1.High expression of AURKB promotes malignant phenotype of osteosarcoma cells by activating nuclear factor-κB signaling via DHX9.
Yanxin ZHONG ; Yu LIU ; Weilai TONG ; Xinsheng XIE ; Jiangbo NIE ; Feng YANG ; Zhili LIU ; Jiaming LIU
Journal of Southern Medical University 2024;44(12):2308-2316
OBJECTIVES:
To investigate the regulatory mechanism of aurora kinase B (AURKB) for promoting malignant phenotype of osteosarcoma cells.
METHODS:
HA-Vector or HA-AURKB was transfected in 293T cells to identify the molecules interacting with AURKB using immunoprecipitation combined with liquid chromatography-tandem mass spectrometry followed by verification with co-immunoprecipitation and Western blotting. In cultured osteosarcoma cells with lentivirus-mediated RNA interference of AURKB or DHX9 or their overexpression, the changes in cell proliferation, migration, and invasion activities were observed with EDU and Transwell assays. Mechanistic analysis was performed using Co-IP and in vivo ubiquitination experiments to detect the interaction between AURKB and DHX9 and the phosphorylation and ubiquitination levels of DHX9. Western blotting was used to detect the effect of AURKB and DHX9 on activation of nuclear factor-κB (NF-κB) signaling.
RESULTS:
AURKB was highly expressed in osteosarcoma cell lines, and in osteosarcoma 143B cells, AURKB silencing significantly reduced cell proliferation, migration and invasion abilities. Interactions between AURKB and DHX9 were detected, and they were both highly expressed in osteosarcoma tissues; silencing AURKB reduced the protein expression of DHX9, and AURKB overexpression increased DHX9 phosphorylation. Silencing AURKB did not significantly affect the transcription and translation of DHX9 but accelerated its degradation and ubiquitination. Overexpression of DHX9 effectively reversed the effects of AURKB silencing on IKBα protein and phosphorylated p65, promoted nuclear translocation of p65 to activate the NF-κB signaling pathway, and enhanced the proliferation, migration, and invasion abilities of cultured osteosarcoma cells.
CONCLUSIONS
AURKB overexpression promotes the malignant phenotype of osteosarcoma cells by activating the NF-κB signaling pathway via regulating DHX9.
Humans
;
Osteosarcoma/genetics*
;
Cell Proliferation
;
NF-kappa B/metabolism*
;
Signal Transduction
;
Cell Line, Tumor
;
Cell Movement
;
DEAD-box RNA Helicases/genetics*
;
Aurora Kinase B/genetics*
;
Phenotype
;
Bone Neoplasms/genetics*
;
Neoplasm Invasiveness
;
Phosphorylation
;
Neoplasm Proteins
2.Longitudinal study of symptoms during chemotherapy in adults with newly diagnosed acute leukemia
Yanxin YE ; Xixi YIN ; Ya YU ; Suting LIU ; Huiqun ZHONG ; Lili ZHANG
Chinese Journal of Practical Nursing 2022;38(17):1292-1297
Objective:To understand the incidence, severity and the change trajectory of symptoms in adult patients with acute leukemia during treatment, so as to provide a reference for clinical medical staff to conduct specific symptom screening and management.Methods:From March 2017 to August 2018, 69 patients who were newly diagnosed with acute leukemia at the Nanfang Hospital of Southern Medical University were conveniently selected. The Memory Symptom Assessment Scale was used to investigate the patients before chemotherapy (T1), after the first chemotherapy (T2), after the second to third chemotherapy (T3) and after the fourth to fifth chemotherapy (T4).Results:The severity score of psychological symptoms in adult patients with acute leukemia at T1, T2, T3, and T4 were 1.00(0.58, 1.42), 1.00(0.83, 1.67), 0.67(0.33, 1.00) and 0.67(0.33, 1.00). The severity score of physical symptoms at T1, T2, T3, and T4 were 0.50(0.21, 0.83), 1.00(0.54, 1.33), 0.75(0.58, 1.17) and 0.92(0.63, 1.08), respectively. The score difference was statistically significant ( H = 28.34, 27.14, both P<0.01) at different time points. The score of physical symptoms reached a peak at T2. In the psychological dimension, the severity and incidence of energy deficiency were higher in T1-T4. Conclusions:Adult acute leukemia patients have different focal symptoms in different treatment stages. Clinical medical staff should provide effective and personalized nursing intervention for patients in different treatment stages.
3.Clinical efficacy of laparoscopic-assisted intersphincteric resection with different surgical approaches for low rectal cancer
Junxing CHEN ; Jianhua XU ; Jian'an LIN ; Wengui KANG ; Wenjin ZHONG ; Chuying WU ; Jintian WANG ; Pengcheng WANG ; Yanxin CHEN ; Kai YE
Chinese Journal of Digestive Surgery 2022;21(6):779-787
Objective:To investigate the clinical efficacy of laparoscopic-assisted inters-phincteric resection (ISR) with different surgical approaches for low rectal cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 90 patients with low rectal cancer who were admitted to the Second Affiliated Hospital of Fujian Medical University from January 2016 to December 2020 were collected. There were 58 males and 32 females, aged (60±9)years. Of 90 patients, 60 cases underwent laparoscopic assisted ISR with transpelvic approach, 30 cases underwent laparoscopic assisted ISR with transabdominal and transanal mixed approach. Observation indicators: (1) clinicopathological characteristics of patients with transpelvic approach and mixed approach; (2) intraoperative and postoperative conditions of patients with transpelvic approach and mixed approach; (3) postoperative complications of patients with transpelvic approach and mixed approach; (4) follow-up. Follow-up was conducted by telephone interview and outpatient examination once every 3 months within postoperative 3 years, once every six months in the postoperative 3 to 5 years and once a year after postoperative 5 years to detect tumor recurrence and metastasis, and survival of patients.Follow-up was up to March 2021 or patient death. Measurement data with normal distribution were represented as Mean± SD, and the t test was used for comparison between groups. Measurement data with skewed distribution were expressed as M(range), and comparison between groups was conducted using the non-parametric Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was performed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed by the non-parametric rank sum test. Kaplan-Meier method was used to draw survival curves and calculate survival rates, and survival analysis was performed by the Log-Rank test. Results:(1) Clinicopathological characteristics of patients with transpelvic approach and mixed approach. The sex (males, females), distance from the distal margin of tumor to anal margin were 34, 26, (4.5±0.5)cm for patients with transpelvic approach, versus 24, 6, (3.5±0.5)cm for patients with mixed approach, respectively, showing significant differences between them ( χ2=4.75, t=8.35, P<0.05). (2) Intraoperative and postoperative conditions of patients with transpelvic approach and mixed approach. The operation time, volume of intraoperative blood loss, distance from the postoperative anastomosis to anal margin were (187±9)minutes, 50(range, 20?200)mL, (3.4±0.7)cm for patients with transpelvic approach, versus (256±12)minuets, 100(range, 20?200)mL, (2.6±0.7)cm for patients with mixed approach, showing significant differences between them ( t=?26.99, Z=?2.48, t=4.67, P<0.05). None of the 90 patients had a positive distal margin. The stoma reversal rates of patients with transpelvic and mixed approach were 93.3%(56/60) and 90.0%(27/30), respectively. Of the 60 patients with transpelvic approach, 3 cases had no stoma reversal due to anastomotic complications, and 1 case was not yet to the reversal time. Of the 30 patients with mixed approach, 2 cases had no stoma reversal due to anastomotic complications, and 1 case was not yet to the reversal time. The 1-, 3-month Wexner scores after stoma reversal were 15(range, 12?17), 12(range, 10?14) for patients with transpelvic approach, versus 16(range, 14?18), 14(range, 12?16) for patients with mixed approach, showing significant differences between them ( Z=?4.97, ?5.49, P<0.05). The 6-month Wexner score after stoma reversal was 10(range, 9?12) for patients with transpelvic approach, versus 11(range, 8?12) for patients with mixed approach, showing no significant difference between them ( Z=?1.59, P>0.05). (3) Postoperative complications of patients with transpelvic approach and mixed approach. The complications occurred to 16 patients with transpelvic approach and 9 patients with mixed approach, respectively, showing no significant difference between them ( χ2=0.11, P>0.05). Cases with postoperative anastomotic fistula, cases with anastomotic bleeding, cases with anastomotic stenosis, cases with intestinal obstruction, cases with incision infection, cases with urinary retention, cases with pelvic infection, cases with pulmonary infection, cases with incisional hernia, cases with chylous fistula, cases with abdominal and pelvic abscess were 5, 2, 1, 7, 0, 1, 5, 3, 1, 1, 1 for patients with transpelvic approach, versus 6, 3, 2, 2, 2, 1, 2, 3, 1, 1, 1 for patients with mixed approach, showing no significant difference between them ( P>0.05). The same patient could have multiple postoperative complications. (4) Follow-up. All the 90 patients were followed up for 27(range, 6?62)months. The follow-up time of 60 patients with transpelvic approach was 27(range, 8?62)months. The follow-up time of 30 patients with mixed approach was 28(range, 6?53)months. Of the 60 patients with transpelvic approach, 3 cases had local recurrence, 4 cases had liver metastasis, 3 cases had lung metastasis, and all of them survived with tumor. Of the 30 patients with mixed approach, 1 case had local recurrence, 2 cases had liver metastasis, 1 case had lung metastasis, and all of them survived with tumor. There was no death. The 3-year disease-free survival rates of patients with transpelvic approach and mixed approach were 84.7% and 87.9%, respectively, showing no significant difference between them ( χ2=0.39, P>0.05). Conclusions:Lapa-roscopic assisted ISR via transpelvic approach or mixed approach for low rectal cancer are safe and feasible. Compared with transanal mixed approach, the transpelvic approach of laparoscopic-assisted ISR has shorter operation time, less volume of intraoperative blood loss and longer distance from the postoperative anastomosis to anal margin.
4.Comparison of difference registration landmarks for image - guided radiotherapy for lung cancer
Yanxin ZHANG ; Zhouguang HUI ; Minghui LI ; Zhong ZHANG ; Guishan FU ; Jianrong DAI
Chinese Journal of Radiation Oncology 2015;(5):552-555
Objective To investigate the impact of anatomical landmarks on registration in image?guided radiotherapy (IGRT) for central and peripheral lung cancer. Methods Twenty?five patients with central or peripheral lung cancer for IGRT were enrolled in this study. Kilo?voltage cone?beam CT ( kV?CBCT) scanning was acquired before irradiotion. Tumor coverage on CBCT was assessed using gross tumor volume (GTV), clinical target volume (CTV), and planning target volume (PTV) contours according to tumor alignment, carina registration, and spine registration, respectively. The grading analysiswas based on visual tumor assessment as follows:grade 0, tumor within GTV;grade 1, tumor outside GTV but inside CTV;grade 2, tumor outside CTV but inside PTV;and grade 3, tumor outside PTV. Results Totally 177 sets of kV?CBCT of 25 patients was collected. According to the registration landmarks of the tumor, carina and spine for central lung cancer, the percentages were 57?55%, 53?77% and 16?04% in grade 0, 39?62%, 45?28%and 58?49% in grade 1, and 1?89%, 0?94% and 25?47% in grade 2, respectively. For peripheral lung cancer, the percentages were 47?89%, 14?08% and 2?82% in grade 0, 43?66%, 29?58% and 45?07% in grade 1, and 8?45%, 40?85% and 35?21% in grade 2, respectively. Conclusions For central lung cancer,the tumor was recommended as the best registration landmark, and the carina was recommended as well, while the spine was not recommended. For peripheral lung cancer, the tumor was recommended as the best registration landmark, while the spine and the carina were not recommended.
5.Clinical characteristics of acute leukemia patients with cross-lineage expression
Ling ZHONG ; Yanxin LI ; Wenfang HUANG ;
International Journal of Laboratory Medicine 2015;(21):3101-3104
Objective To study the clinical characteristics of acute leukemia(AL) patients with cross‐lineage antigen expression . Methods Patients were diagnosed and classified by morphology ,cytochemistry and immunology assay ,and prognostic acting factor were also analyzed .Results According to FAB standards ,acute myeloid leukemia(AML)‐M2 ,acute lymphocytic leukemia (ALL)‐L2 and no‐classified type were common in 320 patients with cross‐lineage antigen expression .The immunophenotype with B and my‐eloid mixed expression was the most common(176 cases) ,followed by cross expression of antigen T and myeloid(131 cases) ,and the co‐expression of B ,T and myeloid antigen was found in only 10 cases .In lymphoid antigenpositive AML(Ly+ AML) ,CD19 anti‐gen was the most common among B lineage ,CD7 was the most common in T lineage .In myeloid antigen positive ALL(My+ ALL) , CD33 was the most common myeloid antigen .Forty‐five cases were with mixed expression of myeloid antigen and CD56 expression . Correlation existed between CD7 and CD34(P< 0 .05) ,CD19 and CD34(P< 0 .05) .There were 9 patients with CD34 ,CD7 and CD19 co‐expression ,7 patients with CD34 ,CD7 and CD56 co‐express .In Ly+ AML patients ,23 cases were with recurrent chromo‐some abnormality ,including 11 cases with t(8 ;21)(q22 ;q22) ,RUNX1‐RUNX1T1 ,3 cases with t(15;17)(q22 ;q11‐12) ,PML/RAR ,6 cases with bone marrow eosinophilia inv(16)(p13 ;q22) ,CBF beta /MYH11 ,and 3 cases with t(9;11)(p22;q23) , MLLT3‐MLL .In My+ ALL ,15 patients were with recurrent chromosome abnormality ,including 9 cases of B‐ALL with t(9;22) (q34 ;q11 .2) ,BCR‐ABL1 ,3 cases of B‐ALL with t(v ;11q23) ,MLL rearrangement ,and 3 cases of T‐ALL with 14q11 .2 .Among the presence of reproducible chromosomal abnormalities in AL ,the antigen expression of mistranslation was still with a certain fea‐ture:Ly+ AML patients often mistranslated CD19 ,CD56 ,CD2 ,and My+ ALL patients often mistranslated CD13 and CD33 .Com‐pared with the lymphoid antigennegative AML(Ly - ALL) group ,CD7+ AML group ,CD19+ AML group and CD56+ AML group had significant difference in survival curves(with P value of 0 .01 ,0 .02 and 0 .02) .There was no significant difference in survival curves between myeloid antigen negative ALL(My -ALL) group and CD13/33+ ALL group(P<0 .05) .CD7 was also positive com‐monly(53 cases) and related with CD34(P<0 .05) .So it significantly influenced the prognosis .If patients were with co‐expression of CD34 ,CD7 and CD19 ,the prognosis could be worse .Conclusion AL with cross‐lineage antigen expression might be a special type and confirmed by immunotype .Furthermore ,expression types of differentiation antigen could be critical for prognosis and sur‐vival .
6.Dose evaluation of conventional radiotherapy using facial-cervical fields in nasopharyngeal carcinoma
Yanxin ZHANG ; Jingwei LUO ; Zhong ZHANG ; Guozhen XU ; Li GAO ; Jianrong DAI ; Junlin YI ; Xiaodong HUANG ; Jianping XIAO ; Suyan LI
Chinese Journal of Radiation Oncology 2009;18(4):308-311
Objective To evaluate the dose distribution of the target volume and the cranial base in nasopharyngeal carcinoma ( NPC ) treated with facial-cervical fields, and to analyze the differences of dose distribution using different isoeenters with the CT-simulator and treatment planning system (TPS). Methods Eleven patients with nasopharyngeal carcinoma were treated by conventional radiotherapy as their primary treatment. All patients were simulated by the conventional simulator and the field borders were marked with thin lead wires on the mask. Then the patients were scanned by the CT-sim with the same immobilization. The planning CT images were transferred to the TPS and the field borders were copied on the DRR, and then GTV and the cranial base were contoured on the coronal CT slices. Two isoeenters were chosen, including one in front of the 1 st cervical vertebra to measeure the depth of the nasopharynx and the other in front of the 3rd cervical vertebra to measure the depth of the upper neck. The prescription dose of 36 Gy was given in 18 fractions. Dose distributions of GTV and the cranial base were calculated with TPS. Results The actual dose of 95% volume of GTV was 33.31 -35.54 Gy (median 34.83 Gy) and 31.43 -33.36 Gy (median 32.44 Gy) when the isoeenters were set in the nasopharynx and the superior neck, respectively. The corre-sponding actual dose of 95% volume of the cranial base was 17.76 - 34.60 Gy ( median 30.28 Gy ) and 16.52 -32.60 Gy (median 28.52 Gy), respectively. Conclusions For NPC patients treated with conven-tional radiotherapy using facial-cervical fields, the actual dose of GTV and the cranial base is lower than the prescribed dose whenever the isocenter is set in the nasopharynx or the upper neck,which is more significant in the latter. The isocenter should be set in the nasopharynx when the conventional radiotherapy is applied and a boost of 4- 8 Gy should be given when the cranial base is involved.

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