Female Malignant Tumors Research Articles

Identification of 10 differentially expressed genes involved in the tumorigenesis of cervical cancer via next-generation sequencing.

The incidence and mortality of cervical cancer remain high in female malignant tumors worldwide. There is still a lack of diagnostic and prognostic markers for cervical carcinoma. This study aimed to screen differentially expressed genes (DEGs) between normal and cervical cancer tissues to identify candidate genes for further research. Uterine cervical specimens were resected from our clinical patients after radical hysterectomy. Three patients' transcriptomic datasets were built by the next generation sequencing (NGS) results. DEGs were selected through the edgeR and DESeq2 packages in the R environment. Functional enrichment analysis, including GO/DisGeNET/KEGG/Reactome enrichment analysis, was performed. Normal and cervical cancer tissue data from the public databases TCGA and GTEx were collected to compare the expression levels of 10 selected DEGs in tumor and normal tissues. ROC curve and survival analysis were performed to compare the diagnostic and prognostic values of each gene. The expression levels of candidate genes were verified in 15 paired clinical specimens via quantitative real-time polymerase chain reaction. There were 875 up-regulated and 1,482 down-regulated genes in cervical cancer samples compared with the paired adjacent normal cervical tissues according to the NGS analysis. The top 10 DEGs included APOD, MASP1, ACKR1, C1QTNF7, SFRP4, HSPB6, GSTM5, IGFBP6, F10 and DCN. GO, DisGeNET and Reactome analyses revealed that the DEGs were related to extracellular matrix and angiogenesis which might influence tumorigenesis. KEGG enrichment showed that PI3K-Akt signaling pathway might be involved in cervical cancer tumorigenesis and progression. The expression levels of selected genes were decreased in tumors in both the public database and our experimental clinical specimens. All the candidate genes showed excellent diagnostic value, and the AUC values exceeded 0.90. Additionally, APOD, ACKR1 and SFRP4 expression levels could help predict the prognosis of patients with cervical cancer. In this study, we selected the top 10 DEGs which were down-regulated in cervical cancer tissues. All of them had dramatically diagnostic value. APOD, ACKR1 and SFRP4 were associated with the survivals of cervical cancer. C1QTNF7, HSPB6, GSTM5, IGFBP6 and F10 were first reported to be candidate genes of cervical carcinoma.

Establishment of predictive models and determinants of preoperative gastric retention in endoscopic retrograde cholangiopancreatography.

Study on influencing factors of gastric retention before endoscopic retrograde cholangiopancreatography (ERCP) background: With the wide application of ERCP, the risk of preoperative gastric retention affects the smooth progress of the operation. The study found that female, biliary and pancreatic malignant tumor, digestive tract obstruction and other factors are closely related to gastric retention, so the establishment of predictive model is very important to reduce the risk of operation. To analyze the factors influencing preoperative gastric retention in ERCP and establish a predictive model. A retrospective analysis was conducted on 190 patients admitted to our hospital for ERCP preparation between January 2020 and February 2024. Patient baseline clinical data were collected using an electronic medical record system. Patients were randomly matched in a 1:4 ratio with data from 190 patients during the same period to establish a validation group (n = 38) and a modeling group (n = 152). Patients in the modeling group were divided into the gastric retention group (n = 52) and non-gastric retention group (n = 100) based on whether gastric retention occurred preoperatively. General data of patients in the validation group and modeling group were compared. Univariate and multivariate logistic regression analyses were performed to identify factors influencing preoperative gastric retention in ERCP patients. A predictive model for preoperative gastric retention in ERCP patients was constructed, and calibration curves were used for validation. The receiver operating characteristic (ROC) curve was analyzed to evaluate the predictive value of the model. We found no statistically significant difference in general data between the validation group and modeling group (P > 0.05). The comparison of age, body mass index, hypertension, and diabetes between the two groups showed no statistically significant difference (P > 0.05). However, we noted statistically significant differences in gender, primary disease, jaundice, opioid use, and gastrointestinal obstruction between the two groups (P < 0.05). Multivariate logistic regression analysis showed that gender, primary disease, jaundice, opioid use, and gastrointestinal obstruction were independent factors influencing preoperative gastric retention in ERCP patients (P < 0.05). The results of logistic regression analysis revealed that gender, primary disease, jaundice, opioid use, and gastrointestinal obstruction were included in the predictive model for preoperative gastric retention in ERCP patients. The calibration curves in the training set and validation set showed a slope close to 1, indicating good consistency between the predicted risk and actual risk. The ROC analysis results showed that the area under the curve (AUC) of the predictive model for preoperative gastric retention in ERCP patients in the training set was 0.901 with a standard error of 0.023 (95%CI: 0.8264-0.9567), and the optimal cutoff value was 0.71, with a sensitivity of 87.5 and specificity of 84.2. In the validation set, the AUC of the predictive model was 0.842 with a standard error of 0.013 (95%CI: 0.8061-0.9216), and the optimal cutoff value was 0.56, with a sensitivity of 56.2 and specificity of 100.0. Gender, primary disease, jaundice, opioid use, and gastrointestinal obstruction are factors influencing preoperative gastric retention in ERCP patients. A predictive model established based on these factors has high predictive value.

Functions and mechanisms of RNA m6A regulators in breast cancer (Review).

Breast cancer (BC) is a major malignant tumor in females and the incidence rate of BC has increased worldwide in recent years. N6‑methyladenosine (m6A) is a methylation modification that occurs extensively in eukaryotic RNA. The abnormal expression of m6A and related regulatory proteins can activate or inhibit certain signal pathways or oncogenes, thus affecting the proliferation, metastasis and prognosis of BC. Numerous studies have shown that m6A regulator disorder exists in BC, and this disorder can be reversed. Therefore, m6A is predicted as a potential therapeutic target for BC. However, the molecular mechanism of m6A RNA methylation regulating the occurrence and development of BC has not been comprehensively elucidated. In this review article, the functions of various m6A regulators and the specific mechanisms of certain regulators of the progress of BC were summarized. Furthermore, the dual role of RNA methylation in tumor progression was discussed, concluding that RNA methylation can not only lead to tumorigenesis but at times give rise to inhibition of tumor formation. In addition, further comprehensive analysis on mechanisms of m6A regulators in BC is conducive to screening effective potential targets and formulating targeted treatment strategies, which will provide new methods for the prevention and treatment of BC.

The mechanism and therapeutic potential of lncRNA MIR497HG/miR-16-5p axis in breast cancer

BackgroundBreast cancer has become a major public health problem in the current society, and its incidence rate ranks the first among Chinese female malignant tumors. This paper once again confirmed the efficacy of lncRNA in tumor regulation by introducing the mechanism of the diagnosis of breast cancer by the MIR497HG/miR-16-5p axis.MethodsThe abnormal expression of MIR497HG in breast cancer was determined by RT-qPCR method, and the correlation between MIR497HG expression and clinicopathological characteristics of breast cancer patients was analyzed via Chi-square test. To understand the diagnostic potential of MIR497HG in breast cancer by drawing the receiver operating characteristic curve (ROC). The overexpressed MIR497HG (pcDNA3.1-MIR497HG) was designed and constructed to explore the regulation of elevated MIR497HG on biological function of BT549 and Hs 578T cells through Transwell assays. Additionally, the luciferase gene reporter assay and Pearson analysis evaluated the targeting relationship of MIR497HG to miR-16-5p.ResultsMIR497HG was decreased in breast cancer and had high diagnostic function, while elevated MIR497HG inhibited the migration and invasion of BT549 and Hs 578T cells. In terms of functional mechanism, miR-16-5p was the target of MIR497HG, and MIR497HG reversely regulated the miR-16-5p. miR-16-5p mimic reversed the effects of upregulated MIR497HG on cell biological function.ConclusionsIn general, MIR497HG was decreased in breast cancer, and the MIR497HG/miR-16-5p axis regulated breast cancer tumorigenesis, providing effective insights for the diagnosis of patients.

Screening of postoperative adjuvant chemotherapy-related serum metabolic markers in breast cancer patients based on 1H NMR metabonomics.

Breast cancer (BC) has the highest incidence rate among female malignant tumors. Adjuvant chemotherapy is commonly used to reduce micrometastasis in postoperative patients. However, monitoring the efficacy of chemotherapy in BC is a major challenge in clinical practice. In this study, 1H nuclear magnetic resonance (NMR) metabonomics was performed to explore the serum metabolic characteristics of BC patients before and after adjuvant chemotherapy. In this study, we collected serum samples from 51 healthy controls and 61 BC patients before and after chemotherapy for 1H NMR metabolomic analysis, and tested the performance of each metabolite and combination segment by the receiver operating characteristic (ROC) curves. Nine metabolites, namely glutamine, citrate, creatine, glycerophosphatidylcholine/phosphatidylcholine, glycine, 1-methylhistidine, lactate, pyruvate and formate had significant changes in BC patients before chemotherapy compared with healthy controls. Lactate, pyruvate, 1-methylhistidine and formate were found to be inversely regulated by chemotherapy. ROC analysis showed that a combination of the four metabolites had good prediction for chemotherapy efficacy with area under the curve of 0.958, sensitivity of 98.36% and specificity of 91.30%. There was no significant correlation between chemotherapy-related metabolites and clinical indicators of cancer patients, indicating that they can be used to evaluate the chemotherapy efficacy of patients with different clinical indicators. Effectively, dynamic and non-invasive metabolic markers for the evaluation of the efficacy of chemotherapy were identified in this study.

Prediction of CCL2 in breast cancer based on enhanced MRI radiomics model with integrated bioinformatics analysis and machine learning.

e12509 Background: Breast cancer is the most common malignant tumor in women. According to the 2023 Cancer Statistics Report, breast cancer has surpassed lung cancer to become the most common malignant tumor. Its incidence and mortality both rank first among female malignant tumors. This study proposes non-invasive prediction of CCL2 mRNA expression in breast cancer tissue through enhanced MRI radiomics, while integrating bioinformatics analysis to explore the underlying molecular mechanisms and their association with the immune microenvironment. Methods: Excluding criteria were applied to select primary solid tumor samples with RNA-seq data (n = 840) from the TCGA-BRCA database. Enhanced MRI imaging data (n = 98) intersecting with the TCGA-BRCA data were obtained from TCIA-BRCA. The imaging data were randomly divided into training (n = 70) and testing sets (n = 28) in a 7:3 ratio. A feature subset was selected, and a model was constructed using the support vector machine (SVM) algorithm in the training set. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and the Hosmer-Lemeshow goodness-of-fit test. The calibration of the radiomics prediction model was assessed using the Brier score, and the clinical utility of the radiomics prediction model was demonstrated by drawing decision curves (DCA). External validation of the model was performed using a validation set. The radiomics score (RS) was calculated using the LR radiomics model and categorized as a binary variable (Low/High RS). Subsequently, KEGG pathway, immune-related genes, and gene mutation analysis were conducted based on the CCL2 high and low expression levels. Results: A total of 1810 radiomic features were obtained with ICC values ≥ 0.75. Subsequently, the mRMR (Maximum relevance, minimum redundancy) method, and the optimal 7 feature subsets were further identified using the RFE (Recursive feature elimination) algorithm. The SVM model demonstrated favorable predictive performance, with an AUC value of 0.822 for the training set and 0.779 for the validation set, as indicated by the ROC curve. Calibration curve and Hosmer-Lemeshow goodness-of-fit test revealed good consistency between the radiomic predictive model for the probability of high gene expression and the actual values (P &gt; 0.05). Additionally, the decision curve analysis (DCA) demonstrated high clinical utility of the model. The TNF-α signaling pathway was found to influence the occurrence and development of breast cancer. Furthermore, the degree of Plasma Cell infiltration was observed to be highest in breast cancer. Conclusions: The CCL2 model constructed using a combination of machine learning and radiomic features, can non-invasively predict the prognosis of breast cancer treatment and exhibits good generalizability.

The Role of Traditional Chinese Medicine in the Management of Cervical Cancer.

Globally, cervical cancer poses a substantial public health challenge, with low and middle-income countries bearing the highest burden [Rajkhowa, P., D.S. Patil, S.M. Dsouza, P. Narayanan and H. Brand. Evidence on factors influencing HPV vaccine implementation in South Asia: a scoping review. Glob. Public Health 18: 2288269, 2023]. The incidence rate ranks second highest among female malignant tumors in China, following only breast cancer. The prognosis of advanced cervical cancer is extremely poor, with a 5-year progression-free survival (PFS) rate of only 15%, and the treatment of advanced recurrent or metastatic cervical cancer remains a huge challenge. An increasing amount of evidence suggests that traditional Chinese medicine (TCM) can significantly enhance sensitivity to chemotherapeutic drugs, strengthen antitumor effects, and notably improve adverse reactions associated with cancer such as fatigue and bone marrow suppression. In recent years, the therapeutic effects and mechanisms of Chinese herbal medicines, such as the Guizhi-Fuling-decoction, the compound Yangshe granule, Huangqi, and Ginseng, herbal monomers (e.g., Ginsenoside Rh2, Tanshinone IIA, and Tetrandrine), and the related extracts and compound formulations, have received extensive attention for the treatment of cervical cancer. This paper reviews the research progress of TCM in cervical cancer. In addition, we reported a case of an advanced cervical cancer patient with multiple abdominal and pelvic metastasis who initially received chemotherapy, was then treated with TCM alone, and subsequently survived for 22 years. The model of whole-process management with TCM can enable more cancer patients to obtain longer survival periods.

Drug resistance in breast cancer is based on the mechanism of exocrine non-coding RNA.

Breast cancer (BC) ranks first among female malignant tumors and involves hormonal changes and genetic as well as environmental risk factors. In recent years, with the improvement of medical treatment, a variety of therapeutic approaches for breast cancer have emerged and have strengthened to accommodate molecular diversity. However, the primary way to improve the effective treatment of breast cancer patients is to overcome treatment resistance. Recent studies have provided insights into the mechanisms of resistance to exosome effects in BC. Exosomes are membrane-bound vesicles secreted by both healthy and malignant cells that facilitate intercellular communication. Specifically, exosomes released by tumor cells transport their contents to recipient cells, altering their properties and promoting oncogenic components, ultimately resulting in drug resistance. As important coordinators, non-coding RNAs (ncRNAs) are involved in this process and are aberrantly expressed in various human cancers. Exosome-derived ncRNAs, including microRNAs (miRNAs), long-noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), have emerged as crucial components in understanding drug resistance in breast cancer. This review provides insights into the mechanism of exosome-derived ncRNAs in breast cancer drug resistance, thereby suggesting new strategies for the treatment of BC.

Discovery of ganoderic acid A (GAA) PROTACs as MDM2 protein degraders for the treatment of breast cancer

Breast cancer is one of the most common female malignant tumors, with triple-negative breast cancer (TNBC) being the most specific, highly invasive, metastatic and associated with a poor prognosis. Our previous study showed that the natural product ganoderic acid A (GAA) has a certain affinity for MDM2. In this study, two series of novel GAA PROTACs C1–C10 and V1–V10 were designed and synthesized for the treatment of breast cancer. The antitumor activity of these compounds was evaluated against four human tumor cell lines (MCF-7, MDA-MB-231, SJSA-1, and HepG2). Among them, V9 and V10 showed stronger anti-proliferative effects against breast cancer cells, and V10 showed the best selectivity in MDA-MB-231 cells (TNBC), which was 5-fold higher than that of the lead compound GAA. Preliminary structure-activity analysis revealed that V-series GAA PROTACs had better effects than C-series, and the introduction of 2O–4O PEG linkers could significantly improve the antitumor activity. Molecular docking, surface plasmon resonance (SPR), cellular thermal shift assay (CETSA), and Western blot researches showed that both V9 and V10 could bind with MDM2, and degrade the protein through the ubiquitin-proteasome system. Molecular dynamics simulation (MD) revealed that V10 is a bifunctional molecule that can bind to von Hippel-Lindau (VHL) at one end and target MDM2 at the other. In addition, V10 promoted the upregulation of p21 in p53-mutant MDA-MB-231 cells, and induced apoptosis via down-regulation of the bcl-2/bax ratio and the expression of cyclin B1. Finally, in vivo experiments showed that, V10 also exhibited good tumor inhibitory activity in xenografted TNBC zebrafish models, with an inhibition rate of 27.2% at 50 μg/mL. In conclusion, our results suggested that V10 has anti-tumor effects on p53-mutant breast cancer in vitro and in vivo, and may be used as a novel lead compound for the future development of TNBC.

Mechanism of regulation of KIF23 on endometrial cancer cell growth and apoptosis

ObjectiveThe global incidence of endometrial cancer, a malignant tumor in females, is on the rise. It is one of the most common gynecological cancers. Early-stage endometrial cancers can often be treated successfully with uterine extirpation. However, those diagnosed at a later stage have a poor prognosis and encounter treatment challenges. Therefore, additional research is necessary to develop primary prevention strategies for high-risk women and improve survival rates among patients with endometrial cancer. Hence, gene therapy targeting KIF23 shows promise as an advanced strategy for the treatment of endometrial cancer.MethodsImmunohistochemistry, Western blotting, and PCR were used to examine the expression of KIF23 and its associated pathway factors in endometrial cancer tissue (specifically Ishikawa and SNGM cells, respectively). We investigated the functional roles of KIF23 using CCK-8, colony-forming proliferation assays, Transwell migration assays, and xenotransplantation in mice.ResultsImmunohistochemistry analysis showed variations in the expression levels of KIF23 between endometrial cancer tissue and normal endometrium tissue. KIF23 downregulated BAX and caspase-3 protein expression while upregulating BCL-2 protein expression. Additionally, knocking out KIF23 inhibits endometrial cancer cell proliferation and migration while promoting cell death. Mechanistically, our study provides evidence that KIF23 promotes endometrial cancer cell proliferation by activating the ERK and AKT/PI3K pathways, while simultaneously inhibiting programmed cell death in endometrial cancer.ConclusionOur study provides evidence to support the inhibition of endometrial cancer by KIF23 knockdown. This offers valuable insights for future research on potential therapeutic strategies for this type of cancer.Graphical

Molecular mechanisms and therapeutic applications of huaier in breast cancer treatment.

Breast cancer is one of the most common female malignant tumors today and represents a serious health risk for women. Although the survival rate and quality of life of patients with breast cancer are improving with the continuous development of medical technology, metastasis, recurrence, and drug resistance of breast cancer remain a significant problem. Huaier, a traditional Chinese medicine (TCM) fungus, is a type of Sophora embolism fungus growing on old Sophora stems. The polysaccharides of Trametes robiniophila Murr (PS-T) are the main active ingredient of Huaier. There is increasing evidence that Huaier has great potential in breast cancer treatment, and its anti-cancer mechanism may be related to a variety of biological activities, such as the inhibition of cell proliferation, metastasis, tumor angiogenesis, the promotion of cancer cell death, and regulation of tumor-specific immunity. There is growing evidence that Huaier may be effective in the clinical treatment of breast cancer. This review systematically summarizes the basic and clinical studies on the use of Huaier in the treatment of breast cancer, providing useful information to guide the clinical application of Huaier and future clinical studies.

Application of Three-dimensional Coding Network in Screening and Diagnosis of Cervical Precancerous Lesions

Globally, the incidence of cervical cancer ranks fourth among female malignant tumors, seriously threatening the physical and mental health of women. Early detection and early treatment can greatly reduce the mortality of cervical cancer "cytology /HPV test, colposcopy and cervical biopsy" is the main method for clinical diagnosis of cervical cancer. The progress of medical technology has significantly improved the early diagnosis of cervical cancer, but due to various factors, there are still many cases of missed diagnosis and misdiagnosis. In recent years, artificial intelligence has developed rapidly in the medical field, and has also shown good applicability in the screening and diagnosis of cervical cancer. In this paper, we design an mcs-SEM structure that contains both channels and space compression excitation modules, which can retain comprehensive spatial information at a low computational cost. Then, the structure is embedded in a three-dimensional coding network to realize the combination of two-dimensional convolutional neural network and three-dimensional spatial information, so as to predict the DVH in the complex distribution scenario of multi-endangered organs with higher accuracy.

Development of monoclonal antibodies targeting Her-2 and EGFR in the treatment of breast cancer

Breast cancer is the highest incidence of female cancer malignant tumors, the global incidence of breast cancer is about 12%, and the mortality rate is about 7%. For patients with breast cancer, surgery, radiotherapy, chemotherapy, targeted therapy, endocrine therapy, and immunotherapy are often used. Throughout history, monoclonal antibodies have revolutionized the breast cancer treatment patients. Her-2 and EGFR antibodies have been particularly important. Cetuximab and panizumab can block EGFR ligand binding, thereby preventing EGFR from functioning. Trastuzumab and pertuzumab are anti-Her-2 monoantibodies that have been clinically proven to be effective. Although endocrine therapy and anti-Her-2 targeted therapy have achieved certain results, these treatments are effective for all patients and have certain side effects. This paper examines the effects of five specific monoclonal antibodies on breast cancer, including benefits, drawbacks, and side effects, using clinical trial materials and academic papers published since 2001. This paper emphasizes Her-2 antibodies and breast cancer, as well as the role of specific Her-2 and EGFR antibodies.

Deep Learning-Assisted Intelligent Artificial Vision Platform Based on Dual-Luminescence Eu(III)-Functionalized HOF for the Diagnosis of Breast and Ovarian Cancer.

Developing an advanced analytical method to detect spermine (Spm) and N-acetylneuraminic acid (NANA), the biomarkers of breast and ovarian cancers, respectively, is critical for the early diagnosis of the two cancers, which is very meaningful for women's health. Here, a deep learning-assisted artificial vision platform based on a dual-emission ratiometric fluorescence sensor is first constructed to monitor Spm and NANA. The ratiometric fluorescence sensor (Eu@TCBP-HOF, 1) can selectively detect Spm with high sensitivity based on "Turn-on" mode. After adding Spm, the new ratiometric fluorescence sensor (1-Spm, named 2) shows high sensitivity for NANA with "Turn-off" mode. Moreover, the fluorescence sensors can achieve an obvious fluorescence color response to Spm and NANA. Even in real saliva and serum samples, 1 and 2 still show high sensitivity and color responsiveness with limit of detection (LODs) of 0.5 μM for Spm and 0.96 μM for NANA. In virtue of different fluorescence responses, the DenseNet algorithm of deep learning assists the fluorescence sensors, which can simulate the human visual systems to identify fluorescence images and distinguish the concentration of Spm and NANA within 1 s with over 99% recognition accuracy. The intelligent artificial vision platform developed in this work may provide a prospective analytical method for the early diagnosis of female malignant tumors.

Diagnosis of Benign and Malignant BI-RADS 4 Breast Masses by Contrastenhanced Ultrasound Combined with Shear Wave Elastography.

Breast cancer, one of the most prevalent malignant tumors in females, usually occurs in the breast epithelial tissues. The study aimed to explore the diagnostic value of contrast-enhanced ultrasound (CEUS) combined with shear wave elastography (SWE) in the diagnosis of benign and malignant breast masses in BI-RADS (Breast Imaging Reporting and Data System) 4. Examination outcomes and clinical information of 83 patients with BI-RADS 4 breast masses were analyzed retrospectively. These included patients who received CEUS, SWE, and pathological examinations. The difference of CEUS in determining the classification of BI-RADS 4 breast masses was evaluated using histopathological outcomes of breast masses as a reference standard. The diagnostic value of CEUS, SWE, and CEUS combined with SWE in the diagnosis of benign and malignant breast masses in BI-RADS 4 was also explored. Pathological biopsy results revealed 63 malignant masses and 20 benign masses among 83 BI-RADS 4 breast masses, with a 75.9% incidence of malignant masses. After the diagnosis of BI-RADS 4 breast masses with CEUS, SWE, and CEUS+SWE, the incidence of malignancy was 56.6%, 78.3%, and 73.5%, respectively. CEUS+SWE showed higher sensitivity (93.7% vs. 81% and 68.3%), specificity (90% vs. 30% and 80%), positive predictive value (96.7% vs. 78.5% and 91.5%), negative predictive value (81.8% vs. 33.3% and 44.4%), and diagnostic coincidence rate (92.8% vs. 68.7% and 71.1%) than SWE and CEUS alone in diagnosing pathological type of breast masses. Moreover, CEUS combined with SWE exhibited a larger area under the receiver operating characteristic (ROC) curve (0.918) than SWE (0.741, p = 0.028) and CEUS (0.555, p < 0.001) alone in the diagnosis of BI-RADS 4 breast masses. Overall, the diagnostic value of CEUS+SWE for the pathological type of BI-RADS is preferred over CEUS and SWE alone. CEUS+SWE showed higher values than CEUS and SWE alone in diagnosing BI-RADS 4 breast masses. Specifically, CEUS+SWE can correctly identify benign and malignant masses, reduce unnecessary trauma, and avoid misdiagnosis. In summary, CEUS combined with SWE can serve as an effective diagnostic method and avoid delaying the best treatment opportunity for some malignant lesions.

Tamoxifen induces ferroptosis in MCF-7 organoid.

Breast cancer is the most common female malignant tumor type globally. The occurrence and development of breast cancer involve ferroptosis, which is closely related to its treatment. The development of breast cancer organoids facilitates the analysis of breast cancer molecular background and tumor biological behavior, including clinical pathological characteristics, drug response, or drug resistance relationship, and promotes the advancement of precision treatment for breast cancer. The three-dimensional (3D) cell culture of breast cancer MCF-7 organoid is more similar to the in vivo environment and thus obtains more realistic results than 2D cell culture. Our study examined the new mechanism of tamoxifen in treating breast cancer through breast cancer MCF-7 organoids. We used 3D cells to culture breast cancer MCF-7 organoid, as well as tamoxifen-treated MCF-7 and tamoxifen-resistant MCF-7 (MCF-7 TAMR) cells. We used transcriptome sequencing. We detected GPX4 and SLC7A11 protein levels using Western blotting and the content of ATP, glutathione, and ferrous ions using the Cell Counting Lite 3D Kit. We assessed cell viability using the Cell Counting Kit-8 (CCK-8) assay. Tamoxifen significantly inhibited the growth of MCF-7 organoids and significantly induced ferroptosis in MCF-7 organoids. The ferroptosis inhibitor reversed the significant tamoxifen-induced MCF-7 organoid inhibition activity. Moreover, the ferroptosis activator enhanced the tamoxifen-induced MCF-7 TAMR cell activity inhibition. Our study revealed that ferroptosis plays an important role in tamoxifen-induced MCF-7 organoid cell death and provides a new research idea for precise treatment of breast cancer through an organoid model.

Breast intervention device for low-field MRI with a customized unilateral coil

With the incidence of breast cancer rising to the top among female malignant tumors, magnetic resonance images guided breast biopsy intervention and minimally invasive treatment have developed as a clinically practical research issue. High field studies have shown the diagnostic value of breast MRI, but the examination costs greatly exceed those of competing conventional mammography. In this case, low-field MRI cannot merely provide typical MRI contrast, but also significantly reduce the cost of diagnosis and treatment for breast cancer patients. This work describes a unilateral breast coil and prototype intervention device, which provides a customized solution for low-field MRI-guided breast intervention. Results demonstrate that the low-field MRI breast intervention device facilitates medical intervention procedures. And the designed positioning device can locate the target lesion within 2–3 mm accuracy. Phantom tests with the customized unilateral coil indicate that the open loops perform as well as the 4-channel commercial closed breast coil, presenting a relatively good SNR (signal-to-noise ratio) and uniformity characteristics. MR scanning images of the volunteer breast using the breast intervention coil also show high SNR, which lays a foundation for further implementation of image-guided breast interventional minimally invasive surgery with the low-field MRI system.

Genome-wide perturbations of A-to-I RNA editing dysregulated circular RNAs promoting the development of cervical cancer

Cervical cancer, the second most common female malignant tumor, seriously threatens women's health and lives. Despite the availability of the HPV vaccine, effective treatment options for cervical cancer are still lacking. New research perspectives now clarify that RNA editing dysregulation and changes in circRNA expression are jointly involved in disease pathogenesis, so molecular changes associated with circRNA and RNA editing may provide clues for the development of new therapeutic strategies for cervical cancer. In this study, we designed a series of pipelines to identify and analyze dysregulated RNA editing events in circRNAs. Our findings indicate a decrease in A-to-I RNA editing levels in cervical cancer compared to normal tissues, and editing may influence the back-splicing process of circRNAs through structural modifications of Alu elements. Moreover, our research reveals that RNA editing could modulate circRNA biogenesis by influencing RNA binding protein (RBP) binding on a transcriptome-wide scale, as well as influence the expression and coding potential of circRNAs. Importantly, we identified three RNA editing sites that could serve as potential biomarkers. In summary, our study presents a comprehensive landscape of RNA editing perturbations in circRNAs, providing new insights into the complex relationship between RNA editing and circRNA dysregulation in cervical cancer.

Knockdown of LIMD2 inhibits the progression of ovarian carcinoma through ERK1/2 pathway.

The incidence rate of ovarian carcinoma (OC) is the third of the female reproductive system malignant tumors, while its mortality rate ranks first among causes of female reproductive system tumor related death in the world. In the present research, we investigated the specific role of LIMD2 through LIMD2 knockdown in OC cells. The results of online analysis and expression detection proved that LIMD2 was up-regulated in human OC tissues and cells. Knockdown of LIMD2 inhibited the proliferation, migration and invasion in OC cells. LIMD2 knockdown promoted the apoptosis, as well as the expression of Cleaved-Caspase3 and Bax. Importantly, knockdown of LIMD2 promotes cell autophagy. LC3-II/I ratio and Beclin1 expression increased in LIMD2 knockdown cells, while P62 expression declined in LIMD2 knockdown cells. Additionally, the phosphorylation of ERK1/2 was inhibited by the knockdown of LIMD2 in SKOV3 and OVCAR3 cells. Knockdown of LIMD2 inhibits cell proliferation, migration, invasion and autophagy, and promotes the apoptosis through the ERK1/2 signaling pathway, suggesting that LIMD2-siRNA may be an effective molecule to prevent OC progression.

ERCC6L facilitates the onset of mammary neoplasia and promotes the high malignance of breast cancer by accelerating the cell cycle

BackgroundBreast cancer (BC) is the leading cause of morbidity and the second leading cause of death among female malignant tumors. Although available drugs have been approved for the corresponding breast cancer subtypes (ER-positive, HER2+) currently, there are still no effective targeted drugs or treatment strategies for metastatic breast cancer or triple-negative breast cancer that lack targets. Therefore, it is urgent to discover new potential targets. ERCC6L is an essential protein involved in chromosome separation during cell mitosis. However, the effect of ERCC6L on the tumorigenesis and progression of breast cancer is unclear.Methods and resultsHere, we found that ERCC6L was highly expressed in breast cancer, especially in TNBC, which was closely related to poor outcomes of patients. An ERCC6L conditional knockout mouse model was first established in this study, and the results confirmed that ERCC6L was required for the development of the mammary gland and the tumorigenesis and progression of mammary gland cancers. In in vitro cell culture, ERCC6L acted as a tumor promoter in the malignant progression of breast cancer cells. Overexpression of ERCC6L promoted cell proliferation, migration and invasion, while knockdown of ERCC6L caused the opposite results. Mechanistically, ERCC6L accelerated the cell cycle by regulating the G2/M checkpoint signalling pathway. Additionally, we demonstrated that there is an interaction between ERCC6L and KIF4A, both of which are closely related factors in mitosis and are involved in the malignant progression of breast cancer.ConclusionsWe first demonstrated that ERCC6L deficiency can significantly inhibit the occurrence and development of mammary gland tumors. ERCC6L was found to accelerate the cell cycle by regulating the p53/p21/CDK1/Cyclin B and PLK/CDC25C/CDK1/Cyclin B signalling pathways, thereby promoting the malignant progression of breast cancer cell lines. There was a direct interaction between KIF4A and ERCC6L, and both are closely associated with mitosis and contribute to growth and metastasis of breast tumor. To sum up, our results suggest that ERCC6L may be used as a promising target for the treatment of BC.