Ovarian cancer screening based on circulating tumor cells (CTCs) in peripheral blood remains highly challenging because of their extreme rarity, pronounced heterogeneity, and the complex blood-cell background in which they are embedded. To address this problem, we propose a label-free semi-supervised anomaly detection framework for ovarian cancer cell screening using digital holographic flow cytometry (DHFC) in a data-level blood-cell-background screening scenario. The framework combines a twin-branch Siamese feature-learning strategy with one-class decision modeling, so that compact representations of normal blood-related cells can be learned while a limited number of known abnormal cells are used to improve anomaly separability. In this way, the method is specifically designed for the practically relevant regime of scarce abnormal supervision and can generalize to an unseen cancer-cell phenotype excluded from training. Validation was performed on a mixed-cell dataset containing red blood cells (RBCs), white blood cells (WBCs), human umbilical vein endothelial cells (HUVECs), and two ovarian cancer cell lines (A2780 and SKOV3). Across five fixed random seeds, the proposed framework achieved an overall detection accuracy of 99.57 ± 0.07%, with both known (A2780) and unseen (SKOV3) cancer cells detected with 100.00 ± 0.00% accuracy. Comparative experiments against modern supervised classifiers, recent anomaly-detection baselines and the related traditional methods further demonstrated that the proposed framework provides more stable and balanced performance when abnormal samples are extremely limited. These results indicate that DHFC-based anomaly detection is a promising route for high-throughput, label-free rare-cell screening in clinically relevant and highly imbalanced environments.

The immunosuppressive tumor microenvironment of ovarian cancer renders it insensitive to immunotherapy. Current immunotherapy strategies, like immune checkpoint inhibitors (ICIs), only focus on “single-point interventions” targeting specific parts of the antitumor immune cycle, but lack systematic coordination throughout the cycle, which shows low therapeutic effect. In this study, we develop an ultrasound-mediated, dendritic cell membrane-driven multifunctional immunotherapy platform (aDCM@mPEG-TK/MSN-DOX-Ce6), comprising a mesoporous silica nanoparticle (MSN) loaded with the chemotherapeutic drug doxorubicin (DOX) and the sonosensitizer Chlorine e6 (Ce6) as the “core”; reactive oxygen species (ROS)-responsive thioketal grafted methoxy polyethylene glycol (mPEG-TK) serving as the “gatekeeper”, and an activated dendritic cell membrane (aDCM) as the “shell”. The antigen peptide-MHC molecules and co-stimulatory molecules CD80/CD86 on the surface of aDCM provide the first and second signals for naive T cell activation and directly initiate the antitumor immune cycle. Targeted chemotherapy synergizing with sonodynamic therapy (SDT) induces potent immunogenic cell death (ICD), releasing a large amount of tumor antigens as sustained, abundant “antigen fuel” to support the restart and positive feedback self-maintenance of the immune cycle. This multifunctional nanoplatform activates local and systemic antitumor immune responses, effectively transforming the “cold” tumor into the “hot” tumor, thereby enhancing ovarian cancer sensitivity to ICIs. Simultaneously, it promotes the generation of memory T cell populations, achieving sustained immune surveillance and memory. This combined immunotherapy nanoplatform represents a significant shift from “single-point intervention” to “systemic regulation”, offering a novel approach for efficient tumor immunotherapy of ovarian cancer.

Although poly (ADP-ribose) polymerase inhibitors (PARPi) have been established to enhance ovarian cancer outcomes, the emergence of drug resistance poses considerable clinical challenges. In this study, we constructed a Hi-C atlas to systematically characterize the effect of olaparib on chromatin organization at multiple hierarchical scales, namely, chromosomes, A/B compartments, topologically associating domains, and chromatin loops. To investigate the effects of PARPi on expression of the cohesion subunit RAD21, we established olaparib-resistant ovarian cancer cell line. Furthermore, we examined the effects of RAD21 on the functions of ovarian cancer cells and spheroids based on cell proliferation, apoptosis, and comet assays. In addition, by performing integrated analyses using ChIP-seq datasets, ChIP-qPCR, and chromosome conformation capture assays, we assessed the influence of RAD21 on the enhancer–promoter interactions of a homologous recombination repair gene. Moreover, on the basis of our findings in previous studies using clinical samples, we further evaluated the clinical value of RAD21 in multiple databases. Genome-wide Hi-C heatmap analysis revealed that olaparib led to a reduction in the genome-wide contact frequency for long distance interactions, altered the degree of chromatin compartmentalization, and promoted compartment switching in ovarian cancer. Differences between the olaparib-treated and control cells with respect to topologically associating domain boundaries and chromatin loops were found to be associated with key cellular functions, such as DNA repair and transcriptional mis-regulation in cancer. Furthermore, PARPi treatment was observed to induce the expression of RAD21, whereas an upregulation of RAD21 promoted proliferation and inhibited apoptosis in ovarian cancer spheroids. Mechanistically, we obtained evidence to indicate that by maintaining enhancer–promoter interactions within chromatin conformation, RAD21 regulates the transcription of RAD51, thereby mediating olaparib resistance in ovarian cancer. The high expression of RAD21 was found to show a significant association with poor overall and progression-free survival in patients with ovarian cancer. Our findings in this study indicate that RAD21 could serve as a potential therapeutic target for overcoming olaparib resistance in ovarian cancer, and provide new insights into the mechanisms underlying the resistance to PARPi from the perspective of chromatin organization.

Ovarian cancer is one of the most lethal gynecological malignancies, frequently accompanied by ascites formation in advanced stages. Accurate identification of ovarian cancer cells within ascitic fluid is clinically important yet technically challenging due to pronounced cellular heterogeneity. Here, we establish a quantitative holographic imaging flow cytometry framework for ovarian cancer cell discrimination under ascites-mimicking conditions using single-cell phase images acquired by microfluidic digital holographic microscopy. A six-cell-type dataset was constructed to emulate the heterogeneous tumor-associated microenvironment, introducing substantial morphological and biophysical overlap. Within this unified experimental setting, we systematically compared multidimensional feature-based machine learning models with end-to-end deep learning approaches to assess their relative performance in cancer cell detection. Deep learning models demonstrated improved robustness and sensitivity in complex backgrounds while preserving high-throughput capability. This study provides a structured evaluation of quantitative phase-driven cell classification and supports the development of rapid, automated, label-free screening strategies for ascites analysis.

BACKGROUND:Cross-resistance is observed between platinum and Poly (ADP-ribose) polymerase inhibitors (PARPi). We aim to propose the definition of PARPi resistance and demonstrate the best therapeutic strategy for patients with PARPi resistance. METHODS:A retrospective analysis was performed on patients diagnosed with epithelial ovarian cancer from October 2015 to November 2022. Patients were treated with PARPi for more than 6 months and received chemotherapy after progression. RESULTS:Totally, 41 patients were enrolled, with 21 receiving PARPi for 6 to 12 months and 20 for more than 12 months. The median duration of PARPi was 12 months, and the median time to second progression (TTSP) was 3.45 months (range, 1.0-20.2 months). The Kaplan-Meier and Cox analysis revealed a significantly shorter TTSP for patients who received PARPi for more than 12 months compared to those for 6 to 12 months. After PARPi resistance, 34 (82.9%) received platinum-based chemotherapy, with an overall response rate (ORR) of 26.5% (9/34). Seven patients (17.1%) received arsenic trioxide (ATO)-based chemotherapy, with an ORR of 57.1% (4/7). During subsequent chemotherapy, 12/34 patients switched to ATO-based chemotherapy due to progression, of which five cases were evaluated as effective (41.7%). CONCLUSION:PARPi resistance has a negative impact on the subsequent chemotherapy. The progression of the disease beyond 6 to 12 months should be considered as acquired resistance. Non-platinum chemotherapy, such as ATO-based combined sequential chemotherapy, may emerge as the preferred option for patients with PARPi resistance.

Objective To investigate firstly Chinese patent medicine Realgar-Indigo Naturalis Formula (RIF), which mainly contains tetra-arsenic tetra-sulfide formula for the maintenance therapy of ovarian cancer.Methods We recruited all patients with ovarian epithelial cancer who were diagnosed at Peking University People's Hospital between January 2018 and January 2021. All these patients received standard chemotherapy and achieved complete remission. The patients took RIF (60 mg/kg daily in an oral divided dose) in a 4-week-on and 4-week-off regimen. The main efficacy indicators, including progression-free interval (PFI) and overall survival (OS), were measured and evaluated regularly. Additionally, the safety and side effects were closely monitored.Results A total of 20 patients were included in this study. Regarding the treatment, patients received oral arsenic for 3-18 courses (the longest treatment interval was equivalent to 3 years). The median follow-up time was 43 months. Subsequently, data analysis was conducted, revealing that the median PFI was 23 months. P53 mutations were worse than P53 wild-type PFI, and the median PFI was 19.2 months (p=0.03). Regarding P53 wt status, the HR for disease progression or death was 0.25 (95% CI 0.07 to 0.91). The 3-year OS was 89%, and the 5-year OS was 77%. The common side effects were abdominal pain and diarrhoea.Conclusions RIF compound proved to be an effective Chinese patent medicine maintenance therapy for ovarian cancer, thus prolonging the PFI of patients and controllable side effects, in particular simple and convenient for the method of administration and better potency ratio. These findings need to be validated in multicentre research studies with large sample sizes.Trial registration number ChiCTR2400090349.

Liver metastasis represents a critical challenge in cancer progression, with particularly complex therapeutic implications. In ovarian cancer patients, ovarian cancer liver metastasis (OCLM) marks a distinct stage of disease progression that demands specialized diagnostic and therapeutic approaches. Despite its clinical significance, guidance for OCLM management remains notably absent in current clinical practice. This comprehensive review synthesizes recent advances in the management of OCLM, with special emphasis on a resectability-based classification system.

Gynecological malignancies are characterized by high morbidity and mortality rates. With the development of society, the status of women continues to improve, yet the social pressure they bear increases daily. The incidence rate of gynecological malignancies in the female population has always remained at a high level, and the age of onset has shown a trend of getting younger. Common gynecological malignancies include cervical cancer, ovarian cancer, and endometrial cancer. Alarmingly, over 70% of patients are diagnosed at an advanced stage. This disease is mainly treated through surgery and radiotherapy, but there is still a relatively high recurrence rate after treatment. In recent years, with the development of traditional Chinese medicine (TCM), the advantages of TCM in the treatment of gynecological malignancies have gradually emerged. The entry of TCM into the treatment of Gynecologic malignancies is a tumor treatment method that has received close attention from the international medical community in recent times. TCM can be used throughout the whole process of tumor treatment. Combining Western medicine at different stages of the tumor, or giving different Chinese medicines alone, can minimize the toxic side effects of Western medicine treatment, alleviate symptoms, prolong survival and improve the quality of survival. Therefore, combining traditional Chinese medicine to provide individualized treatment for patients may become a better approach to cancer treatment. This article reviews the status and important role of TCM in gynecological malignancies in the hope of exploring new treatment modalities to mitigate the impact of gynecological malignancies on women’s health.

Unbiased learning pipeline for label-free single-cell classification.

Digital holography in microscopy is one of the emerging technologies to deal with biological specimen imaging without using exogenous agents. Artificial Intelligence approaches are presented here to classify label-free cells also in presence of bias.

For ovarian cancer patients, paclitaxel remains to be primary chemotherapy drug. Once drug resistance is developed, it will lead to tumor progression and metastasis during chemotherapy. Many studies have shown that the development of drug resistance in cancer cells can cause morphological changes. Digital holographic microscopy is an interferometric imaging technique that can obtain 3D quantitative morphological information of label-free cells. Combining with microfluidics enables high-throughput holographic image acquisition of suspended cells. In this work, four kinds of epithelial ovarian cancer cells with different drug sensitivity, SKOV3 cells, SKOV3_Ta_2μM cells, SKOV3_Ta_8μM cells, and SKOV3_Ta_20μM cells were studied. Several machine learning algorithms were used to perform multi-classification on the extracted morphological features of four types of cells. Then, we employ the SHapley Additive exPlanations (SHAP) method to interpret the classification model. The SHAP value of each feature is calculated and sorted to obtain the important morphological features.

Abstract Introduction An increasing number of young patients with early-stage endometrial cancer are opting for fertility-sparing treatment, and they have achieved reassuring rates of complete remission, with some women achieving pregnancy. However, surgical treatment is still recommended for patients with advanced endometrial cancer. We reported a woman with IVb endometrial cancer (EC) who reached complete remission (CR) and gained a live birth successfully with the help of in vitro fertilization and embryo transfer (IVF-ET). Case report A 30-year-old woman found to have stage IVb EC after hysteroscopy, laparoscopy, and pathological examination. After a combination of chemotherapy and progesterone therapy, the woman achieved complete remission. The woman became pregnant with IVF-ET and got a full-term live birth. In addition, there was no recurrence after 19 months of observation. The molecular classification of POLE and the combination of chemotherapy and progesterone therapy may be associated with a good prognosis of this patient. The use of progestin-primed ovarian stimulation (PPOS) and the combination of letrozole and levonorgestrel-releasing intrauterine device (LNG-IUD) during ovulation induction seemed to be safe for the woman Conclusion This is the first report on fertility-sparing treatment and live birth for advanced EC. IVF-ET is feasible for women with EC who preserve reproductive function. The progestin-primed ovarian stimulation combined with levonorgestrel-releasing intrauterine device and letrozole seems to be safe for these women. Patients still need to be closely watched for tumor recurrence.

Ovarian cancer (OV) is a deadly gynecological cancer. The tumor immune microenvironment (TIME) plays a pivotal role in OV development. However, the TIME of OV is not fully known. Therefore, we aimed to provide a comprehensive network of the TIME in OV. Gene expression data and clinical information from OV patients were obtained from the Cancer Genome Atlas Program (TCGA) database. Non-negative Matrix Factorization, NMFConsensus, and nearest template prediction algorithms were used to perform molecular clustering. The biological functions of differentially expressed genes (DEGs) were identified using Metascape, gene set enrichment analysis (GSEA), gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The copy number variations (CNVs), single nucleotide polymorphisms (SNPs) and tumor mutation burden were analyzed using Gistic 2.0, R package maftools, and TCGA mutations, respectively. Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data and CIBERSORT were utilized to elucidate the TIME. Moreover, external data from the International Cancer Genome Consortium (ICGC) and ArrayExpress databases were used to validate the signature. All 361 samples from the TCGA OV dataset were classified into Immune Class and non-Immune Class with immune signatures. By comparing the two classes, we identified 740 DEGs that accumulated in immune-related, cancer-related, inflammation-related biological functions and pathways. There were significant differences in the CNVs between the Immune and non-Immune Classes. The Immune Class was further divided into immune-activated and immune-suppressed subtypes. There was no significant difference in the top 20 genes in somatic SNPs among the three groups. In addition, the immune-activated subtype had significantly increased proportions of CD4 memory resting T cells, T cells, M1 macrophages, and M2 macrophages than the other two groups. The qRT-PCR results indicated that the mRNA expression levels of RYR2, FAT3, MDN1 and RYR1 were significantly down-regulated in OV compared with normal tissues. Moreover, the signatures of the TIME were validated using ICGC cohort and the ArrayExpress cohort. Our study clustered the OV patients into an immune-activated subtype, immune-suppressed subtype, and non-Immune Class and provided potential clues for further research on the molecular mechanisms and immunotherapy strategies of OV.

卵巢癌是妇科三大常见恶性肿瘤之一.近年来,PARPi在卵巢癌维持治疗领域取得了突破性进展,卵巢癌的治疗已经由既往手术+化疗为主发展为手术+化疗+维持治疗的策略.在新的治疗模式下,卵巢癌患者的生存期得以明显延长,因此,全程管理的内涵及相关策略也应随之转变.卵巢癌患者中约20％携带有胚系BRCA1/2突变,是PARPi维持治疗获益最大的人群,但携带胚系BRCA1/2突变者同时也是罹患乳腺癌的高风险人群,且该风险随着生存期的延长而逐渐增加.而在这部分患者的全程管理中乳腺癌相关筛查并没有得到足够的重视,目前尚缺乏对这部分患者的相关筛查指南或指导意见.本部专家指导意见旨在卵巢癌全程管理过程中对特定的人群采取合适的筛查策略,同时考虑成本效益比,以进一步提高乳腺癌的早诊率及治愈率,减少患者的疾病负担,更好地改善其生存质量.

肠梗阻是妇科恶性肿瘤常见并发症,尤其晚期卵巢恶性肿瘤患者,对合并癌性肠梗阻的患者,多数表现为腹痛、腹胀、恶心和呕吐等,治疗方案主要包括药物、手术、综合支持治疗等,因病情个体差异,目前没有统一的治疗方案,本文总结了近年在肠梗阻治疗方面的进展,以期为临床治疗方案的选择提供一定的参考.

OBJECTIVE:To discuss the impact of chemoradiotherapy (CRT) on the survival of patients with stage III endometrial cancer (EC) compared with chemotherapy (CT) alone.METHODS:Articles involving adjuvant CRT versus CT on survival in stage III EC were retrieved from PubMed and EMBASE. Hazard ratios (HRs) of overall survival (OS) and relapse-free survival (RFS) were collected and pooled, and publication bias was measured by Begg's and Egger's test. Quality of researches was measured by the Newcastle-Ottawa scale and the modified Jadad scale.RESULTS:Eleven were included in the statistical analysis. A significant advantage of CRT over CT on OS was shown (HR 0.59, 95% CI 0.49-0.70). Further subgroup analysis suggested the advantage was mostly associated with stage IIIC (HR 0.63, 95% CI 0.52, 0.76]). A similar result favoring CRT was also reached on RFS (HR 0.66, 95% CI 0.47-0.93). No significant publication bias was observed.CONCLUSION:CRT was associated with a better OS and RFS than CT alone in stage III EC patients.

Arsenic compounds,including various arsenic-containing compounds such as intravenous use of arsenic trioxide(ATO)and an oral tetra-arsenic tetra-sulfide(As4S4)-containing formula named the Realgar-Indigo naturalis formula(RIF).RIF,also known as Compound Huangdai Tablets,which exert anti-tumor effects through a variety of mechanisms,such as the induction of programmed cell death,induction of G1 or G2/M phase arrest,epigenetic regulation of miRNAs,and suppression of cancer stem cell properties.International multicenter clinical studies have shown that ATO and RIF have anti-tumorigenic effects on hematological tumors and some solids.Arsenic compounds also been used in the treatment of cervical cancer,endometrial cancer,ovarian cancer,especially advanced drug-resistant ovarian cancer.This article introduces the progress of ATO in combination chemo-therapy,such as ATO with paclitaxel,adriamycin,cisplatin,etc in solid tumors and gynecological malignant tumors.The side effects associated with arsenic treatment,including cardiac disorders,skin and bone marrow suppression,etc.are also discussed in this review.Oral arsenic drugs also have a good therapeutic effect,it may be an outpatient oral chemotherapy new model for RIF to treatment recurrent ovarian cancer.

目的 总结分析妇科恶性肿瘤合并脑血管疾病化疗患者临床特征及预后.方法 收集2003年1月至2020年1月北京大学人民医院妇科恶性肿瘤合并脑血管疾病,且进行辅助化疗的30例患者临床资料,分为既往有脑血管病史组(既往组,22例)和化疗或手术期间新发脑血管病组(新发组,8例),总结患者临床特征,并分析其发生脑血管病变的危险因素.结果 ①一般资料:30例患者平均年龄61岁.F1GO分期Ⅰ～Ⅱ期13例,Ⅲ～Ⅳ期17例.病理类型多数为腺癌(23例,76.7％).②辅助检查:两组患者的D-二聚体、肿瘤标志物水平均显著升高.③既往组中3例在化疗期间再发脑梗死,余19例化疗期间未发作;但两亚组比较,再发组的Caprini评分更高,差异有统计学意义(P＜0.05),化疗或手术距离既往病史的时间似乎更短,但差异无统计学意义(P＞0.05).④11例新发脑梗死患者中8例(72.7％)合并高血压,9例(81.8％)存在颈动脉斑块,3例(27.3％)合并下肢静脉血栓.4例在术后4.5天(1～14天)发病;7例在化疗后11天(0～29天)发病.7例患者化疗方案均为以铂类为基础的方案(4例顺铂,2例卡铂,1例草酸铂);该组患者发病时较基础状态,D-二聚体、白细胞有升高趋势,血红蛋白显著降低.经治疗后,6例脑梗死患者症状恢复或好转,3例有运动或语言后遗症;4例死亡,其原因为脑梗后未恢复或肿瘤终末期.结论 妇科肿瘤患者辅助化疗期间新发脑梗死,与内科相关危险因素、高凝状态、化疗及手术等有关.距离前次脑血管病史时间较长者多数可以耐受化疗.新发脑梗死的妇科肿瘤患者预后不良.

一、病例摘要 病例1:患者55岁,因绝经7年宫腔占位于2011年7月人院.宫腔镜下诊刮组织病理:子宫内膜样腺癌.行腹腔镜下筋膜外全子宫+双附件切除术+盆腔腹主动脉旁淋巴结切除术.术后病理:子宫内膜中分化腺癌,右输卵管管腔内可见子宫内膜腺癌成分.诊断子宫内膜样腺癌ⅢA期G2,术后表阿霉素+顺铂(AP)方案化疗3个疗程,后进行全盆DT4 600 cGy/25次/5周和阴道断端加量DT1 400 cGy/7次/10天放疗,放疗后继续AP化疗3个疗程.

目的 评估"化疗-放疗-化疗"的"夹心模式"序贯放化疗在早期高危子宫内膜癌患者中疗效及可行性.方法 回顾性分析2004年1月至2015年12月于北京大学人民医院行分期手术,分期(FIGO 2009)I～11期,且术后行"夹心疗法"的内膜癌患者,分析其临床病理特征,复发、生存及副反应.结果 40例纳人研究,平均年龄(57±7)岁;随访51～182个月,仅1例术后66个月发生远处复发,其余均无瘤生存;5年总生存率及无疾病生存率均100％;无疾病生存期(178.7±33)m(95％CI:172.3～185.1);16例出现化疗副反应,仅1例发生Ⅲ度骨髓抑制;8例出现放疗副反应,其中1例发生左侧输尿管狭窄,其余为Ⅰ～Ⅱ度副反应.结论 "夹心疗法"应用于早期高危内膜癌具有较好疗效,副反应可耐受.因病例数有限,有待积累病例,进一步总结.