Expression of Pregnancy Specific β-1 Glycoprotein 1 in Cervical Cancer Cells.

妊娠特异性 β 1 糖蛋白 1 在宫颈癌细胞中的表达。

  • 影响因子:2.10
  • DOI:10.1016/j.arcmed.2020.05.025
  • 作者列表:"Rodríguez-Esquivel M","Romero-Morelos P","Taniguchi-Ponciano K","Mendoza-Rodríguez M","Marrero-Rodríguez D","Bandera-Delgado A","Huerta-Padilla V","Serna-Reyna L","Gómez-Gutiérrez G","Gómez-Virgilio L","Bandala C","López-Romero R","Garrido-Guerrero E","Chanona-Pérez J","Salcedo M
  • 发表时间:2020-06-13

BACKGROUND:Cervical Cancer (CC) is a worldwide public health concern associated with genetic alterations, among these the gain of the 19q chromosome harboring the Pregnancy Specific Glycoproteins (PSG) gene family. These proteins play a critical role in pregnancy, with participation in immunotolerance, angiogenesis, and invasion processes, which are also observed in carcinogenesis. The aim of this study was to determine the molecular alterations of PSG1 and its relationship with CC. METHODS:PSG1 Copy Number Variation (CNV) was evaluated in 31 CC and eight normal cervical tissues by qPCR. PSG1 expression was correlated with HPV detection and IL-10 and TGF-β expression in CC samples. Finally, PSG1 protein expression was evaluated by immunofluorescence in CC cell lines, by immunohistochemistry in a tissue microarray, and by immunoblotting in the sera of women with normal cervix, pre-invasive lesions, and CC. RESULTS:PSG1 showed a gain of 25.6% in CNV and gene expression in CC. There was a lack of PSG1 expression in normal cervical epithelium and positive immunostaining in 57% of CC tissues, while all CC cell lines expressed PSG1. Finally, PSG1 was immunodetected in 90% of pre-invasive lesions and in all CC serum samples, but not in healthy women. PSG1 expression correlates with the expression of IL-10 and TGF-β in CC tissues, but not with the presence of HPV. CONCLUSION:These data show evidence of the differential expression of PSG1 in CC that could explain its participation in tumor-biology and immunotolerance mechanisms. Further, its immunodetection could provide early detection of this cancer.


背景: 宫颈癌 (Cervical Cancer,CC) 是与基因改变相关的全球公共卫生问题,其中包括携带妊娠特异性糖蛋白 (PSG) 基因家族的 19q 染色体的获得。这些蛋白在妊娠中起关键作用,参与免疫耐受、血管生成和侵袭过程,这也在癌变过程中观察到。本研究的目的是确定 PSG1 的分子改变及其与 CC 的关系。 方法: 采用 qPCR 方法对 31 例 CC 和 8 例正常宫颈组织进行 PSG1 拷贝数变异 (CNV) 评价。PSG1 的表达与 HPV 检测及 CC 样本中 IL-10 和 TGF-β 的表达相关。最后,通过 CC 细胞系中的免疫荧光、组织芯片中的免疫组织化学和正常宫颈、浸润前病变、和 CC。 结果: PSG1 在 CNV 中表现出 25.6% 的增益,在 CC 中表现出基因表达。57% 的 CC 组织中 PSG1 在正常宫颈上皮中表达缺乏,免疫染色阳性,而所有 CC 细胞系均表达 PSG1。最后,在 90% 的浸润前病变和所有 CC 血清样本中免疫检测到 PSG1,但在健康女性中未检测到。在 CC 组织中 PSG1 的表达与 IL-10 和 TGF-β 的表达相关,而与 HPV 的存在无关。 结论: 这些数据表明 PSG1 在 CC 中的差异表达可以解释其参与肿瘤生物学和免疫耐受机制。此外,它的免疫检测可以提供这种癌症的早期检测。



作者列表:["Oxley SG","Mallick R","Odejinmi F"]

METHODS:STUDY OBJECTIVE:To evaluate the differences in perioperative outcomes and immediate complication rates between laparoscopic myomectomy for submucous myomas and laparoscopic myomectomy for myomas in other locations. DESIGN:Retrospective cohort study. SETTING:University-affiliated hospital in London. PATIENTS:A total of 350 patients with symptomatic uterine myomas underwent laparoscopic myomectomy. Thirty-three of these were performed for submucous myomas (group 1), and 317 were for myomas in other uterine locations (group 2). INTERVENTIONS:Analysis of prospectively collected data on patient demographics, myoma characteristics, perioperative outcomes, and immediate complications. MEASUREMENTS AND MAIN RESULTS:Patient demographics, including age, body mass index, and parity, were similar in the 2 groups. No significant differences in myoma characteristics were seen between groups 1 and 2, including the mean dimension of largest myoma (7.1 vs 7.8 cm, respectively; p = .35), mean number of myomas removed (3.8 vs 4.1; p = .665), and mean mass of myomas removed (142.0 g vs 227.3 g; p = .186). There were also no significant between-group differences in any perioperative outcomes, including mean blood loss (226.8 mL vs 266.4 mL; p = .373), duration of surgery (103 minutes vs 113 minutes; p = .264), and duration of hospital stay (1.4 days vs 1.7 days; p = .057). No complications arose from laparoscopic resection of submucous myomas. CONCLUSION:Laparoscopic myomectomy for submucous myomas has similar perioperative outcomes and immediate complications as laparoscopic myomectomy for other myomas and can be considered for large or type 2 submucous myomas.

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作者列表:["de Milliano I","Huirne JAF","Thurkow AL","Radder C","Bongers MY","van Vliet H","van de Lande J","van de Ven PM","Hehenkamp WJK"]

METHODS:INTRODUCTION:Laparoscopic myomectomy can be difficult when fibroids are large and numerous. This may result in extensive intraoperative bleeding and the need for a conversion to a laparotomy. Medical pretreatment prior to surgery might reduce these risks by decreasing fibroid size and vascularization of the fibroid. We compared pretreatment with ulipristal acetate (UPA) vs gonadotropin-releasing hormone agonists (GnRHa) prior to laparoscopic myomectomy on several intra- and postoperative outcomes. MATERIAL AND METHODS:We performed a non-inferiority double-blind randomized controlled trial in nine hospitals in the Netherlands. Women were randomized between daily oral UPA for 12 weeks and single placebo injection or single intramuscular injection with leuprolide acetate and daily placebo tablets for 12 weeks. The primary outcome was intraoperative blood loss. Secondary outcomes were reduction of fibroid volume, suturing time, total surgery time and surgical ease. RESULTS:Thirty women received UPA and 25 women leuprolide acetate. Non-inferiority of UPA regarding intraoperative blood loss was not demonstrated. When pretreated with UPA, median intraoperative blood loss was statistically significantly higher (525 mL [348-1025] vs 280 mL[100-500]; P = 0.011) and suturing time of the first fibroid was statistically significantly longer (40 minutes [28-48] vs 22 minutes [14-33]; P = 0.003) compared with GnRHa. Pretreatment with UPA showed smaller reduction in fibroid volume preoperatively compared with GnRHa (-7.2% [-35.5 to 54.1] vs -38.4% [-71.5 to -19.3]; P = 0.001). Laparoscopic myomectomies in women pretreated with UPA were subjectively judged more difficult than in women pretreated with GnRHa. CONCLUSIONS:Non-inferiority of UPA in terms of intraoperative blood loss could not be established, possibly due to the preliminary termination of the study. Pretreatment with GnRHa was more favorable than UPA in terms of fibroid volume reduction, intraoperative blood loss, hemoglobin drop directly postoperatively, suturing time of the first fibroid and several subjective surgical ease parameters.

作者列表:["Liu C","Dillon J","Beavis AL","Liu Y","Lombardo K","Fader AN","Hung CF","Wu TC","Vang R","Garcia JE","Xing D"]

METHODS:AIMS:Hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome is caused by germline mutations in the Fumarate hydratase (FH) gene. In young women, the syndrome often presents with symptomatic uterine leiomyomas, leading to myomectomy or hysterectomy. In this study, we aimed to investigate the incidence and mutational profiles of FH-negative leiomyomas from young patients, thus allowing for early identification and triage of syndromic patients for surveillance. METHODS AND RESULTS:We evaluated 153 cases of uterine leiomyomas from women aged up to 30 years for loss of FH expression by tissue microarray (TMA)-based immunohistochemical staining. Mutational analysis of tumours with loss of FH was carried out by polymerase chain reaction (PCR) amplification of 10 exons within the FH gene and subsequent Sanger sequencing. The status of promoter methylation was assessed by bisulphite sequencing. Loss of FH protein expression was detected in seven (4.6%) of 153 tested uterine leiomyomas from young patients. All FH-negative leiomyomas displayed staghorn vasculature and fibrillary/neurophil-like cytoplasm. We found that six (86%) of seven FH-negative tumours detected by immunohistochemistry harboured FH mutations, 50% of which contained germline mutations. In particular, the germline mutational rate in FH gene was 2.0% (three of 153 cases). Bisulphite sequencing analysis failed to detect promoter methylation in any of the seven tumours. CONCLUSION:Our study showed a relatively high rate of FH germline mutation in FH-negative uterine leiomyomas from patients aged up to 30 years. While genetic mutations confer protein expression loss, epigenetic regulation of the FH gene appears to be unrelated to this phenotype.