MGP+ and IDO1+ tumor-associated macrophages facilitate immunoresistance in breast cancer revealed by single-cell RNA sequencing.

Immunotherapy is widely applied for the treatment of breast cancer, but to which some patients respond poorly or develop resistance. Therefore, the mechanism needs to be further studied. Transcriptomic data of 31 breast cancer patients treated with anti-programmed death receptor 1 (PD-1) was downloaded from the VIB-KULeuven Center for Cancer Biology to analyze the changes in myeloid cells in tumor tissues before and after immunotherapy. And 24 cell populations that may be immune-related were further identified. Representative cell populations were also screened and validated through cellular and animal experiments to evaluate the relevant molecular expression and pathways of tumor-associated macrophages (TAMs) in the tumor microenvironment. The results demonstrated that MGP+ TAMs and IDO1+ TAMs influenced the efficacy of immunotherapy in breast cancer patients. After anti-PD-1 treatment, Increased numbers of MGP+ TAMs and IDO1+ TAMs in breast cancer patients upregulated pro-tumorigenic factors associated with resistance to immunosuppressive therapy. This study provides new biomarkers for immunotherapy to predict therapeutic responses and overcome potential resistance to immunotherapy. It is an important complement to the immunosuppression caused by TAMs after immunotherapy for breast cancer.

Lactylation-related gene signature for prognostic prediction and immune infiltration analysis in breast cancer.

Background: Lactylation is implicated in various aspects of tumor biology, but its relation to breast cancer remains poorly understood. This study aimed to explore the roles of the lactylation-related genes in breast cancer and its association with the tumor microenvironment. Methods: The expression and mutation patterns of lactylation-related genes were analyzed using the breast cancer data from The Cancer Genome Atlas (TCGA) database and GSE20685 datasets. Unsupervised clustering was used to identify two lactylation clusters. A lactylation-related gene signature was developed and validated using the training and validation cohorts. Immune cell infiltration and drug response were assessed. Results: We analyzed the mRNA expression, copy number variations, somatic mutations, and correlation networks of 22 lactylation-related genes in breast cancer tissues. We identified two distinct lactylation clusters with different survival outcomes and immune microenvironments. We further classified the patients into two gene subtypes based on lactylation clusters and identified a 7-gene signature for breast cancer survival prognosis. The prognostic score based on this signature demonstrated prognostic value and predicted the therapeutic response. Conclusion: Lactylation-related genes play a critical role in breast cancer by influencing tumor growth, immune microenvironment, and drug response. This lactylation-related gene signature may serve as a prognostic marker and a potential therapeutic target for breast cancer.

Design, strategies, and therapeutics in nanoparticle-based siRNA delivery systems for breast cancer.

Utilizing small interfering RNA (siRNA) as a treatment for cancer, a disease largely driven by genetic aberrations, shows great promise. However, implementing siRNA therapy in clinical practice is challenging due to its limited bioavailability following systemic administration. An attractive approach to address this issue is the use of a nanoparticle (NP) delivery platform, which protects siRNA and delivers it to the cytoplasm of target cells. We provide an overview of design considerations for using lipid-based NPs, polymer-based NPs, and inorganic NPs to improve the efficacy and safety of siRNA delivery. We focus on the chemical structure modification of carriers and NP formulation optimization, NP surface modifications to target breast cancer cells, and the linking strategy and intracellular release of siRNA. As a practical example, recent advances in the development of siRNA therapeutics for treating breast cancer are discussed, with a focus on inhibiting cancer growth, overcoming drug resistance, inhibiting metastasis, and enhancing immunotherapy.

Authentication of a survival nomogram for non-invasive micropapillary breast cancer.

Purpose: We aimed at establishing a nomogram to accurately predict the overall survival (OS) of non-metastatic invasive micropapillary breast carcinoma (IMPC). Methods: In the training cohort, data from 429 patients with non-metastatic IMPC were obtained through the Surveillance, Epidemiology, and End Results (SEER) database. Other 102 patients were enrolled at the Xijing Hospital as validation cohort. Independent risk factors affecting OS were ascertained using univariate and multivariate Cox regression. A nomogram was established to predict OS at 3, 5 and 8 years. The concordance index (C-index), the area under a receiver operating characteristic (ROC) curve and calibration curves were utilized to assess calibration, discrimination and predictive accuracy. Finally, the nomogram was utilized to stratify the risk. The OS between groups was compared through Kaplan-Meier survival curves. Results: The multivariate analyses revealed that race (p = 0.047), surgery (p = 0.003), positive lymph nodes (p = 0.027), T stage (p = 0.045) and estrogen receptors (p = 0.019) were independent prognostic risk factors. The C-index was 0.766 (95% CI, 0.682-0.850) in the training cohort and 0.694 (95% CI, 0.527-0.861) in the validation cohort. Furthermore, the predicted OS was consistent with actual observation. The AUCs for OS at 3, 5 and 8 years were 0.786 (95% CI: 0.656-0.916), 0.791 (95% CI: 0.669-0.912), and 0.774 (95% CI: 0.688-0.860) in the training cohort, respectively. The area under the curves (AUCs) for OS at 3, 5 and 8 years were 0.653 (95% CI: 0.498-0.808), 0.683 (95% CI: 0.546-0.820), and 0.716 (95% CI: 0.595-0.836) in the validation cohort, respectively. The Kaplan-Meier survival curves revealed a significant different OS between groups in both cohorts (p<0.001). Conclusion: Our novel prognostic nomogram for non-metastatic IMPC patients achieved a good level of accuracy in both cohorts and could be used to optimize the treatment based on the individual risk factors.

PRMT5 reduces immunotherapy efficacy in triple-negative breast cancer by methylating KEAP1 and inhibiting ferroptosis.

BACKGROUND: As an emerging treatment strategy for triple-negative breast cancer (TNBC), immunotherapy acts in part by inducing ferroptosis. Recent studies have shown that protein arginine methyltransferase 5 (PRMT5) has distinct roles in immunotherapy among multiple cancers by modulating the tumor microenvironment. However, the role of PRMT5 during ferroptosis, especially for TNBC immunotherapy, is unclear. METHODS: PRMT5 expression in TNBC was measured by IHC (immunohistochemistry) staining. To explore the function of PRMT5 in ferroptosis inducers and immunotherapy, functional experiments were conducted. A panel of biochemical assays was used to discover potential mechanisms. RESULTS: PRMT5 promoted ferroptosis resistance in TNBC but impaired ferroptosis resistance in non-TNBC. Mechanistically, PRMT5 selectively methylated KEAP1 and thereby downregulated NRF2 and its downstream targets which can be divided into two groups: pro-ferroptosis and anti-ferroptosis. We found that the cellular ferrous level might be a critical factor in determining cell fate as NRF2 changes. In the context of higher ferrous concentrations in TNBC cells, PRMT5 inhibited the NRF2/HMOX1 pathway and slowed the import of ferrous. In addition, a high PRMT5 protein level indicated strong resistance of TNBC to immunotherapy, and PRMT5 inhibitors potentiated the therapeutic efficacy of immunotherapy. CONCLUSIONS: Our results reveal that the activation of PRMT5 can modulate iron metabolism and drive resistance to ferroptosis inducers and immunotherapy. Accordingly, PRMT5 can be used as a target to change the immune resistance of TNBC.

Identification of periductal mastitis and granulomatous lobular mastitis: a literature review.

Background and Objective: Non-puerperal mastitis (NPM) is a breast disease with poor clinical manifestations, which seriously affects women's health and quality of life. Due to the low incidence rate of the disease and the paucity of related research, there is much misdiagnosis and mis-management of periductal mastitis (PDM) and granulomatous lobular mastitis (GLM). Therefore, understanding the differences between PDM and GLM, in terms of etiology and clinical manifestations, is crucial for patient treatment and prognosis. At the same time, choosing different treatment methods may not achieve the best treatment effect, so the appropriate treatment method can often reduce the patient's pain and reduce the recurrence of the patient's disease. Methods: The PubMed database was searched for articles published from 1 January 1990 to 16 June 2022 using the following search terms: "non-puerperal mastitis", "periductal mastitis", "granulomatous lobular mastitis", "mammary duct ectasia", "idiopathic granulomatous mastitis", "plasma cell mastitis", and "identification". The key findings of the related literatures were analyzed and summarized. Key Content and Findings: We systematically described the key points in the differential diagnosis, treatment, and prognosis of PDM and GLM. The use of different animal models for research and novel drugs to treat the disease were also described in this paper. Conclusions: The key points in the differentiation of the two diseases are clearly explained, and the respective treatment options and prognosis are summarized.

Willingness to receive COVID-19 vaccination and adverse effects after vaccination in breast cancer survivors during the COVID-19 pandemic: a cross-sectional retrospective study of a Chinese population.

Background: Breast cancer (BC) patients have a higher mortality rate after COVID-19 infection, but data on vaccination of BC patients and attitude towards COVID-19 vaccination and safety after vaccination are lacking. We wanted to understand the willingness and factors of BC survivors to receive a COVID-19 vaccine, and their adverse reactions. The purpose is to judge the safety of vaccination, and find strategies to promote vaccination in BC patients. Methods: Offline and online questionnaire surveys were provided in outpatient clinics and on an online follow-up platform, respectively, to collect information. Factors influencing vaccination willingness were analyzed by univariate and multivariate logistic regression. All statistical tests were performed bilaterally, and a P value <0.05 was considered statistically significant. Patients who have been vaccinated need to fill in questions about the impact on quality of life after vaccination, the type and frequency of vaccination, and side effects. Results: A total of 497 valid questionnaires were collected; 289 (58.1%) BC survivors were vaccinated with a COVID-19 vaccine, and 379 (76.26%) BC survivors had a fully or basically accepting attitude toward vaccination. Survivors over 70 years of age, educated only to high school level, and those receiving chemotherapy had significantly lower levels of acceptance of COVID-19 vaccines. Multivariate logistic regression analyses suggested that treatment status and cognitive attitude were independent factors influencing COVID-19 vaccination among BC survivors. The main reason for being vaccinated was "doctor recommendation" (57.26%). Unwillingness to receive a COVID-19 vaccine was mainly due to "the unknown safety of the vaccine in cancer patients" (67.80%). A total of 97.56% of the survivors believed that vaccination had no or almost no effect on their quality of life. Among the BC survivors, 18 (6.23%) had adverse reactions after vaccination. All adverse reactions were grade 1 or 2, and no adverse reactions of grade 3 or above were reported. The adverse reactions reported by 15 survivors (83.33%) markedly improved within 1 week. Conclusions: In terms of cognitive attitudes toward COVID-19 vaccines, elderly individuals and those with a lower education level were less receptive to vaccination. Therefore, attention to elderly survivors can help improve the vaccination rate.

Role of STING protein in breast cancer: mechanisms and therapeutic implications.

Breast cancer is one of the most frequent causes of cancer related death worldwide, and despite the significant advances in therapeutic approaches, a significant proportion of patients succumb to metastasis and tumor recurrence. Breast cancer is an immunogenic cancer, and therefore, immunotherapy is considered a major therapeutic strategy. The survival rate has been increased significantly in HER2+ breast cancers after immunotherapy by monoclonal antibodies alone, or combined with chemical anti-cancer agents. Moreover, in triple negative breast cancer (TNBC), a number of novel agents called immune checkpoint inhibitors have shown optimal efficacy. The major hindrance in cancer immunotherapy is frequent development of resistance and cancer remission. cGAS-STING pathway has a key role in anti-cancer immunity as its downstream signals especially type I interferon (IFN) acts as a link between innate and adaptive immunity. Considering the roles of type I IFN in enhancing dendritic cells activity, promoting the functions of CD8+ T cells, and protecting the effector cells against apoptosis, the induction of cGAS-STING pathway demonstrated promising therapeutic effects against breast cancer, especially in triple negative breast cancers. In this review, we discuss the latest findings and the recent advances regarding the role of cGAS-STING pathway and its activation in breast cancer.

Construction of a ferroptosis-related five-lncRNA signature for predicting prognosis and immune response in thyroid carcinoma.

BACKGROUND: Thyroid carcinoma (THCA) is the most common endocrine-related malignant tumor. Despite the good prognosis, some THCA patients may deteriorate into more aggressive diseases, leading to poor survival. This may be alleviated by developing a novel model to predict the risk of THCA, including recurrence and survival. Ferroptosis is an iron-dependent, oxidative, non-apoptotic form of cell death initially described in mammalian cells, and plays an important role in various cancers. To explore the potential prognostic value of ferroptosis in THCA, ferroptosis-related long non-coding RNAs (FRLs) were used to construct model for risk prediction of THCA. METHODS: RNA-sequencing data of THCA patients and ferroptosis-related genes were downloaded from The Cancer Genome Atlas (TCGA) and FerrDb, respectively. A total of 502 patients with complete data were randomly separated into a training cohort and a validation cohort at the ratio of 2:1. The Pearson correlation coefficients were calculated to determine the correlation between ferroptosis-related genes (FRGs) and the corresponding lncRNAs, and those meeting the screening conditions were defined as FRLs. Gene Expression Omnibus (GEO) database and qRT-PCR were used to verify the expression level of FRLs in THCA tissues. Univariate and multivariate cox regression analysis were performed to construct a FRLs signature based on lowest Akaike information criterion (AIC) value in the training cohort, then further tested in the validation cohort and the entire cohort. Gene set enrichment analysis (GSEA) and functional enrichment analysis were used to analyze the biological functions and signal pathways related to differentially expressed genes between the high-risk and low-risk groups. Finally, the relative abundance of different tumor-infiltrating immune cells were calculated by CIBERSORT algorithm. RESULTS: The patients were divided into high-risk group and low-risk group based on a 5-FRLs signature (AC055720.2, DPP4-DT, AC012038.2, LINC02454 and LINC00900) in training cohort, validation cohort and entire cohort. Through Kaplan-Meier analysis and area under ROC curve (AUC) value, patients in the high-risk group exhibited worse prognosis than patients in the low-risk group. GEO database and qRT-PCR confirmed that LINC02454 and LINC00900 were up-regulated in THCA. Univariate and multivariate cox regression analyses showed that the risk score was an independent prognostic indicator. GSEA and functional enrichment analysis confirmed that immune-related pathways against cancer were significantly activated in the low-risk THCA patients. Further analysis showed that the immune cells such as plasma cells, T cells CD8 and macrophages M1, and the expression of immune checkpoint molecules, including PD-1, PD-L1, CTLA4, and LAG3, were remarkably higher in the low-risk group. CONCLUSION: Our study used the TCGA THCA dataset to construct a novel FRLs prognostic model which could precisely predict the prognosis of THCA patients. These FRLs potentially mediate anti-tumor immunity and serve as therapeutic targets for THCA, which provided the novel insight into treatment of THCA.

Modified radical mastectomy for level III axillary lymph node clearance: a case report.

While modified radical mastectomy with level I and level II axillary lymph node clearance is a typical operating method in breast surgery, level III axillary lymph node clearance is necessary in some cases such as those involving apical axillary nodes. Level III dissection can provide accurate postoperative staging and essential guidance for postoperative adjuvant therapy. Although it is often difficult to expose the subclavian region and dissect level III axillary lymph nodes, in this case, the author split the pectoralis major muscle 2 cm inferior to the collarbone and performed a skeletonized complete level III axillary lymph node dissection. The author cut apart the fat on the surface of subclavian vein, lifted the fascia on the surface of the subclavian vein, removed the lymphoid adipose tissue along the fascial space completely and skeletonized subclavian vein. This approach provides less operating space, but it can fully expose the subclavian area, making it easier to dissociate and dissect the parasternal ligament, subclavian vein, medial border of the pectoralis minor muscle, and other important anatomical landmarks. In addition, the pectoralis branches of the thoracoacromial artery and the lateral cutaneous branches of the intercostal nerves were protected when removing the axillary nodes, which reduced postoperative complications such as upper limb numbness, tingling sensation, and muscle atrophy. Axillary lymph nodes were completely resected from inside to outside, and the important anatomical markers of axilla such as axillary vein, long thoracic nerve, thoracodorsal nerve and thoracodorsal vessels were clearly exposed.

Analysis of sentinel lymph node biopsy and non-sentinel lymph node metastasis in invasive ductal and invasive lobular breast cancer: a nationwide cross-sectional study (CSBrS-001).

BACKGROUND: Information regarding the implementation of sentinel lymph node biopsy (SLNB) in invasive lobular carcinoma (ILC) is scarce, and whether ILC patients with 1-2 positive sentinel lymph nodes (SLNs) can be omitted from axillary lymph node dissection (ALND) remains controversial. This study aimed to compare involvement of SLNs and non-SLNs between patients with invasive ductal carcinoma (IDC) and ILC. METHODS: We retrospectively collected the clinical and pathological data of invasive breast cancer patients from 37 medical centers in China from January 2018 to December 2018. The number of resected SLNs, positive rate of SLNs, and non-SLNs metastasis were compared between patients with IDC and ILC. RESULTS: A total of 6,922 patients were included, comprising 6,650 with IDC (96.1%) and 272 with ILC (3.9%). No difference was observed in the number of resected SLNs between patients with IDC and ILC (IDC: 4.0±1.9 vs. ILC: 3.9±1.6, P=0.352). The positive rate of SLNs was significantly higher in patients with IDC than that in patients with ILC (19.3% in IDC vs. 12.9% in ILC, P=0.008). The difference in positive rate of SLNs between IDC and ILC was mainly attributed to macro-metastasis. For patients with positive SLNs who received ALND, and those with 1-2 positive SLNs, the metastatic rate of non-SLNs in the ILC group was higher than that in the IDC group (for patients with positive SLNs: 50.0% in ILC vs. 39.9% in IDC, P=0.317; for patients with 1-2 positive SLNs: 45.4% in ILC vs. 34.8% in IDC, P=0.366), but the differences were not statistically significant. CONCLUSIONS: Patients with ILC had similar number of resected SLNs and lower positive rate of SLNs compared to those with IDC. In participants with 1-2 positive SLNs, the ILC group had an increased tendency for non-SLNs metastasis compared with the IDC group. Surgeons may need to be more cautious about omitting ALND for ILC patients with 1-2 positive SLNs.

3D Printing in Breast Reconstruction: From Bench to Bed.

Surgical management of breast cancer often results in the absence of the breast. However, existing breast reconstruction methods may not meet the need for a replacement tissue. Tissue engineering with the use of emerging materials offers the promise of generating appropriate replacements. Three-dimensional (3D) printing technology has seen a significantly increased interest and application in medically-related fields in the recent years. This has been especially true in complex medical situations particularly when abnormal or complicated anatomical surgical considerations or precise reconstructive procedures are contemplated. In addition, 3D bio-printing which combines cells with bio-material scaffolds offers an exciting technology with significant applications in the field of tissue engineering. The purpose of this manuscript was to review a number of studies in which 3D printing technology has been used in breast reconstructive surgical procedures, and future directions and applications of 3D bio-printing.

A Prognostic Risk Stratification Model to Identify Potential Population Benefiting From Postmastectomy Radiotherapy in T1-2 Breast Cancer With 1-3 Positive Axillary Lymph Nodes.

BACKGROUND AND OBJECTIVES: To establish a prognostic stratification nomogram for T1-2 breast cancer with 1-3 positive lymph nodes to determine which patients can benefit from postmastectomy radiotherapy (PMRT). METHODS: A population-based study was conducted utilizing data collected from the Surveillance, Epidemiology, and End Results database. Chi-square test or Fisher exact test was used to compare the distribution of characteristics. Cox analysis identified significant prognostic factors for survival. A prognostic stratification model was constructed by R software. Propensity score matching was applied to balance characteristics between PMRT cohort and control cohort. Kaplan-Meier method was performed to evaluate the performance of stratification and the benefits of PMRT in the total population and three risk groups. RESULTS: The overall performance of the nomogram was good (3-year, 5-year, 10-year AUC were 0.75, 0.72 and 0.67, respectively). The nomogram was performed to excellently distinguish low-risk, moderate-risk, and high-risk groups with 10-year overall survival (OS) of 86.9%, 73.7%, and 62.7%, respectively (P<0.001). In the high-risk group, PMRT can significantly better OS with 10-year all-cause mortality reduced by 6.7% (P = 0.027). However, there was no significant survival difference between PMRT cohort and control cohort in low-risk (P=0.49) and moderate-risk groups (P = 0.35). CONCLUSION: The current study developed the first prognostic stratification nomogram for T1-2 breast cancer with 1-3 positive axillary lymph nodes and found that patients in the high-risk group may be easier to benefit from PMRT.

Clinical Practice Status of Sentinel Lymph Node Biopsy for Early-Stage Breast Cancer Patients in China: A Multicenter Study.

BACKGROUND: Sentinel lymph node biopsy (SLNB) was introduced over 30 years ago, but the application of SLNB in China is unclear. This study aimed to explore the real-world implementation of SLNB among early-stage breast cancer patients in China. METHODS: A multi-center, retrospective study was conducted among primary breast cancer patients from 37 hospitals in China in 2018. Their clinical data were collected and analyzed, including the implementation status of SLNB in China, subsequent processing of sentinel lymph nodes (SLNs) containing metastases, and the effect of neoadjuvant chemotherapy (NAC) on SLNB. RESULTS: SLNB surgery was performed on 43.5% of early-stage breast cancer patients in China and 11,942 patients who underwent SLNB were enrolled in this study. The majority of SLNBs were performed using a single mapping agent. A combination of blue dye and radiotracer or fluorescence imaging was used in only 14.9% of patients. The mean (SD) number of resected SLNs was 4.0 (2.1). For the patients with 1 or 2 positive SLNs, 83.0% of them continued to receive axillary lymph node dissection (ALND), while others did not. For the patients with three or more positive SLNs, 97.2% of them continued to receive ALND, among which 82.9% accepted radiotherapy simultaneously. Of the patients who underwent SLN surgery, 5.5% (654/11,942) were receiving NAC. Among them, 51.9% received SLNB before NAC, and the rest received SLNB after NAC. In biopsy-proven positive nodes, 64.7% positive SLNs turned negative after NAC. CONCLUSION: SLNB has been promoted in China, but it is not widely used compared to in developed countries. Furthermore, the usage of the dual tracer technique in SLNB is not high. Chinese breast surgeons are more conservative regarding the omission of ALND in 1 or 2 SLNs-positive patients.

Development and Validation of a Nomogram for Individually Predicting Pathologic Complete Remission After Preoperative Chemotherapy in Chinese Breast Cancer: A Population-Based Study.

PURPOSE: To explore the independent predictors of pathologic complete remission response (pCR) for Chinese patients with breast cancer (BC) after preoperative chemotherapy and to develop an individualized nomogram for predicting the probability of pCR. PATIENTS AND METHODS: The clinicopathologic data of clinical stage I-III BC patients who received preoperative chemotherapy in Xijing Hospital were retrospectively analyzed. A total of 689 BC patients diagnosed in 2015-2017 were included in the training set to develop a nomogram. A separate cohort of 357 patients in the same center was regarded as a validation set for externally examining the performance of the model. The area under the receiver operating characteristic curve and calibration curve were used to verify the predictive performance of the nomogram. RESULTS: Multivariate logistic regression analysis showed that independent predictors of pCR were menopause status at diagnosis, family history of BC, initial tumor size, estrogen receptor status, HER2/neu (human epidermal growth factor receptor 2) status, and Ki-67 expression. On the basis of these factors, a nomogram was developed using R software. Our nomogram had good discrimination in the training and validation set (area under the receiver operating characteristic curve, 0.762 and 0.768, respectively). The calibration curves further confirmed that the model performs well. CONCLUSION: Menopause status and family history of BC were independent predictors of pCR after preoperative chemotherapy for the first time. The nomogram can accurately predict pCR rate in BC, which may provide some guidelines for breast surgery options and patient counseling.

In-situ re-melting and re-solidification treatment of selective laser sintered polycaprolactone lattice scaffolds for improved filament quality and mechanical properties.

Selective laser sintering (SLS) is a promising additive manufacturing technique that produces biodegradable tissue-engineered scaffolds with highly porous architectures without additional supporting. However, SLS process inherently results in partially melted microstructures which significantly impair the mechanical properties of the resultant scaffolds for potential applications in tissue engineering and regenerative medicine. Here, a novel post-treatment strategy was developed to endow the SLS-fabricated polycaprolactone (PCL) scaffolds with dense morphology and enhanced mechanical properties by embedding them in dense NaCl microparticles for in-situ re-melting and re-solidification. The effects of re-melting temperature and dwelling time on the microstructures of the SLS-fabricated filaments were studied. The results demonstrated that the minimum requirements of re-melting temperature and dwelling time for sufficient treatment were 65 °C and 5 min respectively and the size of the SLS-fabricated filaments was reduced from 683.3 ± 28.0 µm to 601.6 ± 17.4 µm. This method was also highly effective in treating three-dimensional (3D) PCL lattice scaffolds, which showed improved filament quality and mechanical properties after post-treatment. The treated PCL scaffolds with an initial compressive modulus and strength of 3027.8 ± 204.2 kPa and 208.8 ± 14.5 kPa can maintain their original shapes after implantation in vivo for 24 weeks. Extensive newly-grown tissues were found to gradually penetrate into the porous regions along the PCL filaments. Although degradation occurred, the mechanical properties of the implanted constructs stably maintained. The presented method provides an innovative, green and general post-treatment strategy to improve both the filament quality and mechanical properties of SLS-fabricated PCL scaffolds for various tissue engineering applications.

Regulation of docetaxel chemosensitivity by NR2F6 in breast cancer.

Docetaxel (DTX)-based chemotherapy significantly eliminates rest cancerous cells and decreases the risk of death, thus remaining the mainstay of treatment for operable breast cancer (BCa). However, resistance or incomplete response to DTX occurs frequently, resulting in disease recurrence and poor prognosis. There is an urgent need to identify and understand the key factors and corresponding molecular bases driving this complicated pathogenesis. Herein, both data mining and profiling analysis using clinical BCa biopsies showed that expression levels of the nuclear receptor subfamily 2, group F, member 6 (NR2F6), a recently characterized central transcription factor for cancer immune surveillance, were significantly downregulated in DTX-resistant BCa. This downregulation, possibly regulated by leptin signaling, predicted a poor postoperative chemotherapy survival in DTX-resistant BCa. In both genetically engineered cell models and patient-derived xenograft models, we provided evidence that BCa cells with insufficient NR2F6 expression were less responsive to DTX treatment. Mechanistically, NR2F6 functioned as a potent corepressor of platelet-derived growth factor B receptor gene (PDGFRB) transcription by recruiting HDAC2 onto the PDGFRB promoter. Stable PDGFRB inhibition ameliorated NR2F6 deficiency-impaired response to DTX in BCa cells, indicating that NR2F6's effect on DTX response is mediated, at least in part, through transcriptional repression of PDGFRB. Collectively, our findings define NR2F6 as an negative regulator of cell survival and DTX resistance, probably by serving as a convergent point linking leptin signaling and PDGF-B/PDGFRß axis, in BCa cells.

Small molecule HDAC inhibitors: Promising agents for breast cancer treatment.

Breast cancer, a heterogeneous disease, is the most frequently diagnosed cancer and the second leading cause of cancer-related death among women worldwide. Recently, epigenetic abnormalities have emerged as an important hallmark of cancer development and progression. Given that histone deacetylases (HDACs) are crucial to chromatin remodeling and epigenetics, their inhibitors have become promising potential anticancer drugs for research. Here we reviewed the mechanism and classification of histone deacetylases (HDACs), association between HDACs and breast cancer, classification and structure-activity relationship (SAR) of HDACIs, pharmacokinetic and toxicological properties of the HDACIs, and registered clinical studies for breast cancer treatment. In conclusion, HDACIs have shown desirable effects on breast cancer, especially when they are used in combination with other anticancer agents. In the coming future, more multicenter and randomized Phase III studies are expected to be conducted pushing promising new therapies closer to the market. In addition, the design and synthesis of novel HDACIs are also needed.

Mutational analysis of BRCA1 and BRCA2 in northwest Chinese breast cancer patients.

BACKGROUND: BRCA1 and BRCA2 are the most well-known susceptibility genes in breast cancer, indicating high-risk breast cancer families and influencing both treatment options. However, data of BRCA mutation in Chinese breast cancer population was limited. Here we explored the BRCA1/2 mutation status and analyzed their clinicopathological relationships among breast cancer patients with high hereditary risk in northwest China. METHODS: Breast cancer patients admitted to Xijing Hospital, between November 2015 and May 2016, with high hereditary risk were recruited. Fresh peripheral venous blood samples were collected for BRCA1/2 gene screening. Risk factors for BRCA1/2 mutations were studied via single-factor analysis and multivariable logistic analysis. Furthermore, we reviewed the literature and discussed the possible mechanism of the mutant genome types. RESULTS: Eighty-two patients were enrolled in the study. Twenty (24.4%) of them were found with BRCA1/2 mutation, including 8 BRCA1 mutation and 13 BRCA2 mutation. BRCA1 and BRCA2 co-mutation was observed in only one case. The mutant genome types included pathogenic variant (4/82), potential pathogenic variant (4/82), beneficial mutations (8/82), and chemotherapy sensitivity-related mutations (5/82). Prognosis-related mutations were enriched in BRCA2 gene, while drug-sensitive related mutations were always observed in BRCA1 gene. Multiple logistic analysis showed that HER2 [odds ratio (OR) 4.58; 95% confidence interval (CI), 1.182-17.74; P=0.028) might be independent factor for BRCA1/2 mutation. CONCLUSIONS: The incidence and feature of BRCA1/2 mutation in our center was similar to that in other regions. HER2 expression was independent factor for BRCA1 and BRCA2 mutation. BRCA2 T/-, BRCA2 A/-, BRCA2 G/- and BRCA2 C/-mutation subtypes might be potential harmful mutations for Chinese breast cancer population.