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In recent years, with the emergence of new research evidence, the domestic and foreign guidelines in the field of gastrointestinal stromal tumors (GISTs) have been updated. The adjusted contents cover almost every link of GISTs management, from GISTs diagnosis, biological behavior, surgical treatment to targeted drug treatment. Since 2020, the NCCN of the United States has separated the contents related to GISTs from the clinical practice guide for soft tissue sarcoma for the first time to form 2021 V.1 versions. The CSCO has also adjusted and upgraded the previous consensus of Chinese experts on the diagnosis and treatment of GISTs to 2020 and 2021 versions of the guidelines for the diagnosis and treatment of GISTs. This opens a new model of accurate diagnosis and treatment of GISTs under the guidance of evidence-based medicine. The listing of new targeted drugs afatinib and ripretinib is expected to get rid of the drug-resistant treatment dilemma of metastatic GISTs, enrich the back-line treatment camp, provide more opportunities for surgical intervention, and then bring survival benefits to patients with advanced GISTs.
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BACKGROUND: Human umbilical cord mesenchymal stem cells play a vital role in the repair of the blood-brain barrier after traumatic brain injury. OBJECTIVE: To investigate the protective effect of human umbilical cord blood mesenchymal stem cell transplantation on the blood-brain barrier after traumatic brain injury in rats and its possible mechanism. METHODS: Sixty Sprague-Dawley rats were randomly divided into sham operation group, injury control group (model group), cell transplantation group and Sunitinib group, with 15 rats in each group. Traumatic brain injury model was established by improved hydraulic impact method in all the groups except for the sham operation group. Rats in the sham operation group and model group were injected with 1 mL of normal saline, and those in the cell transplantation group were injected with 1 mL of 2×109/L human umbilical cord blood mesenchymal stem cells. The injection was done via the tail vein at 0.5, 24, and 48 hours after modeling. In the Sunitinib inhibitor group, the rats were given oral PDGFR-β pathway inhibitor, Sunitinib (80 mg/kg), from 1 day before modeling until being executed. Three days after modeling, the water content in brain tissue was measured by dry-wet specific gravity method, the permeability of the blood-brain barrier was measured by Evans blue method, expression of GFAP and vWF was observed by immunofluorescence staining and the expression of blood-brain barrier related proteins and PDGFR-β pathway proteins was detected by western blot method. RESULTS AND CONCLUSION: Compared with the sham operation group, the brain water content of the model group increased significantly (P < 0.05), while that of the cell transplantation group was significantly lower than that of the model group (P < 0.05). The Evans blue content in the model group was significantly higher than that in the sham operation group (P < 0.05), while the Evans blue content in the cell transplantation group was significantly lower than that in the model group (P < 0.05). Compared with the sham operation group, the expression of vWF and GFAP increased significantly in the model group (P < 0.05), while compared with the model group, the expression was significantly reduced in the cell transplantation group (P < 0.05). Western blot showed that ZO-1, Oclaudin-5, and PDGFR-β protein expressions in the model group were significantly lower than those in the sham operation group (P < 0.05), while these expressions were significantly increased in the cell transplantation group as compared with the model group (P < 0.05). To conclude, intravenous injection of human umbilical cord mesenchymal stem cells through the tail ein can reduce the permeability of blood-brain barrier and play a neuroprotective role in rats with traumatic brain injury. Its possible mechanism is related to the promotion of PDGFR-β expression in the injured area.
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@#Gastrointestinal stromal tumors (GISTs) are the most common malignant tumor of abdominal soft tissue. It originates from Cahal (Cajal) interstitial cells or common precursor cells, and is driven by the mutated KIT gene or platelet-derived growth factor receptor alpha (PDGFRa) gene, all expressing type Ⅲ tyrosine kinase receptors. Imatinib mesylate, a tyrosine kinase receptor inhibitor, has been used for the standard treatment of advanced GIST, which has achieved remarkable results. Thus, GIST has become the most successful example of target therapy for solid tumors. In the context of the era of precision medicine, with the deepening in research of GISTs molecular biology，the molecular targeted treatment of GISTs has obtained a clear venation from the first-line, second-line and third-line of the advanced stage to the postoperative auxiliary and preoperative treatment, providing significant survival benefits for GISTs patients. This article systematically and comprehensively combed the preoperative and postoperative molecular targeting therapy from advanced GIST to early GIST, and analyzed the problems, proposed solutions and prospects for the future, aiming to provide reference for clinical application of molecular targeting drug therapy for GIST.
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Objective To evaluate the effect of imatinib in improving myocardial fibrosis in uremic rats through regulating the expression of PDGFRα.Methods Seventy two rats were divided into three groups ,which were Sham group ,5/6 group and 5/6+I group .All The rats in 5/6 group underwent the 5/6 nephrectomy and the rats in 5/6+I group were given imatinib by ga‐vage after the operation of 5/6 nephrectomy .Hearts were harvested for HE and Sirius red staining at 8 weeks post surgery .The ex‐pression of PDGFRαwas assessed with immunohistological staining .The real‐time PCR was employed to detect the PDGFRαmR‐NA level in hear samples .Results The urine protein ,Scr ,BUN of the 5/6 group and 5/6+I group were higher than that of Sham group(P<0 .01) .The myocardial pathological score in Sham group was significantly lower than that of 5/6 group (P<0 .01) ,and the score in 5/6+I group was significantly lower than that of 5/6 group (P<0 .01) .The collagen volume fraction (CVF) in 5/6 group was significantly higher than that in Sham group (P<0 .01) .And the CVF in 5/6+ I group was higher than that in Sham group (P<0 .05) ,but lower than that of 5/6 group (P<0 .05) .The expression ratio of PDGFRαmRNA and staining rate in 5/6 group and 5/6+I group were both much higher than that in Sham group (P<0 .01) ,and the expression in 5/6+I group was signif‐icantly lower than that in 5/6 group (P<0 .05) .Conclusion These data suggest that the tyrosine kinase inhibitor imatinib reduces heart injury and attenuates myocardial fibrosis in uremic rat by mechanisms associated with the inhibition of the expression of PDGFRα.
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Objective To explore the toxic effect of platelet-derived growth factor receptor (PDGFR)-αantisense oligonucleotide (αASODN) on the retina. Methods Twenty-four healthy adult colored rabbits were selected and randomly divided into four groups in six for each group. Intravitreous injections of 0.1ml different density diluents containing PDGFR-αASODN and liposome were performed in the right eyes in 3 groups. The other group was injected with 0.1 mL balanced salt solution (BSS) as the control group. The left eyes of all animals were not rejected. Slit lamp examination, indirect ophthalmoscopy and electroretinogram (ERG) examination were performed at 1, 7, 14 and 28 days after the injection. On the day 28, the right eyes were harvested, and HE、immunohistochemistry and transmission electron microscopy of retinal tissue were performed . Results The slit lamp, indirect ophthalmoscope examination of all groups were normal in each time. ERG examination yielded no difference in the amplitude of b wave between the treated groups and the normal control group. Pathological changes of the retinal tissue were not observed in the examinations of HE and immunohistochemical at the day 28 after injection. Electron microscope observation of retinal photoreceptor cells in the group D showed the parts of gaps between membranous discs were expanding, parts of were fusing, a few of clearances around cell nucleus were slightly enlarged,and the shapes of the cell nucleus were slightly irregular. Conclusions To inject 0.1 mL PDGFR-αASODN/lip2000 into the vitreous chamber, PDGFR-αASODN can be relatively safe when its concentration is less than 1.5μmol/L.
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Although cleft lip and palate are one of the most common craniofacial malformation, little is still known about the mechanism of the palate formation. Retinoic acid (RA) is known a teratogen, and cleft palate is induced by retinoic acid administration in the secondary palate formation stage. Many growth factors and their receptors are involved in the formation of the secondary palate. Here, we investigated the expression of PDGFR-alpha, and PDGFR-beta during palatogenesis after retinoid acid administration in mice by RT-PCR and immunohistochemistry. At E15.5, the opposing palatal shelves fused with one another in the control group, but the palatal shelves were not elevated and cleft palate was induced in the RA-treated group. In RT-PCR, PDGFR-beta was downregulated during palatogenesis after RA administration. In immunohistochemical experiment, PDGFR-alpha and PDGFR-beta were reduced in RA-induced group. Taken together, we suggest that PDGF receptors may be molecules involved in palate formation.
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Animals , Mice , Cleft Lip , Cleft Palate , Immunohistochemistry , Intercellular Signaling Peptides and Proteins , Palate , Receptors, Platelet-Derived Growth Factor , TretinoinABSTRACT
Objective To study the effects of ganoderma applanatum polysaccharides(GAPS) on cell morphology, proliferation and PDGFR -?expression in cell lines MGC - 803 , and to explore its potential mechanisms of anti - tumor of GAPS. Methods Cell morphology was observed by inverting microscope. MTT assay was used to investigate the inhibitory effect of GAPS on MGC -803.Expressions of PDGFR -?was analyzed by flow cytometry (FCW). The fluorescence intensity of expressions of PDGFR -?was observed by fluorescence microscope. Results Cells of GAPS group were irregular shaped and grew poorly. GAPS inhibited the proliferation of MGC -803 cells in dose - dependent and time - dependent manners . After MGC - 803 cells were treated with GAPS for 72h, GAPS could down - regulate expression of PDGFR -?observed by fluorescence microscope which was consistented with the results of FCW with statistic significance difference as compared with control group (P
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Objective This study was to examine the expression of tyrosine kinase receptor(TKRs)C-kit,C-abl and PDGFR?,in ovary carcinoma.Methods The expression of C-kit,C-abl and PDGFR? in tumor tissue of 60 specimens of ovary carcinoma and normal fissue of 20 specimens of overy was examined by immunohistochemistry SP method.Results Immunoreactivity was detected in 79% of the tumor to at least one TKR.The total positive expression rate of C-kit,C-abl and PDGFR? in ovary carcinoma was 58.3%,70%,73.3%,respectively.The positive expression rate of C-kit and PDGFR? is significantly higher in tumor tissues than in normal tissues(P