• 文章类型: Journal Article
    微塑料(MPs)可以进入生殖系统,可能对人类生殖健康有害。在这项研究中,在患者血液中鉴定出13种微塑料(MPs),癌症样本,和使用拉曼光谱的癌旁样本,聚乙烯,聚丙烯和聚乙烯-共-聚丙烯是最丰富的聚合物类型。Futher,在我们的研究中也发现了棉花。血液样本中MPs的多样性和丰度高于癌组织,多样性之间呈显著正相关(p<0.05)。此外,癌组织中MPs的多样性和丰度高于癌旁组织。这些样品中MP的尺寸也非常相似,大多数被检测到的国会议员规模较小。相关分析显示,患者年龄与血样中MPs丰度相关,身体质量指数(BMI)与癌组织中MP的丰度相关。值得注意的是,患者饮用瓶装水和饮料的频率也可能增加MP的丰度.这项研究首次确定了人类宫颈癌患者的癌变和癌旁组织中MP和棉花的存在。这为研究MP暴露与人体健康的风险关系提供了新的思路和基础数据。
    Microplastics (MPs) can enter the reproductive system and can be potentially harmful to human reproductive health. In this study, 13 types of microplastics (MPs) were identified in patient blood, cancer samples, and paracarcinoma samples using Raman spectroscopy, with polyethylene, polypropylene and polyethylene-co-polypropylene being the most abundant polymer types. Futher, cotton was also found in our study. The diversity and abundance of MPs were higher in blood samples than in cancerous tissues, and there was a significant positive correlation between diversity (p < 0.05). Furthermore, the diversity and abundance of MPs in cancerous tissues were higher than in paracancerous tissues. The dimensional sizes of MPs in these samples were also very similar, with the majority of detected MPs being smaller in size. Correlation analysis showed that patient\'s age correlated with the abundance of MPs in blood samples, body mass index (BMI) correlated with the abundance of MPs in cancerous tissues. Notably, the frequency with which patients consume bottled water and beverages may also increase the abundance of MPs. This study identifies for the first time the presence of MPs and cotton in cancerous and paracancerous tissues of human cervical cancer patients. This provides new ideas and basic data to study the risk relationship between MP exposure and human health.
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  • 文章类型: Journal Article
    背景:2023年,国际妇产科联合会(FIGO)更新了子宫内膜癌分期系统(FIGO2023)。我们的研究旨在验证FIGO2023在早期EC(I期和II期)患者中的预后价值。
    方法:从监测中筛选合格的EC患者后,流行病学和最终结果(SEER)数据库,采用Kaplan-Meier癌症特异性生存(CSS)曲线评价不同分期患者的预后。此外,AUC,C指数,Akaike信息标准(AIC),贝叶斯信息准则(BIC),采用决策曲线分析(DCA)综合比较新旧分期系统预测预后的效果。
    结果:共纳入33,156例患者。FIGO2023的引入使II期患者的比例从5.53%显着增加到24.76%。FIGO2023为患者定义了不同的子阶段,它们在CSS中显示出显著的差异。与FIGO2009相比,FIGO2023在辨别方面表现更好,拟合优度和临床决策。
    结论:与FIGO2009相比,FIGO2023在预测SEER数据库中早期EC患者的CSS方面具有更高的准确性。
    BACKGROUND: In 2023, the International Federation of Gynecology and Obstetrics (FIGO) updated the endometrial cancer staging system (FIGO2023). Our study aimed to validate the prognostic value of FIGO2023 in patients with early-stage EC (Stage I and Stage II).
    METHODS: After screening eligible EC patients from the Surveillance, Epidemiology and End Results (SEER) database, Kaplan-Meier cancer-specific survival (CSS) curves were used to evaluate the prognosis of patients with different stages. In addition, AUC, C-index, Akaike Information Criterion (AIC), Bayesian Information Criterion (BIC), and Decision curve analysis (DCA) were used to comprehensively compare the efficacy of the new and the old staging system in predicting prognosis.
    RESULTS: A total of 33,156 patients were enrolled. The introduction of FIGO2023 significantly increased the proportion of stage II patients from 5.53 % to 24.76 %. The FIGO2023 defines different substages for patients, which show significant differences in CSS. Compared with FIGO2009, FIGO2023 performed better in discrimination, goodness of fit and clinical decision making.
    CONCLUSIONS: Compared with FIGO2009, FIGO2023 had a higher accuracy in predicting CSS in patients with early-stage EC in the SEER database.
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  • 文章类型: Journal Article
    本研究的目的是探讨右美托咪定(DEX)联合酮咯酸对术后患者自控镇痛(PCA)的影响。对腹腔镜下宫颈癌根治术后患者Th1/Th2平衡及血管内皮生长因子(VEGF)水平的影响。选取70例宫颈癌患者行腹腔镜下根治性子宫切除术,随机接受右美托咪定联合酮咯酸术后镇痛(DK组)和舒芬太尼术后镇痛(SUF组)。主要结果是血清白细胞介素-4(IL-4)水平,干扰素-γ(IFN-γ)和VEGF,和诱导前30分钟的IFN-γ/IL-4比值(T0),术后24和48h。次要结果包括0h(T0)的数字评定量表得分,4h(T1),12小时(T2),术后24h(T3)和48h(T4),累计抢救镇痛次数,以及术后48h内副作用的发生率。在T2,T3和T4时,DK组的患者报告的镇痛效果与SUF组的患者相似,并且DK组术后恶心和呕吐的发生率显着降低。在DK组中,术后24h和48h血清IFN-γ浓度和IFN-γ/IL-4比值均高于SUF组。相反,术后24h血清IL-4和术后24h和48h血清VEGF浓度显著降低。结果表明,DEX和酮咯酸联合用于PCA可明显改善术后疼痛,降低血清VEGF水平,与肿瘤血管生成有关。此外,它通过将1型T辅助细胞和2型T辅助细胞之间的平衡(Th1/Th2平衡)转移到Th1来维持宫颈癌患者术后免疫功能的稳态(注册号。ChiCTR1900027979;2019年12月7日)。
    The aim of the present study was to explore the effects of dexmedetomidine (DEX) combined with ketorolac on postoperative patient-controlled analgesia (PCA), the balance of Th1/Th2 and the level of vascular endothelial growth factor (VEGF) in patients with cervical cancer following laparoscopic radical surgery. A total of 70 women with cervical cancer undergoing laparoscopic radical hysterectomy were enrolled in the study to randomly receive postoperative dexmedetomidine combined with ketorolac analgesia (DK group) and postoperative sufentanil analgesia (SUF group). The primary outcomes were the serum levels of interleukin-4 (IL-4), interferon-γ (IFN-γ) and VEGF, and the IFN-γ/IL-4 ratio 30 min before induction (T0), and 24 and 48 h after surgery. Secondary outcomes included numerical rating scale scores at 0 h (T0), 4 h (T1), 12 h (T2), 24 h (T3) and 48 h (T4) postoperatively, cumulative times of rescue analgesia, as well as the incidence of postoperative side effects within 48 h from surgery. Patients in the DK group reported similar analgesic effects as patients in the SUF group at T2, T3 and T4, and the incidence of postoperative nausea and vomiting was significantly lower in the DK group. In the DK group, the serum concentration of IFN-γ and IFN-γ/IL-4 ratio at 24 and 48 h after surgery were higher compared with those in the SUF group. Conversely, the serum concentrations of IL-4 at 24 h after surgery and VEGF at 24 and 48 h after surgery were significantly lower. The results indicated that the combination of DEX and ketorolac for PCA significantly improved postoperative pain and decreased the serum level of VEGF, which are associated with tumor angiogenesis. In addition, it maintained the homeostasis of postoperative immune dysfunction of patients with cervical cancer by shifting the balance between type 1 T helper cells and type 2 T helper cell (Th1/Th2 balance) to Th1 (registration no. ChiCTR1900027979; December 7, 2019).
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  • 文章类型: Journal Article
    宫颈癌是全球主要的健康问题。传统上,宫颈癌的预后标志物集中在肿瘤特征上。然而,人们越来越认识到患者的营养状况作为可能的预后指标的重要性。本荟萃分析旨在评估预后营养指数(PNI)在预测宫颈癌患者总生存期(OS)和无进展生存期(PFS)中的作用。Medline,谷歌学者,对ScienceDirect和CochraneCentral数据库进行了系统搜索,以获得报告宫颈癌患者PNI的研究。纳入标准用于选择相关研究,数据提取由两名独立研究者进行。通过纽卡斯尔-渥太华量表(NOS)评估偏倚风险。本荟萃分析包括10项研究,2,352名参与者。汇总分析表明,在宫颈癌患者中,PNI在预测OS[单变量危险比(HR):1.38;95%置信区间(CI):0.77-2.48)或PFS(单变量HR:1.12;95%CI:0.44-2.68)方面没有显着的预后效用。即使在使用多变量分析校正其他混杂因素后,这些结果也是一致的(合并HR:1.06forOS;95%CI:0.64-1.76;合并HR:1.22forPFS;95%CI:0.65-2.30)。还根据区域进行了亚组分析,PNI截止,样本量,证据等级和治疗方案,未显示PNI的任何重大预后价值。漏斗图显示了对称性,这表明没有发表偏倚。目前的荟萃分析表明,PNI在预测宫颈癌女性的OS或PFS方面没有显著的预后效用。需要进一步的研究来探索替代营养指标并确定该患者人群中可靠的预后标志物。
    Cervical cancer is a major global health concern. Prognostic markers for cervical cancer have traditionally focused on tumor characteristics. However, there is a growing recognition of the importaxnce of the nutritional status of the patient as a possible prognostic indicator. The present meta-analysis aims to estimate the role of the prognostic nutritional index (PNI) in predicting overall survival (OS) and progression-free survival (PFS) in patients with cervical cancer. Medline, Google Scholar, Science Direct and Cochrane Central databases were systematically searched for studies reporting PNI in patients with cervical cancer. Inclusion criteria were applied to select relevant studies and data extraction was performed by two independent investigators. Risk of bias was assessed by the Newcastle-Ottawa Scale (NOS). The present meta-analysis included 10 studies with 2,352 participants. The pooled analysis showed that in patients with cervical cancer PNI did not have a significant prognostic utility in predicting OS [univariate hazard ration (HR): 1.38; 95% confidence interval (CI): 0.77-2.48) or PFS (univariate HR: 1.12; 95% CI: 0.44-2.68). These results were consistent even after adjusting for other confounders using multivariate analysis (pooled HR: 1.06 for OS; 95% CI: 0.64-1.76; pooled HR: 1.22 for PFS; 95% CI: 0.65-2.30). Subgroup analyses were also performed based on region, PNI cut-off, sample size, grade of evidence and treatment protocol and did not demonstrate any significant prognostic value of PNI. The funnel plot demonstrated symmetry, suggesting the absence of publication bias. The present meta-analysis indicated that PNI does not have a significant prognostic utility in predicting OS or PFS in women with cervical cancer. Further research is warranted to explore alternative nutritional indicators and identify reliable prognostic markers in this patient population.
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  • 文章类型: Journal Article
    目的:卵巢癌(OC)的特点是高复发率,同源重组缺陷(HRD)是OC临床治疗的重要生物标志物。我们调查了原发性和铂敏感性复发性OC(PSROC)之间临床基因组谱的差异,重点关注人力资源开发状况。
    方法:收集20例OC患者原发肿瘤的福尔马林固定石蜡包埋(FFPE)组织40例及其首次铂类敏感复发组织,并应用FoundationOne®CDx(F1CDx)的综合基因组谱分析(CGP)分析探索原发性和复发性肿瘤的遗传(dis)相似性。
    结果:通过比较配对样本,我们发现基因组杂合性缺失(gLOH)评分具有很高的患者内相关性(r2=0.79)和短变异(包括TP53,BRCA1/2和NOTCH1突变),肿瘤突变负荷(TMB)和微卫星稳定性状态保持稳定。所有样本中(可能)病理性BRCA1/2突变的频率为30%(12/40),与gLOH评分呈正相关,但在原发和复发样本中gLOH高状态(评分>16%)的比例为50%(10/20)和55%(11/20),分别。另外20%(4/20)的患者需要注意,其中四分之一携带病理性BRCA1突变,但具有gLOH低状态(gLOH<16%),在原发-复发对中,四分之三的人有不同的gLOH状态。此外,我们观察到PSROC样本的gLOH评分较高(16.1±9.24与19.4±11.1,p=0.007),更多的CNV(36.1%与15.1%的不一致基因组交替),并且在TGF-β信号传导和Hippo信号传导途径中改变的基因的显著富集(全部p<0.05)比它们的配对初级。最后,突变特征和癌驱动基因分析显示,原发性和复发性肿瘤的计算突变特征相似性与COSMI3特征(HRD的病因)最匹配,并且具有一致的MSH2,NOTCH1和MSH6候选癌驱动基因.
    结论:短变异体的高度遗传一致性在OC复发过程中保持稳定。然而,结果显示,复发设置中的gLOH分数明显高于配对初选中的gLOH分数,支持进一步的临床即时HRD检测策略。
    OBJECTIVE: Ovarian cancer (OC) is characterized by a high recurrence rate, and homologous recombination deficiency (HRD) is an important biomarker in the clinical management of OC. We investigated the differences in clinical genomic profiles between the primary and platinum-sensitive recurrent OC (PSROC), focusing on HRD status.
    METHODS: A total of 40 formalin-fixed paraffin-embedded (FFPE) tissues of primary tumors and their first platinum-sensitive recurrence from 20 OC patients were collected, and comprehensive genomic profiling (CGP) analysis of FoundationOne®CDx (F1CDx) was applied to explore the genetic (dis)similarities of the primary and recurrent tumors.
    RESULTS: By comparing between paired samples, we found that genomic loss of heterozygosity (gLOH) score had a high intra-patient correlation (r2 = 0.79) and that short variants (including TP53, BRCA1/2 and NOTCH1 mutations), tumor mutational burden (TMB) and microsatellite stability status remained stable. The frequency of (likely) pathological BRCA1/2 mutations was 30% (12/40) in all samples positively correlated with gLOH scores, but the proportion of gLOH-high status (score > 16%) was 50% (10/20) and 55% (11/20) in the primary and recurrent samples, respectively. An additional 20% (4/20) of patients needed attention, a quarter of which carried the pathological BRCA1 mutation but had a gLOH-low status (gLOH < 16%), and three-quarters had different gLOH status in primary-recurrent pairs. Furthermore, we observed the PSROC samples had higher gLOH scores (16.1 ± 9.24 vs. 19.4 ± 11.1, p = 0.007), more CNVs (36.1% vs. 15.1% of discordant genomic alternations), and significant enrichment of altered genes in TGF-beta signaling and Hippo signaling pathways (p < 0.05 for all) than their paired primaries. Lastly, mutational signature and oncodrive gene analyses showed that the computed mutational signature similarity in the primary and recurrent tumors were best matched the COSMI 3 signature (Aetiology of HRD) and had consistent candidate cancer driver genes of MSH2, NOTCH1 and MSH6.
    CONCLUSIONS: The high genetic concordance of the short variants remains stable along OC recurrence. However, the results reveal significantly higher gLOH scores in the recurrent setting than in paired primaries, supporting further clinically instantaneity HRD assay strategy.
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  • 文章类型: Case Reports
    背景:Peutz-Jeghers综合征(PJS)的特征是胃肠道中存在错构瘤性息肉和嘴唇上的粘膜皮肤色素沉着,口腔粘膜,鼻子,手指,和脚趾。女性生殖道的同步粘液性化生和瘤形成(SMMN-FGT)是指在至少两个部位发生多灶性粘液性病变,包括子宫颈,子宫,输卵管,和卵巢,在女性生殖道。SMMN-FGT和PJS是发病率非常低的罕见疾病,尤其是同时发生的时候。
    方法:我们报告了一个病例,其中一名左卵巢有较大肿块的妇女接受了妇科手术,被诊断为宫颈胃型腺癌和子宫内膜粘液性病变,双侧输卵管,和卵巢,即,SMMN-FGT,通过术后石蜡病理学检查。患者因腹胀和增大而求医。妇科超声显示骨盆有多房性囊性肿块,而血清肿瘤标志物在正常范围内,碳水化合物抗原199和碳水化合物抗原125水平轻度升高。宫颈薄层细胞学检查结果为阴性。患者有PJS家族史,皮肤和粘膜有黑点,年龄8岁。由于肠梗阻和肠套叠,她接受了多次部分小肠切除术和胃肠道息肉切除术。她接受了左附件切除术,子宫切除术,右输卵管切除术,大网膜切除,阑尾切除术和右卵巢活检,并接受了6个疗程的洛普加卡铂辅助化疗。基因检测显示丝氨酸苏氨酸激酶11种系杂合突变,治疗后18个月随访期间无复发迹象。
    结论:这是一种罕见的病例,其中PJS并发SMMN-FGT。由于其极端稀有,没有指导方针,但报道的病例似乎表明预后不良。我们回顾性回顾了所有PJS和SMMN-FGT之间的碰撞病例,并探讨了临床特征,病理特征,诊断,治疗方法,两种疾病并存时的预后。目的是加深临床医生对这种疾病的认识,以便早期发现,诊断和治疗。
    BACKGROUND: Peutz-Jeghers syndrome (PJS) is characterized by the presence of hamartomatous polyps in the gastrointestinal tract and mucocutaneous pigmentation on the lips, oral mucosa, nose, fingers, and toes. Synchronous mucinous metaplasia and neoplasia of the female genital tract (SMMN-FGT) refers to the occurrence of multifocal mucinous lesions in at least two sites, including the cervix, uterus, fallopian tubes, and ovaries, in the female genital tract. SMMN-FGT and PJS are rare diseases with a very low incidence, especially when occurring simultaneously.
    METHODS: We report a case in which a woman with a large mass on the left ovary underwent a gynecological surgery and was diagnosed with cervical gastric-type adenocarcinoma and mucinous lesions in the endometrium, bilateral fallopian tubes, and ovary, i.e., SMMN-FGT, by postoperative paraffin pathology. The patient sought medical attention for abdominal distension and enlargement. A gynecological ultrasound revealed a multilocular cystic mass in the pelvis, while serum tumor markers were within normal limits, with mildly elevated carbohydrate antigen 199 and carbohydrate antigen 125 levels. Cervical thin-prep cytology test result was negative. The patient had a family history of PJS with black spots on her skin and mucous membranes since the age of 8 years. She underwent multiple partial small bowel resections and gastrointestinal polypectomy owing to intestinal obstruction and intussusception. She underwent left adnexectomy, hysterectomy, right salpingectomy, greater omental resection, appendectomy and right ovary biopsy, and received six courses of adjuvant chemotherapy with Lopressor plus Carboplatin. Genetic testing revealed a heterozygous serine threonine kinase 11 germline mutation and there were no signs of recurrence during the 18-month follow-up period after treatment.
    CONCLUSIONS: This is a rare case in which PJS was complicated by SMMN-FGT. Owing to its extreme rarity, there are no guidelines, but reported cases appear to indicate a poor prognosis. We retrospectively reviewed all cases of collisions between PJS and SMMN-FGT and explored the clinical features, pathological characteristics, diagnosis, treatment methods, and prognosis when the two diseases coexisted. The aim is to deepen the clinicians\' understanding of this disease for early detection, diagnosis and treatment.
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  • 文章类型: Journal Article
    宫颈癌(CC)是全球范围内普遍存在的妇科癌症,严重影响女性的生活质量和身心健康。然而,利用孟德尔随机化(MR)分析来研究免疫细胞与CC之间的联系的研究有限.本研究旨在探讨免疫性状对子宫颈CC和非肿瘤性疾病的因果影响。从FinnGen数据库下载了731种免疫表型的GWAS数据和6种CC的GWAS数据。随后,使用MREgger进行了两个样本的MR分析,加权中位数,反向方差加权(IVW),简单模式,和加权模式方法。我们的研究已经确定了免疫性状对子宫颈炎性疾病的潜在因果效应,子宫颈的其他非炎症性疾病,宫颈原位癌,子宫颈腺癌,鳞状细胞肿瘤和宫颈癌,以及子宫颈恶性肿瘤,分别为8、6、11、8、23和12。揭示了经典单核细胞与各种宫颈疾病之间的强相关性。此外,我们发现表达BAFF-R的B细胞具有阻止恶性CC进展的能力,特别是鳞状细胞肿瘤和宫颈癌。我们的研究表明,通过两个样本孟德尔随机化,免疫特征与子宫颈CC和非肿瘤性疾病之间存在显着关联。为未来的临床研究提供有价值的见解。
    Cervical cancer (CC) is a prevalent gynecological cancer worldwide that significantly impacts the quality of life and the physical and mental well-being of women. However, there have been limited studies utilizing Mendelian randomization (MR) analysis to investigate the connection between immune cells and CC. This study is to investigate the causal effects of immune traits on CC and non-neoplastic conditions of the cervix. The GWAS data for 731 immunophenotypes and six GWAS data for CC from the FinnGen database were downloaded. Subsequently, a two-sample MR analysis was conducted using the MR Egger, Weighted median, Inverse variance weighted (IVW), Simple mode, and Weighted mode methods. Our study has identified the potential causal effects of immune traits on inflammatory diseases of the cervix, other noninflammatory disorders of the cervix uteri, carcinoma in situ of cervix uteri, adenocarcinomas of cervix, squamous cell neoplasms and carcinoma of cervix, as well as malignant neoplasm of the cervix uteri, with the respective numbers being 8, 6, 11, 8, 23, and 12, respectively. A strong correlation between classic monocytes and various cervical diseases was revealed. Furthermore, we discovered that B cells expressing BAFF-R have the ability to impede the advancement of malignant CC, specifically squamous cell neoplasms and carcinoma of cervix. Our study has demonstrated a significant association between immune traits and both CC and non-neoplastic conditions of the cervix through two-sample Mendelian randomization, providing valuable insights for future clinical research.
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  • 文章类型: Journal Article
    背景:宫颈癌(CC)是一种潜在的致命疾病,可能对女性健康造成严重后果。因为早期症状通常只出现在疾病的中晚期,临床诊断和治疗具有挑战性。中药(TCM)已被证明在缓解癌症临床症状方面具有独特的益处,降低手术后复发的风险,减少放疗后的毒副作用和药物耐药性。它还被证明可以改善患者的生活质量。由于其提高了抗肿瘤的有效性和生物安全性,它可以被认为是一种替代疗法。本研究探讨了中药如何通过信号转导引起CC细胞凋亡,包括活性成分和药用补品。旨在为CC的中医治疗提供可靠的临床依据和方案选择。
    方法:以下搜索词在PubMed中使用,WebofScience,Embase,CNKI,万方,VIP,SinoMed,和其他科学数据库检索有关“宫颈癌”的相关文献,“\”凋亡,\"\"信号通路,\"\"中药,“\”草药单体,“\”草药成分,“\”草药提取物,\"和\"草药配方。\"
    结果:已经证明,草药可以诱导子宫颈细胞凋亡,一种癌症,通过影响所涉及的信号通路。
    结论:进行了全面的文献检索,2017年1月至2023年12月期间的148篇论文被确定有资格纳入.经过细致的筛选,消除和总结,泛化,和分析,发现中药可以调节多个细胞内信号通路及相关分子靶点,如STAT3、PI3K/AKT、Wnt/β-catenin,MAPK,NF-κB,p53,HIF-1α,Fas/FasL等等。观察到这种调节能力在宫颈癌细胞中诱导凋亡。中药抗宫颈癌作用机制的研究和新药靶点的筛选对今后该领域的研究具有重要意义。本研究结果将为中医药在宫颈癌诊治中的未来发展提供思路和参考。
    BACKGROUND: Cervical cancer (CC) is a potentially lethal disorder that can have serious consequences for a woman\'s health. Because early symptoms are typically only present in the middle to late stages of the disease, clinical diagnosis and treatment can be challenging. Traditional Chinese medicine (TCM) has been shown to have unique benefits in terms of alleviating cancer clinical symptoms, lowering the risk of recurrence after surgery, and reducing toxic side effects and medication resistance after radiation therapy. It has also been shown to improve the quality of life for patients. Because of its improved anti-tumor effectiveness and biosafety, it could be considered an alternative therapy option. This study examines how TCM causes apoptosis in CC cells via signal transduction, including the active components and medicinal tonics. It also intends to provide a reliable clinical basis and protocol selection for the TCM therapy of CC.
    METHODS: The following search terms were employed in PubMed, Web of Science, Embase, CNKI, Wanfang, VIP, SinoMed, and other scientific databases to retrieve pertinent literature on \"cervical cancer,\" \"apoptosis,\" \"signaling pathway,\" \"traditional Chinese medicine,\" \"herbal monomers,\" \"herbal components,\" \"herbal extracts,\" and \"herbal formulas.\"
    RESULTS: It has been demonstrated that herbal medicines can induce apoptosis in cells of the cervix, a type of cancer, by influencing the signaling pathways involved.
    CONCLUSIONS: A comprehensive literature search was conducted, and 148 papers from the period between January 2017 and December 2023 were identified as eligible for inclusion. After a meticulous process of screening, elimination and summary, generalization, and analysis, it was found that TCM can regulate multiple intracellular signaling pathways and related molecular targets, such as STAT3, PI3K/AKT, Wnt/β-catenin, MAPK, NF-κB, p53, HIF-1α, Fas/FasL and so forth. This regulatory capacity was observed to induce apoptosis in cervical cancer cells. The study of the mechanism of TCM against cervical cancer and the screening of new drug targets is of great significance for future research in this field. The results of this study will provide ideas and references for the future development of Chinese medicine in the diagnosis and treatment of cervical cancer.
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  • 文章类型: Journal Article
    CD8+T细胞是抗癌免疫的主要介质,和CD8+T细胞反应的调节一直是免疫疗法治疗癌症的中心焦点。当CD8+T细胞特异性识别肿瘤细胞上MHC-I呈递的抗原肽时,它们被激活并杀死肿瘤细胞。然而,肿瘤细胞逃避免疫监视的一个重要机制是减少其抗原呈递。为了确定新的免疫治疗靶点,我们特别关注MAL2在子宫内膜癌(EC)免疫逃避中的作用及其潜在机制。MAL2在EC组织和细胞中过表达,其转录被RAD21增强。MAL2或RAD21的敲低通过抑制MHC-I表达和CD8细胞的细胞毒性作用来抑制EC细胞的恶性行为和免疫逃避。相反,在存在RAD21敲低的情况下,MAL2促进小鼠中EC细胞的免疫逃避和肿瘤生长。这些结果表明,MAL2的RAD21激活抑制了MHC-I的抗原加工和呈递,从而诱导EC细胞的免疫逃避。我们进一步建议RAD21和MAL2可能作为EC免疫治疗的新靶点。
    CD8+ T cells are the primary mediators of anticancer immunity, and modulation of the CD8+ T cell response has been a central focus of immunotherapy to treat cancer. When CD8+ T cells specifically recognize antigenic peptides presented by the MHC-I on tumor cells, they become activated and kill the tumor cells. However, one pivotal mechanism through which tumor cells evade immune surveillance is to reduce their antigen presentation. To identify novel immunotherapeutic targets, we specifically focused on the role of MAL2 in immune evasion in endometrial cancer (EC) and the underlying mechanism. MAL2 was overexpressed in EC tissues and cells and its transcription was enhanced by RAD21. Knockdown of MAL2 or RAD21 inhibited malignant behavior and immune evasion of EC cells by repressing MHC-I expression and the cytotoxic effects of CD8+ cells. Conversely, MAL2 promoted immune evasion of EC cells and tumor growth in mice in the presence of RAD21 knockdown. These results indicate that RAD21 activation of MAL2 inhibits antigen processing and presentation of MHC-I, thereby inducing immune evasion of EC cells. We further suggest that RAD21 and MAL2 may serve as novel targets for EC immunotherapy.
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  • 文章类型: Journal Article
    将人乳头瘤病毒(HPV)基因组整合到细胞基因组中是导致病毒癌蛋白E6/E7组成型表达并驱动宫颈癌进展的关键事件。然而,HPV整合模式在相关恶性肿瘤的个案基础上有所不同。下一代测序技术在询问HPV整合位点方面仍然面临挑战。在这项研究中,利用纳米孔长读数测序,我们从宫颈癌细胞系(CaSki和HeLa)和五个组织样本中确定了452和108个潜在的整合位点,分别。基于长的纳米孔嵌合读数,我们能够分析HPV长控制区(LCR)的甲基化状态,控制癌基因E6/E7的表达,并在众多整合体中鉴定转录活性整合体。作为概念的证明,我们在CaSki细胞系的6号染色体上的RUNX2和CLIC5之间鉴定了一个活跃的HPV整合体,由ATAC-SEQ支持,H3K27AcChIP-seq,和RNA-seq分析。敲除活性HPV整合物,通过CRISPR/Cas9系统,显著削弱细胞增殖和诱导细胞衰老。总之,用纳米孔测序鉴定转录活性的HPV整合体可以为针对HPV相关癌症的基因治疗提供可行的靶标。
    Integration of the human papillomavirus (HPV) genome into the cellular genome is a key event that leads to constitutive expression of viral oncoprotein E6/E7 and drives the progression of cervical cancer. However, HPV integration patterns differ on a case-by-case basis among related malignancies. Next-generation sequencing technologies still face challenges for interrogating HPV integration sites. In this study, utilizing Nanopore long-read sequencing, we identified 452 and 108 potential integration sites from the cervical cancer cell lines (CaSki and HeLa) and five tissue samples, respectively. Based on long Nanopore chimeric reads, we were able to analyze the methylation status of the HPV long control region (LCR), which controls oncogene E6/E7 expression, and to identify transcriptionally-active integrants among the numerous integrants. As a proof of concept, we identified an active HPV integrant in between RUNX2 and CLIC5 on chromosome 6 in the CaSki cell line, which was supported by ATAC-seq, H3K27Ac ChIP-seq, and RNA-seq analysis. Knockout of the active HPV integrant, by the CRISPR/Cas9 system, dramatically crippled cell proliferation and induced cell senescence. In conclusion, identifying transcriptionally-active HPV integrants with Nanopore sequencing can provide viable targets for gene therapy against HPV-associated cancers.
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