BACKGROUND: To date, results on relationship between CYP3A4 gene polymorphism were limited and inconclusive, and no study focused on the influence of CYP3A4 gene-obesity interaction on breast cancer risk, especially in Chinese women. The purpose of this study was to evaluate the impact of four single nucleotide polymorphisms (SNPs) of CYP3A4 gene, the SNP-SNP and gene-environment interactions on the susceptibility to breast cancer in Chinese women. METHODS: Logistic regression was used to explore the relationship between four SNPs of CYP3A4 gene and the risk of breast cancer. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best SNP-SNP and gene-abdominal obesity interaction combinations among four SNPs and abdominal obesity. Haplotype examination among 4 SNPs was conducted using the SHEsis web-based platform. RESULTS: Logistic regression analysis showed that carriers of rs2242480- T allele have significantly higher breast cancer risk, than those with rs2242480- CC genotype, adjusted OR (95%CI) was 1.68 (1.23-2.16) and 2.03 (1.53-2.58) for participants with CT genotype and TT genotype under additive model. We did not find any notable interactions between the four SNPs within the CYP3A4 gene. GMDR model found a significant association in a two-locus model involving rs2242480 and obesity, with a p-value of 0.018. Stratified analysis found that breast cancer risk was the highest in obese participants with rs2242480- CT or TT genotype, compared to those non-obese participants with rs2242480- CC genotype, OR (95%CI) was 3.02 (1.83-4.25). We found that all haplotype combinations were not correlated with breast cancer risk. CONCLUSIONS We found that the T allele of rs2242480 within the CYP3A4 gene and interaction between rs2242480 and obesity were associated with an increased risk of breast cancer. However, the results of this study were only applicable to the Han ethnic group and cannot be generalized to other ethnic groups in China, and more SNPs of CYP3A4 gene should been enrolled in the analysis in the future, to verify the results obtained in this study.
Adult ; Aged ; Female ; Humans ; Middle Aged ; Breast Neoplasms/etiology* ; China/epidemiology* ; Cytochrome P-450 CYP3A/metabolism* ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Haplotypes ; Obesity/epidemiology* ; Polymorphism, Single Nucleotide ; Risk Factors ; East Asian People

OBJECTIVE: To explore the application value of dual chamber round tissue expander in immediate breast reconstruction. METHODS: Sixteen patients, who had been provided immediate tissue expander/implant two-stage breast reconstruction using dual chamber round tissue expander in our hospital from March 2022 to October 2023, were involved in this study, and the relevant information was analyzed retrospectively. The overall design of the expander is a round shape, consisting of two equally divided semi-circular chambers. The two expansion chambers are connected by a silicone pad below and are respectively connected to their own water injection tubes. Both chambers are designed to expand unidirectionally towards the surface. The expansion principle, insertion process, and type of expander selection were investigated. The expansion effect and incidence of complications were summarized. The aesthetic effect of reconstructed breasts was evaluated from three aspects after stage Ⅱ surgery: the position of infra mammary fold, the breast protrusion, and the breast volume. RESULTS: Among sixteen patients in this study, three patients were selected with the type of 400 mL expander and thirteen patients were given the type of 600 mL expander. The median time of tissue expansion was 4.0 (2.0, 5.0) months, with an average volume of expansion of (538.8±111.7) mL. The average expansion ratio of upper/lower chamber was 45.4%±8.4%. The position of the infra mammary fold needed not to be adjusted during the prosthesis exchange process. All the patients were applied anatomical prostheses, and the median volume of the prosthesis was 395 (345, 410) mL. One patient developed seroma during expansion period, who got improved after local aspiration. The average follow-up time was (9.0±3.6) months. 81.3% (13/16) of the patients achieved an aesthetic evaluation of "Good" in breast reconstruction, and 75.0% (12/16) of the patients got a grade Ⅰ or grade Ⅱ capsule contracture of the prosthesis. CONCLUSION The application of dual chamber round tissue expander could effectively dilate the lower pole of the breast, personalize the expansion ratio of the upper and lower poles of the breast, and avoid the displacement of the expander during the expansion period. Therefore, it could provide a good foundation for subsequent prosthesis exchange.
Humans ; Tissue Expansion Devices ; Female ; Mammaplasty/instrumentation* ; Tissue Expansion/instrumentation* ; Retrospective Studies ; Adult ; Middle Aged ; Breast Neoplasms/surgery* ; Breast Implants ; Mastectomy

OBJECTIVE: To explore the effect of concurrent administration of goserelin for ovarian function protection on the pathological complete response (pCR) rate and objective response rate (ORR) of neoadjuvant chemotherapy (NAC) in young breast cancer patients. METHODS: The study enrolled breast cancer patients aged 18-45 with clinical stages ⅡA~ⅢC from January 2016 to May 2020. According to patients' willingness, they were divided into two groups: Those who chose to receive goserelin to protect ovarian function during NAC (goserelin group) and those who did not (chemotherapy group). The pCR rate and ORR were compared between the two groups, and subgroup analysis was conducted for patients with different molecular subtypes. RESULTS: A total of 93 patients were included in this study (31 in the goserelin group and 62 in the chemotherapy group). After propensity score weighting (PSW) adjustment, baseline data such as age, preoperative clinical stage, postoperative pathological stage, pa-thological type, hormone receptor status, human epidermal growth factor receptor 2 (HER2) and Ki-67 expression, molecular subtypes, and chemotherapy regimens were well-matched between the two groups. There was no significant difference in the pCR rate between the goserelin group and the chemotherapy group, with rates of 29.0% and 25.8%, respectively (P=0.741). Similarly, there was no significant difference in ORR between the two groups (90.3% vs. 87.1%, P=0.746). Subgroup analysis revealed that among the patients with hormone receptor-positive tumors, there were no significant differences in pCR rate (6.3% vs. 7.7%, P=0.852) or ORR (87.5% vs. 82.1%, P=0.839) between the goserelin and chemotherapy groups. Among the patients with hormone receptor-negative tumors, there were also no significant differences in pCR rate (53.3% vs. 56.5%, P=0.847) or ORR (93.3% vs. 95.7%, P=0.975) between the two groups. One year after the completion of chemotherapy, the incidence of chemotherapy-induced amenorrhea (CIA) was significantly lower in the goserelin group compared with the chemotherapy group (9.5% vs. 33.3%, P=0.036). CONCLUSION For young breast cancer patients with clinical stages of ⅡA~ⅢC, there was no statistical difference in pCR rate and ORR whether or not using goserelin during NAC. However, it is still necessary to expand the sample size and carry out a longer follow-up to evaluate the effect of goserelin on the long-term survival of young patients.
Humans ; Goserelin/administration & dosage* ; Female ; Breast Neoplasms/pathology* ; Neoadjuvant Therapy/methods* ; Adult ; Middle Aged ; Young Adult ; Adolescent ; Chemotherapy, Adjuvant ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Antineoplastic Agents, Hormonal/therapeutic use* ; Treatment Outcome ; Receptor, ErbB-2

OBJECTIVE: To explore the potential apoptotic mechanisms of 3 Morchella extracts (Morchella conica, Morchella esculenta and Morchella delicosa) on breast and colon cancer cell lines using apoptotic biomarkers. METHODS: Human breast cell line (MCF-7) and colon cancer cell line (SW-480) were treated with methanol and ethanol extracts of 3 Morchella species with concentration ranging from 0.0625 to 2 mg/mL. After that their effects on gene expression of apoptosis related markers (pro-apoptotic markers including Bax, caspase-3, caspase-7, and caspase-9, and the antiapoptotic marker including Bcl-2) were determined using reverse transcription polymerase chain reaction. RESULTS: All Morchella extracts reduced breast and colon cancer cells proliferation at half inhibitory concentration (IC₅₀) of 0.02 ±0.01 to 0.68 ±0.30 mg/mL. As expected, all Morchella extracts significantly increased gene expressions of Bax, caspase-3, caspase-7, and caspase-9 and downregulated the gene expression of Bcl-2 in MCF-7 and SW-480 cell lines (P<0.05). CONCLUSIONS Morchella extracts demonstrated significant anti-proliferative activity against breast and colon cancer cell lines via an apoptosis induction mechanism. Anticancer activity of Morchella extracts and activation of apoptosis in breast and colon cancer cells suggest that it may be used to develop chemotherapeutic agents against cancer in future.
Humans ; Apoptosis/genetics* ; Colonic Neoplasms/drug therapy* ; Breast Neoplasms/drug therapy* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Plant Extracts/pharmacology* ; Gene Expression Regulation, Neoplastic/drug effects* ; MCF-7 Cells ; Ascomycota/chemistry*

OBJECTIVE: To entrap carvacrol (CAR) in bovine serum albumin nanoparticles (BSANPs) to form CAR-loaded BSANPs (CAR@BSANPs) and to explore the anti-cancer effects in breast adenocarcinoma cells (MCF-7 cells) treated with CAR and CAR@BSANPs. METHODS: A desolvation method was used to synthesize BSANPs and CAR@BSANPs. The BSANPs and CAR@BSANPs were characterized by several physicochemical methods, including visual observation, high-resolution field emission scanning electron microscopy, Fourier transform infrared spectroscopy, and high-performance liquid chromatography. MCF-7 cells were used and analyzed after 24 h of exposure to CAR and CAR@BSANPs at half-maximal inhibitory concentration. The anti-proliferative, apoptotic, reactive oxygen species (ROS), and nitric oxide (NO) scavenging activity as well as gene expression analysis were investigated by the cell viability assay, phase-contrast microscopy, 2',7'-dichlorofluorescein-diacetate assay, Griess-Illosvoy colorimetric assay, and quantitative real-time polymerase chain reaction, respectively. RESULTS: CAR and CAR@BSANPs showed anti-proliferative, apoptotic, ROS generation, and NO scavenging effects on MCF-7 cells. Expression profile of B-cell lymphoma 2-like 11 (BCL2L11), vascular endothelial growth factor A (VEGFA), hypoxia inducible factor factor-1α (HIF1A), BCL2L11/apoptosis regulator (BAX), and BCL2L11/Bcl2 homologous antagonist/killer 1 (BAK1) ratios revealed downregulated genes; and BAX, BAK1, and CASP8 were upregulated by CAR and CAR@BSANPs treatment. In vitro anticancer assays of the CAR and CAR@BSANPs showed that CAR@BSANPs demonstrated higher therapeutic efficacy in the MCF-7 cells than CAR. CONCLUSIONS CAR and CAR@BSANPs affect gene expression and may subsequently reduce the growth and proliferation of the MCF-7 cells. Molecular targeting of regulatory genes of the MCF-7 cells with CAR and CAR@BSANPs may be an effective therapeutic strategy against breast cancer.
Humans ; Cymenes ; Nanoparticles/ultrastructure* ; MCF-7 Cells ; Breast Neoplasms/genetics* ; Apoptosis/drug effects* ; Serum Albumin, Bovine/chemistry* ; Monoterpenes/therapeutic use* ; Adenocarcinoma/genetics* ; Cell Proliferation/drug effects* ; Reactive Oxygen Species/metabolism* ; Female ; Cell Survival/drug effects* ; Animals ; Gene Expression Regulation, Neoplastic/drug effects* ; Nitric Oxide/metabolism* ; Cattle

OBJECTIVES: The traditional processing method for paraffin-embedded tissues is time-consuming, while the ultrasonic rapid processing method has a short processing time. However, its effects on tissue proteins, DNA, and RNA remain unclear. This study aims to evaluate the effects of the ultrasonic rapid processing method on proteins, DNA, and RNA in paraffin-embedded tissues through hematoxylin and eosin (HE) staining, immunohistochemical staining, and molecular pathological detection. METHODS: Surgical specimens from patients with breast cancer, colorectal cancer, lung cancer, signet-ring cell gastric cancer, liver cancer, and other tumors were selected. Two tissue blocks (1 to 3 mm in diameter) were obtained from each specimen (previously processed and diagnosed by routine pathology). One block was assigned to the control group (traditional processing method), and the other was the experimental group (ultrasonic rapid processing method). Via HE staining, immunohistochemical staining, DNA quality fragment analysis, fluorescent in situ hybrid for HER2 gene expression test, second-generation sequencing for EGFR and ALK gene mutation test, real-time reverse transcription PCR (real-time RT-PCR) for prognosis detection of breast cancer etc, the difference between 2 groups was compared, and further impact of the ultrasonic rapid processing method was analyzed. RESULTS: Compared with the control group, the ultrasound-assisted rapid method efficiently completed fixation, dehydration, clearing, and paraffin embedding, significantly reducing sample preparation time before pathological diagnosis. Results of HE staining, immunohistochemistry, DNA fragment analysis, fluorescence in situ hybridization for HER2 gene, next-generation sequencing for EGFR and ALK gene, and real-time RT-PCR for breast cancer prognosis were entirely consistent with those of the control group. CONCLUSIONS The ultrasonic rapid processing method can quickly and effectively shorten the time for specimen processing before pathological diagnosis, and will not affect the DNA, RNA and proteins of the specimens. It can meet the subsequent HE staining, immunohistochemistry and molecular pathological detection.
Humans ; Paraffin Embedding/methods* ; Female ; RNA/analysis* ; DNA/analysis* ; Breast Neoplasms/pathology* ; Neoplasms/genetics* ; Ultrasonics/methods* ; Proteins/analysis*

The spatio-temporal heterogeneity of breast cell subsets forms the fundamental biological basis for physiological development and pathological progression, including tumorigenesis; however, its complex regulatory mechanisms are not yet fully elucidated. With its high-resolution capabilities, single-cell RNA sequencing (scRNA-seq) technology offers a powerful tool for dissecting this cellular heterogeneity. This technology enables the construction of high-precision breast cell atlases, the accurate identification of distinct cell subsets, and the reconstruction of differentiation trajectories from stem/progenitor cells to functional epithelial cells. By resolving the transcriptional regulatory networks that govern cell fate determination, intercellular communication patterns, and dynamic microenvironmental interactions, scRNA-seq has unveiled the molecular foundations of breast development and provided new perspectives on the pathogenesis of related diseases such as breast cancer and macromastia. Furthermore, scRNA-seq demonstrates significant potential for discovering early molecular markers of disease, deciphering tumor heterogeneity, and elucidating mechanisms of therapeutic resistance. The continued application of scRNA-seq for dissecting breast cell heterogeneity, combined with its integration with multi-modal data such as spatial omics, promises to provide critical evidence and new insights for revealing the molecular mechanisms of breast development-related diseases and for formulating precision therapeutic strategies.
Humans ; Single-Cell Analysis/methods* ; Female ; Breast Neoplasms/pathology* ; Sequence Analysis, RNA/methods* ; Breast/cytology*

Breast cancer is one of the most common and fatal malignancies among women worldwide, and its treatment efficacy is often limited by drug resistance and the presence of undruggable targets. Traditional small-molecule drugs have difficulty effectively modulating certain critical targets such as transcription factors and non-coding RNAs, necessitating new therapeutic strategies. Proteolysis-targeting chimeras (PROTACs) function by recruiting pathogenic proteins to the cellular ubiquitin-proteasome system, thereby inducing their specific degradation. In contrast, ribonuclease-targeting chimeras (RIBOTACs) utilize small-molecule ligands but bind to RNA and direct endogenous RNases to selectively degrade pathogenic RNA molecules. By employing a "degradation rather than inhibition" mechanism, targeting chimera technology broadens the druggable landscape and offers a novel precision therapeutic strategy for breast cancer, particularly for refractory and drug-resistant cases. This approach not only overcomes the limitations of traditional drugs, such as the absence of suitable binding sites or poor selectivity, but also reduces required dosages and potential adverse effects. Recent studies have preliminarily demonstrated the therapeutic potential of PROTACs and RIBOTACs in breast cancer, encompassing target design, mechanistic investigation, and preclinical as well as early clinical applications. Research into these technologies reveals their ability to tackle previously undruggable targets, thereby providing theoretical support for the development of safer and more effective precision therapies for breast cancer. In the future, with advances in drug delivery systems and clinical trials, PROTACs and RIBOTACs are expected to be used synergistically with immunotherapy and chemotherapy, offering breast cancer patients more promising comprehensive treatment options and potentially driving oncology toward broader intervention of undruggable targets.
Humans ; Breast Neoplasms/drug therapy* ; Female ; Proteolysis ; Ribonucleases/metabolism* ; Molecular Targeted Therapy/methods* ; Antineoplastic Agents/therapeutic use*

Objective:To investigate the clinical efficacy of robotic surgery via the bilateral axillo-breast approach（BABA） in lateral lymph node dissection for papillary thyroid carcinoma（PTC）. Methods:Clinicopathological records of 324 PTC patients receiving unilateral neck dissection in Tianjin Medical University Cancer Institute and Hospital from December 2020 to November 2024 were retrospectively analyzed. Of these patients, 108 underwent robotic surgery via BABA（robotic group）, while the remaining patients underwent conventional open surgery（open group）. The extent of lateral neck lymph node dissection included level Ⅱ, Ⅲ and Ⅳ. The differences in surgical indexes, postoperative complication rates and cosmetic outcomes of incisions were compared between two groups. Results:All study subjects completed the operation successfully, and there was no conversion in the robotic group. The average age of patients in the robotic group was lower than that in the open group, and the proportion of female patients was higher in the robotic group compared to the open group（P<0.05）. Patients in the robotic group had a greater number of dissected lymph nodes in level ⅡB and higher cosmetic scores（P<0.05）. There were no statistically significant differences between the two groups in the average dissection time of lateral cervical lymph nodes, the number of dissected lymph nodes and metastatic lymph nodes in level ⅡA, Ⅲ, and Ⅳ, average postoperative drainage volume, average postoperative hospital stay, and postoperative complication rates（P>0.05）. Conclusion:The application of robotic surgical system via BABA in lateral neck lymph node dissection for PTC is safe and feasible, with superior advantages in level ⅡB dissection and better postoperative cosmetic outcomes.
Humans ; Thyroid Neoplasms/surgery* ; Robotic Surgical Procedures/methods* ; Female ; Retrospective Studies ; Neck Dissection/methods* ; Lymph Node Excision/methods* ; Male ; Thyroid Cancer, Papillary ; Axilla/surgery* ; Thyroidectomy/methods* ; Breast/surgery* ; Middle Aged ; Adult ; Lymph Nodes/surgery* ; Treatment Outcome

Anastasis is a phenomenon described as a cellular escape from ethanol-induced cell death. Although the relevant mechanism has not yet been fully elucidated, anastasis is thought to play a role in drug resistance in cancer cells. To date, the regulation of anastasis in normal and cancerous cells has not been clarified. The current cancer treatment strategies are expected to selectively attack cancer cells without negatively affecting normal cell proliferation. Inspired by the anti-cancer potential of bee venom, this study is the first to evaluate whether bee venom has similar selectivity in producing an anastatic effect. The results indicated that bee venom induces anastasis in normal cells (Michigan Cancer Foundation-10A (MCF10A), Adult Retinal Pigment Epithelium cell line-19 (ARPE-19), and National Institutes of Health 3T3 cell line (NIH3T3)) but causes irreversible cell death in breast cancer cells (M.D. Anderson-Metastatic Breast-231 (MDA-MB-231) and Michigan Cancer Foundation-7 (MCF7)). Liver cancer (HepG2) cells were moderately more resistant to permanent cell death after bee venom treatment compared to breast cancer cells. However, cisplatin caused permanent non-selective cell death in both normal and cancerous cells. The selectivity indices after bee venom treatment were higher compared to cisplatin. Taken together, bee venom was shown to induce selective anastasis only in normal cells, not in cancer cells, which suggests that bee venom has significant potential in selective cancer therapy, especially for breast cancer, via promoting the recovery and maintenance of viability of normal cells.
Bee Venoms/pharmacology* ; Humans ; Animals ; Mice ; Cell Survival/drug effects* ; Breast Neoplasms/pathology* ; Female ; Cell Line, Tumor ; NIH 3T3 Cells ; Antineoplastic Agents/pharmacology* ; Cisplatin/pharmacology* ; Cell Death/drug effects* ; Hep G2 Cells ; MCF-7 Cells