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Patients with non-small cell lung cancer (NSCLC) are treated in a variety of ways. In addition to radiotherapy, chemotherapy and targeted therapy, breakthroughs have been made in immune checkpoint inhibitors, in particular, programmed cell death 1 (PD-1) and its ligand (PD-L1) inhibitors have achieved survival benefits for NSCLC patients, and some of them have been approved as first-line drugs by the US Food and Drug Administration. Currently, commonly used PD-L1 inhibitors are atezolizumab, durvalumab and avelumab. Combination therapies include combination with chemotherapy, anti-vascular endothelial growth factor drugs, molecular targeted therapy and immunotherapy.
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Lung cancer is one of the malignant tumors with the highest morbidity and mortality in the world. Non-small cell lung cancer (NSCLC) is one of the most important pathological types of lung cancer. The prognosis of advanced NSCLC is poor and medical treatment is still the main treatment option. Antibody-drug conjugates (ADCs) are the kind of potentially new anti-tumor drugs, consisting of monoclonal antibodies conjugated to the cytotoxic payloads via the synthetic linkers. They have a broad application prospect in solid tumors such as lung cancer. This article focuses on the mechanism of action and research progress of ADCs in advanced NSCLC. .
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Humans , Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Immunoconjugates/therapeutic use , Lung Neoplasms/drug therapyABSTRACT
Triple-negative breast cancer is a subtype of invasive breast cancer, accounting for about 15% of all breast cancers. Its clinical treatment is relatively difficult, prone to recurrence and metastasis, with a short median survival and poor prognosis. Sacituzumab govitecan is the first approved antigen-coupled drug targeting trophoblast surface antigen 2 in the world. It has significant clinical efficacy, high safety and less adverse reactions, which brings new hope to the treatment of triple-negative breast cancer.
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S-1 and capecitabine are relatively ideal agents for maintenance treatment of advanced gas-tric cancer. In clinical trials of using immune and targeted drugs for maintenance treatment of advanced gastric cancer,ipilimumab fails to obtain positive results,ramucirumab has not obtained research data,and trial regimens of maintenance treatment with trastuzumab,bevacizumab and avelumab have all shown initial efficacy. Traditional Chinese medicine therapy has shown some effectiveness in maintenance treatment,which still needs further researches.
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Background and purpose:Inhibitor of apoptosis-stimulating protein of p53 (iASPP) is one of the ASPP family. It binds to p53 to inhibit the transcriptional activity of p53-target genes and cell apoptosis, which is asso-ciated with tumor formation. Previously, we found a new subtype of iASPP, iASPP splice variant (iASPP-SV), which is a nuclear protein containing 407 amino acid residues and can bind to p53, inhibiting p53 transcriptional activity. However, the relationship of iASPP-SV and breast cancer is still obscure. Therefore, the purpose of this research was to study the role of iASPP-SV on breast cancer tumorigenesis and progression.Methods:5’-rapid ampliifcation of cDNA ends (RACE) was used to identify the 5’-end of iASPP-SV mRNA in MCF-7 cells. HEK 293 cells were transfected with pFLAG-iASPP-SV and pFLAG-iASPP (828). Then Western blot was used to identify whether endogenous iASPP-SV was expressed in HEK 293 cells and 8 types of human tumor cell lines. This study established the stable clones of NIH 3T3 expressing FLAG-iASPP-SV and FLAG-iASPP (828). Cell proliferation assay, colony formation and soft agar colony formation assay were used to identify whether iASPP-SV and iASPP (828) can promote cell proliferation and iASPP-SV is an oncogene. Real-time lfuorescent quantitative polymerase chain reactive (RTFQ-PCR) was used to de-tect the levels of iASPP-SV and iASPP (828) mRNA in primary breast cancers. Luciferase assays were used to identify the relationships between iASPP-SV, iASPP (828), p53 and NF-κB p65.Results:The study identiifed that iASPP-SV was encoded by previously reported NF-κB p65 subunit (RelA)-associated inhibitor (RAI), and endogenously expressed in many human cancer cell lines. Analysis of cell proliferation, colony formation assay and soft agar assay for colony formation identiifed that similarly to iASPP (828), iASPP-SV promoted tumor cell proliferation and acted as an onco-gene. RTFQ-PCR result showed that the median values of iASPP-SV and iASPP (828) in breast cancers with wild-type p53 were more signiifcantly over-expressed than those of mutant p53. Luciferase assays showed that iASPP-SV and iASPP (828) could suppress NF-κB p65 transcriptional activity. Thus iASPP family may participate in the regulation of p53 and NF-κB activity, which imply that iASPP perhaps shows pro- or anti-survival activities when it interacts with different proteins.Conclusion:These ifndings indicate that iASPP-SV may be a potential target for breast cancer thera-py.
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ObjectiveTo investigate the impacts of neural stem cells (NSCs) transplantation on spinal pathology and ultrastructure after spinal cord injury (SCI) in rats and probe into the protective role of tacrolimus (FK506) on neural regeneration.MethodsCompressive SCI at T8 was induced in the adult SD rats,which were randomly assigned to the control group,FK506 group,NSCs group and NSCs + FK506 group.The differences of neural regeneration in each group were compared at days 7,14,28 and 56 after injury by motor evoked potentials ( MEP),HE staining,immunohistochemical staining,ultrastructure observation and image analysis of the myelinated fiber. ResultsThe MEP latency in the NSCs + FK506 group was significantly shorter than that in other groups at day 28 ( P ＜ 0.05 ).HE staining revealed that only local necrosis presented in the NSCs + FK506 group at day 56.More BrdU and NF-200 positive cells were detected with immunohistochemical staining in the other three groups as compared with the control group.Moreover,the positive cells in the NSCs + FK506 group also outnumbered the FK506 group and NSCs group.Electron microscope scan showed edema under the membrane of large myelin sheath in the control group,and classic new myelin sheath and neuraxis in the NSCs + FK506 group at day 56.The regeneration of the nerve fiber in the NSCs + FK506 group was better than that of other three groups (P ＜0.01 ).ConclusionAfter NSCs transplantation for SCI rats,the early combination use of FK506 can improve the pathology and ultrastructure of the regenerative nerve fiber and is conducive to nerve regeneration.
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BACKGROUND:The key of stem cells for treating nervous tissue injury is the transplantation of stem coils that have regeneration capacity.The structure and function of central nervous system were re-established by multiple action mechanisms.OBJECTIVE:To explore the effects and mechanisms of bone marrow mesenchymal stem cells(BMSCs)locally transplanted into rats with spinal cord injury on neurological recovery.METHODS:BMSCs were separated with density gradient centrifugation and cell attachment.10 mg/L BrdU was used for labeling before cell transplantation.Adult female Wistar rats were used to establish spinal cord injury models using an aneurysm clip,and they were then randomly divided into control group,saline group and transplantation group.In the transplantation group,BMSCs were transplanted into the damaged spinal cord by stereotaxis at day 7 following damage.In the saline group,an equal volume of saline was utilized.In the control group,the rats were left intact.Basso,Beattie and Bresnahan(BBB)locomotor rating scale was used before and at 7,14,30,60 and 90 days following damage.Rats were sacrificed at day 90.BrdU-positive cells,Brdu+neuron specific enolase,Brdu+glial fibrillary acidic protein(GFAP),Brdu+basic fibroblast growth factor(bFGF),and Brdu+brain-derived nerve growth factor(BDNF)immunohistochemistry double-staining cells and simple staining positive calls were observed.RESULTS AND CONCLUSION:The recovery of BBB function score was better in the transplantation group than in the control group(P＜0.05).The recovery speed of BBB function score was slower in the saline group than in the control group at 30 days following damage(P＜0.05).No significant difference was determined at day 90 compared with the control group(P＞0.05).BrdU-positive cells and double-staining cells of immunohistochemistry could be found at the center of damage site and 1 cm from caudal end to damaged site in rats of the transplantation group.The number of NSE,GFAP,bFGF and BDNF simple staining cells was significantly greater in the transplantation group than in the control and saline groups(P＜0.05).Results indicated that BMSC transplantation can improve the recovery of nervous function of rats with spinal cord injury.Its mechanism may be correlated with the differentiation of transplanted cells into neuron-like and glial cell-like cells,secretion or promoting secretion of neurotrophic factors in host.
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The apoptosis stimulating proteins of p53 (ASPP) are important regulatory proteins of p53 family, consisting of ASPP1, ASPP2 and iASPP. ASPP combine with p53 ,and ASPP1 and ASPP2 promote cell apoptosis of p53 specifically,where as iASPP inhibit the tumor suppressing function of p53 by combining with p53. Thus,ASPP family of proteins,especially iASPP, may be a novel target for cancer therapy.
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0.05), but to the lymphnode metastasis of axillary fossa, estrogen receptor (ER)(P