European journal of gynaecological oncology最新文献

Timing and duration of bevacizumab treatment and survival in patients with recurrent ovarian, fallopian tube, and peritoneal cancer: a multi-institution study. 贝伐单抗治疗的时间和持续时间以及复发性卵巢癌、输卵管癌和腹膜癌患者的生存:一项多机构研究

IF 0.4 4区医学 Q4 Medicine

European journal of gynaecological oncology

Pub Date : 2023-02-01 DOI: 10.22514/ejgo.2023.002

Talayeh S Ghezelayagh, Emily S Wu, Emma L Barber, Minh D Dao, Emese Zsiros, Renata R Urban, Heidi J Gray, Barbara A Goff, Chirag A Shah, Nikki L Neubauer, James Y Dai, Janos L Tanyi, John B Liao

Bevacizumab has demonstrated significant benefit in recurrent ovarian, fallopian tube and peritoneal cancer (OC), but its optimal position within the sequence of systemic therapies remains controversial. Since rebound progression after bevacizumab has been observed in other cancers, and because bevacizumab is incorporated in several regimens used in the recurrent setting, the duration of treatment may impact survival. We sought to identify whether earlier bevacizumab exposure is associated with prolonged bevacizumab therapy and survival by conducting a multi-institution retrospective study of recurrent OC patients treated with bevacizumab from 2004-2014. Multivariate logistic regression identified factors associated with receiving more than six bevacizumab cycles. Overall survival by duration and ordinal sequence of bevacizumab therapy were evaluated using logrank testing and Cox regression. In total, 318 patients were identified. 89.1% had stage III or IV disease; 36% had primary platinum resistance; 40.5% received two or fewer prior chemotherapy regimens. Multivariate logistic regression demonstrated that primary platinum sensitivity (Odds Ratio (OR) 2.34, p = 0.001) or initiating bevacizumab at the first or second recurrence (OR 2.73, p < 0.001) were independently associated with receiving more than six cycles of bevacizumab. Receiving more cycles of bevacizumab was associated with improved overall survival whether measured from time of diagnosis (logrank p < 0.001), bevacizumab initiation (logrank p < 0.001), or bevacizumab discontinuation (logrank p = 0.017). Waiting one additional recurrence to initiate bevacizumab resulted in a 27% increased hazard of death (Hazard Ratio (HR) 1.27, p < 0.001) by multivariate analysis. In conclusion, patients with primary platinum sensitive disease who received fewer prior lines of chemotherapy were able to receive more cycles of bevacizumab, which was associated with improved overall survival. Survival worsened when bevacizumab was initiated later in the ordinal sequence of therapies.

贝伐单抗在复发性卵巢癌、输卵管癌和腹膜癌(OC)中显示出显著的益处，但其在全身治疗序列中的最佳位置仍存在争议。由于在其他癌症中观察到贝伐珠单抗后的反弹进展，并且由于贝伐珠单抗被合并在复发环境中使用的几种方案中，治疗的持续时间可能影响生存。我们通过对2004-2014年接受贝伐单抗治疗的复发性OC患者进行多机构回顾性研究，试图确定早期贝伐单抗暴露是否与延长贝伐单抗治疗和生存率相关。多变量logistic回归确定了接受6个以上贝伐单抗周期的相关因素。使用洛格兰试验和Cox回归评估贝伐单抗治疗持续时间和顺序序列的总生存期。总共确定了318例患者。89.1%为III期或IV期;36%有初级铂电阻;40.5%接受过两次或更少的化疗方案。多因素logistic回归显示，原发性铂敏感性(比值比(OR) 2.34, p = 0.001)或在第一次或第二次复发时开始使用贝伐单抗(OR 2.73, p < 0.001)与接受贝伐单抗治疗超过6个周期独立相关。无论从诊断时间(洛格兰p < 0.001)、贝伐珠单抗起始(洛格兰p < 0.001)还是贝伐珠单抗停药(洛格兰p = 0.017)开始测量，接受更多周期的贝伐珠单抗与改善的总生存率相关。多因素分析显示，等待一次复发再开始使用贝伐单抗导致死亡风险增加27%(风险比(HR) 1.27, p < 0.001)。总之，既往接受较少化疗的原发性铂敏感疾病患者能够接受更多周期的贝伐单抗治疗，这与改善的总生存期相关。当贝伐单抗在常规治疗序列中较晚开始时，生存率恶化。

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引用次数: 1

Effect of multiple disciplinary team led by pain specialist nurses on postoperative analgesia in patients undergoing mastectomy 疼痛专科护士领导的多学科团队对乳房切除术患者术后镇痛的影响

4区医学 Q4 Medicine

European journal of gynaecological oncology

Pub Date : 2023-01-01 DOI: 10.22514/ejgo.2023.066

This study aims to analyze the effect of multiple disciplinary team (MDT) led by pain specialist nurses on postoperative analgesia in patients undergoing mastectomy. 140 patients with breast cancer admitted to our hospital were treated with mastectomy and randomly divided into the control group and the intervention group. Routine pain care was applied in the control group, while pain care of MDT led by pain specialist nurses was applied in the intervention group based on the control group. The degree of pain, total postoperative analgesic dose, the first ambulation time, the time for recovery of surgical wound and hospital stay were compared between both groups. The psychological status, stress response-related indicators before and after intervention were compared between both groups, and the incidence of postoperative complications and analgesic satisfaction were counted. In contrast to the control group, the numerical rating scale (NRS) score of the intervention group was lower (p < 0.05); total postoperative analgesic dose, the first off-bed activity time, the time for surgical wound recovery, the drainage tube placement time and the hospital stay of the intervention group were reduced (p < 0.05); after intervention, self-rating anxiety scale (SAS) and self-rating depression scale (SDS) scores of the intervention group were diminished (p < 0.05); after intervention, decreased noradrenaline (NE), adrenocorticotropic hormone (ACTH) and Cor indexes were presented in the intervention group (p < 0.05); the incidence of postoperative complications of the intervention group was 7.14%, lower than 18.57%of the control group (p < 0.05); the analgesic satisfaction of the intervention group was 95.71%, higher than 84.29% of the control group (p < 0.05). Therefore, we conclude that MDT led by pain specialist nurses is worthy of clinical application.

本研究旨在分析由疼痛专科护士领导的多学科团队(MDT)对乳房切除术患者术后镇痛的影响。对我院收治的140例乳腺癌患者行乳房切除术，随机分为对照组和干预组。对照组采用常规疼痛护理，干预组在对照组的基础上采用疼痛专科护士带领下的MDT疼痛护理。比较两组患者疼痛程度、术后总镇痛剂量、首次下床时间、手术伤口恢复时间及住院时间。比较两组患者干预前后的心理状态、应激反应相关指标，统计术后并发症发生率和镇痛满意度。与对照组相比，干预组的数值评定量表(NRS)得分较低(p <干预组患者术后镇痛总剂量、首次下床活动时间、手术创面恢复时间、引流管放置时间、住院时间均显著减少(p <干预后，干预组焦虑自评量表(SAS)和抑郁自评量表(SDS)得分均显著降低(p <干预后，干预组去甲肾上腺素(NE)、促肾上腺皮质激素(ACTH)及Cor指标均下降(p <干预组术后并发症发生率为7.14%，低于对照组的18.57% (p <干预组镇痛满意度为95.71%，高于对照组的84.29% (p <0.05)。因此，我们认为由疼痛专科护士领导的MDT是值得临床应用的。

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引用次数: 0

Pregnancy-associated breast malignancy mostly presents with an aggressive type of breast cancer 妊娠相关乳腺恶性肿瘤多表现为侵袭性乳腺癌

4区医学 Q4 Medicine

European journal of gynaecological oncology

Pub Date : 2023-01-01 DOI: 10.22514/ejgo.2023.069

Published reports on the prognosis of pregnancy-associated breast cancer are controversial. This study aims to determine the histopathological features of pregnancy-associated breast carcinoma (PABC) and the outcomes of patients with breast cancer during pregnancy and lactation among Turkish women. The study retrospectively analyzed 29 patients diagnosed with pregnancy-associated breast malignancies who underwent surgery between January 1989 and March 2021. Demographic and pathological data were obtained to evaluate the clinicopathological and prognostic characteristics of the patients. The median age was 36 years (range: 26–42 years). Of the 29 patients with breast cancer, 13 (44.8%) were diagnosed during pregnancy, and the remaining 16 (55.2%) were diagnosed during lactation. Most patients had clinical tumor stage (cT) cT2–3 (n = 20, 69%) disease, and 15 patients had clinically node (cN)-positive disease (N1 and N2, 51.7%). The majority (n = 19, 65.5%) had invasive ductal carcinoma with high Ki-67 scores (>20%). Patients with lactation-associated breast cancer were more likely to have a family history of breast cancer (44% vs. 8%, p = 0.04) than those with pregnancy-associated breast cancer. Notably, symptom duration ≥6 months and presenting with cT3–4 or cN(+) disease were associated with poor disease-free and disease-specific survival. However, no difference could be found in outcome among patients with pregnancy- and lactation-associated breast cancer. PABC mostly presents with aggressive tumor molecular subtypes with high Ki-67 scores and more advanced stages associated with poor outcome, possibly due to delayed diagnosis. Therefore, prompt early diagnosis and awareness of this disease might improve survival.

已发表的关于妊娠相关乳腺癌预后的报告存在争议。本研究旨在确定妊娠相关乳腺癌(PABC)的组织病理学特征以及土耳其妇女妊娠和哺乳期乳腺癌患者的预后。该研究回顾性分析了1989年1月至2021年3月期间接受手术诊断为妊娠相关乳腺恶性肿瘤的29例患者。获得人口学和病理资料，以评估患者的临床病理和预后特征。年龄中位数为36岁(范围:26-42岁)。29例乳腺癌患者中，孕期确诊13例(44.8%)，哺乳期确诊16例(55.2%)。大多数患者临床肿瘤分期(cT) cT2-3 (n = 20, 69%)，临床淋巴结(cN)阳性15例(N1和N2, 51.7%)。大多数(n = 19, 65.5%)为浸润性导管癌，Ki-67评分较高(>20%)。与妊娠相关的乳腺癌患者相比，哺乳期乳腺癌患者更有可能有乳腺癌家族史(44%比8%，p = 0.04)。值得注意的是，症状持续时间≥6个月且呈现cT3-4或cN(+)疾病与较差的无病生存和疾病特异性生存相关。然而，妊娠期和哺乳期相关乳腺癌患者的预后没有发现差异。PABC主要表现为侵袭性肿瘤分子亚型，Ki-67评分较高，晚期预后较差，可能是由于诊断延迟所致。因此，及时的早期诊断和意识到这种疾病可能会提高生存率。

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引用次数: 0

BRD4 inhibitor JQ1 may affect the prognosis of cervical cancer through super-enhancer-related genes BRD4抑制剂JQ1可能通过超增强子相关基因影响宫颈癌预后

4区医学 Q4 Medicine

European journal of gynaecological oncology

Pub Date : 2023-01-01 DOI: 10.22514/ejgo.2023.076

To explore the effects of bromine domain protein 4 (BRD4) inhibitor JQ1 on the expression profile of super-enhancer-related genes (SE-genes) in cervical cancer (CC) HeLa cells and construct a prognosis model to explore the potential impact of JQ1 on the prognosis of CC. Whole transcriptome sequencing technology was used to detect changes in the gene expression profiles of JQ1-treated and control cells. Differentially expressed SE-genes were identified by matching via the dbCoRC database and Cistrome Data Browser (Cistrome DB). The prognosis of differentially expressed SE-genes was analyzed in the Cancer Genome Atlas (TCGA) dataset based on gene expression status. The Cox proportional risk model and least absolute shrinkage and selection operator (LASSO) regression were used to construct the prognostic model. A total of 1161 SE-genes were identified from dbCoRC and Cistrome DB, among which 1004 SE-genes were successfully matched to the expression profiles of JQ1 transcriptome sequencing. Differential expression analysis identified 110 differentially expressed SE-genes, among which 72 were down-regulated and 38 were upregulated. Then, a 9 SE-gene prognostic model was constructed, and Kaplan-Meier (K-M) curves showed that the high-risk group had significantly poorer clinical survival outcomes (p < 0.05). Time-dependent receiver operating characteristic (ROC) curves showed that the 1-year, 2-year and 3-year survival estimation of the proposed model was 0.82, 0.86 and 0.87, respectively, demonstrating excellent performance. JQ1 significantly impacts the SE-genes expression profile of HeLa cells, and the proposed model based on 9 differentially expressed SE-genes may effectively predict the survival outcomes of CC patients. As this study was based on exploratory analysis, further prospective studies are needed to v

为探讨溴结构域蛋白4 (BRD4)抑制剂JQ1对宫颈癌(CC) HeLa细胞中超增强子相关基因(se基因)表达谱的影响，构建预后模型，探讨JQ1对CC预后的潜在影响，采用全转录组测序技术检测JQ1处理和对照细胞的基因表达谱变化。通过dbCoRC数据库和Cistrome数据浏览器(Cistrome DB)进行比对，鉴定出差异表达的se基因。在肿瘤基因组图谱(Cancer Genome Atlas, TCGA)数据集中，基于基因表达状态分析se基因差异表达的预后。采用Cox比例风险模型和最小绝对收缩和选择算子(LASSO)回归构建预后模型。从dbCoRC和Cistrome DB中共鉴定出1161个se基因，其中1004个se基因与JQ1转录组测序的表达谱成功匹配。差异表达分析鉴定出110个se基因差异表达，其中72个se基因下调，38个se基因上调。然后构建9 se基因预后模型，Kaplan-Meier (K-M)曲线显示，高危组临床生存结局明显较差(p <0.05)。随时间变化的受试者工作特征(ROC)曲线显示，该模型的1年、2年和3年生存估计分别为0.82、0.86和0.87，表现出良好的性能。JQ1显著影响HeLa细胞se基因表达谱，基于9个se基因差异表达的模型可以有效预测CC患者的生存结局。由于本研究基于探索性分析，需要进一步的前瞻性研究

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引用次数: 0

FloSeal for preventing symptomatic lymphocele after pelvic and/or para-aortic lymphadenectomy in gynecological cancers: a randomized controlled trial FloSeal用于预防妇科癌症盆腔和/或主动脉旁淋巴结切除术后出现症状性淋巴囊肿:一项随机对照试验

4区医学 Q4 Medicine

European journal of gynaecological oncology

Pub Date : 2023-01-01 DOI: 10.22514/ejgo.2023.080

To evaluate the role of FloSeal for preventing symptomatic lymphocele following pelvic and/or para-aortic lymphadenectomy in patients with gynecological cancers. Between October 2014 and April 2015, 40 patients with gynecological cancers planned for surgical management were randomly placed into FloSeal and non-FloSeal groups in a 1:1 ratio. Lymphocele incidence was evaluated using intravenous contrast-enhanced, abdominopelvic computed tomography 3–6 months after surgery. The quality of life questionnaire was completed by patients at 1, 3 and 6 months after surgery. The incidence of symptomatic lymphocele was compared using a chi-square test. All patients underwent bilateral pelvic lymph node dissection, and eight patients in each group (40%vs. 44.4%, p > 0.999) underwent para-aortic lymph node dissection. The mean number of total, right pelvic, left pelvic and para-aortic lymph nodes retrieved was similar between the groups. One patient (1/20, 5%) in the FloSeal group and three (3/18, 16.7%) in the non-FloSeal group developed lymphoceles (p = 0.328). The incidence of symptomatic lymphocele was 0% and 11% (2/18) in the FloSeal and non-FloSeal groups (p = 0.218), respectively. The mean time interval to drain removal (4.8 ± 2.0 days vs. 5.3 ± 2.2 days, p = 0.400) was shorter and the mean drain volume (1656 ± 1362 mL vs. 2022 ± 2301 mL, p = 0.550) was smaller in FloSeal group. The use of FloSeal after pelvic and/or para-aortic lymphadenectomy in patients with gynecological cancers may be effective for preventing symptomatic lymphocele. Clinical Trial registration: NCT01679483.

评价FloSeal在预防妇科癌症患者盆腔和/或腹主动脉旁淋巴结切除术后出现症状性淋巴囊肿中的作用。2014年10月至2015年4月，将40例计划手术治疗的妇科肿瘤患者按1:1的比例随机分为FloSeal组和非FloSeal组。术后3-6个月，通过静脉造影增强腹部骨盆计算机断层扫描评估淋巴囊肿的发生率。患者于术后1、3、6个月分别填写生活质量问卷。用卡方检验比较症状性淋巴囊肿的发生率。所有患者均行双侧盆腔淋巴结清扫术，每组8例(40%vs。44.4%， p >0.999)行主动脉旁淋巴结清扫术。两组间平均总淋巴结、右盆腔淋巴结、左盆腔淋巴结和主动脉旁淋巴结清扫数相似。FloSeal组1例(1/ 20,5%)和非FloSeal组3例(3/ 18,16.7%)出现淋巴细胞瘤(p = 0.328)。FloSeal组和非FloSeal组的症状性淋巴囊肿发生率分别为0%和11% (2/18)(p = 0.218)。FloSeal组平均排尿间隔时间(4.8±2.0天比5.3±2.2天，p = 0.400)更短，平均排尿量(1656±1362 mL比2022±2301 mL, p = 0.550)更小。妇科癌症患者盆腔和/或腹主动脉旁淋巴结切除术后使用FloSeal可能对预防症状性淋巴囊肿有效。临床试验注册:NCT01679483。

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引用次数: 0

High expression of SPINT2 promotes immune infiltration and tumor progression in ovarian cancer SPINT2的高表达促进卵巢癌的免疫浸润和肿瘤进展

4区医学 Q4 Medicine

European journal of gynaecological oncology

Pub Date : 2023-01-01 DOI: 10.22514/ejgo.2023.086

This study aimed to identify the function and mechanism of Serine Peptidase Inhibitor, Kunitz Type 2 (SPINT2) in ovarian cancer (OC). The expression of SPINT2 was analyzed using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to identify enriched functional categories of SPINT2 and its correlated genes. Correlation of SPINT2 with OC immune infiltration level was analyzed using the Tumor IMmune Estimation Resource (TIMER) web server. The effect of SPINT2 on cell proliferation was detected using cell counting kit-8 (CCK-8) and colony formation assay. Its effects on cell migration and invasion were examined using the transwell assay. Function of SPINT2 in M2 macrophage recruitment was detected using the migration assay. The role of SPINT2 on M2 macrophage differentiation was evaluated using M2 macrophage markers and by detection of interleukin 10 (IL-10) release. An OC cohort study (GSE12470) showed that SPINT2 was highly expressed in OC. The high SPINT2 expression was related to shorter overall survival (OS) and poor recurrence-free survival (RFS). GO and KEGG analysis indicated that SPINT2 associated genes played roles in glycoprotein catabolism, cell adhesion and T cell differentiation. SPINT2 also played a key role in infiltration of macrophages in OC. shSPINT2 reduced viability and colony formation ability of ovarian cancer cell line SK-OV-3 cells. Moreover, shSPINT2 also inhibited the cell migration and invasion. Co-culture of shSPINT2 transfected SK-OV-3 cells with macrophages inhibited the migration of M2 macrophages, and inhibited macrophages polarization from M0 to M2. These results suggested that SPINT2 is involved in infiltration of tumor-associated macrophages (TAMs). SPINT2 also plays an important role in the polarization and migration of macrophages. These findings suggested that SPINT2 has the potential to be explored as a biomarker for OC and a potential target.

本研究旨在探讨丝氨酸肽酶抑制剂Kunitz 2型(SPINT2)在卵巢癌(OC)中的作用及机制。利用基因表达图谱(Gene expression Omnibus, GEO)和癌症基因组图谱(The Cancer Genome Atlas, TCGA)数据库分析SPINT2的表达。通过基因本体(GO)和京都基因与基因组百科全书(KEGG)途径分析，确定SPINT2及其相关基因的丰富功能类别。利用Tumor immune Estimation Resource (TIMER) web server分析SPINT2与OC免疫浸润水平的相关性。采用细胞计数试剂盒-8 (CCK-8)和集落形成实验检测SPINT2对细胞增殖的影响。用transwell法检测其对细胞迁移和侵袭的影响。通过迁移实验检测SPINT2在M2巨噬细胞募集中的作用。利用M2巨噬细胞标志物和检测白细胞介素10 (IL-10)释放来评估SPINT2对M2巨噬细胞分化的作用。一项OC队列研究(GSE12470)显示SPINT2在OC中高表达。SPINT2高表达与较短的总生存期(OS)和较差的无复发生存期(RFS)相关。GO和KEGG分析表明，SPINT2相关基因在糖蛋白分解代谢、细胞粘附和T细胞分化中发挥作用。SPINT2在OC中巨噬细胞的浸润中也发挥了关键作用。shSPINT2降低卵巢癌细胞系SK-OV-3细胞的活力和集落形成能力。此外，shSPINT2还能抑制细胞的迁移和侵袭。shSPINT2转染的SK-OV-3细胞与巨噬细胞共培养可抑制M2巨噬细胞的迁移，抑制巨噬细胞从M0向M2极化。这些结果表明SPINT2参与肿瘤相关巨噬细胞(tam)的浸润。SPINT2在巨噬细胞的极化和迁移中也起着重要的作用。这些发现表明，SPINT2有潜力作为OC的生物标志物和潜在靶点进行探索。

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引用次数: 0

Comparison of intraoperative and early postoperative results of patients undergoing laparoscopic versus laparotomic staging surgery for ovarian cancer 腹腔镜与剖腹分阶段卵巢癌手术患者术中及术后早期疗效比较

4区医学 Q4 Medicine

European journal of gynaecological oncology

Pub Date : 2023-01-01 DOI: 10.22514/ejgo.2023.087

Thus far, the traditional method of performing staging surgery in ovarian cancer has been laparotomy. Although randomized controlled trials are lacking, minimally invasive options are deemed safe and sufficient for staging and treatment of early-stage ovarian cancer. This study aims to compare the intraoperative and early postoperative outcomes of patients who underwent staging surgery via laparoscopy or laparotomy because of ovarian cancer. This retrospective study was conducted among 37 patients undergoing staging surgery done via laparoscopy (Group 1) or laparotomy (Group 2) between February 2018 and May 2022 at a single center. Intraoperative and early postoperative results were collected. Regarding postoperative complications between the two groups, the formation of lymphoceles and hernias in Group 2 was significantly higher compared to Group 1 (p = 0.019 and p = 0.050, respectively). When these groups were compared regarding Clavien-Dindo classification, Grade 1 complications were high among the laparoscopy group. In contrast, Grade 2, 3A and 3B complications were significantly higher in the laparotomy group (p = 0.002). Regarding hospital stay during the postoperative period, the patients in Group 2 stayed significantly longer compared to Group 1 (p = 0.001). As an alternative to open surgery for diagnosing and staging ovarian cancer, the laparoscopic approach is reliable and can be applied safely to patients. However, more prospective randomized studies are needed to support the obtained data.

迄今为止，对卵巢癌进行分期手术的传统方法是剖腹手术。虽然缺乏随机对照试验，但对于早期卵巢癌的分期和治疗，微创选择被认为是安全且足够的。本研究旨在比较卵巢癌患者经腹腔镜或开腹分期手术的术中及术后早期预后。本回顾性研究于2018年2月至2022年5月在单一中心对37例通过腹腔镜(1组)或剖腹手术(2组)进行分期手术的患者进行。收集术中及术后早期结果。两组术后并发症方面，2组淋巴囊肿和疝的形成明显高于1组(p = 0.019, p = 0.050)。两组比较Clavien-Dindo分级，腹腔镜组1级并发症发生率较高。相比之下，剖腹手术组2级、3A级和3B级并发症发生率明显高于剖腹手术组(p = 0.002)。术后住院时间方面，2组患者的住院时间明显长于1组(p = 0.001)。作为开放手术诊断和分期卵巢癌的替代方法，腹腔镜方法是可靠的，可以安全地应用于患者。然而，需要更多的前瞻性随机研究来支持所获得的数据。

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引用次数: 0

Identification of immune subtypes of uterine corpus endometrial adenocarcinoma based on tumour microenvironment 基于肿瘤微环境的子宫肌体子宫内膜腺癌免疫亚型鉴定

4区医学 Q4 Medicine

European journal of gynaecological oncology

Pub Date : 2023-01-01 DOI: 10.22514/ejgo.2023.065

Uterine corpus endometrial adenocarcinoma is the prevalent gynaecological malig-nancy. The related morbidity and mortality are high despite the progress made in treatments. Therefore, efficient prognostic indicators and reliable predictive factors for the treatments are vital. In this study, the transcriptome and clinical data of endometrial adenocarcinoma samples were screened and downloaded from The Cancer Genome Atlas Program (TCGA) database. The relation between immune cell types and clinicopathological grade of endometrial adenocarcinoma was explored. The endometrial adenocarcinoma samples were divided into six immune subtypes based on immune microenvironment scores. The differential genes in immune subtypes were classified according to the score, and correlation enrichment analysis was made to explore the immune pathways related to prognosis and survival. They were divided into high and low risk groups according to the median risk score in order to explore the survival outcomes of the various immune scores. Finally, the relationship between tumour mutation burden, immune subtypes, and prognosis was discussed. Herein, the endometrial adenocarcinoma is classified based on immune microenvironment which demonstrates good predictive potential of immune-based classification strategy. The predicted outcomes are described for the patients at high risk of endometrial adenocarcinoma to improve the treatment strategies. Immune risk score can be used as an independent risk factor for overall survival of endometrial adenocarcinoma patients. This immune-based classification system can prognose endometrial adenocarcinoma patients at high risk.

子宫肌体子宫内膜腺癌是常见的妇科恶性肿瘤。尽管在治疗方面取得了进展，但相关的发病率和死亡率仍然很高。因此，有效的预后指标和可靠的预测因素对治疗至关重要。本研究筛选了子宫内膜腺癌样本的转录组和临床数据，并从癌症基因组图谱计划(TCGA)数据库中下载。探讨免疫细胞类型与子宫内膜腺癌临床病理分级的关系。根据免疫微环境评分将子宫内膜腺癌样本分为6个免疫亚型。根据评分对免疫亚型中的差异基因进行分类，并进行相关富集分析，探索与预后和生存相关的免疫通路。根据中位风险评分分为高危组和低危组，探讨各免疫评分的生存结局。最后，讨论了肿瘤突变负荷、免疫亚型与预后的关系。本文基于免疫微环境对子宫内膜腺癌进行分类，显示了免疫分类策略的良好预测潜力。本文描述了子宫内膜腺癌高危患者的预测预后，以改进治疗策略。免疫风险评分可作为子宫内膜腺癌患者总生存的独立危险因素。这种基于免疫的分类系统可以预测高危子宫内膜腺癌患者。

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引用次数: 0

PI3K inhibitor promotes tumor vessel normalization and improves treatment outcomes of breast cancer with doxorubicin PI3K抑制剂促进肿瘤血管正常化，改善阿霉素治疗乳腺癌的效果

4区医学 Q4 Medicine

European journal of gynaecological oncology

Pub Date : 2023-01-01 DOI: 10.22514/ejgo.2023.058

HS-173 is a specific inhibitor of the Phosphoinositide 3-Kinase α (PI3Kα) subtype. Although it was shown to potentially inhibit tumor angiogenesis, experimental validation studies are still needed. This study provides an experimental basis for the role of HS-173 in breast cancer. A mouse model of subcutaneous transplantation breast cancer was constructed. The mice were treated with different concentrations of HS-173. Immunohistochemical staining was used to detect tumor microvessel density, and the appropriate concentration was determined. Immunofluorescence was used to detect the morphology integrity of tumor vessels’ lumen, transmission electron microscopy to detect tight junctions between endothelial cells and the integrity of the basement membrane, Doppler ultrasound to detect tumor blood perfusion, and small animal live imaging to detect the penetration of doxorubicin in the tumor tissues. After HS-173 treatment, the number of tumor interstitial microvessels decreased, the lack of tumor vascular lumen was reduced, and the continuity and integrity of the vascular lumen were increased. Vascular endothelial cells showed complete morphology with good tight junctions. The extracellular matrix was rich in components and tended to form basement membranes. HS-173 also increased the blood perfusion in the tumor tissue compared with the doxorubicin treatment alone. Further, the fluorescence signal intensity of the tumor tissue doxorubicin was significantly enhanced after HS-173 treatment. The PI3K inhibitor HS-173 showed promising potential in inhibiting tumor angiogenesis and improving the structure and function of blood vessels in the tumor microenvironment.

HS-173是磷酸肌肽3-激酶α (PI3Kα)亚型的特异性抑制剂。虽然它被证明可能抑制肿瘤血管生成，但仍需要实验验证研究。本研究为HS-173在乳腺癌中的作用提供了实验依据。建立小鼠皮下移植乳腺癌模型。用不同浓度的HS-173处理小鼠。免疫组化染色检测肿瘤微血管密度，确定适宜浓度。采用免疫荧光检测肿瘤血管管腔形态完整性，透射电镜检测内皮细胞与基底膜紧密连接完整性，多普勒超声检测肿瘤血液灌注，小动物活体成像检测阿霉素在肿瘤组织中的渗透情况。HS-173治疗后，肿瘤间质微血管数量减少，肿瘤血管管腔缺失减少，血管管腔连续性和完整性增强。血管内皮细胞形态完整，紧密连接良好。细胞外基质成分丰富，易于形成基底膜。与单独使用阿霉素治疗相比，HS-173也增加了肿瘤组织的血液灌注。此外，HS-173治疗后肿瘤组织的荧光信号强度明显增强。PI3K抑制剂HS-173在抑制肿瘤血管生成、改善肿瘤微环境血管结构和功能方面显示出良好的潜力。

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引用次数: 0

Overexpression of USP43 induces the growth and stem cell-like properties of cervical cancer by activating ERK1/2 through ZEB1 USP43过表达通过ZEB1激活ERK1/2诱导宫颈癌的生长和干细胞样特性

4区医学 Q4 Medicine

European journal of gynaecological oncology

Pub Date : 2023-01-01 DOI: 10.22514/ejgo.2023.089

Cervical cancer (CC) is the most common type of gynecological malignancy in women, and targeting stem cells and inhibiting tumor stem cell-like properties of CC remains an important field of research as an attempt to improve treatment outcomes. This study focused on Ubiquitin-specific-processing Protease 43 (USP43), a member of the deubiquitinase (DUBs) family known to play a role in tumor progression, and analysis of the The Cancer Genome Atlas (TCGA) data and survival computations revealed that USP43 was highly expressed in CC and correlated with poor prognosis. However, the role of USP43 in CC has been under-reported, and its underlying mechanism remains unclear. To investigate the effect and mechanism of USP43, its expression in CC cells and tissues were examined, and the results showed that it was significantly upregulated. Subsequently, knockdown experiments revealed that reducing USP43 expression suppressed CC cell proliferation, and depleting USP43 inhibited the stem cell-like properties of CC cells and impaired their migration abilities. Further investigations indicated that USP43 promoted Zinc finger E-box binding protein 1 (ZEB1)-induced activation of Extracellular regulatory kinase 1/2 (ERK1/2) signaling in CC. Based on these findings, we propose that USP43 could serve as a promising target for CC.

宫颈癌(Cervical cancer, CC)是女性最常见的妇科恶性肿瘤类型，靶向干细胞并抑制CC的肿瘤干细胞样特性仍是一个重要的研究领域，旨在改善治疗效果。这项研究聚焦于泛素特异性加工蛋白酶43 (USP43)，它是去泛素酶(DUBs)家族的一员，已知在肿瘤进展中起作用，对癌症基因组图谱(TCGA)数据和生存计算的分析显示，USP43在CC中高表达，并与不良预后相关。然而，USP43在CC中的作用报道不足，其潜在机制尚不清楚。为了研究USP43在CC细胞和组织中的作用和机制，我们检测了USP43在CC细胞和组织中的表达，结果显示USP43明显上调。随后，敲低实验表明，降低USP43的表达抑制了CC细胞的增殖，而耗尽USP43则抑制了CC细胞的干细胞样特性并损害了其迁移能力。进一步的研究表明，USP43促进了锌指E-box结合蛋白1 (ZEB1)诱导的CC细胞外调节激酶1/2 (ERK1/2)信号的激活，基于这些发现，我们提出USP43可能是CC的一个有希望的靶点。

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引用次数: 0