Gynecological Tumors Research Articles

Ferroptosis-related genes in cervical cancer as biomarkers for predicting the prognosis of gynecological tumors.

Background: Ferroptosis has been identified as a potent predictor of cancer prognosis. Currently, cervical cancer ranks among the most prevalent malignant tumors in women. Enhancing the prognosis for patients experiencing metastasis or recurrence is of critical importance. Consequently, investigating the potential of ferroptosis-related genes (FRGs) as prognostic biomarkers for cervical cancer patients is essential. Methods: In this study, 52 FRGs were obtained from the GSE9750, GSE7410, GSE63514, and FerrDb databases. Six genes possessing prognostic characteristics were identified: JUN, TSC22D3, SLC11A2, DDIT4, DUOX1, and HELLS. The multivariate Cox regression analysis was employed to establish and validate the prognostic model, while simultaneously performing a correlation analysis of the immune microenvironment. Results: The prediction model was validated using TCGA-CESC and GSE44001 datasets. Furthermore, the prognostic model was validated in endometrial cancer and ovarian serous cystadenocarcinoma cases. KM curves revealed significant differences in OS between high-risk and low-risk groups. ROC curves demonstrated the stability and accuracy of the prognostic model established in this study. Concurrently, the research identified a higher proportion of immune cells in patients within the low-risk group. Additionally, the expression of immune checkpoints (TIGIT, CTLA4, BTLA, CD27, and CD28) was elevated in the low-risk group. Ultimately, 4 FRGs in cervical cancer were corroborated through qRT-PCR. Conclusion: The FRGs prognostic model for cervical cancer not only exhibits robust stability and accuracy in predicting the prognosis of cervical cancer patients but also demonstrates considerable prognostic value in other gynecological tumors.

Silencing of FAM111B inhibits tumor growth and promotes apoptosis by decreasing AKT activity in ovarian cancer.

Ovarian cancer is the most lethal gynecological tumor in women worldwide. FAM111B (family with sequence similarity 111 member B) is an oncoprotein associated with multiple cancers, but its biological functions in ovarian cancer remain elusive. In this study, FAM111B was overexpressed in ovarian cancer tissues and cell lines. Functional studies in vitro revealed that silencing of FAM111B inhibited ovarian cancer cell proliferation, invasion, and migration, as well as increased cell apoptosis. Furthermore, FAM111B silencing arrested the ovarian cancer cell cycle at the G1/S phase. Furthermore, western blot assays demonstrated that silencing of FAM111B resulted in downregulation of phospho-AKT (p-AKT) protein expression, as well as upregulation of p53 and caspase-1 protein expression. The xenograft animal model of ovarian cancer demonstrated that FAM111B silencing inhibited tumor growth, enhanced cell apoptosis, and inhibited Ki-67 and proliferating cell nuclear antigen (PCNA) protein expression in vivo. Conversely, the overexpression of FAM111B exhibited opposite effects on the ovarian cancer xenograft. It was previously established that inactivating AKT inhibited ovarian cancer progression. This study found that silencing of FAM111B inhibits tumor growth and promotes apoptosis by decreasing AKT activity in ovarian cancer. Caspase-1 and p53 signaling also influenced the function of FAM111B in SKOV3 cells. Collectively, our results demonstrate that silencing of FAM111B is a potential therapeutic strategy against ovarian cancer.

Magnetic resonance imaging-radiomics in endometrial cancer: a systematic review and meta-analysis

ObjectiveEndometrial carcinoma is the most common gynecological tumor in developed countries. Clinicopathological factors and molecular subtypes are used to stratify the risk of recurrence and to tailor adjuvant treatment. The...

The Role of MicroRNAs in Uterine Leiomyosarcoma Diagnosis and Treatment.

Uterine sarcomas are rare gynecological tumors arising from the myometrium or the connective tissue of the endometrium with a relatively poor prognosis. MicroRNAs (miRNAs) represent small, single-stranded, non-coding RNA molecules that can function as oncogenes or tumor suppressors under certain conditions. The current review aims at studying the role of miRNAs in uterine sarcoma diagnosis and treatment. In order to identify relevant studies, a literature review was conducted using the MEDLINE and LIVIVO databases. The search terms "microRNA" and "uterine sarcoma" were employed, and we were able to identify 24 studies published between 2008 and 2022. The current manuscript represents the first comprehensive review of the literature focusing on the particular role of miRNAs as biomarkers for uterine sarcomas. miRNAs were found to exhibit differential expression in uterine sarcoma cell lines and interact with certain genes correlating with tumorigenesis and cancer progression, whereas selected miRNA isoforms seem to be either over- or under-expressed in uterine sarcoma samples compared to normal uteri or benign tumors. Furthermore, miRNA levels correlate with various clinical prognostic parameters in uterine sarcoma patients, whereas each uterine sarcoma subtype is characterized by a unique miRNA profile. In summary, miRNAs seemingly represent novel trustworthy biomarkers for the diagnosis and treatment of uterine sarcoma.

Peritoneal carcinomatosis index and overall survival in patients taken to cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy.

The peritoneal carcinomatosis (PC) secondary to gastrointestinal or gynecological cancer has increased its incidence. It has a worse prognosis compared to other sites of metastasis. The peritoneal carcinomatosis index (PCI) establishes overall survival in patients with gastrointestinal or gynecological tumors and carcinomatosis. To evaluate the relationship of PCI to overall survival (OS) and recurrence-free survival (RFS) in patients treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). A descriptive, retrolective study of 80 charts of patients with CP was conducted. We included patients with colon, ovarian, appendicular, pseudomyxoma and gastric tumors with CP treated with CRS plus HIPEC. The OS and RFS were determined according to the type of adenocarcinoma and the degree of differentiation. The OS and RFS were determined in months in patients with PCI > 15 PCI as well as in patients with PCI < 15 considering the tumor of origin. Patients with ovarian tumors and pseudomyxoma with PCI < 15 presented OS > 70 months, compared to patients with gastric tumors (4 months). The PCI and histology are predictors of OS. Patients with ovarian tumors and PCI < 15 have higher OS, similar to pseudomyxomas. RFS was also higher in patients with PCI < 15.

Astragaloside IV suppresses the migration and EMT progression of cervical cancer cells by inhibiting macrophage M2 polarization through TGFβ/Smad2/3 signaling

Cervical cancer (CC) is a gynecological malignant tumor worldwide. Astragaloside IV (AS-IV) has been found to exert antitumor effects on CC. In addition, M2-polarized macrophages, known as tumor-associated macrophages (TAMs), play an important role in promoting cancer cell growth and angiogenesis. Thus, we explored the association between the antitumor effect of AS-IV and macrophage polarization in CC. Flow cytometry, ELISA, and RT‒qPCR assays were applied to detect the levels of CD163, IL-10, TGFβ, and CD206 in M2 macrophages with or without AS-IV treatment. In addition, conditioned medium (CM) was collected from these M2 macrophages, and CC cells were then cultured in various CMs. Wound healing and transwell assays were used to assess the migratory ability of CC cells. In this study, we found that AS-IV significantly inhibited M2 polarization of macrophages, as shown by decreased CD163, IL-10, TGFβ, and CD206 expression. In addition, compared with CM from M2 macrophages, CM from AS-IV-treated M2 macrophages notably inhibited angiogenesis, migration, and epithelial-mesenchymal transition (EMT) in CC cells. Furthermore, compared with CM from M2 macrophages, CM from AS-IV-treated M2 macrophages markedly reduced p-Smad2 and p-Smad3 protein expression in CC cells, and these changes were reversed by TGF-β treatment. Collectively, suppression of M2-like polarization of macrophages by AS-IV could prevent the migration and EMT of CC cells by inactivating TGF-β/Smad2/3 signaling. These findings might provide some theoretical support for exploring novel treatments for CC.

Expression Of Hippo-YAP Signaling Pathway in Gynecological Tumors

Ovarian cancer, breast cancer and cervical cancer are common female malignant tumors. YAP signal is widely activated in human malignant tumors. Hippo-YAP signal pathway affects the proliferation and development of tumors. However, the transmission mechanism of YAP signal in gynecological malignant tumors is still unclear. The function of YAP in the Hippo signal route is examined in this research, along with its functions upstream, middle, and downstream of the Hippo signal route. In addition, the mRNA expression data of YAP in ovarian serous cystadenocarcinoma and normal ovarian tissue is compared. The expression of YAP in breast invasive carcinoma (BRCA) is observed by IHC, and the YAP intensity of cytoplasm and nucleus is evaluated. Through the relationship between YAP and HPV, to further investigate the mechanism of YAP in cervical cancer, the distribution of YAP1 in cells adhering to the cervical surface was studied. These findings are critical in the treatment of YAP as a potential therapeutic target. Furthermore, understanding the role of YAP in female malignant tumors provide an insight in developing drugs that block the activity of YAP or inhibit the activation of YAP, they can play an anti-tumor role in vivo.

An autophagy-related diagnostic biomarker for uterine fibroids: FOS.

Uterine fibroids (UFs) are the most common benign gynecologic tumors in reproductive-aged women. The typical diagnostic strategies of UFs are transvaginal ultrasonography and pathological feature, while molecular biomarkers are considered conventional options in the assessment of the origin and development of UFs in recent years. Here, we extracted the differential expression genes (DEGs) and differential DNA methylation genes (DMGs) of UFs from the Gene Expression Omnibus (GEO) database, GSE64763, GSE120854, GSE45188, and GSE45187. 167 DEGs with aberrant DNA methylation were identified, and further Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed by the relevant R package. We next discerned 2 hub genes (FOS, and TNFSF10) with autophagy involvement by overlapping 167 DEGs and 232 autophagic regulators from Human Autophagy Database. FOS was identified as the most crucial gene through the Protein-Protein Interactions (PPI) network with the correlation of the immune scores. Moreover, the down-regulated expression of FOS in UFs tissue at both mRNA and protein levels was validated by RT-qPCR and immunohistochemistry respectively. The area under the ROC curve (AUC) of FOS was 0.856, with a sensitivity of 86.2% and a specificity of 73.9%. Overall, we explored the possible biomarker of UFs undergoing DNA-methylated autophagy and provided clinicians with a comprehensive assessment of UFs.

Human intravital microscopy in the study of sarcomas: an early trial of feasibility.

ClinicalTrials.gov, identifier NCT03517852; ClinicalTrials.gov, identifier NCT03823144.

Serum expression of tumor marker CA242 in patients with different gynecological diseases.

The aim of this study was to investigate the serum levels of CA242 in different types of gynecological diseases and its clinical significance. A total of 1021 patients with gynecological diseases and 499 healthy female controls were included in the study. The serum CA242 levels were detected and median value, -log10P value, and positive rate were calculated. Serum CA125 and HE4 levels of patients with ovarian lesions were measured, and the predictive value for ovarian cancer was statistically analyzed. Higher serum CA242 levels were observed in patients with mature teratoma, ovarian cancer, and other gynecological tumor diseases than in healthy controls. In contrast, the CA242 levels in patients with cervical intraepithelial neoplasia, uterine polyps, or endometrial hyperplasia were comparable to that of controls. Moreover, serum CA242 expression was increased in malignant uterine and ovarian diseases compared with benign ones (P<.05). Specifically, combining CA242, CA125, and HE4 yielded a higher area under the receiver operating characteristic curve than single biomarkers (P<.05). Heterogeneous increases in tumor marker CA242 expression levels are observed in different gynecological diseases, suggesting its potential value for clinical diagnosis.

Cinobufacini suppresses malignant behaviors of endometrial cancer by regulating NF-κB pathway

ABSTRACT Cinobufagin has inhibitory effects on various tumors, but there are few studies on gynecological tumors. This study explored the function and molecular mechanism of cinobufagin in endometrial cancer (EC). Different concentrations of cinobufagin treated EC cells (Ishikawa and HEC-1). Clone formation, methyl thiazolyl tetrazolium (MTT), flow cytometry, and transwell assays were used to detect malignant behaviors. A Western blot assay was performed to detect protein expression. Cinobufacini was sensitive to the inhibition of EC cell proliferation in a time- and concentration-dependent manner. Meanwhile, EC cell apoptosis was induced by cinobufacini. In addition, cinobufacini impaired the invasive and migratory abilities of EC cells. More importantly, cinobufacini blocked the nuclear factor kappa beta (NF-κB) pathway in EC by inhibiting p-IkBα and p-p65 expression. Cinobufacini suppresses malignant behaviors of EC by blocking the NF-κB pathway.

P16 expression in uterine cervical lesions and its role as diagnostic markers and clinical management

Background: Cervical cancer is one of the world's third most common gynecologic malignant tumors, especially in developing countries. This cancer is the most common cause of cancer-related death. High-risk human papillomavirus (HPV) is the main cause. p16 is a biological marker that can be used as a surrogate marker to increase diagnostic agreement for high-risk HPV infection. This study proved the differences in p16 expression in various age groups in low-grade cervical intraepithelial neoplasm (CIN), high-grade CIN, and squamous cell carcinoma (SCC). Methods: The research design was a cross-sectional analytic observational study, with a total sample of 40, taken from biopsy and surgery specimen patients diagnosed with CIN and SCC whose tissues were examined at the Anatomical Pathology Laboratory Faculty of Medicine Universitas Udayana/ Prof. dr. I G.N.G. Ngoerah General Hospital Denpasar. Histopathological diagnosis and determination of the type of cervical lesion were performed by Hematoxylin and Eosin (H&amp;E) staining. p16 expression was evaluated by immunohistochemistry. The results were analyzed using the chi-square test to prove differences in p16 expression in various age groups and the Kruskal-Wallis Test followed by the Mann-Whitney Test to prove differences in p16 expression in low-grade CIN, high-grade CIN and SCC, with a significance level of p &lt; 0.05. Results: The mean age of low-grade CIN was younger than high-grade CIN, which was 45.5±8.44 compared to 46.1±9.11. The mean age of low-grade and high-grade CIN is also younger than the mean age of SCC, which is 50.9±10.80. There was no significant difference in the expression of p16 in low grade CIN (p=0.34), high-grade CIN (p=0.45) and SCC (p=0.28) in various age groups. The expression of p16 was found significantly differ in all groups (p=0.011). Low-grade CIN significantly differed from high grade CIN (p=0.012) and SCC (p=0.008). However, we found same p16 expression in high-grade CIN and SCC (p = 0.866). Conclusion: p16 can be used as a screening method for diagnostic markers of high-risk HPV infection and a reference for planning therapy.

Application effect of perioperative nursing mediated by 3D printing and mind mapping in gynecological tumor laparoscopy

ABSTRACT Probing influence by perioperative nursing mediated by 3D printing and mind mapping in gynecological tumor laparoscopy. 90 subjects divided into three groups: A (n=30), B (n=30) and C (n=30). Each group was given a different type of nursing intervention postoperative recovery (postoperative anal gas exhausting time, eating time, hospital stay, leaving bed-time, and drainage tube extraction time) were compared among the three groups. Hamilton Anxiety Scale (HAMA)/Hamilton Depression Scale (HAMD), strategies Used by People to Promote Health (SUPPH), Generic quality-of-life Inventory (GQOLI-74) scores and complication rates were compared among the three groups. The postoperative recovery of group A and B was better than group C, and group A was better than group B (P<0.05). Post-intervening, HAMA/HAMD scorings within groups A/B reduced compared with group C, with group A＞group B (P<0.05). The complication rate of group A and B was lower than that of group C (P<0.05). Perioperative nursing mediated by 3D printing and mind mapping works well.

Abstract 512: Identification of SS008871, a novel Polθ inhibitor that effectively inhibits tumors with homologous recombination deficiency in vitro and in vivo

Abstract The repair of DNA double strand break (DSB) is crucial for genome stability and cell survival. There are three main DSB repair pathways: homologous recombination (HR), non-homologous end joining (NHEJ) and microhomology-mediated end joining (MMEJ). HR is a high-fidelity, error-free DSB repair pathway, and the dysfunction of HR confers cell genome instability and leads to tumorigenesis. HR deficiency is especially prevalent in gynecologic tumors, sharing about 10% population of all the gynecologic tumor patients. In situation of HR deficiency, MMEJ, in which DNA polymerase theta (Polθ) plays an essential role, is up-regulated to serve as a backup pathway for DSB repair. Several studies have proved that the inhibition of Polθ causes synthetic lethality with HR deficiency. Hence, Polθ emerges as a potential DNA damage repair target for the treatment of HR deficient tumors. Here we report a novel small molecular Polθ inhibitor, SS008871, which inhibits Polθ activity with an IC50 of 22 nM, and strongly inhibits cellular MMEJ pathway with an IC50 of single-digital nanomolar level. SS008871 strongly inhibits proliferation of HR deficient BRCA2-/- DLD-1 cells, and shows a &amp;gt;125× selectivity folds over DLD-1 parent cells as well as non-malignant cells. Besides, SS008871 elicits synergetic anti-proliferation activities in combination of a PARP inhibitor, olaparib on BRCA2-/- DLD-1 and MDA-MB-436 cells. In the BRCA2-/- DLD-1 xenograft model, SS008871 shows tumor growth inhibition as a single agent, and the combination of SS008871 and olaparib further results in tumor regression. Accordingly, the level of γH2AX, a common DSB marker, correlates well to the anti-tumor efficacy. In a human hematopoietic stem cells based in vitro hematotoxicity assay, SS008871 shows no significant inhibition on lineage-specific (myeloid, erythroid and megakaryocytic) cell differentiation and survival, suggesting the low hematotoxicity risk. In comparison, olaparib significantly attenuated hematopoietic stem cells on both differentiation and survival in the parallel assay, which is consistent with the hematological toxicity observed in human. Furthermore, there is no clinical abnormalities observed after a high dose treatment of SS008871 in mice, demonstrating that SS008871 is well-tolerated. Taken together, SS008871 is proved to be an encouraging Polθ inhibitor with good safety. Citation Format: Feng Zhou, Lu Liu, Lei Jiang, Feng Tang, Zhen Li, Wenqing Yang, Liting Xue, L Chen, Renhong Tang. Identification of SS008871, a novel Polθ inhibitor that effectively inhibits tumors with homologous recombination deficiency in vitro and in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 512.

Abstract 3239: Selective depletion of regulatory T cells by ALD2510, a novel IL-2-sparing anti-CD25 antibody, synergizes with PD-1 blockade in breast and gynecologic cancers

Abstract Background: PD-1 blockade (αPD-1) has shown limited efficacy in breast &amp; gynecologic cancers. In other types of solid tumor, regulatory T cells (Tregs) harbouring markers of highly suppressive effector Tregs (eTregs) correlates with poor responses to PD-1 blockade, prompting combination therapy based on eTregs depletion. Yet, subsets of Tregs remain to be determined in breast &amp; gynecologic cancers, in order to: (i) evaluate the role of eTregs in resistances to PD-1 blockade, (ii) identify the most selective target for eTregs depletion tailored to tumors context and combination strategy. Methods: We collected public single-cell RNA/TCR-sequencing data from primary tumors and metastases of Triple-Negative Breast Cancer patients (TNBC, N = 28) biopsied before and after αPD-1 (pembrolizumab). Microarray data from primary TNBC (N = 124) biopsied before and after αPD-1 were quired for association with clinical responses. Deep phenotyping of Tregs from normal breast tissues (N = 4) and primary breast tumors (N = 8) or gynecologic tumors (N = 17) was performed by mass cytometry. ALD2510 (αCD25NIB, Alderaan Biotechnology) is a novel non-IL-2 blocking Fc-optimized anti-CD25 mAb (1). αPD-1 and αCD25NIB combination was evaluated using: (i) a humanized αCD25NIB in CD34+ humanized NSG mice grafted with human TNBC cell lines, (ii) a murine surrogate of αCD25NIB in a syngeneic TNBC mouse model. Results: CD25high Tregs were accumulating in breast &amp; gynecologic tumor tissues. In TNBC patients treated with αPD-1, fractions of CD25high Tregs were further increased. CD25high Tregs highly expressed eTregs-related molecules in primary tumors, invaded tumor-draining lymph nodes and distant metastases. Amongst the potential therapeutic targets for Treg depletion, only CD25, 4-1BB and CCR8 were largely restricted to intratumoral CD25high eTregs. Yet, CD25 was the best candidate for CD25high eTregs depletion with limited on-target off-Treg effects, as: (i) CCR8 marked a small fractions of CD25high eTregs in primary tumors and was not detected in metastasis, (ii) 4-1BB marked antigen-experienced αβCD8 T cell revigorated by PD-1 blockade, (iii) only CD25high eTregs expressed 4-1BB and CCR8, yet TCR clonotype analysis revealed that CD25high eTregs originate in part from activated CD25+ Tregs, suggesting that anti-CCR8/-4-1BB mAbs may be ineffective due to CD25high eTregs replenishment in tumors. In murine models resistant to αPD-1 alone, αCD25NIB effectively depleted intratumoral CD25high eTregs, with limited effects on peripheral Tregs, and synergized with αPD-1 by restoring a positive effector αβCD8 T cells/Tregs ratio, leading to tumor clearance without adverse effects. Conclusions: This study supports clinical evaluation of CD25high effector Tregs depletion by ALD2510 in patients with breast or gynecologic cancers resistant to PD-1 blockade. Citation Format: Stéphane FATTORI, Aude Le Roy, Jemila Houacine, Lucie Robert, Riad Abes, Laurent Gorvel, Samuel Granjeaud, Marie-Sarah Rouvière, Amira Ben Amara, Nicolas Boucherit, Carole Tarpin, Jihane Pakradouni, Emmanuelle Charafe-Jauffret, Julien Barrou, Gilles Houvenaeghel, Eric Lambaudie, François Bertucci, Philippe Rochigneux, Anthony Gonçalves, Arnaud Foussat, Anne-Sophie Chrétien, Daniel Olive. Selective depletion of regulatory T cells by ALD2510, a novel IL-2-sparing anti-CD25 antibody, synergizes with PD-1 blockade in breast and gynecologic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3239.

Abstract 2164: Patterns of estrogen receptor expression across 18,500 tumor samples obtained from 149 cancer types

Abstract Estrogen receptor alpha (ER) is a nuclear transcription factor with a pivotal role in the function of the reproductive organs and of other organ systems. It constitutes a well-established therapeutic target for various small molecules. ER immunohistochemistry is used in surgical pathology for the distinction of tumors of the breast and gynecological organs. To comprehensively determine ER expression in normal and neoplastic tissues, a tissue microarray containing 18,560 samples from 149 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. ER positivity was found in 55 of 149 tumor categories, and 27 of these tumor categories contained at least one case with strong ER staining. ER positivity was most seen in various subtypes of breast cancer (78.9-95.7%) and in several different tumor categories of the ovary and the endometrium (8.5-75.9%). Other commonly ER positive tumor entities included leiomyoma (65.9%), neuroendocrine tumor of the appendix (43.8%), leiomyosarcoma (22.9%), Sertoli Leydig cell tumor of the ovary (1 of 3 positive), rhabdomyosarcoma (16.7%), angiomyolipoma (10%), colorectal neuroendocrine carcinoma (9.1%), myoepithelial carcinoma of the salivary gland (8.3%), granulosa cell tumor of the ovary (8.3%), epithelial-myoepithelial carcinoma of the salivary gland (7.7%), squamous cell carcinomas of various sites of origin (0.8-6.7%), testicular teratoma (5.3%), Brenner tumor of the ovary (5.1%), Ewing sarcoma (5%), adenocarcinoma NOS of the salivary gland (4.8%), papillary thyroid carcinoma (3.3%), sarcoma, not otherwise specified (NOS) (2.8%), paraganglioma (2.6%), non-invasive papillary urothelial carcinoma, pTa G3 (2.4%), pulmonary adenocarcinoma (2.1%), neuroendocrine tumor of the ileum (2.1%), and adenocarcinoma of the prostate, Gleason 5+5 (1.2%). Among 1,411 evaluable invasive breast carcinomas of no special type (NST), absent or low ER immunostaining was significantly linked to high BRE grade (p&amp;lt;0.0001), advanced pT stage (p&amp;lt;0.0001), distant metastasis (p=0.0012), HER2 overexpression and reduced progesterone receptor expression (p&amp;lt;0.0001 each) but not to nodal metastasis and patient survival. Among 378 high grade serous ovarian cancer, low ER immunostaining was linked to nodal metastasis (p=0.0112). Our data provide a comprehensive overview on the pattern of ER expression in cancer. The data show that ER expression predominated in gynecological and breast tumors. However, occasional (strong) ER expression can also occur in a broad variety of non-breast and non-gynecological neoplasms. Citation Format: Florian Viehweger, David Dum, Anne Menz, Ria Uhlig, Andrea Hinsch, Doris Hoeflmayer, Christoph Fraune, Christian Bernreuther, Patrick Lebok, Soeren Weidemann, Guido Sauter, Maximilian Lennartz, Frank Jacobsen, Till Sebastian Clauditz, Till Krech, Andreas H Marx, Ronald Simon, Stefan Steurer, Sarah Minner, Eike Burandt, Natalia Gorbokon. Patterns of estrogen receptor expression across 18,500 tumor samples obtained from 149 cancer types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2164.

Advances in the application of immune checkpoint inhibitors in gynecological tumors.

Immune checkpoints are regulatory molecules that suppress immune effector cells, and are essential for maintaining tolerance, preventing autoimmune reactions, and minimizing tissue damage by controlling the duration and intensity of the immune responses. However, immune checkpoints are frequently upregulated during cancer and dampen the anti-tumor immune responses. Immune checkpoint inhibitors (ICIs) have been effective against multiple tumors, and have improved patients' survival outcomes. Recent clinical trials have also reported promising therapeutic effects of ICIs in some gynecological cancers. To review the current research and future directions in the treatment of gynecological malignancies, including ovarian, cervical and endometrial cancers, using ICIs. Currently, cervical and ovarian cancers are the only gynecological tumors that are treated by immunotherapeutic approaches. In addition, ICIs, chimeric antigen receptor (CAR)- and T cell receptor (TCR)-engineered T cells targeting endometrial tumors, especially those originating in the vulva and fallopian tubes, are under development. Nevertheless, the molecular mechanism underlying the effects of ICIs, especially in combination with chemotherapy, radiation therapy, anti-angiogenesis drugs and poly ADP ribose polymerase inhibitors (PARPi), needs to be elucidated. Furthermore, novel predictive biomarkers have to be identified in order to increase the therapeutic efficacy of ICIs while reducing adverse reactions.

Nanoparticle-Based Combination Therapy for Ovarian Cancer.

Ovarian cancer is one of the most common malignant tumors in gynecology with a high incidence. Combination therapy, eg, administration of paclitaxel followed by a platinum anticancer drug is recommended to treat ovarian cancer due to its advantages in, eg, reducing side effects and reversing (multi)drug-resistance compared to single treatment. However, the benefits of combination therapy are often compromised. In chemo and chemo/gene combinations, co-deposition of the combined therapeutics in the tumor cells is required, which is difficult to achieve due to dramatic pharmacokinetic differences between combinational agents in free forms. Moreover, some undesired properties such as the low-water solubility of chemodrugs and the difficulty of cellular internalization of gene therapeutics also hinder the therapeutic potential. Delivery of dual or multiple agents by nanoparticles provides opportunities to tackle these limits. Nanoparticles encapsulate hydrophobic drug(s) to yield aqueous dispersions facilitating its administration and/or to accommodate hydrophilic genes facilitating its access to cells. Moreover, nanoparticle-based therapeutics can not only improve drug properties (eg, in vivo stability) and ensure the same drug disposition behavior with controlled drug ratios but also can minimize drug exposure of the normal tissues and increase drug co-accumulation at targeted tissues via passive and/or active targeting strategies. Herein, this work summarizes nanoparticle-based combination therapies, mainly including anticancer drug-based combinations and chemo/gene combinations, and emphasizes the advantageous outcomes of nanocarriers in the combination treatment of ovarian cancer. In addition, we also review mechanisms of synergetic effects resulting from different combinations.

RNA Sequencing of A2780 Cells Treated with CCL2 Identified Genes Associated with A2780 Cell Growth

Introduction: Ovarian cancer is a common gynecological malignancy. It is one of the leading causes of death among women worldwide. The incidence of ovarian cancer ranks third, and mortality is the first among gynecological malignant tumors. CCL2 (Chemokine C-C motif Ligand 2) is associated with the progression of a variety of tumors, including ovarian cancer. However, the mechanism of CCL2 in A2780 cell growth has not been clarified. Method: In this study, we found that exogenous CCL2 promoted A2780 cell activity. RNA sequencing was used to identify the transcriptomic changes in CCL2-treated A2780 cells. Based on a p-value less than 0.05 and |log2 Fold Change| greater than 1, 190 differentially expressed genes were selected. Of these genes, 82 were observed to be upregulated and 108 downregulated. Result: The GO (gene ontology) analysis of differentially expressed genes was used to identify the underlying functions and biological processes. In addition, the expression of the topmost upregulated genes was verified by qPCR. Conclusion: This work may provide new markers and reveal the underlying mechanism of exogenous CCL2 in A2780 cell proliferation.

Physician compliance with multidisciplinary tumor board recommendations for managing gynecological cancers.

Aims: Evaluation of compliance with gynecological multidisciplinary tumor board (MTB) recommendations and its impact. Patients & methods: All patient records discussed in our MTB from 2018 to 2020 were analyzed. Results: We analyzed 437 MTB recommendations concerning 166 patients. Each patient was discussed an average of 2.6 (1.0-4.2) times. Of the 789 decisions, the decision was not followed 102 times (12.9%), corresponding to 85 MTB meetings (19.5%). Of these, 72 recommendations concerned therapeutic changes (70.5%), and 30 concerned non-therapeutic changes (29.5%). Of these 85 MTB decisions, 60 (71%) led to a new MTB submission. Noncompliance with MTB decisions decreased the overall survival (46 vs 138months; p=0.003). Conclusion: Improving compliance with MTB decisions is crucial to enhance patient outcomes.