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OBJECTIVE@#To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective.@*METHODS@#Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ+TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction.@*RESULTS@#TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45+ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01).@*CONCLUSIONS@#TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Subject(s)
Male , Animals , Mice , Tripterygium , Psoriasis/drug therapy , Keratinocytes , Skin Diseases/metabolism , Cytokines/metabolism , Imiquimod/metabolism , Dermatitis/pathology , Disease Models, Animal , Mice, Inbred BALB C , Skin/metabolismABSTRACT
In this study, an ultra-performance liquid chromatography-quadrupole time-of-flight high resolution mass spectrometer(UPLC-Q-TOF-HRMS) was used to investigate the effects of the active ingredients in Periploca forrestii compound on spleen metabolism in rats with collagen-induced arthritis(CIA), and its potential anti-inflammatory mechanism was analyzed by network pharmacology. After the model of CIA was successfully established, the spleen tissues of rats were taken 28 days after administration. UPLC-Q-TOF-HRMS chromatograms were collected and analyzed by principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and MetPA. The results showed that as compared with the blank control group, 22 biomarkers in the spleen tissues such as inosine, citicoline, hypoxanthine, and taurine in the model group increased, while 9 biomarkers such as CDP-ethanolamine and phosphorylcholine decreased. As compared with the model group, 21 biomarkers such as inosine, citicoline, CDP-ethanolamine, and phosphorylcholine were reregulated by the active ingredients in P. forrestii. Seventeen metabolic pathways were significantly enriched, including purine metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism. Network pharmacology analysis found that purine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism played important roles in the pathological process of rheumatoid arthritis. This study suggests that active ingredients in P. forrestii compound can delay the occurrence and development of inflammatory reaction by improving the spleen metabolic disorder of rats with CIA. The P. forrestii compound has multi-target and multi-pathway anti-inflammatory mechanism. This study is expected to provide a new explanation for the mechanism of active ingredients in P. forrestii compound against rheumatoid arthritis.
Subject(s)
Rats , Animals , Periploca , Cysteine , Cytidine Diphosphate Choline , Network Pharmacology , Phosphorylcholine , Metabolomics , Arthritis, Rheumatoid/drug therapy , Biomarkers , Glycerophospholipids , Methionine , Purines , Chromatography, High Pressure LiquidABSTRACT
Objective To evaluate the safety and effectiveness of laparoscopic common bile duct exploration in the treatment of common bile duct stones. Methods A retrospective analysis was conducted for 158 patients with cholecystolithiasis and choledocholithiasis admitted to the Number One Hospital of Zhangjiakou from January 2015 to December 2019.The patients were assigned into three groups according to the diameters of cystic duct and common bile duct,degrees of abdominal infection and tissue edema,and operation method.Group A(16 cases):laparoscopic cholecystectomy,transcystic choledochoscopic exploration for stone removal;Group B(94 cases):laparoscopic cholecystectomy,common bile duct incision exploration combined with choledochoscopy for stone removal,T tube drainage;Group C(48 cases):laparoscopic cholecystectomy,common bile duct incision exploration combined with choledochoscopy for stone removal,primary closure of the common bile duct.The operation time,residual rate of stones,and complication(bleeding,bile leakage,and wound infection) rate were compared between groups. Results The operation time of groups A,B,and C was(95.1±14.7),(102.2±18.1),(110.1±16.4) minutes,respectively,which showed no statistical difference between each other(F=0.020,P=0.887).One case in group A had residual stones,while no residual stone appeared in groups B and C.The overall stone clearance rate was 99.4% and the overall complication rate was 1.9%.There was no perioperative death. Conclusion It is generally safe and effective to carry out laparoscopic cholecystectomy and common bile duct exploration for stone removal in suitable populations.
Subject(s)
Humans , Choledocholithiasis/surgery , Common Bile Duct/surgery , Gallstones/surgery , Laparoscopy/methods , Retrospective StudiesABSTRACT
Objective: Autologous peripheral blood stem cells (PBSC) derived from bone marrow can promote liver regeneration and improve the liver function of patients, but there are few studies on its effect on the long-term outcomes in patients with decompensated cirrhosis. Based on previous work, this study observed the clinical outcomes of PBSC treatment in patients with decompensated cirrhosis for 10 years, in order to provide more data support for the safety and efficacy of stem cells in clinical applications. Methods: Data of patients with decompensated liver cirrhosis who completed PBSC treatment in the Department of Gastroenterology of the First Affiliated Hospital of Air Force Military Medical University from August 2005 to February 2012 were included. The follow-up endpoint was death or liver transplantation, and patients who did not reach the follow-up endpoint were followed-up for at least 10 years. The patients with decompensated liver cirrhosis who met the conditions for PBSC treatment but did not receive PBSC treatment in our hospital during the same period were used as controls. Results: A total of 287 cases with decompensated liver cirrhosis had completed PBSC treatment, and 90 cases were lost to follow-up within 10 years after surgery. A total of 151 cases with complete survival follow-up data were included in the control group. There were no statistically significant differences in baseline information such as gender, age, etiological composition and liver function score between the two groups. The 10-year survival rate was higher in PBSC than control group (37.56% vs. 26.49%, P<0.05). Cholinesterase, albumin, international normalized ratio, Child-Turcotte-Pugh score, model for end-stage liver disease score, and other indicators were gradually recovered within 3 months to 1 year after PBSC treatment, and stabilized at a more desirable level in the long-term after follow-up for up to 10 years. There was no statistically significant difference in the incidence of liver cancer between the two groups (25.22% vs.31.85%, P=0.267). The age of onset of hepatocellular carcinoma was later in PBSC than control group [(56.66±7.21) years vs. (52.69±8.42) years, P<0.05]. Conclusions: This long-term observational follow-up study of more than ten years confirms that PBSC treatment can bring long-term benefits to patients with decompensated cirrhosis, with good long-term safety, thus providing more data support on the safety and efficacy of stem cells for clinical applications.
Subject(s)
Humans , Middle Aged , End Stage Liver Disease , Follow-Up Studies , Liver Cirrhosis/drug therapy , Peripheral Blood Stem Cells , Severity of Illness Index , Treatment OutcomeABSTRACT
Tumor blood and lymphatic vessel growth are necessary conditions for tumor growth, progression and metastasis, which are closely related with infiltrating nnate as well as adaptive immune cells. On one hand, immune cells rely on adhesion molecules on vascular endothelial cells to penetrate into tumor tissues and show anti-tumor characteristics. On the other hand, they can regulate tumor angiogenesis and lymphangiogenesis by secreting chemokines and cytokines, playing an important role in the process of tumor blood metastasis. In addition, the role of immune cells in promoting tumor blood metastasis highlights the shortcomings of t anti-angiogenic therapy. Therefore, targeting immune cells and tumor angiogenesis improve the effect of therapeutic. Based on these, this article summarizes the effects of immune cells on blood and lymphatic vessels n tumor metastasis, as well as related anti-vascular and immune therapies, in order o provide deas for subsequent research.
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Immune checkpoint inhibitor ( ICI) activates the host' s anti-tumor immune response by blocking negative regulatory immune signals. A series of clinical trials showed that ICI could effectively induce tumor regression in a subset of advanced cancer patients. Anti-angiogenesis drugs commonly used to block tumor angiogenesis can inhibit the growth of tumors, but they cannot improve the survival of patients with limitations in application such as drug resistance. Tumor immune response is closely related to angiogenesis. In turn, tumor angiogenesis highly depends on immunosuppressive microenvironment. Recent studies have indicated that ICI resistance could be alleviated by combination therapy with anti-angiogenesis treatment, and the efficacy of combination therapy was superior to that of monotherapy. The reciprocal regulation between tumor vascular normalization and immune reprogramming forms a reinforcing loop that reconditions the tumor immune microenvironment to induce durable antitumor immunity. This review clarifies the latest understanding of ICI combined anti-angiogenesis therapy and provides ideas for subsequent research.
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OBJECTIVE@#To investigate the auxiliary diagnostic value of serum adenosine deaminase (ADA) in acute leukemia (AL) at clinical test.@*METHODS@#123 AL patients hospitalized in Zhejiang hospital from November 2018 to March 2020 were enrolled as the observation group, and 98 healthy people in the same period were randomly enrolled as the control group. AL patients were divided into two groups: 77 acute myeloid leukemia (AML) patients for AML group and 46 acute lymphoblastic leukemia (ALL) patients for ALL group. The levels of adenosine deaminase (ADA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH) and homocysteine (Hcy) in serum of the patients were detected, and the correlation of ADA with these items was analyzed. Receiver operating characteristic curve (ROC) was used to analyze the clinical diagnostic value of ADA, Yoden index was used to confirm the best cut-off point.@*RESULTS@#The serum ADA level in AL patients was significant higher than that in control group (P < 0.05). The results of Pearson correlation analysis showed that there was a significant positive correlation of ADA with Hcy, ALT, AST, GGT, LDH in AML group (r = 0.47, r = 0.28, r = 0.37, r = 0.22, r = 0.55); and also there was a significant positive correlation of ADA with GGT in ALL group (r = 0.54). In AML group, the maximum area under ROC curve was 0.761 (P = 0.00), 95% confidence interval was 0.682-0.841, sensitivity was 54.50%, specificity was 98.90%, and the best cut-off point was 17.1 U/L. In ALL group, the maximum area under ROC curve was 0.785, 95% confidence interval was 0.694-0.877, sensitivity was 65.90%, specificity was 84.00%, and the best cut-off point was 13.45 U/L.@*CONCLUSION@#The detection of ADA in serum can be used as an auxiliary examination in patients with AL, which can provide a certain value for the diagnosis of the disease.
Subject(s)
Humans , Adenosine Deaminase , L-Lactate Dehydrogenase , Leukemia, Myeloid, Acute/diagnosis , ROC Curve , Retrospective StudiesABSTRACT
OBJECTIVE@#To evaluate the classification criteria of early rheumatoid arthritis (ERA) and compare the sensitivity and specificity with the criteria of 1987 American College of Rheumatology (ACR) criteria and 2010 ACR/European League Against Rheumatism (EULAR).@*METHODS@#Patients from 4 hospitals, aged more than 16 years, with arthritis, whose disease duration was ≤1 year, and with ≥1 joint pain and swelling were enrolled in the study. The indicators including clinical manifestations, laboratory tests and imaging examinations were observed. The ERA patients were dignosed by two experienced rheumatologists based on the clinical features, drug therapy information and radiography features.@*RESULTS@#(1) A total of 325 patients with arthritis were enrolled, including 98 males (30.15%) and 227 females (69.85%), The average age was (47.53±14.44) years, and the median disease duration was 5 (2, 8) months. Finally, 236 patients were dignosed with ERA, and 89 patients were dignosed with other diseases (Non-ERA, including osteoarthritis, reactive arthritis, undifferentiated arthritis, spondyloarthritis, etc). (2) The sensitivity of ERA criteria was 87.29%, and the specificity was 84.37%. The sensitivity was higher than that of 1987 ACR criteria (χ2=43.641, P < 0.001), and had no significant difference compared with 2010 ACR/EULAR criteria (χ2=0.446, P=0.593). But the specificity of ERA criteria was lower than that of 1987 ACR criteria (χ2=4.891, P=0.027), which was not statistically significant compared with 2010 ACR/EULAR criteria (χ2=0.044, P=1.000). (3) In the patients with arthritis whose disease duration was ≤3 months and ≤6 months, the sensitivity of ERA criteria was 81.71% and 86.79%, respectively, both were higher than the 1987 ACR criteria (χ2=7.131, P=0.008; χ2=22.015, P < 0.001) and had no statistically difference compared with the 2010 ACR/EULAR criteria (χ2=0.220, P=0.755; χ2=0.473, P=0.491). The differences of the three criteria in specificity were not statistically significant. (4) The three different classification criteria were consistent with the clinical diagnosis, among which the ERA criteria and 2010 ACR/EULAR criteria were slightly higher (Kappa>0.6). The results of the consistency comparison between the three criteria showed that the ERA criteria and 2010 ACR/EULAR criteria had a better consistency (Kappa=0.836).@*CONCLUSION@#The sensitivity of ERA classification criteria in the diagnosis of ERA was higher than that of 1987 ACR criteria, and was equivalent to that of 2010 ACR/EULAR criteria. There is no significant difference in specificity between these three criteria. The ERA criteria can also identify patients with RA at a very early stage in arthritis with disease duration ≤3 months.
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Arthritis, Rheumatoid/diagnostic imaging , Osteoarthritis , Radiography , Rheumatology , Sensitivity and Specificity , United StatesABSTRACT
The tumor contains abundant new vessels, which are unevenly distributed, irregular, and branch-disordered. Angiopoietin (Ang) and tyrosine kinase receptor Tie mediate stable maturation of angiogenesis. Ang1 mainly plays a role in promoting vascular stabilization, and Ang2 is highly expressed in vessels, which makes the structure and function of vessels abnormal. Leaked vessels provide opportunities for invasion and metastasis of circulating tumor cells. Targeting the Ang/Tie axis to correct the abnormal state of vessels and promote its normalization, combined with chemotherapy drugs or immunotherapy, play a synergistic effect against tumors. This article summarizes the role of Ang/Tie axis in tumor angiogenesis and metastasis, and it aims to provide new ideas and strategies for clinical treatment of tumors.
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A s an important member of the body' s innate immunity and the pioneer of anti-tumor immunity, natural killer (NK) cells play a vital role in tumor immunity. Therefore, NK cell-based anti-tumor immunotherapy has increasingly become an emerging field of scientific research. NK cells have a cytotoxic effect on a variety of tumor types, and early clinical means to enhance T cell toxicity can also activate NK cells to exert a dual anti-tumor effect. This review summarizes the role of NK cells in anti-tumor immunity and its related mechanisms, and summarizes monoclonal antibodies .cytokine therapy and adoptive therapy targeting NK cells. In addition, this review clarifies the status and trends of NK cell immunotherapy and provides ideas and lessons for clinical research.
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This study was aimed to screen human papillomavirus (HPV) types associated with esophageal squamous cell carcinoma of Kazakh in Xinjiang using the gene chip technique and study the clinical significance of this application. The DNAs were collected from esophageal squamous cell carcinoma tissues and healthy esophageal mucosa of Kazakh adults in Xinjiang, and amplified firstly using HPV MY09/11 and then using HPV G5+/6+ to screen positive HPV specimens. These positive specimens were further detected by the gene chip technique to screen highly pathogenic HPV types. After determination with nested PCR amplification with HPV MY09/11 and G5+/6+, the infection rate of HPV was 66.67% in the esophageal squamous cell carcinoma group and 12.12% in the healthy control group. By testing the positive HPV specimens from the esophageal squamous cell carcinoma group, the infection rate of HPV16 was 97.72% and the co-infection rate of HPV16 and HPV18 was 2.27%. HPV16 infection may be involved in the development of esophageal squamous cell carcinoma in Xinjiang Hazakh adults.
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<p><b>OBJECTIVE</b>To evaluate clinical efficacy of electroacupuncture at Changqiang (GV 1) and Chengshan (BL 57) 30 min before surgery on postoperative pain and discomforts in patients with mixed hemorrhoids.</p><p><b>METHODS</b>One hundred and twenty cases of mixed hemorrhoids who received Milligan-Morgan operation were randomly divided into an electroacupuncture group, a sham electroacupuncture group and a blank group, 40 cases in each one. At the same time of basic treatment, the electroacupuncture was applied at Changqiang (GV 1) and Chengshan (BL 57) 30 min before surgery in the electroacupuncture group, while shallow needling without electrical stimulation at sham acupoint (1 cm next to acupoint) was applied 30 min before surgery in the sham electroacupuncture group, while no treatment was given before the surgery in the blank group. The total dose of painkillers in the first 24 h after operation, the number of cases who received additional anesthetic in the operation, the self-score of most severity pain in the first 24 h after operation and sleeping time in the night of surgery were observed.</p><p><b>RESULTS</b>The differences of the numbers of cases who received additional anesthetic in the operation had no statistical significance among the three groups (all P > 0.05), but compared with the sham electroacupuncture group and blank group, the total dose of painkillers in the first 24 h after operation was reduced in the electroacupuncture group [(2.43 +/- 1.08) tablets vs (3.23 +/- 1.33) tablets, (3.10 +/- 1.22) tablets], and the score of most severity pain was also decreased (6.65 +/- 1.00 vs 7.48 +/- 0.96, 7.25 +/- 1.19), besides, the sleeping time in the night of surgery was increased [(220.63 +/- 85.50) min vs (162.00 +/- 92.69) min, (151.50 +/- 80.01) min, all P < 0.05].</p><p><b>CONCLUSION</b>The electroacupuncture at Changqiang (GV 1) and Chengshan (BL 57) 30 min before surgery has effects of preemptive analgesia on postoperative pain for patients with mixed hemorrhoids.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Acupuncture Points , Electroacupuncture , Hemorrhoids , General Surgery , Pain, Postoperative , TherapeuticsABSTRACT
This study was aimed to screen human papillomavirus (HPV) types associated with esophageal squamous cell carcinoma of Kazakh in Xinjiang using the gene chip technique and study the clinical significance of this application. The DNAs were collected from esophageal squamous cell carcinoma tissues and healthy esophageal mucosa of Kazakh adults in Xinjiang, and amplified firstly using HPV MY09/11 and then using HPV G5+/6+ to screen positive HPV specimens. These positive specimens were further detected by the gene chip technique to screen highly pathogenic HPV types. After determination with nested PCR amplification with HPV MY09/11 and G5+/6+, the infection rate of HPV was 66.67% in the esophageal squamous cell carcinoma group and 12.12% in the healthy control group. By testing the positive HPV specimens from the esophageal squamous cell carcinoma group, the infection rate of HPV16 was 97.72% and the co-infection rate of HPV16 and HPV18 was 2.27%. HPV16 infection may be involved in the development of esophageal squamous cell carcinoma in Xinjiang Hazakh adults.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Asian People , Carcinoma, Squamous Cell , Ethnology , Genetics , Virology , Case-Control Studies , China , DNA, Neoplasm , Genetics , DNA, Viral , Genetics , Esophageal Neoplasms , Ethnology , Genetics , Virology , Host-Pathogen Interactions , Genetics , Human papillomavirus 16 , Genetics , Human papillomavirus 18 , Genetics , Molecular Typing , Methods , Oligonucleotide Array Sequence Analysis , Methods , Papillomaviridae , Classification , Genetics , Physiology , Papillomavirus Infections , Ethnology , Genetics , Virology , Polymerase Chain ReactionABSTRACT
<p><b>OBJECTIVE</b>To evaluate the therapeutic effect on pain in the dressing change after perianal abscess surgery treated with warm suspending moxibustion at Changqiang (GV 1).</p><p><b>METHODS</b>One hundred and sixty patients were randomized into a moxibustion group and a far-infrared therapy group, 80 cases in each one. In the moxibustion group, the warm suspending moxibustion at Changqiang (GV 1) was applied. In the far-infrared therapy group, the infrared ray was radiated at Changqiang (GV 1). The treatment started in 10 min after dressing change in the two groups. Totally, 8 treatments were required. The time requirement being equal to or less than 2 score in the assessment face scale (AFS), the case number of pain relief in 10 min after treatment and the intention of the two therapies after everyday dressing change were observed in the patients of the two groups.</p><p><b>RESULTS</b>In the moxibustion group, the time of pain relief was shorter than that of the far-infrared therapy group [(11.5 +/- 3.9) min vs (17.8 +/- 3.8) min on the 1st day; (9.4 +/- 3.6) min vs (15.2 +/- 4.3) min on the 2nd day; (7.8 +/- 2.7) min vs (14.3 +/- 3.2) min on the 3rd day; (6.4 +/- 3.3) min vs (10.5 +/- 2.9) min on the 4th day; (5.9 +/- 2.9) min vs (11.2 +/- 1.9) min on the 5th day; (5.3 +/- 2.2) min vs (8.8 +/- 2.3) min on the 6th day; (5.4 +/- 1.8) min vs (9.2 +/- 2.1) min on the 7th day; (5.1 +/- 1.4) min vs (9.5 +/- 2.6) min on the 8th day, all P < 0.05]. The case numbers of pain relief in 10 min after treatment were 74 cases, 75 cases, 77 cases and 78 cases from the 1st to the 4th day separately in the moxibustion group, which were much more than 63 cases, 65 cases, 68 cases and 69 cases in the far-infrared therapy group (all P < 0.05). The treatment intention scores in the moxibustion group were better than those in the far-infrared therapy group (all P < 0.05).</p><p><b>CONCLUSION</b>The warm suspending moxibustion at Changqiang (GV 1) relieves pain rapidly in the dressing change of much more patients after perianal abscess surgery in much shorter time as compared with the far-infrared therapy. Moreover, the patients have more expectation to be treated with moxibustion therapy.</p>
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Abscess , General Surgery , Anus Diseases , General Surgery , Moxibustion , Pain, Postoperative , TherapeuticsABSTRACT
<p><b>OBJECTIVE</b>To verify the clinical efficacy of acupuncture and moxibustion on defecating and pain symptoms in postoperative patient of anal fissure.</p><p><b>METHODS</b>Two hundred cases of postoperation of anal fissure were randomly divided into an acupuncture-moxibustion group and a medication group, 100 cases in each one. The basic treatment after the surgery was the same in two groups, besides, acupuncture was applied at Zhongliao (BL 33) and Xialiao (BL 34) in the morning of first 5 days of postoperative 24 h in the acupuncture-moxibustion group, and suspended moxibusiton was applied at Changqiang (GV 1) within 5 to 10 min after defecation; while two bags of forlax was orally administrated in the morning of first 5 days of postoperative 24 h in the medication group. The pain intensity, defecation willingness, defecation difficulty and stool texture during postoperative defecation were observed.</p><p><b>RESULTS</b>The defecation pain on the first two days after the treatment was not statistically significant between two groups (both P > 0.05). From the third day of treatment, the improvements of defecation pain in acupuncture-moxibustion group were more obvious than those in the medication group (all P < 0.05). The patients in the acupuncture-moxibustion group had more positive defecation willingness than those in the medication group (all P < 0.05). The differences of defecation difficulty and stool properties in two groups had no statistical significance (both P > 0.05).</p><p><b>CONCLUSION</b>The intervention treatment of acupuncture and moxibustion has clinical significance on relieving pain symptoms and improving defecation willingness in postoperative patient of anal fissure.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Acupuncture Therapy , Defecation , Fissure in Ano , Therapeutics , Moxibustion , Postoperative Period , Treatment OutcomeABSTRACT
Acute myeloid leukemia (AML) is a common type of hematopoietic malignancies seriously threatening human life. Resistance to chemotherapy is one of the main reasons for recurrence and refractoriness of acute myeloid leukemia. The mechanisms of chemoresistance are complex. This article reviews the mechanisms of chemoresistance in acute myeloid leukemia,the current research advances and the possible approach for reverse of drug resistance.
Subject(s)
Humans , Drug Resistance, Neoplasm , Physiology , Leukemia, Myeloid, Acute , Drug TherapyABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of histone deacetylase inhibitor suberic bishydroxamate (SBHA) on human acute myeloid leukemia (AML) cell lines.</p><p><b>METHODS</b>AML U937, KG-1 and Kasumi-1 cells were treated with SBHA. Cell growth was measured by MTT assay. Apoptosis was determined using flow cytometry. Activation of Caspase pathway and expression of apoptosis regulator proteins were detected by Western blot.</p><p><b>RESULTS</b>SBHA significantly induced growth arrest and apoptosis in U937, KG-1 and Kasumi-1 cells. Enhanced apoptosis was observed in SHBA group evidenced by strong activation of Caspase-9, Caspase-8 and Caspase-3. SHBA treatment resulted in down-regulation of anti-apoptotic protein Bcl-2 and Bcl-xl expression; down-regulated expression of antiapoptotic proteins survivin, XIAP and cIAP was also detected after SBHA treatment.</p><p><b>CONCLUSION</b>SBHA can effectively kill AML cells by inhibiting cell growth and inducing apoptosis, which is associated with the activation of Caspase pathway and regulation of apoptotic related proteins.</p>
Subject(s)
Humans , Apoptosis , Apoptosis Regulatory Proteins , Metabolism , Caspases , Metabolism , Cell Line, Tumor , Histone Deacetylase Inhibitors , Pharmacology , Hydroxamic Acids , Pharmacology , Leukemia, Myeloid, Acute , Metabolism , PathologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the in vitro effects of fludarabine on apoptosis and gene expression profile in human multiple myeloma (MM) cells.</p><p><b>METHODS</b>Cell growth was measured by a MTT assay. Cells apoptosis was evaluated by flow cytometry. The activation of caspase cascade was determined by Western blot analysis. The expression profile of apoptosis-related genes in human MM cells was detected by cDNA expression array system.</p><p><b>RESULTS</b>The growth of RPMI8226 and KM3 cells was suppressed by fludarabine treatment in a dose and time-dependent manner. After treatment with fludarabine for 24 h, the IC(50) for RPMI8226 cells was 2.13 µg/ml, and 0.36 µg/ml for KM3 cells. Apoptotic cells of RPMI8226 and KM3 increased in a dose- dependent manner after exposure to fludarabine for 24 h. Western blot analysis showed the activation of caspase-3 and PARP in the MM cells treated with fludarabine. The cDNA expression array showed that multiple pathways were involved in the apoptosis induced by fludarabine. Among 97 apoptosis-related genes, 25 genes were differently expressed and 13 expressions were up-regulated in fludarabine treated group, involving in Bcl-2 pro-apoptotic gene, tumor necrosis factor (TNF) and its receptor superfamily gene, and caspase recruitment domain family, 12 genes expression down-regulated, including Bcl-2 antiapoptotic gene, TNF superfamily and its receptor related factor gene and apoptosis inhibitor protein family.</p><p><b>CONCLUSION</b>Fludarabine can significantly inhibit MM cell growth and induce apoptosis in vitro. The multiple pathways may be involved for the apoptosis in MM cells.</p>
Subject(s)
Humans , Apoptosis , Caspase 3 , Metabolism , Cell Line, Tumor , Multiple Myeloma , Metabolism , Proto-Oncogene Proteins c-bcl-2 , Metabolism , TranscriptomeABSTRACT
<p><b>OBJECTIVE</b>To investigate the mechanisms of enhanced antileukemia activity of conditionally replicating adenovirus (CRAd) by interleukin-24 (IL-24).</p><p><b>METHODS</b>The ability of CRAd ZD55 to infect leukemia cells was detected by flow cytometry. The expressions of vascular endothelial growth factor (VEGF) in leukemia cells treated with PBS, ZD55, ZD55-IL-24, and an adenovirus carrying IL-24 (Ad-IL-24) were determined by Western blot analysis. Animal xenograft tumor model was established by Mutz-1 cell line.Deparaffinized tumor sections were incubated with anti-CD31, and VEGF antibody, followed by immunohistochemistry analysis.</p><p><b>RESULT</b>The GFP-positive cells were 5.1% and 42.3% in Mutz-1 cells treated with ZD55-EGFP vector at MOI of 10 and 100 for 48h, respectively. ZD55-IL-24 treatment resulted in the marked down-regulation of VEGF protein expression and ZD55 inhibited VEGF slightly; however, there was no change observed in the cells treated with Ad-IL-24. Immunohistochemistry analysis showed that Ad-IL-24 inhibited slightly angiogenesis and ZD55 treatment resulted in significant inhibition of angiogenesis. ZD55-IL-24 treatment almost completely inhibited angiogenesis in tumor tissues.</p><p><b>CONCLUSION</b>IL-24 enhances the antileukemia activity of ZD55 by inhibiting VEGF protein expression and angiogenesis in vitro and in vivo.</p>
Subject(s)
Animals , Humans , Mice , Adenoviridae , Genetics , Apoptosis , Cell Line, Tumor , Down-Regulation , Genetic Therapy , Genetic Vectors , Interleukins , Genetics , Metabolism , Leukemia , Metabolism , Pathology , Therapeutics , Mice, Nude , Neovascularization, Pathologic , Genetics , Oncolytic Virotherapy , Platelet Endothelial Cell Adhesion Molecule-1 , Metabolism , Transfection , Vascular Endothelial Growth Factor A , Metabolism , Xenograft Model Antitumor AssaysABSTRACT
<p><b>OBJECTIVE</b>To investigate the inhibitive effects of chimeric oncolytic adenovirus SG235 on leukemia cells in vitro.</p><p><b>METHODS</b>The ability of SG235 to infect leukemia cells and the expression of CD46 on blasts from the patient with leukemia were detected by flow cytometry (FACS). The cytotoxicity of the virus was evaluated by MTT assay. Apoptosis induced by SG235 was detected with Annexin-V/PI staining and TUNEL assay followed by FACS analysis.</p><p><b>RESULT</b>The majority of leukemia cells from the patient with acute leukemia was CD46-positive. GFP-positive cells were 45.1%, 35.7%, 54.2%, 37.0%, 30.1%, %67.1, 17.2% and 33.1% in Mutz-1, Kasumi-1, K562, HL60, Molt- 4, RPMI8226, L428, and Jurkat cell lines treated with SG235-EGFP vector at MOI (multiplicity of infection) of 50 for 48 h.SG235 treatment resulted in marked growth inhibition and apoptosis of Kassumi-1 cells, and also significantly inhibited expression of p-Akt.</p><p><b>CONCLUSION</b>The chimeric oncolytic adenovirus SG235 can infect leukemia cell effectively and results in the growth inhibition and apoptosis of Kasumi-1 cells in vitro.</p>