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@#In recent years, the chimeric antigen receptor T-cell (CAR-T) therapy has achieved breakthrough progress in the treatment of hematologic malignancies. However, when it comes to solid tumors, numerous challenges persist.These include limited CAR-T cell infiltration, susceptibility to T cell exhaustion, off-target effects, and more.Thus, novel therapeutic strategies are imperative to enhance the efficacy of CAR-T therapy for solid tumors. In comparison to standalone CAR-T approaches, the combination of CAR-T with other tumor treatment modalities has demonstrated remarkable effectiveness in both preclinical and clinical research.This review article summarizes the advancements in combining CAR-T with various solid tumor treatments: antibody drugs, oncolytic viruses, tumor vaccines, and nanomedicines.The objective is to furnish a theoretical foundation and novel perspectives for the development of innovative CAR-T combination strategies tailored for solid tumor therapy.
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@#Psoriasis is an autoimmune disease characterized by chronic skin inflammation, and its etiology and pathogenesis have not been fully elucidated to date. In the previous study, rhIL23R-CHR/Fc fusion protein had been found to significantly relieve the symptoms of psoriasis mice and the pharmacological mechanism had been initially elucidated.In this study, we established a psoriasis cell model (Act-HaCaT) using TNF-α-activated human immortalized keratinocytes (HaCat).In our current study, the lncRNA that plays a key role in the regulation of Act-HaCaT function by the rhIL23R-CHR/Fc fusion protein was screened by transcriptome sequencing combined with qRT-PCR.The results showed that rhIL23R-CHR/Fc fusion protein significantly inhibited cell proliferation and inflammatory factor production in Act-HaCaT.lncRNA ENST00000522718 was obtained by screening, and knockdown of ENST00000522718 was found to significantly inhibit cell proliferation and inflammatory factor production.Our findings suggest that ENST00000522718 plays an important role in the pathological mechanism of psoriasis.
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Objective:To reconstruct and repair forearm and foot injuries with soft tissue defect using medial sural artery perforator flap (MSAP), and to evaluate the curative effects.Method:From May, 2015 to September, 2017, 13 patients (9 males and 4 females) with soft tissue defect on forearm and foot underwent MSAP reconstruction operations. The age was ranged from 19 to 57 (mean 41) years. Six wounds located in forearms and 7 in foot. Ipsilater- al shank was used as donor for the repair of foot. The donor sites were directly sutured. The area of flaps was ranged from 3.0 cm×4.0 cm-7.0 cm×15.0 cm. All cases were followed-up for flap appearance, sensation and donor healing by visit of clinic and WeChat reviews.Results:All 13 flaps survived well without any vascular crisis nor necrosis. Postoperative superficial infections were found in 3 cases, and the wound healed gradually after daily dress changing and anti-infection treatment. Eleven patients were followed-up for 4 to 18 months (average 12 months). Two provincial patients lost to follow-up. No obvious disfunction was found from the donor shanks. The appearance and texture of flaps were in excellent condition and satisfactory. The sensation of 7 flaps was recovered to S 2-S 3. TPD was 6-9 mm. Conclusion:The free MSAP is rational therapeutic strategy for repairing the soft tissue defect of forearm and foot. It has advantages of long vascular pedicle, constant perforation and relatively thin subcutaneous fat.
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<p><b>OBJECTIVE</b>To investigate the reversal effect of targeted modulation of bcl-2 expression by miR-15a and miR-16 on drug resistance of human colon cancer cells.</p><p><b>METHODS</b>Mimics or inhibitors of miR-15a and miR-16 were transfected into HCT8 or HCT8/VCR cells with the help of Lipofectamine 2000. The expressions of miR-15a and miR-16 mRNA were detected by RT-qPCR. The levels of bcl-2 and P-gp proteins were measured by Western blot. The inhibitory effects of VCR on growth of HCT8 and HCT8/VCR cells were detected by CCK8.</p><p><b>RESULTS</b>After transfection of the mimics, the expression of miR-15a in the blank control group, negative control group and miR-15a mimic group was 1.00, 0.87 ± 0.24, and 223.44 ± 59.07, respectively, and miR-15a was increased significantly (P < 0.001). The expression of miR-16 in the blank control group, negative control group and miR-16 mimic group was 1.00, 0.66 ± 0.19, and 107.32 ± 22.58, respectively, and miR-16 expression was increased significantly (P < 0.001). The Western blot assay showed that the relative expressions of bcl-2 protein in the blank control group, negative control group, miR-15a mimic group and miR-16 mimic group were 1.00, 0.97 ± 0.02, 0.51 ± 0.06, and 0.65 ± 0.03, respectively, and the expression of bcl-2 protein was decreased significantly (P < 0.05), however, the expressions of P-gp protein showed no significant difference. The CCK8 test showed that at 1, 5, 25 and 125 µg/ml concentration of VCR, the survival rates of HCT8/VCR cells were basically the same in the blank control group, negative control group, miR-15a mimic group and miR-16 mimic group, but the survival rate of HCT8/VCR cells was significantly decreased after transfection of mimics (P < 0.05). After transfection of the inhibitors, the expressions of both miR-15a and miR-16 were decreased significantly (P < 0.001). The Western blot showed that the expression of bcl-2 protein was increased (P < 0.05), while the expression of P-gp protein showed no significant difference. The CCK8 test showed that the survival rate of HCT8 cells which were transfected with inhibitors was significantly higher than that of the blank control group (P < 0.05).</p><p><b>CONCLUSIONS</b>miR-15a and miR-16 may reverse the drug resistance in human colon cancer cells. A possible mechanism is regulating the expression of bcl-2.</p>
Subject(s)
Humans , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Apoptosis , Apoptosis Regulatory Proteins , Metabolism , Cell Line, Tumor , Colonic Neoplasms , Drug Resistance , MicroRNAs , Metabolism , Proto-Oncogene Proteins c-bcl-2 , Genetics , Metabolism , RNA, Messenger , TransfectionABSTRACT
Objective To investigate the effect of sodium valproate in suppression of cell proliferation and arrest of cell cycle of in human hepatoma cell line SMMOL/LC-7721 and pancreatic cancer cell line PaTu8988.Methods Hepatoma cell line SMMOL/LC-7721 and pancreatic cancer cell line PaTu8988 were inoculated on the culture plate,cultured in the DMEM medium,they were intervened with sodium valproate in concentration of 0.2 mmol/L (0.2 mmol/L group),1.0 mmol/L (1.0 mmol/L group),5.0 mmol/L (5.0 mmol/L group) and dimethyl sulfoxide (control group) for 48 h respectively.Absorbance was measured by enzymelinked immunosorbentassay equipment,and inhibition ratio was calculated.Cell cycle was detected by flow cytometry.Results The absorbance of hepatoma cell line SMMOL/LC-7721 and pancreatic cancer cell line PaTu8988 in 5.0 mmol/L group were significantly lower than those in control group and 0.2 mmol/L group (0.569 ±0.059 vs.0.706 ±0.033 and 0.760 ±0.020,2.068 ±0.178 vs.2.793 ±0.144 and 2.663 ± 0.078,P ＜ 0.05),the absorbance of pancreatic cancer cell line PaTu8988 in 1.0 mmol/L group (2.432 ± 0.084) was significantly lower than that in control group and 0.2 mmol/L group (P ＜ 0.05).With the sodium valproate concentration increased,inhibition rate of tumor cell increased gradually,the inhibition rate of hepatoma cell line SMMOL/LC-7721 and pancreatic cancer cell line PaTu8988 in 5.0 mmol/L group was 23.5％ and 25.9％ respectively.Compared with control group,with the sodium valproate concentration increased in 0.2,1.0,5.0 mmol/L group,the proportion of G1 phase cell increased gradually in hepatoma cell line SMMOL/LC-7721 [(49.25 ± 1.63)％,(65.26 ± 2.34)％,(83.13 ± 1.78)％ vs.(49.22 ± 4.35)％],the proportion of S phase cell decreased gradually [(26.84 ± 2.30)％,(17.76 ± 3.90)％,(3.38 ± 0.65)％ vs.(29.21 ± 2.35)％],cell cycle showed G1 phase arrest,there was significant difference (P ＜ 0.05).Compared with control group and 0.2 mmol/L group,the proportion of G2 phase cell increased in pancreatic cancer cell line PaTu8988 in 1.0 and 5.0 mmol/L group [(26.80 ± 1.50)％,(36.58 ± 3.78)％ vs.(12.00 ± 4.62)％,(16.54 ± 2.26)％],cell cycleshowed G2 phase arrest,there was significant difference (P ＜ 0.05).Conclusion Sodium valproate mightsignificantly suppress the cell proliferation in hepatoma cell line SMMOL/LC-7721 and pancreatic cancercell line PaTu8988 and induce cell cycle arrest,it is clinically promising antitumor drug.
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Objective To investigate the effects of valproic acid ( VPA) on cell proliferation and cell cycle in human pancreatic cancer cell line PaTu8988 in vitro. Methods PaTu8988 cells were treated with VPA in concentration of 0, 0.2, 1.0 or 5.0 mmol/L for 24 h and 48 h respectively. Cell viability was measured by WST-8 assay. Cell cycles were detected by flow cytometery. Dimethyl sulfoxide added to the medium was used as blank control group, while PBS added to the medium was used as PBS group. Results After VPA treatment for 24 h, the inhibition rate of VPA 5.0 mmol/L group was 18.9% , which was significantly higher than those in control group, PBS group and VPA 0.2, 1.0 mmol/L group (0, 4.4% , 6.8%, 6.1% , P <0.05). After 48 h, the inhibition rates of VPA 1.0, 5.0 mmol/L were 12.9%, 25.9% , which was significantly higher than those in control group, PBS group and VPA 0.2 mmol/L group (0, 6.2% , 4.6% , P <0.01). After VPA treatment for 24 h, the proportions of G2 phase cell in VPA 1.0, 5.0 mmol/L group were ( 26.57 ± 1.88) % , ( 34.11 ± 4.74 ) % , which was significantly higher than those in PBS group, control group, VPA 0.2 mmol/L group [(10.72 ± 2.02)% , ( 13.53 ± 2.28)% , (13.81 ±2.40)%, P <0.01 ], the changes 48 h after VPA treatment was consistent with the changes 24 h after VPA treatment. Conclusions VPA may significantly suppress the cell proliferation of human pancreatic cancer cell line PaTu8988, and induce cell cycle arrest in G2 phase in a time and dose-dependent manner.