1.Bispecific antibodies in cancer therapy: Target selection and regulatory requirements.
Yanze SUN ; Xinmiao YU ; Xiao WANG ; Kai YUAN ; Gefei WANG ; Lingrong HU ; Guoyu ZHANG ; Wenli PEI ; Liping WANG ; Chengliang SUN ; Peng YANG
Acta Pharmaceutica Sinica B 2023;13(9):3583-3597
In recent years, the development of bispecific antibodies (bsAbs) has been rapid, with many new structures and target combinations being created. The boom in bsAbs has led to the successive issuance of industry guidance for their development in the US and China. However, there is a high degree of similarity in target selection, which could affect the development of diversity in bsAbs. This review presents a classification of various bsAbs for cancer therapy based on structure and target selection and examines the advantages of bsAbs over monoclonal antibodies (mAbs). Through database research, we have identified the preferences of available bsAbs combinations, suggesting rational target selection options and warning of potential wastage of medical resources. We have also compared the US and Chinese guidelines for bsAbs in order to provide a reference for their development.
2.Development and clinical advancement of small molecules for ex vivo expansion of hematopoietic stem cell.
Jiaxing LI ; Xiao WANG ; Jiayu DING ; Yasheng ZHU ; Wenjian MIN ; Wenbing KUANG ; Kai YUAN ; Chengliang SUN ; Peng YANG
Acta Pharmaceutica Sinica B 2022;12(6):2808-2831
Hematopoietic stem cell (HSC) transplantation is the only curative therapy for many diseases. HSCs from umbilical cord blood (UCB) source have many advantages over from bone marrow. However, limited HSC dose in a single CB unit restrict its widespread use. Over the past two decades, ex vivo HSC expansion with small molecules has been an effective approach for obtaining adequate HSCs. Till now, several small-molecule compounds have entered the phase I/II trials, showing safe and favorable pharmacological profiles. As HSC expansion has become a hot topic over recent years, many newly identified small molecules along with novel biological mechanisms for HSC expansion would help solve this challenging issue. Here, we will give an overview of HSC biology, discovery and medicinal chemistry development of small molecules, natural products targeting for HSC expansion, and their recent clinical progresses, as well as potential protein targets for HSC expansion.
4.Research update of effects of adipose tissue and component transplantation on scar treatment
Jianghong QI ; Yuan CAI ; Chengliang DENG
Chinese Journal of Burns 2020;36(7):623-626
Scar is a kind of skin fibroproliferative disease characterized by excessive repair of skin tissue and disorganized deposition of extracellular matrix resulting from deep dermal injury caused by burns or trauma. Scar is accompanied by symptoms such as itching and pain, which could lead to appearance damage and psychological disorders, and is one of the common diseases in burns and plastic surgery clinics. Currently, transplantation of adipose tissue and components is considered as one of the most cutting-edge treatments for scar. Adipose components transplantation includes transplantation of nanofat, adipose-derived stem cell matrix gel, stromal vascular fraction, and adipose-derived stem cell. More and more studies showed that adipose tissue and components possess the functions of tissue regeneration, extracellular matrix remodeling, and anti-fibrosis, which could improve the appearance and symptoms of scar by local transplantation. Therefore, this paper reviews the effects of adipose tissue and components transplantation on scar treatment, aiming to provide theoretical reference for adipose treatment of scar.
5. Repair of the defect on midface using perforator flap of facial artery
Linlin JI ; Zairong WEI ; Wei CHEN ; Bo WANG ; Wenduo ZHANG ; Wenhu JIN ; Hai LI ; Shujun LI ; Chengliang DENG ; Yuting YUAN
Chinese Journal of Plastic Surgery 2019;35(4):390-394
Objective:
To explore the clinical application of facial artery perforator flap in repairing medium-size midfacial defects.
Methods:
Sixteen patients with facial tumors or trauma were admitted in the Affiliated Hospital of Zunyi Medical University, from October 2017 to March 2018. The patients were 41—74 years of age, including 8 males and 8 females. The tissue defects were caused by basal cell carcinoma(BCC,
6.Exercise Preconditioning Improving the Pathological Cardiac Hypertrophy in Pressure Over-loaded Rats
Tongyi XU ; Qingqi HAN ; Ben ZHANG ; Dejun GONG ; Yang YUAN ; Chengliang CAI ; Yun DING ; Liangjian ZOU
Chinese Circulation Journal 2014;(9):728-732
Objective: To explore the effect of exercise preconditioning (EP) on pathological cardiac hypertrophy and heart failure (HF) in pressure over-loaded experimental rats.
Methods:A total of 60 SD rats at the age of 6 weeks were randomly divided into 3 groups, n=20 in each group. Sham-operation group, Transverse aortic constriction (TAC) group and EP + TAC group. The cardiac function and structure were evaluated by echocardiography, patholgical changes and HF biomarkers were examined for EP effect at 4 and 8 weeks after TAC.
Results:Compared with Sham-operation group, the cardiac function and structure had obvious changes in the other 2 groups. Compared with TAC group, the ejection fraction in EP+ TAC group increased 15%, the heart weight index and left ventricular weight index decrease 15.7%and 20%respectively at 8 weeks after TAC, all P<0.05. Compared with Sham-operation group, the mRNA and protein expressions of ANP and BNP increased in TAC group at 4 and 8 weeks after TAC, increased in EP+TAC group at 8 week after TAC. Compared with TAC group, the mRNA expressions of ANP and BNP in EP+TAC group decreased 47%and 62%at 4 weeks after TAC, decreased 44%and 28.1%at 8 weeks after TAC, all P<0.05;the protein expression of ANP and BNP in EP+TAC group decreased 22.3%and 48%at 4 weeks after TAC, decreased 21.5%and 38.3%at 8 weeks after TAC, all P<0.01.
Conclusion: EP may improve cardiac pathological hypertrophy in pressure over-loaded rats at the early stage, and delay the heart failure process.
7.Fibroblast seeded on the thoroughly acellular human amniotic membrane with three-dimensional adhesion in vitro
Xuya LU ; Yuan XUE ; Pei WANG ; Chengliang CUI ; Wei LIU ; Yang LI
Chinese Journal of Orthopaedics 2011;31(2):184-190
Objective Three-dimension (3D) cell matrix adhesion in vivo is fundamentally important for a wide variety of cellular physiological and pathological phenomena, however, the cell-matrix 3D adhesion is hardly observed in vitro. We present the human foreskin fibroblasts (HFF) formed 3D adhesion complexes on the thoroughly acellular human amniotic matrix (TAHAM). Methods TAHAM were produced by suspending digestion with trypsin. The HFF were seeded on 6 well plate, matrigel and TAHAM individually.The light microscope, scanning electronic microscope, immunohistochemistry and immunofluorescence were used to observe the micro-structures and detect the type Ⅰ , Ⅲ, Ⅳ, Ⅵ collagen, laminin, fibronectin, TGF-β1, TGF-β2, FGF of the TAHAM. Phase contrast microscope was engaged to observe the morphology of HFF. The time-lapse CCD and the trace analysis software were employed to prescribe the cell migration. The 3D adhesion foci were identified by the laser confocal microscope. The strain of the TAHAM was tested by the universal mechanical testing instrument. Results The fibers of the TAHAM were intact, type Ⅰ , Ⅲ,Ⅳ, Ⅵ collagen, laminin, fibronectin were positive, TGF-β1, TGF-β2, FGF were negative. HFF had a bipolar extension to form multilayer cell clusters networks and grew into the matrix. All of the seeded cells survived three weeks under regular culture without transfer. On TAHAM, HFF moved in a straight line with a speed of 12 μm/h. α5 integrin (green), paxillin (red) and fibronectin (blue) co localized to form 3D adhesion complexes (white). Conclusion The main molecular components and biomechanical properties is preserved in TAHAM. HFF forms 3D adhesion complexes on TAHAM. Cell morphology and migration of HFF on TAHAM correspond to that under 3D adhesion behavior.
8.Clinicopathological features and prognosis of small cell carcinoma of the cervix.
Jie, LIU ; Yuan, LI ; Shuang, LI ; Dan, WANG ; Ting, HU ; Yuhan, MENG ; Ding, MA ; Hongbing, CAI ; Zehua, WANG ; Chengliang, XIONG ; Huiping, ZHANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2010;30(5):626-30
Small cell carcinoma of cervix (SCCC) is a rare disease with highly aggressive behaviour and is pathologically hard to diagnose. In this study, the clinicopathological features, diagnosis, treatment and prognosis of the condition were examined. Clinical records and follow-up data of 7 cases of SCCC were retrospectively studied. Our results showed that five non-recurrent cases initially presented irregular vaginal bleeding or increased apocenosis of varying degrees. Pathological examination revealed that the stroma was diffusely infiltrated with small monomorphous cells ranging from round to oval shape. Three cases were immunohistochemically confirmed. One case was accompanied with squamous cell cancer. Of the 7 cases, one case was classified as stage I b1, two stage I b2, one stage IIa, one stage IIb, and one stage IIIb. On the basis of their stages of condition, one subject with stage III b underwent chemotherapy, and one with stage Ib2 received extensive hysterectomy plus pelvic lymphadenectomy, while the other 5 cases were treated by extensive hysterectomy and pelvic lymphadenectomy in combination with pre- and/or post-operative adjuvant chemotherapy and radiotherapy. Of the 7 patients, 4 had relapse-free survival of 14, 14, 16 and 28 months respectively. It is concluded that SCCC is an aggressive tumor with propensity for early pelvis lymph node metastases. Early-stage patients should be treated by extensive hysterectomy and pelvic lymphadenectomy in combination with pre- and/or post-operative adjuvant chemotherapy and radiotherapy.
9.Clinicopathological Features and Prognosis of Small Cell Carcinoma of the Cervix
LIU JIE ; LI YUAN ; LI SHUANG ; WANG DAN ; HU TING ; MENG YUHAN ; MA DING ; CAI HONGBING ; WANG ZEHUA ; XIONG CHENGLIANG ; ZHANG HUIPING
Journal of Huazhong University of Science and Technology (Medical Sciences) 2010;30(5):626-630
Small cell carcinoma of cervix (SCCC) is a rare disease with highly aggressive behaviour and is pathologically hard to diagnose. In this study, the clinicopathological features, diagnosis,treatment and prognosis of the condition were examined. Clinical records and follow-up data of 7 cases of SCCC were retrospectively studied. Our results showed that five non-recurrent cases initially presented irregular vaginal bleeding or increased apocenosis of varying degrees. Pathological examination revealed that the stroma was diffusely infiltrated with small monomorphous cells ranging from round to oval shape. Three cases were immunohistochemically confirmed. One case was accompanied with squamous cell cancer. Of the 7 cases, one case was classified as stage Ⅰ bl, two stage Ⅰ b2,one stage Ⅱ a, one stage Ⅱ b, and one stage Ⅲb. On the basis of their stages of condition, one subject with stage Ⅲ b underwent chemotherapy, and one with stage Ib2 received extensive hysterectomy plus pelvic lymphadenectomy, while the other 5 cases were treated by extensive hysterectomy and pelvic lymphadenectomy in combination with pre- and/or post-operative adjuvant chemotherapy and radiotherapy. Of the 7 patients, 4 had relapse-free survival of 14, 14, 16 and 28 months respectively.It is concluded that SCCC is an aggressive tumor with propensity for early pelvis lymph node metastases. Early-stage patients should be treated by extensive hysterectomy and pelvic lymphadenectomy in combination with pre- and/or post-operative adjuvant chemotherapy and radiotherapy.
10.P2X3 receptor expression in DRG and bladder detrusor of an animal model of neurogenic bladder and ure-thra
Huiping ZHANG ; Chengliang XIONG ; Changhong ZHU ; Zhong CHEN ; Zhangqun YE ; Guanghui DU ; Yuan CHEN ; Weifeng HU ; Lijuan HU ; Xiaoyong ZENG
Chinese Journal of Physical Medicine and Rehabilitation 2008;30(10):668-670
Objective To investigate the P2X3 receptor expression in L6-S1 dorsal root ganglion (DRG)and bladder detrusor in a rat model of neurogenic bladder and urethra. Methods Eighty Sprague-Dawley rats wererecruited and randomly divided into a sacral injury group, a suprasacral injury group and a control group. Spinal tran-section was performed to establish the animal model of neurogenic bladder and urethra in rats of the sacral injurygroup and suprasacral injury group. Check the P2X3 receptor expression in DBG and bladder detrusor among thethree groups by Western blot test at 20 days after model establishment. Results P2X3 receptor expression in L6-S1DRG of sacral injury group was significantly less than that of the suprasacral injury group, which was in turn signifi-cantly higher than that of the control group. P2X3 receptor expression in bladder detrusor of sacral injury group wassignificantly lower than that of the suprasacral injury group, which was in turn significantly higher than that of thecontrol group. Conclusion There was close relationship between P2X3 receptor expression and dysfunction of blad-der and urethra.

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