Genetic mutations are important molecular biomarkers for cancer diagnosis and surveillance.Therefore,the development of methods for mutation detection characterized with straightforward,highly specific and sensitive to low-level mutations within various sequence contexts is extremely needed.Although some of the currently available methods have shown very encouraging results,their discrimination efficiency is still very low.Herein,we demonstrate a fluorescent probe coupled with blocker and property of melting temperature discrimination,which is able to identify the presence of known or unknown single-base variations at abundances down to 0.1％ within 20 min.The discrimination factors between the perfect-match target and single-base mismatched target are determined to be 10.15-38.48.The method is sequence independent,which assures a wide range of application.The new method would be an ideal choice for high-throughput in vitro diagnosis and precise clinical treatment.

Platinum-based anticancer drugs have been becoming one of the most effective drugs for clinical treatment of malignant tumors for its unique mechanism of action and broad range of anticancer spectrum. But, there are still several problems such as side effects, drug resistance/cross resistance and no-specific targeting, becoming obstacles to restrict its expanding of clinical application. In recent years, supramolecular chemistry drug delivery systems have been gradually concerned for their favorable safety and low toxicity. Supramolecular macrocycles-platinum complexes increased the water solubility, stability and safety of traditional platinum drugs, and have become hot focus of developing novel platinum-based anticancer drugs because of its potential targeting of tumor tissues/organs. This article concentrates in the research progress of the new drug delivery system between platinum-based anticancer drugs with three generations of macrocycles: crown ether, cyclodextrin, cucurbituril and calixarene.
Antineoplastic Agents ; pharmacology ; Calixarenes ; Crown Compounds ; Cyclodextrins ; Drug Delivery Systems ; Humans ; Macrocyclic Compounds ; pharmacology ; Neoplasms ; drug therapy ; Platinum Compounds ; pharmacology

The present study was to investigate the effect of glucagon like peptide-1 (GLP-1) on high glucose-induced oxidative stress of cardiomyocytes and the possible role of the PI3K-Akt signal path in this process in the neonatal SD rats. With enzymatic digestion and immunofluorescence identification, cardiomyocytes after 72-96 h of primary culture were used in experiment. The cells were divided into 5 groups: normal control group, high glucose group, high glucose + GLP-1 group, high glucose + GLP-1 + LY294002 group and high osmolarity control group. The content of MDA was detected by TBA colouration method. The content of SOD was detected by xanthine oxidase method. The change of NADPH P47phox subunit mRNA quantity was detected by PCR gel electrophoresis. The level of ROS was detected by flow cytometry, and was also observed by fluorescence microscope. The DNA ladder was examined by agarose gel electrophoresis, and the cell apoptosis was determined by Annexin-V-FITC/PI flow cytometry, and the phosphorylation of Akt was determined by Western blotting. Compared with those in the normal control group, in the high glucose group, the cells grew poorly, and the beating rate was significantly lower (P < 0.05); The apoptotic rate was significantly increased (P < 0.05); The MDA content was increased (P < 0.05); It showed the typical DNA ladder, which is the characteristic of apoptosis; The SOD activity was decreased (P < 0.05); The level of intracellular ROS increased (P < 0.05); And the expression of NADPH P47phox subunit mRNA was increased; However the phosphorylation level of Akt was decreased. Pretreatment with GLP-1 improved the above-mentioned parameters and decreased the expression of NADPH P47phox subunit mRNA (P < 0.05). However, compared with the high glucose + GLP-1 group, LY294002, an inhibitor of PI3K-Akt signal path, attenuated the protective effect of GLP-1 in the high glucose + GLP-1 + LY294002 group. It is suggested that GLP-1 plays a protective role in the high glucose-induced injury and apoptosis of cardiomyocytes, and the PI3K-Akt signal path is involved in this process.
Animals ; Animals, Newborn ; Apoptosis ; drug effects ; Cells, Cultured ; Female ; Glucagon-Like Peptide 1 ; pharmacology ; Glucose ; pharmacology ; Male ; Myocytes, Cardiac ; cytology ; pathology ; Oxidative Stress ; drug effects ; Phosphatidylinositol 3-Kinases ; metabolism ; Protective Agents ; pharmacology ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction

The non-covalent interactions between 18-crown-6 (18c6) and 20 common types of protonated amino acids were explored by electrospray ionization mass spectrometry (ESI-MS).The mass spectra showed the formation of 1:1 stoichiometric non-covalent complexes between 18c6 and amino acids.The calibration curves and linear equations for the complexes of L-Phe,L-Tyr,L-Lys and L-Asp with 18c6 were established by mass spectrometric titration and used as reference values for competitive ESI-MS.Through competitive equilibrium,the binding constants for the complexes of 18c6 with other L-amino acids and their D-isomers were derived.It was found,as a general trend,lgKa for the complexes of 18c6 with the basic amino acid and the amino acid with alkyl side chain were larger than other complexes,and among the amino acids with alkyl side chain,Gly and Ala exhibited greater 18c6 binding affinities.As for Ser and Thr,the intramolecular hydrogen bond between the nitrogen atom from terminal NH2and the oxygen atom from carboxyl may impede their protonated amino-group to attack the 18c6.Furthermore,Gln and Asn exhibited lower 18c6 binding affinities probably due to effects of electron-withdrawing group of acylamide.Finally,the chiral selectivity of 18c6 for 19 L-,or D-amino acids was measured by ESI-MS,indicating 18c6 could only recognize some neutral amino acid isomers.

Objective To explore inhibition of amlodipine on myocar-dial cell injury induced by ischemia reperfusion .Methods Thirty Wistar rats were randomly into three groups: sham operation group ( n =10 ) , model group group ( n =10 ) , test group ( 2 mg? kg -1 amlodipine , n=10).The model group and test group were made by ligation of left anterior descending coronary artery to make the model of myocardial ischemia reperfusion.Rats in each group were administered 7 d before ligation.Cell apoptosis was examed by flow dual staining method .The activity of cysteinyl aspartate specific proteinase 3 ( Caspase 3 ) was measured by spectrophotometry .The activation of phosphatidylinositol 3 kinase ( PI3K)/protein kinase B ( AKT) signalling pathway, B-cell lymphoma-2 ( Bcl-2 ) , Bcl-2 associated X protein ( Bax ) were assayed by Western blot .Results Compared to sham operation group on early and late myocardial cell apoptosis , myocardial cell apoptosis with ( 2.34 ±0.35 )%, (3.58 ±0.39 )%, that on early and late myocardial cell apoptosis were increased with ( 15.69 ±1.14 )%, (24.74 ±2.56)%in model group ( P <0.05 ) .Compared to sham operation group on the activity of Bax with (0.18 ±0.01) and Caspase 3 activity with (1.00 ±0.10), the expression of Bax express with (0.62 ±0.06) and Caspase 3 activity with (3.98 ±0.18) in model group were increased (P<0.05).Compared to sham operation group on the expre-ssion of Bcl-2 with (0.99 ±0.10 ) and expression of PI3K with (0.89 ±0.06 ), on the expression of Bcl-2 with (0.14 ±0.01) and expression of PI3K with (0.18 ±0.01) in model group were decreased (P<0.05). Compared to sham operation group on phosphorylation of AKT with ( 0.95 ±0.10 ) , the phosphorylation of AKT in model group with (0.13 ±0.01 ) was decreased ( P<0.05 ).Compared with model group , test group could change the variation on the early and late myocardial cell apoptosis with ( 5.23 ±0.13 )%, ( 8.09 ±0.35 )% while on the Caspase 3 activity with ( 1.47 ±0.14 ) ( P<0.05 ) .Conclusion These results suggested that amlodipine inhibited myocardial ischemia reperfusion injury, which was related to activition PI3K/AKT signal pathway.

Objective To discuss the efficacy of Leucogen tablets treatment lessen the hematological reaction and raise the efficacy therapy of interferon in chronic hepatitis B treated with PEG-αinterferon and α interferon.Methods A total of 395 patients with HBeAg-positive chronic hepatitis B (CHB) inpatients from January 2002 to February 2011.Group:All the patients were assigned to A or B according as during the treatment added Leucogen tablets or not.Results ( 1 ) All of 35.9％ patients had neutrophil counts decrease under 1 × 109/L,A group had 29.6％,B had 42.8％ patients,P =0.01 ;neutrophil counts≤0.75 × 109/L A group had 12.6％,B group had 26.4％,P =0.02; neutrophil counts≤ 0.5 × 109/L A group had 4.8 ％,B group had 16.4％,P =0.04.(2) A group had 8.2％ patients interferon-α dose decreased,all the patient finished the period of therapy.B group had 23.3％ patients interferon-α dose decreased,2.1％ of patients had paused.A group had 40.3％ of patients interferon-α beyond conventional dose,B group had only 5.2％.(3)All of 9.8％ patients had hematoblast decrease under 100 × 109/L,A group had 8.7％,B had 11.1％ patients;hematoblast≤ 80 × 109/L A group had 5.3％,B group had 7.9％ ;hematoblast ≤ 50 × 109/L A group had 1.0％,B group had 2.6％.A group had the trend of reducing hematoblast decrease.(4) At the end of therapy A group had 67.4％ patients HBVDNA ＜ 100IU/ml,54.3％ e antigen negative,40.7％ e antigen conversed; B group had 53.9％,41.2％,26.9％,P was respectively 0.02,0.01,0.01.Conclusion Leucogen tablets treatment and prevention interferon-α-related neutrophil counts hematological reaction in CHB treated with a-interferon,and had the trend of reducing interferon-αrelated hematoblast decrease,farther improved the efficacy of α-interferon treatment CHB.

OBJECTIVETo compare the medial-to-lateral approach with the lateral-to-medial approach in laparoscopic right hemi-colectomy for right colon cancer.

METHODSA prospective randomized controlled trial was performed in the Fujian provincial tumor hospital between January 2007 and July 2009. Forty-eight cases with right colon cancer were randomly divided into two groups:medial-to-lateral laparoscopic right hemi-colectomy group(group M) and lateral-to-medial laparoscopic right hemi-colectomy group(group L). Primary outcome(operative time) and secondary outcomes (estimated blood loss, intra-operative complication, post-operative complication, number of lymph node retrieval, hospital stay) were compared between two groups.

RESULTSOperative time was(122.5+/-25.8) min in group M and (162.9+/-30.9) min in Group L (P=0.01). Estimated blood loss was(55.8+/-36.2) ml in group M and (104.6+/-58.2) ml in group L(P=0.01). There were no significant differences between the two groups in intra-operative complications(4.2% vs 8.3%, P=1.00), post-operative complications (8.3% vs 16.7%, P=0.66), number of lymph node retrieval (17.4+/-3.2 vs 17.8+/-3.4, P=0.67), and hospital stay[(7.8+/-2.2) d vs (8.0+/-3.6) d, P=0.81].

CONCLUSIONThe medial-to-lateral approach reduces operative time and blood loss in laparoscopic right hemi-colectomy as compared with the lateral-to-medial approach.

Adult ; Colectomy ; methods ; Colonic Neoplasms ; surgery ; Female ; Humans ; Laparoscopy ; Male ; Middle Aged ; Prospective Studies ; Treatment Outcome

OBJECTIVETo investigate the prognostic factors for nasopharyngeal carcinoma (NPC) with different metastatic status, and to improve the NPC management by multi-level refinement and stratification of M1 stage distant metastases.

METHODSClinicopathological data of 1016 NPC patients with distant metastases were retrospectively reviewed. The M1 stage distant metastases were subdivided into synchronous or metachronous metastases, metastatic sites (lung, bone, liver), number of metastatic organs (solitary, multiple) and number of metastases (solitary, multiple) subgroups to analyze the prognosis and survival of the patients.

RESULTSThe most frequently involved metastatic sites were bone (542, 53.3%), lung (420, 41.3%) and liver (302, 29.7%). There were solitary metastatic lesions in 164 patients (16.2%), synchronous metastases in 376 cases and metachronous metastases in 640 cases. The median overall survival of the whole group of 1016 NPC patients was 30.8 months since the time of diagnosis of metastasis. For the 376 patients in the synchronous metastasis group, the median survival was 23.3 months and the 1-, 3- and 5-year overall survival rates were 74.2%, 27.6% and 18.5%, respectively. For the 640 patients in the metachronous metastases group, the median survival was 36.7 months, and the 1-, 3- and 5-year overall survival rates were 88.1%, 49.6% and 28.6%, respectively, with a significant difference between the two groups (all P < 0.001). Cox multivariate analysis indicated that the number of metastatic lesions, different metastatic sites and N stage at initial diagnosis were independent prognostic factors for patients with metachronous metastases (P < 0.05).

CONCLUSIONSA theory of detailed multi-level metastasis (M1) stratification aiming at different distant metastasis status for nasopharyngeal carcinoma is proposed. To take appropriate individualized treatment scheme according to the prognosis and expected survival should be helpful to improving the diagnosis and treatment of nasopharyngeal cancer.

Adolescent ; Adult ; Aged ; Bone Neoplasms ; pathology ; secondary ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms ; pathology ; secondary ; Lung Neoplasms ; pathology ; secondary ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; pathology ; Neoplasm Staging ; Proportional Hazards Models ; Retrospective Studies ; Survival Rate ; Time Factors ; Young Adult

OBJECTIVETo investigate the expression of multidrug resistance (MDR) gene-associated proteins (MRP) in gastric carcinoma, and their effects on the postoperative adjuvant chemotherapy and the prognosis of patients.

METHODSThe expressions of ToPo II, MRP, GST-pi in 99 patients with gastric carcinoma were detected by immunohistochemistry. The expression and its relationship to the pathological data were analyzed. The positive expression of MRP and GST-pi, and the negative expression of ToPo II were considered as risk factors. Patients were divided into two groups: a high risk drug-resistant group (2-3 risk factors) and the low risk drug-resistant group (0-1 risk factors). Postoperative recurrence, survival rate, and efficacy of adjuvant chemotherapy were compared between two groups.

RESULTSThe positive rate of ToPo II was 74.7%, and the expression was associated with types and differentiation of the tumor. The positive rate of GST-pi was 49.5%, and the expression was related to the gender and the differentiation. The positive rate of MRP was 40.4%, and there was no relationship between the MRP expression and the pathological finding. There were no significant differences in the recurrence, time to recurrence, and the 5-year survival rate between the positive and negative group of the three proteins (P>0.05). Recurrence was found in 25 cases(55.6%) in the high risk drug-resistant group and the mean time to recurrence was (15.2+/-8.1) months. The time to recurrence was shorter in the low risk drug-resistant group [(21.3+/-11.1) months, P<0.05] , but there was no significant difference in the recurrence rate between two groups (P>0.05). The 5-year survival rate of the high risk drug-resistant group and the low risk drug-resistant group was 44.4% and 55.6% (P>0.05). The 5-year survival rates of patients with or without chemotherapy in the high risk drug-resistant group were 45.8% and 42.9% (P>0.05). The 5-year survival rates of patients with or without chemotherapy in the low risk drug-resistant group were 70.4% and 40.7%. The survival rate of patients with chemotherapy was higher than that of the patients without chemotherapy (P<0.05).

CONCLUSIONSThe expression of ToPo II, MRP and GST-pi is associated with the efficacy of postoperative adjuvant chemotherapy. Chemotherapy appears to be more beneficial to patients with low risk drug-resistance.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Adult ; Aged ; Chemotherapy, Adjuvant ; DNA Topoisomerases, Type II ; metabolism ; Female ; Glutathione S-Transferase pi ; metabolism ; Humans ; Male ; Middle Aged ; Multidrug Resistance-Associated Proteins ; metabolism ; Postoperative Period ; Prognosis ; Stomach Neoplasms ; diagnosis ; drug therapy ; metabolism

OBJECTIVETo discuss outcome of thyroid tumor patients treated with surgery.

METHODSTotal number of patients was 2228. These patients of thyroid tumors from 1992-2004 (2072 cases of benign thyroid diseases and 156 cases of thyroid carcinoma) were recruited. The clinical and follow-up datum were retrospective analyzed.

RESULTS(1) Benign thyroid tumors with near-total thyroidectomy including 1761 thyroid adenoma, 207 nodular goiter and 104 Hashimoto thyroiditis, the incidence of recurrent laryngeal nerve paralysis was 0.2%, 55 cases (2.6%) received secondary surgery. All the patients have no hypocalcemia or hemorrhage after operation. (2) Eighty-one cases of papillary carcinoma of the thyroid ( > 1 cm) and 60 cases of microcarcinoma. Unilateral thyroidectomy, contralateral near-total thyroidectomy and ipsilateral modified neck dissection were performed in unilateral papillary carcinoma of thyroid. Among the 9 cases of follicular carcinoma of thyroid, 7 were performed of near-total thyroidectomy without neck dissection, others were the same as papillary carcinoma. Bilateral total thyroidectomy and bilateral modified neck dissection were performed in 2 cases of the medullary thyroid cancer and 1 case of the undifferentiated thyroid cancer. By direct method the 5-year survival was 95.5% (64/67), and by Kaplan-Meier method, it was 98.0%. The treatment of microcarcinoma are multiple. There is no relapse or metastases in 60 cases of papillary thyroid microcarcinoma. The 5-year survival was 100.0%, 1 cases occurred recurrent laryngeal nerve paralysis in thyroid cancer. No hypocalcemia or hemorrhage. Eight case relapsed in 156 cases of thyroid carcinoma,3 cases died.

CONCLUSIONThe correct surgical management for the patients with thyroid tumor should benefit for the prognosis and reduce the complications and the recurrence of the operation.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Humans ; Male ; Middle Aged ; Neck Dissection ; Prognosis ; Retrospective Studies ; Survival Rate ; Thyroid Neoplasms ; mortality ; surgery ; Thyroidectomy ; Treatment Outcome ; Young Adult