exerted asuppressive effect on cancer cell proliferation,probably through a double mechanism ofcreating a state of'Met starvation'adverse tothe tumor cell cycle,and by allowing 5-Fu to killspecifically cells in S phase.Preoperative short-term administration of -MetTPN+5-Fu had littleundesirable effect on host metabolism.展开更多
INTRODUCTIONAlthough the long-term postoperative survival rateof gastric cancer(GC) patients has been improvedsignificantly since the local dissection of lymph nodewas widely used in China,yet the low curativeresectio...INTRODUCTIONAlthough the long-term postoperative survival rateof gastric cancer(GC) patients has been improvedsignificantly since the local dissection of lymph nodewas widely used in China,yet the low curativeresection rate and the high recurrence rate fromperitoneal and hepatic metastases hinder it fromfurther improvement.To alter the currentunsatisfactory status of GC treatment,a展开更多
Objective: Early assessment of response to neoadjuvant chemotherapy (NAC) for breast cancer allows therapy to be individualized. The optimal assessment method has not been established. We investigated the accuracy ...Objective: Early assessment of response to neoadjuvant chemotherapy (NAC) for breast cancer allows therapy to be individualized. The optimal assessment method has not been established. We investigated the accuracy of automated breast ultrasound (ABUS) to predict pathological outcomes after NAC. Methods: A total of 290 breast cancer patients were eligible for this study. Tumor response after 2 cycles of chemotherapy was assessed using the product change of two largest perpendicular diameters (PC) or the longest diameter change (LDC). PC and LDC were analyzed on the axial and the coronal planes respectively. Receiver operating characteristic (ROC) curves were used to evaluate overall performance of the prediction methods. Youden's indexes were calculated to select the optimal cut-off value for each method. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) and the area under the ROC curve (AUC) were calculated accordingly.Results: ypT0/is was achieved in 42 patients (14.5%) while ypT0 was achieved in 30 patients (10.3%) after NAC. All four prediction methods (PC on axial planes, LDC on axial planes, PC on coronal planes and LDC on coronal planes) displayed high AUCs (all〉0.82), with the highest of 0.89 [95% confidence interval (95% CI), 0.83-0.95] when mid-treatment &BUS was used to predict final pathological complete remission (pCR). High sensitivities (85.7%-88.1%) were observed across all four prediction methods while high specificities (81.5%-85.1%) were observed in two methods used PC. The optimal cut-off values defined by our data replicate the WHO and the RECIST criteria. Lower AUCs were observed when mid-treatment ABUS was used to predict poor pathological outcomes. Conclusions:ABUS is a useful tool in early evaluation of pCR after NAC while less reliable when predicting poor pathological outcomes.展开更多
Objective: In patients with chemotherapy-induced amenorrhea (CIA), the menopausal status is ambiguous anddifficult to evaluate. This study aimed to establish a discriminative model to predict and classify the menop...Objective: In patients with chemotherapy-induced amenorrhea (CIA), the menopausal status is ambiguous anddifficult to evaluate. This study aimed to establish a discriminative model to predict and classify the menopausalstatus of breast cancer patients with CIA.Methods: This is a single center hospital-based study from 2013 to 2016. The menopausal age distribution andaccumulated incidence rate of CIA are described. Multivariate models were adjusted for established and potentialconfounding factors including age, serum concentration of estradiol (E2) and follicle-stimulating hormone (FSH),feeding, pregnancy, parity, abortions, and body mass index (BMI). The odds ratio (OR) and 95% confidenceinterval (95% CI) of different risk factors were estimated.Results: A total of 1,796 breast cancer patients were included in this study, among whom, 1,175 (65.42%) werepremenopausal patients and 621 (34.58%) were post-menopause patients. Five hundred and fifty patients wereincluded in CIA analysis, and a cumulative CIA rate of 81.64% was found in them. Age (OR: 1.856, 95% CI:1.732-1.990), serum concentration of E2 (OR: 0.976, 95% CI: 0.972-0.980) and FSH (OR: 1.060, 95% CI:1.053-i.066), and menarche age (OR: 1.074, 95% CI: 1.009-1.144) were found to be associated with the patients'menopausal status. According to multivariate analysis, the discriminative model to predict the menopausal status isLogit (P)=-28.396+0.536Age-0.014E2+0.031FSH. The sensitivities for this model were higher than 85%, and itsspecificities were higher than 89%.Conclusions: The discriminative model obtained from this study for predicting menstrual state is important forpremenopausal patients with CIA. This model has high specificity and sensitivity and should be prudently used.展开更多
BACKGROUND Although pathological response is a common endpoint used to assess the efficacy of neoadjuvant chemotherapy (NAC) for gastric cancer, the problem of a low rate of concordance from evaluations among patholog...BACKGROUND Although pathological response is a common endpoint used to assess the efficacy of neoadjuvant chemotherapy (NAC) for gastric cancer, the problem of a low rate of concordance from evaluations among pathologists remains unresolved. Moreover, there is no globally accepted consensus regarding the optimal evaluation. A previous study based on a clinical trial suggested that pathological response measured using digitally captured virtual microscopic slides predicted patients’ survival well. However, the pathological concordance rate of this approach and its usefulness in clinical practice were unknown. AIM To investigate the prognostic utility of pathological response measured using digital microscopic slides in clinical practice. METHODS We retrospectively evaluated pathological specimens of gastric cancer patients who underwent NAC followed by surgery and achieved R0 resection between March 2009 and May 2015. Residual tumor area and primary tumor beds were measured in one captured image slide, which contained the largest diameter of the resected specimens. We classified patients with < 10% residual tumor relative to the primary tumorous area as responders, and the rest as non-responders;we then compared overall survival (OS) and relapse-free survival (RFS) between these two groups. Next, we compared the prognostic utility of this method using conventional Japanese criteria. RESULTS Fifty-four patients were evaluated. The concordance rate between two evaluators was 96.2%. Median RFS of 25 responders and 29 non-responders was not reached (NR) vs 18.2 mo [hazard ratio (HR)= 0.35, P = 0.023], and median OS was NR vs 40.7 mo (HR = 0.3, P = 0.016), respectively. This prognostic value was statistically significant even after adjustment for age, eastern cooperative oncology group performance status, macroscopic type, reason for NAC, and T- and Nclassification (HR = 0.23, P = 0.018). This result was also observed even in subgroup analyses for different macroscopic types (Borrmann type 4/non-type 4) and histological types (differentiated/undifferentiated). Moreover, the adjusted HR for OS between responders and non-responders was lower in this method than that in the conventional histological evaluation of Japanese Classification of Gastric Carcinoma criteria (0.23 vs 0.39, respectively). CONCLUSION The measurement of pathological response using digitally captured virtual microscopic slides may be useful in clinical practice.展开更多
INTRODUCTIONDevelopment of drug-resistance to chemotherapyand subsequent metastasis of tumor are primarilyresponsible for treatment failure and the death fromcancer. There have been many previous studies onthe relatio...INTRODUCTIONDevelopment of drug-resistance to chemotherapyand subsequent metastasis of tumor are primarilyresponsible for treatment failure and the death fromcancer. There have been many previous studies onthe relationship between expression of multidrugresistance (MDR) phenotype P-glycoprotein (P-gp)and the malignant properties of tumors, but theresults are often conflicting[1-8]. The difference intumor types or MDR phenotype induced by specificagents might account for this discrepancy. Taxotere(TXT), a member of the family of taxanes, hasantitumor activity through its effect of promotingthe polymerization of tubulin[9,10].展开更多
One hundred patients with focal epilepsy were recruited for the present study and their seizures controlled with antiepileptic drugs. The patients then orally received a capsule of tall gastrodis tuber powder, a tradi...One hundred patients with focal epilepsy were recruited for the present study and their seizures controlled with antiepileptic drugs. The patients then orally received a capsule of tall gastrodis tuber powder, a traditional Chinese drug, and underwent single photon emission computed tomography, long-term electroencephalogram, and CT/MRI. Blood drug levels were monitored throughout the study. Before treatment with tall gastrodis tuber, 35 of the 100 cases had abnormal CT/MRI scans; 79 cases had abnormal single photon emission computed tomography images; 86 cases had abnormal electroencephalogram; and a total of 146 abnormal perfusion foci were observed across the 100 subjects. After treatment, the number of patients with normal single photon emission computed tomography images increased by 12; normal electroencephalogram was observed in an additional 27 cases and the number of patients with epileptiform discharge decreased by 29 (34% of 86); the total number of abnormal perfusion foci decreased by 52 (36%) and changes in abnormal loci were visible in 65 patients. These changes indicate that the administration of tall gastrodis tuber in combination with antiepileptic drugs repairs abnormal perfusion foci in patients with focal epilepsy Our results demonstrate that traditional Chinese drugs can repair abnormal perfusion foci and, as such, are a promising new pathway in the treatment of focal epilepsy.展开更多
Aside from the important role of brain natriuretic peptide (BNP) in diagnosis, and differential diagnosis of heart failure, this biological peptide has proved to be an independent surrogate marker of rehospitalization...Aside from the important role of brain natriuretic peptide (BNP) in diagnosis, and differential diagnosis of heart failure, this biological peptide has proved to be an independent surrogate marker of rehospitalization and death of the fatal disease. Several randomized clinical trials demonstrated that drugs such as beta blocker, angiotensin converting enzyme inhibitor, spiro- nolactone and amiodarone have beneficial effects in decreasing circulating BNP level during the management of chronic heart failure. The optimization of clinical decision-making appeals for a representative surrogate marker for heart failure prognosis. The serial point-of-care assessments of BNP concentration provide a therapeutic goal of clinical multi-therapy and an objective guid- ance for optimal treatment of heart failure. Nevertheless new questions and problems in this area remain to be clarified. On the basis of current research advances, this article gives an overview of BNP peptide and its property and role in the management of heart failure.展开更多
AIM:rAAV mediated endostatin gene therapy has been examined as a new method for treating cancer.However, a sustained and high protein delivery is required to achieve the desired therapeutic effects.We evaluated the im...AIM:rAAV mediated endostatin gene therapy has been examined as a new method for treating cancer.However, a sustained and high protein delivery is required to achieve the desired therapeutic effects.We evaluated the impact of topoisomerase inhibitors in rAAV delivered endostatin gene therapy in a liver tumor model. METHODS:rAAV containing endostatin expression cassettes were transduced into hepatoma cell lines.To test whether the topoisomerase inhibitor pretreatment increased the expression of endostatin,Western blotting and ELISA were performed.The biologic activity of endostatin was confirmed by endothelial cell proliferation and tube formation assays. The anti-tumor effects of the rAAV-endostatin vector combined with a topoisomerase inhibitor,etoposide,were evaluated in a mouse liver tumor model. RESULTS:Topoisomerase inhibitors,including camptothecin and etoposide,were found to increase the endostatin exPression level in vitro.The over-expressed endostatin, as a result of pretreatment with a topoisomerase inhibitor, was also biologically active.In animal experiments,the combined therapy of topoisomerase inhibitor,etoposide with the rAAV-endostatin vector had the best tumor- suppressive effect and tumor foci were barely observed in livers of the treated mice.Pretreatment with an etoposide increased the level of endostatin in the liver and serum of rAAV-endostatin treated mice.Finally,the mice treated With rAAV-endostatin in combination with etoposide showed the longest survival among the experimental models. CONCLUSION:rAAV delivered endostatin gene therapy in combination with a topoisomerase inhibitor pretreatment is an effective modality for anticancer gene therapy.展开更多
The application of nanotechnology significantly benefits clinical practice in cancer diagnosis, treatment, and management.Especially, nanotechnology offers a promise for the targeted delivery of drugs, genes, and prot...The application of nanotechnology significantly benefits clinical practice in cancer diagnosis, treatment, and management.Especially, nanotechnology offers a promise for the targeted delivery of drugs, genes, and proteins to tumor tissues and therefore alleviating the toxicity of anticancer agents in healthy tissues.This article reviews current nanotechnology platforms for anticancer drug delivery, including polymeric nanoparticles, liposomes, dendrimers, nanoshells, carbon nanotubes, superparamagnetic nanoparticles, and nucleic acid-based nanoparticles [DNA, RNA interference (RNAi), and antisense oligonucleotide (ASO)] as well as nanotechnologies for combination therapeutic strategies, for example, nanotechnologies combined with multidrug-resistance modulator, ultrasound, hyperthermia, or photodynamic therapy.This review raises awareness of the advantages and challenges for the application of these therapeutic nanotechnologies, in light of some recent advances in nanotechnologic drug delivery and cancer therapy.展开更多
MIT method was applied to assay the cytotoxicityof three reversors, verapamil (VER), dipyridamole (DPM)and cyclosporin (CSA) in K562, K562/ADM and KB celllines. S-P immunocytochemical technique was applied todetect cx...MIT method was applied to assay the cytotoxicityof three reversors, verapamil (VER), dipyridamole (DPM)and cyclosporin (CSA) in K562, K562/ADM and KB celllines. S-P immunocytochemical technique was applied todetect cxpressions of oncoproteins or tumor suppressoroncoproteins in these tumor cell lines before or aftertreatment with these reversors. Results showed that threereversors were capable of inhibiting to a certain extentgrowth of K562 or KB cell lines and reversing greatlyadriamycin (ADM)-resistance in K562/ADM cell line.DPM and CsA were observed to inhibit, partly or wholly,expressions of p53, p16, bcl-2, p21 or cerbB-2oncoproteins. VER showed whole inhibition ofexpressions of P53, p16, p21 and bcl-2 and partlyexpression of p53 oncoprotein in K562 cell line. Theseresults suggest that growth inhibition in K562 or KB celllines by the reversors may be associated with partial orwhole inhibition or expressions of p53, p16, p21 or c-erbB-2 oncoproteins. Inhibitions of expressions p53, p16,p21 oncoproteins by VER but not DPM or CsA, may berespossible for reversing activity of VER for ADM-resistance in K562/ADM cell line.展开更多
Apoptosis,a key mechanism of programmed cell death,is triggered by caspase-3 protein and lowering its levels with gene therapy may rescue cell death after central nervous system damage.We developed a novel,non-viral g...Apoptosis,a key mechanism of programmed cell death,is triggered by caspase-3 protein and lowering its levels with gene therapy may rescue cell death after central nervous system damage.We developed a novel,non-viral gene therapy to block caspase-3 gene expression using small interfering RNA(siRNA)delivered by polybutylcyanoacrylate nanoparticles(CaspNPs).In vitro CaspNPs significantly blocked caspase-3 protein expression in C6 cells,and when injected intraocularly in vivo,CaspNPs lowered retinal capsase-3 immunofluorescence by 57.9%in rats with optic nerve crush.Longitudinal,repeated retinal ganglion cell counts using confocal neuroimaging showed that post-traumatic cell loss after intraocular CaspNPs injection was only 36.1%versus 63.4%in lesioned controls.Because non-viral gene therapy with siRNA-nanoparticles can selectively silence caspace-3 gene expression and block apoptosis in post-mitotic neurons,siRNA delivery with nanoparticles may be promising for neuroprotection or restoration of central visual system damage and other neurological disorders.The animal study procedures were approved by the German National Act on the use of experimental animals(Ethic Committee Referat Verbraucherschutz,Veterinärangelegenheiten;Landesverwaltungsamt Sachsen-Anhalt,Halle,Germany,#IMP/G/01-1150/12 and#IMP/G/01-1469/17).展开更多
The phamacogenetics is being used to predict whether the selected chemotherapy will be really effective and tolerable to the patient. Irinotecan,oxidized by CYP3A4 to produce inactive compounds,is used for treatment o...The phamacogenetics is being used to predict whether the selected chemotherapy will be really effective and tolerable to the patient. Irinotecan,oxidized by CYP3A4 to produce inactive compounds,is used for treatment of various cancers including advanced non small cell lung cancer (NSCLC) patients. CYP3A4*16B polymorphism was associated with decreased metabolism of irrinotecan. Irinotecan is also metabolized by carboxylesterase to its principal active metabolite,SN-38,which is subsequently glucuronidated by UGT1As to form the inactive compound SN-38G. UGT1A1*28 and UGT1A1*6 polymorphisms were useful for predicting severe toxicity with NSCLC patients treated with irinotecan-based chemotherapy. Platinum-based compounds (cisplatin,carboplatin) are being used in combination with new cytotoxic drugs such as gemcitabine,paclitaxel,docetaxel,or vinorelbine in the treatment of advanced NSCLC. Cisplatin activity is mediated through the formation of cisplatin-DNA adducts. Gene polymorphisms of DNA repair factors are therefore obvious candidates for determinants of repair capacity and chemotherapy efficacy. ERCC1,XRCC1 and XRCC3 gene polymorphisms were a useful marker for predicting better survival in advanced NSCLC patients treated with platinum-based chemotherapy. XPA and XPD polymorphisms significantly increased response to platinum-based chemotherapy. These DNA repair gene polymorphisms were useful as a predictor of clinical outcome to the platinum-based chemotherapy. EGFR kinase inhibitors induce dramatic clinical responses in NSCLC patients with advanced disease. EGFR gene polymorphism in intron 1 contains a polymorphic single sequence dinucleotide repeat (CA-SSR) showed a statistically significant correlation with the gefitinib response and was appeared to be a useful predictive marker of the development of clinical outcome containing skin rashes with gefitinib treatment. The other polymorphisms of EGFR were also associated with increased EGFR promoter activity. EGFR gene mutations and polymorphisms were also associated with EGFR kinase inhibitors response and toxicity.展开更多
BACKGROUNDIntracranial Listeria infections are common in newborns and immunocompromisedindividuals, but brainstem abscesses are rare.CASE SUMMARYWe report a rare case of brainstem abscesses caused by Listeria monocyto...BACKGROUNDIntracranial Listeria infections are common in newborns and immunocompromisedindividuals, but brainstem abscesses are rare.CASE SUMMARYWe report a rare case of brainstem abscesses caused by Listeria monocytogenes in apreviously healthy adult patient. The patient’s magnetic resonance imagingexamination showed multiple brain abscesses, and his second cerebrospinal fluidculture test indicated the presence of Listeria monocytogenes. Despite earlyempirical therapy, the patient’s condition progressively deteriorated. Because thepatient's abscesses were located in the brainstem and multiple lobes, surgery wasnot possible. The patient died 40 d after admission.CONCLUSIONThis case highlights the importance of rational clinical use of drugs to avoidpotentially serious infectious complications.展开更多
OBJECTIVE To evaluate the response rate and tolerance of patients with middle-late esophageal carcinoma, who were treated with concurrent chemoradiotherapy (CCRT) plus thalidomide.METHODS Sixty-five eligible patient...OBJECTIVE To evaluate the response rate and tolerance of patients with middle-late esophageal carcinoma, who were treated with concurrent chemoradiotherapy (CCRT) plus thalidomide.METHODS Sixty-five eligible patients with local middle-late esophageal carcinoma were randomly assigned to the treatment group (TG) and the control group (CG). The 33 patients from the TG were treated with CCRT plus thalidomide (a 60-70 Gy of radiation dose, and 5-FU plus cisplatin; oral administration of thalidomide at a dose of 100 mg/d on the first week and 200 mg/d on the second. Both were taken with water, at bedtime until completion of the radiotherapy. In the CG, 32 patients received CCRT only. The clinical effects and tolerance to the CCRT between the 2 groups were compared.RESULTS The response rates of the therapeutic combination in the TG and CG were 87.9% and 68.7%, respectively. There were no statistical differences in comparing the response rates between the 2 groups (P 〉 0.05); the local control rates in the TG and CG were 93% and 91%, respectively, and there were no statistical differences between the 2 groups (P 〉 0.05); the 1-year survival rates of the patients in the TG and CG were 74.0% and 63.0%, respectively, without statistical differences between the 2 groups (P 〉 0.05). The improvement rates of KPS scoring in the TG and CG were 57.6% and 31.3%, respectively. There were significant differences in comparing the improvement rates between the 2 groups (P 〈 0.05). The incidence rates of nausea and vomiting were lower in the TG compared to the CG, with a statistical significance between the 2 groups (P 〈 0.05). However, the incidence rates of constipation, lethargy and fatigue were higher in the TG than in CG, showing a statistically significant difference between the 2 groups (P 〈 0.05). CONCLUSION CCRT combined with thalidomide in treating esophageal carcinoma may improve the quality of life of the patients, the treatment may also raise patients' compliance to chemoradiotherapy, and possibly increase their long-term survival rate. Further studies related to this topic are needed.展开更多
文摘Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: Human stom- ach neoplasms model was established in nude mice. The nude mice were divided into control group, moderate-dose of rhGH group, low-dose rhGH group, 5-FU group, moderate-dose rhGH/5-FU group, and low-dose rhGH/5-FU group. The results of each group were observed after ten days. Results: After therapy, the body mass of rhGH groups was significantly increased compared with control group (P<0.05), the body mass of rhGH/5-FU groups was significantly increased compared with 5-FU group (P<0.05), but it was no significant difference between rhGH/5-FU groups and control group (P>0.05). The average tumor mass and volume of rhGH groups were not significantly increased compared with control group (P>0.05), but they were significantly reduced in 5-FU group and rhGH/5-FU groups (P<0.05). They were no significant difference between rhGH/5- FU groups and 5-FU group (P>0.05). After treatment, the percentages of S, G0/G1 and G2/M phases and proliferation index (PI) were not significantly changed in rhGH groups compared with control group (P>0.05), and the same with rhGH/5-FU groups compared with 5-FU group (P>0.05). The difference caused by dose of rhGH was not significant. Conclusion: rhGH enhances body mass, does not stimulate tumor growth, and has no adverse effects on tumor bearing nude mice. Combined with flurouracil, rhGH does not influence the efficacy of chemotherapy, and has no effect on tumor cell cycle kinetics.
基金supported by Grant of Russian Science Foundation No.17-15-01263.
文摘Here,we discuss an important problem in medicine as development of efctive strategies for brain drug delivery.This problem is related to the blood-brain barrier(BBB),which is a“customs”controlling the entrance of different molecules from blood into the brain protecting the normal function of central nervous system(CNS).We show three interfaces of anatomical side of BBB and two functional types of BBB一physical and transporter barriers.Although this protective mechanism is essential for health of CNS,it also creates a hindrance to the entry of drugs into the brain.The BBB was discovered over 100 years ago but till now,there is no efective methods for brain drug delivery.There ane more than 70 approaches for overcoming BBB incuding physical,chenical and biological techniques but all of these tools have limitation to be widely used in clinical practice due to invasi venes,challenge in performing,very costly or lim-itation of drug concentration.Photodynamic therapy(PDT)is usual clinical method of surgical navigation for the resection of brain tumor and anti-cancer therapy.Nowadays,the application of PDT is considered as a potential promising tool for brain drug delivery via opening of BBB.Here,we show the first sucoessful experimental results in this field discussing the adventures and disadv antages of PDT-related BBB disruption as well as altematives to overcome these limitations and possi ble mechanisms with new pathways for brain clearance via gly mphatic and lymphatic systems.
基金supported by grants from Sanming Project of Medicine in Shenzhen(No.SZSM202211030)the Science and Technology Department Basic Research Project of Shanxi(No.202203021221284)。
文摘Objective:Several studies have been conducted on the effects and toxicity of adding oxaliplatin to fluorouracilbased or capecitabine-based chemoradiotherapy(CRT)regimens as significantly increasing the toxic response without benefit to survival.In this study,we further explored the role of these two postoperative CRT regimens in patients with pathological stage N2 rectal cancer.Methods:This study was a subgroup analysis of a randomized clinical trial.A total of 180 patients with pathological stage N2 rectal cancer were eligible,85 received capecitabine with radiotherapy(RT),and 95 received capecitabine and oxaliplatin with RT.Patients in both groups received adjuvant chemotherapy[capecitabine and oxaliplatin(XELOX);or fluorouracil,leucovorin,and oxaliplatin(FOLFOX)]after CRT.Results:At a median follow-up of 59.2[interquartile range(IQR),34.0−96.8]months,the three-year diseasefree survival(DFS)was 53.3%and 64.9%in the control group and the experimental group,respectively[hazard ratio(HR),0.63;95%confidence interval(95%CI),0.41−0.98;P=0.04].There was no significant difference between the groups in overall survival(OS)(HR,0.62;95%CI,0.37−1.05;P=0.07),the incidence of locoregional recurrence(HR,0.62;95%CI,0.24−1.64;P=0.33),the incidence of distant metastasis(HR,0.67;95%CI,0.42−1.06;P=0.09)and grade 3−4 acute toxicities(P=0.78).For patients with survival longer than 3 years,the conditional overall survival(COS)was significantly better in the experimental group(HR,0.39;95%CI,0.16−0.96;P=0.03).Conclusions:Our results indicated that adding oxaliplatin to capecitabine-based postoperative CRT is safe and effective in patients with pathological stage N2 rectal cancer.
基金Supported by the National Science Foundation of China,No.39270650
文摘AIMS Using a new approach of regional adjuvant chemotherapy to prevent cancer cells hepatic metasta- sis after radical surgery of large bowel cancer. METHODS A model of liver with metastasis of hu- man colonic cancer (HCC) cells in nude mice was used to observe the effect in prevention of metastasis of HCC cells inoculated via spleen applied with early postoper- ative intraperitoneal (IP) chemotherapy using large dose of 5-FU. RESULTS The incidence of metastasis to liver was decreased by 40%,the mean number of metastatic liv- er nodules in each animal was reduced by 50.89% and the mean survival times of each animal was prolonged by 48.21% by using 5-FU 40 mg/NS 40 ml/kg IP for two consecutive days as compared with the controls. CONCLUSIONS IP is a new and more effective re- gional adjuvant chemotheraputic approach in the pre- vention of liver metastasis HCC cells after radical surgery of large bowel cancer.
文摘INTRODUCTIONIn China,primary liver cancer (PLC) ranks secondin cancer mortality since the 1990s.In the field ofPLC treatment,surgical resection remains the best,which includes large PLC resection,small PLCresection,re-resection of subclinical recurrence,aswell as cytoreduction and sequential resection forunresectable PLC.However,recurrence
基金the National Natural Science Foundation of China,No.39370780
文摘AIM To investigate the interference ofmethionine.free parenteral nutrition plus 5-Fu(-MetTPN+5-Fu)in gastric cancer cell kineticsand the side effects of the regimen.METHODS Fifteen patients with advancedgastric cancer were randomly divided into twogroups,7 patients were given preoperatively aseven-day course of standard parenteralnutrition in combination with a five-day courseof chemotherapy(sTPN+5-Fu),while the other8 patients were given methionine-deprivedparenteral nutrition and 5-Fu(-MetTPN+5-Fu).Cell cycles of gastric cancer and normal mucosawere studied by flow cytometry(FCM).Bloodsamples were taken to measure the serumprotein,methionine(Met)and cysteine(Cys)levels,and liver and kidney functions.RESULTS As compared with the resultsobtained before the treatment,the percentage ofG<sub>0</sub>/G<sub>1</sub> tumor cells increased and that of S phasedecreased in the-MetTPN+5-Fu group,while thecontrary was observed in the sTPN+5-Fu group.Except that the ALT,AST and AKP levels wereslightly increased in a few cases receiving-MetTPN+5-Fu,all the other biochemicalparameters were within normal limits.Serum Cys level decreased slightly after the treatmentin both groups.Serum Met level of patientsreceiving sTPN+5-Fu was somewhat higher aftertreatment than that before treatment;however,no significant change occurred in the -MetTPN+5-Fu group,nor operative complications in bothgroups.CONCLUSION -MetTPN+5-Fu exerted asuppressive effect on cancer cell proliferation,probably through a double mechanism ofcreating a state of'Met starvation'adverse tothe tumor cell cycle,and by allowing 5-Fu to killspecifically cells in S phase.Preoperative short-term administration of -MetTPN+5-Fu had littleundesirable effect on host metabolism.
文摘INTRODUCTIONAlthough the long-term postoperative survival rateof gastric cancer(GC) patients has been improvedsignificantly since the local dissection of lymph nodewas widely used in China,yet the low curativeresection rate and the high recurrence rate fromperitoneal and hepatic metastases hinder it fromfurther improvement.To alter the currentunsatisfactory status of GC treatment,a
文摘Objective: Early assessment of response to neoadjuvant chemotherapy (NAC) for breast cancer allows therapy to be individualized. The optimal assessment method has not been established. We investigated the accuracy of automated breast ultrasound (ABUS) to predict pathological outcomes after NAC. Methods: A total of 290 breast cancer patients were eligible for this study. Tumor response after 2 cycles of chemotherapy was assessed using the product change of two largest perpendicular diameters (PC) or the longest diameter change (LDC). PC and LDC were analyzed on the axial and the coronal planes respectively. Receiver operating characteristic (ROC) curves were used to evaluate overall performance of the prediction methods. Youden's indexes were calculated to select the optimal cut-off value for each method. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) and the area under the ROC curve (AUC) were calculated accordingly.Results: ypT0/is was achieved in 42 patients (14.5%) while ypT0 was achieved in 30 patients (10.3%) after NAC. All four prediction methods (PC on axial planes, LDC on axial planes, PC on coronal planes and LDC on coronal planes) displayed high AUCs (all〉0.82), with the highest of 0.89 [95% confidence interval (95% CI), 0.83-0.95] when mid-treatment &BUS was used to predict final pathological complete remission (pCR). High sensitivities (85.7%-88.1%) were observed across all four prediction methods while high specificities (81.5%-85.1%) were observed in two methods used PC. The optimal cut-off values defined by our data replicate the WHO and the RECIST criteria. Lower AUCs were observed when mid-treatment ABUS was used to predict poor pathological outcomes. Conclusions:ABUS is a useful tool in early evaluation of pCR after NAC while less reliable when predicting poor pathological outcomes.
基金supported by Chinese Medical Foundation (CMF, No. 313.2215)
文摘Objective: In patients with chemotherapy-induced amenorrhea (CIA), the menopausal status is ambiguous anddifficult to evaluate. This study aimed to establish a discriminative model to predict and classify the menopausalstatus of breast cancer patients with CIA.Methods: This is a single center hospital-based study from 2013 to 2016. The menopausal age distribution andaccumulated incidence rate of CIA are described. Multivariate models were adjusted for established and potentialconfounding factors including age, serum concentration of estradiol (E2) and follicle-stimulating hormone (FSH),feeding, pregnancy, parity, abortions, and body mass index (BMI). The odds ratio (OR) and 95% confidenceinterval (95% CI) of different risk factors were estimated.Results: A total of 1,796 breast cancer patients were included in this study, among whom, 1,175 (65.42%) werepremenopausal patients and 621 (34.58%) were post-menopause patients. Five hundred and fifty patients wereincluded in CIA analysis, and a cumulative CIA rate of 81.64% was found in them. Age (OR: 1.856, 95% CI:1.732-1.990), serum concentration of E2 (OR: 0.976, 95% CI: 0.972-0.980) and FSH (OR: 1.060, 95% CI:1.053-i.066), and menarche age (OR: 1.074, 95% CI: 1.009-1.144) were found to be associated with the patients'menopausal status. According to multivariate analysis, the discriminative model to predict the menopausal status isLogit (P)=-28.396+0.536Age-0.014E2+0.031FSH. The sensitivities for this model were higher than 85%, and itsspecificities were higher than 89%.Conclusions: The discriminative model obtained from this study for predicting menstrual state is important forpremenopausal patients with CIA. This model has high specificity and sensitivity and should be prudently used.
文摘BACKGROUND Although pathological response is a common endpoint used to assess the efficacy of neoadjuvant chemotherapy (NAC) for gastric cancer, the problem of a low rate of concordance from evaluations among pathologists remains unresolved. Moreover, there is no globally accepted consensus regarding the optimal evaluation. A previous study based on a clinical trial suggested that pathological response measured using digitally captured virtual microscopic slides predicted patients’ survival well. However, the pathological concordance rate of this approach and its usefulness in clinical practice were unknown. AIM To investigate the prognostic utility of pathological response measured using digital microscopic slides in clinical practice. METHODS We retrospectively evaluated pathological specimens of gastric cancer patients who underwent NAC followed by surgery and achieved R0 resection between March 2009 and May 2015. Residual tumor area and primary tumor beds were measured in one captured image slide, which contained the largest diameter of the resected specimens. We classified patients with < 10% residual tumor relative to the primary tumorous area as responders, and the rest as non-responders;we then compared overall survival (OS) and relapse-free survival (RFS) between these two groups. Next, we compared the prognostic utility of this method using conventional Japanese criteria. RESULTS Fifty-four patients were evaluated. The concordance rate between two evaluators was 96.2%. Median RFS of 25 responders and 29 non-responders was not reached (NR) vs 18.2 mo [hazard ratio (HR)= 0.35, P = 0.023], and median OS was NR vs 40.7 mo (HR = 0.3, P = 0.016), respectively. This prognostic value was statistically significant even after adjustment for age, eastern cooperative oncology group performance status, macroscopic type, reason for NAC, and T- and Nclassification (HR = 0.23, P = 0.018). This result was also observed even in subgroup analyses for different macroscopic types (Borrmann type 4/non-type 4) and histological types (differentiated/undifferentiated). Moreover, the adjusted HR for OS between responders and non-responders was lower in this method than that in the conventional histological evaluation of Japanese Classification of Gastric Carcinoma criteria (0.23 vs 0.39, respectively). CONCLUSION The measurement of pathological response using digitally captured virtual microscopic slides may be useful in clinical practice.
基金Supported in part by phone-Poulenc Rorer Pharmaceuticals INC
文摘INTRODUCTIONDevelopment of drug-resistance to chemotherapyand subsequent metastasis of tumor are primarilyresponsible for treatment failure and the death fromcancer. There have been many previous studies onthe relationship between expression of multidrugresistance (MDR) phenotype P-glycoprotein (P-gp)and the malignant properties of tumors, but theresults are often conflicting[1-8]. The difference intumor types or MDR phenotype induced by specificagents might account for this discrepancy. Taxotere(TXT), a member of the family of taxanes, hasantitumor activity through its effect of promotingthe polymerization of tubulin[9,10].
基金funded by the Key Project of Gansu Province, No.2GS054-A43-014-19
文摘One hundred patients with focal epilepsy were recruited for the present study and their seizures controlled with antiepileptic drugs. The patients then orally received a capsule of tall gastrodis tuber powder, a traditional Chinese drug, and underwent single photon emission computed tomography, long-term electroencephalogram, and CT/MRI. Blood drug levels were monitored throughout the study. Before treatment with tall gastrodis tuber, 35 of the 100 cases had abnormal CT/MRI scans; 79 cases had abnormal single photon emission computed tomography images; 86 cases had abnormal electroencephalogram; and a total of 146 abnormal perfusion foci were observed across the 100 subjects. After treatment, the number of patients with normal single photon emission computed tomography images increased by 12; normal electroencephalogram was observed in an additional 27 cases and the number of patients with epileptiform discharge decreased by 29 (34% of 86); the total number of abnormal perfusion foci decreased by 52 (36%) and changes in abnormal loci were visible in 65 patients. These changes indicate that the administration of tall gastrodis tuber in combination with antiepileptic drugs repairs abnormal perfusion foci in patients with focal epilepsy Our results demonstrate that traditional Chinese drugs can repair abnormal perfusion foci and, as such, are a promising new pathway in the treatment of focal epilepsy.
文摘Aside from the important role of brain natriuretic peptide (BNP) in diagnosis, and differential diagnosis of heart failure, this biological peptide has proved to be an independent surrogate marker of rehospitalization and death of the fatal disease. Several randomized clinical trials demonstrated that drugs such as beta blocker, angiotensin converting enzyme inhibitor, spiro- nolactone and amiodarone have beneficial effects in decreasing circulating BNP level during the management of chronic heart failure. The optimization of clinical decision-making appeals for a representative surrogate marker for heart failure prognosis. The serial point-of-care assessments of BNP concentration provide a therapeutic goal of clinical multi-therapy and an objective guid- ance for optimal treatment of heart failure. Nevertheless new questions and problems in this area remain to be clarified. On the basis of current research advances, this article gives an overview of BNP peptide and its property and role in the management of heart failure.
基金Supported by a faculty research grant of Yonsei University College of Medicine for 2002,No.2002-06
文摘AIM:rAAV mediated endostatin gene therapy has been examined as a new method for treating cancer.However, a sustained and high protein delivery is required to achieve the desired therapeutic effects.We evaluated the impact of topoisomerase inhibitors in rAAV delivered endostatin gene therapy in a liver tumor model. METHODS:rAAV containing endostatin expression cassettes were transduced into hepatoma cell lines.To test whether the topoisomerase inhibitor pretreatment increased the expression of endostatin,Western blotting and ELISA were performed.The biologic activity of endostatin was confirmed by endothelial cell proliferation and tube formation assays. The anti-tumor effects of the rAAV-endostatin vector combined with a topoisomerase inhibitor,etoposide,were evaluated in a mouse liver tumor model. RESULTS:Topoisomerase inhibitors,including camptothecin and etoposide,were found to increase the endostatin exPression level in vitro.The over-expressed endostatin, as a result of pretreatment with a topoisomerase inhibitor, was also biologically active.In animal experiments,the combined therapy of topoisomerase inhibitor,etoposide with the rAAV-endostatin vector had the best tumor- suppressive effect and tumor foci were barely observed in livers of the treated mice.Pretreatment with an etoposide increased the level of endostatin in the liver and serum of rAAV-endostatin treated mice.Finally,the mice treated With rAAV-endostatin in combination with etoposide showed the longest survival among the experimental models. CONCLUSION:rAAV delivered endostatin gene therapy in combination with a topoisomerase inhibitor pretreatment is an effective modality for anticancer gene therapy.
基金National Natural Science Foundation of China (No.30811120440)Shanghai Science and Technology Committee (No.08410701800)
文摘The application of nanotechnology significantly benefits clinical practice in cancer diagnosis, treatment, and management.Especially, nanotechnology offers a promise for the targeted delivery of drugs, genes, and proteins to tumor tissues and therefore alleviating the toxicity of anticancer agents in healthy tissues.This article reviews current nanotechnology platforms for anticancer drug delivery, including polymeric nanoparticles, liposomes, dendrimers, nanoshells, carbon nanotubes, superparamagnetic nanoparticles, and nucleic acid-based nanoparticles [DNA, RNA interference (RNAi), and antisense oligonucleotide (ASO)] as well as nanotechnologies for combination therapeutic strategies, for example, nanotechnologies combined with multidrug-resistance modulator, ultrasound, hyperthermia, or photodynamic therapy.This review raises awareness of the advantages and challenges for the application of these therapeutic nanotechnologies, in light of some recent advances in nanotechnologic drug delivery and cancer therapy.
文摘MIT method was applied to assay the cytotoxicityof three reversors, verapamil (VER), dipyridamole (DPM)and cyclosporin (CSA) in K562, K562/ADM and KB celllines. S-P immunocytochemical technique was applied todetect cxpressions of oncoproteins or tumor suppressoroncoproteins in these tumor cell lines before or aftertreatment with these reversors. Results showed that threereversors were capable of inhibiting to a certain extentgrowth of K562 or KB cell lines and reversing greatlyadriamycin (ADM)-resistance in K562/ADM cell line.DPM and CsA were observed to inhibit, partly or wholly,expressions of p53, p16, bcl-2, p21 or cerbB-2oncoproteins. VER showed whole inhibition ofexpressions of P53, p16, p21 and bcl-2 and partlyexpression of p53 oncoprotein in K562 cell line. Theseresults suggest that growth inhibition in K562 or KB celllines by the reversors may be associated with partial orwhole inhibition or expressions of p53, p16, p21 or c-erbB-2 oncoproteins. Inhibitions of expressions p53, p16,p21 oncoproteins by VER but not DPM or CsA, may berespossible for reversing activity of VER for ADM-resistance in K562/ADM cell line.
基金MT was funded by the Leistungsorientierte Mittelvergabe(LOM)scholarship offered by the medical faculty of Magdeburg and the Deutscher Akademischer Austauschdienst(DAAD).
文摘Apoptosis,a key mechanism of programmed cell death,is triggered by caspase-3 protein and lowering its levels with gene therapy may rescue cell death after central nervous system damage.We developed a novel,non-viral gene therapy to block caspase-3 gene expression using small interfering RNA(siRNA)delivered by polybutylcyanoacrylate nanoparticles(CaspNPs).In vitro CaspNPs significantly blocked caspase-3 protein expression in C6 cells,and when injected intraocularly in vivo,CaspNPs lowered retinal capsase-3 immunofluorescence by 57.9%in rats with optic nerve crush.Longitudinal,repeated retinal ganglion cell counts using confocal neuroimaging showed that post-traumatic cell loss after intraocular CaspNPs injection was only 36.1%versus 63.4%in lesioned controls.Because non-viral gene therapy with siRNA-nanoparticles can selectively silence caspace-3 gene expression and block apoptosis in post-mitotic neurons,siRNA delivery with nanoparticles may be promising for neuroprotection or restoration of central visual system damage and other neurological disorders.The animal study procedures were approved by the German National Act on the use of experimental animals(Ethic Committee Referat Verbraucherschutz,Veterinärangelegenheiten;Landesverwaltungsamt Sachsen-Anhalt,Halle,Germany,#IMP/G/01-1150/12 and#IMP/G/01-1469/17).
文摘The phamacogenetics is being used to predict whether the selected chemotherapy will be really effective and tolerable to the patient. Irinotecan,oxidized by CYP3A4 to produce inactive compounds,is used for treatment of various cancers including advanced non small cell lung cancer (NSCLC) patients. CYP3A4*16B polymorphism was associated with decreased metabolism of irrinotecan. Irinotecan is also metabolized by carboxylesterase to its principal active metabolite,SN-38,which is subsequently glucuronidated by UGT1As to form the inactive compound SN-38G. UGT1A1*28 and UGT1A1*6 polymorphisms were useful for predicting severe toxicity with NSCLC patients treated with irinotecan-based chemotherapy. Platinum-based compounds (cisplatin,carboplatin) are being used in combination with new cytotoxic drugs such as gemcitabine,paclitaxel,docetaxel,or vinorelbine in the treatment of advanced NSCLC. Cisplatin activity is mediated through the formation of cisplatin-DNA adducts. Gene polymorphisms of DNA repair factors are therefore obvious candidates for determinants of repair capacity and chemotherapy efficacy. ERCC1,XRCC1 and XRCC3 gene polymorphisms were a useful marker for predicting better survival in advanced NSCLC patients treated with platinum-based chemotherapy. XPA and XPD polymorphisms significantly increased response to platinum-based chemotherapy. These DNA repair gene polymorphisms were useful as a predictor of clinical outcome to the platinum-based chemotherapy. EGFR kinase inhibitors induce dramatic clinical responses in NSCLC patients with advanced disease. EGFR gene polymorphism in intron 1 contains a polymorphic single sequence dinucleotide repeat (CA-SSR) showed a statistically significant correlation with the gefitinib response and was appeared to be a useful predictive marker of the development of clinical outcome containing skin rashes with gefitinib treatment. The other polymorphisms of EGFR were also associated with increased EGFR promoter activity. EGFR gene mutations and polymorphisms were also associated with EGFR kinase inhibitors response and toxicity.
文摘BACKGROUNDIntracranial Listeria infections are common in newborns and immunocompromisedindividuals, but brainstem abscesses are rare.CASE SUMMARYWe report a rare case of brainstem abscesses caused by Listeria monocytogenes in apreviously healthy adult patient. The patient’s magnetic resonance imagingexamination showed multiple brain abscesses, and his second cerebrospinal fluidculture test indicated the presence of Listeria monocytogenes. Despite earlyempirical therapy, the patient’s condition progressively deteriorated. Because thepatient's abscesses were located in the brainstem and multiple lobes, surgery wasnot possible. The patient died 40 d after admission.CONCLUSIONThis case highlights the importance of rational clinical use of drugs to avoidpotentially serious infectious complications.
文摘OBJECTIVE To evaluate the response rate and tolerance of patients with middle-late esophageal carcinoma, who were treated with concurrent chemoradiotherapy (CCRT) plus thalidomide.METHODS Sixty-five eligible patients with local middle-late esophageal carcinoma were randomly assigned to the treatment group (TG) and the control group (CG). The 33 patients from the TG were treated with CCRT plus thalidomide (a 60-70 Gy of radiation dose, and 5-FU plus cisplatin; oral administration of thalidomide at a dose of 100 mg/d on the first week and 200 mg/d on the second. Both were taken with water, at bedtime until completion of the radiotherapy. In the CG, 32 patients received CCRT only. The clinical effects and tolerance to the CCRT between the 2 groups were compared.RESULTS The response rates of the therapeutic combination in the TG and CG were 87.9% and 68.7%, respectively. There were no statistical differences in comparing the response rates between the 2 groups (P 〉 0.05); the local control rates in the TG and CG were 93% and 91%, respectively, and there were no statistical differences between the 2 groups (P 〉 0.05); the 1-year survival rates of the patients in the TG and CG were 74.0% and 63.0%, respectively, without statistical differences between the 2 groups (P 〉 0.05). The improvement rates of KPS scoring in the TG and CG were 57.6% and 31.3%, respectively. There were significant differences in comparing the improvement rates between the 2 groups (P 〈 0.05). The incidence rates of nausea and vomiting were lower in the TG compared to the CG, with a statistical significance between the 2 groups (P 〈 0.05). However, the incidence rates of constipation, lethargy and fatigue were higher in the TG than in CG, showing a statistically significant difference between the 2 groups (P 〈 0.05). CONCLUSION CCRT combined with thalidomide in treating esophageal carcinoma may improve the quality of life of the patients, the treatment may also raise patients' compliance to chemoradiotherapy, and possibly increase their long-term survival rate. Further studies related to this topic are needed.