BACKGROUND The purpose of this work was to unearth the effects and underlying mechanism of long non-coding RNA (lncRNA) MALAT1 in ovarian cancer cell stemness. MATERIAL AND METHODS Western blot, quantitative polymerase chain reaction (qPCR) and sphere forming analysis were performed to evaluate the stem-like traits of cells and MALAT1-induced effects on ovarian cancer cell stemness. Cell viability was performed to evaluate MALAT1 role in the chemoresistance of ovarian cancer cells. RNA immunoprecipitation (RIP) and luciferase reporter analysis were constructed to investigate the underlying mechanisms. RESULTS Here, qPCR assay showed that MALAT1 level was remarkably higher in non-adherent spheres formed by adherent ovarian cancer cells, as well as cisplatin-resistant ovarian cancer cells. Additionally, MALAT1 knockdown reduced ovarian cancer cell stemness, characterized as the decrease of sphere forming ability, expression of stemness regulatory masters, and attenuation of cisplatin resistance. Moreover, MALAT1 interacted with yes-associated protein (YAP), inhibited its nuclear-cytoplasm translocation, promoted YAP protein stability and expression and thus increased its activity. Notably, rescuing expression of YAP attenuated the inhibition of MALAT1 knockdown on ovarian cancer cell stemness. CONCLUSIONS In conclusion, these results demonstrate a MALAT1/YAP axis responsible for ovarian cancer cell stemness.
Background: RNA binding protein RNPC1 has a tumor-suppressive role in various tumors, nevertheless, the role of RNPC1 in human endometrial cancer (EC) are never been reported. Material/Methods: Western blot, quantitative polymerase chain reaction and sphere forming analysis were performed to evaluate the stem-like traits of cells and RNPC1-induced effects on EC cell stemness. RNA immunoprecipitation (RIP) was constructed to investigate the underlying mechanisms. Results: The spheres formed by EC cells, named EC spheres, exhibited a remarkably higher stemness than the parental cells, which is characterized as the increase of sphere forming ability, ALDH1 activity, stemness marker expression and migration ability. Notably, RNPC1 expression was decreased in poorly differentiated EC cells than that in EC cells with moderately differentiated. Additionally, RNPC1 expression was significantly decreased in EC spheres and RNPC1 overexpression attenuated the stemness of EC spheres. Moreover, RNPC1 overexpression decreased the migration ability of EC spheres. Mechanistic studies showed that RNPC1 overexpression activated the Hippo pathway through directly binding to MST1/2. Inhibition of MST1/2 rescued RNPC1-mediated effects on EC sphere stemness. Conclusions: Therefore, our results indicate a novel RNPC1/MST1/2 signaling responsible for EC cell stemness.
目的 研究浙江省丽水地区妇女X-射线交错互补修复基因1(XRCC1)Arg194Trp、Arg280His和Arg399Gln单核苷酸多态性与人乳头瘤病毒(HPV)(16、18、52、58)感染宫颈鳞状细胞癌发病风险的关系.方法 采用实时荧光聚合酶链式反应方法检测2016年5月-2019年7月浙江省丽水市中心医院收治的115例HPV(16、18、52、58)宫颈鳞状细胞癌患者和143例健康对照者血液标本的Arg194Trp、Arg280His和Arg399Gln三个SNP基因型频率分布,分析其与HPV(16、18、52、58)感染宫颈鳞状细胞癌发病风险的关系,28种HPV基因型采用聚合酶链式反应-反向点杂交法对宫颈分泌物标本进行检测.结果 宫颈鳞状细胞癌组和对照组XRCC1-Arg194Trp、Arg280His和Arg399Gln基因型频率分布均符合Hardy-Weinberg平衡定律(P>0.05),宫颈鳞状细胞癌组和对照组XRCC1-Arg194Trp和Arg399Gln基因型和等位基因频率分布差异有统计学意义(P<0.05),宫颈鳞状细胞癌组和对照组XRCC1-Arg280His基因型和等位基因频率分布差异无统计学意义(P>0.05),XRCC1-Arg194Trp多态性位点中,携带Trp基因的个体HPV(16、18、52、58)感染宫颈鳞状细胞癌发病风险是Arg个体的1.793倍(OR=1.793,95%CI=1.190~2.702,P<0.05);XR-CC1-Arg399Gln多态性位点中,携带Gln基因的个体HPV(16、18、52、58)感染宫颈鳞状细胞癌发病风险是携带Arg基因个体的1.668倍(OR=1.668,95%CI=1.126~2.472,P<0.05);而XRCC1-Arg280His的多态性位点与HPV(16、18、52、58)感染宫颈鳞状细胞癌发病风险无关(OR=1.210,95%CI=0.753~1.945,P>0.05).结论 浙江省丽水地区XRCC1-Arg194Trp、Arg399Gln多态性可能与人群HPV(16、18、52、58)感染宫颈鳞状细胞癌发病风险相关,而XRCC1-Arg280His多态性与本地区人群HPV(16、18、52、58)感染宫颈鳞状细胞癌易感性无关.
This study was designed to investigate the expression of RBM8A protein in patients with gastric cancer (GC) and to explore its correlation with clinical pathological features as well as prognosis. One hundred pairs of gastric carcinoma tissues and adjacent tissues from patients undergoing gastrectomy for GC were included in this study. The protein expression level of RBM8A was determined by immunohistochemistry using tissue microarrays. We also detected the mRNA expression level of RBM8A in 16 pairs of gastric carcinoma tissues and adjacent tissues. Meanwhile, we predicted the potential correlation between RBM8A and tumor stages as well as survival condition in patents with GC based on The Cancer Genome Atlas (TCGA) database. The correlation of RBM8A with the clinical pathological features and prognosis of the 100 patients with GC was also elucidated. The expression level of RBM8A was significantly higher in gastric carcinoma tissues compared to the adjacent tissues. The protein level of RBM8A was correlated with tumor size (P=0.031), depth of invasion (P<0.001), lymph node metastasis (P<0.001), TNM stage (<0.001), and distant metastasis (P=0.001). Patients with increased RBM8A expression (P<0.0018, 95%CI=0.322−0.871), higher TNM stage (P<0.001, 95%CI=4.990−11.283), and lymph node metastasis (P<0.001, 95%CI=2.873−4.002) had a lower overall survival. Taken together, our study demonstrated that RBM8A may act as a proto-oncogene, which could be a promising biomarker and therapeutic target in the diagnosis and treatment of GC.
目的 分析浙江省丽水地区人群亚甲基四氢叶酸还原酶(MTHFR)基因C677T和A1298C单核苷酸多态性与人乳头瘤病毒(16、18、52、58)感染的宫颈鳞状细胞癌发病风险的关系.方法 采用实时荧光聚合酶链式反应方法检测在丽水市中心医院住院治疗的115例HPV(16、18、52、58)感染的宫颈鳞状细胞癌患者和143例HPV阴性的健康对照妇女血液标本MTHFR C677T和A1298C两个单核苷酸多态性基因型频率的分布,分析其与HPV(16、18、52、58)感染宫颈鳞状细胞癌发病风险的关系;28种HPV基因型采用聚合酶链式反应-反向点杂交法对宫颈分泌物标本进行检测.结果 病例组和对照组MTHFR C677T和A1298C基因型频率分布均符合Hardy-Weinberg平衡定律(均P>0.05),病例组和对照组MTHFR C677T和A1298C基因型频率分布均有统计学差异(均P<0.05).在MTHFR C677T多态性位点中,携带T的受试者HPV(16、18、52、58)感染的宫颈鳞状细胞癌发病风险是C受试者的1.871倍(OR=1.871,95%CI:1.294~2.705,P<0.05);在MTHFR A1298C多态性位点中,携带C的受试者HPV(16、18、52、58)感染宫颈鳞状细胞癌发病风险是A受试者的1.867倍(OR=1.867,95%CI:1.204~2.896,P<0.05).结论 MTHFR C677T和A1298C多态性可能与浙江省丽水地区人群HPV(16、18、52、58)感染者宫颈鳞状细胞癌发病有关.
目的 分析局限期食管小细胞癌(SCEC)患者接受放化疗后的疗效及预后影响因素.方法 回顾性分析2000年1月至2016年12月江苏省中医院和浙江丽水市中心医院行放化疗治疗的38例局限期SCEC患者的临床资料,患者均行调强或三维适形放疗,放疗总剂量50~66 Gy,每日剂量1.8~2.0 Gy.放疗同步化疗(顺铂和依托泊苷)2周期以及序贯2周期.随访3年并分析患者中位生存时间、1年和3年生存率、治疗期间不良反应,利用Cox回归模型分析患者预后的影响因素.结果 38例患者平均随访时间(30.4±4.6)个月,中位生存时间25.2个月(9~41个月),1年和3年生存率分别为75.12%和32.31%.其中18例(47.37%)患者出现3~4级粒细胞减少,16例(42.11%)患者出现3~4级血小板减少,12例(31.58%)患者出现3级贫血.Cox回归模型结果显示,纵隔或胃周淋巴结转移为影响SCEC预后的危险因素.结论 根治性放化疗对局限期SCEC患者的疗效可期,有无纵隔或胃周淋巴结转移是其预后影响因素之一.
Objective To explore the influence of radiation therapy on CD3 +,CD4 +,CD8 +,CD4 +/CD8 + in patients with lung cancer.Methods The clinical data of 90 patients with lung cancer undergoing radiotherapy in Lishui Central Hospital were studied.The radiation dose and target volume were recorded.The CD3 +,CD4 +,CD8 + and CD4 +/CD8 + in peripheral blood were determined by flow cytometry.Results After radiotherapy,the CD3 + [(61.48 ± 1.86) %] was no significant difference with that before radiotherapy [(61.12 ± 1.83) %],P > 0.05,the levels of CD4 + and CD4 +/CD8 + [(26.85 ± 1.28) %,0.71 + 0.06] were significantly lower than those before the treatment [(36.24 +± 1.25) %,1.22 + 0.08] (P < 0.05),the CD8 + content [(37.92 ± 1.66) %] was higher than that before the treatmnent [(29.79 ± 1.12) %],P < 0.05.After radiotherapy,CD3 + abnormality ratio (32.2%) was no significant difference with that before radiotherapy (34.4%),P > 0.05,the percentage of abnormal CD4 +,CD4 +/CD8 + (85.6%,67.8%) was lower than that before the treatment (53.3 %,31.1%),P < 0.05.The CD3 +,CD4 +,CD8 +,CD4 +/CD8 + radiation therapy dose ≥ 60 Gy patients [(63.43 ± 1.85) %,(27.23 ± 1.28) %,(37.53 ± 1.17) %,0.72 ± 0.07] was not statistically significant with radiation dose < 60 Gy [(61.12 ± 1.77)%,(26.77 ± 1.31)%,(38.08 ± 1.36)% and 0.69 ± 0.05],P >0.05.There was no significant difference of CD3 between target volume > 440 cm3 [(61.88 ± 2.23) %] and target volume≤440 cm3 [(59.99 ±2.17) %],P >0.05,the CD4 +,CD4 +/CD8 + [(24.37 ± 1.68) %,0.68 ±0.06] were significantly lower than those with target volume ≤440 cm3,the CD8 content[(41.46 ± 2.59)%] was higher than that of target volume ≤440 cm3 [(34.27 ± 2.13) %],P < 0.05.Conclusion The immune of lung cancer patients before radiotherapy is dysfunction.The immune function after radiation therapy decreases further.The immune function of patients with lung cancer is related to radiation target volume,the larger the target volume,the lower the immune function.
目的 探讨厄洛替尼联合全脑放疗(whole brain radiotherapy,WBRT)治疗非小细胞肺癌(non-small cell lung cancer,NSCLC)脑转移患者的临床效果及预后影响.方法 选取2013年9月~2015年5月丽水市中心医院收治的NSCLC脑转移患者100例,根据患者是否使用厄洛替尼分为对照组54例和观察组46例,2组均给予WBRT治疗,对比2组患者的近期效果、远期预后及不良反应发生率.结果 观察组的缓解率52.17%显著高于对照组27.78%,观察组总有效率91.30%显著高于对照组72.22%,差异均具有统计学意义(P<0.05);观察组的1年生存率52.17%(24/46)显著高于对照组29.63% (16/54),观察组中位生存时间9.0个月显著高于对照组6.0个月,差异均具有统计学意义(P<0.05);2组治疗过程中不良反应发生率差异均无统计学意义.结论 厄洛替尼联合WBRT治疗NSCLC脑转移患者能够提高近期疗效及远期预后的效果.
目的评价晚期鼻咽癌(NPC)患者应用多希他赛与顺铂联合化疗的临床疗效及安全性。方法 2007年4月至2009年2月采用多希他赛联合顺铂治疗晚期鼻咽癌48例。中位化疗周期数3周期(2周期~5周期)。多希他赛(Docetaxel)75mg/m2,第一天静脉滴注,顺铂(DDP)80mg/m2,分4天静滴,21d为1周期。结果可评价疗效48例,CR13例(27.1%),PR25例(52.1%),NC6例(12.5%),PD4例(8.3%),总有效率(CR+PR)79.1%。中位缓解期(DFS)为6.5(2~12)个月,中位肿瘤进展时间(TTP)7.6(2~14)个月。主要毒性为骨髓抑制和胃肠道反应,Ⅲ度~Ⅳ度白细胞减少发生率为18.7%,无严重并发症发生。结论多希他赛联台顺铂治疗晚期鼻咽癌有较好的疗效,且不良反应可以耐受。
目的观察应用氨磷汀联合含地塞米松漱口液在减轻鼻咽癌放疗反应中的疗效。方法将60例鼻咽癌患者随机分为2组,2组治疗期间均给予氨磷汀使用,治疗组31例在放疗期间予含有地塞米松的漱口液含漱,对照组29例予不含地塞米松漱口液含漱。结果治疗组轻度反应l8例(58%),中度反应lO例(32%),重度反应3例(10%);对照组无轻度反应,中度反应l2例(4l%)。重度反应l7例(59%)。结论治疗组重度反应率占10%,对照组重度反应率占59%,治疗组重度反应明显低于对照组。患者全部能按计划完成全程放疗。
目的 探讨紫杉醇联合顺铂(TP)方案对晚期宫颈癌同步放化疗的临床效果.方法 72例晚期宫颈癌患者随机分为两组,治疗组行放疗(体外放疗+腔内放疗)+同步化疗,化疗方案为紫杉醇联合顺铂,即TP方案;为对照组行放疗(体外放疗+腔内放疗)+同步化疗,化疗方案为5-氟尿嘧啶+博莱霉素+顺铂.结果 TP方案组有效率为94% (34/36),对照组有效率为78% (28/36);5年生存率TP组为75% (27/36),对照组为53% (19/36),(X~2=3.85,P<0.05).结论 紫杉醇联合顺铂(TP)对晚期宫颈癌同步放化疗疗效显著.
目的观察注射用甘氨双唑钠在中晚期宫颈癌放疗中的增敏作用,评价其近期疗效及对远期生存率的影响。方法 66例中晚期宫颈癌患者随机分为2组,放射增敏组34例行根治性放疗,直线加速器进行盆腔对穿外照射,5次/周,DT2Gy/次,剂量达DT28Gy/14次时体中线挡铅3~4cm,变为前后四野照射,外照射总剂量为50Gy/25次,腔内治疗总剂量DT30~36Gy/5~6次,并在每周一、三、五放疗前静脉滴注增敏药注射用甘氨双唑钠。对照组32例行单纯根治性放疗,两组放疗方案相同。结果增敏组肿瘤完全消退率达91.2%,单放组肿瘤完全消退率达71.9%,增敏组优于对照组(<0.05)。3年生存率增敏组为77.4%,而对照组为53%,增敏组优于对照组<0.05)。结论注射用甘氨双唑钠可以使肿瘤消退加速,不增加毒副反应,能提高临床治愈率。
Purpose] To evaluate the long-term efficacy and sequela of radiotherapy with CT simulation for nasopharyngeal carcinoma(NPC).[Method]One hundred and three cases with nasopharyngeal carcinoma proved pathologically were randomized into two groups, 53 patients in group of CT-simulation, 50 patients in group of convention simulation(consim). At CT-simulation, face-neck united beam and under-neck tangent beam were set with the convention fractionation radiotherapy ranging from 36~40Gy.Then,face-neck united beam was moved to avoid the spinal cord damage.The upper-neck tangent beam with electron 9-12MeV was adopted. In the last period, conformal radiotherapy 6MV X was used, the total dose of the nasopharynx, ranged from 68~74Gy.In consim group, face-neck united beam and under-neck tangent beam were set on the bone mark first, ranging from 36~40Gy,then ear-anterior beam, ear-posterior electron beam, and all-neck tangent beam. [Result] All cases were followed up over 5 years. 5 year survival rate, progression-free survival rate and recurrence rate in CT-sim and in consim were 69.8%, 67.9% and 7.5% vs 50.0%, 48.0% and 24.0% respectively. Comparing two treatment groups the differences were significant (P0.05). Some radiotherapeutic sequelas were found: one case with deafness in CT-sim group , one case with abducent paralysis, two cases with deafness and two cases with radioactive encephalopathy in consim group. There was no radioactive myelitis in both groups.[Conclusion] Radiotherapy with CT simulation for NPC can increase efficacy camparing to that with consentimal simulation,and decrease recurrence and radiotherapeutic sequela.
目的对比BVP化疗配合放射治疗与单纯放疗治疗宫颈癌的疗效,探讨综合治疗在中晚期宫颈癌中的疗效及安全性.方法83例Ⅱ-Ⅳ中晚期宫颈癌患者分成两组,放疗同步化疗(A组)47例,在放疗同时给予BVP方案(BLM30mg d1,VCR 2mg d1,DDP 40mg d1~3)化疗2~4周期,化疗第1天开始行放射治疗.单纯放疗组(B组)36例,两组放射治疗均用6Mv-X线全盆对穿两大野照射DT 25~30Gy,随后改成盆腔四野照射并加192铱后装治疗.结果A组和B组近期有效分别为93.6%和72.2%,两组的差异有显著性意义(χ2=7.10,P<0.01).A组和B组的5年生存率分别为72.3%和50%.差异有显著性意义(χ2=4.35,P<0.05).毒性反应方面,同步化放疗组高于单纯放疗组,尤以造血系统和消化道反应为主,但大部分能够耐受.结论中晚期宫颈癌患者BVP方案同步放化疗可提高局部控制率和提高生存率.