BackgroundBreast cancer (BRCA) remains a leading cause of cancer-related mortality among women worldwide. The kinesin family member 5B (KIF5B) has been implicated in various cancers, yet its comprehensive role in BRCA prognosis, tumor microenvironment (TME), and therapeutic response remains poorly understood.MethodsWe integrated single-cell RNA sequencing (scRNA-seq) data and bulk RNA-seq data from multiple datasets. Using hdWGCNA, we identified gene modules related to the unfolded protein response (UPR). Consensus clustering defined UPR-related molecular subtypes, and differential expression analysis revealed key prognostic genes. KIF5B was further evaluated for its prognostic significance, mutational landscape, immune infiltration associations, and potential as a therapeutic target.ResultsMalignant cell-specific KIF5B upregulation drives poor overall survival in pan-cancer cohorts, validating its hazardous molecular function. Functional enrichment analysis linked KIF5B to critical pathways, including immune response, JAK-STAT signaling, and epithelial-mesenchymal transition. Immune infiltration analysis revealed that high KIF5B expression was associated with reduced immune and ESTIMATE scores, but higher tumor purity. Drug sensitivity prediction identified several compounds with potential efficacy in high KIF5B-expressing patients, including Sapitinib and LCL161.ConclusionOur multimodal analysis establishes KIF5B as a prognostic biomarker and potential therapeutic target in BRCA, with implications for understanding immune evasion and guiding precision treatment strategies.

Introduction:Triple-negative breast cancer (TNBC) is a highly aggressive subtype with limited therapeutic options. Reprogramming the tumor immune microenvironment (TIME) has emerged as a promising strategy for breast cancer treatment, and tumor-associated macrophages, the most abundant and heterogeneous immune cells in the solid TIME, play a pivotal role in this process. This study aimed to investigate the TNBC-specific TIME. Methods:Multiplex fluorescence immunohistochemistry and bioinformatic analyses were employed to map the immune landscape and predict potential regulatory mechanisms. These predictions were subsequently validated using in vitro cellular assays and in vivo mouse models. The unique lipid metabolic signature of TNBC was integrated with its distinct immune contexture to identify key regulators. Results:The oxysterol metabolite 25-hydroxycholesterol (25HC) was identified as a key regulator of macrophage polarization. Specifically, we discovered that an aberrantly activated interferon regulatory factor 7-cholesterol-25-hydroxylase-25HC axis in TNBC cells potently inhibits CD163+ macrophage polarization. Discussion:To our knowledge, this is the first study to delineate the link between dysregulated 25HC metabolism within the TIME and the control of macrophage polarization. These findings provide novel insights into the immunometabolic mechanisms underlying TNBC aggressiveness and reveal a potential therapeutic target for this devastating disease.

Inhibitor of differentiation 4 (ID4) is a highly conserved DNA-binding inhibitory protein of mammals, and its main role is to bind basic helix-loop-helix (b-HLH) so that it loses its DNA-binding activity, which in turn regulates the transcription of key genes, regulating cell differentiation and proliferation as the physiological function. Breast tissue is a highly heterogeneous tissue organ with a strong capacity for remodeling and differentiation, and studies of breast carcinogenesis suggest that the mechanisms regulating the differentiation of breast tissue interact critically with tumorigenesis. The expression level of ID4 and its regulatory mechanism play a crucial role in the study of breast cancer, but its oncogenic or oncostatic role has not yet been unanimously identified, and its regulatory mechanism in breast cancer still needs to be further elucidated. This review summarizes and analyzes the relevant studies of ID4 and the research progress in breast cancer, integrating the development of breast tissue and tumorigenesis with the regulatory role of ID4, to provide some insights into develop new treatment strategies and diagnostic biomarkers.

ContextAnaplastic thyroid cancer (ATC) is a relatively rare and extensively malignant kind of thyroid carcinoma. The poor prognosis and high mortality rate of ATC can be attributed to its invasive features and undifferentiated phenotype. At present, there is a lack of efficacious therapeutic options. In light of the elevated fatality rate, it is vital to possess a comprehensive comprehension of the scientific terrain pertaining to ATC. To gather the perspectives of different researchers about the topic of ATC treatment, we did a bibliometric network analysis, which offers a comprehensive view of the scholarly literature.MethodologyA systematic search was conducted on the WoSCC database to identify publications pertaining to ATC treatment between the years 2000 and 2023. In this bibliometric investigation, the tools VOSviewers, CiteSpace, and the R package “bibliometrix” were employed to investigate the general attributes, developmental framework, and academic frontiers of the subject matter.Results1223 publications in total, written by 6937 scholars from 53 areas and 1402 institutions and published in 358 scholarly journals, were analyzed. There has been a gradual increase in the quantity of publications pertaining to ATC treatment. The United States and China emerged as the most prominent nations. The University of Texas MD Anderson Cancer Center and Memorial Sloan Kettering Cancer Counseling Center are prominent research institutions in highly productive countries. The journal Thyroid holds a prominent position within its discipline, being widely recognized as both the most popular and highly co-cited publication. According to the available data, Maria Cabanillas has authored the highest number of published articles, while RC Smallridge has received the highest number of co-citations. It turned out that the prevailing keywords encompassed expression, therapy, apoptosis, survival, activation, proliferation, metastasis, and other related terms. Immunotherapy, targeted therapy, and prognostic factors are the emerging research hotspots and trends.ConclusionsThis paper presents a complete overview of research trends and advancements in the treatment of ATC using bibliometric analysis. The acquisition of information will offer vital insights for funding and potential creative strategies in researching the treatment of ATC, which indicates the research frontiers as well as prevalent directions in recent years.

Triple-negative breast cancer (TNBC) is currently the type of breast cancer with the worst prognosis; it lacks specific treatments, such as ER/PR antagonistic endocrine and anti-HER2 targeted therapies. Although immunotherapy with immune checkpoints has shown some efficacy in many solid tumors, clinical data in TNBC suggest significant limitations. The essence of ferroptosis is the impaired metabolism of intracellular lipid oxides, which in turn causes the activation and abnormalities of the immune system, including ROS, and not only plays an important role in liver injury and organ aging but also a large amount of data points to the close correlation between the ferroptosis process and tumor development. In this study, through the analysis of large-throughput biological data of breast tumors, combined with the characteristics of the biological process of ferroptosis, the specific gene IDH2 was found to be significantly highly expressed in TNBC and functionally correlated with ferroptosis. Through clinical specimens validated at the gene and protein levels, in vitro tumor cell line validation, and in vivo mouse models, we found that the high expression of IDH2 in TNBC has a role in inhibiting the ferroptosis process in TNBC, thus promoting the proliferation of TNBC cells and other malignant features.

Coiled-coil domain-containing protein 69 (CCDC69) is a novel gene and limited knowledge in known in breast cancer. In the present study, we aimed to explore the relationship between CCDC69 and breast cancer, demonstrate the clinicopathological significance and prognostic role of CCDC69 in breast cancer, and analyze the possible mechanism of CCDC69 affecting the prognosis of breast cancer. First, from GEO database, TIMER, GEPIA, and OncoLnc, we select CCDC69 as the potential gene which closely involved in breast cancer progression. Next, by real-time PCR detection, the expression of CCDC69 in breast cancer tissue was notably lower than that in normal breast tissues (p=0.0002). In addition, our immunohistochemistry (IHC) indicated that the positive expression rate of CCDC69 in the triple-negative breast cancer (TNBC) was lower than that in the non-TNBC (p=0.0362), and it was negatively correlated with the expression of Ki67 (p=0.001). Further enrichment analysis of CCDC69 and the similar genes performed on FunRich3.1.3 revealed that these genes were significantly associated with fat differentiation, and most of them were related to peroxisome proliferator-activated receptor (PPAR) signal pathway. Collectively, our findings suggest that CCDC69 is down regulated in breast cancer tissue especially in TNBC which has higher malignant grade and poorer clinical prognosis.

Objective:To establish the xenografts in chicken chorioallantonic membrane (CAM) model with sorafenib-induced drug-resistant hepatocellular carcinoma cell lines.Methods:Applying continuity induction in vitro to obtain hepatocellular carcinoma sorafenib resistant cell lines. Using chicken CAM model to gain xenografts tumors in vivo. Exploring the characteristics of xenografts tumors, analyzing the expression of related target genes and signaling pathway included. For statistical analyses, t-test was used, and the results were considered significant at P<0.05. Results:Sorafenib-resistant HepG2 cell line was screened, named sHepG2, which half maximal inhibitory concentration (IC 50) [(88.7±7.6) μmol/ml] was higher than that of HepG2 significantly ( t=16.416, P<0.01). 5 cases of chick CAM models of HepG2 and sHepG2 cells were established respectively, and the xenograft tumor formation rate was 70% [(3+ 4)/(5+ 5)]. The fresh weight of xenograft tumors in HepG2 group [(0.093 2±0.012 2) g] was significantly lighter than that in sHepG2 group ( t=3.709, P<0.05). ComparedsHepG2 with HepG2, the expression of phosphoinositide 3-kinase (PI3K) ( t=9.336, P<0.01) and phospho-protein kinase B (p-Akt) ( t=7.123, P<0.01) werehigher, while phosphatase and tensin homolog deleted on chromosome ten (PTEN) ( t=6.164, P<0.01) and fibroblast growth factor receptor 1 (FGFR1) ( t=6.297, P<0.01), lowersignificantly. Conclusion:The establishment of sorafenib-induced HepG2 drug-resistant cell lines in vitro, the constructing xenografts in chicken CAM model with HepG2 drug-resistant cells, the exploration growth of xenografts tumors and relative protein expressions indicate that the chicken CAM model could be useful for HCC sorafenib-resistant research in vivo.

Coiled-coil domain-containing protein 69 (CCDC69) is a novel gene and limited knowledge in known in breast cancer. In the present study, we aimed to explore the relationship between CCDC69 and breast cancer, demonstrate the clinicopathological significance and prognostic role of CCDC69 in breast cancer, and analyze the possible mechanism of CCDC69 affecting the prognosis of breast cancer. First, from GEO database, TIMER, GEPIA, and OncoLnc, we selected CCDC69 as the potential gene which closely involved in breast cancer progression. Next, by real-time PCR detection, the expression of CCDC69 in breast cancer tissue was notably lower than that in normal breast tissues (p=0.0002). In addition, our immunohistochemistry indicated that the positive expression rate of CCDC69 in the triple-negative breast cancer (TNBC) was lower than that in the non-TNBC (p=0.0362), and it was negatively correlated with the expression of Ki67 (p=0.001). Further enrichment analysis of CCDC69 and the similar genes performed on FunRich3.1.3 revealed that these genes were significantly associated with fat differentiation, and most of them were related to peroxisome proliferator-activated receptor (PPAR) signal pathway. Collectively, our findings suggest that CCDC69 is down regulated in breast cancer tissue especially in TNBC which has higher malignant grade and poorer clinical prognosis.

Objective:To establish a primary cell tumor model of breast cancer and investigate the effects of intermediate-conductance calcium-activated potassium channel (KCa3.1) expression on proliferation and tumor angiogenesis of breast cancer in vivo. Methods:Twenty-three fresh tissue samples of invasive breast cancer were collected during clinical operations. Twenty-two primary cell tumor models of breast cancer in nude mice were established.Nude mice were randomly divided into experimental group (eleven cases, siRNA interference) and control group (eleven cases, negative control). Cholesterol modified small interfering RNA (siRNA) was synthesized and its transfection efficiency was identified. The effects of KCa3.1 on the proliferation and angiogenesis of breast cancer was detected in vivo. Results:Designed siRNA1 and siRNA2 could effectively interfere with KCa3.1 in primary breast cancer cells. The interference efficiency detected by Western blotting was (71.03±9.97)% and (65.81±9.18)% ( t=21.034, 20.883, P<0.05) respectively. Twenty-two BALB/c nude mice models of primary breast cancer cells were established successfully, and the tumorigenicity rate was 70.96%. The interference efficiency of KCNN4 was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in tumorigenic tissues. The expression of KCNN4 mRNA in Chol-siRNA group was significantly lower than that in the control group ( t=6.541, P<0.05). The expression of tumor cytokines in the tumor tissue was detected by immunohistochemistry. The positive expression rate of VEGF was (43.42±7.89)% in the control group and (13.19±4.32)% in the siRNA group ( t=11.146, P<0.05). The positive rate of CD31 was (17.49±4.15)% in the control group and (9.28±5.86)% in the siRNA group ( t=3.792, P<0.05). The positive expression rate of proliferating cell nuclear antigen (Ki-67) was (88.77±7.61)% in the control group and (58.17±9.62)% in the siRNA group ( t=8.274, P<0.05). Conclusion:KCa3.1 participates in the regulation of cell proliferation and tumor angiogenesis in breast cancer. The verification of the inhibition on tumor formation induced by intervening KCa3.1 was accomplished in vivo.

目的 比较Dunhill术、全切术与次全切术治疗双侧结节性甲状腺肿的临床价值.方法 回顾性分析2016年1月至2019年6月收治的325例双侧结节性甲状腺肿患者的病例资料,根据术式不同,将全切术治疗的患者纳入全切组(102例),将次全切术治疗的患者纳入次全切组(108例),将Dunhill术治疗的患者纳入Dunhill组(115例).采用SPSS 25.0软件包校对全组数据,手术相关指标等计量资料以(珋x±s)描述,多组间比较采用方差分析;临床疗效、并发症、复发情况等计数资料用频数(n)、率(％)描述,行χ2检验,P<0.05为差异有统计学意义.结果 三组治疗总有效率及术后6个月复发率比较,差异无统计学意义(P>0.05);与全切组相比,Dunhill组手术时间较长、术中出血量较多、住院时间较短,Dunhill组和次全切组术后并发症总发生率较高,Dunhill组手术时间比次全切组短,差异有统计学意义(P<0.05).结论 相比甲状腺次全切术与Dunhill术,甲状腺全切术在治疗双侧结节性甲状腺肿时复发率及术后并发症发生率较低,但对患者甲状腺功能影响较大.而Dunhill术可有效兼顾治疗有效性及安全性,在实际临床工作中,可结合患者需要而谨慎选择.

BACKGROUNDWith the significant improvement of the cure rate and survival rate of cancer patients, the survivors face quality-of-life problems, such as a significant decline in reproductive system development, ovarian reserves and function, and even fertility loss and early menopause. These problems are often highly associated with chemotherapy-induced ovarian damage in cancer treatment. However, there are no ideal treatment strategies at present. In our attempt to develop reagents and approaches for delaying ovarian aging and protecting chemotherapy-induced ovarian injury, we recently found that metformin may be the most promising drug to protect female malignant tumor patients from chemotherapy-induced ovarian injury. This trial aims to test whether administration of metformin during chemotherapy can protect the normal ovarian function of patients with early breast cancer.METHODSThis study is prospective, randomized, double-blind and placebo-controlled. Female patients with early breast cancer (N = 314) will be randomly assigned to two groups (placebo, metformin 2000 mg). Metformin will be administered during and after chemotherapy for patients with stage I-IIIa breast cancer. The primary outcome will be the menstruation recovery rate 12 months after chemotherapy, defined as recovery of menstruation twice in a row within 1 year. Patients will be followed up for 5 years to observe long-term ovarian function and prognosis, such as overall survival (OS), objective response rate (ORR), and disease-free survival (DFS). Quality of life and safety will also be assessed.DISCUSSIONOur research will provide a new treatment strategy for fertility protection, and clinical treatment guidance for cancer patients.

目的:探究miR-429在乳腺癌干性维持中所发挥的作用,并探索miR-429对乳腺癌干细胞体内成瘤能力的影响.方法:无血清悬浮培养法用于培养经流式细胞仪分选得到的CD44+CD24-表型乳腺癌细胞系干细胞MCF-7-S、SKBR3-S、MDA-MB-231-S及乳腺正常上皮干细胞MCF-10A-S,实时荧光定量聚合酶链式反应(qRT-PCR)用于检测miR-429在上述4株干细胞中的表达.将包含miR-429的重组慢病毒质粒及其阴性对照空载体质粒vector分别以病毒:细胞数量为15:1的比例感染MDA-MB-231细胞,经2.0 μg/mL嘌呤霉素筛选,成功构建稳定表达miR-429或vector的MDA-MB-231细胞,经流式分选出上述两株稳转细胞株的CD44+CD24-表型干细胞MDA-MB-231-Svector和MDA-MB-231-SmiR-429.无血清悬浮培养后,镜下观察过表达miR-429对肿瘤球形成能力的影响,流式细胞术检测过表达miR-429对CD44+CD24-表型细胞亚群比例的影响,Western Blot检测过表达miR-429对乳腺癌干细胞干性相关因子ALDH1、SOX2和Bmi1蛋白表达的影响,将MDA-MB-231-Svector和MDA-MB-231-SmiR-429干细胞分别注射到BALB/c裸鼠右侧胸壁第二对乳腺脂肪垫中,构建乳腺癌干细胞裸鼠移植瘤模型,观察过表达miR-429对裸鼠体内成瘤能力的影响.结果:与MCF-10A-S相比,miR-429在MCF-7-S、SKBR3-S和MDA-MB-231-S细胞系中的表达水平均异常降低,其中,miR-429在MDA-MB-231-S细胞中表达最低(P＜0.05).与MDA-MB-231-Svector细胞相比,经流式分选后的CD44+CD24-表型MDA-MB-231-SmiR-429干细胞形成的肿瘤球的大小和数量、分选时CD44+CD24-表型细胞亚群的比例、ALDH1、SOX2和Bmi1的蛋白表达水平以及裸鼠体内成瘤的体积和重量均显著降低(P＜0.05).结论:miR-429可降低乳腺癌干细胞的干性和体内成瘤能力,其可能是抑制乳腺癌转移和耐药的关键分子.

Objective To study the expression of KCa3.1 in mammary carcinoma,and its function on cell proliferation and apoptosis in vitro and in vivo.Methods Western blotting was used to detect the expression level of KCa3.1 in various mammary carcinoma cell lines.Immunofluorescence was used to detect the expression and localization of KCa3.1 in cells.Methyl thiazol tetrazolium (MTT) assay was used to research regulation function of KCa3.1 on cell proliferation of mammary carcinoma.Flow cytometry was used to study the function of KCa3.1 on apoptosis of mammary carcinoma.Immunohistochemistry and TdT-mediated dUTP nick end labeling (TUNEL) were used to detect the effect of KCa3.1 on proliferation and apoptosis of mammary carcinoma.Results The expression of KCa3.1 was confirmed in MDA-MB-231 and MCF7,but not in T-47D.The KCa3.1 protein was localized in the plasma membrane of mammary carcinoma cells.Proliferation and apoptosis of mammary carcinoma cells were induced by intervening KCa3.1 in vitro [MDA-MB-231 apoptosis rate:at 48 h tetraethylammonium-34 (TRAM-34),(17.29 ± 2.14) ％,1-EBIO (35.32 ± 3.74) ％,Control (8.41 ± 1.31) ％;at 72 h TRAM-34 (27.47 ± 5.74) ％,1-EBIO (57.62 ± 5.94) ％,Control (9.43 ± 2.12) ％].The activation of KCa3.1 induced by channel opener 1-EBIO could reduce the proliferation and activate the apoptosis of mammary tumor tissues in vivo [apoptosis rate:1-EBIO (11.34 ± 4.75) ％,Control (23.92 ± 5.96) ％].Conclusion KCa3.1 was involved in the regulation of proliferation and apoptosis in mammary carcinoma cells.The verification of the inhibition on tumor formation induced by intervening KCa3.1 was accomplished in vivo.

Treatments for triple-negative breast cancer (TNBC) are limited; intermediate-conductance calcium-activated potassium (SK4) channels are closely involved in tumor progression, but little is known about these channels in TNBC. We aimed to investigate whether SK4 channels affect TNBC. First, by immunohistochemistry (IHC) and western blotting (WB), increased SK4 protein expression in breast tumor tissues was detected relative to that in non-tumor breast tissues, but there was no apparent expression difference between various subtypes of breast cancer (p>0.05). Next, functional SK4 channels were detected in the TNBC cell line MDA-MB-231 using WB, real-time PCR, immunofluorescence and patch-clamp recording. By employing SK4 specific siRNAs and blockers, including TRAM-34 and clotrimazole, in combination with an MTT assay, a colony-formation assay, flow cytometry and a cell motility assay, we found that the suppression of SK4 channels significantly inhibited cell proliferation and migration and promoted apoptosis in MDA-MB-231 cells (p<0.05). Further investigation revealed that treatment with epidermal growth factor (EGF)/basic fibroblast growth factor (bFGF) caused MDA-MB-231 cells to undergo the epithelial-mesenchymal transition (EMT) and to show increased SK4 mRNA expression. In addition, the down-regulation of SK4 expression inhibited the EMT markers Vimentin and Snail1. Collectively, our findings suggest that SK4 channels are expressed in TNBC and are involved in the proliferation, apoptosis, migration and EMT processes of TNBC cells.