1.Therapeutics, genomics and epigenomics of retinoblastoma
Wenping SONG ; Rongguang SHAO ; Liang LI
Chinese Journal of Biochemical Pharmaceutics 2016;36(6):1-5
Retinoblastoma is the most common pediatric retinal tumor initiated by biallelic inactivation of the retinoblastoma gene ( RB1 ) , affecting roughly 1 in 15000 children with 1100 new cases each year.In China, RB remains a potentially devastating disease while lack of early diagnosis and aggressive treatment strategies.Moreover, RB patients individually show a variety of drug response to regular systemic chemotherapy since intensive chemotherapy and long-term follow-up are not as readily available.The majority of patients with advanced diseases require enucleation which affects the future quality of children life.Recent studies showed that alterations in genomics and epigenomics of RB play very important roles in RB progress and therapy.We thereby review current understanding changes of genomics and epigenomics in RB as potential prognostic and therapeutic targets.
2.Advances in antibody drug for cancer targeted therapy
Rui CAO ; Rongguang SHAO ; Liang LI
Chinese Journal of Biochemical Pharmaceutics 2016;36(6):15-18
With the recent understanding of cancer biology, physiopathology, and cancer genetics& genomics, new treatments and methodologies are constantly developed, including on the development and application of molecular targeted drugs for cancer therapy have been widespread concerned.Antibody-based drugs targeting over-expressed oncogenes or other functional proteins in cancer with its high specificity, less side-effects and significant clinical efficacy became rapidly the hot-spot of anti-tumor drug research.Currently, there are already more than 20 of anti-tumor antibody-based drugs approved for clinical application, and achieved remarkable results.This article summarizes the development and current situation of monoclonal antibody-based drug research for cancer therapy, as well as their anti-tumor mechanism of action.At the same time summarizes the new advances in cancer research in the field of monoclonal antibody drugs made,and its prospects as well as shortcomings were outlined.
3.Detection of WFS1 gene mutations in the Chinese pedigree with low frequency sensorineural hearing loss
Qiong LIU ; Rongguang WANG ; Qingzhong LI
Medical Journal of Chinese People's Liberation Army 2001;0(07):-
Objective To analyze the mutations of candidate WFS1 gene in the Chinese pedigree with Low frequency sensorineural hearing loss. Methods PCR were performed with fourteen pairs of primers in the coding sequence of WFS1 gene. The PCR products were subsequently sequenced in the 38 individuals of LFSNHL family for screening the gene mutations. Results The PCR amplification fragments showed well quality in the five pairs of primer, and further analysis with frequencing showed no polymorphism and mutations in the members. Conclusion The present study rule out the possibility that the deafness gene WFS1, which locates on the 4p16, lead up to the hearing loss of LFSNHL pedigree.
4.Absorbable screw fixation repairs simple lateral malleolus fracture:a finite element analysis
Xiaowei HUANG ; Zhonghua GONG ; Baoqing YU ; Zexiang LI ; Rongguang AO
Chinese Journal of Tissue Engineering Research 2016;20(4):559-563
BACKGROUND: Compared with the metal screws, absorbable screws have more obvious advantages, such as does not have to conduct internal fixation removal, non-metal ic components, no influence on the magnetic resonance imaging of patients after implantation, relatively simple operations, namely dril ing-tapping-screws fixation, more in line with the principles of minimal y invasive in orthopedics. OBJECTIVE: To investigate the biomechanical characteristics of absorbable screw fixation in repair of simple lateral mal eolus fractures by means of finite element technology. METHODS: The three-dimensional model of simple lateral mal eolus fractures and absorbable screw model were established, and then fixed according to standard orthopedic surgical techniques. The reference load when the load bearing of fibulotalar joint reaching the peak value in a normal adult gait cycle was loaded. The stress distribution and displacement of fibula and absorbable screws were analyzed. RESULTS AND CONCLUSION: There were total y 38 542 units, 8 790 nodes in the single screw fixation model. When the articular facet of lateral mal eolus loading 300 N, the maximum stress of screws was 89.35 MPa, the maximum displacement was 0.5 mm, the maximum displacement of the distal fracture was 0.5 mm. When the articular facet of lateral mal eolus loading 450 N, the maximum stress of screws was 152.58 MPa, the maximum displacement was 0.59 mm, the maximum displacement of the distal fracture was 0.77 mm. There were total y 43 115 units, 9 496 nodes in the double screws fixation model. When the articular facet of lateral mal eolus loading 300 N, the maximum stress of screws was 38 MPa, the maximum displacement was 0.44 mm, the maximum displacement of the distal fracture was 0.44 mm. When the articular facet of lateral mal eolus loading 450 N, the maximum stress of screws was 66.68 MPa, the maximum displacement was 0.48 mm, the maximum displacement of the distal fracture was 0.49 mm. The experiment verified the biomechanical feasibility of absorbable screw fixation in repair of simple lateral mal eolus fractures. For simple involving only the lower lateral fibular fracture, absorbable screw fixation is entirely feasible, and usual y requires at least two screws to maintain the stability of the articular surface of the reset.
5.Dynamic hip screw and Gamma nail fixation repair unstable intertrochanteric fracture:a three-dimensional finite element analysis
Xiaowei HUANG ; Baoqing YU ; Zexiang LI ; Rongguang AO
Chinese Journal of Tissue Engineering Research 2015;(53):8603-8608
BACKGROUND:For unstable intertrochanteric fracture repair, there are two views:extramedul ary fixation or intramedul ary fixation. Theoretical y, intramedul ary fixation is in line with the principles of minimal y invasive, more mechanical and biological advantages. However, evidence-based medicine and related studies have shown that compared with the extramedul ary fixation, intramedul ary fixation did not reflect the proper theoretical advantage. OBJECTIVE:To compare the biomechanical performance of two kinds of internal fixation systems:dynamic hip screw and Gamma nail which commonly used in repair of intertrochanteric fractures by finite element method, and to evaluate the advantages and disadvantages of dynamic hip screw and Gamma nail in treatment of unstable intertrochanteric fracture. METHODS:Three-dimensional finite element model of human femur unstable intertrochanteric fractures (31-A2;AO fracture classification), and the three-dimensional finite element models of dynamic hip screw and Gamma nail were established respectively, and were fixed according to the requirement of orthopedic surgery. The reference load which the joint bearing was at the peak time in adult step state period with the body mass of 700 N was stimulated. The stress distribution of bone, bone-internal fixation model, nail or screw, the strain and deformation of fracture location on the surface of the bone and bone-internal fixation model, the stress distribution along the femur and the loading transfer condition along the internal fixator and the like were analyzed. RESULTS AND CONCLUSION:Dynamic hip screw and Gamma nail have good sliding compression features which could make the continuous and dynamical y axial compression of the fractured section. Under the load conditions, the displacement value of dynamic hip screw was larger. In the treatment of unstable intertrochanteric fracture, Gamma nail was stronger than dynamic hip screw. Two kinds of internal fixations al make the bearing load of the proximal femur reduce. In the treatment of 31-A2 type unstable intertrochanteric fractures, we should choose dynamic hip screw for fixation if the femoral calcar was not seriously crushed, little defect or no defects and can immediately rebuild the stability of femoral calcar during operation, otherwise, stronger internal fixation, namely Gamma nail fixation should be chosen.
6.Analysis of radiotherapy curative effects on pains of bone metastases of breast cancer
Haoyuan ZOU ; Guangjin ZHENG ; Hanxiong ZHANG ; Rongguang LI
Chinese Journal of Tissue Engineering Research 2001;5(24):147-
Objective To investigate the radiotherapy curative effects on pains of bone metastases of breast cancer. Methods To analysis 32 patients retrospectively, in which 22 patients received radiotherapy(17 moderate pain, 5 severe pain, 6 dysfunction). Result 16 patients obtained complete remission with 6 cases partial response to radiation. Karnorfsky's score was improved and malfunction disappeared. Conclusion Radiotherapy is a simple and effective treatment on bone metastases of breast cancer with quick and persistent pain relieves.
7.Comparison of the antitumor activities of immunoconjugates composed of lidamycin and monoclonal antibody fab' fragment with different linkers
Yun FENG ; Rongguang SHAO ; Yao DAI ; Baowei LI ; Hongwei HE ; Kaihuan REN
Acta Pharmaceutica Sinica 2010;45(5):571-5
To investigate the antitumor activities of the immunoconjugates composed of anti-type IV collagenase monoclonal antibody Fab' fragment and lidamycin (LDM) prepared with different linkers. The immunoconjugates were prepared by linking Fab' to lysine-69 of LDM apoprotein by SPDP, LCSPDP, SMBS or SSMPB as the intermediate drug linkers. Immunoreactivities of the conjugates were determined by ELISA. The cytotoxicities of the conjugates were examined by clonogenic assay. In vivo antitumor effects of the conjugates were evaluated in nude mice bearing subcutaneously implanted HT-1080 tumor. ELISA assay showed that the conjugates retained part of the immunoreactivity of 3G11 against the antigen. The cytotoxicities of the Fab'-SMBS-LDM and Fab'-SSMPB-LDM to HT-1080 cells were significantly potent, compared with Fab'-SPDP-LDM, Fab'-LCSPDP-LDM and free LDM. In animal models at the same condition, free LDM, Fab'-SPDP-LDM and Fab'-LCSPDP-LDM inhibited the growth of HT-1080 tumor by 70.9%, 74.8% and 72.3%, while Fab'-SMBS-LDM and Fab'-SSMPB-LDM reached 78.0% and 87.7%, respectively. The median survival time of the mice treated with free LDM, Fab'-SPDP-LDM and Fab'-LCSPDP-LDM were prolonged by 71.9%, 82.2% and 107.5%, respectively, compared with that of untreated group. Whereas, the median survival time of Fab'-SMBS-LDM and Fab'-SSMPB-LDM were prolonged by 145.2% and 165.8%, respectively, indicating that Fab'-SSMPB-LDM was more effective than Fab'-SMBS-LDM in tumor suppression and life span prolongation. Fab'-SSMPB-LDM has more marked selective antitumor efficacy and lower toxicity, and might be a novel candidate for cancer therapy.
8.Subclavicular angiography with brachial-axillary artery externally and temporally occluded in interventional treatment of hemoptysis
Xiaomei WU ; Rongguang LIANG ; Qing LAI ; Yuanxin QIAN ; Zhiyuan CHEN ; Ping LI
Chinese Journal of Radiology 2011;45(7):670-673
Objective To evaluate subclavicular angiography with brachial-axillary artery externally and temporally occluded in depicting hemoptysis-related ectopic arteries originating from shoulder, neck and chest wall in the interventional treatment of hemoptysis. Methods A retrospective analysis of the medical records and angiograms of 103 patients who underwent transarterial procedures for hemoptysis was carried out. The arteries originating from the subclavicular arteries supplying the shoulder, the neck and the chest wall, ectopic bronchial arteries (EBA) as well as non bronchial systemic arteries (NBSA), were depicted by subclavicular angiography with brachial-axillary artery externally and temporally occluded. The number and distribution of the responsible aberrant arteries were investigated. Results Of the hemoptysis-related arteries(n=372) depicted and embolized in the studies, 51.9% was normally-originated bronchial arteries(n=193),6.7% was ectopic bronchial arteries (n=25),41.4% was NBSA(n=154).Both anomalous and NBSA arising from subclavicular-axillary area(n=80) were accounted for 21.5% (80/372) of all aberrant arteries, and 44.7%(80/179) of all anomalous and NBSA (n=25+154=179).Of those arising from subclavicular-axillary arteries,56.3%(45/80) were found to be originated from the internal thoracic artery (n=45),98.2%(112/114)of responsible internal thoracic arteries and their distal branches were well depicted by subclavicular angiography with brachial-axillary artery externally and temporally occluded. Conclusion Subclavicular-axillary artery is a very important vessel where EBA and NBSA originate. Subclavicular angiography with brachial-axillary artery externally and temporally occluded could help to determine the abnormal arteries in the region quickly. The method should be taken as a routine procedure for interventional treatment of hemoptysis.
9.Synthesis and structure-activity relationship of N-(2-arylethyl) isoquinoline derivatives as anti-cancer agents.
Yanxiang WANG ; Wuli ZHAO ; Chongwen BI ; Yangbiao LI ; Rongguang SHAO ; Danqing SONG
Acta Pharmaceutica Sinica 2012;47(2):200-5
A series of novel N-(2-arylethyl) isoquinoline derivatives were designed, synthesized and evaluated for their anti-cancer activities. Among these analogs, compound 9a exhibited the potential anti-cancer activities on HepG2 and HCT116 cells with IC50 values of 2.52 and 1.99 microg x mL(-1), respectively. Cell cycle was blocked at S phase of HepG2 cells treated with 9a by flow cytometry detection. Our results provided a basis for the development of a new series of anti-cancer candidates.
10.Study of the relationship between antibody level and protection induced by human papillomavirus(HPV) L2-peptide
Xueling WU ; Junsheng CUI ; Shufang MENG ; Baowei LI ; Chuntao ZHANG ; Jinping FAN ; Rongguang SHAO ; Youchun WANG
Chinese Journal of Microbiology and Immunology 2010;30(2):159-163
Objective To detect the protection induced by HPV-58 L2 11-200 AA in animal, and analyze the relationship between antibody or neutralizing antibody titers and the protection generated by the immunizmg agent. Methods The peptide of HPV-58 L2 11-200 AA was expressed in E. coli and the mice were immunized with the peptide after purification and adsorption with aluminum adjuvant. The protection provided by different immunizing doses was detected in the mouse model against the challenge of the pseud-ovirions of human papiilomavirus types 58. The total antibodies and neutralizing antibody titers of serum were tested with ELISA and neutralization assay against HPV-58 pseudovirus, respectively. The total antibodies or neutralizing antibody titers that can protect the mouse from infection were analyzed. Results The mice can be protected from the challenge with HPV pseudovirus when the immunizing dose was 8 μg. The neutralizing antibody can not be detected in the immune serum by neutralization assay against pseudovirus. The total anti-body level has a corresponding relationship with the protection showed in mouse model. The results of total antibodies detected by ELISA showed that when the titer of total antibodies was ≥25 000, luminescent signal can not be detected and the mice can be protected from pseudovirus infection. Conclusion HPV-58 L2 11-200 AA peptide can protect mice from pseudovirus infection. L2 peptide has a promising perspective to be a candidate vaccine and the level of total antibodies in the immune serum can be used as a surrogate for the evaluation of protection against HPV infection.