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1.
Article in English | WPRIM | ID: wpr-880862

ABSTRACT

Oral squamous cell carcinoma (OSCC) has a high incidence of metastasis. Tumour immunotherapy targeting PD-L1 or PD-1 has been revolutionary; however, only a few patients with OSCC respond to this treatment. Therefore, it is essential to gain insights into the molecular mechanisms underlying the growth and metastasis of OSCC. In this study, we analysed the expression levels of protein kinase D3 (PKD3) and PD-L1 and their correlation with the expression of mesenchymal and epithelial markers. We found that the expression of PKD3 and PD-L1 in OSCC cells and tissues was significantly increased, which correlated positively with that of mesenchymal markers but negatively with that of epithelial markers. Silencing PKD3 significantly inhibited the growth, metastasis and invasion of OSCC cells, while its overexpression promoted these processes. Our further analyses revealed that there was positive feedback regulation between PKD3 and PD-L1, which could drive EMT of OSCC cells via the ERK/STAT1/3 pathway, thereby promoting tumour growth and metastasis. Furthermore, silencing PKD3 significantly inhibited the expression of PD-L1, and lymph node metastasis of OSCC was investigated with a mouse footpad xenograft model. Thus, our findings provide a theoretical basis for targeting PKD3 as an alternative method to block EMT for regulating PD-L1 expression and inhibiting OSCC growth and metastasis.


Subject(s)
Animals , B7-H1 Antigen/metabolism , Carcinoma, Squamous Cell , Cell Line, Tumor , Feedback , Head and Neck Neoplasms , Humans , Mice , Mouth Neoplasms , Protein Kinase C , STAT1 Transcription Factor , Squamous Cell Carcinoma of Head and Neck
2.
Article in Chinese | WPRIM | ID: wpr-805287

ABSTRACT

Although the combination of surgery, radiotherapy and chemotherapy is the main methods of cancer treatment, it still fails to solve certain tumors, especially metastatic tumors. With the in-depth study of tumorigenesis and development mechanism, and the exploration and clinical application of tumor immunotherapy, the survival period of patients with malignant tumors has been significantly prolonged. Tumor immunotherapy has become an effective anti-tumor method by activating the body′s own immune system to achieve tumor suppression. The combination of chemotherapy and immunotherapy has a significant effect and has become a feasible solution for cancer treatment. The rationally designed nanomedicines can effectively combine chemical drugs and immunological preparations, and have become an effective delivery carrier basis and treatment means for clinically targeting tumor tissues, synergistic immune mechanisms to kill tumor cells, and treating tumors. In this paper, the types of multifunctional nanomedicines used in chemotherapy and various immunotherapies in recent years and their advantages in cancer therapy were reviewed.

3.
Article in Chinese | WPRIM | ID: wpr-823497

ABSTRACT

Although the combination of surgery, radiotherapy and chemotherapy is the main methods of cancer treatment, it still fails to solve certain tumors, especially metastatic tumors. With the in-depth study of tumorigenesis and development mechanism, and the exploration and clinical application of tumor immunotherapy, the survival period of patients with malignant tumors has been significantly prolonged. Tumor immunotherapy has become an effective anti-tumor method by activating the body's own immune system to achieve tumor suppression. The combination of chemotherapy and immunotherapy has a significant effect and has become a feasible solution for cancer treatment. The rationally designed nanomedicines can effectively combine chemical drugs and immunological preparations, and have become an effective delivery carrier basis and treatment means for clinically targeting tumor tissues, synergistic immune mechanisms to kill tumor cells, and treating tumors. In this paper, the types of multifunctional nanomedicines used in chemotherapy and various immunotherapies in recent years and their advantages in cancer therapy were reviewed.

4.
Frontiers of Medicine ; (4): 610-617, 2019.
Article in English | WPRIM | ID: wpr-771242

ABSTRACT

Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarkable clinical effects, this therapy has side effects that cannot be underestimated. Cytokine release syndrome (CRS) is one of the most clinically important and potentially life-threatening toxicities. This syndrome is a systemic immune storm that involves the mass cytokines releasing by activated immune cells. This phenomenon causes multisystem damages and sometimes even death. In this study, we reported the management of a patient with recurrent and refractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T treatment. The early application of tocilizumab, an anti-IL-6 receptor antibody, according to toxicity grading and clinical manifestation is recommended especially for patients who suffer continuous hyperpyrexia, hypotensive shock, acute respiratory failure, and whose CRS toxicities deteriorated rapidly. Moreover, low doses of dexamethasone (5-10 mg/day) were used for refractory CRS not responding to tocilizumab. The effective management of the toxicities associated with CRS will bring additional survival opportunities and improve the quality of life for patients with cancer.

5.
Article in Chinese | WPRIM | ID: wpr-699839

ABSTRACT

As the outermost part,cornea plays a critical role in protecting the eyeball and functions as main component of the dioptric media. Trauma,inflammation,malnutrition,inherited diseases,tumors,contact lens problems and complications of refractive surgeries may cause corneal injury. However,there are still no perfect treatments for severe corneal damage. Progresses have been made in the research field of corneal stem cells in recent years. Epithelial stem cells play an important role in corneal wound healing, whereas the contribution of stromal and endothelial stem cells is less studied. Moreover, corneal cells differentiated from alternative cell sources have a brilliant prospect in transplantation. This article reviewed the recent research progress of stem cells in the corneal epithelial,stromal and endothelial wound healing.

6.
Article in Chinese | WPRIM | ID: wpr-617470

ABSTRACT

Bromodomain and extra-terminal domain(BET)Bromodomain has become a new target for the treatment of cancers and other human disorders. Nowadays,several classes of its potent and selective small-molecule inhibitors have been identified,many of which are in clinical trials. Preclinical and clinical data have shown that BET Bromodomain inhibitors have good prospects. Howev-er,there are potential therapeutic deficiencies,such as drug resistance. At present,attempts are being made to develop BET Bromodo-main inhibitors and degraders based on polypharmacology,combining BET Bromodomain with other targets of different mechanisms. In this paper,small-molecule kinase/BET inhibitors,small-molecule histone deacetylases(HDAC)/BET inhibitors and BET protein degraders are reviewed,which may provide guidance for further research on BET protein.

7.
Article in Chinese | WPRIM | ID: wpr-489576

ABSTRACT

Objective To study the biocompatibility of bone marrow mesenchymal stem cells (BMSCs) on acellular collagen matrix double-layer material.Methods BMSCs with acellular collagen matrix double-layer material were trained as experimental group,while separately cultured BMSCs as control group.The growth and proliferation of BMSCs on acellular collagen matrix double-layer material were investigated.Scanning electron microscope was used to observe the adherence of cells,and cell vitality was detected by CCK-8 method.Results The acellular collagen matrix double-layer material did not influence the growth and proliferation of BMSCs.The difference between the growth curves of experimental group and control group was not significant (P>0.05).Conclusions The acellular collagen matrix double-layer material has acceptable biocompatibility.This research provides a scientific basis for the application of this composite material.

8.
Clinical Medicine of China ; (12): 417-419, 2015.
Article in Chinese | WPRIM | ID: wpr-481974

ABSTRACT

Objective To investigate the clinical effect and security of spraying Zhikang Capsules guided by gastroscopy in treatment elderly upper gastrointestinal bleeding.Methods Eighty-four elderly gastric duodenal ulcer bleeding patients were randomly assigned to group A,B and C (n =28 for each group).Patients in group A were used noradrenalin to spray with gastroscopy,in group B were used thrombin and in group C were used Zhikang Capsules.The total effective,the immediate homeostasis rate,the incidence of rebleeding,the emergency operation rate and the incidence of adverse reaction were recorded and analyzed.Results Total effective rate of group C was 96.4% (27/28),significantly higher than that in group A (71.4%,20/28),B (75.0%,21/28) and the difference was significant(P<0.05).The incidence of rebleeding in group A,B,C were 28.6% (8/28),17.9% (6/28),3.6% (1/28) respectively,and the difference was significant (P <0.05).The same trend was seen regarding of the incidence of adverse reaction among three groups (25.0%,7/28;10.7%,3/28;0,0/28;P<0.05).Conclusion Spraying Zhikang Capsules guided by gastroscopy is showed with good therapeutic effect in treating elderly upper gastrointestinal bleeding and high safety,and with less adverse reaction.

9.
Article in Chinese | WPRIM | ID: wpr-601605

ABSTRACT

Objective To study the radioresistance increased by low level laser irradiation (LLLI) in stem cells.Methods Umbilical cord mesenchymal stem cells (UC-MSCs) were divided into control group and experimental groups (LLLI only,γ-ray irradiation only and LLLI combined with γ-ray irradiation groups).635 nm (10 mW/cm2,12 J/cm2) laser irradiation was applied using for 3 days (twice a day),and cells were exposed in 2 Gy dose γ-ray irradiation on the third day.DNA injury was detected by alkaline single cell gel electrophoresis,reactive oxygen species (ROS),superoxide dismutase (SOD) and catalase (CAT) activity were valued using detection kits.Results DNA injury in LLLI combined with γ-ray irradiation group was lower than that in γ-ray irradiation exposed group,activity of oxidation stress kinases was enhanced,and level of ROS was inhibited.Conclusions Ironizing radioresistance of UC-MSCs can be increased after treatment of 635 nm LLLI,which will induce the radiation sensitivity of transplanting cells.

10.
Journal of Medical Postgraduates ; (12): 127-130, 2015.
Article in Chinese | WPRIM | ID: wpr-461178

ABSTRACT

Objective Folate receptors ( FRs) , overexpressed on the surface of a variety of tumor cells , are potential targets for tumor targeting therapy .This study aimed to prepare an FR-mediated drug nanocarrier with folate conjugated pullulan acetate ( FPA) to target chemotherapeutic agents to FR-overexpressed tumor cells and investigate its tumor-suppressing effect in vitro. Methods The cytotoxicity of epirubicin-loaded FPA nanoparticles ( FPA/EPI NP) against HepG2 and Hela cells was evaluated by MTS assay.The HepG2 and Hela cells were divided into five groups to be treated with NPs (NP control), chlorpromazine, chloro-quine, amiloride, and folate, respectively, followed by detection of the fluorescence intensity by flow cytometry . Results FPA/EPI NP was successfully formulated into NPs , with the mean particle size of (268.5 ±12.0) nm, by dialysis with an almost spherical shape . The drug-loading rate and entrapment rate of FPA/EPI NP were (6.45 ±1.04) and (72.45 ±11.50) %, respectively.The survival rates of the HepG2 and Hela cells were both >95%after 24 hours of incubation with FPA NP at 5, 40, 200, 400 and 1000μg/mL and 90.0%after 72 hours.The survival rates of the HepG2 cells treated with 5, 40, 200, 400 and 1000μg/mL FPA/EPI NP for 24 hours were (92.3 ±5.2), (70.4 ±4.6), (50.0 ±4.0), (41.1 ±4.1) and (27.0 ±3.6) %, respectively.Compared with the NP control group, the Hela cells of the chlorpromazine , amiloride and folate groups showed a significantly lower rate of NP uptake (P<0.05), and so did the HepG2 cells pretreated with chlorpromazine or amilo-ride (P<0.05).At 72 hours, the half maximal inhibitory concentrations (IC50) of FPA/EPI NP against HepG2 and Hela cells were 168 and 105μg/mL, respectively . Conclusion Clathrin-mediated endocytosis and macropinocytosis are involved in the internaliza-tion of FPA/EPI NP in HepG2 cells, while clathrin-and FR-mediated endocytosis in that of Hela cells .FPA NP may serve as a new drug carrier for tumor-targeted therapy .

11.
Article in Chinese | WPRIM | ID: wpr-811944

ABSTRACT

@#Recognizing acetyl-lysine of histone is a key process of epigenetic regulation that is mediated by a protein module called bromodomain(BRD). The bromodomain inhibitors of the bromodomains and extra-terminal(BET)family have shown great potential in anti-inflammatory and antiproliferative effects. Through a review of diseases and structures about BET bromodomain, different kinds of inhibitors were analyzed and their structure-activity relationships were summarized. Herenin, the recent advances reported are reviewed for discovering more excellent small molecule inhibitors.

12.
Clinical Medicine of China ; (12): 64-66, 2014.
Article in Chinese | WPRIM | ID: wpr-445085

ABSTRACT

Objective To investigate the effect of Zhikang capsules on treatment of gastric duodenal ulcer bleeding.Methods Eighty patients with gastric duodenal ulcer bleeding were randomly divided to therapy group(patients received Pantoprazole(20 mg) + Zhikang capsules(1.2 g),2 time/d,n =46) and control group (patients received Pantoprazole,20 mg,2 time/d,n =34).All treatment period was a week.The clinical efficacy were evaluated.Results The rate of total effective of therapy group was 95.7% (44/46),and control group was 79.4% (27/34).The difference was statistically significant (x2 =5.164,P < 0.05).Conclusion Zhikang capsules is proved to be an efficacy drug to treatment of gastric duodenal ulcer bleeding,and with less adverse reaction.

13.
Article in Chinese | WPRIM | ID: wpr-444165

ABSTRACT

Objective To investigate the pharmacokinetic characteristics of PSD-007 in BN rats.Methods Blood of the BN rats was collected from the inner canthus after iv administration of PSD-007,and the plasma drug concentrations at different times were determined by fluorescent spectrometry.The best compartment model and the pharmacolinetic were calculated by the software of DNS 2.0.Results The elimination process of PSD-007 fitted three-compartment open model after iv administration.The principal pharmacokinetic parameters were t1/2α=0.096 h,t1/2β=1.299 h,t12γ=19.387 h,V1=0.259 L/kg,A UC=15.263 mg/(L ·h).Conclusions The sensitivity of fluorescent spectrometry was high and the operation is sinple and the progress is short.PSD-007 has fast absorption,quick effect and elimination without accumulation phenomenon.

14.
Article in Chinese | WPRIM | ID: wpr-470914

ABSTRACT

Objective To study the structure and function changes of erythrocyte in hypercholesterolemia rabbits that treated with irradiation in auricle root by low level 650 nm laser.Methods Sixteen male rabbits were selected to establish the model animal of hypercholesterolemia,successful model rabbits were divided into 2 groups (model and treatment groups),6 rabbits per group,and 6 normal rabbits were selected as control group.650 nm laser of 100 mW were given in auricle root in rabbits of treatment group for 16 weeks (6 d one week,twice a day,30 min one time).Blood from ear vein was collected every 4 weeks to perform routine and biochemical blood examination,and one-drop blood test under microscope was used for blood accumulation observation.Results Total number of red blood cells of treatment group decreased,while model group showed an increasing trend than normal group (P<0.05).Hemoglobin in three groups were lower than other two groups (P>0.05).Hematocrit (HCT) in treatment group were lower than that in normal group,while HCT in model group were higher than that in other two groups and showed a higher aggregation degree also.Less than model group,treatment group showed less aggregation degree but with higher total bilirubin.Conclusions Low level laser of 650 nm showed an effect on total number of erythrocytes,HCT and red blood cells aggregation,high dose of laser might be injury for erythrocytes and lead to total bilirubin increasement.

15.
Article in Chinese | WPRIM | ID: wpr-599460

ABSTRACT

Objective The dose and type of light and photosensitizer could seriously affect the curative effect of photodynamic therapy (PDT).The purpose of this study was to observe whether or not PDT with hematoporphyrin monomethyl ether (HMME) can cure laryngocarcinoma in the solid tumor model,and to define the proper laser amount for killing the cancer cells.Methods Forty eight BALB/c mouse models with subcutaneous Hep-2 laryngeal carcinomas were prepared.Mice were divided into six groups depending on the amount of laser received from 30 J/cm2 to 480 J/cm2 including a control group,tumor size in each group was between 8 mm and 10 mm.Tail vein injection were given with HMME prior to applying the laser light,and then illumination was carried out on the tumor at 3 h after HMME administration.Tumor volume,animal weight and histopathologic changes were observed after PDT.Results All mice apparently showed positive results via PDT,and the cancer had been cured in 120 J/cm2 and 480 J/cm2 groups.The laryngeal cancer lesions began to form scab 1 d after PDT and the scab became hard and black after 5 d.The tumor regression began simultaneously and completed around 30 d after PDT.Conclusions PDT may treat laryngeal cancers which sized less than 10 mm in mouse models.The optimum energy to destruct the laryngeal cancer cells may be 120 J/cm2.

16.
Acta Pharmaceutica Sinica ; (12): 25-31, 2013.
Article in Chinese | WPRIM | ID: wpr-445496

ABSTRACT

The steroidal enzyme cytochrome P45017alpha catalyzes the conversion of progesterone and pregnenolone into androgens, androstenedione and dehydroepiandrosterone, respectively, the direct precursors of estrogens and testosterone. Dihydrotestosterone is the principal active androgen in the prostate, testosterone is also an active stimulant of the growth of prostatic cancer tissue. Inhibition of this enzyme as a mechanism for inhibiting androgen biosynthesis could be a worthwhile therapeutic strategy for the treatment of PCA. In this paper, four categories of steroidal inhibitors of cytochrome P45017alpha will be reviewed, a diverse range of steroidal inhibitors had been synthesized and shown to be potent inhibitors of P45017alpha.

17.
Article in Chinese | WPRIM | ID: wpr-425899

ABSTRACT

Microspheres made of poly-lactic-co-glycolic acid (PLGA) have been frequently proposed as drug delivery systems.A very significant challenge in the development of controlled PLGA releasing systems is the instability of drugs especially therapeutic peptides and proteins.Additional approaches,particularly the use of additives,are needed to optimize PLGA delivery of drugs.This article reviews the effects of additives,especially the effects of stabilizing protein during the preparation of PLGA microsphere and the sustained drug releasing processes.

18.
Article in Chinese | WPRIM | ID: wpr-420320

ABSTRACT

Objective To investigate and compare the killing effect of photodynamic therapy (PDT)induced by hematoporphyrin derivative (HpD),hematoporphyrin monomethyl ether (HMME) and photocarcinorin (PsD007) on human leukemia cells K562 in vitro.Methods Human leukemia cells were cultured with serial concentrations of photosensitizers followed by irradiation of different dosage of laser light,then MTT colorimetric assay was applied to measure the relative survival rate of PDT for the cells.Results Significant difference in the inhibitory between the PDT group and control group was observed (P<0.05).The survival rate of PDT for the cells elevated along with the increase in the concentration of sensitizer and dose of laser light.When the photosensitizer concentration was bigger (25 μg/ml) or the energy density was bigger (7.2 J/cm2),the effect of PsD007 was better than HMME,and they were significantly better than HpD (P<0.05).Conclusion PDT has significant killing effect on human leukemia cells K562,and its relative inhibitory rate appears to be correlated with the dose of sensitizer and laser light irritation.The effect of PDT is related to the photosensitizers.The effect of HpD-PDT is not as effective as PsD007 and HMME.On the conditions of higher energy density and larger photosensitizer concentration,the effect of PsD007-PDT is better than HMME-PDT.

19.
Article in Chinese | WPRIM | ID: wpr-589788

ABSTRACT

ObjectiveTo study the feasibility of analyzing photosensitizers absorbing process by cells based on image processing technology.MethodsFluorescence images of Laryngeal cells were taken by inverted fluorescence microscope after adding photosensitizers for a certain time.Parameter L that reflects the fluorescence intensity of cells in different times was obtained and the calculation results were compared.ResultsThe fluorescence intensity of cells increased over time.Sobel operater and Otsu algorithm can both reflect the fluorescence intensity of images.ConclusionImage processing technology can effectively analyzes the process of photosensitizers absorbed by cells.

20.
Article in Chinese | WPRIM | ID: wpr-247376

ABSTRACT

<p><b>OBJECTIVE</b>To study the influences of different processing methods on the content of Angelica sinensis polysaccharides (APS) from the same origin.</p><p><b>METHOD</b>The contents of neutral polysaccharides and acidic polysaccharides in various samples of A. sinensis were determined by phenol-sulfuric acid and carbazole-sulfuric acid method, respectively. The proliferation ability of lymphocyte was detected by MTT method after the cells were cultured with different concentrations of APS from two samples processed by different methods.</p><p><b>RESULT</b>The different processing methods had different effects on the contents of polysaccharide. The maximum content of APS (26.03%) was found in the sample processed by microwave drying medium-fired, but the minimum content of APS (2.25%) was found in the sample processed by vacuum drying at 50 TC. Furthermore, the APS (high concentration group, P < 0.01) processed by microwave drying medium-fired could both accelerate proliferation of spleen lymphocytes directly and increase proliferation of T cells of mice induced by Con A. However, the APS processed by far-infrared drying did not show conspicuous immune enhancement activity.</p><p><b>CONCLUSION</b>Different processing methods have different effects on the contents of APS and the proliferation ability of lymphocytes.</p>


Subject(s)
Angelica sinensis , Chemistry , Animals , Cell Proliferation , Drug Compounding , Methods , Drugs, Chinese Herbal , Chemistry , Mice , Polysaccharides , Chemistry , Pharmacology , Spleen , Cell Biology , T-Lymphocytes , Cell Biology
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