1.Growth suppression of human lung cancer cells and implanted tumors by adenovirus-mediated transfer of the PTEN gene.
Journal of Huazhong University of Science and Technology (Medical Sciences) 2010;30(2):149-54
This study examined the effects of a recombinant adenovirus Ad-PTEN-EGFP on the proliferation of A549 cells, a human lung carcinoma cell line, in vitro and on the growth of the implanted tumors in the nude mice in vivo, explored the underlying mechanisms and evaluated the in vitro transfection efficiency of Ad-PTEN-EGFP into A549 cells. The expression of Ad-PTEN-EGFP in the A549 cells was determined. The proliferation and the apoptosis rates of the A549 cells with Ad-PTEN-EGFP transfection or not was detected by MTT and flow cytometry. Ad-PTEN-EGFP at different doses was injected intratumorally to the tumor-bearing mice induced by the A549 cells. Tumor sizes were measured on an alternate day. After all the mice were sacrificed, the implanted tumors were removed for routine histological examination, weight test, HE staining and immunohistochemical staining. The expressions of Bax, P16 and P53 in the tumor tissues and those of caspase-3, CD34 and VEGF in the mouse sera were detected. Tumor cell apoptosis was measured by TUNEL method. The results showed that the vitality of the A549 cells after transfection with Ad-PTEN-EGFP declined. The expression of green fluorescent protein was observed under fluorescent microscope. The transfection rate was in excess of 50%. The mRNA and protein expression of PTEN in the transfected cells was confirmed. The proliferation rate of the transfected cells was significantly decreased when compared with that of the non-transfected cells (P<0.05). The number of the apoptosis cells was increased in the transfected cells (P<0.05). The models of implanted tumors were successfully established by injection of the A549 cells in the flank of Balb/c nude mice. Administration of Ad-PTEN-EGFP to the tumor-bearing nude mice resulted in a suppression of tumor growth. There were statistically significant differences in the tumor weight and tumor volume between the Ad-PTEN-EGFP-treated group and the control groups (P<0.05). In contrast to those in the control groups, tumor tissues in the Ad-PTEN-EGFP-treated group were shown to have typical extensive vacuolar degeneration and massive hemorrhagic necrosis. Apoptotic bodies were also observed in the tumor cells. The expressions of Bax, caspase-3 and P16 were increased (P<0.05) while those of CD34, VEGF and P53 decreased (P<0.05) in the Ad-PTEN-EGFP-treated group. It is concluded that Ad-PTEN-EGFP could induce the apoptosis of the A549 cells and inhibit their proliferation. And it could also substantially suppress the tumor growth in the tumor-bearing nude mice and induce apoptosis of the tumor cells as well. These findings carry significant implications for adenovirus vector-based PTEN gene therapies for lung cancers.
2.Correlation between lysyl oxidase-like protein 2 and neoplasms and its mechanism
Journal of International Oncology 2012;39(4):246-248
Lysyl oxidase-like protein 2 (LOXL2) is one of the lysyl oxidases (LOX) families.At present,most of scholars consider that LOXL2 is a neoplasm metastasis gene,whereas some others belleve that LOXL2 is a neoplasm suppressor gene.Studies found that LOXL2 gene combined with other oncogenes promotes neoplasm invasion,metastasis and indicates a poor prognosis.Related researches provide new ideas for judging tumor metastasis and prognosis and looking for new targets for cancer therapy.
3.ATM and resistance of gliomas to chemotherapy and radiotherapy
Shiming ZHEN ; Lijuan YANG ; Zhixiong LIN
Journal of International Oncology 2011;38(7):506-509
The resistance mechanism of gliomas to chemotherapy and radiotherapy is a complex network of many signaling pathways. It remains unclearhow the pathways interact with each other and how they were regulated. Recent studies have shown that DNA damage checkpoint pathway ( ATM、 ATR、 Chk1、 Chk2、 Rad17、 Radl 、Rad9、Hus1 et al. ) plays an important role in cell proliferation、genomic stability、tumorigenesis and the resistance to chemoradiotherapy of tumors. Inhibiting DNA damage checkpoint can increase tumor sensitivity to chemoradiotherapy and therefore improve the therapeutic effect. We review here the role of ATM in chemoradiotherapy resistance of gliomas and its associated mechanisms.
4.Correlation and expression of COX-2 and P53 protein in basal cell carcinoma of eyelid.
Zhixiong, CHEN ; Jiong, YANG ; Qiong, HUANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2009;29(3):383-6
The correlation between the expression of COX-2 and p53 protein in basal cell carcinoma (BCC) of eyelid and apoptosis was investigated. Specimens of BCC were collected from 40 cases (aged 28-68 y) at the Department of Pathology, Renmin Hospital of Wuhan University, and Department of Pathology, Zhongnan Hospital of Wuhan University during from 1999 to 2006. Five specimens of paracancerous tissues served as control group. Immunohistochemical staining was performed to detect the expression of COX-2 and p53 in the tissues. The average absorbance (A) and the average positive area rate of COX-2 and p53 protein were measured by image analysis. The positive area rate of COX-2 and p53 protein was analyzed by linear correlation analysis. It was found that COX-2 and p53 proteins were highly expressed in BCC of eyelid, and weakly expressed in paracancerous tissues. Image analysis revealed that the expression of COX-2 and p53 proteins in BCC of eyelid was significantly higher than that in paracancerous tissues (P<0.01). Spearman rank correlation analysis demonstrated a positive correlation between the expression of COX-2 and p53 (r=0.113, P=0.421). It was concluded that COX-2 can increase the expression of p53 protein, therefore suppressing apoptosis.
Apoptosis
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Carcinoma, Basal Cell/*metabolism
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Cyclooxygenase 2/*metabolism
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Eyelid Neoplasms/*metabolism
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Tumor Suppressor Protein p53/*metabolism
5.Factors affecting the recovery of spinal functions in patients with spinal metastatic carcinoma
Sihai LIAO ; Zhixiong YANG ; Zhi TANG
Chinese Journal of Tissue Engineering Research 2006;10(8):166-167
BACKGROUND: Tumor spinal metastasis is often complicated with pain,limitations in movement, paralysis and poor prognosis.OBJECTIVE: To investigate the factors affecting the recovery of the spinal functions in patients with spinal metastatic carcinoma and its therapeutic methods so as to improve the living quality of the patients with a terminal cancer.DESIGN: A case-controlled observation.SETTING: The Department of Tumor and Department of Radiotherapy of the Affiliated Hospital of Guangdong Medical College.PARTICIPANTS: We selected 162 patients with spinal metastatic carcinoma with different degrees of paralysis who received treatment at the Department of Oncology and the Department of Radiotherapy of the Affiliated Hospital of Guangdong Medical College between March 1992 and June 2001. They participated in this experiment voluntarily.METHODS:①Radiotherapy and chemotherapy; All the patients were given symptomatic treatment with simple radiotherapy or a combined therapy of simple radiotherapy and chemotherapy, in which the dose of chemotherapy was 2 Gy/time,5 times a week,3 weeks in total. A combined method was used for chemotherapy according to the nature of the different primary tumors. The chemotherapy was conducted for 3 therapeutic courses in average ranging from 2 to 6 courses of treatment with 21 days for each course. ② Physical rehabilitation therapy included exercise therapy, massage (twice/day), functional electrical stimulation (once a day),bladder training and toilet training (once or twice every day), 10 days as a therapeutic course, 3 successive therapeutic courses in total. After the treatment, analgesic pain, muscle power of the limbs and the recovery of defecation function were observed.MAIN OUTCOME MEASURES: Pain-alleviating, muscle power of the limbs and the recovery of defecation function after the operation. RESULTS: Totally 162 patients with spinal metastasis carcinoma were recruited, and all the patients entered the stage of result analysis at the end of therapy with no loss in the midway. ① Pain complete alleviating was in 97 cases (59.88%); no alleveclting in 0 case. ② The condition was remarkably improved in 127 cases(78.40%), and it was not improved in 35 cases (21.60%). The improved rate of muscle power of the patients with one focus and 2 adjacent focuses was 92.98%. The improved rate of the patients with multiple foci was 64.59%. The muscle power of the patients with a disease history of less than 2 weeks was improved remarkably, but there was no change in muscle power in patients with a disease history of more than 2 months. CT or MRI showed that spinal cord at the affected segment of the 21 patients suffered severely compression before the treatment, and only 2 cases were improved in muscle power, with no other changes.③The defecation function of 162 patients all became normal.CONCLUSION: Patients with spinal metastatic carcinoma complicated with paralysis have different degrees of relief and amelioration in pain,muscle power of the limbs and defecation function after radiotherapy,chemotherapy and synthetic rehabilitation therapy. Factors affecting the recovery of spinal function mainly included the length of disease course,compressed degree of the spinal cord, the quantity of metastatic focus, the health status of the patients and therapeutic time and the quality of primary rehabilitation and so on. Mental help to the patients should be paid attention to so as to improve the quality of life at the same time.
6.Roles of miR-494 in tumors
Mingchun LI ; Aibing WU ; Zhixiong YANG
Journal of International Oncology 2013;40(10):726-729
MiR-494 involves in cell cycle regulation,differentiation and apoptosis processes of normal ceils.Recent study shows that abnormal expression of miR-494 is associated with oncogenesis closely,and it participates in the invasion and metastasis of tumor cells and so on.MiR-494 is not only a tumor suppressor gene,but also can be considered as a cancer-promoting gene.MiR-494 can regulate the oncogenesis and development of the tumor through a variety of target genes and signaling pathways.
7.Serum KL-6 in radioactive pneumonia with lung cancer
Lingli BAO ; Aibing WU ; Zhixiong YANG
Journal of International Oncology 2013;40(8):593-595
Serum KL-6 is a category of glycoprotein coded by the epithelium of sticky protein 1(MUC1) gene,which has already been regarded as an indicator of interstitial lung diseases,and later found highly expressed in part of malignant tumor patients.In recent years,studies has found that serum KL-6 is associated with the incidence of radioactive pneumonia,and monitoring serum KL-6 can predict the occurrence of radioactive pneumonia as well assess the severity and prognosis of disease.
8.MORPHOLOGICAL OBSERVATION IN VITRO MODEL OF BLOOD-TUMOR BARRIER OF GLIOMA
Zhixiong LIN ; Qiang HUANG ; Lijuan YANG ; Zhenbin CHEN ; Jianhu LIN
Acta Anatomica Sinica 1955;0(03):-
Objective To study the morphological characteristics of blood-tumor barrier(BTB)model of glioma in vitro. Methods After C 6 glioma cells/endothelia ECV 304 co-cultured mixed or in Transwell or on both sides of membrane of Transwell,the morphological characters of fenestra of endothelial cells,the junction between ECV 304 cells,the interface between C 6 cells and ECV 304 cells,and perivascular-end-feet of C 6 cells were observed under transmission electron microscope(TEM)and scanning electron microscope(SEM),and compared to BTB in 4 cases with human brain glioma. Results ECV 304 cells grown to confluence were not fenestrated,but with fomation of tight junction between ECV 304 cells after co-cultured with C 6 cells mixedly,in Transwell or on both sides of membrane of Transwell;It was not found that pseudopodia from C 6 cells as co-cultured in Transwell reaching into pore of Transwell;C 6 cells co-cultured on both sides of membrane of Transwell often sticked out to the ECV 304 cells,but with no pseudopodia from C 6 cells surrounded ECV 304 cells of penetrated the endothelia clefts.Perivascular-end-feet of C 6 cells were not integrant.These characters were similar to BTB in human brain glioma.Conclusion C 6 glioma cells/endothelia cell ECV 304 co-cultures on both sides of membrane of Transwell may simulate the morphological characters of BTB in vivo in some degree.;
9.Hedgehog signaling pathway in chemocarcinogenesis and progression of breast cancer
Dong CUL ; Linqing YANG ; Yun HE ; Zhixiong ZHUANG
Chinese Journal of Pharmacology and Toxicology 2015;(2):328-332
The controversial results of several studies suggest that certain everyday-use chemicals may be linked to breast cancer. ln recent years, extensive researches have been carried out to under-stand breast carcinogenesis and the hedgehog(Hh) signaling pathway has emerged as a critical determi-nant of human breast cancer. Aberrant Hh signaling in adults results in carcinogenesis, angiogenesis, and metastasis. This review is focused on the Hh signaling pathway and chemicals in the regulation of breast cancer development and provide an updated survey of pre-clinical and clinical trials of novel strategies to target them.
10.Relation of radiotherapy dose and sternocleidomastoid muscle (SM) mass or late response in patients with nasopharyngeal carcinoma
Xuejin SANG ; Xiaoyan WANG ; Zhining YANG ; Baotian HUANG ; Zhixiong LIN
Chinese Journal of Radiation Oncology 2017;26(1):1-5
Objective To investigate the relationship of radiation dose with the volume and late toxicity of the sternocleidomastoid muscle ( SM) in patients with nasopharyngeal carcinoma. Methods SM was divided into upper part and lower part based on the lower edge of cricoid cartilage. Patients were divided into three groups according to the prescribed dose for clinical target volume at the lower neck ( CTV2 ) ( 0, 54,60 Gy) . The dosimetric parameters included Dmean , V66 , and V60 for the upper, lower, and whole SM. SM was delineated and the volume was calculated on computed tomography images in the treatment planning system before and at 6, 12, and 18 months after treatment. The anteroposterior and transversal diameters of SM at C3?C4 , C4?C5 , C5?C6 , and C6?C7 levels were measured and recorded. Late toxicity of neck skin and SM was evaluated according to the Common Terminology Criteria for Adverse Events V4 .0 criteria. Between?group comparison was made by t?test or Kruskal?Wallis non?parametric test. Between?group comparison of the sample rate was made by one?way analysis of variance. The correlation analysis was made by Spearman correlation. Results There were significant difference in SM volume between the three time points after treatment ( P=0. 000) . At 12 or 18 months after treatment, the volume of SM wasignificantly reduced ( P=0. 000,0. 000);the reduction in SM volume was significantly correlated with V66 of the SM and the upper SM ( P=0. 015,0. 020) . At 18 months after treatment, SM fibrosis was significantly correlated with V60 of the upper SM ( P=0. 030);the fibrosis of neck skin was significantly correlated with the Dmean and V60 of the upper SM ( P=0. 029,0. 005) . Conclusions In order to prevent the incidence of the fibrosis of neck skin and SM, the dose homogeneity should be as high as possible, while the number of hot spots should be as small as possible.