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Objective:To screen the key miRNA downstream of TLR2 and explore the function of the miR-21.Methods:Wild type (WT) and TLR2 KO mice were irradiated with 60Co γ-ray to compare their survivals. The downstream miRNAs of TLR2 signaling pathway were screened by RNA sequence in BMCs, and their expressions were verified by QT-PCR. Cell lines with overexpression or knockdown of a miRNA were established to evaluate the function of miRNA. Results:The radiosensitivity of TLR2 KO mice was higher than that of TLR2 WT mice( χ2=4.490, 13.100, 7.928, P<0.05). The bone marrow transplantation experiment proved that the increased radiosensitivity of TLR2 KO mice was related to BMCs ( χ2=4.291, P<0.05). A total of 55 differentially expressed genes were screened by RNA sequence ([log2 Fold Change]>0.95, Q<0.05), of which 28 were up-regulated and 27 were down-regulated. QT-PCR assay determined that miR-21 was down-regulated in BMCs of TLR2 KO ( t=9.420, P<0.01) and MyD88 KO ( t=10.700, P<0.01) mice. It was proved by QT-PCR that the expressions of IL-6 ( t=13.790, P<0.05) and TNF-α ( t=14.280, P<0.05) were increased in a TLR2 dependent manner after PAM3CSK4 stimulation. Overexpression of miR-21 promoted viability of EL4 cells ( t=5.951, P<0.05) and NIH/3T3 cells ( t=4.786, P<0.05) and reduced BMCs apoptosis in WT ( t=4.842, P<0.05) and TLR2 KO ( t=10.520, P<0.05) mice after radiation. Inhibition of miR-21 decreased the viability of EL4 cells ( t=4.815, P<0.05) and NIH/3T3 cells ( t=4.042, P<0.05). Conclusions:miR-21 plays a key regulatory role in the process of TLR2 radioprotection, which may be related to the up-regulation of IL-6 and TNF-α.
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Objective To investigate the changes of component and morphology in internal carotid vulnerable plaque,for helping to make clinical intervention strategy individually. Methods A total of 47 patients with internal carotid vulnerable plaques and primary hypertension underwent 2 high-resolution and multi-contrast MRI scans, from March 2008 to April 2014 were retrospectively reviewed. At baseline, the plaque was mainly located at the proximal internal carotid artery,and maximum plaque thickness ≥1.5 mm with intraplaque hemorrhage(IPH)and(or)thin or ruptured fibrous cap.Interscan interval was 0.5 years and above. Patients with carotid occlusion or surgery were excluded. Morphological measurements included maximum plaque thickness, maximum plaque area and cross-sectional vessel area (CSVA) on the level of plaque with maximum thickness. The paired-samples t test was performed to compare the difference of plaque morphology between baseline and follow-up carotid MRI.Results The interscan interval was 1.83 (1.59,1.99)years for 47 internal carotid vulnerable plaques.One case(interscan interval 2.16 years)showed IPH within those 11 plaques without IPH at baseline,and one case(interscan interval 1.42 years)had new incident IPH within those 36 plaques with IPH at baseline. Maximum plaque thickness increased significantly from(3.94±1.44)mm to(4.24±1.68)mm(t=2.30,P<0.05)by 5.14%(-3.83,11.34)% per year. Maximum plaque area increased significantly from(49.19±21.15)mm2to(56.03±24.91)mm2(t=3.87,P<0.01)by 6.67%(-2.26,19.60)% per year.CSVA increased significantly from(66.22±27.51)mm2to(73.68±31.47)mm2(t=4.08,P<0.01)by 5.18%(-1.63,12.34)% per year.Conclusion The progression of component,burden and outer remodeling in the internal carotid vulnerable plaque may be faster in hypertension, therefore reasonable intervention strategy and regular follow-up carotid MRI should be performed.
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Objective To study the relationship of carotid atherosclerosis score (CAS) with carotid atherosclerotic disease and its clinical indexes in ischemic stroke patients.Methods Ninety-six patients with ischemic stroke (＜2 weeks) or transient ischemic attack underwent high-resolution MRI of bilateral carotid arteries to measure their carotid atherosclerotic luminal stenosis,maximal wall thickness (MaxWT) and plaque involvement size.The carotid plaque images with unstable components of lipid-rich core (LRC) were analyzed with CASCAD software.The CAS value was calculated and divided into low risk group and high risk group.The relationship between CAS and its clinical indexes was analyzed.Results LRC was detected in plaques of 148 carotid arteries of the 96 patients with a CAS value of 21.6％±17.5％.The CAS value was related with the carotid luminal stenosis,MaxWT and plaque involvement size (r =0.610,r=0.569,r =0.527,P＜ 0.001).A significant difference was found in carotid luminal stenosis,MaxWT and plaque involvement size with a different CAS value (P＜0.01).The CAS value was related with LDL and HDL/TC ratio (r=0.469,P＜0.01;r=-0.269,P=0.035).The SBP,DBP and LDL level were higher in high risk group than in low risk group (P＜0.05).Conclusion CAS is closely related with carotid atherosclerotic disease and lipid metabolism.The higher the CAS value is,the higher the risk of carotid plaque hemorrhage and fibrous cap rupture is.
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Objective To study the role of dynamic contrast enhanced MRI (DCE-MRI) in assessing early curative effect of rosuvastatin on carotid atherosclerotic plaques.Methods Twenty-five patients with lipid-rich necrotic core carotid atherosclerotic plaques received intensive rosuvastatin treatment (5-20 mg/d) for 2 years,and carotid artery DCE-MRI at baseline before treatment and at months 3,12 and 24 after rosuvastatin treatment.Their adventitial transfer constant (K) and fractional plasma volume (Vp) were measured and compared during the rosuvastatin treatment.Results The Vp was significantly smaller at months 3,12 and 24 after rosuvastatin treatment than at baseline before rosuvastatin treatment (0.09±0.05,0.07±0.04 and 0.06±0.05 vs 0.12± 0.06,P＜0.05) with a reduction of 25.0％ after 3 months of rosuvastatin treatment and a gradual reduction after 24 months of rosuvastatin treatment (P＜0.05).The adventitial K was mildly reduced after 24 months of rosuvastatin treatment (P＞0.05).Conclusion DCE-MRI can assess the early curative effect of rosuvastatin on carotid atherosclerotic plaques.
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Objective To study the relationship between progression and clinical characteristics of carotid plaques at different sites in elderly carotid atherosclerosis patients.Methods Fifty-one elderly carotid atherosclerosis patients who underwent twice of high resolution MRI in our hospital were included in this study.The MRI data of 75 carotid arteries,annual progression of stenosis,maximum wall thickness,wall size,lumen size at plaques in common carotid artery (CCA),carotid bifurcation (BIF) and internal carotid artery (ICA) were analyzed.Results Of the 131 plaques in 75 carotid arteries,42 were detected in ICA,54 were detected in BIF.The annual progression rates of wall size and maximum wall thickness were higher at plaques in ICA than at those in CCA and BIF (P=0.036,P=0.028).The wall size of plaques in ICA was related with age,hypertension and diabetes (r=0.39,P=0.011;r=0.37,P=0.016;r=0.31,P=0.041).Conclusion The progression of plaques in ICA is faster than that of those in CCA and BIF,and is related with the high clinical risk factors.MRI follow-up can characterize the progressive plaques in elderly carotid atherosclerosis patients.
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With the strengthening of nuclear weapon development and the expanding of neutron application in economic area,the injury accidents of neutron radiation are happening from time to time.Neutron exposure,with high linear energy transfer,has high casualty rate,severe symptom and poor prognosis.In comparison with low-LET radiation damage,neutron irradiation induced injuries are more difficult to rescue.This review focused on the recent research progresses of radiation effects,intrinsic mechanisms and clinical prevention measures of neutron radiation,and to provide a theoretical clue for establishing an effective prevention protocol of neutron radiation damage.
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Objective To investigate the effect pre‐injection of dexmedetomidine(Dex) on hemodynamics during intratracheal intubation period of general anesthesia with propofol or etomidate induction .Methods Eighty ASA Ⅰ - Ⅱ patients with elective surgery were randomly assigned to 4 groups:propofol group(P) ,P combined with Dex group(PD) ,etomidate group(E) and E com‐bined with Dex group(ED) ,20cases in each group .SBP ,DBP ,BIS and HR in 4 groups were recorded at the time points of before an‐esthesia after entering the operation room (T0 ) ,at l min after beginning for giving Dex(T1 ) ,10 min of infusing Dex(T2 ) ,3 min af‐ter anesthetic induction (T3 ) ,immediate intubation(T4 ) ,at l min after intubation(T5 ) ,3 min after intubation(T6 ) and 5 min after intubation(T7 ) .The SpO2 values and Ramesay scores were recorded at T 0 and T2 .Results HR at T2 and T3 in the group PD and Ed was decreased compared with those at T0 ,and lower than those in the group P and E(P<0 .01);DBP and SBP at T3 in the group ,PD and E were decreased compared with at T 0 (P<0 .05) ,while SBP and DBP in the group ED were higher than those in the group P and PD (P<0 .05) ,SBP and DBP in the group P were lower than those in the other 3 groups(P<0 .05) ;SBP and DBP at T4 in the group E were significantly higher than those in other 3 groups (P<0 .01);the blood pressure at T5 in the group E was significantly higher than that at T0 and in other 3 groups(P<0 .05);SBP and DBP at T6 and T7 in the group P and PD was de‐creased to the preoperativel levels (P<0 .05) .The SpO2 value at T2 in the group PD was lower than that at T0 (P< 0 .05);the Ramsay score at T2 in the group PD and ED was higher than that in the group P and E(P<0 .05) .The BIS value at T2 in the group PD and ED was lower than that at T0 ,which at T3 -T7 in the four groups was lower than that at T0 (P<0 .05) .Conclusion Pre‐injection of Dex can maintain the hemodynamic stability during endotracheal inbubation period by etomidate induction and also re‐duce the cardiovascular reaction caused by endotracheal intubation .
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With continued ozone deletion and increased ultraviolet application,ultraviolet (UV) induced eye injury receives more attention,especially for astronauts,residents on high elevation plateaus and other people exposed to intense beams of UV.Continuous exposure to UV can lead to damage of conjunctiva,cornea,crystalline lens and retina,which are correlated with conjunctivitis,keratitis,ocular tumor,climatic droplet keratopathy,and pterygium.This paper focuses on the effect of UV on eyes,with a systematic elaboration of UV-induced eye injury.
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Objective To investigate the role of miR-203 in radiation-induced thymic lymphoma (RITL).Methods A 60Co irradiator was used for total-body irradiation.MicroRNAs(miRNAs) level was assayed by qRT-PCR.Cell proliferation was assayed by MTT assay.Cell apoptosis was examined by fluorescence activated cell sorter (FACS).Dual luciferase reporter assay system was used to detect the 3'UTR reporter.Results MiR-203 was down-regulated in RITL tissues.Overexpression of miR-203 strongly inhibited the proliferation of both NIH3T3 cells and EL4 cells and vice versa.MiR-203 inhibited cells proliferation and induced apoptosis via TANK-binding kinase (TBK1),SLUG (SNAI2) and Cyclin D1 (CCND1).Conclusions Radiation down-regulated the level of miR-203 in thymic,which promoted radiation-induced thymic lymphoma by targeting TBK1,SNAI2 and CCND1.
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<p><b>OBJECTIVE</b>To assess the value of high-resolution three-dimensional black-blood magnetic resonance imaging (3D-BB-MRI) in quantitative measurement of carotid atherosclerotic plaque by comparison with two-dimensional black-blood magnetic resonance imaging (2D-BB-MRI).</p><p><b>METHODS</b>Forty patients were scanned with routine 2D and oblique-sagittal 3D-BB-MRI. The original oblique-sagittal 3D images were reformatted to an axial 2D-like dataset. Two experienced radiologists identified the interested slice in consensus for every patient (unilateral carotid artery) in 2D-BB-MRI images and matched the axial reformatted 3D images with 2D black-blood images. Plaque thickness (PT), lumen area (LA) and total vessel area (TVA) were measured, and lumen stenosis (LS) and normalized wall index (NWI) were calculated.</p><p><b>RESULTS</b>There was no measurement difference between 2D-BB-MRI and reformatted 3D-BB-MRI (P>0.05), and these two methods had a good correlation (r<0.9). The Bland-Altman chart showed that 2D-BB-MRI and 3D-BB-MRI were in good agreement in the measurement of PT, LA and TVA.</p><p><b>CONCLUSION</b>3D-BB-MRI and 2D-BB-MRI have no obvious difference in quantitative measurement of the carotid plaques. 3D-BB-MRI can demonstrate the vessels and plaques by multiplanar reconstruction and thus have better performance in evaluating carotid atherosclerosis compared with 2D-BB-MRI.</p>
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Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Carotid Artery Diseases , Pathology , Imaging, Three-Dimensional , Magnetic Resonance Imaging , Methodsالملخص
<p><b>OBJECTIVE</b>To evaluate the feasibility by oblique sagittal T(1)-weighted (QIR-FSE) black-blood sequence for measurement of the carotid bifurcation angle.</p><p><b>METHODS</b>Twenty-three patients undergoing carotid magnetic resonance imaging (MRI) were divided in normal group and plaque group. Carotid bifurcation angle was measured by both 2D-TOF and oblique sagittal T(1)W (QIR-FSE) black-blood sequence, and the measurement was repeated after 3 months to evaluate the reproducibility. The measurement results using 2D-TOF and oblique sagittal T(1)W (QIR-FSE) black-blood sequence were compared to assess the consistency of the two sequences. Four different angles of each carotid artery were measured from different locations on oblique sagittal T(1)W. The ratio of the bilateral carotid bifurcation angle (Right/Left) was compared.</p><p><b>RESULTS</b>Ten patients in each group were enrolled after excluding 3 patients. Strong correlations were found between the results of the first and the second measurements for both 2D-TOF and oblique sagittal T(1)W sequences. No significant difference was found between the two sequences in the ratio of bilateral carotid bifurcation angle (right/left), nor in the 4 angles from different locations.</p><p><b>CONCLUSION</b>Oblique sagittal T(1)-weighted (QIR-FSE) black-blood sequence can be used to measure the carotid bifurcation angle.</p>
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Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Carotid Arteries , Pathology , Carotid Artery Diseases , Pathology , Feasibility Studies , Magnetic Resonance Imaging , Methods , Reproducibility of Resultsالملخص
<p><b>OBJECTIVE</b>To reduce the acquisition time of carotid high-resolution contrast-enhanced magnetic resonance imaging (CEMRI), we designed a small field-of-view (FOV) quadruple-inversion-recovery (SF-QIR) T1WI and evaluated the image quality.</p><p><b>METHODS</b>Twenty-four subjects with carotid plaque were enrolled in our study. All the subjects were imaged using the same 3.0T MRI by SF-QIR and standard rectangular FOV QIR (SrF-QIR) with identical parameters except for the phase-encoding step numbers and the RF excitation methods. Three independent readers qualitatively evaluated the differences between the two sequences in regard of the carotid outer wall border delineation, fibrous cap and lipid-rich necrotic core (LR-NC) border delineation, and diagnostic confidence. The quantitative measurements included maximal stenosis, wall area, LR-NC area, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). The inter-reader variability was assessed.</p><p><b>RESULTS</b>The application of SF-QIR combined with orthogonal radio frequency excitation resulted in nearly half of the scan time with the SrF-QIR. Both qualitative and quantitative assessment by the readers revealed no significant differences between the two sequences except for SNR and CNR (Pgt;0.05). Since the mean loss of SNR with SF-QIR was 37.7%, SrF-QIR demonstrated a superior performance in SNR (P<0.001).</p><p><b>CONCLUSION</b>The small FOV QIR sequence is effective in high-resolution CEMRI for evaluating carotid plaques and can effectively reduce the scan time and eliminate motion artifacts.</p>
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Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Carotid Artery Diseases , Diagnosis , Pathology , Image Enhancement , Methods , Magnetic Resonance Imaging , Methodsالملخص
Objective To evaluate the modification of C_(60) on the radiation effects of ~(60)Co-γ irradiation on zebrafish.Methods The adult and embryonic zebrafish were used as model organisms to examine the potential of C_(60) to elicit oxidative stress responses on the surviving rate,hatching rate and malformation occurrence,both upon exposure to light or in the dark.Reactive oxygen species (ROS) production and DNA damage were examined as the possible underlying mechanism.Results 500 × 10~(-9) nano-C_(60) waterborne exposure could enhance the γ-irradiation effects by decreasing adult fish survival upon light exposure,which resulted in ROS and DNA damage increasing.The hatching rates were also inhibited with higher malformation,though dark exposure did not make any enhancement,except that the 5000× 10~(-9) C_(60) would inhibit larvae hatching and induced more malformation.Conclusions Waterborne nano-C_(60) exposure may enhance the radiation effects on zebrafish,ROS production and DNA damage increasing may be the underlying mechanism.
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Objective To investigate the application prospective of carboxyfullerene C_3 as a radioprotectant or assistant for tumor radiotherapy.Methods Different concentrations of C_3 were incubated with K562 and AHH-1 cell,CCK-8 assay and trypan blue rejection test were performed to examine the influence of C_3 on the cell viability.Annexin V/PI staining and flow cytometry assay were applied to assess the cell cycle and apoptosis after 7-ray irradiation.Results C_3 showed little toxicity to AHH-1 cell with the survival rate over 95% ,but 600 mg/L of C_3 markedly inhibited the growth of K562 cell (82%) .Pretreatment of 100 mg/L C_3 significantly increased the survival rate of AHH-1 cell after 4 Gy irradiation compared with the single radiation group(71.3% vs 90.3%) ,but decreased the apoptosis rate (26.3% vs 12.6%) ,while the survival rate of K562 cell was decreased and the apoptosis rate was elevated with the increase of C_3 concentration.Moreover,the cell cycle analysis revealed the G_2 phase block in AHH-1 cell after radiation exposure was mitigated by C_3 pretreatment,but that in K562 cell was aggravated.Conclusions C_3 has good radioprotective effects on AHH-1 cells.For K562 cell,C_3 could inhibit the cell proliferation,promote the radiation induced apoptosis and aggravate the G_2 phase block.
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Objective To determine the correlation between coronary artery calcium score (CACS) and carotid calcification, and their risk factors. Methods 162 cases underwent coronary and carotid pre-contrast CT scan with dual-source CT scanner within 2 weeks. The reconstructed parameters were the same. The calcifications of coronary and carotid arteriae were quantified by calculating the Agatston score. The main risk factors such as age, sex, hypertension, total cholesterol, low-density-lipoprotein cholesterol (LDL), high-density-lipoprotein cholesterol (HDL), diabetes, smoking and coronary heart disease history were recorded. The CACS and carotid calcium scores were comparatively analyzed using Spearman's correlative analysis. The relativity between the risk factors and CACS scores, carotid calcium scores. Results In 162 subjects, there was positive relativity between CACS and carotid cal-cium score(r=0.690, P<0.01). Logistic regression analysis showed that CACS were of relativity with age, diabetes, total cholesterol and LDL cholesterol,otherwise, carotid calcium scores only with age and diabetes. Conclusion There is significant correlation be-tween CACS and carotid calcium score, but their risk factors are not same.
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Objective To investigate alteration of SHP-2 mRNA and protein of bone marrow cells of leukemia mice after ?-ray exposure.Methods A total of 318 BALB/c mice were exposed to ~(60)Co ?-ray once a week for 4 weeks,and the total dose of ?-ray received by mice was 7.00 Gy.By pathological examination,39 mice developed thymic lymphoma,14 acute lymphoblastic leukemia,21 T-lymphoblast leukemia/lymphoma,1 spiroma,4 malignant yolk sac tumors.Exposed to ?-ray,the mice that developed leukemia or were free of canceration were used in our study(n=10 in each group),and another 10 mice free from irradiation served as control.SHP-2 mRNA and protein in femoral bone marrow cells were detected by real time fluorescence quantitative PCR(FQ-PCR) and Western blotting respectively.Results SHP-2 mRNA was(5.08?2.87) in leukemia mice,(4.59?2.36) in mice free of canceration and(3.54?1.02) in controls.SHP-2 protein was(0.956?0.125) in leukemia mice,(0.892?0.236) in mice free of canceration and(0.712?0.368) in controls.The enzyme catalytic activity of SHP-2 was(0.156?0.069),(0.118?0.065),(0.098?0.048).No significant difference in mRNA,protein or enzyme catalytic activity of SHP-2 was found in leukemia mice,mice free from canceration and control mice.Conclusion SHP-2 mRNA and protein was significantly increased in bone marrow cells of leukemia mice induced by ?-ray irradiation.
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Objective To investigate the expression and function of SH2 domain containing protein tyrosine phosphatase SHP 2 of thymocytes in ? ray irradiation induced leukemia in mice. Methods BALB/c mice were divided into canceration group, non canceration group, and control group. The expression, level of tyrosine phosphorylation, and enzyme catalytic activity of SHP 2 in thymocytes were detected by Western blotting, immunoprecipitation, and biochemical method. Results There was obvious correlation among the expression, level of tyrosine phosphorylation, and enzyme catalytic activity of SHP 2, which were significantly higher in the canceration group than those in the non canceration group and the control group ( P
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Objective To investigate alteration of SHP-1 mRNA and protein of bone marrow cells of leukemia mice after ?-ray exposure.Methods A total of 318 BALB/c mice were exposed to ~(60)Co ?-ray once a week for 4 weeks,and the total dose of ?ray received by mice was 7.00 Gy.By pathological examination,39 mice developed thymic lymphoma,14 acute lymphocytic leukemia,21 T-lymphoblast leukemia/lymphoma,1 spiroma,4 malignant yolk sac tumor.Exposed to ?-ray,the mice that developed leukemia or were free of canceration were used in our study(n=10 in each group),and another 10 mice free from irradiation served as control.SHP-1 mRNA and protein in femoral bone marrow cells were detected by real-time fluorescence quantitative PCR(FQ-PCR) and Western blotting respectively.Results SHP-1 mRNA in leukemia mice was(5.26?2.14),significantly higher than that of mice free of canceration(3.68?1.27) and controls(2.95?1.09)(P
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Objective To compare the accuracy of CE MRA and Gated 2D TOF MRA in evaluation of internal carotid artery stenosis. Methods 34 patients (male 27, female 7, age range 45-78 years) were evaluated with contrast enhanced three dimensional magnetic resonance angiography (CE MRA) and unenhanced ECG gated two dimensional time of flight MRA (Gated 2D TOF MRA). Digital subtraction angiography (DSA) was used as the “gold standard”. The MRA images were reprojected with maximum intensity projection (MIP) algorithm. Sensitivity, specificity, diagnositic accuracy,overestimation and underestimation were assessed. Results (1) DSA provided 68 diagnostic judgments: 23 were negatives and 45 were positives (mild stenosis 10, moderate stenosis 14, severe stenosis 17, occlusion 4). CE MRA was in agreement with angiography in 66 (97%), but overestimation resulted in 2 cases. Gated 2D TOF MRA was in agreement with angiography in 56 (82%), with 9 overestimation and 3 underestimation. (2) Taking negative and positive cases as judgement, CE MRA showed higher sensitivity, specificity, and diagnostic accuracy than Gated 2D TOF MRA (100% versus 95 6%, 100% versus 78.3%, 100% versus 89.4%, respectively). (3) Taking 70% stenosis as judgement, CE MRA also showed higher sensitivity, specificity, and diagnostic accuracy than Gated 2D TOF MRA (100% versus 95 2%, 97.8% versus 93.6%, 98.5% versus 94.1%, respectively). Gated 2D TOF MRA vs DSA, CE MRA vs DSA and Gated 2D TOF MRA vs CE MRA all had no significant difference (? 2=3.000 with P =0.083, ? 2=2.000 with P =0.157, and ? 2=1.600 with P =0.206 respectively) Conclusion Compared with Gated 2D TOF MRA,CE MRA is more accurate in evaluation of carotid artery stenosis.
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Irradiation induced tumorigenesis is a complicated process involving several phases such as initiating, promoting and progressing, just like the tumorigenesis induced by other factors. While irradiation induced tumorigenesis has its particularity on molecular mechanism, though the precise process remain unclear. Generally, irradiation can cause serious damage on DNA, which may bring irreversible consequences. For example, the double strand breaks (DSB) can induce the mismatch repair reaction, resulting in mutation of some specific genes or chromosomes in irradiated cells. The mutagenesis then make for the activation of oncogene, inactivation of tumor suppressor gene, uncontrolled cell proliferation and alterations of signal transduction pathway, all these work together to promote tumorigenesis. In addition, the gene instability, cytoplast mutation and cell group by stand effects induced by irradiation also play crucial roles in the process of tumorigenesis. [