Study on the mechanism of Fangxia Dihuang Formula(FXDH) in treating breast cancer complicated with depression through the regulation of M1/M2 microglial polarization via the PERK/eIF2α axis. In addition to control group and 4T1 group, a mouse model of breast cancer complicated with depression was established using 4T1 cells combined with corticosterone. The mice were divided into model group, PERK/eIF2α signaling axis agonist(CCT020312, 2 mg·kg~(-1)·d~(-1)) group, CCT020312(2 mg·kg~(-1)·d~(-1)) + FXDH(13.65 g·kg~(-1)·d~(-1)) group, FXDH(13.65 g·kg~(-1)·d~(-1)) group, FXDH(13.65 g·kg~(-1)·d~(-1)) + Capecitabine Tablets(CAP, 390 mg·kg~(-1)·d~(-1)) group, and Fluoxetine Hydrochloride Capsules(FXT, 2.6 mg·kg~(-1)·d~(-1)) + CAP(390 mg·kg~(-1)·d~(-1)) group, with continuous intervention for 21 d. Depression-like behaviors in mice were assessed through sugar preference test and open field test. Hematoxylin-eosin(HE) staining was used to evaluate the morphology of tumor and hippocampal DG region neurons. Nissl staining was employed to detect changes in Nissl bodies in the hippocampal CA3 region. Immunofluorescence was used to observe cluster of differentiation 86(CD86)/ionized calcium-binding adapter molecule 1(Iba-1) and cluster of differentiation 206(CD206)/Iba-1 in hippocampal tissue. Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) was used to detect the mRNA expression of M1-type microglia [interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)] and M2-type [arginase-1(Arg-1), IL-10] in hippocampal tissue. Western blot was used to detect the protein expression of key factors in the PERK/eIF2α axis, including PERK, eIF2α, activating transcription factor 4(ATF4), and C/EBP homologous protein(CHOP) in hippocampal tissue. The results showed that compared to model group/CCT020312 + FXDH group, FXDH group increased sugar preference index, total movement distance, central zone distance, and central zone entries; reduced tumor mass and volume; tumor cells were sparsely arranged, with a smaller nuclear-to-cytoplasmic ratio and reduced nuclear division figures, increased Nissl body count, and alleviated neuronal nuclear pyknosis; increased CD206-positive M2-type microglia expression, decreased CD86/Iba-1-positive M1-type microglia expression; reduced IL-6 and TNF-α mRNA expression, and increased Arg-1 and IL-10 mRNA expression; downregulated PERK, eIF2α, ATF4, and CHOP protein expression levels. The results indicate that the mechanism of FXDH in treating breast cancer complicated with depression may be related to inhibiting the activity of the PERK/eIF2α axis, reducing the proportion of M1-type microglia, increasing the proportion of M2-type microglia, thereby suppressing neuronal immune inflammation, improving depressive symptoms, and subsequently delaying the progression of breast cancer.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Female ; Microglia/cytology* ; Mice ; Depression/complications* ; eIF-2 Kinase/genetics* ; Humans ; Breast Neoplasms/psychology* ; Eukaryotic Initiation Factor-2/genetics* ; Mice, Inbred BALB C ; Signal Transduction/drug effects* ; Cell Line, Tumor

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*

Human breast milk is the most natural and ideal food for the baby. Breastfeeding provides benefits for maternal and child health, child immune function, growth and development, and society. The operation of human milk bank and the use of donor human milk undoubtedly provides a new way of nutrition support for the preterm infants without their own mother's milk and a new kind of treatment for other diseases. Present research on the composition of breast milk focuses on the variety and quantity of proteins, bioactive substances, probiotics and cell population.Future research may focus on the bioactive substances, the mechanism of regulation and effect of cell population, the application of probiotics and the clinical application of donor human milk.
Breast Feeding ; Female ; Humans ; Milk Banks ; Milk, Human ; chemistry ; cytology ; Probiotics ; pharmacology

OBJECTIVETo investigate the predictive factors of pathological complete response (pCR) in primary human epidermal growth factor receptor 2 (HER2)-positive breast cancer treated with trastuzumab-based neoadjuvant chemotherapy (NAC).

METHODSTotally 101 patients of primary HER2-positive breast cancer treated with trastuzumab-based NAC and subsequent curative surgical therapy in the Breast Disease Center of Peking University First Hospital from September 2007 to December 2014 were retrospectively reviewed. All patients were female with a median age of 53 (range 23 to 70) years.All patients received a taxanes- and carboplatin-containing chemotherapy, and trastuzumab was administered concurrently.A pCR, defined as the absence of invasive tumor cells in the breast and axillary lymph nodes, was achieved in 37.6% of patients (38/101). For analysis of the associations between clinicopathological factors and pCR, the χ(2) test or Fisher's exact test was used for univariate analysis, and multivariate Logistic regression analysis was performed to estimate OR and 95% CI.

RESULTSTumor-infiltrating lymphocytes (χ(2)=14.981, P=0.000), hormone receptor (HR) status (χ(2)=9.513, P=0.002), and tumor grade (χ(2)=4.005, P=0.045) were significantly associated with pCR in univariate analysis. Tumor-infiltrating lymphocytes positive (OR=4.74, 95% CI: 1.87 to 12.01, P=0.001) and HR-negative (OR=3.28, 95% CI: 1.31 to 8.20, P=0.011) were independent predictive factors of pCR in multivariate analysis.

CONCLUSIONTumor-infiltrating lymphocytes-positive and HR-negative were independent predictive factors of pCR in primary HER2-positive breast cancer treated with trastuzumab-based NAC.

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Axilla ; Breast Neoplasms ; drug therapy ; metabolism ; Female ; Humans ; Lymph Nodes ; Lymphocytes, Tumor-Infiltrating ; cytology ; Middle Aged ; Neoadjuvant Therapy ; Receptor, ErbB-2 ; metabolism ; Retrospective Studies ; Trastuzumab ; therapeutic use ; Young Adult

OBJECTIVETo explore the effects of radiofrequency ablation(RFA) on immune system and lung metastasis in a mouse model of triple negative breast cancer 4T1.

METHODSMouse breast cancer 4T1 cells were injected into the right hind limb of female Bal B/c mice. When the tumor size was 6-8 mm in diameter, RFA was used to treat the transplanted breast cancer in mice. We examined the splenic lymphocyte subsets by flow cytometry at different time points after RFA. Fourteen days after treatment, we sacrificed the mice of both control and treatment groups, counted the number of lung metastatic nodules, and detected the changes of splenic lymphocyte subsets by flow cytometry.

RESULTSRFA basically eliminated the orthotopic carcinoma with a low local recurrence rate. After the RFA treatment, the amount of spleic CD4⁺ T cells, CD8⁺ T cells, B cells, NK and NKT cells was increased. Fourteen days after the RFA treatment, all mice were sacrificed, and the lung metastatic nodules were 24 ± 18 in the control group and 81 ± 35 in the RFA-treated group (P = 0.012). The mechanism of suppression of metastatic lung cancers was related to the increase of splenic CD4⁺ T cells, CD8⁺ T cells, B cells and NK cells, and the decrease of myeloid-derived suppressor cells.

CONCLUSIONSRFA can enhance the anti-tumor immunity and effectively inhibit lung metastasis of 4T1 cell-induced breast cancer, and has a good potential effect in the treatment of triple-negative breast cancer and the control of distant metastasis.

Animals ; B-Lymphocytes ; cytology ; CD4-Positive T-Lymphocytes ; cytology ; CD8-Positive T-Lymphocytes ; cytology ; Catheter Ablation ; Female ; Flow Cytometry ; Humans ; Killer Cells, Natural ; cytology ; Lung Neoplasms ; immunology ; prevention & control ; secondary ; Mice ; Mice, Inbred BALB C ; Neoplasm Recurrence, Local ; Triple Negative Breast Neoplasms ; immunology ; pathology ; surgery ; Tumor Burden

Breast cancer is a heterogeneous disease. The formation and progression of tumor and the sensitivity to treatment differs from patient to patient. In addition to the widely used molecular subtype, novel markers are needed to better personalize the treatment of breast cancer. Tumor infiltrating lymphocyte (TIL) have been consistently documented in breast cancer lesions especially in triple negative and human epidermal growth factor receptor-2 positive breast cancer. Several clinical trials have revealed that TIL are associated with prognosis and can predict therapeutic efficacy of special therapy. TIL could be divided to different subtypes including CD8 + TIL, CD4 + TIL, cytotoxic T lymphocyte-associated antigen-4 + TIL, programmed death-1 + TIL. They play different roles in the process of anti-tumor immunity and can predict different prognosis. Screening out special TIL subtype which is well associated with prognosis and therapeutic efficacy and developing targeting immunotherapy can help to improve outcomes of breast cancer patients.
Breast Neoplasms ; diagnosis ; immunology ; Humans ; Lymphocytes, Tumor-Infiltrating ; classification ; cytology ; Prognosis

OBJECTIVETo explore the feasibility of the transdiferentiation of human breast adipose-derived stem cells (hbASCs) into mammary epithelial-like cells after co-culturing in Transwell in vitro.

METHODSThe third passage hbASC and the HBL-100 cell line were co-cultured in a Transwell culture system for 15 days. The hbASCs were observed and identified by inverted phase contrast microscope and transmission electron microscopy, and immunocytochemistry staining in the induced and control groups.

RESULTSBoth the third passage hbASCs and the HBL-100 cell line cells could adhere and grow rapidly after co-culture in the Transwell system. After co-culture for 15 days, the morphology of some induced hbASCs changed into epithelial-like cells. Some induced hbASCs showed positive expression of CK18, CK19 by immunocytochemistry staining, and typical epithelium cells with microvilli, desmosomes and tonofilaments observed under TEM. The positive rate of CK18 and CK19 was (24.4 +/- 12.0)% and (21.6 +/- 16.4)% in experimental group, and (1.8 +/- 1.7)% and (1.1 +/- 0.6)% in control group.

CONCLUSIONThe data suggests that hbASCs may have the potential to transdifferentiate into human mammary epithelial-like cells after co-culturing in Transwell in vitro.

Adipose Tissue ; cytology ; Breast ; cytology ; Cell Differentiation ; Cells, Cultured ; Coculture Techniques ; Epithelial Cells ; cytology ; Female ; Humans ; Stem Cells ; cytology

During normal postnatal mammary gland development and adult remodeling related to the menstrual cycle, pregnancy, and lactation, ovarian hormones and peptide growth factors contribute to the delineation of a definite epithelial cell identity. This identity is maintained during cell replication in a heritable but DNA-independent manner. The preservation of cell identity is fundamental, especially when cells must undergo changes in response to intrinsic and extrinsic signals. The maintenance proteins, which are required for cell identity preservation, act epigenetically by regulating gene expression through DNA methylation, histone modification, and chromatin remodeling. Among the maintenance proteins, the Trithorax (TrxG) and Polycomb (PcG) group proteins are the best characterized. In this review, we summarize the structures and activities of the TrxG and PcG complexes and describe their pivotal roles in nuclear estrogen receptor activity. In addition, we provide evidence that perturbations in these epigenetic regulators are involved in disrupting epithelial cell identity, mammary gland remodeling, and breast cancer initiation.
Animals ; Breast Neoplasms ; genetics ; pathology ; physiopathology ; Cell Transformation, Neoplastic ; Chromatin ; genetics ; metabolism ; Epigenesis, Genetic ; physiology ; Epithelial Cells ; cytology ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Histone-Lysine N-Methyltransferase ; Humans ; Mammary Glands, Animal ; cytology ; growth & development ; Mammary Glands, Human ; cytology ; growth & development ; Myeloid-Lymphoid Leukemia Protein ; genetics ; physiology ; Polycomb-Group Proteins ; genetics ; physiology ; Receptors, Estrogen ; metabolism

OBJECTIVETo evaluate the cardioprotective effects of dexrazoxane (DEX) on breast cancer patients who received anthracycline-containing chemotherapy.

METHODSA total of 122 breast cancer patients after operation were randomly divided into two groups: The experimental group of 61 cases treated with EPI plus DEX (DEX:EPI = 10:1) as adjuvant chemotherapy regimen, and the control group of 61 cases treated with EPI but without DEX. All patients received four cycles of adjuvant chemotherapy and their changes of specific cardiac functional status and hematology status before and after chemotherapy, as well as non-cardiac toxicity were observed and analyzed.

RESULTSBrain natriuretic peptide (BNP) before chemotherapy and after four cycles of chemotherapy in the control group was (106.78 ± 4.52)×10(-6) µg/ml and (187.19 ± 8.71)×10(-6) µg/ml, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (102.34 ± 8.76)×10(-6) µg/ml and (105.29 ± 7.21)×10(-6) µg/ml, respectively, without a significant difference (P > 0.05). Cardiac troponin T (cTnT) before chemotherapy and after four cycles of chemotherapy in the control group was (12.55 ± 2.73)×10(-3) µg/ml and ( 31.05 ± 7.10 )×10(-3) µg/ml, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (12.70 ± 2.15)×10(-3) µg/ml and (13.65 ± 7.82)×10(-3) µg/ml, respectively, without a significant difference (P > 0.05). The hart rate (HR) before chemotherapy and after four cycles of chemotherapy in the control group, was 75.32 ± 7.14 bpm and 89.60 ± 9.21 bpm, respectively, with a significant difference (P < 0.05). It in the experimental group was 78.60 ± 6.29 bpm and 83.10 ± 7.56 bpm, respectively, without a significant difference (P > 0.05). The left ventricular ejection fraction (LVEF) before chemotherapy and after four cycles of chemotherapy in the control group was (65.23 ± 7.82)% and (55.21 ± 7.23)%, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (64.12 ± 6.25)% and (59.6 ± 4.72)%, respectively, without a significant difference (P > 0.05). The absolute neutrophil count before chemotherapy and after four cycles of chemotherapy in the control group was (3.95 ± 1.36)×10(9)/L and (3.50 ± 1.52)×10(9)/L, respectively, without a significant difference (P > 0.05). It in the experimental group, was (4.96 ± 1.41)×10(9)/L and (3.10 ± 1.26)×10(9)/L, respectively, with a significant difference (P < 0.05). The incidence of grade I-IV bone marrow suppression in the experimental group was 21.3%, 16.4%, 24.6%, and 4.9%, respectively. It in the control group was 16.4%, 11.5%, 9.8%, and 5.5%, respectively, with a significant difference (P < 0.05).

CONCLUSIONSCardiac toxicity after anthracycline treatment in breast cancer patients may be significantly reduced by DEX, without increase of non-cardiac and and non-hematologic toxicity. DEX combined with anthracycline increases the risk of bone marrow suppression, therefore, peripheral blood picture should be monitored or routine bone marrow support may be needed.

Adolescent ; Adult ; Aged ; Antibiotics, Antineoplastic ; adverse effects ; therapeutic use ; Bone Marrow ; drug effects ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; physiopathology ; surgery ; Cardiovascular Agents ; adverse effects ; therapeutic use ; Chemotherapy, Adjuvant ; Epirubicin ; adverse effects ; therapeutic use ; Female ; Follow-Up Studies ; Heart Rate ; drug effects ; Humans ; Leukocyte Count ; Middle Aged ; Natriuretic Peptide, Brain ; metabolism ; Neutrophils ; cytology ; Razoxane ; adverse effects ; therapeutic use ; Stroke Volume ; drug effects ; Young Adult

OBJECTIVETo detect the inhibitory effect of all-trans retinoic acid(ATRA) on breast cancer stem cells (CSCs).

METHODSThe inhibitory effect of ATRA on MCF-7 and SK-BR-3 cell lines was analyzed using a Cell Counting Kit-8 (CCK-8). The proportion of CD44(+)CD24(-) tumor cells of the two cell lines were measured before and after the ATRA treatment, and the role of ATRA in the regulation of CSC self-renewing ability was evaluated with a tumor sphere assay. The tumor spheres were grown in an adherent culture to evaluate the ATRA-induced differentiation of breast cancer stem cells.

RESULTSATRA effectively inhibited the unsorted cells and stem cells, but the CSCs were more sensitive to ATRA. At a concentration of 10(-6) mol/L, the inhibitory rate of MCF-7 unsorted cells and stem cells were (8.66 ± 1.06)% and (21.09 ± 3.25)%, respectively (P = 0.004). For SK-BR-3 cells, the rates were (39.19 ± 1.47)% and (51.22 ± 2.80)%, respectively (P = 0.005). The self-renewing ability of the CSCs was impaired by ATRA at a concentration of 10(-6) mol/L. The rate of MCF-7 and SK-BR-3 stem cells to form tumor sphere was 5.2% (5/96) and 13.5% (13/96), respectively. For the control group, it was 86.5% (83/96) and 93.8% (90/96), respectively (P < 0.001). ATRA also promoted the CD44(+)CD24(-) subpopulation to differentiate. SK-BR-3 stem cells were grown in an adherent culture. After using ATRA, the proportion of CD44(+)CD24(-) cells was (48.1 ± 2.5)% and that of the control group was (86.6 ± 2.5)% (P < 0.001).

CONCLUSIONSATRA effectively inhibits breast NCSCs and CSCs, but CSCs are more sensitive to ATRA. ATRA impairs the self-renewing ability of CSCs and promotes CSCs to differentiate.

Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; metabolism ; pathology ; CD24 Antigen ; metabolism ; Cell Differentiation ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Female ; Humans ; Hyaluronan Receptors ; metabolism ; Neoplastic Stem Cells ; cytology ; drug effects ; Tretinoin ; pharmacology