ABSTRACT
O-GlcNAcase (OGA) is implicated in several important biological and disease-relevant processes. Here, we synthesized fluorogenic probes for OGA by grafting GlcNAc directly or using a self-immolative linker to the hydroxyl position of 4-hydroxylisoindoline (BHID), a typical excited-state intramolecular proton transfer (ESIPT) probe. The probe was used for a fluorogenic assay to determine the half maximal inhibitory concentration of a known OGA inhibitor and differentiate between OGA and hexosaminidase when GlcNAc is replaced by GlcNPr, where a propionyl group is used instead of an acetyl group.
Subject(s)
Fluorescent Dyes , Isoindoles , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Isoindoles/chemistry , Isoindoles/chemical synthesis , Humans , beta-N-Acetylhexosaminidases/metabolism , beta-N-Acetylhexosaminidases/antagonists & inhibitors , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemical synthesis , Molecular Structure , Spectrometry, FluorescenceABSTRACT
QUINAPs have emerged as a pivotal class of axially chiral compounds with remarkable features in the stereoinduction of diverse enantioselective transformations. However, the confined substrate range and extravagant price still pose challenges, limiting their broader utilization. Herein, we describe the first atroposelective oxidation of an N atom using a chiral ketone catalyst, allowing the kinetic resolution of QUINAPOs to give both the unreacted substrates and their corresponding N-oxides with excellent enantioselectivity. Importantly, the enantioenriched products can be readily converted into the QUINAP targets without any loss of stereochemical integrity. Mechanistic investigations indicate that a dioxirane, generated through the oxidation of the ketone with oxone, acts as the active catalytic species. Furthermore, we have successfully extended this catalytic system to the kinetic resolution of QUINOLs and the dynamic kinetic transformation of pyridine analogues of QUINAPO possessing a labile stereogenic axis. The practicality of the developed protocol is further demonstrated by the successful application of QUINAPO N-oxide as a Lewis base catalyst in a series of enantioselective transformations.
ABSTRACT
We report the efficient syntheses of chiral tetrahydroindole pyrazolinones by the asymmetric [3 + 2] cascade cyclizations (indolizations) of simple aniline derivatives with pyrazolinone ketimines as 2C synthons. The chiral phosphoric-acid-catalyzed system uses a concerted π-π interaction/dual H-bond control strategy to catalytically direct the asymmetric aniline, which undergoes a highly chemo-, regio-, and enantioselective [3 + 2] cascade annulation, furnishing a series of optically active tetra-hydroindole pyrazolinones with two contiguous chiral aza-quaternary carbon centers in excellent yields with excellent enantioselectivities. This method features a relatively broad substrate scope for amines and 2-naphthylamines and highlights the emerging value of direct chiral indolizations from simple amine sources in organic synthesis.
ABSTRACT
Lanthanide oxo compounds are of vital importance in lanthanide chemistry, as well as in environmental and materials sciences. Praseodymium, as an exceptional element in lanthanides which can form a +V formal oxidation state (OSf) besides the dominant +III among the 4f-block element, displays the significant participation of the Pr 4f orbitals in bonding interactions which is commonly crucial in stabilizing the high oxidation state of Pr in PrO2+ and NPrO species. Here, we report a systematic theoretical study on the structures and stabilities of a series of XPrO (X: B, Al, C, Si, N, P, As, O, S, F, Cl) compounds along with [XPrO]+ cation (X: O, S) and [X3PrO] complexes (X: F and Cl). This work reveals that Pr is able to achieve the lowest and highest OSf and the OSf exhibits periodic variation from +I in BOPr and AlOPr to +II in SiOPr to +III in CPrO, FPrO, ClPrO and AsPrO to +IV in OPrO and SPrO and even to +V in NPrO, [OPrO]+, [SPrO]+, F3PrO and Cl3PrO. We found that the molecular structures are correlated to the Pr oxidation state due to the highly important 4f orbital in the chemical bonding of the high oxidation state compounds. Thus, not only the electronegativity of the ligand but also the quasi-degenerate Pr valence 4f orbitals, namely energetic covalency, control the oxidation state and play a fundamental role in affecting the electronic structural stability of Pr(v) compounds as well. This work demonstrates the structurally directing role of the f-orbital in the formation of the linear structure and is constructive for achieving the higher oxidation state of a given element by tuning the ligand.
ABSTRACT
Asymmetric catalytic synthesis of 2,3-allenamides from hydrogen-bond-stabilized enynamides in the presence of quinine-based bifunctional squaramide organocatalysts is described. This protocol forms a variety of 2,3-allenamides in high yields and excellent stereoselectivities, in which the elaborated introduction of intramolecular H-bonds within the N, N-bidentate amide group constitutes one of the keys to this highly enantioselective transformation. The synthetic practicality of this reaction has been demonstrated by the axis-to-center chirality transfer of allenamides to furnish enantiomerically enriched building blocks.
ABSTRACT
RATIONALE: Hemangiomas are benign tumors characterized by an abnormal proliferation of blood vessels, most often occur in the skin and subcutaneous tissue, intramuscular hemangioma, a distinctive type of hemangioma within the skeletal muscle, account for <1% of all hemangiomas, temporalis muscle is a very uncommon site, cavernous hemangioma of the temporalis muscle with prominent formation of phleboliths is rare reported. PATIENT CONCERNS: A 62-year-old man presented with a slowly increased mass in his right temporal fossa. DIAGNOSES: Computed tomography (CT) scan showed the lesion across the zygomatic arch, with many calcified nodules differ in sizes and no erosion to the bone, magnetic resonance imaging (MRI) showed an oval lesion with hypointense and isointense on T2-weighted imaging within the temporal muscle, and preoperation diagnosis was hemangioma. INTERVENTIONS: The tumor was resected under general anesthesia. OUTCOMES: The mass was excised completely, and the histopathology examination confirmed the diagnosis of cavernous hemangioma with prominent formation of phleboliths. The patient recovered very well without dysfunctions. LESSONS: Cavernous hemangioma should be suspected when mass occurs in this region. CT and MRI are important for the early diagnosis of tumor, and resection the tumor completely is recommended.
Subject(s)
Hemangioma, Cavernous/complications , Muscle Neoplasms/complications , Vascular Calcification/complications , Diagnosis, Differential , Hemangioma, Cavernous/diagnostic imaging , Hemangioma, Cavernous/pathology , Hemangioma, Cavernous/surgery , Humans , Male , Middle Aged , Muscle Neoplasms/diagnostic imaging , Muscle Neoplasms/pathology , Muscle Neoplasms/surgery , Temporal Muscle/diagnostic imaging , Temporal Muscle/pathology , Temporal Muscle/surgery , Vascular Calcification/diagnostic imaging , Vascular Calcification/pathology , Vascular Calcification/surgeryABSTRACT
The co-adsorption of O2 and CO on anionic sites of gold species is considered as a crucial step in the catalytic CO oxidation on gold catalysts. In this regard, the [Au2 O2 (CO)n ]- (n=2-6) complexes were prepared by using a laser vaporization supersonic ion source and were studied by using infrared photodissociation spectroscopy in the gas phase. All the [Au2 O2 (CO)n ]- (n=2-6) complexes were characterized to have a core structure involving one CO and one O2 molecule co-adsorbed on Au2- with the other CO molecules physically tagged around. The CO stretching frequency of the [Au2 O2 (CO)]- core ion is observed around νË =2032-2042â cm-1 , which is about 200â cm-1 higher than that in [Au2 (CO)2 ]- . This frequency difference and the analyses based on density functional calculations provide direct evidence for the synergy effect of the chemically adsorbed O2 and CO. The low lying structures with carbonate group were not observed experimentally because of high formation barriers. The structures and the stability (i.e., the inertness in a sense) of the co-adsorbed O2 and CO on Au2- may have relevance to the elementary reaction steps on real gold catalysts.
ABSTRACT
This study was aimed to characterize clinicopathological features and prognosis of patients with adenosquamous lung carcinoma (ASC). Among the 2531 patients with lung cancer who underwent surgery between January 2000 and June 2012 in our hospital, 59 were histologically diagnosed as having ASC. The clinicopathological features and follow-up data of ASC patients were collected and analyzed statistically. Superior lobectomy was accomplished in 40 patients, middle and inferior lobectomy in 3, lobectomy plus partial resection of contralateral lung in 5, partial lung resection in 4, and pneumonectomy in 7. Moreover, 22 cases were found to be adenocarcinoma-predominant, and 18 to be squamous cell carcinoma-predominant. The median survival time was 13.6 months, and the 1-, 3-, and 5-year survival rates were 59.9%, 36.4% and 31.2%, respectively. Of the 52 cases with tissue specimens available, 11 had an EGFR mutation (21.2%) and 2 had a KRAS mutation (3.8%). Multivariate analysis showed that histology subtype, pleural invasion, TNM stage, and postoperative treatment were all independent prognostic factors. The data from the current study demonstrated that SCC-predominant histology represents a better prognosis of ASC. Histology subtype, pleural invasion, TNM stage, and postoperative treatment are independent prognostic factors for ASC and adjuvant therapy may help control the disease.
Subject(s)
Carcinoma, Adenosquamous/pathology , Carcinoma, Adenosquamous/surgery , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Adult , Aged , Carcinoma, Adenosquamous/genetics , Diagnosis, Differential , ErbB Receptors/genetics , Female , Humans , Lung Neoplasms/genetics , Male , Middle Aged , Mutation , Prognosis , Proto-Oncogene Proteins p21(ras)/genetics , Retrospective Studies , Survival AnalysisABSTRACT
OBJECTIVE: To present pathological and molecular characterizations of a rare case that was diagnosed as nasal-type natural killer (NK)/T cell lymphoma primarily arising in the cervix. CASE REPORT: An Asian woman was admitted to hospital with a hysteromyoma, and laparotomy was performed. A large tumor of the uterus was found, which was limited to the cervix. Pathological examination showed NK/T cell lymphoma, which was supported by histological and immunohistochemical studies and was confirmed by evidence of Epstein-Barr virus infection. Less commonly, this case concerned a cytotoxic T cell phenotype, as molecular studies showed evidence of a clonal T cell receptor γ chain gene rearrangement. Microscopically, prominent and extensive necrosis was the distinctive feature of this case, which reminded us of considering it as a tumor. CONCLUSION: Primary NK/T lymphoma of the cervix is rare. Our experience in this case provided variable information on both pathological and molecular studies. This case may be of value in the differential diagnosis of lymphoid lesions and other small cell tumors of the cervix.
Subject(s)
Cervix Uteri/pathology , Lymphoma, T-Cell, Peripheral/diagnosis , Natural Killer T-Cells/pathology , Uterine Cervical Neoplasms/diagnosis , DNA, Neoplasm/analysis , Diagnosis, Differential , Electrophoresis, Polyacrylamide Gel , Female , Humans , Hysterectomy/methods , Laparotomy , Lymphoma, T-Cell, Peripheral/genetics , Lymphoma, T-Cell, Peripheral/surgery , Middle Aged , Polymerase Chain Reaction , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/surgeryABSTRACT
Meropenem is a carbapenem antibiotic with a wide spectrum of activity against both Gram-positive and Gram-negative bacteria. Because of its clinical efficacy, meropenem is an excellent choice for the treatment of serious infections in both adults and children. The knowledge of tissue concentrations of antibiotic in an infection site is valuable for the prediction of treatment outcome. The aim of the present study is to investigate the effect of borneol on the concentration of meropenem in rat brain and blood and to find the potential relationships of the combined use of medicine and traditional Chinese medicine. Analysis of meropenem in the dialysates was achieved using the microdialysis technique and HPLC. At 40 min after the administration of an intraperitoneal injection of meropenem, the concentration of meropenem in brain in borneol+meropenem group was 2.25 (0.35) µg ml(-1), which was significantly higher than that in meropenem group [1.20 (0.12) µg ml(-1); P < 0.01]. Within 80 min of drug administration, the AUCbrain/AUCblood (area under the curve, AUC) in the borneol+meropenem group was 1.2 times that of the meropenem group. Borneol can increase the concentration of meropenem in the cerebrospinal fluid, but has no influence on its blood concentration. This study represents a successful application of the microdialysis technique, which is an effective method for the study of pharmacokinetics of meropenem.
Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Camphanes/pharmacokinetics , Thienamycins/analysis , Thienamycins/pharmacokinetics , Adult , Animals , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/blood , Blood-Brain Barrier/drug effects , Brain/drug effects , Camphanes/analysis , Camphanes/blood , Camphanes/chemistry , Child , Chromatography , Chromatography, High Pressure Liquid , Female , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Male , Medicine, Chinese Traditional , Meropenem , Microdialysis , Molecular Structure , Rats , Rats, Wistar , Thienamycins/administration & dosage , Thienamycins/blood , Thienamycins/chemistryABSTRACT
PURPOSE: Alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and Golgi protein 73 (GP73) levels have been widely used as tumor markers for the diagnosis of hepatocellular carcinoma (HCC). The aim of this study was to investigate whether these tumor markers could be used to monitor short-term treatment response and recurrence of HCC in patients undergoing radiofrequency ablation (RFA). METHODS: Between July 2012 and July 2013, 53 consecutive patients with newly diagnosed HCC were prospectively enrolled in this study. Among these, 32 patients underwent RFA, after which they were followed up prospectively at the First Hospital of Jilin University in China. RESULTS: AFP, AFP-L3, and GP-73 values pre-RFA were not associated with tumor size, whereas AFP and GP-73 levels tended to be associated with tumor number, the presence of vascular invasion, deterioration of liver function, advanced-stage disease, and a poor performance status. GP-73 levels were dramatically elevated in the patients with hepatitis C-associated HCC. Neither pre-RFA nor 1-month post-RFA tumor marker values were associated with short-term outcome. The short-term recurrence rate of AFP-positive patients measured 1 month post-RFA was obviously higher than that of AFP-negative patients. CONCLUSIONS: AFP and GP-73 values were associated with clinical variables representing tumor growth and invasiveness, and the AFP value measured 1 month post-RFA was a strong predictor of short-term recurrence in patients with HCC.
Subject(s)
Carcinoma, Hepatocellular/blood , Liver Neoplasms/blood , Membrane Proteins/blood , Neoplasm Recurrence, Local/blood , alpha-Fetoproteins/metabolism , Adult , Aged , Biomarkers, Tumor/blood , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/radiotherapy , Catheter Ablation , Female , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/radiotherapy , Male , Middle Aged , Plant Lectins , Prognosis , Treatment Outcome , Tumor BurdenABSTRACT
OBJECTIVE: To screen serum biomarkers for minimal residual disease (MRD) monitoring according to differential peptidomics profile in the serum from the patients with acute leukemia (AL) and healthy controls. METHODS: Serum polypeptides from 90 AL patients, 60 healthy controls and 20 patients with benign hematological disorders were enriched by copper chelate magnetic beads, and the peptidomics profile was obtained by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) analysis. And the intensities of differential peptides were calculated to assess MRD level. RESULTS: The diagnostic models by using support vector machine (SVM) algorithm according to differential peptides between AL patients and healthy controls with P<0.01 by t-test were established. The sensitivity and specificity of distinguishing AL patients from healthy controls were 98% and 99%, respectively. The model obtained a sensitivity of 98% and a specificity of 96% for distinguishing newly-diagnosed AL patients from AL patients with hematological complete remission (AL-HCR). Then a sensitivity of 92% and a specificity of 93% were obtained for distinguishing patients with AL-CR from AL patients with molecular complete remission (AL- MR). The intensity of peptide with m/z (mass-to-charge ratio) 4468 was significantly higher in newly- diagnosed AL patients compared to healthy controls, and gradually decreased with the increase of remission degree, and it was not found increase in patients with benign hematological disorders. CONCLUSION: The SVM diagnostic model established by differential serum peptide profile could be used to discriminate AL patients with different stages of remission and to evaluate the treatment efficacy. The peptide of m/z 4468 could be used for MRD assessment, and continuous monitoring of its expression level will play an important role in the individual treatment and recurrence prediction.
Subject(s)
Leukemia/blood , Leukemia/diagnosis , Neoplasm, Residual/diagnosis , Acute Disease , Adolescent , Adult , Aged , Biomarkers, Tumor/blood , Case-Control Studies , Female , Humans , Leukemia/pathology , Male , Middle Aged , Neoplasm, Residual/blood , Peptides , Protein Interaction Mapping , Sensitivity and Specificity , Young AdultABSTRACT
OBJECTIVE: To analyze the cytogenetic characteristics of different age subgroups in patients with acute myeloid leukemia (AML), and to explore the relationship between age and cytogenetics. METHODS: Between January 2004 and December 2011, Bone marrow (BM) samples from 640 patients with de novo AML were analyzed retrospectively. The analyses were performed according to standard culturing and banding techniques, and clonal abnormalities were defined and described according to the International System for Human Cytogenetic Nomenclature (ISCN 2009). The cytogenetic subtypes were performed as normal, balanced, and unbalanced karyotypes. In the last group, the age distribution of complex and monosome karyotypes were further analyzed. The patients were divided into 8 age groups: 0 - 9, 10 - 19, 20 - 29, 30 - 39, 40 - 49, 50 - 59, 60 - 69, and ≥ 70 year old groups. RESULTS: The distribution of normal, balanced, and unbalanced karyotypes showed age specific characteristics. The incidence of normal karyotype increased from 6.67% (0 â¼ 9 year old) to 58.33% (≥ 70) (χ(2) = 20.68, P = 0.001) and balanced karyotype decreased from 73.33% (0 â¼ 9) to 11.11% (≥ 70) (χ(2) = 48.22, P < 0.01). The frequency of unbalanced karyotypes increased from 20.0% (0 â¼ 9) to 30.56% (≥ 70) (χ(2) = 18.963, P = 0.008). The frequency of complex karyotype was 6.67% in 0 - 9 year old group, followed by 0% in 10 - 19 and 20 - 29 year old group, and from 1.72% to 11.11% from 30 - 39 to ≥ 70 year old group (χ(2) = 8.341, P = 0.08). Monosome karyotype was only detected in patients in 30 year old or older groups. Although an increased tendency was observed with ages, there was no significant difference (χ(2) = 4.778, P = 0.311). CONCLUSION: The different age profiles of the cytogenetic subtypes may indicate the different mechanisms of the pathogenesis of AML, which may also offer beneficial information for etiological research of AML.
Subject(s)
Leukemia, Myeloid, Acute/genetics , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Karyotype , Karyotyping , Male , Middle Aged , Retrospective Studies , Young AdultABSTRACT
RIG-I/MDA5 plays a pivotal role in innate immunity by detecting intracellular double-stranded RNA (dsRNA) and activating the transcription of type I interferons and proinflammatory factors, but the exactly regulating mechanism of RIG-I/MDA5 signaling remains elusive. In this study, UbL-UBA domain containing protein RAD23A was identified as a negative regulator of RIG-I/MDA5-mediated signaling activation through a small interfering RNA (siRNA)-based screening. Knockdown of RAD23A augmented the expression of RIG-I/MDA5-mediated expression of proinflammatory cytokines and IFN-ß whereas ectopic expression of RAD23A showed the converse effect. Moreover, we confirmed the interaction between RAD23A and tumor necrosis factor receptor-associated factor 2 (TRAF2), an essential mediator of RIG-I/MDA5 signaling, and found that RAD23A down-regulated TRAF2 protein level through ubiquitin-proteasome system. Therefore, this study identified RAD23A as a novel negative regulator of RIG-I/MDA5 mediated anti-virus response.
Subject(s)
DEAD-box RNA Helicases/metabolism , DNA Repair Enzymes/metabolism , DNA-Binding Proteins/metabolism , TNF Receptor-Associated Factor 2/metabolism , Ubiquitination , DEAD Box Protein 58 , DNA Repair Enzymes/genetics , DNA, Viral/immunology , DNA-Binding Proteins/genetics , Gene Knockdown Techniques , HEK293 Cells , Humans , Interferon-Induced Helicase, IFIH1 , Interferon-beta/biosynthesis , NF-kappa B/metabolism , Proteasome Endopeptidase Complex/metabolism , Protein Structure, Tertiary , Proteolysis , RNA, Small Interfering/genetics , RNA, Viral/immunology , Receptors, Immunologic , Signal Transduction , Ubiquitin/metabolismABSTRACT
The aim of this study was to detect the efficiency of arsenic trioxide (ATO) alone or together with bortezomib to inhibit proliferation and induce apoptosis in a multiple myeloma (MM) RPMI 8266 cells. Mechanisms of action were also investigated. RPMI 8266 cells were treated with ATO alone and in combination with bortezomib for 24 hours, and cell viability was assessed by modified MTT. Annexin V-F1TC and PI staining was used to detect the apoptosis rate and cell cycling was investigated by flow cytometry, along with expression of cell surface death receptor-4(DR4) and death receptor-5 (DR5). Western blotting was applied to detect the expression of bcl-2, caspase-3, caspase-8, and caspase-9. As a result, the ATO combined with bortezomib group showed more inhibition of RPMI 8266 cell viability than the ATO group. Expression of DR4 and DR5 on the cell surfaces, and the apoptosis rate were increased after treatment by ATO alone or combined with bortezomib. The cells appeared to arrest in G2/M phase after treatment. Expression of bcl-2 was more significantly decreased in the combination group, and that of caspase-3, caspase-8 and caspase-9 was significantly increased as well. Therefore, bortezomib can enhance ATO actions to induce apoptosis in RPMI 8266 cells, with decrease in expression of bcl-2 and increase of caspase-3, caspase-8 and caspase-9 proteins.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Arsenicals/pharmacology , Boronic Acids/pharmacology , Multiple Myeloma/drug therapy , Oxides/pharmacology , Pyrazines/pharmacology , Apoptosis/drug effects , Apoptosis/genetics , Arsenic Trioxide , Arsenicals/administration & dosage , Boronic Acids/administration & dosage , Bortezomib , Caspases/genetics , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Proliferation/genetics , Cell Survival/drug effects , Cell Survival/genetics , G2 Phase Cell Cycle Checkpoints/drug effects , G2 Phase Cell Cycle Checkpoints/genetics , Humans , Multiple Myeloma/genetics , Multiple Myeloma/pathology , Oxides/administration & dosage , Proto-Oncogene Proteins c-bcl-2/genetics , Pyrazines/administration & dosageABSTRACT
The aim of this study was to investigate the traditional meridian theory using speckle laser blood flow scanning technology to observe microcirculation of the Hegu acupoint area after acupuncture stimulation on distant points. An observational study was conducted to observe the microvascular perfusion of Hegu (LI4) and control points after acupuncturing Quchi (LI11). Thirty healthy volunteers (mean age 31.6 ± 8.7 years) received deqi acupuncture on Quchi (LI11, right side), and simultaneously changes in microvascular perfusion of Sanjian (LI3), Hegu (LI4), Yangxi (LI5), and two control points were observed before, during, and after needling using a MOOR speckle laser. The results showed that the changes in microvascular perfusion of the observed points are not regular. After correction, the experiment showed that the blood perfusion on 3 meridian acupoints was increased while the perfusion on 2 control points was decreased following acupuncture stimulation, the changes at Hegu (LI4) being the statistically most significant ones. Deqi acupuncture can help in regulating the body's blood flow, with a certain degree of meridian specificity.
ABSTRACT
This study was aimed to explore the anti-leukemic effect of scutellaria extract SBX in human leukemia cell lines and its mechanism. The leukemia cell lines, including HL-60, NB4, U937, K562 and Jurkat, were cultured in vitro and proliferative inhibition of these cell lines was detected by CellTiter-Glo Luminescent Cell Viability Assay in order to screen the most sensitive cell line. The effect of SBX on cell cycle was analyzed by flow cytometry and the protein expressions determined by Protein Pathway Array respectively. The results indicated that SBX (10 - 200 µmol/L, for 72 h) significantly inhibited the proliferation of different leukemia cell lines in a dose-dependent manner (r value was 0.86, 0.88, 0.95, 0.94, 0.96, respectively), the HL-60 was the most sensitive cell line. Flow cytometric analysis showed that SBX (50, 10 µmol/L, for 48 h) arrested HL-60 cells in the G(0)/G(1) phase. In addition, protein expression of p-PKC α/ßII, p-p38, Cdc25B, XIAP of HL-60 cells increased, and p-AKT, p-SAPK/JNK, Notch4, Cdk4, Cdc2, cyclin E, Akt, Bcl-2, Bax, cdc42, TNF-α, p27, CaMKKa decreased after exposure to SBX (50 µmol/L, for 48 h). It is concluded that SBX can inhibit the proliferation of different leukemia cell lines, and HL-60 is a sensitive cell line. SBX significantly influences EGFR, Ras/Raf/MAPK and Notch signaling pathway, through which effects the expression of cell cycle-related proteins resulting in arrest of HL-60 cells in G(0)/G(1).
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Leukemia/drug therapy , Scutellaria , Signal Transduction/drug effects , Cell Cycle , Cell Cycle Proteins/metabolism , Cell Line, Tumor , Drugs, Chinese Herbal/pharmacology , Humans , Leukemia/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Tumor Necrosis Factor-alpha/metabolism , bcl-2-Associated X Protein/metabolismABSTRACT
The COPS3 gene has stimulating effect on cell proliferation and progression of osteosarcomas and related cells. However, the features of COPS3 and its potential application as a therapeutic target in other cancers has not yet been studied. In this study, therefore, the effect of COPS3 silencing via COPS3 siRNA on lung cancer cell proliferation was examined. Expression levels of COPS3 gene in COPS3 siRNA infected cells and control siRNA infected cells were compared with real time PCR and Western blot analysis. Cell proliferation levels were comprehensively analyzed by MTT, BrdU incorporationy, and colony formation assays. For mechanistic assessment the effects of COPS3 silencing on cell cycle and apoptosis were analyzed using flow cytometry. Results showed that successful silencing of the COPS3 gene at both translational and transcriptional levels significantly reduced the proliferation and colony formation by lung cancer cells (p<0.01). Flow cytometry showed cell cycle arrest in the G0/G1 phase after COPS3 silencing, and more importantly, apoptosis was induced as a result of COPS3 knockdown, which negatively affected cell survival. Therefore, these results provide another piece of important evidence that the COPS3 gene expressed in lung cancer cells may play a critical role in stimulating proliferation. Down-regulation of COPS3 could significantly inhibit lung cancer cell growth, which was most likely mediated via induction of cell cycle arrest in G0/G1 phase and apoptosis.
Subject(s)
Apoptosis/genetics , Cell Cycle Checkpoints/genetics , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Proto-Oncogene Proteins/genetics , RNA Interference , COP9 Signalosome Complex , Cell Line, Tumor , Cell Proliferation , HEK293 Cells , Humans , Lung Neoplasms/therapy , RNA, Small InterferingABSTRACT
In this study we investigated the effect of repeated low-dose radiation exposure (75 mGy X ray) on skin wound healing in a rat model of diabetes. A skin wound was made on the backs of diabetic and age-matched control rats 60 days after diabetes was induced by a single injection of streptozotocin. Rats with skin wounds were immediately treated with whole-body radiation daily for 5, 10 or 15 days with a 2-day break every 5 days. Wound size was estimated 5, 10 and 15 days after wound formation. Repeated exposure of diabetic rats to low-dose radiation significantly accelerated skin wound healing compared to the nonirradiated diabetic group. Furthermore, low-dose radiation-induced improvement in healing was associated with increases in bone marrow and circulating CD31(+)/CD34(+) stem cells, vessel regeneration and cell proliferation in the wound tissue, and matrix metalloproteinase 2 and 9 expression. Therefore, we conclude that the acceleration of wound healing in diabetic rats by repeated exposure to low-dose radiation is associated with stimulation of bone marrow stem cell proliferation and peripheral mobilization.
Subject(s)
Bone Marrow Cells/cytology , Cell Movement/radiation effects , Diabetes Mellitus, Type 1/immunology , Stem Cells/cytology , Stem Cells/radiation effects , Wound Healing/radiation effects , Animals , Blood Vessels/physiopathology , Blood Vessels/radiation effects , Cell Proliferation/radiation effects , Dose-Response Relationship, Drug , Gene Expression Regulation/radiation effects , Male , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/genetics , Rats , Rats, Wistar , Skin/immunology , Skin/injuries , Skin/metabolism , Skin/radiation effects , Stem Cells/metabolism , Time Factors , Tissue Inhibitor of Metalloproteinase-1/geneticsABSTRACT
The aim of this study was to explore the mechanism underlying the blast crisis of chronic myeloid leukemia. Analysis of gene expression profiles of chronic myeloid leukemia patients in chronic phase and blast crisis were analyzed by using cDNA microarray representing 4096 genes for finding the differential expression genes. The results indicated that 74 differential expression genes were identified in at least 3 gene chips in blast crisis compared with chronic phase, among them 52 genes were down-regulated and 22 genes were up-regulated in blast crisis. The differential expression genes were involved in these genes including genes related to cell structure/mobility, signal transduction, transcription factor, related immunity, metabolism, cell cycle, oncogene/anti-oncogene, cell receptor, protein translation/synthesis and some unknown functions. It is concluded that the blast crisis of CML is resulted from abnormality and interaction of multigene, among them functional abnormal genes related to signal transduction, cell cycle, cell differentiation and immunity may be the critical genes for chronic myeloid leukemia blast crisis.