Triple-negative breast cancer (TNBC) is a highly invasive subtype of breast cancer. This study explored the molecular mechanism and influences of metallothionein 1 J, pseudogene (MT1JP), microRNA-138 (miR-138), and hypoxia-inducible factor-1α (HIF-1α) on TNBC cell proliferation and migration. We confirmed TNBC cases by immunohistochemistry (IHC) staining. The expression of MT1JP in two types of tissue collected from 78 TNBC patients was detected by performing real-time quantitative fluorescence PCR (RT-qPCR). To further evaluate the relationship among MT1JP, miR-138 and HIF-1α, expression vectors of MT1JP and HIF-1α, as well as miR-138 mimic and inhibitor, were delivered into BT-549 cells. We observed that MT1JP was downregulated in TNBC. MT1JP was positively correlated with miR-138 but negatively correlated with HIF-1α in TNBC tissues. In TNBC cells, upregulation of miR-138 and downregulation of HIF-1α were observed after overexpression of MT1JP. In addition, overexpression of miR-138 resulted in downregulation of HIF-1α but did not affect the expression of MT1JP. Decreased proliferation rate of TNBC cells was observed after overexpression of MT1JP and miR-138. HIF-1α increased cell proliferation and migration. HIF-1α also suppressed the role of MT1JP and miR-138 in TNBC cell proliferation and migration. In conclusion, our findings demonstrated that MT1JP inhibited TNBC by regulating the miR-138/HIF-1α axis, indicating that MT1JP might serve as a biomarker or target for TNBC treatment.
Objective:To study the expression of 5-fold transmembrane protein (CD133) and POU3 homobox gene 3-related long non-coding RNA (PANTR1) in breast cancer and their relationship with cell proliferation and invasion ability in vitro. Methods:A total of 50 breast cancer patients admitted to the Department of Breast Cancer, Beijing Obstetrics and Gynecology Hospital, Capital Medical University from February 2019 to February 2021 were enrolled in this study. The expression of CD133 and PANTR1 in breast cancer tissues and adjacent normal tissues was detected by reverse transcription polymerase chain reaction (PCR). In addition, McF-7 cells were divided into control group, CD133 overexpression group, PANTR1 overexpression group, CD133 inhibition group and PANTR1 inhibition group. The CD133 overexpression group was given Lipofectamine 2000 and CD133 sequence, and the PANTR1 overexpression group was given Lipofectamine 2000 and PANTR1 sequence. Lipofectamine 2000 and si-cd133 were given in CD133 inhibition group, and si-pantr1 inhibition group were given Lipofectamine 2000 and si-pantr1. The differences in proliferation and invasion ability, Pum1 and E2F3 protein expression levels in each group were analyzed. The SPSS 22.0 software was used to carry out t test. Results:The relative expression levels of CD133 and PANTR1 mRNA in breast cancer tissues were higher than those in adjacent normal tissues (0.021±0.001 vs. 0.006±0.001, 0.016±0.002 vs. 0.005±0.001, t=75.000, 74.785, P<0.01). After transfection for 24, 48 and 72 h, the proliferation rate of CD133 overexpression group was higher than that of control group (3.05±0.26, 5.40±0.47 and 10.74±1.27 vs. 2.17±0.25, 4.38±0.42, 6.97±0.84, t=4.226, 2.783, 4.298, all P<0.05), and the number of invasive cells at 24 h after transfection was greater than that of the control group (75.29±7.19 vs. 54.01±6.27, t=3.865, P<0.05). After transfection for 24, 48 and 72 h, the proliferation rate of PANTR1 overexpression group was higher than that of the control group (3.11±0.28, 5.45±0.51 and 10.05±1.24 vs. 2.17±0.25, 4.38±0.42, 6.97±0.84, t=4.372, 3.003, 3.570, all P<0.05), and the number of invasive cells at 24 h after transfection was greater than that of the control group (76.03±7.26 vs. 54.01±6.27, t=3.977, P<0.01). The expression levels of Pum1 and E2F3 protein in CD133 overexpression group were higher than those in control group (4.52±0.75, 3.38±0.56 vs. 1.00±0.04, 1.00±0.03, t=8.118, 7.351, P<0.05). The expression levels of Pum1 and E2F3 protein in PANTR1 overexpression group were higher than those in control group (4.55±0.76, 3.41±0.59 vs. 1.00±0.04, 1.00±0.03, t=8.079, 7.066, P<0.01). The expression levels of Pum1 and E2F3 protein in CD133 inhibition group were lower than those in control group (0.45±0.02, 0.37±0.03 vs. 1.00±0.04, 1.00±0.03, t=21.301, 25.720, P<0.01). Pum1 and E2F3 protein expression levels in panTR1-inhibition group were lower than those in control group (0.47±0.03, 0.38±0.02 vs. 1.00±0.04, 1.00±0.03, t=18.360, 29.784, P<0.01). Conclusion:Both CD133 and PANTR1 are significantly overexpressed in breast cancer, and can enhance cell proliferation and invasion ability in vitro, which deserves clinical attention.
目的:探讨绝经前乳腺癌患者化疗致闭经(CIA)的影响因素.方法:收集2016至2018年的305例行辅助化疗的绝经前乳腺癌患者,随访其化疗后月经变化情况,分析CIA发生的影响因素.结果:CIA发生率为69.51%(212/305),其中月经恢复率为44.8%(95/212).年龄与CIA发生率、月经恢复情况均显著相关(P<0.05).年轻的患者表现出更低的CIA发生率和更高的月经恢复率.但孕产次、腋窝淋巴结转移与否、雌激素受体(ER)、孕激素受(PR)、HER-2状况、病理分期等因素与CIA发生率均无显著相关性(P>0.05).行AC-T和TAC/AT化疗方案的患者CIA发生率高于行TC方案的患者(P<0.05).用他莫昔芬内分泌治疗的患者CIA发生率为72.63%,略高于未使用者,但无统计学差异(P>0.05).结论:年龄显著影响绝经前乳腺癌患者的CIA发生率,且随着年龄的增大,CIA发生几率增加,月经恢复几率减少.此外,蒽环类与紫杉类药物联合或序贯使用可导致CIA发生率较高.
目的 探讨曲妥珠单抗联合新辅助化疗治疗人表皮生长因子受体2(HER2)阳性乳腺癌的临床疗效及对患者生存质量的影响.方法 采用抽签法随机将30例HER2阳性女性乳腺癌患者分为对照组和观察组,每组15例.对照组患者术前接受新辅助化疗,观察组患者术前接受曲妥珠单抗联合新辅助化疗,比较两组患者的临床疗效、治疗前后的肿瘤相关炎性因子[白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)]水平以及治疗前和治疗后8个月的生存质量.结果 观察组患者的总有效率为86.67%(13/15),高于对照组患者的53.33%(8/15),差异有统计学意义(P﹤0.05).治疗前,两组患者的血清IL-6、IL-8、TNF-α、IL-1β水平比较,差异均无统计学意义(P﹥0.05);治疗后,观察组患者的血清IL-6、IL-8、TNF-α、IL-1β水平均明显低于对照组患者,差异均有统计学意义(P﹤0.01).治疗前,两组患者的生存质量评分比较,差异无统计学意义(P﹥0.05);治疗后8个月,观察组患者的生存质量评分明显高于对照组患者,差异有统计学意义(P﹤0.01).结论 与术前单纯新辅助化疗相比,术前曲妥珠单抗联合新辅助化疗治疗HER2阳性乳腺癌可获得更好的临床疗效,且可有效改善患者的生存质量.
Gemcitabine-based chemotherapy is commonly applied for the treatment of breast cancer in a clinical setting. However, acquired resistance to chemotherapy primarily results in treatment failure and eventually culminates in patient mortality. Aberrant expression of microRNAs (miRNAs) has been demonstrated to be implicated in the development of chemoresistance; however, the role of miR-873 in the chemoresistance of breast cancer and its underlying mechanism have not been completely elucidated. Herein, using cell viability assays, the present study demonstrated that overexpression of miR-873 sensitized triple-negative breast cancer (TNBC) cells (MDA-MB-231 and BT549) towards gemcitabine treatment, while inhibition of miR-873 promoted resistance of TNBC cells to gemcitabine exposure. The 3 ' untranslated region of zinc finger E-box binding homeobox 1 (ZEB1) was predicted as a candidate target of miR-873, and the regulatory association between ZEB1 and miR-873 was validated with a dual luciferase assay. Reverse transcription-quantitative polymerase chain reaction and western blot analysis confirmed that miR-873 mimics reduced ZEB1 at mRNA and protein levels in MDA-MB-231 and BT549 cells. As ZEB1 was previously reported to interact with Yes associated protein (YAP) to promote cancer progression. The present study observed that miR-873 overexpression decreased the expression of YAP target genes AXL receptor tyrosine kinase, connective tissue growth factor and cysteine rich angiogenic inducer 61 at mRNA and protein levels. Additionally, elevation of the ZEB1 level and reduction of the miR-873 level were detected in gemcitabine-resistant MDA-MB-231 (MDA-MB-231GEMr) cells, which were accompanied with stronger proliferative ability, compared with parental cells. Overexpression of miR-873 or ZEB1 knockdown reversed chemoresistance of MDA-MB-231GEMr cells by inducing a notable cell growth arrest upon gemcitabine exposure. In conclusion, the data obtained by the present study demonstrated that the decrease of miR-873 promoted the development of gemcitabine resistance in TNBC via elevation of ZEB1 expression, which indicated that miR-873 may be a promising predictor for gemcitabine sensitivity in patients with TNBC.
Objectives: To investigate the relationship between the expression of ER, PR, HER-2 and Ki-67 and the effective rates of neoadjuvant chemotherapy (NAC), and to study the influence of NAC on the expression of ER, PR, HER-2 and Ki-67 in breast cancer patients.
目的 探讨原发性浸润性乳腺癌患者发生脉管浸润的相关危险因素.方法 采用多因素Logistic回归模型分析365例原发性浸润性乳腺癌患者发生脉管浸润的独立危险因素.结果 365例原发性浸润性乳腺癌患者中,91例患者发生了脉管浸润.单因素分析结果显示,不同腋窝淋巴结转移数量、TNM分期、组织学分级、Ki-67表达水平和分子分型原发性浸润性乳腺癌患者的脉管浸润发生率比较,差异均有统计学意义(P﹤0.05).多因素分析结果显示,腋窝淋巴结转移数量﹥3个、TNM分期为Ⅲ期、分子分型为Luminal B型、分子分型为HER2阳性型、分子分型为三阴性均是原发性浸润性乳腺癌患者发生脉管浸润的独立危险因素(P﹤0.05).结论 腋窝淋巴结转移数量﹥3个、TNM分期为Ⅲ期、分子分型为Luminal B型、分子分型为HER2阳性型、分子分型为三阴性的原发性浸润性乳腺癌患者发生脉管浸润的风险较高,因此要对该部分患者重点关注,早发现、早治疗,降低脉管浸润的发生率.
原发性乳腺神经内分泌癌是乳腺癌当中的一种罕见的特殊类型,从其第一次被描述至今已有50余年历史,因业内对其认识的不断改变和加深,诊断标准也多次更新,直到2003年世界卫生组织(WHO)才首次明确了定义和诊断标准.该病发病率低,病例数少,目前对其疾病起源尚无定论,亦无针对性的临床治疗指南或规范,大样本,前瞻性的临床研究也有所缺乏,治疗往往参考非特殊型乳腺癌的方案.本文通过查阅相关文献对原发性乳腺神经内分泌癌目前的研究现状进行综述,以期对未来临床研究方向提供建议和参考,为今后的临床实践提供更多借鉴和帮助.
目的 分析乳腺浸润性导管癌(invasive ductal carcinoma of breast)的分子分型与其临床病理特征的关系.方法 选择首都医科大学附属北京妇产医院2015年1月至2016年10月诊治的女性乳腺浸润性导管癌患者198例,根据免疫组化检测结果将乳腺癌分为4个分子亚型,即Luminal A型、Luminal B(HER-2阴性/HER-2阳性)型、HER-2过表达型和三阴性乳腺癌,分析不同分子亚型在发病部位、年龄、肿瘤大小、腋窝淋巴结转移、病理分期、组织学分级、脉管癌栓和手术方式方面的差异,以及Ki-67表达与雌激素受体(estrogen reseptor,ER)、孕激素受体(proges-terove,receptor,PR)表达的关系.结果 乳腺浸润性导管癌的病灶位置、发病年龄、手术方式在分子各亚型组间差异均无统计学意义(P>0.05);肿瘤大小、淋巴结转移、pTNM分期、组织学分级及脉管癌栓情况在各亚型组间差异均有统计学意义(P<0.05).Ki-67的表达水平与ER、PR的表达存在相关性(P< 0.05).结论 乳腺浸润性导管癌的分子分型与患者生存及转移模式密切相关,对指导临床个体化治疗具有重要意义.
Objective:To evaluate the diagnosis and curative value of double localization method that mammary ductoscopy combined with methylene blue staining for tumor-like lesion in mammary duct of patients with pathological nipple discharge.Methods: The documents of 80 patients with tumor-like lesion in mammary duct who underwent the detection of double localization that mammary ductoscopy combined with methylene blue staining before operation were researched by using retrospective analysis, and then the diagnostic results were compared with pathological results so as to evaluate the curative effect of surgery.Results: The coincidence rate of the diagnosis of intraductal papilloma between mammary ductoscopy and post-operative pathological results was 83.3%, and the coincidence rate of breast carcinoma was 80%. The differences of distributions of benign lesion and malignant lesion in mammary duct of I-III grade were significant (x2=30.026,P<0.05). Besides, all of operations were accuracy in localization, and the surface of wound were small, and the recurrent cases never been found since the start of follow-up.Conclusion: The double localization method that mammary ductoscopy combined with methylene blue staining has important value in the diagnosis and operative treatment.
<正>脾脏切除作为经典断流术的一个主要步骤,应用于肝硬化门脉高压相关消化道出血的预防及治疗已有近60年的历史。脾切除可以改善肝功能及脾功能亢进相关的低白细胞、低血小板血症。此外,在活体肝移植术中,脾切除术可以有效治疗移植物因门静脉过度灌注引起的小肝综合征,而受到关注。但脾