The miR-17-92 cluster,consisting of six individual microRNAs,including miR-17,miR-20a,miR-18a,miR-19a,miR-19b and miR-92a-1,is a kind of typical oncogenic polycistron microRNA.MiR-19 (containing miR-19a and miR-19b),as the key oncogenic component in miR-17-92 cluster,is overexpressed in human cancers including lymphomas,leukaemia,lung cancer,breast cancer and multiple myeloma,and has been one of research focus in recent years.It is found that miR-19 promotes tumor growth,invasion and metastasis through negative regulation of target genes such as PTEN,PP2A,Bim,SOCS1,and is correlated strongly with PI3K-AKT-mTOR pathway.MiR-19 plays an important role in tumor genesis and development.

Objective To investigate the irfluence of PET/CT positioning on the effect of late-course accelerated hyperfractionated and three-dimensional conformal radiotherapy for stage Ⅲ lung squamous cell carcinoma.Methods 79 stage Ⅲ lung squarnous cell carcinoma patients were enrolled and divided into PET/CT group(n =37 cases,PET/CT positioning) and general CT group (n =42 cases,general CT positioning) according to the way of positioning.The conventional fractionated 3 DCRT( about 40 Gy) was used in previous 2/3 time and hyperfractionated( about 1.5 Gy) was used in later 1/3 time.Both groups used chemotherapy as adjuvant therapy.Full course of the treatment was a month or so.And the clinical efficacy and a variety of adverse reactions of the two groups was observed.Results The total rate of remission in PET/CT group were 73.0％,and 71.4％ in general CT group,and there was no significant difference in the two groups (x2 =1.347,P ＞ 0.05 ).The major radiation injury were radioactive pulmonary injury and tracheal damage,incidence rates were 56.8％and 57.1％ in acute stage,and there was no significant difference in the two groups( x2 =2.178,P ＞ 0.05 ) ; but in late stage 69.0％ in general CT group was significantly higher than 62.2％ in PET/CT group(x2 =4.142,P ＜0.05).Ater followed-up 1 year,the recurrence rate of hillar and mediastinal lymph node in PET/CT group was 43.7％,lower than that of the general CT group( 59.4％ ) ( x2 =4.732,P ＜ 0.05 ).Conclusion PET/CT positioning in late-course accelerated hyperfractionated and three-dimensional conformal radiotherapy for stage Ⅲ lung squamous cell carcinoma could reduce late stage radioactive pulmonary injury and tracheal damage,lower the recurrence rate of hillar and mediastinal lymph node.

Objective To study the inhibitory effect of knocking down miR-30a-5p on the U87 human glioma xenograft growth and its possible mechanism.Methods Nude mice bearing subcutaneous U87 human glioblastoma were established and separated into three groups (eight for each group) by randomized digital table method,including control group,scr-ODN treated group and AS-miR-30a-5p treated group.After relevant subcutaneous injection treatment,tumor size was measured every other day until the observation period ended.Researchers executed the animals after the treatment,stripped tumor tissues and extracted RNA and protein.Real-time PCR was conducted to detect the expression of miR-30a-5p.The histopathological characteristics and proliferation and apoptosis biological characters (including SEPT7,PCNA,cyclin D1,MMP-2,apoptosis related factor P53,bcl-2 and caspase3) were evaluated by HE and immunohistochemical staining,Westem blot analysis respectively,and the cell apoptosis was detected by TUNEL method.Results In AS-miR-30a-5p treated group,the tumor growth was delayed and the final tumor volume was smaller than that in the control and scr-ODN treated group (F =7.167,P ＜0.05),and the expression of miR-30a-5p was knocked down.The expression of PCNA,cyclin D1 were significantly downregulated while P53,SEPT7 and caspase3 up-regulated.Apoptotic index was increased significantly.Conclusion As-miR-30a-5p suppresses the growth of U87 human gliomas xenografts significantly.Malignant phenotype of tumors are reversed to a considerable degree.Therefore,miR-30a-5p can be a candidate for targeted therapy of human glioma.

BACKGROUNDBrain metastasis has become one of the most important factors of the failure of treatment of locally advanced non-small cell lung cancer (LANSCLC). There is no conclusion whether NSCLC patients should receive prophylactic cranial irradiation (PCI) or not. The aim of this study is to analyze the risk factors of brain metastasis of LANSCLC after surgery to find out the sign of PCI for LANSCLC.

METHODSA total of 223 patients with stage III NSCLC who received surgical resection were retrospectively analyzed. The risk factors of brain metastasis were determined to set up a mathematic model for brain metastasis.

RESULTSThe median survival time after surgery was 28.0 months. The 1-, 2- and 3-year survival rate was 84.3%, 56.9% and 44.8% respectively. The incidence of brain metastasis was 38.1% (85/223). Patients with extensive mediastinal lymph node metastasis, more node metastasis and non-squamous carcinoma showed significantly higher incidence of brain metastasis than those with limited mediastinal lymph node metastasis, fewer positive mediastinal lymph nodes and squamous carcinoma (P=0.000, P=0.000, P=0.013). The mathematic model of brain metastasis was: logit(P)=8.215-0.903×NPN-0.872×RT-0.714×HG-1.893×LE-0.948×HS-1.034×PC (NPN=No. of positive nodes, RT=resection type, HG=histology, LE=location and extent of mediastinal lymph node metastasis, HS=histologic stage, PC=postoperative chemotherapy). P≥0.44 meant high risk for brain metastasis.

CONCLUSIONSHigh risk factors of brain metastasis in LANSCLC patients after complete resection of the cancer include non-squamous carcinoma, extensive and more mediastinal lymph node metastasis. P≥0.44 may be considered a sign of PCI in clinical trial.

OBJECTIVESTo identify predictors of survival following pneumonectomy for non-small cell lung cancer (NSCLC) and provide evidence for the revision of patient selection criteria.

METHODS81 cases of pneumonectomy for NSCLC from January 1990 to May 1996 at our hospital were reviewed retrospectively. There were 65 men (80.2%) and 16 women (19.8%), with a mean age 53.4 +/- 9.4 years (range 20 - 68 years). Predominant histological types included squamous cell carcinoma (54.3%), adenocarcinoma (24.7%), and squamoadenocarcinoma (17.3%). After follow-up for more than 5 years, data were examined using the chi-square test, Kaplan-Meier method, and Cox-mantel test. The possible factors affecting survival were tested with univariate and multivariate analysis.

RESULTSThe 5-year survival of N(0), N(1) and N(2) disease of NSCLC following pneumonectomy was (20.8 +/- 9.9)%, (15.4 +/- 10.0)% and (4.0 +/- 2.8)%, respectively. There was no perioperative death. The operative complications morbidity was 22.2%. Factors adversely affecting survival with univariate analysis included age over 60 years for right pneumonectomy, cardiopulmonary complications, adenocarcinoma, peripheral location, tumor greatest dimension more than 10 cm, chest wall involvement and N(2) disease. Factors adversely affecting survival with multivariate analysis included cardiopulmonary complications, greatest tumor dimension more than 10 cm, chest wall involvement and N(2) disease.

CONCLUSIONSPneumonectomy provides survival benefit with a high operative complications morbidity. Old age (>/= 60 years) for right pneumonectomy, cardiopulmonary complications, adenocarcinoma, and N(2) disease may be negative prognostic factors of long-term survival. Patient selection should be based on cardiopulmonary evaluation and the stage of disease.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; mortality ; pathology ; surgery ; Female ; Humans ; Lung Neoplasms ; mortality ; pathology ; surgery ; Male ; Middle Aged ; Neoplasm Staging ; Pneumonectomy ; Prognosis ; Retrospective Studies ; Survival Rate

OBJECTIVETo evaluate the value of mediastinoscopy in diagnosing unknown mediastinal disease and staging of lung cancers.

METHODSFrom October 2000 to August 2001, 41 patients were examined by cervical mediastinoscopy with or without anterior mediastinotomy for diagnostic and staging purposes. Of these 41 patients, 12 were for diagnosis of unknown mediastinal disease, 3 for diagnosis and staging of pulmonary nodule or mass clinically suspected to be malignancy and 26 for the staging of lung cancer.

RESULTSTen of 12 patients with unknown mediastinal disease were diagnosed pathologically as thymoma in 1, metastatic lesion from lung cancer in 1, metastatic thyroid carcinoma in 1, lymph node hyperplasia in 1, teratoma in 1, sarcoidosis in 1, inflammatory pseudotumor in 1 and tuberculosis in 3, giving a diagnostic rate of 83.3%. Of three patients with suspected malignancy, one was diagnosed as tuberculosis by cervical mediastinoscopy and the other two as lymphoma and pulmonary inflammatory pseudotumor by thoracoscopy and thoracotomy. The sensitivity and specificity of mediastinoscopy for the staging of mediastinal nodes in 26 lung cancers were 87.5% and 100%. Only one wound infection but no other major complication was found.

CONCLUSIONMediastinoscopy is a safe procedure which can accurately provide information on diagnosis and staging.

Adult ; Aged ; Female ; Humans ; Lung Neoplasms ; diagnosis ; Male ; Mediastinal Neoplasms ; diagnosis ; Mediastinoscopy ; Middle Aged ; Neoplasm Staging

OBJECTIVETo compare the short-term efficacy and treatment-related adverse reaction between preoperative three dimensional conformal radiotherapy (3D-CRT) and volumetric modulated arc therapy (VMAT) concurrently combined with chemotherapy in the treatment of locally advanced rectal carcinoma (LARC).

METHODSClinical data of 334 patients with LARC undergoing preoperative 3D-CRT(172 cases) or VMAT(162 cases) with concurrent Xelox chemotherapy (main protocol: capecitabine plus oxaliplatin) and surgery in Sun Yat-sen University Cancer Center from May 2007 to April 2013 were retrospectively analyzed. The total radiation dose of VMAT group was: 50 Gy/2.0 Gy per fraction ×23 fractions for planning target volume 1(PTV1) and 46 Gy/1.84 Gy per fraction ×25 fractions for PTV2; the total radiation dose of 3D-CRT group was: 46 Gy/2.0 Gy per fraction ×23 fractions for PTV. The treatment-related adverse reaction of both groups during chemoradiotherapy was measured according to the criteria of Common Terminology Criteria for Adverse Events v3.0 (CTCAE 3.0). Rate of adverse reaction and short-term efficacy between 3D-CRT and VMAT group were compared, in terms of radiotherapy break, hematological and non-hematological toxicity, average duration of surgery and perioperative hospitalization, intraoperative blood loss, surgical procedures, R0 excision, sphincter preservation, postoperative complications, pathological complete response (pCR), and postoperative pathological staging.

RESULTSThere were no significant differences in baseline clinical parameters between 3D-CRT and VMAT group (all P>0.05), except for the distance from lower tumor margin to anal verge (P=0.009). The median radiation dose for all the patients was 46 (45 to 70) Gy. There was no significant difference in the rate of radiotherapy cessation between 3D-CRT and VMAT group [1.7%(3/172) vs. 1.2%(2/162), P=1.000]. During concurrent chemotherapy, incidences of grade 2 to 3 hematological toxicities, grade 2 diarrhea, and grade 3 non-hematological toxicities were not significantly different(all P>0.05), while in grade 2 non-hematological toxicities, ratio of radiodermatitis and hand-foot syndrome was higher in VMAT group as compared to 3D-CRT group [25.9%(42/162) vs. 10.5%(18/172), P=0.000; 3.7%(6/162) vs. 0, P=0.012]. There was no grade 4 adverse event in both groups. Surgical procedure, average duration of surgery, R0 excision, anus preservation, postoperative complications, pCR, and postoperative pathological staging were not significantly different(all P>0.05). As compared to 3D-CRT group, VMAT group had less intraoperative blood loss [(114.6±100) ml vs. (169±143.9) ml, P<0.001] and shorter perioperative hospitalization [16(8 to 84) d vs. 20(10 to 47) d, P<0.001]. There was no death case in two groups within 30 days after operation.

CONCLUSIONSCompared with 3D-CRT technique, preoperative VMAT technique can not significantly reduce the incidence of treatment-related adverse reaction and improve the short-term efficacy in the treatment of LARC.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Chemoradiotherapy ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Female ; Fluorouracil ; analogs & derivatives ; therapeutic use ; Humans ; Male ; Middle Aged ; Organoplatinum Compounds ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Conformal ; Radiotherapy, Intensity-Modulated ; Rectal Neoplasms ; radiotherapy ; Retrospective Studies

Sulfonylureas are widely used oral anti-diabetic drugs. However, its long-term usage effects on patients' lifespan remain controversial, with no reports of influence on animal longevity. Hence, the anti-aging effects of chlorpropamide along with glimepiride, glibenclamide, and tolbutamide were studied with special emphasis on the interaction of chlorpropamide with mitochondrial ATP-sensitive K⁺ (mitoK-ATP) channels and mitochondrial complex II. Chlorpropamide delayed aging in Caenorhabditis elegans, human lung fibroblast MRC-5 cells and reduced doxorubicin-induced senescence in both MRC-5 cells and mice. In addition, the mitochondrial membrane potential and ATP levels were significantly increased in chlorpropamide-treated worms, which is consistent with the function of its reported targets, mitoK-ATP channels. Increased levels of mitochondrial reactive oxygen species (mtROS) were observed in chlorpropamide-treated worms. Moreover, the lifespan extension by chlorpropamide required complex II and increased mtROS levels, indicating that chlorpropamide acts on complex II directly or indirectly via mitoK-ATP to increase the production of mtROS as a pro-longevity signal. This study provides mechanistic insight into the anti-aging effects of sulfonylureas in C. elegans.